Sluggish glucose tolerance in tuberculosis patients.

OBJECTIVE: To examine glucose tolerance in sputum-positive non-treated pulmonary tuberculosis (TB) patients as part of a general metabolic profile. Subjects. Sixty-three sputum-positive non-treated patients (male and female) attending the pulmonary clinic at Mthatha General Hospital in the Eastern Cape and 89 apparently healthy sex and age-matched volunteers. METHODS: Sixty-three untreated TB patients who came to the Mthatha General Hospital's pulmonary clinic with classic symptoms of TB, confirmed by sputum analysis, were recruited for the study. Eighty-nine apparently healthy sex and age-matched volunteers served as the control group. Anthropometric measurements were taken using an electronic scale. Standard oral glucose tolerance tests (OGTTs) were performed in both groups in the morning after an overnight fast. Anticoagulant-treated blood was analysed for glucose and insulin using Peridochrome Glucose (Boehringer Mannheim, Mannheim, Germany) and radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, USA) respectively. RESULTS: There was sluggish response to glucose and insulin in the TB patient group compared with the control group. Glucose and insulin levels were significantly higher in patients at 0, 30, 60, 120, and 180 minutes. Analysis of variance gave the following p-values, viz. p = 0.0000, 0.0004, 0.0000, 0.0000 and 0.0000 for glucose, and p = 0.0317, 0.0071, 0.0000, 0.0005 and 0.0000 for insulin respectively. CONCLUSIONS: The results of this study suggest an altered glucose/insulin metabolism in TB patients. This might play an important role in the clinical course of the disease.     

Immune activation and oxidative damage in HIV-positive and HIV-negative adolescents

In a cross-sectional study involving subjects from the Reaching for Excellence in Adolescent Health cohort, we examined the associations between HIV status, disease severity, immune activation, and oxidative damage. Subjects (265 HIV-positive and 127 HIV-negative) were young (range: 14-23 years of age) and primarily female (75%) and black (67%). Many subjects, particularly female subjects, were overweight or obese. Relatively few HIV-positive subjects had advanced HIV disease (13%), and 54% were taking antiretroviral therapy (ART). The 2 markers of oxidative damage used in this study (plasma malondialdehyde and protein carbonyl concentrations) did not correlate with each other, and neither was higher in HIV-positive subjects than in HIV-negative controls. Increased oxidative damage was seen in association with male gender, cigarette smoking, marijuana use, immune activation (as indicated by activated CD8 T-cell counts and plasma C-reactive protein concentration), and use of ART, however. Plasma ceruloplasmin was associated with decreased oxidative damage in HIV-positive subjects, although this association was not seen in those taking ART.     

Cyclin alterations in giant cell tumor of bone.

Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone.     

Characteristics of the 19S and 7S response to bacteriophage ΦX174 in the fowl

After intravenous injection of 10¹⁰ plaque forming particles of ØX174 bacteriophage into White Rock fowls, immune elimination began at 30 hours and viable phage was cleared from the circulation by 50–52 hours, the approximate time at which detectable antibody appeared. Little change was noted in the serum neutralizing activity in the interval from 44 to 217 days after injection, at which time the birds were reinjected with ØX174.

Sephadex Peak I (19S globulin) accounted for most of the early activity of the primary response. By Day 9 most of the activity had shifted to Peak II (7S globulin). In the secondary response, the shift had occurred by Day 4. Both 19S and 7S globulin fractions showed an increase in activity when compared to the same days of the primary response, but the 7S increase was proportionately greater.

All sera and serum fractions (whether 19S or 7S) were sensitive to reduction with 2-mercaptoethanol, but became, less sensitive during the course of immunization.

With regard to the production of 19S antibody, White Rock fowls showed a different response to the particulate antigen ØX174 compared with the response to injection of the soluble antigen, bovine serum albumin. There is evidence of immunological memory in the 19S response to ØX174.

     

Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration

Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclear inclusions were frequent findings. Collagenous stroma was seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c-kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen, CD117 was positive in the c-kit-negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis.     

Randomised controlled trial of pelvic floor muscle exercises and manometric biofeedback for erectile dysfunction.

BACKGROUND: The pelvic floor muscles are active in normal erectile function. Therefore, it was hypothesised that weak pelvic floor muscles could be a cause of erectile dysfunction.AIMS: To compare the efficacy of pelvic floor muscle exercises and manometric biofeedback with lifestyle changes for men with erectile dysfunction.Design of study: Randomised controlled trial.SETTING: The Somerset Nuffield Hospital, Taunton, United Kingdom.METHOD: Fifty-five men with erectile dysfunction (median age 59.2 years; range 22-78 years) were enrolled from a local urology clinic. Of these, 28 participants were randomised to an intervention group and engaged in pelvic floor exercises, as well as receiving biofeedback and suggestions for lifestyle changes. Twenty-seven controls were solely advised on lifestyle changes. Baseline, 3- and 6-month assessments were: erectile function domain of International Index of Erectile Function (IIEF), Partner's International Index of Erectile Function (PIIEF), Erectile Dysfunction-Effect on Quality of Life (ED-EQoL), anal manometry, digital anal measurements, and clinical assessment by an assessor blind to treatment allocation. After 3 months, the control group were transferred to the active arm.RESULTS: At 3 months, compared with controls, men in the intervention group showed significant mean increases in the erectile function domain of the IIEF (6.74 points, P = 0.004); anal pressure (44.16 cmH(2)O, P <0.001); and digital anal grades (1.5 grades, P <0.001). All showed further improvement in these outcomes at 6 months. Similar benefits were seen in men of the control arm after transfer to active treatment. A total of 22 (40.0%) participants attained normal function, 19 (34.5%) participants had improved erectile function, and 14 (25.5%) participants failed to improve.CONCLUSION: Pelvic floor muscle exercises and biofeedback are an effective treatment for men with erectile dysfunction.     

Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF

BACKGROUND: Lead remains in high levels in the environment and is known to reduce fertility in animal models, but a direct link between lead exposures and human infertility has not yet been established. METHODS: In a prospective, double-blind study of the metal ion levels and sperm function, semen was obtained from partners of 140 consecutive women undergoing their first IVF cycle. Lead in seminal plasma was determined by atomic absorption spectroscopy. Motile sperm populations were assessed for surface receptors for mannose binding, and the ability to undergo premature ('spontaneous'), and free mannose-induced acrosome reactions. Fertile donor (n = 9) sperm were exposed to exogenous lead during capacitating incubations and then assessed for mannose receptor expression and acrosome loss. RESULTS: Lead levels were negatively correlated with IVF rates. Lead levels were negatively correlated to two of the three sperm function biomarkers (mannose receptors, mannose-induced acrosome reactions). Lead levels positively correlated with the spontaneous acrosome reaction. These findings were mimicked by in-vitro exposure of fertile donor sperm to lead. CONCLUSIONS: Multiple sperm parameters are affected as lead levels rise. Increased lead levels may contribute to the production of unexplained male infertility.     

Reproducibility of Immunological Tests Used To Assess Multiple Chemical Sensitivity Syndrome

Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by ≤3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4⁺ cells, ranging from minor to eightfold for CD25⁺ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.     

Comparison of Ashdown's medium, Burkholderia cepacia medium, and Burkholderia pseudomallei selective agar for clinical isolation of Burkholderia pseudomallei

Ashdown's medium, Burkholderia pseudomallei selective agar (BPSA), and a commercial Burkholderia cepacia medium were compared for their abilities to grow B. pseudomallei from 155 clinical specimens that proved positive for this organism. The sensitivity of each was equivalent; the selectivity of BPSA was lower than that of Ashdown's or B. cepacia medium.