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9679_36	Hemodialysis catheter Hemodialysis catheters are large diameter catheters (up to 16 French or 5.3mm) capable of flow rates of 200–300 ml/min, which is necessary to maintain the high flow rates of hemodialysis. There are two channels: one is used to carry the patient's blood to the dialysis machine, while the other is used to return blood back to the patient. These catheters are typically placed in the internal jugular vein. Introducer sheaths Introducer sheaths are large catheters (8–9 French) that are typically placed to facilitate the passage of temporary vascular devices such as pulmonary artery catheters. The introducer sheath is placed first, and the device is then threaded through the sheath and into the vessel. These catheters can also serve as stand-alone devices for rapid infusion given their large diameter. When paired with a pressurized infusion system, flow rates of 850 ml/min have been achieved. Routine catheter care
9679_37	The catheter is held in place by an adhesive dressing, suture, or staple which is covered by an occlusive dressing. Regular flushing with saline or a heparin-containing solution keeps the line open and prevents blood clots. There is no evidence that heparin is better than saline at preventing blood clots. Certain lines are impregnated with antibiotics, silver-containing substances (specifically silver sulfadiazine) and/or chlorhexidine to reduce infection risk. Specific types of long-term central lines are the Hickman catheters, which require clamps to make sure that the valve is closed, and Groshong catheters, which have a valve that opens as fluid is withdrawn or infused and remains closed when not in use. Hickman lines also have a "cuff" under the skin, to prevent bacterial migration. The cuff also causes tissue ingrowth into the device for long term securement. See also Peter Pronovost Quinton catheter References External links
9679_38	Central Venous Catheter Placement & Pulmonary Artery Catheter – Vìdeo Dailymotion (without ultrasound guidance) Video tutorial on how to start central venous lines in various locations Central line care, comparison, indications, complications and uses Catheters Articles containing video clips
9680_0	Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is injected by unique fangs during a bite, whereas some species are also able to spit venom. The glands that secrete zootoxins are a modification of the parotid salivary glands found in other vertebrates and are usually located on each side of the head, below and behind the eye, and enclosed in a muscular sheath. The venom is stored in large glands called alveoli in which it's stored before being conveyed by a duct to the base of channeled or tubular fangs through which it's ejected.
9680_1	Venom contains more than 20 different compounds, which are mostly proteins and polypeptides. The complex mixture of proteins, enzymes, and various other substances has toxic and lethal properties. Venom serves to immobilize prey. Enzymes in venom play an important role in the digestion of prey, and various other substances are responsible for important but non-lethal biological effects. Some of the proteins in snake venom have very specific effects on various biological functions, including blood coagulation, blood pressure regulation, and transmission of nerve or muscle impulses. These venoms have been studied and developed for use as pharmacological or diagnostic tools, and even drugs.
9680_2	Chemistry
9680_3	Proteins constitute 90-95% of venom's weight and are responsible for almost all of its biological effects. The hundreds, even thousands, of proteins found in venom include toxins, neurotoxins in particular, as well as nontoxic proteins (which also have pharmacological properties), and many enzymes, especially hydrolytic ones. Enzymes (molecular weight 13-150 KDa) make up 80-90% of viperid and 25-70% of elapid venoms, including digestive hydrolases, L-amino-acid oxidase, phospholipases, thrombin-like pro-coagulant, and kallikrein-like serine proteases and metalloproteinases (hemorrhagins), which damage vascular endothelium. Polypeptide toxins (molecular weight 5-10 KDa) include cytotoxins, cardiotoxins, and postsynaptic neurotoxins (such as α-bungarotoxin and α-Cobratoxin), which bind to acetylcholine receptors at neuromuscular junctions. Compounds with low molecular weight (up to 1.5 KDa) include metals, peptides, lipids, nucleosides, carbohydrates, amines, and oligopeptides, which
9680_4	inhibit angiotensin-converting enzyme (ACE) and potentiate bradykinin (BPP). Inter- and intra-species variation in venom chemical composition is geographical and ontogenic. Phosphodiesterases interfere with the prey's cardiac system, mainly to lower the blood pressure. Phospholipase A2 causes hemolysis by lysing the phospholipid cell membranes of red blood cells. Amino acid oxidases and proteases are used for digestion. Amino acid oxidase also triggers some other enzymes and is responsible for the yellow colour of the venom of some species. Hyaluronidase increases tissue permeability to accelerate the absorption of other enzymes into tissues. Some snake venoms carry fasciculins, like the mambas (Dendroaspis), which inhibit cholinesterase to make the prey lose muscle control.
9680_5	Snake toxins vary greatly in their functions. The two broad classes of toxins found in snake venoms are neurotoxins (mostly found in elapids) and hemotoxins (mostly found in viperids). However, exceptions occur – the venom of the black-necked spitting cobra (Naja nigricollis), an elapid, consists mainly of cytotoxins, while that of the Mojave rattlesnake (Crotalus scutulatus), a viperid, is primarily neurotoxic. Both elapids and viperids may carry numerous other types of toxins. Toxins Neurotoxins The beginning of a new neural impulse goes as follows:
9680_6	An exchange of ions (charged atoms) across the nerve cell membrane sends a depolarizing current towards the end of the nerve cell (cell terminus). When the depolarizing current arrives at the nerve cell terminus, the neurotransmitter acetylcholine (ACh), which is held in vesicles, is released into the space between the two nerves (synapse). It moves across the synapse to the postsynaptic receptors. ACh binds to the receptors and transfers the signal to the target cell, and after a short time, it's destroyed by acetylcholinesterase.
9680_7	Fasciculins These toxins attack cholinergic neurons (those that use ACh as a transmitter) by destroying acetylcholinesterase (AChE). ACh, therefore, cannot be broken down and stays in the receptor. This causes tetany (involuntary muscle contraction), which can lead to death. The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting (5-7 h) fasciculations (rapid muscle contractions). Snake example: found mostly in the venom of mambas (Dendroaspis spp.) and some rattlesnakes (Crotalus spp.) Dendrotoxins Dendrotoxins inhibit neurotransmissions by blocking the exchange of positive and negative ions across the neuronal membrane lead to no nerve impulse, thereby paralyzing the nerves. Snake example: mambas α-neurotoxins
9680_8	Alpha-neurotoxins are a large group; over 100 postsynaptic neurotoxins having been identified and sequenced. α-neurotoxins attack the Nicotinic acetylcholine receptors of cholinergic neurons. They mimic the shape of the acetylcholine molecule, and so fit into the receptors, where they block the ACh flow, leading to a feeling of numbness and paralysis. Snake examples: king cobra (Ophiophagus hannah) (known as hannahtoxin containing α-neurotoxins), sea snakes (Hydrophiinae) (known as erabutoxin), many-banded krait (Bungarus multicinctus) (known as α-bungarotoxin), and cobras (Naja spp.) (known as cobratoxin)
9680_9	Cytotoxins
9680_10	Phospholipases Phospholipase is an enzyme that transforms the phospholipid molecule into a lysophospholipid (soap) → the new molecule attracts and binds fat and ruptures cell membranes. Phospholipase A2 is one specific type of phospholipases found in snake venom. Snake example: Okinawan habu (Trimeresurus flavoviridis) Cardiotoxins / Cytotoxins Cardiotoxins are components that are specifically toxic to the heart. They bind to particular sites on the surface of muscle cells and cause depolarisation → the toxin prevents muscle contraction. These toxins may cause the heart to beat irregularly or stop beating, causing death. An example is the three-fingered cardiotoxin III from Chinese cobra, an example of the short three-fingered family (). Snake example: mambas, and some Naja species Hemotoxins
9680_11	Hemotoxins cause hemolysis, the destruction of red blood cells (erythrocytes), or induce blood coagulation (clotting, e.g. mucrocetin). A common family of hemotoxins includes snake venom metalloproteinases such as mucrolysin. Snake examples: most vipers and many cobra species: The tropical rattlesnake Crotalus durissus produces convulxin, a coagulant.
9680_12	Myotoxins Myotoxins are small, basic peptides found in rattlesnake and lizard (e.g. Mexican beaded lizard). venoms This involves a non-enzymatic mechanism that leads to severe skeletal muscle necrosis. These peptides act very quickly, causing instantaneous paralysis to prevent prey from escaping and eventually death due to diaphragmatic paralysis. The first myotoxin to be identified and isolated was crotamine, discovered in the 1950s by Brazilian scientist José Moura Gonçalves from the venom of tropical South American rattlesnake Crotalus durissus terrificus. Its biological actions, molecular structure and gene responsible for its synthesis were all elucidated in the last two decades. Determining venom toxicity (LD50)
9680_13	Snake venom toxicity is assessed by a toxicological test called the median lethal dose, LD50, (abbreviated as "lethal dose, 50%"), which determines the concentration of a toxin required to kill half the members of a tested population. The potency of wild snake venom varies considerably because of assorted influences such as biophysical environment, physiological status, ecological variables, genetic variation (either adaptive or incidental), and other molecular and ecological evolutionary factors. This is true even for members of one species. Such variation is smaller in captive populations in laboratory settings, though it cannot be eliminated. However, studies to determine snake venom potency must be designed to minimize variability.
9680_14	Several techniques have been designed to this end. One approach is to use 0.1% bovine serum albumin (also known as "fraction V" in Cohn process) as a diluent in determining LD50 values. It results in more accurate and consistent LD50 determinations than using 0.1% saline as a diluent. For example, fraction V produces about 95% purified albumin (dried crude venom). Saline as a diluent consistently produces widely varying LD50 results for nearly all venomous snakes. It produces unpredictable variation in precipitate purity (35-60%). Fraction V is structurally stable because it has seventeen disulfide bonds; it's unique in that it has the highest solubility and lowest isoelectric point of major plasma proteins. This makes it the final fraction to be precipitated from its solution. Bovine serum albumin is located in fraction V. The precipitation of albumin is done by reducing the pH to 4.8, near the pH of the proteins, and maintaining the ethanol concentration at 40%, with a protein
9680_15	concentration of 1%. Thus, only 1% of the original plasma remains in the fifth fraction.
9680_16	When the ultimate goal of plasma processing is a purified plasma component for injection or transfusion, the plasma component must be highly pure. The first practical large-scale method of blood plasma fractionation was developed by Edwin J. Cohn during World War II. it's known as the Cohn process (or Cohn method). This process is also known as cold ethanol fractionation, as it involves gradually increasing the concentration of ethanol in the solution at 5 °C and 3 °C. The Cohn Process exploits differences in plasma proteins properties, specifically, the high solubility and low pI of albumin. As the ethanol concentration is increased in stages from 0 to 40%, the pH declines from neutral (pH ~ 7) to about 4.8, which is near the pI of albumin. At each stage, proteins are precipitated out of the solution and removed. The final precipitate is purified albumin. Several variations to this process exist, including an adapted method by Nitschmann and Kistler that uses fewer steps, and
9680_17	replaces centrifugation and bulk freezing with filtration and diafiltration. Some newer methods of albumin purification add additional purification steps to the Cohn process and its variations. Chromatographic albumin processing emerged in the 1980s, however, it was not widely adopted until later due to the scarity of large-scale chromatography equipment. Methods incorporating chromatography generally begin with cryo-depleted plasma undergoing buffer exchange via either diafiltration or buffer exchange chromatography, to prepare the plasma for following ion exchange chromatography steps. After ion exchange, generally purification steps and buffer exchange occur.
9680_18	However, chromatographic methods began to be adopted in the 1980s. Developments were ongoing between when Cohn fractionation started emerge in 1946, and when chromatography emerged, in 1983. In 1962, the Kistler and Nistchmann process was created as a spin-off of the Cohn process. In the 1990s, the Zenalb and the CSL Albumex processes were created, which incorporated chromatography with variations. The general approach to using chromatography for plasma fractionation for albumin is: recovery of supernatant I, delipidation, anion exchange chromatography, cation exchange chromatography, and gel filtration chromatography. The recovered purified material is formulated with combinations of sodium octanoate and sodium N-acetyl tryptophanate and then subjected to viral inactivation procedures, including pasteurization at 60 °C. This is a more efficient alternative than the Cohn process because:
9680_19	smooth automation and a relatively inexpensive plant was needed, easier to sterilize equipment and maintain a good manufacturing environment chromatographic processes are less damaging to the albumin protein a more successful albumin end result can be achieved. Compared with the Cohn process, albumin purity increased from about 95% to 98% using chromatography, and the yield increased from about 65% to 85%. Small percentage increases make a difference in regard to sensitive measurements such as purity. The big drawback has to do with the economics. Although the method offered efficient, acquiring the necessary equipment was difficult. Large machinery is necessary, and for a long time, the lack of equipment availability limited its widespread use. Evolution
9680_20	Venom evolved just once among all Toxicofera about 170 million years ago, and then diversified into the huge venom diversity seen today. The original toxicoferan venom was a very simple set of proteins that were assembled in a pair of glands. Subsequently, this set of proteins evolved independently in the various lineages of toxicoferans, including Serpentes, Anguimorpha, and Iguania. Several snake lineages have since lost the ability to produce venom, often due to a change in diet or a change in predatory tactics. In addition to this, venom strength and composition has changed due to changes in the prey of certain snake species. For example, the venom of the marbled sea snake (Aipysurus eydouxii) became significantly less toxic after the diet of this species changed from fish to strictly fish eggs. The evolution of venom is thought to be responsible for the enormous expansion of snakes across the globe.
9680_21	The mechanism of evolution in most cases has been gene duplication in tissues unrelated to the venom, followed by expression of the new protein in the venom gland. This was followed by natural selection for adaptive traits following the birth-and-death model, where duplication is followed by functional diversification, resulting in the creation of structurally related proteins that have slightly different functions. The study of venom evolution has been a high priority for scientists in terms of scientific research, due to the medical relevance of snake venom, in terms of making antivenom and cancer research. Knowing more about the composition of venom and the ways it can potentially evolve is very beneficial. Three main factors that affect venom evolution have been closely studied: predators of the snake that are resistant to snake venom, prey that are in an evolutionary arms race with snakes, and the specific diets that affect the intraspecific evolution of venom. Venoms continue to
9680_22	evolve as specific toxins and are modified to target a specific prey, and toxins are found to vary according to diet in some species.
9680_23	Rapid venom evolution can also be explained by the arms race between venom-targeted molecules in resistant predators, such as the opossum, and the snake venom that targets the molecules. Scientists performed experiments on the opossums and found that multiple trials showed replacement to silent substitutions in the von Willebrand factor (vWf) gene that encodes for a venom-targeted hemostatic blood protein. These substitutions are thought to weaken the connection between vWf and a toxic snake venom ligand (botrocetin), which changes the net charge and hydrophobicity. These results are significant to the venom evolution because it's the first citation of rapid evolution in a venom-targeted molecule. This shows that an evolutionary arms race may be occurring in terms of defensive purposes. Alternative hypotheses suggest that venom evolution is due to trophic adaption, whereas these scientists believe, in this case, that selection would occur on traits that help with prey survival in
9680_24	terms of venom evolution instead of predation success. Several other predators of the pit viper (mongooses and hedgehogs) show the same type of relationship between snakes, which helps to support the hypothesis that venom has a very strong defensive role along with a trophic role. Which in turn supports the idea that predation on the snakes can be the arms race that produces snake venom evolution.
9680_25	Some of the various adaptations produced by this process include venom more toxic to specific prey in several lineages, proteins that pre-digest prey, as well as a method to track down prey after a bite. The presence of digestive enzymes in snake venom was once believed to be an adaptation to assist digestion. However, studies of the western diamondback rattlesnake (Crotalus atrox), a snake with highly proteolytic venom, show that venom has no impact on the time required for food to pass through the gut. These various adaptations of venom have also led to considerable debate about the definition of venom and venomous snakes. Injection
9680_26	Vipers
9680_27	In vipers, which have the most highly developed venom-delivery apparatus, the venom gland is very large and is surrounded by the masseter or temporal muscle, which consists of two bands, the superior arising from behind the eye, the inferior extending from the gland to the mandible. A duct carries venom from the gland to the fang. In vipers and elapids, this groove is completely closed, forming a hypodermic needle-like tube. In other species, the grooves are not covered, or only partially covered. From the anterior extremity of the gland, the duct passes below the eye and above the maxillary bone, to the basal orifice of the venom fang, which is ensheathed in a thick fold of mucous membrane. By means of the movable maxillary bone hinged to the prefrontal bone and connected with the transverse bone, which is pushed forward by muscles set in action by the opening of the mouth, the fang is erected and the venom discharged through the distal orifice. When the snake bites, the jaws close
9680_28	and the muscles surrounding the gland contract, causing venom to be ejected via the fangs.
9680_29	Elapids In the proteroglyphous elapids, the fangs are tubular, but are short and do not possess the mobility seen in vipers. Colubrids Opisthoglyphous colubrids have enlarged, grooved teeth situated at the posterior extremity of the maxilla, where a small posterior portion of the upper labial or salivary gland produces venom. Mechanics of biting Several genera, including Asian coral snakes (Calliophis), burrowing asps (Atractaspis), and night adders (Causus), are remarkable for having exceptionally long venom glands, extending along each side of the body, in some cases extending posterially as far as the heart. Instead of the muscles of the temporal region serving to press out the venom into the duct, this action is performed by those of the side of the body.
9680_30	Considerable variability in biting behavior is seen among snakes. When biting, viperid snakes often strike quickly, discharging venom as the fangs penetrate the skin, and then immediately release. Alternatively, as in the case of a feeding response, some viperids (e.g. Lachesis) bite and hold. A proteroglyph or opisthoglyph may close its jaws and bite or chew firmly for a considerable time. Differences in fang length between the various venomous snakes are likely due to the evolution of different striking strategies. Additionally, it has been shown that the fangs of different species of venomous snakes have different sizes and shapes depending on the biomechanical properties of the snake's prey.
9680_31	Mechanics of spitting Spitting cobras of the genera Naja and Hemachatus, when irritated or threatened, may eject streams or a spray of venom a distance of 4 to 8 ft. These snakes' fangs have been modified for the purposes of spitting; inside the fangs, the channel makes a 90° bend to the lower front of the fang. Spitters may spit repeatedly and still be able to deliver a fatal bite. Spitting is a defensive reaction only. The snakes tend to aim for the eyes of a perceived threat. A direct hit can cause temporary shock and blindness through severe inflammation of the cornea and conjunctiva. Although usually no serious symptoms result if the venom is washed away immediately with plenty of water, blindness can become permanent if left untreated. Brief contact with the skin is not immediately dangerous, but open wounds may be vectors for envenomation. Physiological effects
9680_32	The four distinct types of venom act on the body differently: Proteolytic venom dismantles the molecular surroundings, including at the site of the bite. Hemotoxic venom acts on the cardiovascular system, including the heart and blood. Neurotoxic venom acts on the nervous system, including the brain. Cytotoxic venom has a localized action at the site of the bite.
9680_33	Proteroglyphous snakes The effect of the venom of proteroglyphous snakes (sea snakes, kraits, mambas, black snakes, tiger snakes, and death adders) is mainly on the nervous system, respiratory paralysis being quickly produced by bringing the venom into contact with the central nervous mechanism that controls respiration; the pain and local swelling that follow a bite are not usually severe. The bite of all the proteroglyphous elapids, even of the smallest and gentlest, such as the coral snakes, is, so far as known, deadly to humans. However, some mildly venomous elapids remain, such as the hooded snakes (Parasuta), bandy-bandies (Vermicella), etc.
9680_34	Vipers Viper venom (Russell's viper, saw-scaled vipers, bushmasters, and rattlesnakes) acts more on the vascular system, bringing about coagulation of the blood and clotting of the pulmonary arteries; its action on the nervous system is not great, no individual group of nerve-cells appears to be picked out, and the effect upon respiration is not so direct; the influence upon the circulation explains the great depression, which is a symptom of viperine envenomation. The pain of the wound is severe and is rapidly followed by swelling and discoloration. The symptoms produced by the bite of the European vipers are thus described by Martin and Lamb:
9680_35	The bite is immediately followed by the local pain of a burning character; the limb soon swells and becomes discolored, and within one to three hours great prostration, accompanied by vomiting, and often diarrhea, sets in. Cold, clammy perspiration is usual. The pulse becomes extremely feeble, and slight dyspnoea and restlessness may be seen. In severe cases, which occur mostly in children, the pulse may become imperceptible and the extremities cold; the patient may pass into coma. In from twelve to twenty-four hours these severe constitutional symptoms usually pass off; but in the meantime, the swelling and discoloration have spread enormously. The limb becomes phlegmonous and occasionally suppurates. Within a few days recovery usually occurs somewhat suddenly, but death may result from the severe depression or from the secondary effects of suppuration. That cases of death, in adults as well as in children, are not infrequent in some parts of the Continent is mentioned in the last
9680_36	chapter of this Introduction.
9680_37	The Viperidae differ much among themselves in the toxicity of their venoms. Some, such as the Indian Russell's viper (Daboia russelli) and saw-scaled viper (E. carinatus); the American rattlesnakes (Crotalus spp.), bushmasters (Lachesis spp.), and lanceheads (Bothrops spp.); and the African adders (Bitis spp.), night adders (Causus spp.), and horned vipers (Cerastes spp.), cause fatal results unless a remedy is speedily applied. The bite of the larger European vipers may be very dangerous, and followed by fatal results, especially in children, at least in the hotter parts of the Continent; whilst the small meadow viper (Vipera ursinii), which hardly ever bites unless roughly handled, does not seem to be possessed of a very virulent venom, and although very common in some parts of Austria and Hungary, is not known to have ever caused a serious accident.
9680_38	Opisthoglyphous colubrids Biologists had long known that some snakes had rear fangs, 'inferior' venom injection mechanisms that might immobilize prey; although a few fatalities were on record, until 1957, the possibility that such snakes were deadly to humans seemed at most remote. The deaths of two prominent herpetologists, Robert Mertens and Karl Schmidt, from African colubrid bites, changed that assessment, and recent events reveal that several other species of rear-fanged snakes have venoms that are potentially lethal to large vertebrates. Boomslang (Dispholidus typus) and twig snake (Thelotornis spp.) venoms are toxic to blood cells and thin the blood (hemotoxic, hemorrhagic). Early symptoms include headaches, nausea, diarrhea, lethargy, mental disorientation, bruising, and bleeding at the site and all body openings. Exsanguination is the main cause of death from such a bite.
9680_39	The boomslang's venom is the most potent of all rear-fanged snakes in the world based on LD50. Although its venom may be more potent than some vipers and elapids, it causes fewer fatalities owing to various factors (for example, the fangs' effectiveness is not high compared with many other snakes, the venom dose delivered is low, and boomslangs are generally less aggressive in comparison to other venomous snakes such as cobras and mambas). Symptoms of a bite from these snakes include nausea and internal bleeding, and one could die from a brain hemorrhage and respiratory collapse.
9680_40	Aglyphous snakes Experiments made with the secretion of the parotid gland of Rhabdophis and Zamenis have shown that even aglyphous snakes are not entirely devoid of venom, and point to the conclusion that the physiological difference between so-called harmless and venomous snakes is only one of degree, just as various steps exist in the transformation of an ordinary parotid gland into a venom gland or of a solid tooth into a tubular or grooved fang. Use of snake venoms to treat disease Given that snake venom contains many biologically active ingredients, some may be useful to treat disease. For instance, phospholipases type A2 (PLA2s) from the Tunisian vipers Cerastes cerastes and Macrovipera lebetina have been found to have antitumor activity. Anticancer activity has been also reported for other compounds in snake venom. PLA2s hydrolyze phospholipids, thus could act on bacterial cell surfaces, providing novel antimicrobial (antibiotic) activities.
9680_41	The analgesic (pain-killing) activity of many snake venom proteins has been long known. The main challenge, however, is how to deliver protein to the nerve cells: proteins usually are not applicable as pills. Immunity
9680_42	Among snakes
9680_43	The question whether individual snakes are immune to their own venom has not yet been definitively settled, though an example is known of a cobra that self-envenomated, resulting in a large abscess requiring surgical intervention, but showing none of the other effects that would have proven rapidly lethal in prey species or humans. Furthermore, certain harmless species, such as the North American common kingsnake (Lampropeltis getula) and the Central and South American mussurana (Clelia spp.), are proof against the venom of the crotalines, which frequent the same districts, and which they are able to overpower and feed upon. The chicken snake (Spilotes pullatus) is the enemy of the fer-de-lance (Bothrops caribbaeus) in St. Lucia, and in their encounters, the chicken snake is invariably the victor. Repeated experiments have shown the European grass snake (Natrix natrix) not to be affected by the bite of the European adder (Vipera berus) and the European asp (Vipera aspis), this being
9680_44	due to the presence, in the blood of the harmless snake, of toxic principles secreted by the parotid and labial glands, and analogous to those of the venom of these vipers. Several North American species of rat snakes, as well as king snakes, have proven to be immune or highly resistant to the venom of rattlesnake species. The king cobra, which does prey on cobras, is said to be immune to their venom.
9680_45	Among other animals
9680_46	The hedgehog (Erinaceidae), the mongoose (Herpestidae), the honey badger (Mellivora capensis), the opossum, and a few other birds that feed on snakes, are known to be immune to a dose of snake venom. Recently, the honey badger and domestic pig were found to have convergently evolved amino-acid replacements in their nicotinic acetylcholine receptor, which are known to confer resistance to alpha-neurotoxins in hedgehogs. Whether the pig may be considered immune is still uncertain, though early studies show endogenous resistance in pigs tested against neurotoxins. Though the pig's subcutaneous layer of fat may protect it against snake venom, most venoms pass easily through vascular fat layers, making this unlikely to contribute to its ability to resist venoms. The garden dormouse (Eliomys quercinus) has recently been added to the list of animals refractory to viper venom. Some populations of California ground squirrel (Otospermophilus beecheyi) are at least partially immune to
9680_47	rattlesnake venom as adults.
9680_48	Among humans The acquisition of human immunity against snake venom is ancient (from around 60 CE, Psylli tribe). Research into development of vaccines that will lead to immunity is ongoing. Bill Haast, owner and director of the Miami Serpentarium, injected himself with snake venom during most of his adult life, in an effort to build up an immunity to a broad array of venomous snakes, in a practice known as mithridatism. Haast lived to age 100, and survived a reported 172 snake bites. He donated his blood to be used in treating snake-bite victims when a suitable antivenom was not available. More than 20 so-treated individuals recovered. Amateur researcher Tim Friede also lets venomous snakes bite him in the hopes of a vaccine against snake venom being developed, and has survived over 160 bites from different species as of January 2016. Traditional treatments
9680_49	The World Health Organization estimates that 80% of the world's population depends on traditional medicine for their primary health-care needs. Methods of traditional treatments of snakebites, although of questionable efficacy and perhaps even harmful, are nonetheless relevant.
9680_50	Plants used to treat snakebites in Trinidad and Tobago are made into tinctures with alcohol or olive oil and kept in rum flasks called snake bottles, which contain several different plants and/or insects. The plants used include the vine called monkey ladder (Bauhinia cumanensis or Bauhinia excisa, Fabaceae), which is pounded and put on the bite. Alternatively, a tincture is made with a piece of the vine and kept in a snake bottle. Other plants used include mat root (Aristolochia rugosa), cat's claw (Pithecellobim unguis-cati), tobacco (Nicotiana tabacum), snake bush (Barleria lupulina), obie seed (Cola nitida), and wild gri gri root (Acrocomia aculeata). Some snake bottles also contain the caterpillars (Battus polydamas, Papilionidae) that eat tree leaves (Aristolochia trilobata). Emergency snake medicines are obtained by chewing a three-inch piece of the root of bois canôt (Cecropia peltata) and administering this chewed-root solution to the bitten subject (usually a hunting dog).
9680_51	This is a common native plant of Latin America and the Caribbean, which makes it appropriate as an emergency remedy. Another native plant used is mardi gras (Renealmia alpinia) (berries), which are crushed together with the juice of wild cane (Costus scaber) and given to the bitten. Quick fixes have included applying chewed tobacco from cigarettes, cigars, or pipes. Making cuts around the puncture or sucking out the venom had been thought helpful in the past, but this course of treatment is now strongly discouraged, due to the risk of self-envenomation through knife cuts or cuts in the mouth (suction cups from snake bite kits can be used, but suctioning seldom provides any measurable benefit).
9680_52	Serotherapy Serotherapy using antivenom is a common current treatment and has been described back in 1913. Both adaptive immunity and serotherapy are specific to the type of snake; venom with identical physiological action do not cross-neutralize. Boulenger 1913 describes the following cases: A European in Australia who had become immune to the venom of the deadly Australian tiger snake (Notechis scutatus), manipulating these snakes with impunity, and was under the impression that his immunity extended also to other species, when bitten by a lowland copperhead (Austrelaps superbus), an allied elapine, died the following day.
9680_53	In India, the serum prepared with the venom of monocled cobra Naja kaouthia has been found to be without effect on the venom of two species of kraits (Bungarus), Russell's viper (Daboia russelli), saw-scaled viper (Echis carinatus), and Pope's pit viper (Trimeresurus popeiorum). Russell's viper serum is without effect on colubrine venoms, or those of Echis and Trimeresurus. In Brazil, serum prepared with the venom of lanceheads (Bothrops spp.) is without action on rattlesnake (Crotalus spp.) venom.
9680_54	Antivenom snakebite treatment must be matched as the type of envenomation that has occurred. In the Americas, polyvalent antivenoms are available that are effective against the bites of most pit vipers. Crofab is the antivenom developed to treat the bite of North American pit vipers. These are not effective against coral snake envenomation, which requires a specific antivenom to their neurotoxic venom. The situation is even more complex in countries such as India, with its rich mix of vipers (Viperidae) and highly neurotoxic cobras and kraits of the Elapidae. Notes See also Antivenom Venomoid Snakebite Toxicofera References Further reading External links
9680_55	An overview of the diversity and evolution of snake fangs. Snake Venoms - Calculated orientations of snake venom phospholipases A2 and myotoxins in the lipid bilayer. LD50's for most toxic venoms. Australian Venom Research Unit - a general source of information for venomous creatures in Australia. biomedcentral.com - Medicinal and ethnoveterinary remedies of hunters in Trinidad. reptilis.net - How venom works. snakevenom.net - Drying and storage of snake venom. Vertebrate toxins Wilderness medical emergencies
9681_0	Between 1901 and 1949 Manchester Corporation Tramways (known as Manchester Corporation Transport Department from 1929 onwards) was the municipal operator of electric tram services in Manchester, England. At its peak in 1928, the organisation carried 328 million passengers on 953 trams, via 46 routes, along of track. It was the United Kingdom's second-largest tram network after the services of 16 operators across the capital were combined in 1933 by the London Passenger Transport Board. Other large systems were in Glasgow (which had 100 miles of double track at its peak and Birmingham (80 miles).
9681_1	The central and south-central Manchester area had one of the densest concentrations of tram services of any urban area in the UK. MCT services ran up to the edge of routes provided by other operators in (what is now) Greater Manchester, and in some instances had running rights over their lines and vice versa. There were extensive neighbouring systems in Salford, Oldham, Ashton, Hyde, Middleton, Rochdale, and elsewhere. Services were withdrawn earlier than most other British cities to be replaced by trolleybus and motor buses. Trams did not return to the city until the modern light-rail system Manchester Metrolink opened in 1992. History
9681_2	Though horse-drawn omnibuses were first introduced in Manchester as early as 1824 (arguably the world's first bus service it was run by John Greenwood and ran between Market Street and Piccadilly and Pendleton toll gate in Salford). In the subsequent years, other companies joined the rush to provide services culminating by 1850 in 64 omnibuses serving the centre of Manchester from outlying areas. Passenger carrying trams had first began urban operation in Birkenhead in 1860. By 1865 Greenwood merged with the other operators to become the Manchester Carriage Company. The earliest proposals for the construction of rails on the streets of Manchester were made by Henry Osborn O'Hagan in 1872. Though these were resisted (partly because raised tram tracks had been the source of many accidents elsewhere), by 1875, road congestion was so great that the 'tramway' could not be delayed much longer. Working with the Corporation of Salford, Manchester successfully gained orders under the Tramways
9681_3	Act 1870, which permitted them to build and lease, but expressly not to operate, tramways. The first tracks, therefore, were built to allow the already existing lines from neighbouring Salford to run into the city along Deansgate.
9681_4	As extensions and new lines were agreed, the Manchester Suburban Tramways Company was formed in 1877 to operate horse-drawn trams on the lines constructed by both local authorities. The company had a total fleet of more than 90 horse-drawn vehicles, and, in 1877, it was they who gained the concession to operate the tramway, using the name 'Manchester & Salford Tramways'. By 1901 this company used 5,000 horses to pull 515 tramcars over 140 route miles. Their first service, therefore, began on 17 May 1877, between Deansgate and Grove Inn on the Bury New Road. Just three years later a new organisation was formed called the Manchester Carriage and Tramways Company that continued with the expansion. By the 1890s it had turned itself into the most important transit operator in Lancashire. At their height, the company had 5,300 horses, pulling 515 tram cars on almost 90 miles of route using 515 cars. By 1896 outlying areas served included; Ashton-under-Lyne, Audenshaw, Droylsden, Failsworth,
9681_5	Gorton & Denton, Heaton Norris, Kersal, Levenshulme, Lower Broughton, Moss Side, Peel Green, Stalybridge, Stockport, Stretford, Swinton, Waterhead and Withington. There were also other horse-drawn tram services operating independently in some of the other settlements surrounding Manchester – notably Bolton and Stockport.
9681_6	Another company which had been set up by Henry O'Hagan proposed a tram network for all the urban areas east of Manchester, from Bacup in the north via Rochdale, Oldham and Ashton to Hyde. The first Manchester, Bury, Rochdale and Oldham Steam Tramways Company line opened in 1883, though by 1887 the company was declared bankrupt. A new company with almost the same name was begun in 1888 (simply by deleting the word "Manchester" from its name) and successfully ran steam tramways until the municipalities began building and operating routes at the turn of the 20th century. The Wigan and District Tramways Company ran tram services between 1880 and 1902. On the other side of Manchester, the Trafford family sold their land following the opening of the Manchester Ship Canal in 1894, creating the Trafford Park Estates Company, which built a gas-powered tramway to serve the new factories in 1897. It was replaced by an electric-powered tram line within the industrial estate from July 1903. The
9681_7	idea of local authorities running tram systems was developed locally in both Bolton and Wigan when in 1899 the corporations bought the routes of the E. Holden & Company. This enabled investment and conversion of the Bolton lines to electric traction during December of that year (followed in 1901 by Wigan). In 1900 the South Lancashire Tramways Company was formed (later renamed Lancashire United Tramways and again Lancashire United Transport in 1905), which ran an extensive inter-urban system from Atherton.
9681_8	Birth of Manchester Corporation Tramways
9681_9	The Manchester Carriage and Tramways Company leases were due to expire between 1898 and 1901, so the Corporation of Manchester agreed in 1895 to take over and modernise the existing tramways themselves. They sent inspectors to view the systems operated elsewhere in order to assess the best means of traction power and delivery for Manchester. The systems examined were: underground conduit, storage batteries, cable-hauled (used in Edinburgh), steam-powered (used by Leeds trams), oil, gas (used in Lytham St Annes), and a delegation was even sent to Paris to examine their compressed air system. The decision was then taken to use electrical power carried overhead but the track itself needed a complete overhaul from the horse-drawn days and at some junctions the track needed was to be so complex it even had to be ordered from the United States. It was thought that the initial requirement would be for as many as 600 electric cars but although this estimate was revised down to 400 it was
9681_10	still such a large number that it was beyond the manufacturing capacity of the period. Instead of having the entire network and fleet ready for the proposed opening in 1901, the Corporation gradually replaced the old Manchester & Salford Tramway routes as vehicles became available. Notwithstanding, over one hundred cars were delivered before the system opened from 1899 onwards.
9681_11	The location for a new electrically equipped depot needed to be accessible to the first route so land on Queen's Road, Cheetham (part of a later extension to that depot is now home to the Greater Manchester's Museum of Transport) was purchased and on 12 June 1900, the foundation stone was laid. Following the installation of power lines between Albert Square and Cheetham Hill, this first part of the new operation was inaugurated on 6 June 1901 with public services starting the next day. It took £1,500,000 and until 1903 to rebuild and re-equip the rest of the then 140-mile network, and to receive delivery of the full set of new tram cars (mainly double-deck but with some single decks (known as California cars)—mainly used on the L-shaped route 53—were also ordered), but on 13 April that year, horses pulled their last trams within Manchester. Horse-drawn trams in London by comparison continued until 1915. By the end of 1901, further sections had been opened between Cheetham Hill Road
9681_12	and Rochdale Road; Deansgate and Hightown; High Street and Blackley; High Street and Moston Lane; and High Street and Queens Park. Only 252 cars could be housed at the Queen's Road depot so a further depot was constructed at Devonshire Street / Hyde Road in Ardwick—and it was opened at the end of 1902.
9681_13	Expansion and peak 1901–1910
9681_14	From 1902 onwards both Salford and Manchester tram systems, uniquely in Britain, employed uniformed "trolley boys" – over a thousand at their peak (Jan 1930) – whose job it was to assist guards on double-truck trams by giving the driver a bell signal at the stops and helping passengers on and off. Because by the early 1900s multiple organisations were owning various sections of tramways in Manchester and surrounding areas, Manchester took the lead in rebuilding and electrifying their routes so that they could be leased back for operational services. The largest boroughs (Ashton-under-Lyne, Oldham, and Salford) continued to operate their own lines and began their own modernisation. At Bury, Oldham, and Rochdale, the steam services were also brought under the control of the local municipalities. In 1904 the Glossop Urban District Supply Company was set up to provide electric trams to Dukinfield, Glossop, Hyde, Mossley, and Stalybridge. The short 2.5 mile run in Trafford Park came under
9681_15	the joint control of the Corporations of Manchester and Salford.
9681_16	The tracks arrived in Piccadilly, home of the Corporation Tramway offices, on 1 June 1902. By the end of the following year services from Piccadilly reached: Alexandra Park, Audenshaw, Denton, Hollinwood, Moss Side, Old Trafford, Openshaw, Newton Heath, St. Peter's Square and Stretford. By 1903 Manchester Corporation had just over 300 cars. The trams were also used to carry parcels from 1905. As late as winter 1905, horse-drawn buses still ran between Palatine Road and Cheadle and on down to Northenden, as well as on the route between Chorlton-cum-Hardy and Hulme. Manchester Corporation Tramways proposed an experimental motor bus to replace them from 1906, effectively and portentously becoming both a tram and bus operator. By 1910, the 582 cars in service running over 100 route miles were generating a profit of £150,000. Yet another depot was needed and Princess Road in Moss Side was opened on 9 June 1909 which would house nearly 300 tram cars. 1911–1920
9681_17	In the run-up to the start of the First World War, there was an enormous expansion and consolidation of tram services to the extent that by 1915 trams were the most popular form of transit; the Manchester system was carrying 200 million passenger journeys a year on 662 vehicles (there were only a handful of buses at this time). It was then possible to traverse by tram the entire urban area now known as Greater Manchester, and far into the surrounding towns of Lancashire and Cheshire, many of which had their independent services. The extent of this inter-urban tram running compares with that found in parts of Belgium. Many of these services were also amalgamating or joint running. Stockport trams ran directly into Manchester with routes to Cheadle, Hazel Grove and Hyde. By 1913 there were so many services running in and out of Manchester city centre that the route names had to be replaced with route numbers – up to 46 MCT numbered routes are known though there were also some sub-sets
9681_18	of these routes. Despite the arrest of development and damage of the war years between 1914–1918 transport expansion was quick to be re-established. Women had been employed during the war as tram guards but there were shortages of materials and maintenance staff that led to the deterioration of both the track and the vehicle fleet. In 1918 the city's Medical Officer of Health closed the tram network to help stop the spread of Spanish flu.
9681_19	1921–1930
9681_20	In 1921 the Manchester Corporation formed a new body with Ashton Corporation and Stalybridge Joint Board which took over the Oldham, Ashton, and Hyde Tramway allowing Manchester trams to run on the Ashton via Guide Bridge section. Due to price rises after the war, operational costs rose from £681,000 in 1919 to £1,520,000 by 1922. This led to calls from some quarters for tram expansion to be halted. Middleton Electric Traction Company was jointly taken over by Middleton, Chadderton and Rochdale authorities in 1923. Middleton then granted Manchester a lease to operate on their former tracks in exchange for allowing them to run Corporation trams right into Rochdale. Buses became one of the fastest-growing areas (Manchester Corporation went from 16 vehicles in 1923 to 51 in 1926). However new tram lines were still being commissioned especially on the south side of the city (serving Anson Rd, Birchfields Rd, Kingsway, Platt Lane, Princess Road, Seymour Grove) and also in the north (at
9681_21	Heywood, Middleton and on Victoria Avenue). A final addition to the tram system came in 1928 when it was connected with the Bury Corporation system from the Middleton line to Hopwood in Heywood. This expansion signalled the maximum extent the MCT system reached in 1929–30 with 123 route miles (292 track miles) and 953 electric cars, making it the third-largest system in the country. Only the tram networks serving (what became Greater) London (around 400 route miles) and Glasgow (about 170 route miles) were bigger.
9681_22	Decline and replacement In spring 1929 a decision was needed to replace the track on the circular 53 route. Because the tracks passed beneath a number of low bridges, running double-deck trams had been impossible. In order to increase capacity, it would have been necessary to increase the bridge height and that was seen as prohibitively expensive so the decision was taken by the new general manager Mr. Stuart Pilcher, to replace the trams with motorbuses between Stretford Road and Cheetham Hill. The effect was to increase passenger numbers by 11 percent and the route became profitable to operate; thus commencing the start of tramway abandonment. In recognition of the growing importance of bus services, Pilcher managed to get the company name changed to Manchester Corporation Transport this year.
9681_23	Elsewhere profits were being made on Express bus services, 27 in all, many running on the same routes as trams. In the early 1930s, tramcar revenue was lower than operating costs on some services and yet more replacement work was due and more buses were introduced. The City Council decided to abandon plans to extend the tramway to the new and rapidly expanding large council housing estate of Wythenshawe and to withdraw the trolley boys. No more new trams were ordered. Pilcher organised the UK's first major conversion of an intensively used tram route to buses in the United Kingdom when on 6 April 1930 the service from Cheetham Hill to Stretford Road was abandoned to the motorbus. Manchester's bus fleet then numbered over 100, and with lower overheads and profits increasing after conversion, Pilcher was seen as the man who persuaded some cynics that trams were outdated for British cities and that buses were the future. Thirty years after their initial opening, the old tram routes were
9681_24	showing the need for capital expenditure on new infrastructure – Pilcher used this as one of the main reasons to push ahead with conversion to buses.
9681_25	Major investment was needed for bridge widening on the long route to Altrincham, therefore in June 1931, the trams were replaced by buses. It was followed a month later by the line to Sale Moor and in 1932 the long run-up to Middleton got the chop. 12 November 1932 saw the Rochdale to Manchester trams being pulled out of service by Rochdale Corporation. In 1936 the council decided to replace the old trams on Ashton Old Road with new trolleybuses. A depot for the Manchester trolleybus system was opened on Rochdale Road in 1936. By March 1938, 75 miles of single track tramway had been abandoned and 21 tram routes converted to motor or trolleybus. In 1939, 351 new motor buses and 77 trolleybuses were ordered (although 236 of the motor buses arrived before the start of the Second World War).
9681_26	The final decision to completely abandon the tram system in favour of trolleybuses and motor buses was taken on 7 July 1937 but the onset of war delayed some of this. However, during the war 4917 tons of steel were turned over to the war effort by removing abandoned tram tracks. In 1945 the final SHMD Joint Board tramcar ran, the last tram in Oldham followed in 1946, and those in Bolton and Salford ended in 1947. By 1949 just a few miles of track were left in Manchester and the last tram ran on 10 January of that year. The last of the old tram cars were stored at Hyde Road depot until on 16 March they were set ablaze in a huge bonfire, permanently signifying an end to what was once the third-largest tramway system in the country. A few trams were sold to other operators: the last of these in public service were in Aberdeen, in 1956.
9681_27	The trams continued in Bury for a further month and the last tram ran in Stockport during 1951. The trolley bus routes remained until they were also abandoned by December 1966.
9681_28	Museums A short line in Heaton Park has been restored to occasional service, and currently has an operating fleet of 3 electric trams and one horse tram. One of these, tramcar, No 765, was used as a chicken coop for many years before being restored in the 1960s by a group of enthusiasts working under the guidance of retired tramways employees at MCTD's Birchfields depot. Once work had been completed it was stored at the museum at Crich in Derbyshire, before permanently moving to Heaton Park in 1979. See also Transport in Manchester Daniel Boyle (politician) References Notes Bibliography External links http://www.gmts.co.uk http://www.lrta.org/hh/hhlist06.html http://www.petergould.co.uk/local_transport_history/fleetlists/manchester1.htm http://www.tundria.com/trams/GBR/Manchester-1944.shtml Manchester Corporation Tramways at the British Tramway Company Badges and Buttons website. Transport in Manchester Tram transport in England Tram transport in Greater Manchester
9682_0	Matthew David McConaughey (; born November 4, 1969) is an American actor. He first gained notice for his supporting performance in the coming-of-age comedy Dazed and Confused (1993), which was considered by many to be his breakout role. After a number of supporting roles in films including Angels in the Outfield (1994) and Texas Chainsaw Massacre: The Next Generation (1994), his breakthrough performance as a leading man came in the legal drama A Time to Kill (1996). He followed this with leading performances in the science fiction film Contact (1997), the historical drama Amistad (1997), the comedy-drama The Newton Boys (1998), the satire EDtv (1999), the war film U-571 (2000), and the psychological thriller Frailty (2001).
9682_1	In the 2000s, McConaughey became best known for starring in romantic comedies, including The Wedding Planner (2001), How to Lose a Guy in 10 Days (2003), Failure to Launch (2006), Fool's Gold (2008), and Ghosts of Girlfriends Past (2009), establishing him as a sex symbol. After a two-year hiatus from film acting, McConaughey began to appear in more dramatic roles beginning with the legal drama The Lincoln Lawyer (2011). He was acclaimed for his supporting performances in Bernie (2011), Magic Mike (2012) and The Wolf of Wall Street (2013), and for his leading roles in Killer Joe (2011) and Mud (2012).
9682_2	McConaughey's portrayal of Ron Woodroof, a cowboy diagnosed with AIDS, in the biopic Dallas Buyers Club (2013) earned him widespread praise and numerous accolades, including the Academy Award for Best Actor. In 2014, he starred as Rust Cohle in the first season of HBO's crime anthology series True Detective, for which he was nominated for the Primetime Emmy Award for Outstanding Lead Actor in a Drama Series. His film roles since have included Interstellar (2014), The Sea of Trees (2015), Free State of Jones (2016), Gold (2016), The Dark Tower (2017), and The Gentlemen (2019), earning varying degrees of commercial and critical success, as well as voice work in Kubo and the Two Strings (2016) as well as Sing (2016) and Sing 2 (2021).
9682_3	Early life Matthew David McConaughey was born on November 4, 1969, in Uvalde, Texas. His mother, Mary Kathleen "Kay"/"KMac" (née McCabe), is a former kindergarten teacher and published author who taught him. She was originally from Trenton, New Jersey. His father, James Donald "Jim" McConaughey, was born in Mississippi in 1929 and raised in Louisiana, where he ran an oil pipe supply business; he played for the Kentucky Wildcats and the Houston Cougars college football teams. In 1953, Jim was drafted in the 27th round by the NFL's Green Bay Packers. He was released before the season began and never played an official league game in the NFL.
9682_4	McConaughey's parents married each other three times, having divorced each other twice. He has two older brothers, Michael and Patrick (who was adopted). Michael, nicknamed "Rooster", is a self-made millionaire who starred in the CNBC docu-series West Texas Investors Club and the 2018 A&E reality show Rooster & Butch with Wayne (Butch) Gilliam. McConaughey's ancestry includes English, German, Irish, Scottish, and Swedish, with some of his Irish roots being from the Cavan/Monaghan area. He is a relative of Confederate brigadier general Dandridge McRae. He had a Methodist upbringing.
9682_5	McConaughey moved to Longview, Texas, in 1980, where he attended Longview High School. He lived in Australia for a year, in Warnervale, New South Wales, as a Rotary Youth Exchange student in 1988. He attended the University of Texas at Austin (UT-Austin), where he joined Delta Tau Delta fraternity. He began in the fall of 1989 and graduated in the spring of 1993 with a Bachelor of Science in Radio-Television-Film. His original plan had changed as he wanted to attend Southern Methodist University until one of his brothers told him that private school tuition would have been a burden on the family's finances. He also had planned to attend law school after graduation from college, but he realized he was not interested in becoming a lawyer. Career Early 1990s to 2000: Rise to prominence and breakthrough In the early 1990s, McConaughey began working in television commercials.
9682_6	In 1992, he was cast as the boyfriend "Walkaway Joe'', a music video for Trisha Yearwood's collaboration with Don Henley. Also that year, he acted in an episode of Unsolved Mysteries.
9682_7	Bob Balaban's My Boyfriend's Back premiered on August 6, 1993, where McConaughey made his first big screen appearance as ''Guy 2''. On September 24, Richard Linklater's Dazed and Confused premiered. McConaughey played Wooderson in a large ensemble cast of actors who would later become stars, including Jason London, Ben Affleck, Milla Jovovich, Cole Hauser, Parker Posey, Adam Goldberg, Joey Lauren Adams, Nicky Katt, and Rory Cochrane. He was not originally cast in the film, as the role of Wooderson was originally small and meant to be cast locally for budget purposes. At the time of casting, he was a film student at the University of Texas in Austin, who went out with his girlfriend to the Hyatt hotel bar, where he approached casting director Don Phillips. Phillips recalls, "The bartender says to him, 'See that guy down there? That’s Don Phillips. He cast Sean Penn in Fast Times.' And Matthew goes, 'I’m gonna go down and talk to this guy.'" Phillips also recalls that Linklater didn't
9682_8	like McConaughey at first "because he was too handsome". During production, another character named Pickford was meant to be a larger role. Due to the behavior of the actor playing Pickford with other cast members, his screen time was cut in favor of McConaughey's character, Wooderson. Linklater recalled "There was another actor who was kind of the opposite [of McConaughey]. He wasn’t really getting along with everybody. I could tell the actors weren’t responding to him." Much of the Wooderson role was improvised or written on the spot. Dazed and Confused was released on September 24, 1993, in 183 theaters, grossing $918,127 on its opening weekend. It went on to make $7.9 million in North America. The film received positive reviews from critics. The film generally gets favorable reviews. On review aggregator Rotten Tomatoes, it has a 92% approval rating. The website's critical consensus reads: "Featuring an excellent ensemble cast, a precise feel for the 1970s, and a killer
9682_9	soundtrack, Dazed and Confused is a funny, affectionate, and clear-eyed look at high school life." In her review for The Austin Chronicle, Marjorie Baumgarten gave particular praise to Matthew McConaughey's performance: "He is a character we're all too familiar with in the movies but McConaughey nails this guy without a hint of condescension or whimsy, claiming this character for all time as his own".
9682_10	In 1994, McConaughey acted in Angels in the Outfield, Texas Chainsaw Massacre: The Next Generation, and Daniel Johnston‘s music video “Life in Vain”.
9682_11	McConaughey actied in Herbert Ross' Boys on the Side, which premiered on February 3, 1995. That year he also acted in a crime thriller, Brian Cox's Scorpion Spring.

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