Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients.

OBJECTIVES: The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks. METHODS: An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naïve HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks. Secondary outcome measures were changes in metabolic abnormalities, body composition, renal function, and virological and immunological efficacy over 48 weeks. Patients who had used at least one dose of trial drug were included in the analysis. RESULTS: Data for 118 patients were analysed (57 patients on SQV/r and 61 on ATV/r). At week 24, changes in lipids were modest, without increases in triglycerides, including a significant rise in high-density lipoprotein (HDL) cholesterol and a nonsignificant decrease in the total:HDL cholesterol ratio in both arms with no significant difference between arms. Lipid changes at week 48 were similar to the changes observed up to week 24, with no significant change in the homeostasis model assessment (HOMA) index. Adipose tissue increased regardless of the regimen, particularly in the peripheral compartment and to a lesser extent in the central abdominal compartment, with an increase in adipose tissue reaching statistical significance in the ATV/r arm. A slight decline in the estimated glomerular filtration rate (eGFR) was observed in both arms during the first 24 weeks, with no progression thereafter. The immunological and virological responses were similar over the 48 weeks. CONCLUSIONS: Combined with TDF/FTC, both SQV/r 2000/100 mg and ATV/r 300/100 mg had comparable modest effects on lipids, had little effect on glucose metabolism, conserved adipose tissue, and similarly reduced eGFR. The virological efficacy was similar.

Preparation of TEM foils from Nb-10 a/o Si.

Ductile phase toughened composites contain phases with significantly different physical properties. Consequently, these phases thin at different rates depending on the sample preparation procedure. A new TEM foil preparation method for the ductile phase toughened Nb-10 a/o Si material has been developed. The method involves chemical thinning in a 70% nitric acid/30% hydrofluoric acid solution followed by electropolishing in a 12.5% sulfuric acid/87.5% methanol electrolyte at -40 degrees C. This procedure for making TEM foils results in large thin areas with the minimum of artifacts. Mechanical grinding of a sample followed by either ion milling, dimpling, or electropolishing produced foils with large electron transparent areas, but with uncharacteristic features of the original Nb-10 a/o Si alloy microstructure. These artifacts were identified as dislocations, surface mottling, and antiphase domains.

Blue nevus of the prostate: ultrastructural study.

A case of blue nevus of the prostate in a sixty-five-year-old black patient was studied by light and electron microscopy. In the melanocytes only fully melanized melanosomes were present; melanosomes in early stages of development were entirely absent. It was concluded that the formation of melanosomes within the melanocytes in blue nevus of the prostate is probably under genetic control.

Gonadal stromal tumor in black male.

A twenty-five-year-old black male presented with a right testicular mass which had progressively increased in size over three years. He was in good health and noted no other general abnormalities. Taking all malignant precautions, excisional biopsy of the lesion revealed gonadal stromal tumor by frozen section. The testis was left in situ, and the patient has continued to remain asymptomatic.

Mixed mesodermal tumor of urinary bladder: a light and electron microscopic study.

Light and ultrastructural findings in a mixed mesodermal tumor of the urinary bladder are reported. The mesenchymal component of the tumor contained undifferentiated mesenchymal cells and cells with chondroblastic differentiation. The neoplastic chondrocytes displayed an abundance of cytoplasmic microfilaments and had a scalloped cell surface.

Sarcoidosis of the testis: a case report.

A left testicular mass was found in a 34-year-old black man with a history of multisystem sarcoidosis of 7½ years duration. Microscopic examination of the excised testicle revealed noncaseating granulomas throughout, as well as a few such lesions in the epididymis. This is the seventh reported, microscopically proven case of sarcoidosis of the testis without significant epididymal involvement occurring in a living individual.A review of the other cases of testicular sarcoidosis in the literature reveals that most of them had a number of organs involved with this disease, similar to the subject of this report. Over one half of these patients had skin lesions with or without bone or joint manifestations, suggesting that the testis should be evaluated with particular care when any of these areas are involved. If there is a consistent association of skin, bone, and testicular lesions in this disease, genital sarcoidosis may be more common than presently thought.

The effect of citrate and polyamines on human benign prostate in organ culture.

A technique for short-term cultivation of slices of human benign prostate tissue in an organ culture environment is described. Minimum essential medium utilized was supplemented with 10 percent fetal bovine serum and 25 mg/mL of citrate, spermine, and spermidine. Spermine in the presence of testosterone in the culture medium induced morphological changes, enhancing the morphology of the tissue. The epithelium was well preserved morphologically. Citrate or spermidine together with testosterone does not enhance any morphological change. After seven days of culture, necrosis was developed. The spent culture medium showed a pattern of prostatic acid phosphatase production. When treated with spermine, the maximum level was reached at four days, after which it decreased. With spermidine or citrate, the maximum level is reached at two days of culture. Tissue ß-glucuronidase activity was enhanced by either spermidine, spermine, or citrate together with testosterone. The biochemical studies suggested that explants of human benign prostate can be well maintained in organ culture for a few days.

A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis.

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection.

Penile prosthesis in the management of priapism.

Priapism is the abnormal persistence of erection, painful and not sexually induced. Many cases resolve spontaneously, but if it persists for a long time there is anoxic injury and fibrosis of the corporal tissues and the sequelae is impotence. The main problem with priapism is pain and the probability of a resultant impotence. We have managed 2 patients with recurrent priapism with insertion of penile prosthesis with satisfactory results.

The ultrastructural localization of tri-n-butyltin in human erythrocyte membranes during shape transformation leading to hemolysis.

Scanning electron microscopy, transmission electron microscopy, freeze-fracture, and x-ray energy dispersive spectrometry were used to localize tri-n-butyltin (TBT) in human erythrocytes (RBC's). TBT induced a rapid shape transformation of the RBC discocyte to an echinocyte, which led to hemolysis at concentrations at or above 10 microM TBT. Electron dense spheres or ellipsoids were observed in association with blood cell membranes at or above 10 microM TBT. These structures were visualized initially in thin sections when postfixed with osmium tetroxide. Control cell preparations without TBT did not exhibit these structural densities when fixed with osmium. Freeze-fracture replicas confirmed the presence of TBT aggregates associated with cell membranes as intercalations in the lipid bilayer. In thin sections, these structures measured 71.5 +/- 18.2 nm in diameter. In freeze-fracture replicas of TBT-treated RBC's, particulate structures measuring 60 +/- 18.5 nm in diameter were present on membrane exoplasmic fracture faces and 59.6 +/- 10.8-nm depressions on membrane protoplasmic fracture faces. Qualitative x-ray energy dispersive spectrometry analysis of ultrathin sections of glutaraldehyde-carbohydrazide-embedded samples revealed that the membrane-associated aggregates contained tin. TBT-treated RBC's that were washed with normal saline resulted in a paucity of TBT aggregates associated with the membranes and a reduction in the RBC hemolysis rate. RBC shape transformation occurred at each concentration examined from 0.1 to 100 microM TBT, but was reversible below 1 microM TBT.

The role of diet in prostate cancer.

This is a one-to-one, age- and race-matched case-control study involving 55 histologically confirmed black prostate cancer patients and 55 controls who were seen at three major hospitals in Washington, DC from 1982 to 1984. Personal interviews were conducted to obtain the number of times food items of specified serving size were consumed per week by cases and controls; the subjects were grouped according to the age periods 30-49 and 50 years and older. We then calculated the average daily consumption of each of 18 nutrients per 1,000 calories. There was a significant negative association between linoleic acid (p less than 0.04) for the 50 years and older group, thiamin (p less than 0.05) for those 30-49 years old, riboflavin (p less than 0.03) for the 50 and older group, and iron (p less than 0.05) for those 30-49 years old. The results of this study suggest that the intake of thiamin and iron (in subjects 30-49 years old), linoleic acid and riboflavin (in subjects 50 years and over) could be protective because control subjects consumed more of these nutrients than did the cases.

Characterization of prostatic carcinoma among blacks: a comparison between a low-incidence area, Ibadan, Nigeria, and a high-incidence area, Washington, DC.

A comparison of carcinoma of the prostate gland in a low-incidence Nigerian (Ibadan) population and a high-incidence U.S. Afro-American (Washington, D.C.) population was the purpose for this study, initiated in 1973. The frequency of carcinoma (micro- and invasive) was determined in consecutive necropsy cases from hospitals in Ibadan, Nigeria, Accra, Ghana and Washington, D.C. The results of these clinical, epidemiologic and morphologic studies are reported. Clinically, the peak incidence of carcinoma of the prostate in Nigerian males in Ibadan and in American males in Washington, D.C. was in the 65-74 age group. The median age of patients was 66.4 years in Ibadan and 69.2 years in Washington, D.C. Seventy-five percent of Nigerian and 49% of American patients were in stages III and IV. Overall, the distribution by grade of neoplasms in surgical material from Ibadan and Washington, D.C. was similar. Plasma testosterone and estrone levels were significantly higher (p < 0.05 and p < 0.001) in U.S. patients than in U.S. controls and higher (p < 0.001 and p < 0.05) in U.S. patients than in Nigerian patients with prostatic carcinoma. Plasma testosterone levels were significantly lower (p < 0.05) in Nigerian patients than in Nigerian controls. Estrone levels were not significantly different in Nigerian patients than controls. Nigerian patients were more sexually active throughout their lives than American patients; however, they reported a higher incidence of impotence than U.S. patients in the immediate 5 years preceding the diagnosis of prostatic carcinoma. Nigerian respondents (patients and controls) arrived at puberty later than their American counterparts. Within each of the two population groups, the factor with the highest relative risk ratio was lower urinary tract symtoms occurring 10 years or longer before the onset of the present complaints which led to the diagnosis of prostatic carcinoma. Nigerian and U.S. patients were more sexually active than controls. Microcarcinoma (incidental, latent) of the prostate gland occurred with a frequency of 11.8% and at an age-adjusted incidence rate (world standard) of 40.6 per 1000 necropsies in the sampled U.S. black male population. The age-adjusted incidence rate (world standard) for microcarcinoma in the combined West African (Accra and Ibadan) series (36.7/1000) was almost equal to the rate (40.6/1000) in the Washington, D.C. series.

Racial differences in clinically localized prostate cancers of black and white men.

PURPOSE: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. MATERIALS AND METHODS: A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. RESULTS: Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. CONCLUSIONS: The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

Characterization of prostatic carcinoma among blacks: a continuation report.

A clinical and pathologic comparison of carcinoma of the prostate in a high-risk US (Washington, DC) black population and in a low-risk Nigerian (Ibadan) black population is presented. Fifty-two percent of American patients were in clinical stages I and II, whereas only 10% of Nigerian patients were in the same stages. Testosterone and estradiol blood levels were significantly lower (P less than 0.05) in patients with carcinoma of the prostate from Ibadan compared with American black prostate cancer patients from Washington, DC. Age-standardized incidence rates (world standard) for 1000 autopsies for micro (incidental)-carcinoma were approximately equal in American and African black men. The incidence rate of invasive carcinoma was, however, even after adjustment for age, higher in American black men than in African men.

Nutrition and prostate cancer: a case-control study.

This one-to-one, age- and race-matched case-control study involved 181 histologically confirmed black prostate cancer patients and 181 controls seen at three major hospitals in Washington, DC, during the period 1979-1982. Personal interviews were conducted to obtain the number of times food items of specified serving size were consumed per week by cases and controls during the age periods 30-49 and 50 years and older. Then the average daily consumption of each of 18 nutrients per 1,000 calories was calculated. There was risk enhancement associated with increased intake of proteins, total fat, saturated fat, oleic acid, and vitamin A during the age period 30-49 years. The association was highly significant for vitamin A and approached statistical significance for the other four nutrients. A hypothesis based on disturbance of the zinc-retinol binding protein-vitamin A axis was put forward to explain the relative risk enhancement effect of vitamin A on prostate cancer.

Characterization of prostatic carcinoma among blacks: a preliminary report.

This study was designed to compare United States (Washington, DC) black prostatic carcinoma patients (high-risk group) with Nigerian (Ibadan) black prostatic carcinoma patients (low-risk group). Although the material is meager, preliminary analyses suggest that carcinoma of the prostate is a common disease in both US black men (196 of 1000 autopsies) and in Nigerian black men (67 of 1000 autopsies). The tumor tends to be of a higher histologic grade (less well differentiated) and the carcinomatous foci are more numerous in the Nigerian patients. Fifty-three percent of US patients are in stages I and II when the disease is first discovered. Plasma testosterone, estrone, and estradiol concentrations did not differ significantly between US patients and controls. A statistically significant positive association is indicated between carcinoma of the prostate and the following epidemiologic variables: racial admixture, age of puberty, and age of first coitus. The median age of necropsy cases with carcinoma was 50.0 years in Nigeria and 68.3 years in the US.