Senna Research - OAWHealth

Senna Research

Senna Research

Senna Research

Colon-Cleanse-Constipation Resource Center

Senna is toxic to animal muscle tissue, yet this substance is a common ingredient utilized every day in herbal teas, weight-loss supplements, vitamins, and especially laxatives—in fact, Senna is often prescribed as a “natural” medicine for curing constipation. Despite the alarming fact of its toxicity, Senna continues to be included in hundreds of products while simultaneously causing a host of very serious health conditions, diseases, and even death in high enough amounts. The journal abstracts below detail the results of accidental overdoses in human beings as well as clinical experiments in both humans and animals. When Senna becomes highly concentrated in the organs or bloodstream, through over-consumption by whatever means, this herb can lead to the recipient developing a variety of detrimental health concerns. Senna seems to attack primarily body systems related to the blood and/or natural cellular functions but can severely damage the liver also due to its job of eliminating toxins from the body. Common diseases and conditions caused by Senna overuse or toxicity include:

  • Decreased enzyme production
  • Blood diseases (such as Hepatitis)
  • Liver failure
  • Musculoskeletal tissue damage
  • Nervous system impairment
  • Decreased energy production
  • Unhealthy weight loss
  • Severe diarrhea
  • Diaper rash and blisters (in kids)
  • Necrosis of colorectal tissue (possibly leading to colon cancer)

A recent search on with the keyword “Senna” resulted in over 230 nonprescription, commercially available products containing this potentially life-threatening ingredient. Different parts of wild herbs actually contain different amounts of any given substance; and some unscrupulous manufacturers utilize all parts of herbal plants in their zeal to maximize profit. Unless severe protocols are maintained, you may receive uneven concentrations of the herb in that attractively packaged tea or laxative you pick up off the shelf.

Admittedly, these abstracts are written in very scientific language you may not understand, but you can skim through them and get the gist of things. Just because something is widely available and doesn’t require a prescription doesn’t necessarily mean it’s safe; think about how easy it is to abuse cough syrup for example. If you need a weight-loss or colon cleansing supplement, take the time to conduct your own research and seek out products certified as truly “organic” and thus safe for extended use. You can learn more about Senna and other potentially unsafe herbs (such as Psyllium and Cascara sagrada) by reading the following abstracts and other articles within the Colon Cleansing and Constipation Resource Center archives. Take good care of your body. After all, it’s the only one you have!

Subacute cholestatic hepatitis likely related to the use of senna for chronic constipation

Summary: Senna overuse may have led to diminished enzyme production within the liver and blood disease.

We report a case of senna-induced cholestatic hepatitis which was not diagnosed at presentation. A 77 year old male was referred with abdominal pain, jaundice and elevated transaminase levels. A diagnosis of extrahepatic cholestasis was first suspected, due to the observation of a duodenal diverticulum and dilated proximal choledocus. However, the sphincterotomy did not improve cholestasis. At further evaluation, HBsAg was positive but serological work up was compatible with a healthy-carrier status. Further interrogation of the patient revealed a history of chronic senna intake to treat a chronic constipation. Liver biopsy showed bridging hepatocellular necrosis as well as canalicular cholestasis. Drug withdrawal resulted in a slow and progressive reduction in bilirubin levels and liver enzymes. In this case senna was likely the cause of a subacute cholestatic hepatitis exemplifying again the potential role of herbal related liver injury.[1]

Gulhane School of Medicine, Department of Internal Medicine, Ankara, Turkey.
[1] Sonmez, A., Yilmaz, M. I., Mas, R., Ozcan, A., Celasun, B., Dogru, T., Taslipinar, A. and I. H., Kocar.  “Subacute cholestatic hepatitis likely related to the use of senna for chronic constipation.”  Acta gastro-enterologica Belgica. Vol. 68, Issue 3.  pp 385-7.  Pub. 2005 Jul-Sep.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available: PubMed PMID: 16268429 [PubMed – indexed for MEDLINE].

Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides

Summary: Concentrated amounts of senna in the bloodstream, either by acute or prolonged exposure, may lead to liver failure.

“OBJECTIVE: To report a case of chronic ingestion of very large amounts of senna fruits as an herbal tea, possibly leading to severe hepatotoxicity.
CASE SUMMARY: A 52-year-old woman who had ingested, for >3 years, one liter of an herbal tea each day made from a bag containing 70 g of dry senna fruits, developed acute hepatic failure and renal impairment requiring intensive care therapy. The severity of the hepatic failure was reflected by the increase in prothrombin time (international normalized ratio >7) and the development of encephalopathy. Liver transplantation was discussed, but the patient ultimately recovered with supportive therapy. Renal impairment was consistent with proximal tubular acidosis, also with marked polyuria refractory to vasopressin administration. Suprisingly, large amounts of cadmium were transiently recovered in the urine.
DISCUSSION: Cassia acutifolia and angustifolia plants are widely used as laxatives. Their chronic abuse may be associated with serious manifestations, including fluid and electrolyte loss, with chronic diarrhea. Severe hepatotoxicity is unusual, but could be explained by the exposure of the liver to unusual amounts of toxic metabolites of anthraquinone glycosides (sennosides). An objective causality assessment suggests that hepatotoxicity was possibly related to senna laxative abuse. Regarding nephrotoxicity, there are no available human data on sennosides, while experimental models suggest that anthraquinone derivatives may also accumulate in the kidneys. The finding of high urinary concentrations of cadmium would suggest contamination of the herbal tea by metals, but this hypothesis could not be verified.
CONCLUSIONS: Ingestion of large doses of senna laxatives may expose people to the risk of hepatotoxicity.[2]

Department of Nephrology, Cliniques Saint-Luc, Universite catholique de Louvain, Brussels, Belgium.
[2] Vanderperren, B., Rizzo, M., Angenot, L., Haufroid, V., Jadoul, M. and P. Hantson.  “Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides.”  The Annals of pharmacotherapy. Vol. 39, Issue 7-8.  pp. 1353-7.  Pub. 2005 Jul-Aug. Epub. 2005 Jun 14.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available: PubMed PMID: 15956233 [PubMed – indexed for MEDLINE].

Sub-acute intoxication by Senna occidentalis seeds in rats

Summary: Commonly included as an ingredient in commercial laxatives and some weight-loss supplements, Senna use can lead to severe musculoskeletal and nervous system damage.

“Senna occidentalis (So) is a weed that grows in pastures along fences and in fields cultivated with cereals such as corn and soybean, and many reports have been showing intoxication with this plant in different animal species. It is also used in many medicinal purposes. The objective of the present study was to better evaluate the toxic effects of prolonged administration of So seeds to rats. Forty male Wistar rats were divided into four groups of 10 animals each, three of them respectively fed rations containing 1%, 2% and 4% So seeds, and the last one (control) fed commercial ration for a period of 2 weeks. Fourteen rats were also used in a pair-feeding (PF) experiment. The rats of the experimental groups showed lethargy, weakness, recumbency, depression and emaciation. Two rats of the 4% group and two of the PF group died during the experiment. Histopathological study showed fiber degenerations in the skeletal (Tibial, pectoral and diaphragm) and cardiac muscles. In the liver parenchyma, was observed vacuolar degeneration and, in the kidney, mild nefrosis in the proximal convoluted tubules. All of these alterations occurred in a dose-dependent fashion. Moderate to severe degeneration and spongiosis in the central nervous system, especially in cerebellum. Electron microscopy revealed mitochondrial lesions in all analyzed tissues.[3]

Research Center of Veterinary Toxicology (CEPTOX), Department of Pathology, Faculty of Veterinary Medicine, University of Sao Paulo-SP, Brazil.
[3] Barbosa-Ferreira, M., Dagli, M. L., Maiorka, P. C. and S. L. Gorniak.  “Sub-acute intoxication by Senna occidentalis seeds in rats.”  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. Vol. 43, Issue 4.  pp. 497-503.  Pub. 2005 Apr.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:   PubMed PMID: 15721195 [PubMed – indexed for MEDLINE].

Effects of long-term administration of Senna occidentalis seeds in the large bowel of rats

Summary: Senna use may lead to diminished cellular energy production and to weakened colon function.

"Plants of the genus Senna that contain anthranoides derivatives are frequently used as cathartics. Radiological studies have demonstrated that patients with chronic constipation who have used stimulant laxative have colonic redundancy and dilatation more frequently than patients who have not. The objective of the present work was to study morphological and histochemical changes of the lower gut after administration of Senna occidentalis seeds for a long period to rats, as observed in skeletal muscle fibers. Fragments of the lower gut of young and adult rats treated with S. occidentalis seeds (2% for 171 days and 3% for 61 days in the diet) were submitted to histological and histochemical analysis and to densitometry. The most important finding was decreased oxidative enzyme activity in smooth muscle cells and in myenteric neurons of the large bowel. As oxidative metabolism is essential for ATP and energy production, these results suggest that the functional intestinal disturbance caused by the chronic use of Senna occidentalis as a laxative can be due to a metabolic effect involving energy production, which would decrease colonic motility and cause functional colonic dilatation, but without any irreversible anatomic change."[4]

Emilio Ribas Infectology Institute, Sao Paulo, SP, Brazil.
[4] Nadal, S. R., Calore, E. E., Manzione, C. R., Puga, F. R. and N. M. Perez.  “Effects of long-term administration of Senna occidentalis seeds in the large bowel of rats.”  Pathology, research and practice. Vol. 199, Issue 11.  pp. 733-7.  Pub. 2003.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 14708639 [PubMed – indexed for MEDLINE].

Effects of Senna occidentalis on chick bursa of Fabricius

Summary: Though widely available in commercial laxative products, Senna is toxic to animal muscle tissue and can cause weight loss and lymph damage.

"Senna occidentalis (L) Link (formerly called Cassia occidentalis) is a toxic leguminous plant found ubiquitously as a contaminant of crops. All parts of the plant are toxic, but most of the S. occidentalis toxicity is found in the seeds. S. occidentalis has been shown to be toxic to several animal species, causing degenerative lesions mainly in muscles. This is the first report describing alterations in chick lymphoid organs caused by S. occidentalis seeds. The objectives of this study were to describe the effects of the treatment with seeds and its fraction external tegument (TE) on the development of chicks and their lymphoid organs bursa of Fabricius and spleen. Chicks that received a commercial ration with 1% TE had reduced body and lymphoid organ weights. The bursa of Fabricius presented reduction in the diameters of the follicles, and in the thickness of the cortical and medullary regions. The spleen presented depleted lymphoid tissue in the white pulp. These results indicate that the active principle of S. occidentalis is more concentrated on its TE fraction, and that it can cause weight loss as well as alterations in the lymphoid organs in chicks. The consequences of these alterations should be further investigated."[5]

Department of Pathology, Faculty of Veterinary Medicine and Zootechny, University of Sao Paulo, Av Prof Dr Orlando Marques de Paiva 87, CEP 05508-900 Sao Paulo, SP, Brazil.
[5] Silva, T. C., Gorniak, S. L., Oloris, S. C., Raspantini, P. C., Haraguchi, M., and M. L. Dagli.  “Effects of Senna occidentalis on chick bursa of Fabricius.”  Avian pathology : journal of the W.V.P.A.  Vol., 32, Issue 6.  pp. 633-7.  Pub. 2003 Dec.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).  
Available:  PubMed PMID: 14676015 [PubMed – indexed for MEDLINE].

Skin breakdown and blisters from senna-containing laxatives in young children

Summary: Senna, widely available in non-prescription laxatives, can cause diarrhea, severe diaper rash, blisters, and breakdown of skin tissue within approximately 7 to 24 hours of accidental ingestion by a young child.

"BACKGROUND: At the direction of the Food and Drug Administration, phenolphthalein was removed from all over-the-counter laxatives in 1999. Phenolphthalein was then replaced in most laxative products with the natural product senna from Cassia acutifolia Delile, which contains various anthraquinones. No data are available on the safety of senna use in children <6 years of age.
OBJECTIVE: To describe the clinical outcomes of exposure to unintentional ingestion of senna-containing laxatives in young children.
METHODS: All ingestion exposures of senna-containing laxatives in children <5 years of age from 6 poison centers over a 9-month period were evaluated. Inclusion criteria required 24-hour follow-up and the presence of diarrhea to confirm ingestion. Parents were told routinely that severe diaper rash was possible and to protect the perianal area with frequent cleansing and a barrier ointment if the child was wearing diapers.
RESULTS: During the study period, 111 cases were reported: 19 children experienced no diarrhea, 4 were lost to follow-up, and 88 exposures were evaluated. Fifty-two children (59%) were Twenty-nine children (33%) experienced severe diaper rash. The mean +/- SD time to recognition of the diaper rash was 15.6 +/- 8.6 hours. Ten children (11%) had blisters and skin sloughing. There was a significant increase in severe diaper rash (p < 0.05) and onset of blisters and skin breakdown (p < 0.05) in children wearing diapers versus those who were fully toilet trained. The mean time to onset of blisters was 14.5 +/- 6.8 hours. Skin burns and loss were seen primarily on the buttocks and perineum, loosely following the diaper area.
CONCLUSIONS: Unintentional ingestion of senna-containing laxatives in young children may potentially cause severe diaper rash, blisters, and skin sloughing."[6]

Kentucky Regional Poison Center, Louisville, KY 40232-5070, USA.
[6] Spiller, H. A., Winter, M. L., Weber, J. A., Krenzelok, E. P. and D. L. Anderson.  “Skin breakdown and blisters from senna-containing laxatives in young children.”  The Annals of pharmacotherapy. Vol. 37, Issue 5.  pp. 636-9.  Pub. 2003 May.  Online.  Accessed: 23 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 12708936 [PubMed – indexed for MEDLINE].

Toxicological interactions of Cassia Senna and Nerium oleander in the diet of rats

Summary: In highly concentrated levels, Senna caused diarrhea and eventually death in rats.

"The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1:1 mixture (5% + 5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed."[7]

College of Pharmacy, Riyadh, King Saud University, Saudi Arabia.
[7] Al-Yahya, M. A., Al-Farhan A. H. and S. E. Adam.  “Toxicological interactions of Cassia Senna and Nerium oleander in the diet of rats.”  The American journal of Chinese medicine.  Vol 30, Issue 4.  pp. 579-87.  Pub. 2002.  Online.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 12568285 [PubMed – indexed for MEDLINE].

Distribution of COX-negative mitochondria in myofibers of rats intoxicated with Senna occidentalis seeds

Summary: Ingestion of Senna seeds (the most concentrated part of the plant) caused extensive cellular damage in muscle tissue of hens and rats.

"We have described that administration of seeds or parts of the seed of Senna occidentalis (coffee senna) for long periods, induces histochemical changes in the skeletal muscles of hens and rats that are characteristic of a mitochondrial myopathy–as decrease of SDH and COX activity, with some COX negative fibers. In this experimental model of mitochondrial myopathy, as in many human mitochondrial diseases, there is a random distribution of COX negative fibers. Some fibers are completely COX negative while others are partially negative and others are completely positive. In the present work we have studied the distribution of COX negative mitochondria at transmission electron microscopy in skeletal muscle of rats in this experimental myopathy. In myofibers of intoxicated animals the expression of COX was heterogeneous. The histochemical reaction was observed in the internal membrane (more evident in mitochondrial cristae) of all mitochondria of some myofibers, while it was almost absent in other myofibers. In these myofibers the great part of the mitochondria were negative for COX reaction while other ones had a weak expression of this enzyme (dot or focal expression of COX). Our results indicated that the COX mitochondrial activity is heterogeneously impaired in myofibers of rats intoxicated with S. occidentalis. These abnormalities remember those observed in some types of human mitochondrial myopathies."[8]

Pharmacology Department, Biomedical Institute, Sao Paulo, Brazil.
[8] Calore, N. M. and E. E., Sesso, A., Correia, H., Marcondes, M. C. and L. Vilela de Almeida.  “Distribution of COX-negative mitochondria in myofibers of rats intoxicated with Senna occidentalis seeds.”  Journal of submicroscopic cytology and pathology.  Vol. 34, Issue 2.  pp. 227-31.  Pub. 2002 Apr.  Online.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 12117285 [PubMed – indexed for MEDLINE].

Toxicity testing of Senna occidentalis seed in rabbits

Summary: Congestion of concentrated amounts of Senna by rabbits led to significant weight loss, damaged heart function, muscle tissue loss, and even death within three weeks of reaching toxicity within the body.

"The effect was investigated of administering ground Senna occidentalis seeds to rabbits in different concentrations (1%, 2%, 3% and 4%) in the ration. The experiment lasted 30 days and the toxic effects of the plant were evaluated on the basis of weight gain, histopathological, biochemical and morphometric parameters, as well as histochemistry and electron microscopy. Animals that received the ration containing 4% ground S. occidentalis seeds gained less weight (p < 0.05) and died in the third week. Histopathology revealed that the heart and liver were the main organs affected, with myocardial necrosis and centrolobular degeneration. There was a reduction in cytochrome oxidase activity in the glycogenolytic fibres, together with muscle atrophy, confirmed by the morphometric studies. Electron microscopy of the liver cells revealed dilated mitochondria, with destruction of the internal cristae."[9]

Research Center for Veterinary Toxicology (CEPTOX), Department of Pathology, Faculty of Veterinary Medicine, University of Sao Paulo, Sao Paulo, Brazil.
[9] Tasaka, A. C., Weg, R., Calore, E. E., Sinhorini, I. L., Dagli, M. L., Haraguchi, M. and S. L. Gorniak.  “Toxicity testing of Senna occidentalis seed in rabbits.”  Veterinary research communications.  Vol. 24, Issue 8.  pp. 573-82.  Pub. 2000 Dec.  Online.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center). 
Available:  PubMed PMID: 11305748 [PubMed – indexed for MEDLINE].

Mitochondrial metabolism impairment in muscle fibres of rats chronically intoxicated with Senna occidentalis seeds

Summary: A correlation exists between the amount of Senna consumed and muscle tissue damage, with higher amounts leading to greater damage.

"The chronic administration of S. occidentalis seeds was found to induce a mitochondrial myopathy in hens. This study was undertaken to determine if the chronic treatment with S. occidentalis seeds of rats (as a mammalian model) would induce a mitochondrial myopathy similar to those described in humans and to determine if the histological changes could be correlated with the amount of ingested seeds. Twenty-one days old rats were fed S. occidentalis seeds at different diet concentrations (1, 2, 3%). Rats fed 1% S. occidentalis seeds had only a few COX-negative muscle fibers in the pectoralis major muscle. Rats fed 3% Senna occidentalis seeds had a greater number of COX-negative fibers. Rats fed 2% had an intermediate number of COX-negative fibers. Activity of SDH and NADH-tr were decreased in rats of groups 2% and 3%. Our data indicate that a progressive mitochondrial metabolism impairment can be produced in rats fed S. occidentalis seeds and that this impairment can be correlated with the amount of ingested seeds."[10]

Department of Pathology, Sao Paulo University Medical School, Brazil.
[10] Calore, E. E., Weg, R., Haraguchi, M., Calore, N. M., Cavaliere, M. J. and A. Sesso.  “Mitochondrial metabolism impairment in muscle fibres of rats chronically intoxicated with Senna occidentalis seeds.”  Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.  Vol. 52, Issue 4.  pp. 357-63.  Pub. 2000 Aug.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 10987191 [PubMed – indexed for MEDLINE].

Influence of a highly purified senna extract on colonic epithelium

Summary: High amounts of Senna extract dramatically reduced cellular reproduction within the colon, possibly leading to tissue necrosis and/or colon cancer.

"BACKGROUND: Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls.
AIMS: To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression.
METHODS: Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically.
RESULTS: Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased.
CONCLUSION: Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use. Copyright 2000 S. Karger AG, Basel."[11]

Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands.
[11] van Gorkom, B. A., Karrenbeld, A., van Der Sluis, T., Koudstaal, J., de Vries, E. G. and J. H. Kleibeuker.  “Influence of a highly purified senna extract on colonic epithelium.”  Digestion. Vol. 61, Issue 2.  pp. 113-20.  Pub. 2000.  Online.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 10705175 [PubMed – indexed for MEDLINE].

Constipation in childhood: a controlled comparison between lactulose and standardized senna

Summary: In a clinical study, lactulose demonstrated much more effectiveness and fewer side effects than Senna when used to relieve constipation in children.

"Twenty-one children under 15-years' old with chronic constipation were treated in a crossover trial lasting 3 weeks. In the first week they received either lactulose or senna, in the next week no treatment, and in the third week the alternative treatment. Patient diaries were kept by parents on the number and character of stools passed, and of side-effects reported, during the 3 weeks. There was a significant difference, in favour of lactulose, in the number of days on which normal stools were passed during the treatment weeks. The number and frequency of the side-effects reported in the senna treatment week were very much higher (p less than 0.001) than in the lactulose week. Lactulose is recommended as an effective and very well tolerated treatment for the constipated child."[12]

[12] Perkin, J. M.  “Constipation in childhood: a controlled comparison between lactulose and standardized senna.”  Current medical research and opinion.  Vol. 4, Issue 8.  pp. 540-3.  Pub. 1977.  Online.  Accessed: 24 Jan 2007.  (Highlighted text by Colon Cleanse and Constipation Resource Center).
Available:  PubMed PMID: 872608 [PubMed – indexed for MEDLINE].

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