Response rates for providing a blood specimen for HIV testing in a population-based survey of young adults in Zimbabwe

Background  

To determine differences among persons who provided blood specimens for HIV testing compared with those who did not among those interviewed for the population-based Zimbabwe Young Adult Survey (YAS).     

CD154 is expressed during treatment with calcineurin inhibitors after organ transplantation

BACKGROUND: CD154 (CD40 ligand) monoclonal antibody prevents allograft rejection in rodents and monkeys. Inasmuch as calcineurin inhibitors (CI) inhibit CD154 expression by pharmacologic agents in vitro, we investigated whether CD154 is also inhibited by CI in vivo and in vitro during allogeneic stimulation. METHODS: CD154 expression was determined by immunohistochemistry and flow cytometry in human lymph nodes and spleen sections from rhesus monkeys with or without CI treatment. The effect of CI on induction of CD154 expression was studied by stimulating lymphocytes with phorbol 12-myristate 13-acetate (PMA) and ionomycin or with allogeneic monocyte-derived mature dendritic cells. RESULTS: Lymph nodes from patients with or without CI cyclosporine (CsA) or FK506 (FK) treatment showed comparable CD154 expression, which was present on the cell surface of T cells. CD154-expressing cells were also present in spleens from monkeys treated with CsA in comparable numbers to those in the nontreated group. Moreover, in several liver transplant rejection biopsies taken during CI therapy CD154-expressing cells were observed. In vitro, CsA and FK strongly inhibited induction of CD154 expression on peripheral blood mononuclear cells by pharmacologic stimuli. Maximum inhibition was found at 50 ng/ml CsA and 20 ng/ml FK. CD154 expression induced by dendritic cells in peripheral blood mononuclear cells or spleen cells was also almost completely inhibited by CsA. CONCLUSION: Although CI strongly suppressed pharmacologic and allogeneic induction of CD154 expression on T cells in vitro at concentrations at approximately clinical trough levels, CD154 is prominently expressed during CI therapy in lymphoid tissue and (sporadically) in liver allografts. This suggests that the CD154-CD40 pathway remains functional during CI therapy, which may contribute to allograft rejections in the clinical setting.     

Intermediate-dose cytarabine treatment delivered at moderate infusion rates for de novo acute myeloid leukemia-results of a phase I-II study

Published randomized trials on different cytarabine doses for the treatment of acute myeloid leukemia (AML) provide evidence of a dose-response effect. However, high-dose cytarabine (HIDAC) regimens correlate with increased morbidity and toxicity related mortality. Typical HIDAC regimens deliver 6 g/m2/d in infusion rates of 500-3000 mg/m2/h. However, pharmacokinetic measurements indicate that intracellular Ara-CTP formation is saturated at lower infusion rates than used in HIDAC schedules, probably causing cytarabine accumulation in the plasma and increased toxicity. It was our objective to investigate in a prospective non-randomized phase I-II study feasibility and efficacy of intermediate doses of cytarabine delivered at the presumptive saturating moderate infusion rate (mir-IDAC), as induction therapy in order to optimize intensified treatment for acute myeloid leukemia. Forty previously untreated patients younger than 60 years of age with de novo AML received intermediate doses of cytarabine (2-4 g/m2/d) at moderate infusion rates (250-667 mg/m2/h) over 6 or 8 h. Cytarabine was applied on alternate days (day 1, 3, 5, 7) in combination with an anthracycline as induction and consolidation therapy. Thirty-two of the 40 patients (80%, 95%CI:64-91%) achieved CR after induction treatment. Treatment-related mortality during induction chemotherapy was 2.5%. No cerebellar toxicity was observed. After two to four mir-IDAC courses stem cell harvesting was successful in 71% of the patients eligible for high-dose chemotherapy. After three years 56% (95%CI:40-72%) of all patients are alive and 59% (95%CI:42-76%) of the patients who entered CR are free of leukemia. In conclusion, favorable long-term outcomes and moderate acute toxicities were observed in patients with de novo AML treated with IDAC schedules delivered at moderate infusion rates (mir-IDAC) starting as induction treatment. The data suggest that a randomized trial should now be undertaken to examine whether mir-IDAC has clinical advantages over HIDAC.     

Schizophrenics show a failure in the decoding of violations of conversational implicatures

OBJECTIVES: Recent approaches to the 'theory of mind' and pragmatics support that, if we did not have any idea about what other people know, we could hardly use language effectively. Successful communication (the pragmatic aspect of language) depends on inferring the beliefs and intentions of the partner in the conversation. Such successful communication is linguistically realized in part by cohesion and in part by abiding by the maxims derived from the cooperative principle. However, the violations of the Gricean implicatures are generally used in everyday language, mainly to point at a hidden, most commonly negative opinion on others. We hypothesize that schizophrenics have difficulties in the decoding of these violations, as the core deficit in this disorder is around social cognition, theory of mind and pragmatic language use. MATERIAL AND METHOD: We have examined 26 paranoid schizophrenic patients and 26 normal control subjects by using 4 'question and answer' vignettes, where the Gricean maxim of relevance was violated to express a hidden, negative opinion by one partner during the communicative act. The subjects were asked to judge these opinions and were evaluated by the investigators on a score from 0 to 2 points. In a pilot study, interrater reliability was judged to be satisfactory. The data were analysed statistically by parametric and non-parametric tests. RESULTS: Statistical analyses of our data have shown that schizophrenics made significantly more mistakes during the decoding of the violated maxim as compared with controls (p < 0.0001), reflecting on the difficulties during the correct exploration of the social context, i.e. recognition of the speaker's hidden opinion. CONCLUSION: We conclude that patients with schizophrenia fail to decode intentional violations of conversational implicatures. These results point at a dysfunctional pragmatic language use among schizophrenic patients.     

Poly(sodium 4-styrene sulfonate): an effective candidate topical antimicrobial for the prevention of sexually transmitted diseases

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.     

Hepatic derangement following N‐Acetylcysteine enemas in an infant with cystic fibrosis

We discuss an infant with MI secondary to cystic fibrosis, who was managed surgically by a double barrel ileostomy for mid – small bowel atresia and developed severe faecal impaction in the post – operative period. The faecal impaction was treated successfully with oral NAC and 0.2% NAC contrast enemas. The patient's liver function tests revealed a dramatic increase in transaminases and bilirubin contemporaneous with the administration of the enemas. The levels showed a spontaneous improvement after discontinuation. This is only the second reported case of hepatotoxicity secondary to NAC enemas in the literature. While our experience offers modest support for the use of NAC, its efficacy is not yet proven and paediatric surgeons using NAC in the enema form need to closely monitor liver function contemporaneous with this agent's administration and adjust their treatment accordingly.     

Laparoscopic surgery for the cure of colorectal cancer

PURPOSE: The aim of this study was to assess the feasibility and safety of laparoscopic surgery for the cure of colorectal cancer with emphasis on oncologic follow-up in particular. METHODS: A study was performed of patients with colorectal cancer treated by laparoscopy in five German centers between May 1991 and September 1997. Surgical and pathologic data were recorded in an anonymous registry database and analyzed by type of resection. Standard procedures were sigmoid or left colectomy, anterior resection, abdominoperineal resection, and right hemicolectomy. Follow-up information included incidence of local, distant, and port site recurrence and cancer-related death. RESULTS: A total of 399 patients (212 females) with a mean age of 66.6 years underwent laparoscopic curative resections (sigmoid resection, 89; left colectomy, 11; anterior resection, 157; abdominoperineal resection, 102; right hemicolectomy, 40). Conversion was necessary in 6.3 percent (n=25). Complications requiring reoperation occurred in 9 percent (n=35). Complications that were treated conservatively occurred in 27.6 percent (n=110). Thirty-day mortality was 1.8 percent (n=7). First bowel movements resumed on the third postoperative day; patients did not use analgesics after a mean of five days. Mean postoperative hospitalization was two weeks. According to International Union Against Cancer classification, 147 patients had Stage I cancer, 35 had Stage II cancer, and 217 underwent curative resection for Stage III cancer. Mean number of lymph nodes resected was 12.1. At a mean follow-up of 30 months, one port site recurrence was documented. No local recurrence was observed after curative resection of Stage I colorectal cancer. Of 399 patients, local recurrence occurred in 6 patients (Stage II, 2; Stage III, 4), and distant metastases were documented in 25 patients (Stage I, 3; Stage II, 3; Stage III, 19). The highest incidence of cancer-related death occurred after abdominoperineal resection (4.9 percent). CONCLUSION: To assess the role of laparoscopic colorectal surgery for the cure of cancer objectively, prospective randomized trials are necessary.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.     

Kinetic and mechanistic studies of the peroxynitrite-mediated oxidation of oxymyoglobin and oxyhemoglobin

Kinetic studies of the peroxynitrite-mediated oxidations of oxymyoglobin (MbFeO(2)) and oxyhemoglobin (HbFeO(2)) showed that the mechanisms of these reactions are more complex than what had previously been reported; both reactions proceed in two steps. For myoglobin, we found that the small amount of deoxymyoglobin (MbFe(II)) which is in equilibrium with MbFeO(2) is first oxidized by peroxynitrous acid to ferryl myoglobin (MbFe(IV)=O). Then, in the second step, MbFe(IV)=O is reduced by peroxynitrous acid to metmyoglobin (metMb). The second-order rate constant values obtained at pH 7.3 and 20 degrees C for the two steps are (5.4 +/- 0.2) x 10(4) and (2.2 +/- 0.1) x 10(4) M(-)(1) s(-)(1), respectively. Analogous studies with hemoglobin suggest that its reaction with peroxynitrite follows the same mechanism. In this case, the second-order rate constant values measured at pH 7.0 and 20 degrees C for the two steps are (8.8 +/- 0.4) x 10(4) and (9.4 +/- 0.7) x 10(4) M(-)(1) s(-)(1), respectively. A possible mechanism in the absence as well as in the presence of CO(2) and the relevance of these reactions in vivo are discussed.