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October 18, 2006
STEVEN WHEATLEY, PETITIONERv.EDWARD KLEM, ET. AL, RESPONDENTS
Magistrate Judge Blewitt
The Petitioner, Steven Wheatley ("Petitioner") an inmate incarcerated at the State Correctional Institution at Mahanoy filed this pro se Petition for Writ of Habeas Corpus ("Petition") pursuant to 28 U.S.C. § 2254. In the Petition, Petitioner challenges his March 9, 2001 conviction in the Monroe County Court of Common Pleas with respect to his shooting of a police officer victim on three grounds; (1) insufficient evidence to support attempted criminal attempt to commit murder and aggravated assault convictions; (2) ineffective assistance of trial counsel in failing to adequately investigate and obtain forensic testimony; and (3) ineffective assistance of trial counsel in failing to request an appropriate jury instruction. (Rec. Doc. 1 at 6-9).
The case was referred to United States Magistrate Judge Thomas M. Blewitt.*fn1 Thereafter, on September 20, 2006, Magistrate Judge Blewitt issued a Report and Recommendation (doc. 15) recommending that the Petition for Habeas Corpus be denied with respect to its three claims. The Magistrate Judge further recommended that the Petitioner's Motion for Leave to Conduct Discovery and for Appointment of an Expert (doc. 12) be denied because no further information is required to decide Petitioner's habeas claims.
Objections to Magistrate Judge Mannion's report were due by October 6, 2006. On September 29, 2006, Petitioner filed objections to the report. (Rec. Doc. 16). The matter is therefore ripe for our review.
When objections are filed to a report of a magistrate judge, we make a de novo determination of those portions of the report or specified proposed findings or recommendations made by the magistrate judge to which there are objections. See United States v. Raddatz, 447 U.S. 667 (1980); see also 28 U.S.C. §636(b)(1); Local Rule 72.3l. Furthermore, district judges have wide discretion as to how they treat recommendations of a magistrate judge. See id. Indeed, in providing for a de novo review determination rather than a de novo hearing, Congress intended to permit whatever reliance a district judge, in the exercise of sound discretion, chooses to place on a magistrate judge's proposed findings and recommendations. See id., see also Mathews v. Weber, 423 U.S. 261, 275 (1976); Goney v. Clark, 749 F.2d 5, 7 (3d Cir. 1984).
On March 9, 2001 Petitioner was found guilty, by a jury, in the Court of Common Pleas of Monroe County, Pennsylvania, of attempted homicide and related charges, namely aggravated assault and reckless endangerment with respect to his shooting of Police Officer Rice. The Court also found the Petitioner guilty of possession of a firearm by a former convict. On April 11, 2001, the Petitioner was sentenced to an aggregate term of fifteen to thirty years incarceration.
On April 23, 2001, Petitioner filed a post-sentence motion raising several issues regarding his finding of guilt and sufficiency of the evidence against him. On June 4, 2001, Petitioner also filed a motion challenging his sentence. The trial court denied these post-sentence motions on June 29, 2001.
On July 24, 2001, the Petitioner filed a direct appeal of his judgment of his sentence with the Superior Court of Pennsylvania. The Superior Court affirmed the Petitioner's conviction on August 16, 2002. On September 15, 2002, the Petitioner filed a Petition for Allowance of Appeal with the Pennsylvania Supreme Court, which the Supreme Court denied on August 26, 2003.
On April 22, 2004, the Petitioner filed a pro se Petition for Post Conviction Relief Act ("PCRA") with the Court of Common Pleas. Counsel was appointed to represent Petitioner relative to his PCRA petition. On October 13, 2004, Petitioner, through his counsel, filed an amended PCRA petition, limiting his ineffective assistance of counsel claims to four issues, including the two ineffective assistance of counsel claims included in the present Petition.
The Court of Common Pleas denied the PCRA petition on February 17, 2005. The Petitioner appealed to the Superior Court of Pennsylvania on March 3, 2005, and the Superior Court affirmed the Court of Common Pleas's "excellent" decision on October 27, 2005. (Rec. Doc. 5, Ex. 9). On November 15, 2005, the Petitioner filed a Petition for Allowance of Appeal with the Pennsylvania Supreme Court, which the Supreme Court denied on May 25, 2006. The current Petition was filed on June 19, 2006.
A. Magistrate Judge's Summary of Standard of Review
Magistrate Judge Blewitt begins his analysis of the merits of Petitioner's Petition by summarizing the standard of review for challenging state convictions under the Antiterrorism and Effective Death Penalty Act ("AEDPA").*fn2 For purposes of completion, we shall reiterate the Magistrate Judge's summary.
"Section 2254(d), as amended, states as follows:
(d) An application for writ of habeas corpus on behalf of a person in custody pursuant to the judgment of a State court, shall not be granted with respect to any claim that was adjudicated on the merits in State court proceedings unless the adjudication of the claim --
(1) resulted in a decision that was contrary to, or involved an unreasonable application of, clearly established Federal law, as determined by the Supreme Court of the United States; or
(2) resulted in a decision that was based on an unreasonable determination of the facts in light of the evidence presented in the State court proceeding.
The "contrary to" provision contained in Section (d)(1) is evaluated as follows:
[T]he inquiry must be whether the Supreme Court has established a rule that determines the outcome of the petition. Accordingly, we adopt O'Brien's holding that 'to obtain relief at this state, a habeas petitioner must show that Supreme Court precedent requires an outcome contrary to that reached by the relevant state court.' In other words, it is not sufficient for the petitioner to show merely that his interpretation of Supreme Court precedent is more plausible than the state court's; rather, the petitioner must demonstrate that Supreme Court precedent requires the contrary outcome.
Matteo v. Superintendent, SCI Albion, 171 F.3d 877, 888 (3d Cir. 1999)(citing O'Brien v. Dubois, 145 F.3d 16, 24-25 (1st Cir. 1998). The appropriate standard for the "unreasonable application clause is: whether the state court's application of Supreme Court precedent was objectively reasonable. The federal habeas court should not grant the petition unless the state court decision, evaluated objectively and on the merits, resulted in an outcome that cannot reasonably be justified under existing Supreme Court precedent . . . The primary significance of the phrase 'as determined by the Supreme Court of the United States' is that federal courts may not grant habeas corpus relief based on the state court's failure to adhere to the precedent of a lower federal court on an issue that the Supreme Court has not addressed.
Thus in certain cases it may be appropriate to consider the decisions of inferior federal courts as helpful amplifications of Supreme Court precedent.
Matteo, 171 F.3d at 889-890. Further, as the Third Circuit stated in Beneshunas v. Klem, C.A. No. 04-2469, June 30, 2005, 2005 WL 1532441 (3d Cir.), slip op. p. 7 (Non-precedential), a writ under §2254(d)(2) may also be granted "if the state court decision was based on an objectively unreasonable factual determination." (internal citations omitted).
Section (d)(2) contains the presumption of correctness provision which greatly heightens the degree of deference paid to a state court's findings of fact. The burden is on the Petitioner to rebut the presumption by clear and convincing evidence. 28 U.S.C. § 2254(e)(2)(B).*fn3
The standard of review for claims pursuant to the AEDPA has also been stated in Lewis v. Johnson, 359 F.3d 646, 652 (3d Cir. 2004):
The AEDPA "modifie[d] the roles of federal habeas courts in reviewing petitions filed by state prisoners." Williams v. Taylor, 529 U.S.362, 403 (2000). "[W]e are to review the state court's determinations on the merits only to ascertain whether the court reached a decision that was 'contrary to' or an 'unreasonable application' of clearly established Supreme Court law, or whether it made an 'unreasonable determination' of the facts." Marshall v. Hendricks, 307 F.3d 36, 51 (3d Cir. 2002). "[T]he determination whether or not a rule is clearly established at the time a state court renders its final judgment of conviction is a question as to which the 'federal courts must make an independent evaluation." Williams, 529 U.S. at 382 (quoting Wright v. West, 505 U.S. 277, 305 (1992). The AEDPA does, however, confine the authorities on which federal courts may rely in making this determination to the decisional law of the Supreme Court, that is the "Federal law, as determined by the Supreme Court of the United States."
Id. at 381-382 (quotation omitted).
In Early v. Packer, 537 U.S. 2 (2002), the Court indicated that as long as the state court adjudicates a claim substantively rather than procedurally, even if the federal law is not identified as the rule of the decision, it has adjudicated the claim on the merits for the purposes of the AEDPA." (Rec. Doc. 15 at 6-9).
B. Merits of the Petition
1. Claim One: Insufficient Evidence to Support Attempted Murder and Aggravated Assault Convictions
Petitioner objects to the standard of review applied by Magistrate Judge Blewitt to his sufficiency of the evidence claim. In particular, Petitioner alleges that Magistrate Judge Blewitt should have applied the standard of review for habeas claims brought pursuant to §2254(d)(2) espoused in Breighner v. Chesney, 301 F. Supp. 2d 354 (M.D. Pa. 2004)(Connor, J.)(aff'd Breighner v. Chesney, 156 Fed Appx. 539 (3d Cir. 2005)).
In Breighner, the district court held that §2254(e)(1), which states: In a proceeding instituted by an application for writ of habeas corpus by a person in custody pursuant to the judgment of a State court, a determination of a factual issue made by a State court shall be presumed to be correct. The applicant shall have the burden of rebutting the presumption of correctness by clear and convincing evidences does not apply to §2254(d)(2). The district court held that "[t]he federal habeas court's analysis under this subsection is limited to the record available to the state trial court . . . and encompasses two questions: (1) whether a factual determination of the state court was "unreasonable" in light of the state record, and (2) whether the state court's decision was "based" on that unreasonable determination. Id. at 368. Moreover, the district court held that "a factual determination should be adjudged "unreasonable" under paragraph (2) only if the court finds that a rational jurist could not reach the same finding on the basis of the evidence in the record.
A review of the Magistrate Judge's report reveals that he indeed applied subsection (e)(1) to subsection (d)(2) despite the holding of Breighner. Accordingly, because the standard has since evolved, we find it incumbent upon the Court to apply the Breighner standards to Petitioner's sufficiency of the evidence claims. Because we find that Magistrate Judge Blewitt, who is more intimately familiar with the complexities of the record than we are, is in a better position to undertake the necessary analysis under Breighner, we shall remand this issue for his consideration. It may well be that an analysis of Petitioner's claims under Breighner will lead the Magistrate Judge to the same result, however, in the interests of justice and caution, we shall remand the issue for the Magistrate Judge's analysis.
The Petitioner also objects to the portion of the Magistrate Judge's report that quotes the Superior Court's opinion, stating that Officer Vacarro sprayed the Petitioner in the face with pepper spray. Petitioner notes that the Magistrate Judge misquoted the Superior Court's opinion in that that Officer Rice, the victim of the shooting, in fact "emerged from a secreted position to shock and awe Petitioner by spraying mace directly into Petitioner's face. This distinction is important." (Rec. Doc. 16 at 1). The Magistrate Judge did, in fact, misquote the Superior Court's opinion. (Rec Doc. 15 at 12; doc. 5, Ex. 2 at 3).
Despite Petitioner's allegation that the distinction of whom sprayed him with pepper spray is an important one, we disagree. It is of no moment to the Magistrate Judge's analysis which officer actually sprayed the mace into the Petitioner's face, because Petitioner's theory of accidental or involuntary shooting does not depend on which individual sprayed him with pepper spray. Therefore, regardless of whether Magistrate Judge Blewitt misquoted the Superior Court's opinion, he did not appear to rely on the misquoted fact. However, inasmuch as this claim will be remanded for the Magistrate Judge's analysis, he will have an opportunity to correct the misquoted portion of the Superior Court's opinion, or clarify for the record that Officer Rice, not Officer Vacarro, deployed pepper spray upon the Petitioner.
2. Claim Two: Ineffective Assistance of Trial Counsel in Failing to Adequately Investigate and Obtain Forensic Testimony
Petitioner objects to Magistrate Judge Blewitt's recommendation that this Court deny his ineffective assistance of counsel claim based upon his allegation that trial counsel was ineffective by failing to adequately investigate and obtain forensic testimony. Specifically, Petitioner alleges that if proper forensic testimony had been obtained, it would have shown that the center-mass of the shotgun discharge "widely missed" Officer Rice, raising an inference that Petitioner did not shoot Officer Rice intentionally.
As noted by the Magistrate Judge, Strickland v. Washington, 466 U.S. 668, 687 (1984) lays out a two-part test to determine whether trial counsel was ineffective. First, a petitioner must show that trial counsel's performance fell below an objective standard of reasonableness under the prevailing professional norms. In order to prove trial counsel was deficient, a petitioner must show that "counsel made errors so serious that counsel was not functioning as the 'counsel' guaranteed the defendant by the sixth amendment." Id. Furthermore, the court is to grant deference to trial counsel in evaluating his performance. Id. With respect to the second prong, a petitioner must show that the deficient performance so prejudiced the defense that the defendant was deprived of a fair trial. Id. Accordingly, a petitioner must show that but for the deficient performance of trial counsel, there would have been a reasonable probability of a different outcome. Reinert v. Larkins, 2004 WL 1774593, *17 (3d Cir. 2004).
Petitioner's trial counsel testified at Petitioner's PCRA hearing that he contacted three ballistics experts prior to Petitioner's trial. Counsel testified that he was told by one expert that he could not testify regarding the projectory in the Petitioner's case because it was a close range shooting with a shotgun. As aforementioned, the theory of Petitioner's defense was that the shooting was accidental and not intentional, and Petitioner's belief was that a ballistics expert's testimony could raise an inference that Petitioner did not intend to shoot Officer Rice due to the location of the gunshot wound and the scattering of the shotgun pellets.
We agree with Magistrate Judge Blewitt's holding that Petitioner cannot and did not show that his counsel's performance was deficient with respect to failure to call a ballistics expert. Counsel testified that he did in fact contact ballistics experts and discuss the facts of Petitioner's case with them. As noted, counsel further testified that he was told by an expert that due to the nature and proximity of the shooting, testimony to support Petitioner's theory could not be produced. Based upon trial counsel's testimony, we cannot find his failure to call a ballistics expert to be objectively unreasonable. It is apparent that trial counsel took the necessary steps to determine whether a ballistics expert's testimony could support the defense theory of the case. When trial counsel was informed that no such testimony could be rendered, his decision not to call a ballistics expert was reasonable in light of the circumstances. We thus cannot find that trial counsel's performance was deficient in this regard, and accordingly, we will adopt the Magistrate Judge's recommendation that Petitioner's ineffective assistance of counsel claim with respect to forensic testimony be denied.*fn4
3. Claim Three: Ineffective Assistance of Trial Counsel in Failing to Request an Appropriate Jury Instruction
Petitioner objects to Magistrate Judge Blewitt's recommendation that this Court deny his ineffective assistance of counsel claim based upon his allegation that trial counsel was ineffective by failing to request an appropriate jury instruction. Petitioner alleges that his action of shooting Officer Rice was involuntary, and that counsel should have requested a jury instruction addressing the same. Therefore, Petitioner alleges that Magistrate Judge Blewitt's analysis regarding trial counsel's failure to request a jury instruction for homicide by misadventure or self-defense fails to address the nature of his third habeas claim.
Although not precisely stated, a review of Petitioner's Petition and brief in support of his Petition (docs. 1 and 4) indicates that he claims counsel was ineffective by failing to request a jury instruction regarding involuntariness. In his Petition, Petitioner cites as ground three for his claim that "[t]rial counsel rendered ineffective assistance when he failed to request an appropriate jury instruction. There was no reasonable basis for counsel's failure to request an appropriate and meritorious jury instruction which would have guided jurors in the relevant law toward a correct evaluation of the defense case/testimony." (Rec. Doc. 1 at 8).*fn5
While the language found in the Petition is broad, in his brief, Petitioner specifically cites a case dealing with the failure of counsel to request a charge regarding the involuntariness of the defendant's actions. (Rec. Doc. 4 at 16-18); See Commonwealth v. Fierst, 620 A.2d 1196 (Pa. Super. 1993).
Inasmuch as the Report and Recommendation does not address trial counsel's alleged ineffectiveness regarding the failure to request an involuntariness instruction, in the interest of caution and completeness, we also find it prudent to remand this issue to the Magistrate Judge for his consideration. As aforementioned, the Magistrate Judge is better suited to dispose of this issue than are we, due to his familiarity with the case and issues at hand.
1. The Report and Recommendation (doc. 15) is ADOPTED to the following extent:
a. Claim Two of the Petition, Ineffective Assistance of Counsel in Failing to Adequately Investigate and Obtain Forensic Testimony, is DENIED.
b. Petitioner's Motion for Leave to Conduct Discovery and for Appointment of an Expert (doc. 12) is DENIED.
2. Claims One and Three are remanded to the Magistrate Judge for the reasons cited herein.
3. The Magistrate Judge shall issue a further Report and Recommendation in conformity with this Memorandum and Order on Claims One and Three.
John E. Jones III United States District Judge
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Send Back My Heart
Gary AllanBuy this song
By now I really should be over you But I might as well just give up tryin` You've got what's missin` deep inside me And I want it back, girl you know it's mine [Chorus] Send back my heart if you don't want it Send back my heart girl, the one you stole away You've made it plain, your names not on it S don't put me through one more blue and lonely day Send back my heart I've found somebody else wants my love But I can't give her what she needs The very thing she's wantin` still ain't mine to give So won't you let it go, please baby please I've tried to forget you girl just like you told me to But baby that's impossible, so now it's up to you
Written by: GEORGE DUCAS, JOHN DAVID
Lyrics © Universal Music Publishing Group
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"Send Back My Heart Lyrics." Lyrics.com. STANDS4 LLC, 2016. Web. 3 Dec. 2016. <http://www.lyrics.com/lyric/1354186>.


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Americans are expected to spend $47.7 billion on their pets this year, up by $10 billion in just five years. APPA President Bob Vetere said many people treated their pets "in human terms" and pay for indulgences such as designer clothing, strollers and spa treatments.
Full Story:Connecticut Post (Fairfield County-Bridgeport)


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Ted Vaill: The Bush tax cuts decreased the top personal income tax rate from 39.6% to 35%. A hypothetical millionaire who had $1,000,000 in adjusted gross income in each of the past 10 years benefitted by over $200,000. It is time for payback. Do it.
Republican "Bubble" — Yet to Pop
Joseph Palermo: The rubbish that House Speaker John Boehner and other congressional Republicans keep dishing out about the federal budget shows the multimedia "bubble" that envelops the GOP and its mouthpieces is pretty durable.
Why Austerity Economics Hurts Low-Wage Workers the Most
Robert Reich: encouraged by the economic recovery and perhaps also by the election returns, low-wage workers have started to organize.
America's Real Religion
Lawrence Wittner: The recently-concluded Black Friday provided the occasion not only for an orgy of consumer spending, but for ferocious action by screaming mobs of shoppers who engaged in mass riots in their desperate attempts to obtain a variety of products.
Walmart: Discounting Lives to Maximize Profits
Walter Brasch: Imitating Sgt. Schultz of "Hogan's Heroes," Walmart executives claimed they knew nothing—NOTHING—about working conditions in a garment factory in Bangladesh where 112 workers died and more than 150 were injured in a fire.
Bungee-Jumping Over the Fiscal Cliff
Robert Reich: Excuse me for sounding impertinent, but isn't this fear-mongering likely to buttress Republican arguments that the Bush tax cuts should be extended for everyone — including the rich?
Fiscal Cliff: Wall Street's Latest Scam
RJ Eskow: The CEOs of America's largest corporations have banded together to lecture us on the importance of debt reduction. And despite their lack of qualifications and their very obvious self-interest, the media can't get enough of them.
Blame Politicians for Homelessness and Hunger in America
Randy Shaw: While the media's highlighting "the unfortunate" during the holiday season raises vital private donations to help their needs, letting the politicians responsible off the hook perpetuates the crisis.
Wall Street Agitates for Social Security Cuts
Richard "RJ" Eskow: On the same day that Goldman Sach's CEO issued his "balanced" demand for Social Security and Medicare cuts, a Wall Street-funded group published a poll precisely reflecting the wishes of Goldman Sach's CEO. Coincidence? I report, you decide.
Taxpayers Should Stop Subsidizing Walmart
Tina Dupuy: Since Walmart, the largest private employer in the country, generally doesn't pay its "associates" or "Walmart family members" enough to live on – the giant multi-national corporation is relying on the U.S. government to feed its employees.
Boycott Black Friday: Walmart Edition
Lauren Windsor: Apparently the good life does not extend to Wal-Mart's workers–half of the company's one-million American hourly employees earn less than $10 per hour.
Can Democrats Fix California?
Dotty Lemieux: All is not gloom and doom for the Golden State after all. And if we tackle the inequities in Proposition 13, especially the ones favoring the largest corporate abusers, the outlook could become all the more rosy.
Stop Obsessing About the Budget Deficit
Robert Reich: I wish President Obama and the Democrats would explain to the nation that the federal budget deficit isn't the nation's major economic problem and deficit reduction shouldn't be our major goal.
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|Publication number
|Publication type
|Application number
|Publication date
|Sep 4, 1984
|Filing date
|Jan 10, 1983
|Priority date
|Jun 23, 1981
|Fee status
|Publication number
|Thomas L. Schulte
|Original Assignee
|Schulte Thomas L
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (2), Referenced by (20), Classifications (4), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a continuation-in-part of application Ser. No. 276,566, filed June 23, 1981, now U.S. Pat. No. 4,369,190.
This invention relates to novel topical analgesic compositions and to their use to alleviate deep pain and debriding wounds and enhancing the healing thereof.
The treatment topically of deep or intractable pain, i.e., pain non-responsive to local anesthetics, with analgesics historically has not met with significant success, primarily because the surface presented by the affected area, typically skin or mucous membrane, provides an effective barrier to the analgesic agent reaching the situs of the pain. Therefore, physicians must resort to injections to achieve absorption of the analgesic, which usually also requires that the analgesic agent be in a vehicle which retards the rate of absorption, or to the oral administration of systemic analgesic agents, such as the barbituates. Both of these approaches have obvious limitations and pose well-known problems. There therefore is a long standing need for an effective topical analgesic agent which is effective in ameliorating localized deep or intractable pain and can safely be applied to the situs of the pain by the person in pain.
The compositions of this invention comprise biphenamine (β-diethylaminoethyl 3-phenyl-2-hydroxybenzoate) base or pharmaceutically acceptable acid addition salt thereof. Salts of this compound are known to have a variety of activities, including local anesthetic (U.S. Pat. No. 1,976,922); treatment of seborrhea (U.S. Pat. No. 3,123,531); as well as antihistaminic and bactericidal activity and fungicidal properties (U.S. Pat. No. 2,594,350; Report Annual Meeting So. Med. Assoc., Nov. 6, 1961).
Biphenamine hydrochloride has been sold as a 1% ointment, under the trademark "Melsaphine," as a topical anesthetic agent possessing bactericidal, fungicidal and antihistamine properties and as a 1% aqueous shampoo under the trademark "Alvinine," Federal Register, Vol. 34, No. 189, page 153, Oct. 2, 1969. See also U.S. Pat. No. 3,123,531.
Although its use orally or subcutaneously for treating arthritis and related conditions is claimed in U.S. Pat. No. 4,073,897, nothing was known concerning its topical analgesic activity or its usefulness for the treatment of localized deep or intractable pain because the compound is ineffective for ameliorating deep or intractable pain by the topical application thereof, in the absence of a tissue penetrant.
The compositions of this invention also comprise an amount of a skin penetrant, e.g., DMSO (dimethyl sulfoxide) or propylene glycol, which by itself has no analgesic activity or debriding or wound healing enhancement effects. U.S. Pat. Nos. 3,551,554 and 3,711,602 disclose that DMSO is effective as an agent for enhancing tissue penetration of physiologically active agents. U.S. Pat. No. 3,549,770 discloses (Example 36) the topical application of a mixture of acetylsalicylic acid and DMSO is more effective than DMSO alone to relieve the pain and muscle spasm of rheumatoid spondylitis. See also U.S. Pat. Nos. 3,711,602; 3,711,606; and 3,743,727 and references cited therein. These patents disclose that the tissue penetration of physiologically active compounds, inter alia, steroidal agents and certain antimicrobial agents, can be enhanced by DMSO. U.S. Pat. No. 3,740,420 discloses DMSO compositions for topical administration containing thickening agents.
The foregoing patents disclose that concentrations of DMSO of 10% by weight and above can effect penetration of such agents through various mucous membrane barriers and that concentrations of 50% by weight and above are effective to achieve penetration thereof through the skin. DMSO is also known to enhance the antiperspirant activity astringent of aluminum, zinc and zirconium salts (U.S. Pat. No. 3,499,961).
DMSO has been disclosed as useful for treating a variety of pathological conditions. U.S. Pat. No. 3,549,770 discloses topical application as a particularly advantageous route. This patent claims methods of relieving the signs and symptoms of tissue inflammation; of vascular insufficiency in the blood and lymph circulatory system; of respiratory distress; of arthritis and a method of promoting tissue repair, by administering an effective amount of DMSO, preferably topically. Dosages as low as 0.01 g/kg and up to 1.0 g/kg per day and sometimes higher dosages are contemplated with 0.1-0.2 g/kg individual doses being average. Higher concentrations of DMSO, such as at least 25% and more often at least about 50% are preferred for topical application. Treatment of pain with such solutions of DMSO, preferably by direct application to the involved area, is expressly contemplated. In one example (Example 27) the pain associated with skin abrasion was relieved with 15% DMSO in isotonic saline. 10% to 90% water solutions of DMSO, preferably 20% to 40%, in water, alcohol or glycerine are useful for topical application to the mucous membranes of the body although ". . . lower concentrations of DMSO say down to 3% by weight may be useful in some instances."
The use of DMSO as an ataratic agent is disclosed in U.S. Pat. No. 3,790,682. Pharmaceutical compositions containing DMSO and thickening agents are disclosed in U.S. Pat. No. 3,740,420, along with their use to treat and repair damaged tissue, as an anti-inflammatory agent, as an analgesic agent, as a muscle relaxant, as an agent for treating vascular insufficiency, and relieve the signs and symptoms of certain specific syndromes, viz., respiratory distress, arthritis and burns. None of the foregoing references disclose or suggest that intractable pain can be treated with low concentrations of DMSO, e.g., topically on the skin at concentrations below 10%, although U.S. Pat. No. 3,549,770 discloses (Col. 10, lines 42-49) that for pharyngitis or hiccups, the subject may gargle with a more dilute aqueous solution, e.g., containing 1% or preferably 10% by weight of DMSO, and (Col. 28, lines 44-56) that concentrations of DMSO down to 3% by weight may be useful in some instances, with 10% to 90% water solutions being particularly suitable. The effectiveness of DMSO topically for treating pain at concentrations below 10% by weight is not suggested in the prior art. Moreover, I have found that low concentrations of DMSO alone have little if any effect topically upon intractable pain. Propylene glycol has no analgesic activity at any concentration.
In a method of use aspect, this invention relates to a method for amelioration of deep pain which comprises applying topically proximate the situs of the pain an analgesically effective amount of an aqueous mixture of biphenamine and a water soluble topically acceptable skin penetrant in a pharmaceutically acceptable carrier, the concentrations of biphenamine and skin penetrant in the mixture each being ineffective to ameliorate the pain when applied separately from the other to the situs.
In a composition aspect, this invention relates to an analgesic composition adapted for topical administration and comprising an aqueous mixture of biphenamine and a topically acceptable skin penetrant in a pharmaceutically acceptable carrier, the concentrations of biphenamine or salt thereof and the skin penetrant in the composition being collectively effective to render the composition capable of ameliorating intractable pain when the composition is applied topically proximate the situs of intractable pain but ineffective for either component of the composition to do so in the absence of the other.
The aqueous mixture of biphenamine (basc or acid addition salt thereof) and the skin penetrant are applied topically to the patient proximate the suits of the deep pain, viz., to the skin and/or the mucous membrane of the mouth, throat, nasal passages, ear canals and drums, anal or vaginal regions, bladder or urethra, as a mixture in a pharmaceutically acceptable carrier or diluent, preferably aqueous. The mixture preferably is liquid, e.g., in the form of clear solutions, such as drops, aerosols or sprays, or in the form of lotions or other viscous aqueous liquids. The mixture can also be semi-solid or solid, e.g., in the form of ointments, creams, suppositories. Viscosity regulating agents, such as thickeners and gelling agents, e.g., glycerin, sodium carboxymethyl-cellulose, etc., can also be used to regulate flowability. See U.S. Pat. Nos. 3,740,420 and 3,711,602, whose disclosures are incorporated herein by reference. Propylene glycol itself is useful as a viscosity raising agent. They can be in the form of an oil-in-water or water-in-oil emulsion, as disclosed in U.S. Pat. No. 3,740,420, or as a single phase aqueous solution, the latter being preferred. Organic solvents, e.g., ethanol or isopropanol, can also be present.
The skin penetrant is present in the mixture at a concentration of at least about 1% which is not analgesic topically in the absence of the biphenamine. DMSO is employed at concentrations of less than 10%, e.g., 3-7%, preferably about 5%. At these concentrations, DMSO exhibits neither the analgesic effect achieved when it is applied to the skin in the absence of the biphenamine nor the side effects observed at higher concentrations, e.g., skin rash. Propylene glycol is employed at concentrations of about 1% to 90%, preferably about 5% to 15%, more preferably about 10%. Propylene glycol has desirable emollient and thickening qualities, which therefore makes it preferable in some formulations and with some patients.
The biphenamine is present in the liquid mixture at a concentration of up to 1% by weight, e.g., from about 0.1% to 1%, except for instillations, where lower concentrations of about 0.001 to 0.01% should be employed, preferably present in the form of a pharmaceutically acceptable salt thereof, e.g., hydrochloride, hydrobromide, sulfate, phosphate, acetate, succinate, tartrate, benzoate, citrate, lactate or maleate, preferably the hydrochloride. Although acid addition salts of biphenamine are disclosed in U.S. Pat. No. 1,976,922 as having local anesthetic activity at a 2% concentration, neither its ability to ameliorate localized intractable pain when applied topically nor its effectiveness on the skin for any purpose at lower concentrations is suggested.
The mixture of biphenamine and skin penetrant can be applied topically as frequently as every hour or as infrequently as daily or longer, depending on the degree of amelioration of the pain achieved with each application and the duration thereof. In the case of burns, it is desirable to apply the mixture promptly after the burn occurs and on successive occasions thereafter, e.g., once every 2-12 hours for 2-14 days or until the burn is healed.
The amount of the mixture applied will depend on such factors as the level and nature of the pain, the degree of localization thereof, the concentration of biphenamine and skin penetrant therein and the individual's responsiveness to analgesics generally. As little as two or three drops may be effective and as much as a fluid ounce may be required. The effectiveness of successively greater or smaller dosages can determine the optimum effective individual dose. The mixture can be applied to small areas with an eye dropper or a piece of cotton and to larger areas as a spray or aerosol or with a surgically gloved hand.
The compositions of this invention are effective for the amelioration of deep pain, i.e., pain non-responsive to local anesthetics, e.g., structural pain associated with influenza and other infectious diseases, arthritis, bursitis, tendonitis, trauma pain, e.g., strains, such as pulled muscles, and sprains, and other forms of intractable pain, i.e., pain which is substantially non-responsive to non-sedating systemic analgesics such as aspirin, phenacetin and acetaminophen. The method of this invention is useful for the treatment of localized intractable pain resulting from a wide variety of pathological conditions, e.g., severe sprains, debriding wounds, degenerative disc syndrome, bursitis and severe thermal or traumatic burns. From clinical observations, when a composition of this invention is applied to the affected area promptly after a skin burn and on successive occasions thereafter, not only is pain ameliorated or eliminated, the healing process is facilitated, apparently by the suppression of the inflammatory response and infection. The compositions of this invention are also useful for the amelioration of pathological conditions of the skin and other topical areas of the body caused by viral, bacterial, fungal and other microorganism infections and localized inflammatory conditions generally which cause itching or pain, e.g., herpes virus lesions, pain, itching and fungus infections of the perineum, feet, hands, ear canal, inflammation or sclerosis of the ear drum, urinary bladder, urethra, abscess cavities, leg ulcers, bed sores, infected sinuses, senile keratosis, animal and insect bites, painful muscle spasms and pain from "pinched nerves."
It is postulated on the basis of studies at the cellular level that enzyme imbalances cause physiological abnormalities which are corrected according to this invention by the skin penetrant carrying the biphenamine to the situs of the abnormality. Consequently, in addition to ameliorating the pain associated with wounds and burns, the healing thereof is facilitated by the compositions of this invention by the suppression of the inflammatory response. Additionally, the biphenamine inhibits infection of the situs of the wound and debriding of dead or injured tissue.
Although biphenamine hydrochloride as a 1% ointment is known to be useful for the treatment of minor burns, minor skin irritations or insect bites and to have bactericidal, fungicidal and antihistiminic properties at that concentration, it is surprising that concentrations thereof of only about 0.1% are equally or more effective when employed as an aqueous mixture with a skin penetrant such as DMSO or propylene glycol. Although U.S. Pat. NO. 2,594,350 teaches that a 0.14% solution of the mandelic acid salt of biphenamine is useful as a urinary antiseptic and germicide, the activity thereof is due in part to the known urinary bactericidal activity of mandelic acid.
Contemplated equivalents of the compositions and methods of treating pain of this invention are compositions otherwise corresponding thereto containing a different topically acceptable skin penetrant, in place of the DMSO or propylene glycol, and the use thereof topically to treat intractable pain.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever.
The following are examples of compositions of this invention.
a. An aqueous solution of DMSO and biphenamine hydrochloride can be produced by dissolving 50 grams of the former and 1 gram of the latter in 950 cc of sterile isotonic water. The viscosity thereof can be increased with any conventional viscosity enhancing agent, e.g., carboxymethylcellulose.
b. A solution of propylene glycol and biphenamine hydrochloride can be prepared by mixing 10 grams of the former with 900 grams of sterile water containing 1 gram of the latter dissolved therein. The propylene glycol acts as a viscosity enhancing agent, producing a viscous solution.
a. A lotion can be formulated in the conventional manner from the following ingredients, after dissolving the biphenamine hydrochloride and buffer in the water.
______________________________________Biphenamine � HCl 1 gmDMSO 50 ccCetyl alcohol 200 gmPropylene glycol 100 gmSodium laural sulfate 15 gmWater q.s. 1000 cc______________________________________
b. The above lotion can also be prepared with the DMSO omitted therefrom.
a. An ointment can be produced from the following ingredients, after dissolution of the biphenamine hydrochloride in water.
______________________________________Biphenamine � HCl 1 gmDMSO 50 ccGlyceryl monostearate, 180 gmAcid TypeStearyl alcohol 50 gmPolysorbate 80 20 gmWater q.s. 1,000 cc______________________________________
b. An ointment can also be prepared in which the DMSO is replaced by 50 grams of propylene glycol.
a. An aqueous alcoholic ointment can be prepared by blending the following ingredients, with the biphenamine hydrochloride first dissolved in the water.
______________________________________Biphenamine � HCl 100 mgDMSO 5 gmEthanol 10 gmCorbowax 1,500 20 gmWater q.s. 1,000______________________________________
b. An ointment in which the DMSO is replaced by 10 gm of propylene glycol can similarly be prepared.
a. Suppositories can be cast from a melt of the following ingredients, after first dissolving the biphenamine hydrochloride in the water.
______________________________________Biphenamine � HCl 70 mgDMSO 3.4 gmSodium stearate 10 gmGlycerin 45 gmWater 10 gm______________________________________
b. Suppositories in which the DMSO is replaced by 7 gm of propylene glycol can also be produced.
The following examples illustrate the method of this invention.
The acute pain resulting from collapsed discs in the neck of a female age 71 was successfully ameliorated for periods of 1 to 10 hours by the topical application of 1 to 16 drops of the composition of Example 1a to the occiput, the situs of the pain. As a result, the necessity of traction and the wearing of a neck collar which immobilized the neck was eliminated.
A male age 68 who experienced consistent severe lower back pain after a lumbar disc operation had attempted to no avail to alleviate the pain variously with Percodan, aspirin, 90% DMSO applied topically to the lower back region, and alcohol consumption. Within eight minutes after the application of 8 drops of the composition of Example 1a topically with manual spreading around the lower back at the situs of the pain, the pain was gone and remained eliminated for 8 days. The patient used the composition in this manner off and on at various intervals and found the relief from pain superior to 90% aqueous DMSO, with none of the redness or skin irritation associated with the use of the latter.
The same superior results were achieved with this patient in relieving the pain associated with a sprained knee which was swollen and the knee could not be bent. Several drops of the composition of Example 1a spread around the knee area produced marked relief from the pain occurring within a few minutes. Movement of the knee was possible within a few hours thereafter.
A 78 year old arthritic patient with a painful knee of unknown etiology obtained immediate relief from the pain after a few drops of the composition of Example 1a was spread on the knee area. Previously, 90% aqueous DMSO had been tried by the patient without much relief.
The index finger of a 38 year old woman had been damaged by an automatic riveting gun, resulting in severe pain and infection of the tendon. Although treatment with 90% DMSO had given some relief, after 9 months she had limited motion in the finger and the pain precluded her use of the riveting gun. Within 24 hours after applying a few drops of the composition of Example 1a to the injured finger, it could be extended nearly to normal position without pain. After repeated treatments over a period of about 2-3 weeks, she had normal movement of the finger without pain.
A 74 year old artist had such severe bursitis in his right shoulder that he could not paint. He obtained relief from the pain after one application of several drops of the composition of Example 1a to the shoulder area and was able to drive several hundred miles in his automobile. Upon his return, the bursitis flared up again but the pain was ameliorated by a second application.
A male (66 years) had a virus respiratory and intestinal infection that did not respond to treatment, including vertigo medicine, either for infection or for dizziness. After 6 weeks he was still suffering and toxic and had a sore inflammed throat. He placed a few drops of the composition of Example 1a in his ears and after 2 hours he put 1/2 teaspoon (2cc) thereof in a quarter glass of water and gargled with the mixture. Overnight he was greatly improved. He repeated the treatment after 24 hours and 48 hours. He required no further treatment and remained free of symptoms.
A female (43 years) developed symptoms and clinical condition similar to those of Example 11. Her doctor examined her ears, nose and throat as part of a general physical examination. He also prescribed medication for the dizziness and respiratory and intestinal symptoms, but the condition remained. Drops of the composition of Example 1a were inserted into each ear canal, once a day for 5 days. After the first day, the patient was relieved of the symptoms and after stopping the treatment, the symptoms did not reoccur.
A male (78 years) had buzzing or ringing in the ears (tinnitus) for 50 years. All treatments and medicines failed and the symptoms became increasingly bothersome with age. All treatment failed. He also had a fungus infection in both ear canals. Drops of the composition of Example 1a were applied 4 times in one day, from late afternoon until bedtime. The next morning there was a change in the tone of the tinnitus which appeared to be ameliorated by the treatment.
A male (39 years) twisted his spine and displaced a thoracic disc in his back while riding a horse. He developed a severe spasm and swelling of the erector spinae muscles on the left side of his back. He had to lie flat on his back to relieve the pain and could not walk without stooping over. The composition of Example 1a was applied to the area of tenderness in his back. Within 15 minutes there was a definite improvement in the severity of the pain. Another application was made 1/2 hour later and a third 1 hour after that. He developed a slight redness at the site of application, which appeared to be the result of an increase in the capillary circulation rather than an irritation of the skin. There was no pain, no itching, no burning and no discomfort and he was entirely comfortable.
The following examples illustrate the use of compositions of this invention to ameliorate the pain associated with wounds and burns and the promotion of the healing thereof.
A construction worker received a ragged cut from a saw which was approximately two cm. long and about one cm. deep on the medial portion of the left hand. The wound bled profusely and was very painful. First aid was instituted and the bleeding was stopped. The wound was disinfected and a tetanus shot administered. The wound was very painful for several days. Aqueous propylene glycol (10%) was applied to keep the wound pliable but there was no improvement and the pain persisted. Then a solution of Example 1b was applied and relief of pain, which was observed within approximately 20 minutes, persisted for 4 hours. The same solution was again applied and was used over the course of the healing with application about every 4 hours. The wound healed without any further complications or further pain.
A female (72) patient developed acitinic keratitis, which corresponds to senile keratosis and is a precursor to squamous epithelioma. A dermatologist diagnosed and treated the condition with 5-flurouracil topically, which produced an intensely inflammed area with redness and pain. After the treatment was completed, an inflammed red area remained which was painful, swollen and unsightly. The application of the solution of Example 1a resulted in immediate relief of pain. After several days the lesion disappeared and the skin appeared normal. Pain did not reoccur since the first application.
A female (15) with severe sunburn over her front and back applied the solution of Example 1a to the back but not the front. The pain and inflammation disappeared promptly from the back but naturally persisted in the front, which was treated with an oily emollient solution which was ineffectual by comparison.
A female (20) with a severe sunburn to the entire body applied the solution of Example 1a to the left arm and shoulder and applied conventional medication to the other arm and shoulder. The former area was promptly relieved of pain whereas the right side was only slightly improved.
A male (63) with severe sunburn to face and chest treated one side of his face and one side of his chest with the solution of Example 1a and the other sides with conventional sunburn medication. There was an immediate improvement in the former areas whereas the latter areas were only slightly improved. The following day the former areas were normal and the latter areas were still inflammed and tender.
A female (72) spilled hot grease over the back of the left hand. Pain was severe. Immediately (2 min.) after the burn, the solution of Example 1a was applied to the burn area. Pain disappeared in 3-5 minutes and never recurred. Twelve hours later, no blister had appeared. The solution was again applied to the burn area. The epithelial skin was darkened by the burn but there was neither blistering nor pain. The solution was applied 2-3 times daily for 7 days. On the 7th day, the dead epithelium flaked off leaving slightly pinker than normal skin underneath. In 10 days, the burned area was normal. There never was any pain, blister, cracking of the tissues or exudation of tissue fluid. Slight pigmentation was the only residual effect of the burn.
A male (73) was burned by the sharp corner of a red hot iron door of a Finnish Sauna oven left ajar, which branded the lateral mid-thigh on the left side. There was the odor of burnt flesh and intense pain. The solution of Example 1a was applied topically to the burned area within 1 minute of the burn and spread around the area. Within 3 minutes, there was no further pain. The solution was applied again several times over the next hour. After 12 hours, there still was no pain. No blister appeared but there was an obvious brand where the hot iron had penetrated the tissue. Further applications of the solution was made on 2 or 3 occasions the day of the burn and the day following, although they did not seem necessary because of the lack of pain. However, because the branding was so severe, the treatment was repeated, although there never was any further pain or blistering. The only evidence of the burn was a brand the shape of a V, where the corner of the red hot door made pressure contact with the tissue, and a wedge-shaped area below the branded area which appeared to be similar to the ecchymosis following trauma. However, the difference was that in the case of ecchymosis of trauma there is a more diffuse and rounded appearance to the ecchymotic area. The brownish wedge shaped area on the dependent side of the brand was outlined sharply, as if cut out of a piece of paper or cloth with straight sides coming together to form a point. It is assumed that this discoloration was the result of the tissue damage caused by the brand and the tissue fluids which diffused by gravity dependently. Presumably because of the immediate application of the solution of Example 1a, there was no diffuse area of tissue damage surrounding the brand. After 10 days, the burn was healed and the brownish discoloration proximate the branded area returned to its normal color, except a slightly bluish hue.
A male (45) welder, who was welding a heavy iron rod, picked up the rod in his bare hands to put it on the table on which he was working. He inadvertently picked up the hot portion of the rod, which promptly branded his hand. Immediately (within 1-2 minutes) he applied the solution of Example 1a and spread it over the palm of the hand and between the fingers. He was seen the following day. There was no evidence of any burn and no blistering, except for a small area between the fourth and fifth fingers where he neglected to apply the medication. There never was any pain although the solution was applied only once immediately after the burn.
A male (43) smoking a cigarette accidentally pinched the lighted end of the cigarette between his fingers as he was attempting to remove the cigarette from his mouth. The solution of Example 1a was applied within 2 minutes. The pain was relieved in a few minutes and no blister developed. There was no pain on the following day and the burn was healed in one week, although there was slight pigmentation in the area which lasted several months before disappearing.
A boy (6) fell from a horse, striking his face and head on the gravelled road. This resulted in a deep ithelization of the skin and a traumatic burn into the subcutaneous tissues of the face and forehead. The boy was in mild shock and severe pain but was able after some time to return home, which took 2 hours. Once home, the solution of Example 1a was applied to the traumatized area by the child himself because he would not let anyone touch him. There was no cleaning or disinfection of the area because the child would not permit it. Instead, he applied the solution to himself liberally with cotton. In 20 minutes the boy fell asleep and awoke the next morning with swelling of the face and forehead but a minimal of pain. He permitted someone else to apply the solution again to the affected areas. Although these two applications were the only ones, there was no further pain and there was no infection that developed. After several weeks of healing, there was no scarring, pigmentation or other abnormality.
A male (23) playing soccer fell while running and skidded on the dry ground on his thigh, resulting in a burn that took off the skin and exposed a raw bleeding area. After a shower and soap and water (about 1 hour after the injury), the solution of Example 1a was applied to the traumatized area. There first was a slight burning sensation followed a few minutes thereafter by complete relief of pain. The solution was applied again later the same day and the following morning. This was the only treatment. There was normal healing, no infection, never any pain and after the usual pigmentation resulting from such a trauma, this disappeared after a few weeks without scarring or evidence of injury.
A male (23) polo player took a spill going at a speed of about 30 miles an hour and skidded on the turf landing on his shoulder, arm, forearm and side of the face and received severe burns. Following the game, a shower, soap and water and cleaning the affected areas, the solution of Example 1a was applied to all the affected areas except the forearm, which was used as a control. The areas where the solution was applied resulted in relief of pain in a few minutes whereas the area untreated on the forearm continued to be painful and did not heal as quickly as the areas where the solution had been applied.
The following examples illustrate the healing and/or pain relieving effect of the compositions of this invention.
Several species of animals, viz., horses, dogs and cats, had severe traumatic penetrating and secondarily infected wounds. Most were foul smelling. Some were burns due to ropes, cinches, straps or saddle sores and assorted causes. The topical use of the solution of Example 1a was effective in all cases in debriding and cleaning the infected areas and promoted healing without leaving angry appearing granulation tissue.
A female (72) with a mosquito bite on the base of the right thumb was treated with the solution of Example 1a. Relief of itching was observed but a spread of the noxious material from the bite occurred and there was a continuation of the itching to a minor degree. On the following day a similar bite on the other thumb in the same place was treated with the solution of Example 1b. The propylene glycol (10%) did not cause spread of the noxious material from the bite and there was a complete relief of itching which was much more marked than with the bite treated on the other thumb.
A female (70) with dermatitis of unknown etiology on the upper outer leg with raised areas that itched considerably was treated with a solution of Example 1b which gave prompt relief of the itching and swelling.
A male (58) cut himself at the base of the left thumb with a chain saw. The area was extremely painful at the site of the cut and in the surrounding area. The application of the solution of Example 1b relieved the pain, especially in the areas of trauma around the cut area. The following morning, there was very little pain and reapplication resulted in disappearance of all pain. There was prompt and complete healing without infection or residual soreness.
A pastured horse received a penetrating wound that became infected and fly blown with maggots falling out of the wound and the odor was bad enough so that none of the grooms would go near the horse. The wound was about six inches deep and about eight inches wide. The serum had exuded from the wound as is the case in horses with an open would that leaks serum and tissue fluid and the hair inferior to the wound was missing due to the action of the tissue fluid exuding from the wound. The solution of Example 1a was injected into the wound until it filled the wound and the excess ran out over the area that had been epilated. Within a few minutes the offensive odor was gone. The treatment was repeated daily, there was no odor, no maggots,no attraction to flies and the wound healed cleanly without leaving any granulation tissue that usually accompanies such a wound in the horse. The area where the hair was lost promptly grew back and the wound healed without leaving an ugly scar.
A 3-year old female Laborador ran in front of an automobile, which braked and then ran over the left forefoot of the dog and dragged it along the gravel road for a distance of 20 feet, before stopping and backing off the dog's foot. The dog was immediately taken to a veterinarian who treated the dog and bandaged it tightly as well as treating with antibacterial medication. The following day there was a great amount of pain and swelling and the dog was taken to his regular veterinarian, who removed the pressure dressing and examined the damaged foot. The entire skin of the top, sides and bottom of the foot was missing. The pads on the bottom of the foot were also missing and there remained a raw swollen mass that was obviously quite painful and the dog whimpered whenever any part of the foot was touched. Thereafter, the only treatment was the solution of Example 1a which was applied daily and a loose bandage was applied. The dog naturally walked on 3 legs for some time. After several days no bandage was used and the solution was applied from time to time but not at regular intervals. After a few weeks the dog's foot was normal.
Pain was relieved by the solution, as evidenced by the fact that the dog did not whimper when the loose bandage was applied or when the foot was touched when examined or when the solution was applied and rubbed on the area. There never was any infection and the area healed completely, including regrowth of the foot pads and the nails that had been lost.
The following examples illustrate the use of the solutions of this invention by instillation.
On the basis of animal experimentation and because of the established safety of the solution of Example 1a by various routes of administration including orally, that solution was used to treat patients with interstitial cystitis. This is an extremely painful inflammatory condition of the urinary bladder which is thought to be an autoimmune disease and for which there is no cure. At times it is necessary to remove the bladder because of intractable pain. DMSO as a 50% solution is approved by the FDA for this condition.
A female (38) had a confirmed diagnosis of interstitial cystitis which was refractory to all treatment, including several courses of DMSO. Cortisone had also been administered intramurally (injected into the bladder wall) with only temporary benefit. Before considering cystectomy, it was decided to administer by local instillation topically the solution of Example 1a. Despite the prior intractable nature of her condition, the patient was relieved of her pain for several weeks. Following a second local instillation, there was a relief of pain for a longer time. The intervals of relief of pain increased with each application of the solution. Although her condition was not cured, the topical local instillation was a definite benefit to the patient.
A female (58) with recurring hemorrhoids and rectal fissures with severe pain and itching was treated by the topical application of the solution of Example 1a. Pain and itching were relieved promptly.
A male (65) with severe hemorrhoids and a severe fungus infection of the area of the anus and perineum was treated by topical application of the solution of Example 1a. Pain and itching were relieved although the fungus infection had been present for many years and there was never any relief, in spite of frequent bathing and changing underwear twice or more daily.
A female (49) following a removal of the left kidney, developed a fecal fistula post operatively. The fecal material and flatus passed copiously from the sinus. Prior to considering surgical treatment, the wound was cleansed with the solution of Example 1a. Surprisingly, not only was a debriding effect achieved and a clean wound obtained, the fistula healed and closed in 3 days.
A mare (12 years) with a severe uterine infection and a purulent discharge from the uterus had been treated with all known medications for infections by systemic and local administration including intrauterine packs of antibacterial drugs, in an attempt to clear up the infection prior to considering the possibility of getting her in foal. Her condition was noted by the farm manager, a verterinarian and several grooms, all of whom had seen and examined the mare previously on many occasions, including a speculum inspection of the cervix to determine her present condition. Thereafter, the solution of Example 1a was instilled into the mare's vagina on three successive occasions. Two weeks later, the mare was found to be clean and the infection which had been refractory to all other treatment was gone.
A female (44) with a severe infection of the cervix uteri refractory to other treatment took a vaginal douche using the solution of Example 1a diluted with one tablespoonful of 1000 cc water. This was repeated once in 24 hours. After 2 weeks there was no evidence of infection or inflammation. This treatment was repeated on several cases and always improved the patient's condition.
The following examples illustrate the use of the compositions of this invention for the treatment of respiratory and sinus inflammation and allergies.
A mare (3 years) had been roaring and bleeding on the race track as a result of the stress of racing. The solution of Example 1a was sprayed into the nostrils once with complete relief of roaring and no bleeding as the result of racing. Thereafter, she won several races and was never ruled off the track because of bleeding. Several other race horses have been similarly treated.
A male groom (32) had severe allergies and would wake up in the morning with swollen eyes and puffy face. He applied the solution of Example 1a directly into the nostrils at night before retiring. The following morning he awoke with none of the swelling of the eyes and face which he routinely suffered from. The treatment was repeated whenever necessary and was always effective.
Similar results were achieved in several other patients with similar allergy symptoms.
A man (63) had severe vertigo due to inflammation of the middle ear which did not respond to conventional treatment including several kinds of seasick pills. He placed the solution of Example 1a in his external ear canal and a few hours thereafter used the solution, diluted one tablespoon to one ounce of water, as a gargle in the evening before retiring. The following morning the vertigo had disappeared.
A female (48) with symptoms similar to those of Example 41 was given the same treatment, with the exception that she did not instill the medication in the external ear canal. The solution of Example 1a was used as a gargle diluted as before one tablespoon (15 cc) in one ounce (30 cc) water. The following morning, there were no symptoms.
This gargle treatment has been used by many people for sore throat or with systemic flu-like symptoms with consistent benefit.
The following examples illustrate the use of the compositions of this invention for the treatment of herpes lesions.
The topical application of the solution of Example 1a to an 8 year old boy with anal herpes resulted in their disappearance. The condition recurred after a few months and a repeat of the topical application of the solution again resulted in a prompt disappearance of the perpetic lesions.
The solution of Example 1a was applied to the lesions of a male (32) with genital herpes topically several times (3-4) a day. The lesions disappeared in a few days.
A male (59) with recurrent herpes labialis applied the solution of Example 1a to the lesions as soon as a raised inflammed area appears. The lesion does not fully develop but instead disappears.
A male (44) developed severe intercostal herpes, possibly zoster. The topical application of the solution of Example 1a resulted in a disappearance of the lesions.
A female (40) with herpes of the eye had a lesion in the internal canthus (inner corner of the eye). The lesion was a crusted lesion present for two days. The topical application of the solution of Example 1a caused a prompt disappearance of the lesion.
A male (73) developed herpes of the inguinal nerve in the groin. The solution of Example 1a was applied topically daily, which caused a rapid disappearance of the lesions. A pigmented area remained at the site but this also disappeared after several months.
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
|Cited Patent
|Filing date
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|Aug 16, 1968
|Dec 29, 1970
|Crown Zellerbach Corp
|Enhancing tissue penetration of physiologically active agents with dmso
|Nov 15, 1976
|Feb 14, 1978
|Diagnostic Data, Inc.
|Treatment of arthritis and allied conditions with xenylsalate
|Citing Patent
|Filing date
|Publication date
|Jul 17, 2001
|Oct 15, 2002
|George F. El Khoury
|Topical application of muscarinic and opioid agents for treatment of tinnitus
|Feb 10, 1998
|Dec 7, 2010
|Dermex Pharmaceuticals, Llc
|Chelated 8-hydroxyquinoline and use thereof in a method of treating epithelial lesions
|Sep 11, 2006
|Jun 7, 2011
|Abela Pharmaceuticals, Inc.
|Systems for removing dimethyl sulfoxide (DMSO) or related compounds or odors associated with same
|May 16, 2006
|Sep 6, 2011
|Dermex Pharmaceuticals, Llc
|Chelated 8-hydroxyquinoline and use thereof in a method of treating epithelial lesions
|May 2, 2011
|Oct 30, 2012
|Abela Pharmaceuticals, Inc.
|Systems for removing dimethyl sulfoxide (DMSO) or related compounds, or odors associated with same
|Sep 11, 2006
|May 7, 2013
|Abela Pharmaceuticals, Inc.
|Materials for facilitating administration of dimethyl sulfoxide (DMSO) and related compounds
|Oct 24, 2012
|May 14, 2013
|Abela Pharmaceuticals, Inc.
|Systems for removing dimethyl sulfoxide (DMSO) or related compounds, or odors associated with same
|May 2, 2011
|Jul 9, 2013
|Abela Pharmaceuticals, Inc.
|Activated carbon systems for facilitating use of dimethyl sulfoxide (DMSO) by removal of same, related compounds, or associated odors
|Jun 9, 2006
|Aug 20, 2013
|The Board Of Regents Of The University Of Texas System
|Antiseptic compositions
|May 2, 2011
|Mar 18, 2014
|Abela Pharmaceuticals, Inc.
|Methods for facilitating use of dimethyl sulfoxide (DMSO) by removal of same, related compounds, or associated odors
|May 3, 2013
|Nov 17, 2015
|Abela Pharmaceuticals, Inc.
|Materials for facilitating administration of dimethyl sulfoxide (DMSO) and related compounds
|May 10, 2013
|Nov 17, 2015
|Abela Pharmaceuticals, Inc.
|Devices for removal of dimethyl sulfoxide (DMSO) or related compounds or associated odors and methods of using same
|Sep 11, 2006
|Aug 30, 2016
|Abela Pharmaceuticals, Inc.
|Compositions comprising dimethyl sulfoxide (DMSO)
|Feb 10, 1998
|May 13, 2004
|Russel T. Jordan
|Chelated 8-hydroxyquinoline and use thereof in a method of treating epithelial lesions
|Mar 17, 2005
|Sep 22, 2005
|Bausch & Lomb Incorporated
|Carboxylic acid derivatives of doxepin formulations preserved with low-irritation preservative
|May 16, 2006
|Sep 14, 2006
|Jordan Russel T
|Chelated 8-hydroxyquinoline and use thereof in a method of treating epithelial lesions
|Apr 20, 2006
|Dec 14, 2006
|Cardinal Associates, Inc.
|Treatment and prevention of elevated homocysteine
|Oct 4, 2006
|Apr 5, 2007
|Bohan J Stephen
|Method and system for systematically treating hemorrhoids
|May 2, 1986
|Nov 20, 1986
|Chemex Pharmaceuticals, Inc.
|Pharmaceutical vehicles for recucing transdermal flux
|May 26, 2000
|Mar 21, 2002
|Khoury George F El
|Topical application of muscarinic and opioid agents for treatment of tinnitus
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Feb 23, 1988
|Fee payment
Year of fee payment: 4
|Apr 9, 1992
|Maintenance fee reminder mailed
|Sep 6, 1992
|Lapse for failure to pay maintenance fees
|Nov 10, 1992
|Expired due to failure to pay maintenance fee
Effective date: 19920906


text:
Featured Member
"Robyn Lane Books happened because of how much Robyn and Lane love books, and writers. We are an independent publisher of strong voices and compelling stories, committed to the notion that great work defies genre. Our authors write with wit and wisdom, to make you think, make you laugh, and to create a lasting impression."
Why did you become a book publisher? Robyn Lane Books happened because of how much Robyn and Lane love books, and writers. We are an independent publisher of strong voices and compelling stories, committed to the notion that great work defies genre. Our authors write with wit and wisdom, to make you think, make you laugh, and to create a lasting impression. We take a boutique approach to publishing. Each author is treated to an individualized, tailored publication, and marketing process. We select our voices carefully, then cultivate their work through a series of edits, walking with our writers every step of the way. We became book publishers because we want to be the platform from which the best stories are told.
What do you like best about publishing? The partnership between Robyn Rasberry and Lane Buckman is what makes Robyn Lane Books unique. Robyn's strong background in editing, and writing make her a force of nature when it comes to polishing a manuscript. Lane's decades-long experience in writing, marketing, and social media make her a machine when it comes to selling the finished product. Robyn loves the grammar/syntax/spruce-it-up side of the business, and Lane loves the prime it/package it/sell it side.
What do you publish? Literary Fiction, and Essay Collections
What is the most effective form of marketing for your press? We utilize every form of marketing available to us, and tailor each approach to the project.
How do you define a successful title? A successful title is one that generates interest, conversation, and finds an audience through word of mouth. We want people to read our titles and start telling their friends, "You have GOT to read this book!"
Tell us about one of your titles about which you are especially proud. We are really looking forward to the launch of A Fairytale for Mothers, our first illustrated storybook for grown-ups. Our author, Leslie Gibbons, has written a beautiful story for mothers and their children to share. This will be one for the ages.
What has been your biggest challenge in achieving success? As newcomers, we are focused on networking and making inroads. But we believe the challenge is half the fun of the success.
What advice do you have for newcomers to book publishing? Just do it. And then read all you can about it, ask a lot of questions, and make yourself available to answer questions about what you know. Treat people well. Treat your authors exquisitely.
How will you and your company be positioned in five years? In five years, we will be on track to have published 25 titles, and should have grown to the point that we can hire another hand, and increase our yearly publication schedule to include 6 to 9 new titles per year. At current, we are scheduled to produce between 4 and 6 titles per year.
When you're not fully immersed in publishing, what do you do for fun? We both have active families, and spend a lot of time at recitals, rehearsals, and games. We also read a lot. If you had to wager on where you would find us in our downtime, you'd be smart to bet on "curled up in the living room with a good book, and a cup of coffee." If we aren't in a living room, you might find us in a bubble bath, but we would scream and be really confused as to how you found us.
From mailings to exhibits, see how IBPA's marketing programs help you grow your sales.Educational Opportunities
Attend a seminar, ask an expert, and get more free advice with our educational programs.Become a member
Access exclusive members-only benefits starting at just $10.


text:
Celebrity Gossip and Soap News
By Stuart Leaver
Open iTunes to buy and download apps.
Celebrity Gossip and Soap News, Shopping and Horoscopes? There's an app for that - this app. The No.1 unofficial source for celebrity and soap fans. If there's a top story, whether it's about your favorite pop star or movie star …… you'll be the first to know.
"Simple to use, quick to update - Celebrity Gossip and Soap News"
"A great resource for all celebrity fans"
"Easy to get to all the best Celebrity Gossip sites without using Google"
"Awesome if you can't get enough of your celebrity gossip"
Celebrity Gossip and Soap News contains the best sources of news for UK and Hollywood celebrities and UK soaps. No need to scan dozens of newspapers, magazines or websites, it's all here brought together in one app.
Download this app today and follow all your favorite celebrity gossip and soap news where ever you are!
- The best Celebrity Gossip and Soap News.
- View stories from your three favorite sources in one view.
- Shopping links direct to sites like Topshop, H&M etc.
- Horoscopes.
- Switch news on or off as desired.
- View each story in the app or via a website.
- Share interesting stories on Facebook and Twitter.
- Email your friends stories that they will find interesting.
If you enjoy the app please post positive feedback to encourage me to add new sources of celebrity gossip whether it's pop stars to movie stars or footballers to super stars shopping links to make things convenient to any new feature that are suggested. This app is for you and so you can influence they way it goes.
Note - If you know of, or find any feeds that you would like to see in future upgrades please leave a comment at http://www.inewsapps.co.uk/celebrity-gossip-amp-soap-news/ or email your suggestions to email@example.com
Please note all trademarks, logos and copyrights are property of their respective owners. WiFi or Internet connection required to update news feeds and external sites.
What's New in Version 1.1
Minor performance enhancements.
More iNewsApps applications.
Please remember to rate this app as the app can grow and improve through your feedback.
If you experience any issues please do not hesitate to contact us at email@example.com and provide more information on the issue or if you have any improvements you would like to suggest it would be great to hear them.
Visit our site at http://www.inewsapps.co.uk
Celebrity Gossip and Soap News site can be found at http://www.inewsapps.co.uk/apps/celebrity-gossip-amp-soap-news
Follow us on Facebook at http://www.facebook.com/inewsapps
Follow us at http://twitter.com/inewsappsuk
Note - If you know of, or find any feeds that you would like to see in future upgrades please leave a comment at http://www.inewsapps.co.uk/apps/celebrity-gossip-amp-soap-news or email your suggestions to firstname.lastname@example.com
Customers Also Bought
- Category: Entertainment
- Updated: 12 September 2011
- Version: 1.1
- Size: 7.9 MB
- Language: English
- Developer: Stuart Leaver
- © iNewsApps 2011
Compatibility: Requires iOS 3.0 or later. Compatible with iPhone, iPad, and iPod touch.


text:
Thread: Problem with specific container
12-01-2013, 02:01 PM #1WHT Addict
- Join Date
- Dec 2012
- Posts
- 128
Problem with specific container
Not sure if this fits here, but I have an OpenVZ node currently running about 30 pure IPv6 containers. All of them are running fine, except for one of them.
This one container just doesn't work. If I ping it using an online IPv6 ping utility(I don't have IPv6 on my end), I get 100% packet loss.
If I do a ping6 google.com on the VPS, it stays blank for a really long while, but I haven't been patient enough to wait for any response, probably I'd get a timeout.
Alright, after waiting for like 5 minutes, I get this:
ping6 google.com
unknown host
Now all my other containers work absolutely fine, I get a latency of 5 ms from all other containers, but this one, don't know whats going wrong.
Here's the conf file of the container:
ONBOOT="yes" CPUUNITS="1000" CPUS="1" CPULIMIT="50" PRIVVMPAGES="32768" PHYSPAGES="unlimited" DISKSPACE="5242880:5242880" QUOTATIME="0" KMEMSIZE="unlimited" LOCKEDPAGES="unlimited" SHMPAGES="unlimited" NUMPROC="unlimited" VMGUARPAGES="unlimited" OOMGUARPAGES="unlimited" NUMTCPSOCK="unlimited" NUMFLOCK="unlimited" NUMPTY="unlimited" NUMSIGINFO="unlimited" TCPSNDBUF="unlimited" TCPRCVBUF="unlimited" OTHERSOCKBUF="unlimited" DGRAMRCVBUF="unlimited" NUMOTHERSOCK="unlimited" DCACHESIZE="unlimited" NUMFILE="unlimited" AVNUMPROC="unlimited" NUMIPTENT="unlimited" DISKINODES="200000:220000" VE_ROOT="/vz/root/$VEID" VE_PRIVATE="/vz/private/$VEID" OSTEMPLATE="centos-5.0-x86" ORIGIN_SAMPLE="fvps" HOSTNAME="hostname" IP_ADDRESS="The IPv6 addresses" NAMESERVER="2001:4860:4860::8888 2001:4860:4860::8844"
Or if the config file's okay, any other suggestions/solutions?
The container config looks okay. Is the container running a virtual ethernet (veth) or virtual network (venet) configuration?
Would be helpful to see the output of ifconfig to determine whether the default route to the node is in place. Would also help to know any other troubleshooting you've done so I'm not repeating myself and taking up your time.| John Edel Jetfire Networks L.L.C. Trusted Hosting Solutions
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12-10-2013, 09:41 PM #3Web Hosting Master
- Join Date
- Mar 2005
- Location
- Ten1/0/2
- Posts
- 2,509
Is it the container config (thinking firewall) itself that is the problem?CPanel Shared and Reseller Hosting, OpenVZ VPS Hosting. West Coast (LA) Servers and Nodes
Running Linux since 1.0.8 Kernel!
Providing Internet Services since 1995 and Hosting Since 2004
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