text:
TITLE: Lymphomas for the Otolaryngologist
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: May 15, 2002
RESIDENT PHYSICIAN: Michael E. Decherd, MD
FACULTY PHYSICIAN: Anna M. Pou, MD
SERIES EDITORS: Francis B. Quinn, Jr., MD and Matthew W. Ryan, MD
material was prepared by resident physicians in partial fulfillment of
educational requirements established for the Postgraduate Training Program of
the UTMB Department of Otolaryngology/Head and Neck Surgery and was not
intended for clinical use in its present form. It was prepared for the purpose
of stimulating group discussion in a conference setting. No warranties, either
express or implied, are made with respect to its accuracy, completeness, or
timeliness. The material does not necessarily reflect the current or past
opinions of members of the UTMB faculty and should not be used for purposes of
diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
Lymphomas are a diverse group of neoplasms that comprise 4% of all new cancers annually. Once the diagnosis is established, most care is rendered by radiation oncologists and medical oncologists. The role of the otolaryngologist is usually limited to biopsy. However, for many patients the otolaryngologist serves as the entry point into the medical system. Awareness of the current knowledge and the proper workup of lymphomas is important for the otolaryngologist to assure timely care of these cancer patients and to prevent the otolaryngologist from being a mere technician in the multidisciplinary care of these patients.
Immunology Review
To understand the pathophysiology of lymphoid neoplasia, an understanding of normal lymphocyte activity is necessary. White blood cells are comprised of neutrophils, monocytes, eosinophils, basophils, and lymphocytes. Lymphocytes are subdivided into three types: B-cells, T-cells, and NK, or natural killer cells.
The path to becoming a lymphocyte begins with a pluripotent stem cell. Once it begins differentiating, a number of molecular changes take place. Cells that mature in the thymus are destined to become T-cells (the "T" refers to thymus). These cells express initially neither CD4 and CD8, then both, and finally one or the other. In the thymus a process of "thymic education" occurs in which the cells, which each express a different random rearrangement of the T-cell receptor (TCR) are culled out by inducing apoptosis in all cells except those which do not recognize "self" as foreign and which additionally are capable of reacting with the major histocompatibility complex (MHC). The cells that then remain are those in which foreign antigens are recognizable, and the cells can then interact with other immune cells to initiate appropriate responses.
T-cells are subdivided into CD4+ cells, which are helper, or TH cells, and CD8+ cells, which are cytotoxic or TC-cells. The helper T-cells serve primarily regulatory functions, whereas the cytotoxic T-cells serve primarily effector functions. When an antigen is presented in an MHC class II molecule by an antigen-presenting cell (which is usually a macrophage, but can also be B-cells, dendritic cells of the spleen, and Langerhans cells of the skin), the helper T-cells are activated. The activated TH-cell then serves a variety of functions, mostly mediated by cytokines. The three main functions effected by TH-cells are to 1) help B-cells activate 2) activate CD8+ T-cells and 3) effect delayed hypersensitivity. TH1 cells mediate the latter two functions, whereas TH2 cells mediate the first function. TH1 cells primarily use IL-2 and IFN-gamma, whereas TH2 cells primarily use IL-4 and IL-5. Cytotoxic T-cells interact with antigens presented in MHC class I molecules, which are present in all cells. When activated, cytotoxic T-cells serve to induce cell death by inserting proteins known as perforins into the cell membrane of the recipient cell, most commonly in virus, tumor, and allograft cells. Some CD8+ cells also serve to suppress certain cell functions and are called suppressor, or TS cells. CD4+ cells comprise about 65% of peripheral T-cells, and CD8+ cells compromise about 35%.
B-cells are so named for the Bursa of Fabricius, an organ found in birds rich in these lymphocytes. The equivalent in humans is thought to be in gut-associated lymphoid tissue. These cells do not require the thymus for maturation, and they exist in germinal centers of lymph nodes, in the spleen, in the bone marrow, and in mucosa-associated lymphoid tissue (MALT). They evolve from pre-pre-B cells to pre-B cells to B-cells, and upon activation they then mature into plasma cells. Through rearrangement of areas of DNA known as the V, D, and J segments, cells with a random variety of different immunoglobulins are produced, each cell having a unique arrangement of its own particular immunoglobulin. When stimulated by an appropriate antigen, the B-cell undergoes clonal expansion and matures into immunoglobulin-secreting plasma cells. Some then persist as memory cells which provide a rapid response upon antigen reintroduction. Approximately 30% of peripheral lymphocytes are B-cells, and they have a short lifespan. Approximately one billion new ones are made each day.
Natural killer cells, or NK-cells, are cytotoxic to cells, but they do not require prior exposure to antigen, are not enhanced by exposure, and are not specific to a particular antigen. They do not require antibody, but their action is enhanced by antibody through a process known as antibody-dependent cellular cytotoxicity (ADCC). They do not mature in the thymus. Approximately 5-10 % of peripheral lymphocytes are NK-cells.
Classification of Lymphomas
The term "malignant lymphoma" was first used by Billroth in 1871. Of course, this is now somewhat redundant, as there are no "benign lymphomas". Lymphomas can be considered a subset of the larger group lymphoproliferative disorders. This group includes benign reactive lymphoproliferative disorders, histiocytosis X (more recently termed Langerhans-cell histiocytoses), plasma cell neoplasms, as well as Hodgkin's disease and non-Hodgkin's lymphomas. The latter two will be the focus of this discussion.
Classification of lymphoid neoplasms remains one the most challenging and controversial subjects in pathology. Rappaport conceived one of the first useful systems in 1956. He divided non-Hodgkin's lymphomas according to whether the cell type appeared to be a lymphocyte or histiocyte, and by whether the histologic architecture was nodular or diffuse.
Subsequently other systems arose, including the Kiel, Lukes-Collins, British National Lymphoma Investigation (BNLI), World Health Organization (WHO), and Dorfman classification systems. This resulted in some degree of chaos, as trials and outcomes from one system were difficult to apply to another. Of these, the Kiel classification remained active the longest, particularly in Europe and Asia. Interestingly, as part of the NCI proposal of the Working Formulation (discussed shortly), these systems were examined by looking at test-retest reproducibility for the individual pathologists shown previously reviewed slides a second time, and the reproducibility varied from 0.53 to 0.93. Also, when concordance among different pathologists was examined, it varied from 0.21 to 0.65.
In 1982, a group from the National Cancer Institute proposed a "Working Formulation", which was intended to be a way to translate among the different systems. Instead, people began using this as a freestanding classification system and began designing trials based upon it. This system was largely based upon the Rappaport system, with "histiocytic" becoming "large cell" and being subdivided into "large cell" and "large cell immunoblastic". It segregates the different categories into low-grade, intermediate grade, high grade, or miscellaneous.
Some problems with the Working Formulation were noted, however. For one thing, it is not based upon the cell of origin of the neoplasm, as is the Kiel system. Also, different groups were segregated according to treatment outcome, not by disease pathogenesis. Thus, in 1994 the International Lymphoma Study Group proposed the Revised European-American Lymphoma classification (REAL). This system segregates lymphomas initially by the cell of origin (B-cell or T-cell), and it uses morphologic features, immunophenotype and/or stage of differentiation, genotype, etiology, epidemiology, and clinical behavior. It also includes Hodgkin's disease in it classification, as the line between NHLs and HD is occasionally difficult to discern. The authors recognize that it is a work in progress and that later modifications may need to be made. Currently, the World Health Organization is working on an updated system based largely on the REAL classification.
Hodgkin's disease (HD) is named for Thomas Hodgkin who described the disease in 1832. At the time, lymphadenopathy was generally thought to be caused by syphilis, inflammation, tuberculosis, or by spread from cancer. He described a series of patients who appeared to have nodal spread of tumor in the absence of a primary tumor or inflammation. He noted, "This enlargement of the glands appeared to be a primitive affectation of those bodies rather than the result of an irritation propagated to them from some ulcerated surface or other inflamed texture." Although known more in his time for other accomplishments, such as public health initiatives, introduction to England of the stethoscope, and clinicopathologic correlations, the disease that bears his name was initially described by him (before common use of the microscope, amazingly enough) and then assigned his name in later publications by Wilks. Hodgkin noted that Malpighi had actually described this sometime earlier.
Hodgkin's disease is characterized by the presence of the pathological cell known as the Reed-Sternberg cell. This cell was originally described decades earlier, but Carl Sternberg (1898) and Dorothy Reed (1902) published thorough descriptions and illustrations of this cell, and it thus bears their names today. (Interestingly, Sternberg thought the process to be tuberculous in origin, and Reed inflammatory. As late as the 1940s, many considered HD to be infectious in origin.) The Reed-Sternberg cell (also known as the Hodgkin cell) is characterized by its large size and its classically bilobulated nucleus with eosinophilic "owl-eyed" nucleoli surrounded by a clear halo. It often is sparsely found throughout a field of reactive lymphocytes. Although considered necessary for diagnosis in the past, some pathologists may call Hodgkin's disease without it if enough other corroborative data are present. Conversely, presence of Reed-Sternberg cells alone is not pathognomonic for HD, as a variety of other conditions may produce Reed-Sternberg cells (such as infectious mononucleosis). A variant of the Reed-Sternberg cell exists which is called the L&H cell, or the popcorn cell. This is so-named because of the lymphocytes and histiocytes seen in the background in the nodular
Precursor B-cell neoplasms |
Precursor B-lymphoblastic leukemia/lymphoma |
Peripheral B-Cell Neoplasms |
1) B-cell CLL/PLL/SLL |
2) Lymphoplasmacytoid
lymphoma/immunocytoma |
3) Mantle cell lymphoma |
4) Follicular center
lymphoma, follicular Provisional cytologic grades: I (small), II (mixed), III (large) Provisional subtype:
diffuse, predominantly small cell |
5) Marginal zone B-cell
lymphoma Extranodal (MALT +/- monocytoid B-cells) Provisional category: Nodal (+/- monocytoid B-cells) |
6) Provisional entity: Splenic marginal zone lymphoma |
7) Hairy cell leukemia |
8) Plasmacytoma
/ myeloma |
9) Diffuse large B-cell
lymphoma |
10) Burkitt's
lymphoma |
11) Provisional entity:
high-grade B-cell lymphoma, Burkitt's-like |
Precursor T-cell neoplasms |
Precursor T-lymphoblastic leukemia/lymphoma |
Peripheral T-Cell and NK-Cell Neoplasms |
1) T-cell CLL/PLL |
2) Large granular
lymphocyte leukemia |
3) Mycosis fungoides/Sézary
syndrome |
4) Peripheral T-cell
lymphomas, unspecified Provisional categories:
medium, mixed, large, lymphoepithelioid Provisional subtypes: Hepatosplenic γδT-cell lymphoma
panniculitic T-cell lymphoma |
5) Adult T-cell lymphoma/leukemia |
6) Angioimmunoblastic
T-cell lymphoma |
7) Angiocentric
lymphoma / nasal T/NK-cell lymphoma |
8) Intestinal T-cell
lymphoma |
9) Anaplastic
large cell lymphoma |
10) Provisional: ALCL
Hodgkin's-like |
Lymphocyte predominance (nodular +/- diffuse) |
2) Nodular sclerosis |
3) Mixed cellularity |
4) Lymphocyte depletion |
5) Lymphocyte-rich classic HD (provisional subtype) |
B-cell |
Lymphoplasmacytoid lymphoma |
Follicular center
lymphoma, follicular (small and mixed) |
zone B-cell lymphoma |
Hairy cell leukemia |
/ myeloma |
T-Cell |
Large granular lymphocyte
leukemia |
ATL/L (smoldering) |
Mycosis fungoides/Sézary syndrome |
B-cell |
Mantle cell lymphoma |
Follicular center lymphoma
(follicular large cell) |
T-Cell |
ATL/L (chronic) |
Angiocentric lymphoma |
Angioimmunoblastic lymphoma |
B-cell |
Large B-cell lymphoma |
T-Cell |
T-cell lymphomas |
Intestinal T-cell
lymphoma |
Anaplastic large cell lymphoma |
B-cell |
Precursor B-lymphoblastic leukemia/lymphoma |
Burkitt's lymphoma |
High-grade B-cell
lymphoma, Burkitt's-like |
T-Cell |
Precursor T-lymphoblastic leukemia/lymphoma |
ATLL (acute and lymphomatous) |
Table 1. Revised European-American Lymphoma Classification and Suggested Clinical Grouping of Entities
lymphocyte-predominant HD in which it mainly occurs. Another variety is the lacunar cell, which mainly occurs in the nodular sclerosis type.
The Rye classification has been the dominant
system for classifying HD for the last 25 years. This includes the categories of nodular
sclerosis (NSHD), mixed cellularity (MCHD),
lymphocyte predominant (LPHD), and lymphocyte depletion (LDHD). Recently the REAL classification (and now apparently
the WHO classification) has made subtle modifications, recognizing the
different biology of nodular lymphocyte-predominant HD.
Staging can be defined as determining the extent of the malignant disease within a given patient. For lymphomas, traditional TNM staging is difficult to apply, as one is often not able to distinguish between T, N, and M. The Ann Arbor system, proposed in 1971, has been the gold standard for both HD and NHLs since that time. Staging is important for assessing prognosis and determining the best course of treatment.
Ann Arbor staging classification |
Stage |
Characteristics |
of a single lymph node region (I), or a single extranodal
organ or site (IE) |
of two or more lymph node regions on the same side of the diaphragm (II),
or localized involvement of an extranodal site or
organ (IIE) and one or more lymph node regions on the same
side of the diaphragm. |
of lymph node regions on both sides of the diaphragm (III), which may also be
accompanied by either localized involvement of an extranodal
site or organ (IIIE), involvement of the spleen (IIIS),
or both (IIIES) |
or disseminated involvement of one or more extralymphatic
organs with or without associated lymphatic involvement. The organs may be designated by a symbol: H
for liver, L for lung, M for bone marrow, P for pleura, O
for bone, D for skin. |
absence or presence of any of the following: fever > 38o, night
sweats, or weight loss of >10% body weight over prior 6 months should be
designated with the suffix A or B, respectively. |
Table 2. Ann Arbor staging classification
Lymphatic structures include lymph nodes, spleen, thymus, appendix, Peyer's patches, and Waldeyer's ring. These do not therefore count as extranodal (or more properly extralymphatic) sites, although this is not uniformly reflected in the literature, with the more recent trend to classify Waldeyer's ring as extranodal. Extralymphatic sites may also be characterized as local or diffuse. This has relevance inasmuch a localized extralymphatic site may be considered for treatment with radiation. In practice there is disagreement among clinicians about what constitutes a localized extralymphatic site. Prior designations of "CS" for clinical stage and "PS" for pathologic stage have been largely abandoned as the staging workup has become less invasive over time and there has thus been less pathologic tissue and less need to point out the difference, as the quality of clinical (non-invasive) staging is currently high.
The Ann Arbor system does have limitations, especially for NHLs. For one thing, the prognosis is not always very different among the stages, especially between IV and III, and to some degree even II. Prognosis may be better assessed by indirect measures of tumor burden such as number of nodal and extranodal sites, size of tumor masses (>10 cm is considered bulky disease), percentage of bone marrow involvement, and performance status. Also, NHLs are a diverse set of tumors which do not all behave similarly and, as such, are difficult to stage with a "one-size-fits-all" system. They often present extralymphatically, which is less well addressed by the Ann Arbor system. Also, whereas HD patients present somewhat evenly by stage, NHL patients tend to present with advanced disease. Although a number of tertiary cancer centers are investigating newer staging systems, none have supplanted the Ann Arbor system at present.
Hodgkin's Disease
Hodgkin's disease has a bimodal age-incidence curve that is more common among economically advantaged populations such as in the United States. This bimodal peak has led some to speculate that an infectious agent is responsible for the younger cluster whereas the later peak represents cellular changes of aging. HD is more common in men than women, and by race it is more common in whites than in blacks and is least common in Asians. Geography also plays a role in the incidence of HD that is independent of race. There are about 7,500 new cases in the US annually and about 1,500 deaths. This corresponds to an age-adjusted incidence rate of 2.9 in the US. The incidence has decreased about 16% since the 1970s. This decrease is partly due to prior misclassification of NHL as HD, but much of the reason for this decrease is not known. Mortality has decreased about 65%, largely due to improved treatment and technology. Among the subtypes, nodular sclerosis has increased in incidence, particularly among young white women. It also is the subtype that shows an association with economic advantage. The subtypes ranked according to incidence are: NSHD>MCHD>LPHD>LDHD.
Non-Hodgkin's Lymphomas
Non-Hodgkin's lymphoma is the fifth-most common cancer in the US, with about 55,000 cases in the year 2000. From 1973 to 1997, the age-adjusted incidence rates rose about 80%. This is faster than most other cancers, and it is not known why this increase is occurring. HIV-associated NHLs account for some, but not all, of this increase. Over the same period the mortality of NHLs has increased by about 45%. The rise in incidence is worldwide, independent of the higher incidence rates observed in developed countries such as Western Europe, North America, and Australia. Family history plays a role, and the odds ratio for persons with a first-degree relative with lymphoma is 3.0 (95% CI 1.7-5.2). Within NHLs, 90% are B-cell derived.
Etiologic Factors
HIV/immunosuppression: While any form of immunodeficiency increases the risk of acquiring lymphoma, the current HIV epidemic has caused its own explosion of NHLs. Between 1982 and 1990, NHL incidence rates increased nearly 800% among men aged 20 to 59 in San Francisco County. HD, although not as strong an association initially, is now thought to be about 10 times as common among persons with HIV that in the general population. The risk of NHL in AIDS patients is 72 times that of the general population. It is estimated that 3% of AIDS cases present with NHL as the AIDS-defining condition. The increases appear to be mostly in the higher-grade lymphomas, and there is a higher incidence of extralymphatic disease. Since 1996, the incidence rate of NHLs in the HIV population has been falling dramatically, and this is thought to be due to the introduction of highly active antiretroviral therapy (HAART).
Recipients of bone marrow transplant are 5-6 times more likely to develop HD, supporting the link of immunosuppression to lymphomas. Other organ transplant recipients are also at risk, but the risk appears to be getting smaller as the science of transplantation has improved and resulted in better matches and less immunosuppression. Additionally, survivors of HD treatment are at increased risk to develop NHLs, which may in part be due to immunosuppression. Genetic immunodeficiency syndromes such as common variable immunodeficiency and Wiskott-Aldrich syndrome are at increased risk of developing a number of malignancies, of which NHLs comprise about 50%.
EBV: Epstein-Barr virus was originally isolated in a cell line developed from African Burkitt's lymphoma. Denis Burkitt recognized that a previously unrecognized cancer affecting the jaws of African children had a distribution similar to that of endemic malaria, and he hypothesized that an infectious agent might be at work. This led Tony Epstein and Yvonne Barr in 1964 to examine tumor biopsies with electron microscopy where they identified a new herpesvirus, later named Epstein-Barr virus (EBV). Since then EBV has been clearly implicated as a factor in both HD and NHLs. In HD, it is most strongly associated with MCHD and LDHD subtypes. A diagnosis of infectious mononucleosis increases the risk of HD development between 2 and 13-fold. It can be isolated in between 20 and 50% of Reed-Sternberg cells. In NHLs, EBV is most strongly associated with Burkitt's lymphoma. In the endemic (African) form, EBV association approaches 100%, whereas in the sporadic form, it is in the 10-20% range. It appears to transform the c-myc oncogene. EBV has also been associated with a number of other lymphomas (post-transplant, AIDS-related, T-cell/NK-cell (nasal and non-nasal), and anaplastic large cell) and a number of other malignancies (nasopharyngeal carcinoma, sinonasal undifferentiated carcinoma, lymphoepithelial carcinoma of salivary glands, oral squamous cell carcinoma, and basaloid squamous cell carcinoma).
HTLV-I: Human T-cell lymphotropic virus-I has been associated with an excess of peripheral T-cell NHL in the Caribbean and Japan. HTLV infection is rare in the US.
Helicobacter pylori: H. pylori has been associated with MALT lymphoma. One study found that individuals with a diagnosis of peptic ulcer had a relative risk of 5.6 for gastric NHL, mostly of the MALT variety.
Medical conditions: NHLs have been associated with a number of medical conditions, including hepatitis C, diabetes mellitus, prior blood transfusion, Sjögren's syndrome, rheumatoid arthritis, lupus, pyelonephritis, tuberculosis, malaria, and psoriasis, although not all reported associations have been later validated. Of note to the otolaryngologist, lymphomas associated with Sjögren's syndrome appear to be low-grade marginal zone lymphomas and are not associated with viruses.
Genetic Factors: Certain HLA phenotypes have been associated with lymphomas, such as DPB1*0301 and HD. A study of monozygotic twins who developed HD showed a relative risk of 128 (95% CI:42-299) in the other twin. Familial clustering of NHLs is much less common.
Occupational risk: Although many occupational exposures have been studied and suggested as etiologic factors, the most compelling data appear to show an association of woodworking with HD and show an association of pesticide and herbicide exposure (mostly in farmers) with NHLs.
Negative/Weak Associations: Investigations have failed to show any definitive link between NHLs and smoking, radiation exposure, and physical activity. A possible link between tonsillectomy and HD has been suggested but appears to have been refuted in later studies. Some suggestions have been made that body-mass index over 30, certain dietary factors, prior blood-transfusion, phenytoin use, and long-term black or brown hair dye use may increase the risk of developing NHLs. Human herpesvirus-6 (HHV-6) has been found in both HD and NHLs, but causality remains speculative at present. Another more recently discovered herpesvirus, HHV-8, is also being investigated as a cause of lymphomas.
As always, the medical evaluation begins with the history and physical examination. The classic presenting sign is painless adenopathy. Other items to note in the history include age, gender, presence or absence of fever and its duration, unexplained night sweating and its severity, unexplained weight loss and its magnitude and timecourse, unexplained pruritus, alcohol-induced pain, family history of cancers, prior immunosuppressive illness, and prior cancer and cancer treatments. Alcohol-induced pain is a phenomenon of unknown etiology that causes affected lymph node groups to have significant pain upon consumption of even a little ethanol. This phenomenon is relatively specific for lymphoma.
Unexplained constitutional symptoms, adenopathy that persists greater than 2-3 weeks, increasing adenopathy, or patients at high risk should be considered for tissue evaluation. At our institution, fine-needle aspiration (FNA) is the usual initial investigation. This is particularly important in the head and neck- if the FNA suggests lymphoma an excisional biopsy is often indicated, whereas if it suggests squamous cell carcinoma (the most common head and neck cancer) excisional biopsy is usually contraindicated. Excisional biopsy is needed in lymphoma to examine tissue for architecture and acquire tissue for additional studies such as flow cytometry.
Comparing HD to NHLs, HD has more of a tendency to present in a localized set of nodes, whereas NHLs tend to present in multiple sites. HD spreads in an orderly, contiguous fashion, whereas NHLs have more likelihood of noncontiguous spread. NHLs are more likely to involve Waldeyer's ring, and they are more likely to be extranodal.
Once the diagnosis is made, appropriate staging investigations are undertaken. Appropriate staging is important to avoid the morbidity of overtreatment or the mortality of undertreatment. In addition to a CBC with smear, LFTs with LDH, blood chemistries, ESR, and serum ß2-microglobulin, a CT of the chest, abdomen, and pelvis should be obtained. Many patients will also need bone marrow biopsies, and some will need a spinal tap to assess for meningeal involvement. MRI images bone marrow well and has the possibility of decreasing false-negative bone marrow aspirations by providing directed sites for biopsy.
Adjunctive imaging modalities include bone scanning, gallium scanning, ultrasound, and FDG-PET scanning. Also, lymphangiography is an older imaging technique that is being used less often today. Gallium-67 is a nuclear medicine isotope that has an affinity for lymphomas. Studies have shown that gallium scanning is highly sensitive and specific. One study by Kaplan found that when gallium-positive tumors become gallium-negative after treatment, a complete and lasting remission was likely.
Positron emission tomography (PET), which uses 2-[18F]-fluoro-2-deoxy-D-glucose (FDG), detects tissues that are actively metabolizing glucose. It, too, has been shown to have a high sensitivity and specificity. Early data suggest that it may be particularly useful for extralymphatic tumors. It is also helpful in assessing the post-treatment mass, as this may represent either residual tumor or sterilized, fibrotic tumor, and FDG-PET can help differentiate between the two metabolically. Also, some have suggested that using carbon-11 methionine instead of fluorine-18 may improve the sensitivity. Research into the applications of PET is ongoing.
The role of staging laparotomy has been evolving and debated over the last few decades. The concept is this: if a potential Stage I or II supradiaphragmatic disease has crossed the diaphragm, then it is a Stage III disease and the treatment may need to be altered (e.g. it is no longer a candidate for localized radiation only). Risks include overwhelming sepsis by encapsulated organisms in both the immediate and late post-operative period. As non-invasive imaging techniques have improved, the role of staging laparotomy has decreased. Laparoscopy may be a newer technique that is less morbid yet still allows for tissue diagnosis.
Treatment options for both HD and NHLs include observation, involved-field radiation, subtotal lymphoid radiation, chemotherapy with or without radiation, and bone marrow transplant. Also, newer biologic therapies are being applied in the treatment of HD and NHLs.
Chemotherapy: The first chemotherapeutic agent was found when an explosion in Bari, Italy during World War II exposed US servicemen to an intense amount of mustard gas. Profound marrow and lymphoid aplasia were noted, and nitrogen mustard was isolated and applied to humans by Goodman and Gilman. The first six patients treated had HD and lymphosarcoma, and striking dissolution of the tumor masses was noted (unfortunately to return shortly thereafter).
With failure of monotherapy, combinations of chemotherapeutic agents arose. The first popular treatment regimen for HD was MOPP – cyclophosphamide, vincristine, procarbazine, and prednisone. Although revolutionary in the treatment of HD, certain treatment failures led to the search for other regimens. This led to the development of ABVD – doxorubicin, bleomycin, vinblastine, and dacarbazine. This proved to have similar efficacy as MOPP but different toxicities. It was also found to be effective in salvaging MOPP failures.
Since then, other chemotherapeutic agents and combinations have been developed and been efficacious in the chemotherapeutic treatment of lymphomas. Some regimens may have similar efficacy but be selected for different toxicities. The first regimen to show efficacy in NHLs was CHOP – cyclophosphamide, doxorubicin, vincristine, and prednisone. CHOP therapy is still employed today.
Radiation therapy: The first reported treatment of HD with XRT was by Dr. William Pusey, a dermatologist at the University of Illinois in 1901. He reported successful shrinkage of nodes in HD patients. Since then radiation alone or in combination with chemotherapy has been a mainstay of treatment of lymphomas. Much controversy exists regarding the optimum treatment of lymphomas, particularly for early-stage HD where monotherapy (either chemo or XRT alone) is likely to be efficacious.
Bone marrow transplant: One of the limiting factors in chemotherapy is myelosuppression. If this restriction is removed, it is possible to escalate the dose of chemotherapy agent, which is beneficial for certain agents. However, hematologic reconstitution must occur to avoid a fatal outcome. This is accomplished with marrow transplant. It can either be autologous, in which the patients own marrow is harvested, or allogeneic, from a matched donor. Autologous donors avoid the problem of graft-versus-host disease but may run the risk of transplanting disease back in. Also, much of the efficacy in allogeneic transplants is thought to come from a graft-versus-tumor effect, as the tumor cells are less hardy than the native cells. Bone marrow transplants are usually performed for NHLs rather than for HD, as NHLs are frequently more difficult to treat conventionally. Allogeneic stem cells have been traditionally harvested from the iliac crest, but newer techniques involve leukopheresis after marrow stimulation with G-CSF.
Novel therapies: Novel therapies involving immunotherapy, vaccination, radioimmunoconjugates, interferons, immunotoxins, vascular targeting, and other novel therapies are currently under investigation. The monoclonal antibody rituximab (trade name Rituxan) became the first FDA-approved monoclonal antibody for treatment of cancer. It selectively targets CD20, a protein found on malignant and normal B-cells but not on other normal tissues.
It is estimated that approximately 80% of patients with HD will be cured of their disease. Early-stage, favorable HD, has a cure rate of over 90%. After treatment, HD survivors have a higher incidence of death from cardiac, infectious, and second malignancies. One problem is estimating prognosis is that disease-specific survival has not been separated from overall survival in many of the studies. Advanced stage has been shown to have a negative impact on prognosis. Tumor histology has been shown to have prognostic implications as MCHD/LDHD had an inferior overall survival than NSHD/LPHD. This is thought to be due to the former subtypes tendency to relapse infradiaphragmatically, which is usually bulkier and harder to salvage. Factors that segregate early-stage HD into the unfavorable category (which may mean adding chemo to radiation) include age over 50, ESR>50, B-symptoms with ESR>30, and a large mediastinal mass.
NHLs have a worse prognosis than HD. Five-year survival rates (considering all NHLs) are around 50%, but this varies by subtype and by aggressiveness. Ten-year survival rates for low, intermediate, and high-grade lesions are approximately 45, 26, and 23%, respectively. In general, follicular (or nodular) architecture is better than diffuse architecture on histology. In low-grade NHLs approximately 30% will undergo a process known as Richter's transformation in which a clone of high-grade aggressive cells will emerge. Median survival is less than one year after this occurs. Ironically, the low-grade lymphomas are much less curable than the high-grade lymphomas. They may not move quickly, but due to the small percentage of the cells in the growth phase, therapy is not usually as effective as in high-grade, aggressive lymphomas. Many will elect to observe certain low-grade lymphomas until treatment becomes necessary due to symptoms.
One study by Shipp et al identified risk factors for poor prognosis. They were age greater than 60, late-stage disease, elevated LDH levels, impaired performance status, and extralymphatic involvement. Five-year survival by number of risk factors was: 0-1—73%, 2—51%, 3—43%, 4-5—26%. Ki-67 has been shown to be a negative prognostic factor when this nuclear proliferation antigen was present in greater than 60% of cells. The faster one achieves a complete remission has a positive prognosis for survival. Gallium-negativity after treatment improves survival, as well. ß2-microglobulin, a component of the MHC class I molecule detectable in serum, has a negative prognostic correlation when elevated.
Issues for the Otolaryngologist / Head & Neck Surgeon
While squamous cell carcinoma represents the most common malignancy in the head and neck, lymphoma comprises the second-most common. As discussed before, FNA is essential prior to consideration of excisional biopsy to exclude squamous cell.
A recent study by Hanna et al summarized 98 patients with extranodal lymphomas of the head and neck. They found that Waldeyer's ring was the most common site of presentation at 36%, followed by the sinonasal tract (25%). Fifty percent of patients had nodal disease, and only 20% had B-symptoms. Tonsillar lymphoma had a 20% chance of having associated GI lymphoma. Two-thirds of patients had intermediate grade lymphomas, and three-fourths had Stage I or II disease. Overall and disease-free survival was 60 and 50%, respectively. High grade and advanced stage had the worst prognosis.
Burkitt's Lymphoma: One type of lymphoma that presents in the head and neck is Burkitt's lymphoma. This was originally described by Burkitt in Africa (see the section on EBV). This endemic form is clinically distinct from a sporadic form, which occurs in the US, although they are histologically identical. The African form usually presents as a mass in the maxilla or mandible, whereas abdominal presentation is more common in the sporadic form. These respond relatively well to aggressive chemotherapy although long-term relapse is not uncommon.
Lethal Midline Granuloma: Lethal midline granuloma, which has also been called lymphomatoid granulomatosis and polymorphic reticulosis, is now known to be a T-cell lymphoma. Some feel that idiopathic midline destructive disease is a separate entity, whereas others feel it is another variant of this disease. Men are affected more than women, and this usually occurs in the 5th and 6th decade of life. Patients commonly present with cough, shortness of breath, and hemoptysis. On exam the patient has ulcerating lesions of the upper respiratory tract, usually in the sinonasal cavity. Clinically this is impossible to distinguish from Wegener's, but histologically it lacks granulomas and palisading histiocytes. Mortality is relatively high.
A summary of the classification, etiology, epidemiology, staging, workup, and treatment of lymphomas is presented.
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Selby PJ, MacLennan K, Armitage
JO (eds) Malignant Lymphoma. Arnold: London,
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Z. History of tonsillectomy and
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Goldberg D, Golz A, Netzer A, et al. Epstein-Barr virus and cancers of the head
and neck. Am J Otolaryngol
22(3):197-205, 2001.
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TW. Developmental and functional biology
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Head Neck Surg 112:654-8, 1986 Jun.
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In Mauch PM, Armitage
JO, Diehl V, et al (eds) Hodgkin's Disease Lippincott: Philadelphia, 1999.
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Clin North Am 80(4):1111-26, 2000 Aug.
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Non-Hodgkin's Lymphomas. Arnold:
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Robbins KT, Fuller LM, Vlasak M, et al.
Primary lymphomas of the nasal cavity and paranasal
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Shipp, MA, Harrington DP,
Anderson JR, et al. A predictive model
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Engl J Med 329:987-94, 1993.
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Opin Oncol 11:370-4,


text:
J.M. (Mickey) Breaux
Director District 13
Effective July 1, 2006, the International Executive Board appointed a former USW District 13 International representative, J.M. (Mickey) Breaux, as Director for District 13. Re-elected in 2009, Breaux is originally from Local 13-423.
Breaux is responsible for 50,000 USW members in Texas, Louisiana, Oklahoma and Arkansas. In addition, Breaux chairs the Temple-Inland and Boise-Cascade councils.
Breaux is from Port Arthur, Texas, and his father, who worked at Texaco, now Shell Motiva, was a member of the Oil, Chemical & Atomic Workers (OCAW) Local 4-23, the predecessor to USW 13-423.
Breaux joined OCAW Local 4-23 in 1969 when he went to work at Atlantic Richfield. As a rank-and-filer, he served or chaired various union committees including negotiations, health and safety, workers compensation, strike strategy and the United Way.
OCAW President Bob Wages appointed him to be an International representative in 1996, and he then headed the Crown Central Petroleum lockout negotiations for four years. He also served as the District 13 coordinator for Rapid Response for three years.
In addition, Breaux was active in the United Way, Texas AFL-CIO and the Democratic Party.
The headquarters for District 13 is in Baytown, Texas.
USW District 13
1300 Rollingbrook Drive, Suite 504
Baytown, TX 77521
832.556.0370 – Telephone
State(s): AR, LA, OK, TX

subset: commoncrawl


text:
Celebrants at the 2012 DuPage Symphony Orchestra Gala. (Posted By JAMES KUNZE, Community Contributor / February 28, 2013) |
The DuPage Symphony Orchestra (DSO) is pleased to announce its 2013 fundraising event, "A WINE TASTING", on Saturday, April 6, 2013, 6 to 8 p.m. at the Chicago Marriott Naperville, 1801 North Naper Boulevard in Naperville. The event will feature four wine tasting stations each of which will include an exquisite food pairing with wine hand-selected by the Marriott Executive Chef. A string quartet featuring DuPage Symphony musicians will provide light classical musical entertainment.
The DSO is also excited to offer an art show and sale sponsored by the Naperville Art League. The show will feature six distinct local artists and their works including art, sculpture and decorated musical instruments. The instruments were donated specifically for the event and are one-of-a kind treasures. A silent auction will offer additional items donated by local merchants and friends of the orchestra. The evening will close with a light buffet, and a cash bar will be available throughout the evening.
Tickets are $60 per person and may be purchased through the DSO website at www.dupagesymphony.org, by calling the DSO business office at 630.778.1003 or through email at email@example.com. Corporate/business sponsorship packages are also available upon request. Proceeds from the event support the DSO's mission to "Surround our Community with Music" through the orchestra's 5-subscription concert series, chamber concerts, and free summer concerts. Money raised will also help fund chamber concerts at the DuPage Children's Museum and the 95th Street Library in Naperville, pre-concert lectures, Brownies with Barbara, Young Artists Auditions, annual DSO School Day Concert, and more. Don't miss this opportunity to help a great organization make a difference in the community while enjoying a fabulous evening.


text:
If you are serving or have served in the
military, please consider joining the Student Veterans Organization (SVO).
Experience camaraderie with fellow
student veterans as you transition to
college as well as participate in a
variety of veteran related
activities on campus and within the
community. To join this group or to get
more information, please contact:
Kathy Ierace
To our Student Veterans
Western Connecticut State University is dedicated to helping student veterans achieve academic and personal success. Whether vets are transitioning back to campus after active duty or facing deployment during their course of study, the university wants to make this a smooth and seamless process.
Enrollment Management and the Division of Student Affairs currently
are working together to expand programs and services to our veteran
student population. The Coordinator of Veterans Affairs, which is a new
position, will report to the Associate Vice President for Enrollment
Services and certifies students for US Department of Veterans Affairs
(DVA) educational benefits; provides academic program advising for
veterans; and assures compliance with federal, state and college
directives in relation to veteran/dependent educational benefits.
Additionally, the coordinator provides support for all student veterans,
reservists, and National Guard members to ensure a smooth transition to
student life by assisting with issues such as financial aid, academic
preparedness, health and wellness, socialization issues, and
administrative requirements.
Until this position is filled, Nancy
Barton, Director of Student Financial Services (203-837-8860), will be
assisting with financial aid matters, and Isabel Carvalho, Director of
the Advisement Center (203-837-8397), is available to assist with
academic preparedness.
Within the Division of Student Affairs, Daryle Dennis, Assistant Dean of
Students (203-837-8549), has agreed to be the advisor to our veterans.
In this role, Mr. Dennis will be an on-campus resource and point of
contact for our veterans. In addition to providing support, Mr. Dennis
will be working with our veterans to promote and plan events and gather
opportunities for our veterans, i.e. Veterans Day Celebration; Iraq War
Vets Celebration; Wounded Warrior Program, etc. Additionally, Mr. Dennis
will be working with Kathy Ierace, who is the current advisor to the
Student Veterans Organization (203-837-8772), and with the Women's
Auxiliary of Greater Danbury on student veteran efforts.
Finally, both the coordinator and advisor will establish and co-chair a
Veterans Advisory Committee. This committee will replace the Veterans
Task Force.
Contact Information:
Tuition waiver and financial aid related benefits questions: Nancy Barton Director of Student Financial Services |
Academic Preparedness: Isabel Carvalho Director of Academic Advisement |
Advisor: Daryle Dennis Assistant Dean of Student Affairs/Veterans
Liaison |
Advisor to the Student Veterans Organization: Kathy Ierace Science
Technical Specialist/SVO Advisor |


text:
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text:
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Legacy contaminants are decreasing more quickly than previously reported in three of the Great Lakes, but have stayed virtually the same in two other lakes, according to new research.
"These are very positive results. The lakes are improving and slowly cleaning themselves up," said Thomas Holsen, co-director of Clarkston University's Center for the Environment and co-author of the study.
Even with the decreases, it will be 20 to 30 years until the decades-old contaminants in Great Lakes fish decline to the point that consumption advisories can be eliminated, Holsen said. In addition, the older contaminants are being replaced by newer ones, mostly flame retardants, that are building up in fish and wildlife.
Polychlorinated biphenyls (PCBs), the pesticide DDT and other banned compounds dropped about 50 percent in fish in Lakes Michigan, Ontario and Huron from 1999 through 2009, although there were no significant changes in Lakes Superior and Erie fish, according to the study to be published this month in the journal Science of the Total Environment.
The status quo at Superior and Erie – which have lower levels of contaminants than the other lakes – is not surprising, Holsen said. Lake Superior is big, deep and cold, so changes happen more slowly. And Lake Erie's walleye have a shorter food chain than the trout tested in the other lakes, so the contaminants did not build up as much.
PCBs – industrial compounds that are the most prevalent pollutants tested – are decreasing at the slowest pace, at about 3 to 8 percent per year, while DDT declined about 11 to 16 percent per year. The pesticide mirex, which is only detected in Lake Ontario, decreased 15 to 25 percent per year.
That is substantially faster than previous rates for the contaminants: 2 to 4 percent annual decreases between 1980 and 2003. PCBs and DDT concentrations stayed relatively stable from 2000 to 2003.
"If you look at PCBs in the region, there are still very high concentrations in urban areas," Holsen said.
All of the compounds studied were phased out in the 1970s after they began building up in the environment, particularly in the Great Lakes. Because they are slow to break down, they persist in the lakes' sediments and still are accumulating in fish and other wildlife.
Fish consumption warnings remain throughout the basin for PCBs, which have been linked to an array of health effects, including cancer and reduced IQs in people.
PCBs also seem to affect the reproduction of lake trout. Their populations are rebounding as the PCB levels decline, but they face other threats, too, such as invasive species.
"There is significant evidence that contaminants contribute to a lack of reproduction in the lakes," said Deborah Swackhamer, co-director of the University of Minnesota's Water Resources Center. "PCBs and dioxin are going down in Lake Ontario and contaminants are going down in Superior, and you're seeing more successful lake trout reproduction in these lakes."
Since bans have eliminated manufacture and use of the compounds, they are now getting into the lakes mostly through what's circulating in the air.
"We've tackled the low-hanging fruit," said Ronald Hites, a professor at Indiana University's School of Public and Environmental Affairs who specializes in air monitoring in the Great Lakes basin.
Through atmospheric deposition, the chemicals move from the air to the Earth's surface. "The trends in the air are much the same. These old chemicals are decreasing," Hites said. "Especially in the more remote regions like northern Lake Michigan and Lake Superior, it's almost all atmospheric deposition."


text:
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IHS Tackles HIV Issues with Online Training and New Initiatives
WASHINGTON, DC—Providers play an important role in HIV prevention and care, and IHS is hoping to help providers carry out that role through online training that was developed last year.
Aging Population Provides New Challenges in Treating HIV
WASHINGTON, DC—VA not only has the largest HIV care program in the country, but the largest HIV geriatric care program in the country. VA cares for over 24,000 HIV-positive patients, 120 of whom are older than 80. This gives VA physicians and researchers a front-row seat to the newest discoveries on how the physical effects of aging impact HIV symptoms and how they present.
Servicemembers and Veterans Use Programs to Help Each Other Overcome Stigma
WASHINGTON, DC—Veterans and servicemembers may be able to help each other overcome stigma in seeking psychological help, officials said during a webinar on combating stigma in the military hosted by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE).
IDCRP Investigates HIV Questions
BETHESDA, MD—At the Infectious Disease Clinical Research Program (IDCRP), headquartered at the Uniformed Services University of the Health Sciences, researchers are in the business of asking tough questions and then going after the answers. "We are not a funding agency. We are not a granting agency, where people bring ideas and we fund them. We are a research organization that works in collaboration with others to conduct investigations," Brian Agan, MD, director of IDCRP's HIV/STI Working Group (WG), said of IDCRP.
Many Smokers Also Use Smokeless Tobacco, CDC Says
WASHINGTON, DC—Many who smoke are also using smokeless tobacco. New data compiled by CDC that covers use of smokeless tobacco in all 50 states, the District of Columbia, the US Virgin Islands, Puerto Rico, and Guam found that the rates of smokers who also use smokeless tobacco, including chew tobacco and snuff, range from 0.9% in Puerto Rico to 13.7% in Wyoming.
New Smart Phone Application Designed to Help Users Monitor Emotional Health
WASHINGTON, DC—Servicemembers, veterans, and their families will need to look no further than their smart phone for help in monitoring their emotional health.
Navy Seeks To Address Combat Stress Through Graphic Novel
WASHINGTON, DC—The Navy is seeking to help prepare its hospital corpsmen to deal with the psychological stresses of war through a new novel.
DoD Rolls Out Computerized Medical Records for Anesthesia
WASHINGTON, DC—DoD is in the midst of deploying a tool that will automate recordkeeping for anesthesiologists.
New Drugs Hold Promise for Veterans with HCV
WASHINGTON, DC—The hepatitis C (HCV) treatment program in VA marks its 10-year anniversary this year on a note of hopeful expectation. For years the only treatment for HCV has been combination pegylated interferon and ribavirin—a treatment with harsh side effects and a cure rate between 20% and 25% among VA patients. But several new drugs currently in development promise to almost double that success rate, which is good news for VA's 150,000 HCV patients.
Report Examines How to Increase Flu Vaccination Rates
WASHINGTON, DC—A report released last month by a nonprofit organization calls for increased education efforts to encourage flu vaccination, especially among minority groups.
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text:
I have never seen Otis take the lead live before!
I have never seen Otis take the lead live before!
Love those Cholly Atkins steps at the end. I've seen him sing leads live over the years, usually when The Tempts were taking a "blow". This was one of the few Temptation songs that they speeded up and punched up for their live act, I hated this arrangement, although it was released as a single and I understand the thinking behind it but they actually ruined a very good song. You're right Step, if you mean released video product, this is rare indeed. This particular video has been up for a couple years so I am familiar with it, good post.
Are there any 60s songs Otis sings parts in,i think I C an't get next to you,, and a couple from DRATS Join the Temptations album any others , not a bad singer bit like Jimmy Ruffin cheers
One that immediately comes to mind besides the DRATS is "Dont Send Me Away" ...a very nice lead ballad. But he also sang a series of parts like in Psy. Shack, Cloud Nine etc.
Could some of you point out Otis's lines in Cloud 9 and Psychedelic Shack.
This is the first time I ever heard the sped up version of this song. Not sure yet...But Otis is a good singer!
There is a song during the Atlantic era called Read between the lines that he sings lead in.
Here's Otis singing the absent EK's parts on I Can't Get Next To You on the UK's Top Of The Pops in 1970.
This is a song we talked about briefly in another thread, Otis on lead with an able assist from Louis Price sounding like a young Jerry Butler.....lol.....a sad song about divorce and the effect on the child....good song.....
Could some of you point out Otis's lines in Cloud 9 and Psychedelic Shack.
Psy. Shack: " peace signs running everywhere", I may have been mistaken about Cloud Nine the way I wrote it, I meant to comment on them all singing parts of songs during that particular era.
Darling stand by me is from the[house party lp]which otis hates but the song is basically his lead!
Always thought this was the stand out track from a mediocre album, didn't realise that it was Otis on lead. Thanks for that. I also love "Don't send me away". Otis should have taken more leads over the years.
Great performance from the temps and i agree that otis should've taken more leads,another great lead from him is[i ain't got nothin],have you noticed that most of the speaking parts were done by otis because he had the smoothest speaking voice[and with each beat of my heart for everyday we're apart i'll hunger for every wasted hour]cooooool...otis forever!!
Good call Jai, this record was nibbling away at my subconscious and if not for the drink of champions, I might not have ever remembered....good call.....although they stole the background and mood of "I Only Have Eyes For You " and thanks for mentioning his part of I'm Gonna Make you Love me, I Ain't Got Nothing was a great throwback doo wop tune.........although a true collab, you know from all those voices that its the Tempts.......unmistakeable.....
hey paladin,ain't the temps fun?and while we're talking about otis let's not forget his opening on the early classic[check yourself]...by an by you know that you make me cry,but my love for you will never die that's why i had to find out on my own....he may not take many leads but when he does it's special...otis forever!!
So true Jai, now Otis begins and ends this song in his traditional fashion............


text:
Thursday, May 17, 2012 12:00am by London Newsdesk
Behind-the-scenes footage of Lady Gaga's 'The Simpsons' episode emergesLady Gaga's cameo on the season finale of 'The Simpsons' is on the horizon and she has unveiled behind-the-scenes footage of her visit to the animated city of Springfield for her Little Monsters to check out. The pop icon's episode, entitled 'Lisa Goes Gaga', will premiere on Sunday, May 20 on FOX in the USA and in this new preview, Gaga can be seen recording her parts for the show along with talking about being asked to appear on the popular series. Creator of 'The Simpsons', Matt Groening, explained that the 'Marry The Night' superstar was fantastic to work with and said: "we ruined many takes by laughing out loud." Referring to the episode's plot, Gaga revealed: "I come to Springfield on a train with huge shoes on it and I come make the people of Springfield happy for a moment. Along the way, I run into Lisa. I decide it's my mission to pull Lisa out of her slump." Watch the exciting footage below: Latest 10 LADY GAGA News Stories


text:
Audra Cashmere Leather Sweater
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Our crewneck Audra sweater features edgy leather shoulder patch accents and a soft, long-sleeved cashmere silhouette in three fall-ready colorways, making it a closet essential for cool days.
- Crewneck. Long sleeves.
- Cashmere. Quilted leather patches at shoulders.
- Ribbed hemlines.
- Cashmere, leather. Dry clean. Imported.
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text:
Carvery Creations™ Beef Short Rib Flavor in a savory sauce
Carvery Creations™ celebrates everything you and your dog love about real meat: the cut, quality, cooking method and special touches.
- Prepared with real beef
- Marinated in a savory sauce
- Made with tender, pull-apart shreds that look as good as they taste
Nutritional Info
Where to Buy
Crude Protein (Min) .............. | 11.0% | Crude Fat (Min) .................. | 2.5% |
Crude Fiber (Max) ................ | 1.0% | Moisture (Max) ................... | 80.0% |
Chef Michael's Carvery Creations™ Beef Short Rib Flavor in a savory sauce is formulated to meet the nutritional levels established by the AAFCO Dog Food Nutrient Profiles for growth of puppies and maintenance of adult dogs.
Water sufficient for processing, beef, liver, wheat gluten, meat by-products, chicken, soy flour, corn starch-modified, artificial and natural flavors, added color, salt, calcium phosphate, potassium chloride, natural beef short rib flavor, choline chloride, calcium carbonate, zinc sulfate, Vitamin E supplement, ferrous sulfate, niacin, copper sulfate, thiamine mononitrate, manganese sulfate, calcium pantothenate, pyridoxine hydrochloride, Vitamin B-12 supplement, riboflavin supplement, Vitamin A supplement, potassium iodide, folic acid, Vitamin D-3 supplement, biotin, sodium selenite. A-5950
Please call 1-866-738-3663 Mon. – Fri., 7 a.m. – 7 p.m. CT for information on stores in your area that carry Chef Michael's® food for dogs, or contact us through our online form for a timely email response.


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If you think the drivers are tired, working those 12 hour shifts, think of how much stress the trucks are under going 24/7. The last couple of storms have dropped nearly a foot of snow in Salt Lake and this snow was heavy.
Jack Brown UDOT Roadway Operations Manager explained, "With 10 inches of snow, when you have 6 to 8 lanes wide, the end truck gets to push a lot of snow."
That takes a heavy toll on the equipment. Brown says almost every truck has been in the shop for some reason over the last two weeks.
"When we're not plowing snow we're trying to get our trucks back up and going that involves changing blades, changing tires, mechanical problems," said Brown. "Our mechanics are working around the clock to make sure we stay on the road for the traveling public."
With 400 lane miles, mostly covered in concrete, they can go through plow blades in a single 12 hour shift.
It's not just snow these UDOT crews have been dealing with; because of the recent inversion the freezing temperatures kept ice covering the roadways and crews working around the clock.
Brown said, "We're constantly using the trucks, running the sander, you're out and about the trucks are basically non-stop."
These trucks aren't cheap. They go for upwards of a $100,000. The oldest in the fleet, of course, needs the most care.
Brown said, "We have a 1996 and still going strong and the new guys drive that."
No matter how old the beasts may be, the crew knows to treat their machines with care.
"People depend on us to keep our equipment running and our guys take pride in what we take care of," said Brown.


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Chicago Rosas Lounge Hotels + Gay Friendly
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Topic Review (Newest First) |
shepherdmom |
Kahrg4 |
My husky, Finder, was a rescue and came from some pretty bad circumstances. He would submissively urinate every time anyone would approach him. But he was house trained otherwise. I realize your pup may not be quite as reactive as Finder was but here are some of the specific things I did to help him. Maybe have the guys in your life try some of these: 1. I started out by holding my palms out at my sides any time I would walk past him in the house. Note, I only walked past and did not approach him. I ignored all accidents and cleaned them up after he had skittered away. 2. I also spent a lot of time sitting on the floor completely ignoring him. Watched tv in front of the couch, read leaning up against my footboard, anything that would make me seem less big and looming. 3. When he finally started to approach me I held still and let him inspect without making any move towards him. Started with just a sniff and then backing away. Then two sniffs, then two sniffs and a look. Slowly it built up. 4. After he would approach with some regularity I started setting treats in my hand, laying my hand on the floor, and letting him come take them or not. I never moved my hand toward him and did not speak or try and entice him to take it. I just ignored it and him. At first he was suspicious, but eventually he did come take one. 5.When hand treats became a yummy happy thing I slowly introduced petting while he would take the treat. This part had to go very, very slowly. 6. During all this, I could never ever speak to him in anything but happy baby voice, never correct (didn't need to anyway), and never approach too quickly. 7. Lastly if he ever started to urinate while we were interacting I immediately ceased the activity and turned away from him. I only wanted our interactions to have positive connotations. Overly submissive behavior never equals treats, pets, or attention for Finder. It has been slow work (4+ months), an enormous exercise in patience and discipline for me, but it has paid off immensely. He can still be startled into an accidental piddle these days but otherwise has revealed himself to be the wonderfully sweet and playful pup I knew he could be. And boy is he a cuddle bug! This past week I've had some sort of flu/cold and been stuck in bed, Finder has been cuddled up next to me almost constantly. These dogs will make you wrack your brain and want to cry from the frustration of it all. But the little victories along the way are so sweet, and on that day when they finally let it all go and curl up to cuddle with you it makes all the messes, all the tiptoeing, all the work more than worth it. I wish you all the best with your boy. If you ever need to vent or if there is any way I can help feel free to pm me. |
wolvie1174 |
I appreciate all if the suggestions and they are in line with a lot of other things I have read. Not sure what his deal is but I wanted to catch and work on it as early as possible. The urinating has been an on and off thing for the last 5 months more off than on until the last 2 weeks and then the whole not coming when called thing just sprung up last night. He seemed ok later in the night but I have had little to no interaction with him since then because I am at work. My wife said he seems perfectly fine to her but he hasn't had any issue with him ever Sent from Petguide.com Free App |
MadLab |
Build up the dogs confidence through ball games, tug, cycling, swimming. Exercise it a lot. Avoid any aggressive movements towards him. When you walk in the room with the dog ignore it for a while. NO touch, no talk or eye contact for 5 minutes will take the pressure off the dog. He'll start to feel less like the center of attention. Ask you friends to do the same. Some of you might have been rough housing or correcting the dog and this started to happen. Don't feel sorry for the dog as it will simply get over it soon. Good not to even verbally correct the dog for a while. Use a gentle voice. Let the dog come to you rather than you going to it or calling it to you One dog i know who had this turned out to be fine. She grew out of it. |
Harbud |
On a personal note I am dealing with this in my 19mth old. He had a leg injury and lameness. He became fearful of the male vet who had checked him out twice and manipulated his leg. Ozzy built an immediate association after the first visit that this vet caused him discomfort and by the second follow up he was certain that all men would eat him alive. Bring in the submissive roll over and urination on site. I cant speak for your circumstance or what may have caused him to behave this way though. Presently the way I am handling it (Under guidance of my trainer) is to set up many interactions with males where they come up to him and touch him then feed him a treat then walk away. If he rolls over or urinates they walk away with no treat. If this happen then I come in and touch him on his body, treat him and walk away then the man comes back and attempt again. As quickly as he seemed to have learned to be fearful submissive he seems to have almost equally fast learned to be accepting of men again. We will do this for many months still to ensure he doesn't have any other 'scary' encounters that may cause him to revert back again. Not sure if that helps you at all, seems like you have started to do something similar already. It may be worth considering that he may also be in the middle of a fear period. |
wolvie1174 |
Yes he's been checked out and the vet said he is as healthy as can be. They are assuming it's just a submissive things and have suggested your typical solutions but I was hoping to find someone that's has had something similar. They seemed to give me generic tips and ideas Sent from Petguide.com Free App |
MaggieRoseLee |
Check him out medically like shepherdmom recommended... And if he's ok then you need to up YOUR game on the positive only training. If you aren't using tons of treats/toys and calm praise daily, then that's where you need to start. Plus if you are male with that deep voice, you need to know that just a normal tone may be off putting to him. There is a reason you hear all those Police officers and Military K-9 Trainers have that high pitched crazy happy tone in their voices. It's because the TONE of the voice is way more important than what the words are saying to our pups. Have you started up clicker training? It's a HUGE help to teach us how to train our pups properly. It forces us to reward with treats (and toys) frequently. It forces us to pay attention to whats going on. It makes us be PATIENT (hard for humans, we tend to want to MAKE our pups do something rather than wait for them to figure it out). Initial training has us not talk at all! So our tone won't mess up the dogs thought processes as we have to shut up while they figure it out. Have you seen this link? If you can read thru and start adding the ideas to your training you will be AMAZED at the changes in your relationship with your dog. Soft dogs ARE a challenge. But the good news is that 'soft' dogs make us much better dog owners and trainers. The link: http://www.germanshepherds.com/forum...s-puppies.html Good luck! |
shepherdmom | Have you had him checked for a bladder infection? | |
wolvie1174 |
Submissive urination Maize is a 9 month old Male German shepherd and he has on and off been showing signs of submissiveness to myself and my other male friends. He starts to pee(not much) when a male interacts with him. He stopped doing it for about a month and the just recently started it up again and last night wouldn't even come to me when he was called but instead looked as if he was scared of me. I finally went over to him and he once again started to pee. Not sure how to respond to this, I have been told to ignore it and work on being on hands with him and I have. I'm not sure what else to do, he has only ever had 1 accident in the house that wasn't related to this submissiveness so he seems to understand and have good bladder Attachment 125217control Sent from Petguide.com Free App |


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Pimlico People list all of the Pimlico education businesses and professional tutors in the Pimlico area. If you are looking for adult education, private tuition or music schools in Pimlico, Pimlico People have them all listed for your convenience. Be sure to check the reviews from our local users too!
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Washington, DC
5 Stars
I would recommend this item to a friend. |
Very Unique!!
December 20, 2012
I haven't worn them yet but I love the look for these sneaker wedges, I haven't seen these anywhere else so I'm excited. They do look a tad big so but hopefully once on they won't look super huge..


text: I stopped by The Jay Leno Show Tuesday night and as promised in my 10@10 interview, I just had to give Jay one of my favorite deserts and indulgent snacks… deep fried Oreos!! Guy Fieri helped Jay and I make them… I'm not too convinced by Jay's reaction after tasting them though!! Is he crazy!?


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Andrisoft WANGUARD is an enterprise-grade traffic monitoring and DDoS detection and protection solution that delivers the functionality NOC, IT, and security teams need to effectively monitor and protect their network through a single, integrated package. WANGUARD Sensor relies on sFlow, NetFlow, IPFIX, or Port Mirroring / SPAN.
Andrisoft WANSIGHT is a fully featured network traffic analyzer and collector. It provides in-depth traffic analysis, traffic accounting, and bandwidth monitoring, and enables you to generate complex traffic reports, graphs, and tops, instantly pin down the cause of network incidents, understand patterns in application performance, and make the right capacity planning decisions. It supports 10GbE packet sniffing and NetFlow, sFlow, and IPFIX.
Astaro Security Gateway (formerly Astaro Security Linux) is an all-in-one network security gateway that includes a firewall, intrusion protection, antivirus, spam protection, URL filtering, and a VPN gateway. Features include a modern packet filter, intrusion detection and prevention, portscan detection, application control, content filtering, virus detection for email and Web traffic, profile handling, L2TP, IPSec, SSL, and PPTP VPN tunneling, spam blocking, proxies for HTTPS, HTTP, FTP, POP3, SMTP, DNS, VoIP, SOCKS, and Ident, logging, and reporting. It supports Ethernet, VLAN, PPP, PPPoE, PPPoA, Cable Modem, IPv6, QoS, Link Aggregation, and WAN-Uplink-Load balancing in routing, and bridge mode. The WebAdmin GUI, Install Wizard, Change Tracking, Printable Configuration, and Up2Date service make it easy to install, manage, and maintain.
Borderline is a firewall generator. It takes a generic rule specification as input and generated an highly optimized firewall. It features IPv6 rule generation, support for multiple interfaces, and integrated support for network zones. It currently only supports firewall generation for Linux 2.6 (netfilter).
IP Tables State implements the "state top" feature from IP Filter for IP Tables. "State top" displays the states held by your stateful firewall in a "top"-like manner. Since IP Tables doesn't have a built-in way to easily display this information once, an option was added to iptstate to do this.
IPv6 CARE, "IPv6 Compliant Automatic Runtime Environment", provides an environment where applications instantly become IPv6-compliant ('patch' mode, see RFC6535). It can also generate a diagnosis about the IPv6 compliance of an application ('check' mode). It uses an LD_PRELOAD-based library injection technique.
RackTables is a tool to manage tens of racks, hundreds of servers, and thousands of MAC and IP addresses. It will work with a single rack as well. It features a real-life rackspace model, typed rack objects with flexible attribute sets, a tagging system, IP address management ready for NAT, virtual routers and load balancers, accurate network connection handling, a universal search function, a multi-user access model, and an extensible dictionary.


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Strong violence
Directors: | Ethan Coen, Joel Coen |
Actors: | Tommy Lee Jones, Javier Bardem, Josh Brolin, Woody Harrelson, Kelly Macdonald, Garret Dillahunt, Tess Harper, Barry Corbin |
The time is our own, when rustlers have given way to drug- runners and small towns have become free-fire zones. The story begins when Llewelyn Moss (Josh Brolin) finds a pick-up truck surrounded by a sentry of dead men. A load of heroin and two million dollars in cash are still in the back. When Moss takes the money, he sets off a chain reaction of catastrophic violence that not even the law - in the person of aging, disillusioned Sheriff Bell (Tommy Lee Jones) - can contain. As Moss tries to evade his pursuers - in particular a mysterious mastermind who flips coins for human lives (Javier Bardem) - the film simultaneously strips down the American crime drama and broadens its concerns to encompass themes as ancient as the Bible and as bloodily contemporary as this morning's headlines.
Status: | QuickPick |
Run time: | 121mins |
Origin: | UNITED STATES |
Aspect Ratio: | 16:9 |


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You're watching...
Finding Balance Between Gun Control and 2nd Amendment Rights
New York Post Columnist Michael Goodwin on the debate over gun control.
Dec 20, 2012
You're watching...
New York Post Columnist Michael Goodwin on the debate over gun control.
Dec 20, 2012
Also in this playlist...
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Auto-advanceThis transcript is automatically generated
-- -- My next guest says the president must act now on gun control.
Without touching the Second Amendment joining us now is Pulitzer Prize winning columnist Fox News contributor Michael Goodwin.
And -- party.
Your in your column you talked about that balancing act that seems all to me at least it seems all but impossible.
And that is to control guns without infringing upon the Second Amendment.
But a guy named President Obama has two challenges and and this the first is.
As someone else put it I give credit it is to take the maps out of mass murder I think that is what's scaring the country although the user.
-- fairly small number of the overall homicides in this country they are the ones that terrorize people as we saw in Connecticut the the ability to just target children just put took over the cliff now doing it -- music and small fraction.
We should point out is and small -- we're talking about point 00.
Right because we're talking must how many thousand that's right -- -- -- my -- There are roughly it -- -- from nine to 121000 a year dependent ranges -- -- not including suicide of course which are actually more pork.
So you you have this is small number of other hard horrible horrible crimes and I think that the taking the mass out of the mass murder.
Has to -- and already has dole.
This all sounds great and I don't think anybody anywhere in the country.
Would do anything but say I'm against.
Mass murder I'm against murder I'm agents violent death.
But what people are for is the freedom to choose.
Have a constitutional rights absolutely and I support and -- and as you pointed out.
I mean there's it's a fraction.
Yeah we're talking about most of the murders in this country are with one shot one victim one perpetrate.
And and the content and these laws that are being talked about or even be -- try to address -- -- Act and the guns that would be in -- involve the most murders are handguns that would be legal you know depending on the state law but.
They would they would not be under federal ban the one program would be very narrow targeted to the semiautomatic.
You know rifles in the and -- -- macho man in Russia in the congress -- watching right now trying to deal with us.
But again watching the president United States dealing with the fiscal issue.
The emotional content of this is over is created such -- reflexive.
Response on the part of leaders they can't help but Democrat again it's in their DNA to do so we understand -- But what we're talking about in this instance is really a young man who was mentally ill I I was talking with number of psychologist will continue to do so.
One of them would not even -- it is -- mental illness this young man's heart condition that there are some there's so much to talk about the the mental health.
Profession itself -- psychology and psychiatry.
As well as the need to -- to bring services and provide services to those desperately ill.
20% of us have a mental disorder of some kind in the course of -- year.
-- -- Look I mean from a well and there's -- pharmacology issues there's a confidentiality.
Issues there's -- the treatment itself.
Voluntary that's -- constitutional halts all kinds of privacy and freedom issues which is why I think that should be part to.
But what President Obama has to do -- has to be a consensus remember the old days -- we used to be -- in this country were Smart enough.
We were committed -- we were focused enough energetic enough.
We didn't have to -- do things sequentially but it have to have a part one part two part a part B at a -- have to have quote unquote comprehensive we have.
We we could it's a problem right -- their intellect and our values brought to bear.
It's -- a world.
That's it's -- around so well in enemy anyways it's a it's a better world tell me that things are more complicated in part because we have so many wonderful freedoms because we have science and technology that have made treatment options that were not available so.
Which we have to I think.
Bring our solutions up to date with our problems and that's where I think that's the larger conversation has to be aimed at the video game issue.
Right pharmacology and mental illness.
Sort of currency thank you thank you.
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text:
Forums >Off the Beaten Path>Tattoo Ideas
mileage hound
Yup, that's the link I posted, I was just keeping it a little more PG
2013 goals: Somehow get healthy again.
"If you want to be a bad a$s, then do what a bad a$s does. There's your pep talk for today. Go Run." -- Slo_Hand
"Determined is what I am. Maybe a little sick in the head? Ok who am I kidding ALOT sick in the head" -- rockenmamaof5
She's very courteous!
"I aim to misbehave."
I'll be back
Ah, sorry, missed that.
2014 goals: functional hamstrings < 2:55 at Napa < 24 at Western States
A half hour ago while in the subway, returning home from work, a man approached meand mumbled something incoherent.. No big deal. This happens all the time. What struck me was his tattoo. It read, "I hate my mom". It went right across his forehead.
I'm running somewhere tomorrow. It's going to be beautiful. I can't wait.
Poor baby
Interval Junkie --Nobby
If there's such a thing as a classy tattoo, that's it.
2013 Goals: 18:49 5K • 1:25 HM • sub-3 Marathon (3:04) • run lots of races • other delusions
Current Status 11/05: Basking in post-marathon glow . . . and pain.
finnegan begin again
"... the harder the conflict, the more glorious the triumph. What we obtain too cheap, we esteem too lightly: it is dearness only that gives every thing its value..." Thomas Paine Dec 23, 1776 The Crisis
Adversity is the first path to truth. Lord Byron
I stand corrected.
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Are Eva Mendes and Ryan Gosling thinking about that next step?
No, not marriage! The next next step! Kids!
The couple played parents on the set of The Place Beyond The Pines, and according to Eva, Ryan was a natural! She says:
"He's really good.
He loves babies and he loved playing with the little boy we used in the film to play our son. It was adorable to see him in that light."
"There's one intense scene in particular where everyone has been screaming, including the baby. The beauty of that scene comes when Ryan picks up the baby and he immediately quietens down and starts to fall asleep on him. That's just magical.
That happened a lot, too. We did a lot of takes and that was one of the most beautiful moments in the film, because babies don't act."


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- December 11, 2012
- 12:35 p.m.
- Suggest removal
- Reply to this post
Vegeta writes:
in response to SeatoSea:
Obesity is caused by a myriad of problems…sometimes linked to an emotional trauma, but not always. Lack of self-discipline (portion control), lack of physical activity, high fructose corn syrup and hydrogenated oils…All can be controlled. First the emotional issues must be addressed. Nobody can make someone eat healthy or exercise if they do not wish to do so. You can lead a horse to water, but you cannot make them drink. The obese person must be the one to make the choice to change. Life style/habits are a choice. As long as an obese person believes that they are a victim, they will never be able to lose the weight. Disclaimer: Yes I know; there are cases where obesity is caused by a medical condition…less than 1%. Not a valid argument for most people. Obesity is at its worse when it is in a child. Adults are able to make their own choices of what they put in their mouths or how active they are. When a child is obese it is only due to lack of parental guidance and supervision (granted the parent may believe they are doing what is best, or loving, or whatever-best of intentions I'm sure). The fact is, adults buy the food and control what is in the home or how active a child is. Poor eating habits are formed when a child is very young. These are behaviors of which a parent should be in control. Parents are not a child's best friend. Picky eaters are by and large created by their parents. Just because you do not like something does not mean your child will not. The first time a child refuses to eat something healthy and the parent buys McNuggets, the cycle begins. Every time there after, the behavior is reinforced. Junk food and fast food should be a rare special treat not a daily meal. Dessert is for a special occasion, birthday, graduation, holidays etc., not after every meal. When a child is allowed to become overweight their chance of illness is increased- risking an early death. Not to mention the challenges imposed on a young child's emotional and physical development. Making meals at home, from scratch, is the best way to eat as you are in control of ingredients and portions. Stay clear of processed foods with hydrogenated oils and high fructose corn syrup and GMOs. This can be done and does not need to be expensive. Be mindful of portion sizes. Use a smaller plate. Read all labels. The sooner people realize that they are in control of their own behaviors then they can make the changes required to better their life and health. Make small changes one at a time and gradually add healthier habits as you go. Get up and move. It doesn't have to be a lot. Just do it. Go for a walk in the morning and in the evening. Walking right after a meal helps increase metabolism and can have a carry-over effect in burning calories. Take responsibility for your health. You will feel better, look better and increase your chances of living longer. The cost of eating healthier will far offset the cost of your healthcare down the road. Nobody can do it for you.
I sure do wish they had a "like" button for C&P comments. Couldn't agree with you more.
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My stay at Hotel Breesen was just fine. The location is fantastic for people visiting the Bockenheim campus of the university; it's really just a stone's throw, and the walk to the U-Bahn was just two blocks. My room was fine - very clean and with everything advertised (except the free bottle of mineral water promised in the hotel's ad... More
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Orbitz, Cheap Tickets, Travelocity, Booking.com, Asiatravel.com Holdings, Hotels.com and Otel so you can book your The Breesen Hotel reservations with confidence. We help millions of travellers each month to find the perfect hotel for both holiday and business trips, always with the best discounts and special offers.


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Opposite the hot pools, and everything on your doorstep although rooms still very quiet. The owners are fantastic and can't do enough for you. They will give you advice on restaurants, and make you feel incredibly welcome.
- Also Known As:
- Glenalvon Hotel Hanmer Springs
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- TripAdvisor is proud to partner with Booking.com, Olotels and Agoda so you can book your Glenalvon Lodge Motel and B&B reservations with confidence. We help millions of travellers each month to find the perfect hotel for both holiday and business trips, always with the best discounts and special offers.


text:
Patients with diabetes have to keep a close eye on their blood sugar, and new technology might make that a little easier.
Normally diabetics have to carry around a separate glucose meter with them at all times, in addition to their phone, but smartphones can now double as a life-saving diabetes monitoring device. The Gmate app uses brand new technology to test blood sugar levels on your smartphone. It keeps track of all the results, and is even capable of emailing the results to your doctor.
James Winchester, who is diabetic, travels around the country demonstrating how to turn phones into blood glucose meters.
"Diabetics have to carry around a lot of stuff. The great thing about smart phone technology is it's one less thing they now have to carry," says Winchester.
Since your cell phone is basically a hand held computer, the app keeps track all your results, and charts out your blood sugar results over time. You can instantly email all these results to your doctor or family members.
Pediatric endocrinologist Kevin Kaiserman says this is just one of many advances that uses new technology to help people manage their diabetes.
"The greatest advantage is to help people gather, and be able to synthesize, analyze the information in a way that helps them not just have a single piece of information but to look for trends and analyze over time how their diabetes is being managed, where they can make adjustments to better manage their diabetes going forward," says Kaiserman.
Right now the Gmate only works with iPhone, not Android phones.
It's already in use in Europe and is currently pending FDA approval here in the USA.
(Information courtesy NBC News)


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Gotta admit that I was considering RBBlitz primarily for the extra RB3 songs in one easy download (although I'm sure I'd try out the actual Blitz game, too). As the song list was revealed, "One Week" was the standout, since I've been wanting it for a long time.. the rest, though.. well.......
But Spoonman???? Seriously???? AWWWWWW YEEEAAAAAHHHHH, that made it an insta-buy. Spoonman was the one song that everyone in my RB group loved to play. Drums, bass, guitar, vocals... everyone just dug playing it and it got into the setlist at every party.
The prospect of adding keys and (maybe) harmony vocals just upped it even farther.
Also, Give it Away for the vocals - the rest of the group hates it, especially the drummer.
Good call, HMX! I'd have gladly paid the $15 just for Spoonman and One Week, so now I feel like the rest of the songs are a "but wait, look what else you get!" bonus.