Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.

People afflicted with Hirschsprung disease (HS) lack intestinal nerve cells, resulting in a grossly enlarged colon. Besides distended abdomen, patients suffer from constipation, vomiting and enterocolitis inflammation of the mucus membranes of intestines, large and small.

HS, also known as congenital megacolon, strikes one in 6,250 newborns. The affected bowel is unable to transmit peristalsis waves of alternate circular contraction and relaxation of the intestinal tract, by which fecal contents are propelled onward. The disease is also marked by toxic megacolon, diarrhea, lethargy, fever, dehydration and/or sepsis.

A sign of intestinal obstruction calls for the patient’s prompt transfer to a tertiary (teaching) hospital for surgery. Surgical options include a temporary colostomy to restore colonic function, and definitive anastomosis excision of the affected bowel segment. A majority of patients achieve fecal continence, and normal lives.

The eponymic disorder gets its name from a Danish physician, Harald Hirschsprung (1830-1916), who first recognized the disease in 1888.

A paper in Nature Genetics, released online April 15, 2002, bears the title: “Segregation at three loci explains familial and population risk in Hirschsprung disease.” It leads off by pointing out that HS, “the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance.” The authors describe their finding as the first case of complete dissection of a complex genetic disorder. By combing through the genomes of 49 families, they found 67 affected sibling pairs and 106 affected individuals with multiple cases of HS. Gene linkage analysis detected three chromosomal regions in which mutations are necessary and sufficient to cause the disease.

One of the three loci revealed the RET gene, which resides on the long arm of human chromosome 10. Two other loci, on chromosomes 3 and 19, harbor genes that are yet to be identified.

An accompanying News & Views commentary, titled “Dissecting Hirschsprung disease,” makes the point, “In complex (multifactorial or multigenic) disorders, it has not so far been possible to identify the particular contributions of individual genes, making it difficult to correlate genotype with phenotype.” N&V commends the main article’s approach “as a model for the analysis of other complex diseases.”

Three Triggers To Kaposi’s Sarcoma: Immune System Suppression, Herpesvirus On Scene, An Open Cut

At the University of North Carolina school of dentistry in Chapel Hill, a 38-year-old HIV-positive man volunteered to take part in a study of AIDS-associated salivary gland disease. Researchers collected blood and throat secretions, and cut off a tiny biopsy of salivary gland tissue for analysis. Several days later, the volunteer came back with a sizeable, reddish-purple lesion growing inside his lip at the biopsy site. Despite antibiotics, it continued to enlarge, and soon extended outward to his chin. A second biopsy revealed the growth to be Kaposi’s sarcoma a tumor found traditionally only in elderly, heterosexual men in countries abutting the Mediterranean sea. Radiation treatment caused its disappearance from the volunteer, who had no recurrence in two years.

The U.C. dentistry researchers report this case history in the New England Journal of Medicine (NEJM), dated April 18, 2002. The paper’s title: “Development of Kaposi sarcoma in a surgical wound.”

KS is the commonest cancer that develops in HIV-positive patients who are progressing to full-blown AIDS. The NEJM’s article bore out that at least three key elements are central to development of KS. First is suppression of the immune system which HIV causes, and organ transplantation imposes. Second is the presence of human herpesvirus 8 (HHV8) at the lesion’s site. Third is trauma, after which healing begins. The authors surmised that what kick-started KS in that volunteer was that the natural healing process called in certain cells to help restore the damaged tissue. But since these cells were already infected with the cancer-causing HHV8, that caused the KS malignancy to get going.

The NEJM article adds that this work may explain why some people who have surgery, including organ transplantation, develop KS at the site of their sutures. It also suggests that antiviral agents targeted at HHV8 might help prevent KS in immunosuppressed patients, either by HIV or by organ grafting. They conclude that their examination of saliva, rather than the customary blood, achieved their KS diagnosis.

Often-Lethal Subarachnoid Hemorrhage Curbed In Stricken Rabbits Dosed With Erythropoietin

Cerebral stroke, neurological disability and premature death are the all-too-frequent sequelae of subarachnoid hemorrhage. This aneurysmal event usually follows cerebral vasoconstriction. The lack of an adequate treatment for the condition has stimulated numerous experimental and clinical studies for development of effective therapeutic strategies.

Neurosurgeons at the University of Messina in Italy have come up with a novel agent the anti-anemia drug erythropoietin (EPO). They report their finding in the Proceedings of the National Academy of Sciences dated April 16, 2002, in a paper titled: “Beneficial effects of systemic administration of recombinant human erythropoietin in rabbits subjected to subarachnoid hemorrhage.”

“Of eight rabbits,” the paper stated, “those in the placebo group showed progressive neurological deterioration. The neurological status of those treated with EPO was significantly better. At 72 hours after incurring the experimental subarachnoid hemorrhage, three animals showed minimal deficits, and the other five were normal.”