Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils

We investigated the mechanism(s) responsible for differences in the effects of acidic pH on Ca2+ activation of the activity of adult and neonatal rat heart myofilaments. Studies on preparations of myofilaments reconstituted with adult troponin-tropomyosin (Tn-Tm) and either adult or neonatal thick filaments indicated that the difference in effect of acidic pH is related to differences in Tn-Tm and not other myofilament proteins. Immunoblotting analysis showed that development of the rat heart myofibrils is associated with isoform switching from slow skeletal TnI to cardiac TnI and from a slow mobility isoform of TnT (TnT1) to a faster Mr isoform (TnT2. Expression of slow skeletal TnI was associated with a relative insensitivity of myofilament Ca2+ activation to deactivation by acidic pH. Moreover, the effect of acidic pH on Ca2+ activation of ATPase activity of soleus myofibrils, which contain cardiac TnC and slow skeletal TnI, was essentially the same as the effect of acidic pH on rat cardiac myofibrils in the early neonatal period. Neonatal myofilaments also contained a relative abundance of a set of polypeptides copurifying with the thin filaments. We have identified these proteins as histones. The relative amount of histones among a variety of preparations from different species was not correlated with the pH sensitivity of myofibrillar Ca2+ activation. Shifts in TnT isoforms among these species were also not correlated with an altered response to acidic pH. Our data provide evidence in support of the hypothesis that the relative insensitivity of neonatal myofilament activity to acidic pH is due to the presence of slow skeletal TnI in the thin-filament regulatory complex.     

Sexual Risk Intervention In Multiethnic Drug And Alcohol Users

An estimated 38.6 million persons globally are living with HIV, of whom over 1.1 million reside in Zambia. Of the 2 million cases in the US, 64% of new cases among women are among African Americans. Alcohol and drug use represents a significant risk factor for HIV transmission among both Zambians and African Americans. In addition, gender dynamics in both the US and Zambia promote transmission. This study examines two interventions targeting HIV risk behavior among HIV positive substance users, women in Miami, USA (the New Opportunities for Women (NOW) Project) and men in Lusaka, Zambia (the Partner Project). The study compares the efficacy of these two culturally tailored sexual behavior interventions provided in group and individual session formats. US and Zambian participants increased sexual barrier use and reduced substance-related sexual risk. Comparatively greater gains were made by higher risk Zambian males than US females in both group and individual conditions. Among lower risk participants, women in the group condition achieved and sustained the greatest comparative risk reductions. Results suggest that cost effective group HIV transmission risk reduction interventions for multiethnic individuals can be successfully implemented among both female and male drug and alcohol users in multinational settings.     

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

Postoperative Intravenous Drip Infusion is not Required after Minilaparotomy Cholecystectomy

Objective: To determine if drip infusion should be discontinued after full recovery of the patient from anaesthesia after minilaparotomy cholecystectomy in uncomplicated cases.Design: A randomised controlled clinical trial on 60 patients, from the waiting list, of cholelithiasis/cholecystitis operated by minilaparotomy cholecystectomy between November 1995 to March 1996. 30 patients did not receive postoperative IV drip infusion and in 30 patients 12–24 hours of standard drip transfusion was continued according to the current practice.Setting: Single Surgical Unit, SS Hospital, Banaras Hindu University, Varanasi, India.Main outcome measure: Recognition of clinical indication for continuation of. IV drip infusion after full recovery from anaesthesia.Results: In the cohorts of 30 patients each who were or were not given IV drip infusion after full recovery from anaesthesia following minilaparotomy cholecystectomy the observations on pulse rate, blood pressure, time to first voiding of urine and time to start first oral intake of fluids were identical. However postoperative urinary retention occured in 6 (20%) patients in whom the IV drip infusion was given.Conclusion: There is no clinical indication to continue IV drip infusion after full recovery from anaesthesia in patients operated for minilaparotomy cholecystectomy.