Pineal gland: influence on gonads of male rats treated with androgen 3 days after birth.

Either blinding or the injection of 1 milligram of testosterone propionate into male Sprague-Dawley rats, 3 days old, results in testes and accessory organs (seminal vesicles and coagulating glands) that are smaller than normal when the rats are 72 days old. The response to blinding is prevented by removal of the pineal gland, whereas the response to treatment with testosterone is unaffected by pinealectomy. Combination of the two treatments in 3-day- old rats causes testes to be less than one-third their normal size at 72 days of age; pinealectomy in these rats permits the reproductive organs to grow to the same size as those in the androgen-treated animals.

Intravenous cyclosporine in refractory pyoderma gangrenosum complicating inflammatory bowel disease.

BACKGROUND: Pyoderma gangrenosum complicates inflammatory bowel disease in 2-3% of patients and often fails to respond to antibiotics, steroids, surgical debridement or even colectomy. METHODS: We performed a retrospective chart analysis of 11 consecutive steroid-refractory pyoderma patients (5 ulcerative colitis, 6 Crohn's disease) referred to our practice and then treated with intravenous cyclosporine. Pyoderma gangrenosum was present on the extremities in 10 patients, the face in 2, and stomas in 21. At initiation of intravenous cyclosporine, bowel activity was moderate in 3 patients, mild in 4, and inactive in 4. All patients received intravenous cyclosporine at a dose of 4 mg/kg/d for 7-22 days. They were discharged on oral cyclosporine at a dose of 4-7 mg/kg/d. RESULTS: All 11 patients had closure of their pyoderma with a mean time to response of 4.5 days and a mean time to closure of 1.4 months. All seven patients with bowel activity went into remission. Nine patients were able to discontinue steroids, and nine were maintained on 6-mercaptopurine or azathioprine. One patient who could not tolerate 6-mercaptopurine had a recurrence of pyoderma. No patient experienced significant toxicity. CONCLUSION: Intravenous cyclosporine is the treatment of choice for pyoderma gangrenosum refractory to steroids and 6-mercaptopurine should be used as maintenance therapy.

Hierarchy.

Dominance hierarchies (sometimes called "pecking orders") are virtually universal in social species, including humans. In most species and in ancestral and early human societies, these hierarchies allocate scarce resources, including food and often access to females. Humans sometimes use hierarchies for these allocational purposes, but humans use hierarchies for productive purposes as well-as in firms, universities, and governments. Productive hierarchies and dominance hierarchies share many features. As a result, people, including students of human behavior, often confuse types of hierarchies. For example, the Communist Manifesto attributes features to productive hierarchies that are actually characteristic of dominance hierarchies. Government hierarchies are particularly confusing, as they have many features of both types. In modern societies with socially mandated monogamy and voluntary attachment to hierarchies in the form of competitive labor markets, productive hierarchies are generally useful for all members, and it is important not to confuse the two types, either in policy or in scientific analysis.

Pharmaceutical advertising as a consumer empowerment device.

Pharmaceutical companies have greatly increased their level of "direct-to-consumer" (DTC) advertising in recent years. For 1998, estimates are that over $1.1 billion was spent on this form of advertising, increased from $850 million in 1997 and $600 million in 1996. In 1998, 84 separate drugs were advertised to consumers. The impetus was a decision in August of 1997 by the Food and Drug Administration to reduce the restrictions on DTC advertising on television. As a result, such ads have become very common on TV, and 32 products were advertised on TV in 1998. Pharmaceutical companies advertise because they think that advertising will make money for them. But how will this make money? It will make money by providing consumers with the information they need to make proper decisions about medication. That is, DTC advertising is profitable exactly because it empowers consumers and enables them to purchase useful drugs. The goals of advertising companies and consumers are both for consumers to have information about the most beneficial drug for particular conditions, and so advertising is beneficial both to manufacturers and to consumers. This article describes emerging trends in DTC within the context of the life sciences sector.

Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease.

A private practice was surveyed for prevalence of inflammatory bowel disease (IBD) in husband-wife partners and in their children. Among approximately 2500 patients with IBD in our files, 19 couples were identified. They were subdivided into group A (n = 5) in which both partners had symptoms of IBD before marriage; group B (n = 7) in which only one spouse had IBD before marriage and the other partner experienced symptoms afterwards; and group C (n = 7) in which neither spouse had symptoms before marriage but IBD subsequently developed in both. In group B, the disease developed in the second spouse 2-16 years after marriage (mean, 6.4 years). In group C, IBD developed in the first spouse 0.3-41 years after marriage and in the second spouse 1-14 years after the first spouse (mean, 6.8 years). Thirty-five children have been born to 16 of the couples. Two children died before age 20. Of the surviving 33 children, IBD has already developed in 12 (36%). Among the other 21 unaffected children, 1 had uveitis at age 9 and 10 are still under the age of 21, perhaps too young to have yet developed IBD. The frequency of IBD in children was slightly higher if both parents had already developed IBD at the time of conception (67%) compared with when only 1 parent (50%) or neither parent (50%) had developed IBD when conception occurred. Although these data do not distinguish genetic from environmental factors, they show a higher risk of IBD in children when both parents have this illness.

Desensitization to sulfasalazine after hypersensitivity reactions in patients with inflammatory bowel disease.

Desensitization to sulfasalazine was successful in 40/47 (85%) patients with IBD who previously had hypersensitivity reactions. The desensitization with sulfasalazine was well-tolerated with no serious complications in short- or long-term follow-up. The course of IBD was subsequently favorable in 35/40 (87%) for extended periods including 17/17 (100%) with ulcerative colitis. Desensitization should be attempted in patients who have had typical hypersensitivity reactions to sulfasalazine.

Maintenance oral sulfasalazine prolongs remission in ulcerative proctitis and proctosigmoiditis.

We have retrospectively compared the effectiveness of five different regimens for inducing and maintaining clinical remission in 206 patients with idiopathic proctitis (n = 115) and proctosigmoiditis (n = 91). The five therapeutic regimens were: corticosteroid enemas, 5-aminosalicylic acid (5-ASA) enemas, oral 5-ASA (sulfasalazine or mesalamine), corticosteroid enemas plus oral 5-ASA, or 5-ASA enemas plus oral 5-ASA. Clinical remission was achieved within 28 days of therapy in 47%, and eventually in 94% of these patients. No significant differences in efficacy were found among the five regimens. Most patients ultimately experienced a recurrence of symptoms, but the duration of remission was significantly longer with maintenance oral sulfasalazine or mesalamine (17.2 months) than with no therapy (11.8 months), P less than 0.01. We conclude that several regimens are equally effective in inducing remission of proctitis and proctosigmoiditis, although prolonged therapy may be needed to accomplish this goal. Maintenance oral 5-ASA significantly prolongs symptomatic remission in proctitis and proctosigmoiditis.

Screening and surveillance colonoscopy in chronic Crohn's colitis.

BACKGROUND & AIMS: Unlike ulcerative colitis, there are few reports on the efficacy of surveillance colonoscopy in patients with chronic Crohn's colitis and therefore little agreement as to whether routine surveillance is indicated. We report on 259 patients with chronic Crohn's colitis who underwent screening and subsequent surveillance colonoscopy and biopsy since 1980. METHODS: Biopsies were performed at 10-cm intervals and from strictures and polypoid masses. Pathology was classified as normal, dysplasia (indefinite, low-grade, high-grade), or carcinoma. RESULTS: A total of 663 examinations were performed on 259 patients. The median interval between examinations was 24 months; examinations were performed more frequently (1-6 months) in patients with dysplasia on biopsy. A thinner-caliber colonoscope was required to complete 12% of screening examinations and 23% of surveillance examinations. The pediatric colonoscope helped increase our yield of neoplasia by 19%. The screening and surveillance program detected dysplasia or cancer in 16% (10 indefinite, 23 low-grade, and 4 high-grade dysplasias and 5 cancers). A finding of definite dysplasia or cancer was associated with age >45 years and increased symptoms. By life table analysis, the probability of detecting dysplasia or cancer after a negative screening colonoscopy was 22% by the fourth surveillance examination. CONCLUSIONS: Colonoscopic surveillance should be strongly considered in chronic extensive Crohn's colitis.

The long-term outcome of ulcerative colitis treated with 6-mercaptopurine.

OBJECTIVES: To determine the long term outcome of ulcerative colitis in patients treated with 6-MP. METHODS: The charts of 105 chronic refractory ulcerative colitis patients treated with 6-MP from 1973-1992 were reviewed. The focus was placed on clinical response, subsequent breakthrough while maintaining 6-MP, and relapse rates when 6-MP was discontinued. RESULTS: Complete clinical remission was achieved in 68 patients (65%), partial remission was achieved in 25 patients (24%), and 12 patients (11%) failed to achieve remission. Of complete responders who continued 6-MP, 35% had a breakthrough, although complete remission was restored in 88% with the majority not requiring systemic steroids. Of complete responders who discontinued 6-MP, 87% subsequently relapsed. There were few major toxicities associated with 6-MP use. CONCLUSION: 6-MP is a reasonably safe and effective treatment for refractory ulcerative colitis. Patients who discontinue 6-MP after successful treatment have high relapse rates, therefore, 6-MP must be maintained long term to sustain remission.

Medical decompression of toxic megacolon by "rolling". A new technique of decompression with favorable long-term follow-up.

We treated 19 consecutive patients with toxic megacolon complicating inflammatory bowel disease with the usual intensive medical regimen, but also added a new technique, namely, the frequent rolling of the patient to the prone position in order to redistribute colonic gas and thereby promote decompression. In all 19 patients (100%) the colon was decompressed within 1-13 days (mean 4.9 days). Two patients (10.5%) died. In long-term follow-up (mean 6.5 years), only 4 of the 17 survivors (21%) ultimately required colectomy; the remaining 13 (68%) were either completely well or only minimally symptomatic and did not require steroids. Most reports on the management of toxic megacolon stress the need for early surgical intervention, but our success in decompression with the addition of the "rolling technique" suggests an improvement in the nonoperative management of toxic megacolon.

Refractory pouchitis: does it reflect underlying Crohn's disease?

Typical 'pouchitis' is a well recognised complication of ileal pouches in ulcerative colitis. Infrequently, a refractory pouchitis (RP) presents with certain clinical, endoscopic, and pathological features resembling Crohn's disease and is often ascribed to misdiagnosis of the initial colitis. To test that hypothesis and to identify risk factors for RP, this study reviewed cases of presumed ulcerative colitis with ileal pouches constructed at The Mount Sinai Hospital between 1973 and 1986. Twenty four cases with RP (16 Kock pouches and eight pelvic pouches) and 21 controls were compared for eight clinical variables. The original colectomy slides from 15 RP and 18 control cases were reviewed blindly, classified into five histological categories (corresponding to definite ulcerative colitis, definite Crohn's disease, and three indeterminate groups), and scored for 23 histological features. There were no significant clinical differences between RP and control cases except for more frequent extraintestinal manifestations (38% v 5%) and male preponderance (79% v 43%) in RP. There were also no significant differences between the distributions of RP cases and controls among the five histological categories or in the 23 histological features studied. Refractory pouchitis therefore does not seem to reflect underlying Crohn's disease, but may be linked to immunological mechanisms that are manifested clinically as extraintestinal complications.

Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps.

BACKGROUND & AIMS: Adenomatous polyps are by definition dysplastic and pathologically indistinguishable from the dysplasia-associated lesion or mass (DALM) described in 1981. Yet, adenomatous polyps in noncolitic colons are usually removed definitively endoscopically, whereas DALMs are regarded as harbingers of colon cancer, mandating colectomy. METHODS: Since 1988, all of our patients with chronic ulcerative or Crohn's colitis and dysplastic polyps and no coexistent dysplasia in flat mucosa underwent colonoscopic polypectomy. Biopsy specimens were obtained also adjacent to polypectomy sites, from strictures, and throughout the colon at 10-cm intervals. Follow-up colonoscopies and biopsies were performed within 6 months after polypectomy and yearly thereafter. RESULTS: Colonoscopy in 48 patients with chronic colitis (mean duration, 25.4 years) resected 70 polyps (60 in colitic and 10 in noncolitic mucosa). Polyps were detected on screening colonoscopies (29%) and on surveillance (71%). Pathology was tubular adenoma in all polyps from noncolitic mucosa and low-grade dysplasia (57), high-grade dysplasia (2), or carcinoma (1) in polyps from colitic mucosa. Subsequent colonoscopies (mean follow-up, 4.1 years) revealed additional polyps in 48% but no carcinomas. Surgical resection (6 patients) for recurrent polyps confirmed colonoscopic findings. No dysplasia or cancers in flat mucosa were found at surgery or on follow-up colonoscopies. CONCLUSIONS: In patients with chronic colitis who have no dysplasia in flat mucosa, colonoscopic resection of dysplastic polyps can be performed effectively, just as in noncolitic colons.