Total Lymphocyte Count as surrogate marker for CD4 Cell Count in HIV-Infected Individuals in Gondar University Hospital, Northwest Ethiopia

ABSTRACT: BACKGROUND: The high cost of CD4 count estimation in resource-limited countries is a major challenge in initiating patients on highly active antiretroviral therapy (HAART). Therefore, assessment of inexpensive and simple laboratory diagnostic marker is mandatory to diagnose immunosuppression. OBJECTIVE: To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected patients. Materials and Methods In this cross sectional study, 400 ART-naive HIV-positive patients enrolled in Gondar University Hospital, from March 2011 to May 2011, were tested for CD4 count & TLC. The cutoffs were determined as: 200 cells/muL for CD4 count and 1200 cells/muL for TLC by using BD FACS count and CELL DYN 1800 Flow Cytometrys respectively. Spearman correlation between TLC and CD4 cell count were assessed. Sensitivity, specificity, positive and negative predictive values for different age a group, TLC [less than or equal to]1200 was computed for CD4 count [less than or equal to]200 cells/cu.mm. RESULTS: Among 400 ART naive HIV infected patients, 278 (69.5%) were females. The mean age of the study participants was 33.7. TLC and CD4 count were positively correlated (r = 0.33, p = 0.001). A TLC of [less than or equal to]1200 cells/m m3 was found to have a sensitivity (32.86%), specificity (95.33%), PPV (79.7%), and NPV (71.9%) for predicting a CD4 count of <200 cells/mm3. CONCLUSION: This study showed that low sensitivity and specificity of TLC as a surrogate measure for CD4 count. Moreover, CD4 cell counts of < 200 cells/mm3 were found in 96 cases (24%) with TLCs of [less than or equal to]1200 cells/mm3. Thus, 1 in 4 individuals would have been deprived of needed treatment. Therefore, we recommend keep on expansion of access to CD4 counter.     

Sertraline as a first-line treatment for cholestatic pruritus

Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo (P=0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score. CONCLUSION: Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch.     

The role of serpinb9/serine protease inhibitor 6 in preventing granzyme B-dependent hepatotoxicity

Virally infected hepatocytes are resistant to cytotoxic lymphocyte killing by perforin-dependent and granzyme-dependent effector mechanisms. The present studies were designed to examine the role of serine protease inhibitor 6 (SPI-6) in limiting granzyme B-dependent cytotoxic effector mechanisms in the liver. SPI-6-specific small interfering RNA (siRNA) administration to C57Bl/6J (B6) mice elicited transient alanine aminotransferase (ALT) elevations that were not observed in either granzyme B-deficient B6 (B6.gzmb(-/-)) or natural killer (NK) cell-depleted B6 mice. When SPI-6 expression was abolished by siRNA administration at the time of infection with a recombinant, replication-deficient adenovirus [E1-deleted adenovirus encoding beta-galactosidase (AdCMV-LacZ)], earlier and dramatically increased, and earlier ALT elevations were observed in wild-type B6 but not in B6.gzmb(-/-) or NK cell-depleted mice. When a 3-fold higher dose of AdCMV-LacZ was administered to B6 mice, the coadministration of SPI-6 siRNA resulted in the early onset of lethal, acute liver failure. Of note, the accelerated clearance of AdCMV-LacZ was observed in recipients of SPI-6 siRNA. CONCLUSION: These results indicate that the regulated expression of SPI-6 in hepatocytes during viral infection or following noninfectious causes of liver injury protects hepatocytes against excessively vigorous granzyme B-dependent killing but may also delay immune clearance of virally infected hepatocytes.     

Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice

Acetaminophen (APAP) hepatotoxicity results from cytochrome P450 metabolism of APAP to the toxic metabolite, n-acetyl-benzoquinone imine (NAPQI), which reacts with cysteinyl residues to form APAP adducts and initiates cell injury. As APAP is commonly used during viral illnesses there has been concern that APAP injury may be additive to that of viral hepatitis, leading physicians to advise against its use in such patients; this has not been investigated experimentally. We infected C57BL/6 male mice with replication-deficient adenovirus to produce moderately severe acute viral hepatitis and observed that APAP doses that were hepatotoxic or lethal in control mice produced neither death nor additional increase in serum ALT when administered to infected mice at the peak of virus-induced liver injury. Moreover, the concentration of hepatic APAP-protein adducts formed in these mice was only 10% that in control mice. Protection from APAP hepatotoxicity also was observed earlier in the course of infection, prior to the peak virus-induced ALT rise. Hepatic glutathione limits APAP-protein adduct formation but glutathione levels were similar in control and infected mice. Cyp1a2 (E.C. 1.14.14.1) and Cyp2e1 (E.C. 1.14.13.n7) mRNA expression decreased by 3 days post-infection and hepatic Cyp2e1 protein levels were reduced almost 90% at 7 days, when adduct formation was maximally inhibited. In vitro, hepatocytes from virally infected mice also were resistant to APAP-induced injury but sensitive to NAPQI. Rather than potentiating APAP-induced liver injury, acute viral hepatitis in this model resulted in selective down-regulation of APAP metabolizing P450s in liver and decreased the risk of APAP hepatotoxicity.     

In-hospital mortality and length of stay of patients with hypertensive crisis treated at public hospitals in Harari Regional State,Eastern Ethiopia

Hypertensive crisis poses substantial cardiovascular morbidity and mortality. This study aimed to assess in-hospital mortality, length of stay (LOS), and their predictors among patients with hypertensive crisis treated at public hospitals in Harari Regional State, Eastern Ethiopia. An institutional-based retrospective cohort study was conducted from October 1 to 31, 2022. The medical records of 328 patients with hypertensive crisis treated at two public hospitals between September 1, 2017 and August 31, 2022 were reviewed. Cox proportional hazards regression and negative binomial regression were used to identify predictors of in-hospital mortality and LOS, respectively. The in-hospital mortality rate of patients with hypertensive crisis was 18.94 (95% confidence interval (CI): 12.08–29.70) per 1000 person-day observation. The median (interquartile range) LOS of these patients was 10 (4–120) hours. Age ≥65 years (adjusted hazard ratio (AHR): 3.30; 95% CI: 1.17– 9.33); increment in initial systolic blood pressure (AHR: 1.040; 95% CI: 1.014–1.066); and having acute brain-related damage (AHR: 4.02; 95% CI: 1.48–10.88) were predictors of in-hospital mortality. Rural residence (adjusted incident-rate ratio (IRR): 1.34; 95% CI: 1.03–1.75); having a history of medication discontinuation (adjusted IRR: 1.59; 95% CI: 1.16–2.18); comorbidity (adjusted IRR: 1.90; 95% CI: 1.49–2.43); acute brain-related damage (adjusted IRR: 13.32; 95% CI: 9.22–19.24), acute cardiac-related damage (adjusted IRR: 7.40; 95% CI: 4.90–11.16); and acute kidney injury (adjusted IRR: 7.64; 95% CI: 5.46–10.69) were predictors of LOS. Thus, it is necessary to develop strategies that allow early screening and follow-up of patients at risk.     

Nocardiosis in HIV seropositive clinically suspected pulmonary tuberculosis patients

To determine the frequency of nocardiosis in HIV-positive individuals clinically suspected of having tuberculosis (TB), 140 sputum samples were collected and processed by Gram stain, modified Ziehl-Neelsen staining and by culture on Lowenstein Jensen medium. Four (2.85%) patients were positive for nocardia by microscopy and five (3.6%) had positive culture for Nocardia asterioides. In areas where HIV-associated TB is common, some patients diagnosed as smear-negative pulmonary TB will actually have nocardiosis. Clinicians should be aware of this entity in HIV/immunocompromised patients with respiratory infections who fail to respond to antituberculous treatment.     

Prevalence of Physical,Verbal and Nonverbal Sexual Harassments and Their Association with Psychological Distress among Jimma University Female Students: A Cross-Sectional Study

Background

A number of studies conducted on sexual harassment focused on general magnitude rather than specific details of the various forms of sexual harassment and their effect on psychological health. Thus, the objective of this study was to assess the prevalence rates of the various forms of sexual harassments and their associations with psychological distress among Jimma University female students.

Methods

Three hundred and eighty five (385) female participants were selected from all colleges using stratified and systematic sampling techniques. A structured questionnaire consisting of items on the various forms of sexual harassment and psychological distress was administered.

Result

The prevalence rates of physical, verbal and nonverbal sexual harassments were 78.2%, 90.4% and 80.0%, respectively, while the prevalence rate of psychological distress among students who had experienced sexual harassment was 63.0%. The multivariable logistic regression analyses indicated that students who were physically [adjusted OR = 3.950, 95% CI = (1.979, 7.884)] and nonverbally [(adjusted OR = 12.099, 95% CI= (5.190, 28.205] harassed were 4 and 12 times more likely to experience psychological distress, respectively, adjusted for all other variables.

Conclusion

The prevalence of various forms of sexual harassment were higher and strongly associated with psychological distress. Important implications for University officials and policy makers including creating harassment free University have been drawn. Otherwise, female students tend to dropout and their academic achievements suffer a lot as a result of psychological distress; and the government''s effort for realizing the gender parity in education would be compromised.