The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"

Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 "seroreverters" before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo "HCV seroreversion" are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.     

Microbiological understandings and mysteries of noma (cancrum oris)

The microbiologic history of noma was reviewed. Studies have associated the disease process with large numbers of fusiform bacilli and spirochetal organisms. In order to study the microbiology of the staging and infection periods of noma 62 Nigerian children, aged 3-14 years, 22 children had acute necrotizing ulcerative gingivitis (ANUG) and were also malnourished, 20 exhibited no acute necrotizing ulcerative gingivitis but were malnourished and 20 were free of acute necrotizing ulcerative gingivitis and in good nutritional state) were evaluated for the presence of viruses and oral microorganisms. The ANUG cases in the malnourished children had a higher incidence of Herpesviridae, the main virus being detected was cytomegalovirus. There were more anaerobic microorganisms recovered, with Prevotella intermedia as the predominant isolate, in the malnourished children as compared to the healthy children. A study of the predominant microflora in active sites of noma lesions was carried out in eight noma patients, 3-15 years of age, in Sokoto State, northwestern Nigeria. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms isolated included Prevotella intermedia, alpha-hemolytic streptococci and Actinomyces spp. which were isolated from 75.0, 50.0 and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus and Pseudomonas spp. were each recovered from one lesion. All strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia which showed resistance to penicillin. The pathogenic mechanisms of F. necrophorum as a trigger organism were discussed. The isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.     

Percutaneous brachial artery catheterization

We describe modifications and suggestions for safer percutaneous catheterization of the brachial artery based in part on the anatomy of the axillary-brachial artery and surrounding nerves of the brachial plexus. The brachial artery approach should be nearly as safe as the femoral artery approach for percutaneous catheterization and should not be avoided if the femoral arteries cannot be used.     

Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy

Objectives

The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV‐infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.

Methods

Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C_trough) were compared independently [using analysis of variance (anova )] and on a longitudinal basis (using a paired t‐test).

Results

Forty‐six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15–36) weeks and median (range) baseline CD4 count and viral load were 346 (14–836) cells/μL and 8724 (<50–267408) HIV‐1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild‐type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823–4227) ng/mL; n=16] and third [3346 (2813–3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693–6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851–4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM‐guided dose adjustment in certain cases.     

Evaluation of the Toxicity and Reversibility Profile of the Aqueous Seed Extract of Hunteria Umbellata (K. Schum.) Hallier F. in Rodents

Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for the folkloric management of labour, pain and swellings, stomach ulcers, diabetes, obesity, and anaemia, with no scientific report of its toxicity and reversibility profile. The present study was, therefore, aimed at investigating the in vivo toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were determined in Swiss albino mice while its 90-day oral toxicity and toxicity reversibility profile on anthropometric, biochemical, haematological and histopathological parameters were also assessed using standard procedures. Results showed that the LD₅₀ values for the acute oral and intraperitoneal toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg, respectively. Visible signs of immediate and delayed toxicities including starry hair coat, respiratory distress, and dyskinesia were observed. For the chronic oral toxicity study, HU administered for 90 days produced significant (p<0.001) reductions in the weight gain pattern and significant (p<0.001) and dose related increases in the relative weights of liver, stomach, spleen, testis, lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also produced significant (p<0.05, p<0.001) dose related reductions in the serum levels of fasting blood glucose, bicarbonate, urea and creatinine while causing non-significant (p>0.05) alterations in the serum levels of sodium, potassium, alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and conjugated bilirubin, total protein and albumin. Also, chronic oral treatment with HU produced significant (p<0.05, p<0.01, p<0.001) and dose-related increases in the red cell count, packed cell volume, haemoglobin concentration, platelet count, total leucocyte count and lymphocyte differential while producing significant (p<0.05) reductions in neutrophil and granulocyte differentials. HU also produced histological features of proliferations of the stomach epithelia, lung tissues, splenic white and red pulps, and testicular spermatogenic series. Following 14 days of oral toxicity reversibility test, there was no significant (p>0.05) reversal in the serum levels of the biochemical and haematological parameters investigated, including the HU-induced histological lesions.Overall, results of this study showed that HU has a relatively low oral toxicity profile but its prolonged use, particularly, at high doses should be with great caution.Key words: Hunteria umbellata, Toxicity and reversibility profile, Haematology, Liver and Renal function tests, Histopathology, Rodents     

Biochemical and Toxicological Studies of Aqueous Extract of Syzigium Aromaticum (L.) Merr. & Perry (Myrtaceae) in Rodents

The effects of long-term administration of boiled aqueous extract of Syzigium aromaticum (SYZ), commonly known as clove (which has been locally employed for treating gastrointestinal tract diseases and also used as food spices), on some biochemical indices, such as body weight, liver functions and blood parameters were studied in adult albino rats of both sexes. Selected doses of 300 and 700 mg kg⁻¹ were given orally through cannular to groups of animals for a period of 90 days, while the control group received distilled water throughout the duration of study via the same route. Blood samples collected after therapy and assayed for activities of some liver enzymes recorded a significant (p<0.05) and prominent effect on ALP and AST. Measurement of haematological parameters also revealed significant effects (p<0.05; p<0.001) on Hb, RBC (p<0.05), PCV (p<0.001), platelets (p<0.001) and granulocytes (p<0.001). An insignificant reduction was recorded for total WBC. The histopathological study conducted was in consonance with the results of the biochemical investigations that the aqueous extract of SYZ even at moderate doses, significantly affects body organs, their enzymes as well as the various functions. LD₅₀ for both intraperitoneal and oral routes of SYZ were 263 and 2500 mg kg⁻¹ respectively. The present work has revealed the toxicity of sub chronic administration of SYZ, which suggests that its prolonged usage must be avoided.