Cyclodextrin nephrosis in the rat.

The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death.     

Subcellular distribution of beta-adrenoceptors in brain following administration of antidepressant drugs

The distribution of specific binding of [3H]dihydroalprenolol([3H]DHA) in sucrose gradients (0.2-1.75 M), containing homogenates of the cortex of rat brain, centrifuged to equilibrium (110,000 g/16 hr), was examined in controls and after treatment with antidepressant drugs. There were no significant changes in the specific binding of [3H]DHA after acute administration of desipramine (DMI, 50 mg/kg) or clorgyline (20 mg/kg), either in terms of the number of receptors or distribution in the sucrose gradient. There was a significant decrease (29%) in the number of beta-adrenoceptors after the chronic regimen with DMI, but again no apparent alteration in the density of the receptor-containing membranes, both samples having a maximum distribution at approximately 1.1 M sucrose. Non-specific binding was maximal at 0.65 M sucrose. Electron microscopy showed that the non-specific binding was largely to myelin and the fraction containing most specific binding was composed of membrane fragments. The activity of Na+ K+ ATPase had a single broad peak (maximum at 1.1 M sucrose). Thus, at the times studied, in vivo desensitisation/internalisation of cortical beta-adrenoceptors did not apparently occur following large acute doses of antidepressant drugs and furthermore the down-regulation which followed the chronic regimen with DMI did not involve migration of receptors into "light density fractions" which are reported to be present after acute exposure to agonists in vitro.     

Is there a glass ceiling at national trauma meetings?

BackgroundThe purpose of this study was to evaluate the roles of women at national trauma meetings.MethodsAvailable scientific programs for the American Association for the Surgery of Trauma (2013-19), Eastern Association for the Surgery of Trauma (2010-19), and Western Trauma Association (2010-19) as well as the Scudder Oration at the American College of Surgeons (1963–2019), were reviewed for names of participants and categorized by gender.ResultsWomen made up 963 of 2746 (35.1%) of presenters, 252 of 1020 (24.7%) of discussants, 116 of 622 (18.6%) of moderators of scientific sessions, 189 of 707 (26.7%) of panelists, and 69 of 254 (27.2%) of panel moderators. Only 12 of 126 (9.5%) of named lectures or presidential addresses were given by women.ConclusionsThe low rate of female named speakers suggests that there remains a “glass ceiling” when it comes to upper-level participation in national trauma meetings.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

An analysis of decision making in discharge planning

A repeated-measures design was used to examine medical professionals' discharge planning strategies. Physicians, residents, nurses, and social workers were presented with 16 hypothetical case scenarios and asked to: (1) rate the appropriateness of four discharge options (nursing home, community nursing, adult day, and outpatient clinic care), and (2) select the most appropriate discharge plan for each case. Four within-group variables were included in the scenarios: physical impairment, caregiver availability, follow-up required, and patient compliance. Decisions were greatly influenced by caregiver availability. When a caregiver was available, respondents preferred community-based options (i.e., community nursing care or outpatient clinic); if the case involved complications (i.e., severe physical impairment, heavy follow-up, noncompliant patient), they considered community nursing care more appropriate than outpatient clinic. When a caregiver was unavailable, respondents preferred institution-based options (i.e., nursing home or adult daycare); if there were complications, they considered nursing home more appropriate than adult daycare.     

Incidental cholecystectomy during colorectal surgery.

OBJECTIVE: To assess the risks and benefits of incidental cholecystectomy in patients having colorectal surgery. SUMMARY BACKGROUND DATA: Cholelithiasis is found commonly during abdominal surgery. Previous studies used disparate methods to assess the risks and benefits of incidental cholecystectomy and have reached contradictory conclusions. METHODS: All patients in whom asymptomatic cholelithiasis was noted during colorectal surgery between January 1982 and December 1986 were studied. Operative morbidity and long-term outcome were assessed by chart review and questionnaire. RESULTS: Three hundred five patients were identified, of whom 195 (63.9%) had an incidental cholecystectomy and 110 (36.1%) did not. The two groups were similar in terms of age, sex, primary disease, and associated medical conditions, although fewer emergency procedures, abdominoperineal resections, and Hartmann's procedures were needed in the cholecystectomy group. The overall operative morbidity rate was the same in both groups. The long-term risk for developing small bowel obstruction was also similar. After a median follow-up of 6 years after hospital discharge, biliary pain or cholecystitis developed in 16 patients (14.6%) in the "no cholecystectomy" group, 12 of whom have had cholecystectomy. Two additional patients had cholecystectomy for acute postoperative cholecystitis while still in the hospital. Six more patients have had incidental cholecystectomy at subsequent laparotomies. The cumulative probability of needing cholecystectomy at 2 and 5 years after the initial colorectal operation was 12.1% and 21.6%, respectively. CONCLUSIONS: Incidental cholecystectomy was not associated with increased postoperative morbidity, whereas the long-term risk that previously asymptomatic gallstones would become symptomatic was substantial. Unless there are clear contraindications, patients with asymptomatic gallstones who have colorectal surgery should have concomitant cholecystectomy.     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs