Prevalence of serum antibodies to human papilloma virus in patients with genital ulcer disease in an urban population of Tanzania

BACKGROUND: The epidemiology of human papillomavirus (HPV) in Tanzania is largely unknown both in risk groups and in the general population. OBJECTIVE: To determine the cumulative seroprevalence of selected HPV types in order to evaluate exposure to HPV in urban Tanzania. METHOD: In a cross-sectional study, sera of 200 patients of both sexes with genital ulcer disease (GUD) and sera of 60 male blood donors and 60 pregnant women were tested for antibodies to the oncogenic HPV types 16, 18, 31, 33, 35, 51 and 52 using an ELISA based on virus-like particles (VLP). RESULTS: The overall seroprevalence of HPV types for all patients with GUD was 83% and 77% for women and men, respectively. For pregnant women and male blood donors, the corresponding percentages were 55% and 15%, respectively. The most common HPV types were 16, 18 and 52. Infection with multiple types was more than 10 and 5 times more frequent than infection with a single type 16 in patients with GUD and in pregnant women, respectively. The seroprevalence to HPV types 16, 18, 51 and 52 was considerably higher in HIV-positive patients with GUD than in HIV-negative patients. CONCLUSIONS: Infections with the oncogenic HPV types 16, 18 and 52 are common among patients with GUD and pregnant women in urban Tanzania, emphasising the need for control, treatment and implementation of appropriate HPV vaccine programmes.     

Microglial GLT-1 is upregulated in response to herpes simplex virus infection to provide an antiviral defence via glutathione

Herpes simplex virus (HSV) can enter the central nervous system and cause encephalitis (HSV-1) or meningitis (HSV-2). Microglia, the immunocompetent cells of the central nervous system, are potentially able to detect viral infections. Microglia have been shown to express the glutamate transporter GLT-1 during pathological events, leading to increased microglial glutamate uptake and glutathione synthesis. This study aims to address the role of GLT-1 and glutathione, a major antioxidant with antiviral properties, during HSV infections. Using neuron-enriched mixed primary cultures from rat, it was found that microglia have higher resistance to HSV infections than neurons or astrocytes after 24 h incubation with HSV. Purified microglia in culture were used to further address this. It was found that microglia were able to detect HSV and responded by releasing tumor necrosis factor-alpha (TNF-alpha) and upregulating GLT-1 after 24 h incubation with 1 PFU/cell HSV-1 or HSV-2. Furthermore, the microglial glutathione levels were not significantly diminished after 24 h. Inhibition of the microglial glutathione synthesis with 200 microM buthionine sulfoximide (BSO) led to significantly more infected cells after 24 h incubation with 1 PFU/cell HSV-1 or HSV-2. These data indicate that the higher resistance in microglia against HSV infections may be due to the expression of GLT-1, which can maintain the glutathione levels and provide a mechanism for microglial self-defense against HSV.     

Effect of restorative proctocolectomy on gastric acid secretion and serum gastrin levels

PURPOSE: The aim of the present study was to analyze gastric acid secretion after restorative proctocolectomy, because it has been shown that ileal resection or exclusion may increase gastric acid secretion. An increased output of gastric acids may decrease the intestinal passage time and contribute to looser stools. METHODS: Eleven patients who had elective colectomy and ileoanal pouch because of ulcerative colitis were investigated. Eight patient were males. Eight S-pouches and three J-pouches were constructed. Gastric acid secretion (retention, basic, and stimulated) was studied, together with serum gastrin, pentagastrin, and pepsinogen, in patients before colectomy and after having had the pelvic pouch functioning for 12 months. RESULTS: A significant increase, compared with preoperative levels, in retention, basic, and stimulated gastric acid secretion was found after 12 months with the pouch functioning. Levels of serum gastrin, pentagastrin, and pepsinogen were unchanged. CONCLUSION: Restorative proctocolectomy leads to a significant increase in gastric acid secretion. These findings may be of importance with regard to intestinal passage time and consistency of the stools.     

Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis

We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re-stimulated splenic CD4⁺ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.     

Biliary lipid output and bile acid kinetics in cholesterol gallstone disease. Evidence for an increased hepatic secretion of cholesterol in Swedish patients

Sweden has one of the highest incidences of gallstone disease in the Western world. It is therefore important to characterize the mechanisms responsible for the formation of cholesterol gallstones in this population. In the present study, we have determined the kinetics of the two primary bile acids, cholic acid and chenodeoxycholic acid, and the hepatic secretion rates of the biliary lipids in 21 normolipidemic, nonobese gallstone patients (13 with functioning and 8 with nonfunctioning gallbladder) and in 23 healthy controls. The cholesterol saturation of fasting gallbladder bile averaged 110% in the gallstone patients with functioning gallbladder and 82% in the controls. The pool sizes of cholic acid and chenodeoxycholic acid were reduced by about 40% in the two groups of gallstone patients, whereas the rates of synthesis were close to normal. The fractional catabolic rate of both bile acids was increased in both groups of gallstone patients. The gallstone patients with functioning gallbladder had an increased (about 50%) cholesterol secretion but normal bile acid and phospholipid secretion rates. In the gallstone patients with nonfunctioning gallbladder the secretion rates of biliary lipids were not significantly different from those of the controls. The ratio between cholesterol and bile acids was about 50% higher in the gallstone patients with functioning gallbladder than in the controls or in those with nonfunctioning gallbladder. The results indicate that the hepatic secretion of cholesterol is an important determinant for the development of saturated gallbladder bile in Swedish gallstone patients.     

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.     

Early identification of acute myocardial infarction and prognosis in relation to mode of transport to hospital.

Of 2,840 consecutive patients who were admitted to the emergency department of a Swedish university hospital due to suspected acute myocardial infarction (AMI), only 25% were reached by the mobile coronary care unit (MCCU), and only 4% simultaneously fulfilled traditional criteria for prehospital thrombolysis (ie, had ST-segment elevation on admission electrocardiogram and a delay time of less than 6 hours). In the subset of patients who fulfilled criteria for a confirmed AMI, 31% were reached by an MCCU and 11% fulfilled criteria for prehospital thrombolysis. Among patients with confirmed AMI, the hospital mortality rate was highest in patients transported by standard ambulance (19%) versus 15% in those transported by an MCCU and 8% in those transported by other means. The authors conclude that AMI patients transported by ambulance are high-risk patients for early death. Prehospital thrombolysis might reduce their rate of mortality. However, according to the authors' experience only a minor fraction of patients are available for prehospital thrombolysis.     

Negative effects of dihydroergotamine (Orstanorm) on central haemodynamics and aorto-coronary bypass blood flow. An intraoperative study

Dihydroergotamine (DHE), Orstanorm, because of its strong constrictor action on capacitance vessels, is used in the treatment of hypotension caused by orthostatism or spinal or epidural anaesthesia. Lately Orstanorm has also been used in combination with heparin as prophylaxis against postoperative thromboembolism. In the present study, Orstanorm (0.01 mg/kg b.w.) was given intravenously to 20 patients after coronary bypass surgery. Coronary bypass blood flow, heart rate, systemic mean and systolic blood pressures, right and left atrial pressures, pulmonary artery pressure and cardiac output were measured. Stroke volume, cardiac index, stroke index, systemic and regional myocardial vascular resistance and cardiac work index were then calculated. The results showed that despite increased filling pressures there was no rise in cardiac output, and despite increased cardiac work the bypass flow significantly decreased. The significant increase in regional myocardial vascular resistance found after administration of DHE may explain the absence of expected increase of cardiac output and coronary bypass flow.     

Effect of clindamycin prophylaxis on the colonic microflora in patients undergoing colorectal surgery.

Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut wall were taken at surgery. The highest serum concentrations observed occurred 30 min after administration of clindamycin and varied between 6.8 and 37.9 microgram/ml (mean, 14.8 +/- 2.0 [standard error] microgram/ml). The clindamycin concentrations in the tissue samples were between 1.8 and 13.0 microgram/g. Clindamycin concentration in the fecal samples varied between 2.1 and 460 microgram/g. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Among the aerobic bacteria, enterococci and streptococci decreased during the prophylaxis period. Anaerobic bacteria also decreased significantly during the same period. After the clindamycin administration period, enterococci, streptococci and anaerobic bacteria proliferated. No anaerobic strains resistant to clindamycin were isolated. Postoperative infections due to Streptococcus faecalis and different enterobacteria such as Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Klebsiella occurred in five patients.