Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Summary: Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35 ± 6 years vs 42 ± 9 years) and had worse histological scores for tubular atrophy (1.7 ± 0.7 vs 1.1 ± 0.5) and arteriolar hyperplasia (1.4 ± 0.7 vs 0.7 ± 0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9 ± 0.3 mg/dL to 2.5 ± 1.2) or reduction in creatinine clearances (52 ± 20mL/min to 52 ± 27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1 ± 0.5 mg/dL to 3.3 ± 1.1, P < 0.01) and a fall in creatinine clearances (51 ± 26 mL/min to 31 ± 22, P = 0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2 ± 1.2 g/day to 1.3 ± 1.1, non-treatment group: 1.9 ± 1.4 to 1.5 ± 1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.     

Comparative genome analysis of Ureaplasma parvum clinical isolates

Ureaplasma parvum colonizes human mucosal surfaces, primarily in the respiratory and urogenital tracts, causing a wide spectrum of diseases, from non-gonococcal urethritis to pneumonitis in immunocompromised hosts. Although the basis for these diverse clinical outcomes is not yet understood, more severe disease may be associated with strains harboring a certain set of strain-specific genes. To investigate this, whole genome DNA macroarrays were constructed and used to assess genomic diversity in 10 U. parvum clinical strains. We found that 7.6% of U. parvum genes were dispersed into one or more strains, thus defining a minimal functional core of 538 U. parvum genes. Most of the strain-specific genes (79%) were of unknown function and were unique to U. parvum. Four hypervariable plasticity regions were identified in the genome containing 93% of the variability in the gene pool (UU32-UU33, UU145-UU170, UU440-UU447 and UU527-UU529). We hypothesized that one of them (UU145-UU170) was a pathogenicity island in U. parvum and we characterized it. Thus, we propose that the clinical outcome of U. parvum infection is probably associated with this newly identified pathogenicity island.     

A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome)

Rump P, Niessen RC, Verbruggen KT, Brouwer OF, de Raad M, Hordijk R. A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome). Opitz–Kaveggia syndrome is a rare X‐linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty‐three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz–Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.     

Pattern and antibiogram of urinary tract infection at the University of Port Harcourt Teaching Hospital

ObjectiveTo explore the prevalence, pathogenicity, and antibiotic susceptibility patterns of urinary tract infections at the University of Port Harcourt Teaching Hospital.MethodsSamples from 400 patients with a presumptive diagnosis of urinary tract infection including 250 non pregnant females and 150 males were used for this study. They were distributed into two groups: children aged 2 to 17 (Group A) and adults aged 18 to 75 (Group B). The standard wire loop and agar diffusion technique were employed for culture and susceptibility testing, respectively. Data obtained were analysed using SPSS, version 14.Results30.0% of Group A and 41.0% of Group B had significant bacteriuria with 66.7% and 79.3% as females, respectively. The commonest isolates cultured were Escherichia coli (32.8%), Staphylococcus aureus (17.2%), and Klebsiella spp. (16.4%). About 76.6% of isolates were sensitive to the fluorinated quinolones, 31.2% to the aminoglycosides, and 22.7% to the urinary antiseptic, nitrofurantoin. The isolates were non-sensitive to tetracycline (93.8%), cotrimoxazole (92.2%), and nalidixic acid (86.7%). Most isolates showed non-uniform sensitivity patterns to the cephaloporins (cefuroxime and ceftazidime). Pseudomonas spp. isolates were generally resistant to the fluorinated quinolones.ConclusionThough the fluorinated quinolones are still largely effective for empirical therapy in urinary tract infections, the importance of prior sensitivity testing in checking the emergence of bacterial antibiotic resistance can not be overemphasized.     

Clinico-pathological correlates in IgA nephropathy

Summary: There were 2758 biopsies of glomerulonephritis diagnosed in the Department of Pathology in the 20 years from 1976 to 1995. Of these 1893 (76.1%) were of primary glomerulonephritis while 577 (23.2%) were of secondary glomerulonephritis. Immunofluorescence studies were available in 1494 (80%) cases. Predominantly mesangial IgA staining was seen in 49.1% of cases, thus identifying them as IgA nephropathy. Mesangial glomerulonephritis was found in 79.1% of cases whilst 17.7% had sclerotic lesions either focal or global. One hundred and fifty-one patients were followed up. Of these, 98 (65%) were detected through health screening while 53 (35%) presented with symptoms. Uncontrolled hypertension, proteinuria of more than 2 g, the presence of crescents and glomerulosclerosis on biopsy were unfavourable prognostic factors. Hypertensive patients also had a higher incidence of medial hyperplasia of the blood vessels. However IgA nephropathy is a benign disease with a cumulative renal survival of 91% after 6 years.