SEARCH · PubMed Health

Results for “CHOLESTYRAMINE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,639 records · Page 91Linked to original sources

PubMed1987

Mode of action of lipid-lowering drugs.

Following the recent demonstration that both cholestyramine and nicotinic acid decrease mortality from coronary heart disease, there is a new enthusiasm for hypolipidaemic therapy. The agents in current use are, however, insufficiently active or are accompanied by unacceptable side effects. An understanding of the mode of action is necessary, both to optimize treatment guidelines (e.g. regarding combination therapy or use in specific subsets of patients) and to develop new agents with preferred actions on rate-limiting steps. A reduction in LDL cholesterol concentration remains the principal desired action, although an elevation in HDL may also be beneficial. The main categories of commercially available agent comprise the anion exchange resins (inhibitors of bile acid absorption); cholesterol absorption inhibitors; fibrates (probably acting by enhancing lipoprotein lipase); and probucol (affecting LDL clearance). The most interesting of the new agents in clinical trials are the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitors, but other types of agent are at an earlier stage of evaluation, e.g. acyl-CoA: cholesterol acyltransferase inhibitors and peptide cofactors. It is not yet certain whether all the approaches to cholesterol lowering have equal validity, although an effect on biological endpoints is obtained for a variety of agents. Future evaluation will be aided by the implementation of noninvasive methods to quantify atherosclerosis and by the use of simple, 'dry-chemistry', cholesterol assays to screen populations.

Adrenergic beta-Antagonists↗

PubMed1995

Currently available hypolipidaemic drugs and future therapeutic developments.

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.

Anticholesteremic Agents↗

PubMed1995

The pruritus of cholestasis.

The pruritus of cholestasis is a difficult clinical problem to manage. The pathogenesis of this symptom is unknown. All conventional therapies have been unsuccessful in isolating a particular group of substances that could be implicated as direct or indirect causative agents. It should be emphasized that nonspecific treatment modalities that lower the plasma concentrations of a variety of substances (such as cholestyramine, colestipol, charcoal hemoperfusion, plasmapheresis, partial external diversion of bile, and drugs that induce hepatic enzymes), can potentially ameliorate the pruritus of cholestasis by lowering the circulating levels of an undefined pruritogen or a factor responsible for inducing the primary mechanism of the pruritus. The encouraging results reported by the use of antibiotic therapy for this condition merits investigation. Increased opioidergic neurotransmission is part of the syndrome of cholestasis and it contributes, at least in part, to the pruritus associated with it. Opiate antagonists seem to be an effective alternative therapy for some patients. Recent preliminary reports suggest that other neurotransmitter systems, eg, serotoninergic, may be involved in the pruritus of cholestasis. The need for quantitation of scratching activity cannot be over emphasized. The use of quantitative methodology offers the opportunity to facilitate the study of scratching behavior that is a biological phenomenon secondary to liver disease.

Anti-Bacterial Agents↗

PubMed2003

Drug-induced cholestasis.

Drug-induced cholestasis is a common entity, seen with numerous classes of pharmacological agents. A high index of suspicion is required for the correct diagnosis. Different clinical syndromes may be recognized, with variable degrees of hepatitis in association with cholestasis. The most important aspect of treatment is prompt discontinuation of the offending drug. Several agents have been used for symptomatic relieve of the pruritus associated with cholestasis, including cholestyramine, ursodeoxycholic acid, and opiate antagonists, with limited results. Prognosis is usually good, with few cases of prolonged cholestasis leading to vanishing bile duct syndrome. Liver failure may rarely occur if diagnosis goes unrecognized and the inciting drug is not withdrawn.

Animals↗

PubMed2003

Factors affecting gallbladder motility: drugs.

Various drugs and medications that inhibit or stimulate gallbladder contraction and basal tone in humans are described. Active gallbladder contraction may be achieved using synthetic hormones such as cholecystokinin, caerulein and motilin, cholinomimetic drugs such as bethanecol, prostigmine, and erythromycin due to its motilin-like effect. Furthermore, cisapride and cholestyramine, may have some excitatory activity on the gallbladder muscle. Intravenous amino acids also induce gallbladder contraction through the release of cholecystokinin. Inhibition of gallbladder contraction induced by a meal, or reduction of the basal fasting tone may be achieved by using atropine and other cholinergics, and by inhibitory hormones such as somatostatin, the nitric acid releaser arginine, the calcium channel antagonist nifedipine, and progesterone. Other drugs such as trimebutine, loperamide and ondansetron may negatively affect gallbladder contraction.

Gallbladder↗

PubMed2004

Functional properties, lipoxygenase activity, and health aspects of Lupinus albus protein isolates.

To utilize lupin seeds for food and pharmaceutical applications, lupin seeds were pretreated to remove oil using hexane or carbon dioxide. Two types of lupin protein isolate were prepared. Both types of protein isolate showed good foaming activity, comparable to egg white. Protein isolate extracted under acid conditions showed higher foaming activity than protein isolate extracted at neutral pH. The lipoxygenase activity was much reduced in both of the protein isolates. The protein isolate extracted at neutral pH showed a stronger angiotensin converting enzyme inhibition than the protein isolate extracted under acidic pH. In contrast, the protein isolate extracted under acid conditions had a greater sodium cholate binding capacity, comparable to that of cholestyramine. Lupin samples showed less DPPH radical scavenging activity than deoiled soybean. The deoiling method did not affect the functional properties, lipoxygenase activity, angiotensin converting enzyme inhibition, sodium cholate binding, and radical scavenging activity.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

In vitro bile acid binding of flours from oat lines varying in percentage and molecular weight distribution of beta-glucan.

Two experimental high beta-glucan oat (Avena sativa) lines (7.64 and 8.05%) and two traditional lines (4.77 and 5.26% beta-glucan) were used to evaluate the effect of beta-glucan quantity and molecular weight on bile acid (BA) binding. The oat flour samples were digested by an in vitro system that simulated human digestion. No significant differences among oat type were found in the overall beta-glucan, starch, and pentosan digestibilities. Considering the standard, cholestyramine, as 100% bound, the relative BA binding for the oat flour samples on a dry matter basis was in the range of 7.5-14.8%, which is higher than the values determined for some other grains and plant materials in the literature. Although the high beta-glucan flours bound a high amount of BA, no significant correlations were found between beta-glucan content in the flours and BA binding. Significant correlations were found between BA binding and insoluble dietary fiber content. Partial hydrolysis with lichenase of the beta-glucan molecules did not affect the BA binding. A summary of all data suggested that BA binding is a multicomponent-dependent process.

Avena↗

PubMed1992

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs.

Substitution of hydroxy and hydroxyalkyl functionality at C-7 of the hexahydronaphthalene nucleus of simvastatin has provided novel analogs. The synthetic strategy employed epoxidation or Lewis acid-catalyzed aldol reaction of the 8-keto silyl enol ether as a key reactive intermediate. These analogs were evaluated as potential hypocholesterolemic agents via initial determination of their ability to inhibit HMG-CoA reductase in vitro. Oral activity of these compounds was determined in an acute rat model and a three-week study in cholestyramine-primed dogs. Compounds were identified that possessed in vitro and in vivo activity comparable to that of simvastatin.

Administration, Oral↗

PubMed1991

3-Hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. 7. Modification of the hexahydronaphthalene moiety of simvastatin: 5-oxygenated and 5-oxa derivatives.

Modification of the hexahydronaphthalene ring 5-position in simvastatin 2a via oxygenation and oxa replacement afforded two series of derivatives which were evaluated in vitro for inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acutely in vivo for oral effectiveness as inhibitors of cholesterogenesis in the rat. Of the compounds selected for further biological evaluation, the 6 beta-methyl-5-oxa 10 and 5 alpha-hydroxy 16 derivatives of 3,4,4a,5-tetrahydro 2a, as well as, the 6 beta-epimer 14 of 16 proved orally active as hypocholesterolemic agents in cholestyramine-primed dogs. Subsequent acute oral metabolism studies in dogs demonstrated that compounds 14 and 16 evoke lower peak plasma drug activity and area-under-the-curve values than does compound 10 and led to the selection of 14 and 16 for toxicological evaluation.

Acetates↗

PubMed1982

Lipoproteins as potential site-specific delivery systems for diagnostic and therapeutic agents.

Despite the paucity of literature dealing with the effect of plasma lipoproteins upon drug disposition, evidence is accumulating that shows that these macromolecular complexes can play important roles in the absorption and transport of lipid-soluble agents. Moreover, preliminary studies have demonstrated that radiotracers can be directed to specific tissues by prior incorporation into the hydrophobic core of specific lipoproteins. Although these studies offer encouragement for the possible use of lipoproteins in the site-specific delivery of radiopharmaceuticals that are used in tracer doses, the use of lipoproteins in the transport of drugs at pharmacological concentrations represents a much greater challenge. Nothing is known at this time about the saturation kinetics of drug incorporation into lipoproteins or partially delipidated lipoproteins. Nor is there any assurance that drug-laden lipoproteins will participate in receptor-mediated uptake processes similar to native lipoproteins. Moreover, receptor-mediated uptake of lipoproteins is a saturable process and may not permit attainment of sufficient drug concentrations within cells. It could be argued, however, that receptor-mediated uptake could be enhanced by prior treatment with hypocholesterolemic drugs as has been shown for cholestyramine. In any event, the possible use of lipoproteins for the site-specific delivery of intravenously administered radiodiagnostics or highly potent drugs (e.g., anticancer agents) appears promising. Only the results of ongoing studies will determine the practicality of this approach.

Animals↗

PubMed2001

Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function.

1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and/or rat to determine whether ezetimibe would affect the absorption of molecules other than free cholesterol, namely cholesteryl ester, triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid. In addition, to determine whether exocrine pancreatic function is involved in the mechanism of action of ezetimibe, a biliary anastomosis model, which eliminates exocrine pancreatic function from the intestine while maintaining bile flow, was established in the rat. 3. Ezetimibe reduced plasma cholesterol and hepatic cholesterol accumulation in cholesterol-fed hamsters with an ED(50) of 0.04 mg kg(-1). Utilizing cholesteryl esters labelled on either the cholesterol or the fatty acid moiety, we demonstrated that ezetimibe did not affect cholesteryl ester hydrolysis and the absorption of fatty acid thus generated in both hamsters and rats. The free cholesterol from this hydrolysis, however, was not absorbed (92 - 96% inhibition) in the presence of ezetimibe. Eliminating pancreatic function in rats abolished hydrolysis of cholesteryl esters, but did not affect the ability of ezetimibe to block absorption of free cholesterol (-94%). Ezetimibe did not affect the absorption of triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid in rats. 4. Ezetimibe is a potent inhibitor of intestinal free cholesterol absorption that does not require exocrine pancreatic function for activity. Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would.

Animals↗

PubMed2001

Cholesterol biosynthesis from lanosterol: molecular cloning, chromosomal localization, functional expression and liver-specific gene regulation of rat sterol delta8-isomerase, a cholesterogenic enzyme with multiple functions.

Sterol Delta(8)-isomerase (SI) (EC 5.3.3.5), also known as emopamil binding protein or sigma receptor, catalyses the conversion of the 8-ene isomer into the 7-ene isomer in the cholesterol biosynthetic pathway in mammals. Recently, mutations of SI have been found to be associated with Conradi-Hünermann syndrome in humans. To investigate the in vitro and in vivo modes of molecular regulation of SI and its role in cholesterol biosynthesis in mammals, we isolated a full-length cDNA encoding rat SI. The deduced amino-acid sequence of rat SI predicts a 230-residue protein (26737 Da) with 87% and 80% amino-acid identity to mouse and human counterparts. The rat SI gene was mapped to chromosome 12q1.2 using fluorescence in situ hybridization (FISH). The biological function of the cloned rat SI cDNA was verified by overexpressing recombinant Myc-SI in Saccharomyces cerevisiae. It showed a characteristic pattern of inhibition on exposure to trans-2-[4-(1,2-diphenylbuten-1-yl)phenoxy]-N,N-dimethylethylamine (tamoxifen; IC(50)=11.2 microM) and 3beta-[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A; IC(50)=4.2 microM), two well known potent inhibitors of SI. Northern-blot analysis of 3-week-old rats compared with 2-year-old rats showed that SI mRNA expression in both age groups was restricted to liver, where a 70% reduction in mRNA levels was observed in 2-year-old rats. The FISH studies revealed ubiquitous expression of SI mRNA in rat hepatocytes. The in vitro studies showed that the SI mRNA was highly suppressed by 25-hydroxycholesterol in H4IIE cells. Treatment of H4IIE cells grown in medium supplemented with fetal bovine serum with tamoxifen for 24 h resulted in a dose-dependent induction of SI mRNA, with a concomitant suppression of sterol regulatory element binding protein-1 mRNA. Interestingly, this effect was not seen in emopamil-treated cells. The in vivo experiments also indicate that both mRNA expression and enzymic activity of SI in liver were induced approx. 3-fold in rats fed 5% (w/w) cholestyramine plus 0.1% (w/w) lovastatin in normal chow for 2 weeks. With this newly cloned rat SI cDNA, it becomes possible to gain molecular understanding of previously unknown and tamoxifen-mediated gene regulation of SI that is involved in cholesterol metabolism, ischaemia and genetic diseases.

Amino Acid Sequence↗

PubMed1998

Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells.

Molecular mechanisms of the bile acid active transport system in the ileal enterocytes remain unknown. We examined whether bile acids affect human enterocyte gene expression of intestinal bile acid-binding protein (I-BABP), a component of this transport system. Differentiated Caco-2 cells were incubated in the presence of human bile, bile acids or other lipids. The level of I-BABP expression was evaluated by Northern and Western blot analyses. A 24 h incubation of Caco-2 cells in a medium containing either bile or bile acids resulted in a remarkable 7.5-fold increase in the I-BABP mRNA level over the control level. Neither cholesterol, palmitic acid, phosphatidylcholine nor cholestyramine treated bile showed any difference in I-BABP mRNA expression from the control. Bile acid treatment increased the level of I-BABP mRNA in Caco-2 cells in a time- and dose-dependent manner. Western blot analysis showed that this induction led to increase in cytosolic I-BABP. Chenodeoxycholic acid and deoxycholic acid showed greater induction effects than other hydrophilic bile acids, including their own glycine conjugates. Pretreatment by actinomycin D or cycloheximide completely inhibited the up-regulation of I-BABP expression by bile acid. Bile acids, especially lipophilic bile acids, increase the I-BABP expression in Caco-2-cells, suggesting that luminal bile acids play an important role in regulating the I-BABP gene expression.

Bile Acids and Salts↗

PubMed2003

Review article: pruritus in cholestatic and other liver diseases.

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.

Anion Exchange Resins↗

PubMed2002

Effects of ileal bile salts on fasting small intestinal and gallbladder motility.

In the fasting state, gallbladder emptying is related to phase III of the intestinal migrating motor complex. The effects of ileal infusion of mixed taurocholate-phospholipid micelles on fasting small intestinal motility (by a 17-channel catheter with side holes located in duodenum, jejunum and ileum) and gallbladder motility (by ultrasound) were investigated in eight healthy volunteers. After bile salt depletion by cholestyramine, 0.9% NaCl or mixed micelles were infused in the ileum during phase II of the migrating motor complex. Time to onset of subsequent phase III was significantly shorter after infusion of mixed micelles compared with 0.9% NaCl (32 +/- 5 min vs. 60 +/- 5 min, P = 0.01). Distal to the infusion port, numbers of pressure waves and their amplitudes were significantly lower during bile salt infusion compared with 15 min before infusion (11 +/- 6 per 15 min vs. 21 +/- 8 per 15 min, and 2.4 +/- 0.6 kPa vs. 2.8 +/- 0.5 kPa, respectively). Micellar infusions increased fasting gallbladder volumes to 170 +/- 5% of starting volumes (P < 0.0001). In conclusion, ileal infusion of mixed micelles influences the timing of phase III of the intestinal migrating motor complex, inhibits ileal motility and increases fasting gallbladder volumes. These findings may have important consequences for enterohepatic circulation of bile salts.

Adult↗

PubMed2000

Refractory amiodarone-associated thyrotoxicosis: an indication for thyroidectomy.

BACKGROUND: Tasmania is an area of endemic iodine deficiency. Amiodarone is a class III anti-arrhythmic drug that is widely used for the management of ventricular and supraventricular tachydysrhythmias. Individuals from areas of endemic iodine deficiency appear more likely to manifest hyperthyroidism following amiodarone therapy, whereas hypothyroidism is a more frequent complication in iodine-replete communities. METHODS: Cases series. The clinical and biochemical response to medical and surgical management of five consecutive Tasmanian patients presenting with severe type-II amiodarone-associated thyrotoxicosis was reviewed. RESULTS: Five patients were identified. Combinations of antithyroid therapy including propylthiouracil, lithium carbonate, dexamethasone and cholestyramine were used. Thyroidectomy was required in two cases (40%) due to severe unremitting thyrotoxicosis despite combined drug regimens. Anaesthesia and total thyroidectomy were undertaken without complication despite the presence of severe hyperthyroidism at the time of surgery. In both cases thyroid histopathology demonstrated degenerative and destructive follicular lesions with multinuclear cell infiltrate and focal fibrosis. CONCLUSION: Amiodarone-associated thyrotoxicosis may be severe and refractory to medical therapy. Despite the potential risks of anaesthesia associated with uncontrolled thyrotoxicosis, thyroidectomy should be considered in the setting of life-threatening thyrotoxicosis.

Acute Disease↗

PubMed2002

Extrahepatic manifestations of cholestasis.

Pruritus, fatigue and metabolic bone disease represent three major extrahepatic manifestations of chronic cholestatic liver disease that considerably affect the patient's quality of life. The present article reviews pathogenetic aspects of and current therapeutic approaches to extrahepatic manifestations of cholestatic liver disease. Pathogenesis of pruritus of cholestasis remains poorly understood. The involvement of putative peripherally acting pruritogens, such as bile acids or endogenous opioids, is being discussed. More recently, central mechanisms, including an increased central opioidergic tone and pertubations in the serotonergic system have been proposed. Treatment of the underlying disease is beneficial also for the control of cholestasis-associated pruritus. Current therapeutic recommendations include ursodeoxycholic acid, cholestyramine, rifampicin and opioid antagonists. Liver transplantation may be indicated when severe pruritus is refractory to medical treatment. Fatigue is being recognized as the most frequent and one of the most disabling complaints in chronic cholestasis. Fatigue is presumably of central origin and its association with other neuropsychiatric disorders (e.g. depression, obsessive-compulsive disorders) is consistent with defective central neurotransmission. No specific therapies are currently available and a healthy lifestyle, regular sleep and avoidance of unnecessary stress and other precipiting factors are recommended. Antidepressant therapy may be warranted in selected patients. Osteopenia and osteoporosis are common in chronic cholestatic liver disease, whereas osteomalacia is rare. The pathophysiology of cholestasis-associated metabolic bone disease is regarded as multifactorial. Therapeutic recommendations include regular exercise, calcium and vitamin D supplementation in late stage disease, hormone replacement therapy in postmenopausal women and bisphosphonates.

Bone Diseases, Metabolic↗

PubMed2000

Characterization of a culture method to recover Helicobacter pylori from the feces of infected patients.

BACKGROUND: Helicobacter pylori is difficult to culture from stool. Multiple efforts from multiple laboratories have been unsuccessful, and the optimal conditions to recover H. pylori from stool are still not known. Recovery of H. pylori from feces of infected individuals is important for the performance of molecular epidemiological investigations, especially in children, where their symptoms do not warrant endoscopy to recover the organism. METHODS: Fresh fecal specimens (noncathartic) were obtained from 19 known H. pylori-infected patients and were processed to recover the organism. Fresh fecal specimens (noncathartic) were also obtained from three known H. pylori-negative individuals (controls) to determine whether H. pylori could be isolated from stools seeded with known concentrations of the organism. Treatment of the fecal suspensions with cholestyramine, a basic anion exchange resin that binds bile acids, was used in an attempt to enhance recovery of H. pylori by sequestering bile acids that are inhibitory to H. pylori growth. H. pylori was identified based on colony morphology, cell morphology, Gram's stain, biochemical reactions, and polymerase chain reaction for two H. pylori genes. RESULTS: Among 19 patients, H. pylori was cultured at least once from 3 and three times from 2 (5 of 19). Feces that were seeded with H. pylori and obtained from three H. pylori-negative volunteer controls yielded positive recovery in all instances. CONCLUSION: We have confirmed that it is possible to culture H. pylori from human stool, but the procedure for optimal recovery has still not been defined.

Bacteriological Techniques↗