Twenty-year review of the surgical management of perianal Crohn's disease

PURPOSE: A retrospective analysis of 48 patients treated over a 20-year period (March 1973–April 1993) was undertaken to assess the results of our practice of early surgical intervention in suppurative complications of perianal Crohn's disease. METHODS: All patients were either seen in the office within the last six months or contacted by phone. RESULTS: The average age of our patients was 30 years at initial diagnosis. Thirty-four patients (71 percent) initially presented with intestinal disease and four (8 percent) with only perianal disease. Thirteen patients (27 percent) initially presented with simultaneous intestinal and perianal disease. The various fistulas at initial presentation included 8 intersphincteric (17 percent), 14 transphincteric (29 percent), 11 complex or multiple (23 percent), 5 rectovaginal (10 percent), and 2 unclassified, for a total of 40 patients. Eight patients (17 percent) presented with only an abscess. Eighty five percent of our patients healed after their first procedure, with an average time to heal of 2.8 months. Thirteen (27 percent) patients had recurrences after initial healing of their wounds. The mean time to recurrence after healing was 5.25 years. Fifty-four percent of our recurrences (7 patients) were treated by incision and drainage of an abscess only. Seven of 13 recurrences healed after the second procedure (54 percent), and 5 of 6 healed after a third procedure (83 percent). Only seven (14 percent) of our patients underwent a proctocolectomy during the study period, through September, 1993. Our overall probability of avoiding proctectomy and healing perineal wounds of 86 percent is consistent with published literature. CONCLUSIONS: Early aggressive surgical management of suppurative complications of perianal Crohn's disease before complex management problems ensue results in a high incidence of healing and a low risk of subsequent proctectomy.     

Disruption of temporal discrimination by drugs of abuse: I. Unmasking of a color bias

Pigeons were trained to discriminate the length of a delay period (3s vs. 10s). Under control conditions, pigeons were able to discriminate between the two delay period lengths with a high degree of accuracy (>90%). When delays of 1, 3, 5, 7, 9 and 11s were randomly presented, the percentage of responses appropriate to the 10s delay increased as a function of increasing delay length. Dose-response curves determined for a series of drugs of abuse showed that pentobarbital, diazepam and phencyclidine displayed the greatest efficacy in disrupting the discrimination. The decrease in accuracy was a function of both a decrease in the ability of the pigeon to discriminate the passage of time, and the expression of a drug-induced red color bias. When the stimulus colors were changed, these drugs still decreased accuracy of the discrimination without any evidence of a color bias. Morphine disrupted the discrimination at doses which produced marked response suppression; there was no evidence of a drug-induced color bias. Delta(9)-THC failed to produce any significant effect on the discrimination. d-amphetamine and cocaine initially had no effect; however, upon subsequent determinations and when the stimulus colors were changed during the last part of the experiment, they did disrupt discrimination performance. These results show that drugs of abuse have differential effects on temporal discrimination, with some drugs affecting temporal discrimination at doses that do not suppress responding, some affecting the discrimination at doses that decrease response rates, and others that do not appear to affect temporal discrimination. Only sedative/hypnotic drugs disrupted temporal discrimination in part by producing a red-color bias.     

Distribution of knowledge is the distribution of power

Earlier this year the Journal published an article by Brian Watkin in which he criticised the contribution made to the NHS by many health authority members. Now Charlotte Williamson, a member of the North Yorkshire AHA, takes the debate a stage further. The specific remit of members, she argues, is to protect the interests of patients by ensuring resources are allocated in accordance with need, and proper standards of care are achieved.     

Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy.

A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of "nongenetic" determinants in the development of "genetic" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes.     

The need to embrace molecular profiling of tumor cells in prostate and bladder cancer.

PURPOSE: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment. EXPERIMENTAL DESIGN: A Medline search of publications relating to MP of prostate and bladder cancer was carried out. A review article was written combining the relevant published literature along with the clinical and scientific experience of both centers. RESULTS: The advent of MP now provides a strategy by which these molecular abnormalities can be assessed. As well as being of diagnostic and prognostic use, these molecular profiles will identify putative molecular abnormalities within tumor cells that may be appropriate for therapeutic modulation. CONCLUSIONS: In prostate and bladder cancer, mapping out the molecular abnormalities could be translated into a valuable tool to help solve difficult issues regarding patient management decisions.     

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease

AIM—To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease.METHODS—A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required.RESULTS—Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months ?0.50, 95% confidence interval ?1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians ?2, 95% CI ?4, 0). The study was stopped early because of failure to recruit babies at the expected rate.CONCLUSIONS—R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.     

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.