Improving the ambulatory surgical services on the basis of the work experience of the Center of Ambulatory Surgery

Centers of ambulatory surgery made on the basis of large city polyclinics and regional medical formations are considered to be a perspective and economically effective form of perestroika of the ambulatory surgical aid to people. Specificity of the operative procedures performed at the Center and specific features of postoperative management of the patients should be taken into consideration, and the staff of such units must consist of highly trained surgeons of wide type. The ambulatory surgery Center must occupy its place in the system of dispensary examinations of the population.     

Immunohistochemical detection of p53 in Wilms' tumors correlates with unfavorable outcome.

The role of p53 in the pathogenesis and progression of Wilms' tumors is only partly understood. Although p53 mutations were initially reported only in anaplastic Wilms' tumors, we had reported that, of two of twenty-one cases that had a p53 mutation, one tumor showed no evidence of anaplasia. To determine the significance of p53 expression in all clinical stages of Wilms' tumor, twenty-eight cases were analyzed for p53 immunoreactivity. Paraffin sections were immunolabeled with two different monoclonal antibodies, recognizing both mutant and wild-type p53. Fifteen of sixteen tumors in the recurrent/metastatic group and three of twelve tumors in the nonmetastatic/nonrecurrent group showed p53 immunopositivity. Only one of three positive tumors in the latter group showed moderate to strong positivity, whereas twelve of sixteen metastatic/recurrent tumors revealed a similar degree of p53 positivity. The positivity was stronger in the metastasis/recurrences as compared with the corresponding primary tumor. Western blot analysis revealed p53 expression in all of the Wilms' tumors tested, suggesting its involvement in the development of Wilms' tumors. Single-strand conformation polymorphism analysis performed on twenty-three of these tumors revealed p53 mutations in four of fourteen recurrent/metastatic tumors and none in the nonmetastatic/nonrecurrent group. Our results show that, whereas 60% of cases were immunopositive for p53 protein, mutations were detected in only 16% of tumors, indicating that wild-type p53 protein is retained in the other tumors. We conclude that p53 immunopositivity strongly correlates with recurrence/metastasis in Wilms' tumors. Furthermore, the accumulation of p53 in these tumors is not only due to mutations but may also involve stabilization of normal p53 with other proteins.     

Voluntary HIV counseling and testing: experience among the sexually active population in Bangui,Central African Republic

OBJECTIVES: In July 1997, the National Reference Center for Sexually Transmitted Diseases of Bangui, Central African Republic (CAR), was expanded by the creation of an anonymous and voluntary counseling and testing (VCT) unit for HIV infection, the Anonymous Surveillance Unit (Unité de Dépistage Anonyme [UDA]). The goal of the UDA was to initiate and promote voluntary HIV testing in the general adult population of Bangui. We carried out an observational and comprehensive survey over a 4-year period to document and analyze the experience of VCT in the UDA, with special attention to risk factors associated with HIV infection. METHODS: All clients for VCT were given adequate pretest counseling by trained counselors focused on knowledge about HIV infection and sexually transmitted infections, individual risks of acquiring HIV, and anticipation of the client's attitude about test results. After consent was obtained, a blood sample was drawn and tested for HIV by two ELISAs in parallel. The client paid a standard cost of $1.20 at the initial visit. After a week, test results were given to the client during the posttest visit, at which time HIV-seropositive individuals received emotional support and were referred to specific social or medical structures. Seronegative clients received reinforcement of prevention messages and were asked to come back for serologic follow-up free of charge after 3 (M3) and 12 (M12) months. RESULTS: From July 1997 to March 2001, 5686 individuals aged 14 to 65 years (mean age, 27 years) had an initial visit for VCT (V1). Peaks of UDA visitation (250-450 clients) were observed on the annual AIDS Day in the CAR, at which time HIV serologic testing was offered free of charge. A total of 5060 (89%) clients came back for a second visit (V2) to receive test results. Among those, 18.3% were infected with HIV type 1. Multivariate analysis of risk factors demonstrated marked association of HIV seropositivity with age, female gender, widowed/divorced women, poor or low education level, occupations such as civil servants or merchants, presence of symptoms of sexually transmitted infections, and lack of systematic condom use. Single young women were at higher risk for HIV infection compared with men of the same age (OR = 7.7 for women aged 15-24 years, 95% CI: 4.0-14.0; OR = 2.8 for women aged 25-34 years, 95% CI: 1.7-4.5). Widowed women older than 44 years of age were more likely to be HIV-seropositive than men (OR = 10.0; 95% CI: 1.7-83.6). A total of 885 (21%) HIV-seronegative individuals returned for follow-up at 3 months (M3; 0.45% rate of seroconversion). Seventy-nine (9%) individuals returned at 12 months (M12), without any new cases of HIV infection. HIV-negative clients consulting at M3 and M12 showed a significant reduction in unprotected intercourse with occasional sexual partners. CONCLUSION: This experience demonstrates that VCT for HIV infection is feasible in Central Africa.     

Epidemiology of genital herpes simplex virus infection in developed countries

Comparisons of the seroepidemiology of genital herpes simplex virus (HSV) infection within and between countries are hampered by variations in tests, methods and populations sampled. Differences in seroprevalence may partly reflect variability in diagnostic efforts and healthcare awareness, expectations and utilization. To allow comparison between surveys and to improve their performance, seroepidemiological studies should use validated HSV type-specific tests, report age-specific or age-adjusted prevalence and define the period of time over which samples were collected. Despite the difficulty of comparing studies, the prevalence of HSV-2 infection varies between developed countries. Among healthy adult populations, HSV-2 seroprevalence is higher in the USA than in Europe. Furthermore, HSV-2 seroprevalence varies widely among European countries. For example, in 1989 HSV-2 seroprevalence among pregnant women was reported to be 33% in Sweden compared with 8.3% in Germany. In some, but not all, countries, HSV-2 seroprevalence appears to be increasing. In the USA, the National Health and Nutrition Examination Surveys found that HSV-2 seroprevalence increased by almost one third from 16.4% to 21.8% from 1976 to 1994 in people over 12 years old. The incidence of HSV infection is a measure of primary infection. HSV incidence is difficult to quantify, partly due to unrecognized or asymptomatic infections. However, estimates of incidence in North American and European populations range from 5 to 24 per 100 people per year. Prevention programmes should recognize that HSV-2 seroprevalence increases rapidly in early adult life. The proportion of genital herpes infections caused by HSV-1 is increasing in the developed world, possibly due to changes in oral-genital sexual behaviour and lower rates of HSV-1 acquisition in childhood.     

Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia,Croatia

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex‐specific dependence on age were under control of the same putative large‐effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed. Am. J. Hum. Biol. 13:398–408, 2001. © 2001 Wiley‐Liss, Inc.     

PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells

We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease.     

Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis

We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001).     

Large sample test of defibrillation waveform sensitivity

INTRODUCTION: An unknown mechanism causes defibrillation efficacy to be sensitive to the temporal pattern (waveform) of the delivered energy. Using a guinea pig model, we tested hypotheses in 140 defibrillation waveforms. METHODS AND RESULTS: Two hundred seven male guinea pigs (950 +/- 100 g) were instrumented to continuously monitor the ECG and an optical plethysmographic signal from a forepaw. Two amplifiers served as a voltage-based defibrillator with a maximum output of 400 V at 2 A. Defibrillation electrodes (12-mm diameter) were placed 40 mm apart on the thorax. Thirty ventricular fibrillation episodes were induced where the first 10 episodes were used to estimate ED50 for a biphasic pulse (7/2 msec) and the remaining episodes were defibrillated with 18 test waveforms and two control waveforms all at the ED50 energy. Seven groups of 20 waveforms were tested. We directly tested hypotheses based on charge banking/burping, frequency concentration, and stimulus strength/duration. Of the hypotheses tested, nine are able to predict at least a 10% change in efficacy (P < 0.05): parabolic fit to duration; maximum, minimum, and remaining delivered charge; power at peak frequency; stimulus charge; and maximum, minimum, and maximum of the absolute value of stimulus strength. However, of these, only three are independent predictors of waveform efficacy (P < 0.05, near-minimum residual variance): power at peak frequency; parabolic fit to the stimulus duration; and minimum stimulus strength. CONCLUSION: Stimulus strength and duration are the main determinants of the efficacy of a defibrillation waveform.