Combination drug therapy for cryptosporidiosis in AIDS

Aside from effective antiretroviral therapy, there is no consistently effective antiparasitic therapy for cryptosporidiosis in AIDS. The purpose of this study was to assess safety, efficacy, and durability of combination therapy with paromomycin and azithromycin for chronic cryptosporidiosis. Patients with AIDS, chronic cryptosporidiosis, and < 100 CD4 cells/microL were treated with open-label paromomycin (1.0 g twice a day) plus azithromycin (600 mg once a day) for 4 weeks, followed by paromomycin alone for 8 weeks. In 11 patients, median stool frequency decreased from 6.5/day (baseline) to 4.9/day (week 4) and 3.0/day (week 12). Median reductions in 24-h oocyst excretion were 84%, 95%, and >99% at 2, 4, and 12 weeks, respectively. None of the responses were attributable to antiretrovirals. Of 5 survivors at 12-30 months of follow-up, 3 remain asymptomatic off medications, and 2 have chronic, mild diarrhea. Treatment of cryptosporidiosis with azithromycin and paromomycin was associated with significant reduction in oocyst excretion and some clinical improvement.     

Highly active antiretroviral therapy decreases the incidence of bacteremia in human immunodeficiency virus-infected individuals

Dandruff is a clinical alteration of the skin that consists histologically of orthokeratotic clumps with minute parakeratotic foci found in inflammatory pathologies such as seborrheic dermatitis and psoriasis. Therefore, some nucleated cells should be found in dandruff and hence there is a possibility that forensically typeable DNA could be extracted from dandruff. Because of a particular case in which we were involved, a study was carried out to determine whether or not DNA could be extracted from dandruff, and if the two most widely used extraction techniques (Chelex and organic) would be applicable. Results show that sufficient quantities of DNA (more than 30 to 40 ng) can be obtained from as little as 1.0 to 1.5 mg of dandruff. Both methods yield DNA, although the organic procedure seems to yield more (72.5 ng Chelex vs. 183.3 ng organic). All the DNA samples extracted were typed correctly for the loci HUMTH01 and HUMvWA. Therefore, dandruff can be considered a potential source of DNA for forensic identification.     

The impact of antiretroviral therapy on AIDS survival observed in a province-wide drug treatment programme

Erythrocytosis is a relatively common complication of renal transplantation. Recent observations indicate that angiotensin-converting enzyme inhibitors correct renal transplant erythrocytosis. Other drugs to inhibit the renin-angiotensin system have been developed recently. The newest of these is losartan, a specific antagonist of the angiotensin II type I receptor. We report three patients in which the use of losartan controlled posttransplant erythrocytosis. Our findings suggest that losartan can be effective and safe in the treatment of posttransplant erythrocytosis.     

Changing trends in melanoma incidence and mortality

OBJECTIVES: This article analyzes trends in melanoma incidence and mortality rates. Information on sun exposure supplements these statistics. DATA SOURCES: Melanoma incidence data were obtained from the National Cancer Incidence Reporting System and from the Canadian Cancer Registry. Cancer mortality data were extracted from the Canadian Vital Statistics Data Base. Information on sun exposure is from the 1996 Sun Exposure Survey. ANALYTICAL TECHNIQUES: Incidence and mortality rates were age-standardized to the 1991 Canadian population to account for changes in the age structure of the population over time. The average annual percentage changes in age-specific rates were calculated for selected time periods. MAIN RESULTS: After years of steady increases, melanoma incidence and mortality rates have levelled off as a result of declining rates in younger age groups, and for melanoma of the trunk among men and of the leg among women. Incidence rates for men are now higher than those for women; mortality rates for men are twice as high as for women.     

Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators

CONTEXT: Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. OBJECTIVE: To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters). DESIGN: Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model. SETTING: The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh, Pa). PARTICIPANTS: A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population. MAIN OUTCOME MEASURES: Time from seroconversion to development of AIDS and to death and change in CD4 cell count. RESULTS: A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01 ) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. CONCLUSIONS: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.     

Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors

Intravascular Doppler is widely used for experimental studies in the coronary circulation. We designed this study to assess baseline bloodflow and arteriolar resistance in the porcine renal circulation and to study the vasomotor responses of vasoactive drugs. In anesthesized piglets (n = 15), renal arterial diameter was measured with quantitative angiography and blood flow velocity with a Doppler wire (Cardiometrics). Bloodflow and resistances were calculated at baseline and after injection of vasoactive drugs (isosorbide dinitrate, papaverine). This allowed us to determine the renal bloodflow reserve (the capacity of the kidney to augment basal bloodflow). Injection of isosorbide dinitrate was associated with an increase in average peak velocity of 64% (P < 0.01) and a small (from 4.5 to 4.74, P < 0.01) but significant increase in renal artery diameter, resulting in an increase in bloodflow of 82% (P < 0.01) and a decrease in arteriolar resistance of 46% (P < 0.01). Bloodflow returned to baseline (4.76 +/- 1.48 mL/s) approximately 5 min after isosorbide injection. Average Peak Velocity increased almost twofold after papaverine injection (60 +/- 10 to 108 +/- 24 cm/sec, P < 0.01). There was a significant (P < 0.01) increase in arterial bloodflow of 96% in the right and 79% in the left renal artery after injection of papaverine with a corresponding significant (P < 0.01) decrease in arteriolar resistance of 49% in the right and 44% in the left renal artery. Using a combination of quantitative angiography and intravascular Doppler allows easy measurement of baseline renal blood flow and of the effects of vasodilator drugs on bloodflow and resistance. The results show that a vasodilatator reserve exists in the renal circulation but is less marked than that reported in the coronary circulation.     

Estimation of AIDS morbidity and mortality in Spain

BACKGROUND: To obtain corrected estimates of the cumulative incidence and mortality, as well as prevalence of AIDS in Spain on June 1992. METHODS: The number of cases in the National Register of AIDS by December 1992 was adjusted for reporting delays to estimate the cumulative incidence by June 1992. The prevalence and mortality in this date were obtained using this figure and the probabilities of survival after diagnosis from the AIDS Register of Madrid. This methodology was used for Spain as all, and for each Autonomous Community. RESULTS: The estimated cumulative incidence of AIDS in Spain by June 1992 was 16,486 cases, 13.4% greater than that reported by the same date. The prevalent cases were 6,351 (95% CI, 5,996-6,708) and the remaining 10,135 (61.5%) would have died. This number of deaths is 69.6% greater than the reported figure. There were considerable differences among Autonomous Communities. Some of them exhibited rates more than six times greater than others. CONCLUSIONS: The adjusted estimations provide a view of the actual situation more accurate than the raw figures from the register. These great differences should be taken into account for appropriate allocation of health care resources.     

Rhabdomyolysis in antiretroviral therapy with Lamivudin

HISTORY AND CLINICAL FINDINGS: Six weeks after antiretroviral treatment with lamivudin (a nucleoside analogue) had been started (300 mg daily) in a 31-year-old man with AIDS developed pain and weakness in his muscles. On admission he had myalgia on pressure and movement as well as weakness of the entire body musculature, especially of the arms. The history and findings suggested bacterial or HIV-associated myositis. INVESTIGATIONS: Creatinekinase activity (4442 U/l) and myoglobin concentration (3250 micrograms/l) were greatly increased, while creatine (96 mumol/l) and C-reactive protein (22 mg/l) levels were only slightly raised. Serology was negative for acute and bacterial infections and autoimmune myositis. Magnetic resonance imaging and biopsy indicated marked rhabdomyolysis without myositis. DIAGNOSIS, TREATMENT AND COURSE: After excluding other causes, lamivudin and other drugs were discontinued, drug-induced rhabdomyolysis being suspected. This and the administration of prednisolone (100 mg daily) improved the symptoms. Creatinekinase activity and myoglobin level became normal within 14 days. On renewed administration of lamivudin creatinekinase and myoglobin concentrations in serum doubled to 180 U/l and 110 micrograms/l, respectively. Cessation of medication once again restored them to normal. CONCLUSION: Rhabdomyolysis is a serious but rare side effect of lamivudin treatment. Appropriate biochemical monitoring should therefore be undertaken when it is used in the treatment of HIV-positive patients.     

Cancer incidence and mortality in France in 1975-95

The aims of the European Network of Cancer Registries (ENCR) are to improve the quality, comparability and availability of cancer registry data in Europe. This paper on cancer incidence and mortality in France presents the most recent available data, with short-term projections to 1995, and a commentary based, where possible, on epidemiological research carried out in France. Cancer incidence in men in France increased throughout the study period 1975 to 1995, from 92,000 new cases in 1975 to about 135,000 in 1995. This increase was partly due to the ageing of the French population, but incidence rates have also increased, particularly from 1975 to 1985. The trend appears to be levelling off in the 1990s, with an incidence rate in 1995 of about 482 per 100,000 (this and subsequent rates quoted are standardized to the European Standard Population). Among women, the all-cancer incidence rates also increased during the 1970s and 1980s. Although the rate of increase was less pronounced than in men, the trend is continuing in the 1990s. The estimated age standardized rate in 1995 was 309 per 100,000, representing 104,000 new cases. The main components of these changes in the last decade were, for men, increases in large bowel and prostate cancer, which have been partly compensated for by decreases in oral cavity, larynx and stomach cancer. For women the trend was dominated by the continuing increase in breast cancer with increases also in large bowel and lung cancers. Of the numerically important cancers in women, only stomach cancer has shown a clear decline. The situation in 1995 was that breast cancer remained the predominant cancer affecting women in France, accounting for almost one third of all new cases of cancer diagnosed and one fifth of cancer deaths. The next most frequent cancers in women were those of the large bowel. Regrettably, incidence rates of both breast and bowel cancer are increasing in women. For men in France the most frequent cancers in 1995 were those of the prostate, large bowel and lung, all of which increased in incidence since 1975. Although it is estimated that there will be more newly diagnosed cases of prostate cancer than lung cancer in 1995, the latter will cause many more deaths, particularly of young men.