RENAL DISEASE ASSOCIATED WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODY: 39 PATIENTS OVER A 5-YEAR PERIOD

SUMMARY We have reviewed 39 adult patients who presented over a 5-year period with biopsy confirmed renal disease in association with positive antineutrophil cytoplasmic antibody (18 with C-ANCA, 21 with P-ANCA). Twenty-three (59%) had primary systemic vasculitis, typically with aggressive renal histology including focal necrotising and crescentic glomerulonephritis. In the remaining patients a wide range of clinical syndromes and renal histological appearances were apparent: 30 had abnormal renal function (serum creatinine >140 μmol/l), including 17 who were initially dialysis-dependent. Intensive immunosuppression was administered in 33 cases. When response was assessed at 3 months, renal function was stable or improved in 17 (52%), 5 of whom were able to discontinue dialysis. There was, however, an appreciable early mortality and, at latest follow-up (1–57 months), 12 patients had died and 8 were on the dialysis programme. On immunosuppression, ANCA became negative in the majority (median time 1.5 months) but recurred during clinical relapse in 11 cases. In asymptomatic patients (12 cases), the reappearance of ANCA positivity did not herald clinical relapse. The ANCA assay has increased awareness of systemic vasculitis but not removed the need for histological confirmation before instituting immunosuppression.     

Hematological profile of pregnant women in southwest of Nigeria

ObjectiveTo evaluate the values of some major hematological parameters at different trimesters of pregnancy.MethodsThe research involved 33 healthy pregnant women as the study group and 11 non-pregnant women as control. The age range of these women was 20-40 years. Ethical approval was obtained from Olabisi Onabanjo University Teaching Hospital, Sagamu. Three milliliters of venous blood collected from the median cubital vein with minimum stasis were put into K⁺EDTA bottle. The blood was properly mixed and analyzed for packed cell volume (PCV), total white cell count, differential counts and erythrocyte sedimentation rate (ESR). Hematology was done according to standard methods.ResultsThe result showed that study group exhibited statistically significant lower values of PCV, monocyte and lymphocyte while WBC, eosinophil and ESR were not significantly changed. There was no significant difference in all hematological parameters among the three trimesters.ConclusionsHealthy pregnancy may have effect on hematological parameters. Therefore, there is a need to monitor these parameters during pregnancy. We also find that stages of pregnancy have no influence on hematological parameters.     

Randomized controlled trial of pulse methyl prednisolone × placebo in treatment of pulmonary involvement associated with severe leptospirosis. [ISRCTN74625030]

Background

The lungs are involved in up to 70% of cases of leptospirosis. In the more severe forms-bleeding from the lungs and acute respiratory distress syndrome-the lethality is high. The treatment proposed for leptospirotic pneumonitis includes just care for patients in critical condition. Clinical and experimental studies point to the involvement of immunological mechanisms in the physiopathology of lung damage caused by leptospirosis. The aim of this study is to evaluate pulse treatment with methylprednisolone × placebo for leptospirotic pneumonitis.

Study design

This is a randomized double-blind clinical trial to test the efficacy of pulse treatment with methylprednisolone in patients with leptospirotic pneumonitis, compared with a placebo. The patients are recruited from three hospitals in the city of Recife, in the Brazilian State of Pernambuco. The exclusion criteria include patients aged under 15 years, a history of hypersensitivity to the use of corticosteroids, the presence of active infection of fungal, tuberculous or bacterial origin apart from the infection by leptospira itself, the presence of hemoconcentration or atypical lymphocyte count on admission to hospital, the presence of co-morbidities that could be responsible for the radiological and gasometric alterations used to diagnose leptospirotic pneumonitis, evidence of recent cranial trauma, neurosurgery, peptic ulcer, and participation in another clinical trial. The patients are followed until they are discharged from hospital or die. The intervention consists of endovenous pulse treatment with 1 g methylprednisolone for three consecutive days in the study group and a placebo in the control group. The primary end-point is mortality from leptospirotic pneumonitis. The secondary end-points are: evolution of lung disease; the occurrence of nosocomial respiratory infection; duration of mechanical ventilation; duration of intensive care unit (ICU) stay; duration of hospital stay; occurrence of other infection-related complications; other respiratory complications; and adverse effects of methylprednisolone. The study is designed to recruit 266 patients and has a statistical "power" of 80% to detect a 50% reduction in mortality.

Discussion

Lung involvement in leptospirosis is a serious manifestation, with a high and variable mortality rate. There is still no specific clearly-established treatment. Well-designed studies are needed to pave the way towards development of such a treatment.

     

Salmon calcitonin nasal spray in the prevention of corticosteroid- induced osteoporosis

The objectives were to determine the efficacy and safety of nasal salmon calcitonin 200 IU daily in the prevention of corticosteroid- induced osteoporosis. A minimized, double-blind, placebo-controlled trial was carried out in corticosteroid-treated patients with polymyalgia rheumatica. The setting was a tertiary care university- affiliated hospital and a total of 31 patients were enrolled. The primary outcome measure was the percentage change in bone mineral density of the lumbar spine in the two treatment groups from baseline to 1 yr of follow-up. The mean +/- S.D. bone mineral density of the lumbar spine in the calcitonin-treated group decreased by 1.29 +/- 6.76% and in the placebo group by 4.95 +/- 3.50% after 12 months. The observed difference of 3.65 +/- 2.10% between groups is statistically significant (P < 0.05). Nasal salmon calcitonin prevented loss of bone in the lumbar spine as measured by dual-energy X-ray absorptiometry.      

Overexpression of cyclin D1 in the Dami megakaryocytic cell line causes growth arrest

The maturation of megakaryocytes in vivo requires polyploidization or repeated duplication of DNA without cytokinesis. As DNA replication and cytokinesis are tightly regulated in somatic cells by cyclins and cyclin-dependent kinases, we sought to determine the pattern of cyclin gene expression in cells that undergo megakaryocytic differentiation and polyploidization. The Dami megakaryocytic cell line differentiates and increases ploidy in response to phorbol 12-myristate 13-acetate (PMA) stimulation in vitro. We used Northern blotting to analyze mRNA levels of cyclins A, B, C, D1, and E in PMA-induced Dami cells and found that cyclin D1 mRNA levels increased dramatically (18-fold). Similar increases in cyclin D1 mRNA were obtained for other cell lines (HEL and K562) with megakaryocytic properties, but not in HeLa cells. The increase in cyclin D1 was confirmed by Western immunoblotting of PMA-treated Dami cells. This finding suggested that cyclin D1 might participate in megakaryocyte differentiation by promoting endomitosis and/or inhibiting cell division. To address these possibilities, we constructed two stable Zn+2-inducible, cyclin D1-overexpressing Dami cell lines. Cyclin D1 expression alone was not sufficient to induce polyploidy, but in conjunction with PMA-induced differentiation, polyploidization was slightly enhanced. However, unlike other cell systems, cyclin D1 overexpression caused cessation of cell growth. Although the mechanism by which cyclin D1 may affect megakaryocyte differentiation is not clear, these data demonstrate that cyclin D1 is upregulated in differentiating megakaryocytic cells and may contribute to differentiation by arresting cell proliferation.     

Hazardous drinking is associated with an elevated aspartate aminotransferase to platelet ratio index in an urban HIV-infected clinical cohort

Objectives

The aim of the study was to determine the relationship between alcohol consumption and liver fibrosis as assessed by aspartate aminotransferase to platelet ratio index (APRI) in HIV‐infected adults and to explore the relative contributions of alcohol and hepatitis C virus (HCV) to APRI among HIV/HCV‐coinfected adults.

Methods

We performed a cross‐sectional analysis of data from an observational clinical cohort. Alcohol consumption was categorized according to National Institute on Alcohol Abuse and Alcoholism guidelines. We defined significant liver disease as APRI>1.5, and used multinomial logistic regression to identify correlates of increased APRI.

Results

Among 1358 participants, 10.4% reported hazardous drinking. It was found that 11.6% had APRI>1.5, indicating liver fibrosis. Hazardous drinking was associated with increased APRI [adjusted relative risk ratio (RRR) 2.30; 95% confidence interval (CI) 1.26–4.17]. Other factors associated with increased APRI were male gender, viral hepatitis, and HIV transmission category of injecting drug use. Among coinfected individuals, 18.3% had APRI>1.5, and hazardous drinking was not associated with APRI. Among non‐HCV‐infected individuals, 5.3% had APRI>1.5 and hazardous drinking was associated with increased APRI (adjusted RRR 3.72; 95% CI 1.40–9.87).

Conclusions

Hazardous drinking is an important modifiable risk factor for liver fibrosis, particularly among non‐HCV‐infected patients. Clinicians and researchers must address alcohol use as the burden of liver disease increases among HIV‐positive individuals.     

Association of HLA-DR with susceptibility to and clinical expression of rheumatoid arthritis: re-evaluation by means of genomic tissue typing

The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re- examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.      

Posttraumatic intrahepatic arterial pseudoaneurysm: treatment with direct percutaneous puncture.

The authors describe a patient with a posttraumatic intrahepatic false aneurysm. In this case, transcatheter embolization was not possible because of previous right hepatic artery embolization. To avoid the morbidity associated with surgery, direct percutaneous puncture of the pseudoaneurysm was performed under fluoroscopic guidance to permit embolization with Gianturco coils. Direct percutaneous embolization of intrahepatic aneurysms and pseudoaneurysms can be a safe and effective alternative to surgery when transcatheter techniques are not feasible.