Eosinophilic glomerulonephritis in children in Southwestern Uganda.

Acute renal disease is common in sub-Saharan Africa, with high mortality. Its etiology is poorly understood; quartan malaria owing to Plasmodium malariae was implicated in previous series. Few previous studies have included histological data; furthermore, much of the literature pre-dates the human immunodeficiency virus (HIV) epidemic. We report prospective analysis of acute proteinuric renal disease in children in rural Uganda. Clinical and laboratory data are presented on 65 patients (aged 2-14 years, mean 8.4; 35 male, 30 female) in 41 of whom histological diagnosis was obtained by renal biopsy. The most frequent histological finding was endocapillary proliferative glomerulonephritis (GN) in 27/41 cases, in 20 of which eosinophils were very prominent. No cases showed features of HIV nephropathy. Malarial films were positive in 11 cases: all owing to Plasmodium falciparum. Patients were treated with diuretics, antihypertensives, and supportive measures. Corticosteroids were rarely used, being reserved for patients with minimal changes on renal biopsy. Clinical outcomes were fair: 91% of patients survived to discharge. We conclude that acute GN is common in children in Uganda, that an unusual eosinophilic proliferative GN is the most frequent histological finding, that HIV is not implicated as an important factor in this age group, and that good outcomes can be achieved using simple clinical and laboratory diagnostic methods. Renal biopsy in selected cases is feasible and helpful, especially in allowing rational use of corticosteroids and other potentially toxic treatments. Symptomatic treatments and careful supportive care will allow the majority of children to recover.

Clinical value of renal biopsy in patients with asymptomatic microscopic hematuria with and without low-grade proteinuria.

BACKGROUND: The decision whether to perform renal biopsy on patients with persistent asymptomatic microscopic hematuria (AMH) with and without low-grade proteinuria (LGP) remains controversial as, although often diagnostic, the information gained seldom alters clinical management. Our study investigates the clinical value of renal biopsy in patients with isolated AMH versus those with AMH and LGP. METHODS: Between 1996 and 2002, we identified 89 patients with AMH and 46 with AMH and LGP. The patients were asymptomatic, free from systemic illness, had a sterile urine, normal serum creatinine, normal renal and bladder ultrasound, less than 2.5 g proteinuria/day, underwent successful renal biopsy and were followed-up for a mean period of 46 +/- 12 months. RESULTS: In patients with isolated AMH, thin basement membrane nephropathy (TBMN) was diagnosed in 43%, IgA nephropathy in 20%, minor abnormalities in 19% and normal biopsies in 18%. In patients with AMH and LGP, IgA nephropathy was diagnosed in 46%, other major nephropathies in 26%, minor abnormalities in 17%, TBMN in 7% and normal biopsies in 4%. At follow-up, 32% of AMH patients and 38% of AMH with LGP patients had a GFR of less than 90 ml/min and 36% and 56%, respectively were hypertensive. CONCLUSIONS: The results support the current consensus that routine renal biopsy is not indicated for isolated AMH but suggest that biopsy is indicated for AMH and LGP identifying major and potentially progressive nephropathies in 70% of patients, who should be managed by specialist nephrologists.

Her-2/neu oncogene amplification in clinically localised prostate cancer.

AIM: To examine the incidence of Her-2/neu oncogene amplification in clinically localised prostate cancer using in situ hybridisation. METHODS: One hundred and seventeen patients, who had undergone radical prostatectomy, were identified and in situ hybridisation was performed on formalin fixed, paraffin wax embedded tissue using the Quantum Appligene probe for Her-2/neu. The enzyme peroxidase was used to detect the probe because this enabled a permanent record to be kept. Tumours in which there were five or more signals in each nucleus in > 20% of the tumour cells were considered to have a significantly increased copy number. A serial section from these tumours was then hybridised with the chromosome 17 alpha satellite probe. The ratio of the percentage of cells showing an increase in Her-2/neu copy number to the number showing polysomy for chromosome 17 was calculated. A ratio above 2 was considered amplified. RESULTS: Biochemical recurrence occurred in 50 (43%) patients and 24 (21%) had clinical recurrence. In situ hybridisation for Her-2/neu was accessible in 114 (97%) patients. A significant increase in copy number was present in two patients (1.75 %), but chromosome 17 hybridisation showed that the increase was the result of polysomy rather than true amplification. Both these patients had a Gleason score of 7 and stage T3; they also had recurrent clinical disease with distal metastasis within two and 19 months. CONCLUSIONS: Increased Her-2/neu oncogene copy number appears to be rare in clinically localised prostatic adenocarcinoma and is related to chromosome 17 polysomy rather than true amplification. As a result, it would not be a useful biomarker for identifying those patients who will have recurrences after radical prostatectomy.

Expression of neuropilin-1 by human glomerular epithelial cells in vitro and in vivo.

Vascular endothelial growth factor (VEGF) is a potent promoter of endothelial mitogenesis and of endothelial permeability. Within the kidney it is synthesized primarily in the visceral glomerular epithelial cells (vGECs); however, the role of VEGF in the glomerulus remains unknown, as does the target cell upon which it acts. Although the target cells may be those of the glomerular endothelium, there are micro-anatomical reasons why this might not be the case. This, therefore, led us to consider the possibility that glomerular VEGF may bind to the vGECs themselves. Since it has been shown that vGECs do not express the main tyrosine kinase VEGF receptors, we chose to study vGEC expression of the more recently described VEGF isoform-specific receptors, the neuropilins. The expression of mRNAs for neuropilin-1, neuropilin-2 and soluble neuropilin was studied in whole kidney, sieved glomeruli and cultured podocytes by reverse transcription-PCR, and neuropilin-1 mRNA expression in isolated single glomeruli was analysed by nested reverse transcription-PCR. The expression of neuropilin-1 protein was investigated in cultured vGECs by Western blotting and immunocytochemistry, and in normal kidney sections by immunohistochemistry. Neuropilin-1 mRNA was detected in whole kidney, single and sieved glomeruli and cultured vGECs. Neuropilin-1 protein was detected in cultured vGECs and in vGECs in normal kidney sections by immunohistochemistry. Thus the present study suggests that vGECs may have the potential to bind the VEGF that they secrete. Functional studies will be required to address the potential significance of this finding in terms of an autocrine loop or VEGF sequestration.

Hypertension and facial palsy in middle aortic syndrome.

A female infant presented with facial palsy and was found to be severely hypertensive. Plasma renin activity was raised and an angiogram showed middle aortic syndrome. This condition is of unknown aetiology, but positive antineutrophil cytoplasmic antibodies may indicate a vasculitis which heals by intimal fibrosis, causing the observed findings.

Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx.

BACKGROUND: The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea. METHODS: Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0-38)/h, apnoea-hypopnoea index (AHI) 28(9-45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration. RESULTS: AI decreased to a median (range) value of 0 (0-6)/h (p<0.01) and AHI to 8 (1-28)/h (p<0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p<0.02) in the hypopharynx and by 25% (11 to 69) (p<0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p = 0.01). CONCLUSIONS: A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep apnoea by maintaining patency of the velopharynx, particularly in its lateral dimension.

Histological evaluation of endometrium on the day of oocyte retrieval after gonadotrophin-releasing hormone agonist-follicle stimulating hormone ovulation induction for in-vitro fertilization.

The objective of this study was to evaluate the histopathological characteristics of endometrial biopsies taken on the day of oocyte recovery in in-vitro fertilization (IVF) cycles with a satisfactory response to ovulation induction. A group of 33 patients who went through ovulation induction for IVF, and in whom an endometrial polyp was suspected on transvaginal ultrasonography during the monitoring phase, were studied. Following oocyte recovery, hysteroscopy, polypectomy and endometrial curettage were performed. Dating of endometrial glands and stroma was carried out in the tissue not containing the polyps. The total dose of follicle stimulating hormone (FSH), duration of ovulation induction, peak oestradiol and luteinizing hormone (LH) concentrations, thickness of endometrium and number of oocytes were recorded and compared to the endometrial dating of the specimens. In 15 cycles (45.5%), the endometrium was classified as 'in phase' (group I), 'advanced' by 2-4 days in a further 15 (45.5%, group II), and in the remaining three cycles (9%) it was delayed in maturation (group III). Younger age was correlated with advanced staging of the endometrium (r = -0.42; P = 0.015). Women with 'in phase' and 'advanced' maturation were similar in their response to ovulation induction; however, there was a strong correlation between advanced dating of endometrium and number of oocytes retrieved (r = 0.49; P = 0.04). Endometrial staging on the day of oocyte retrieval varied widely in patients treated by the same gonadotrophin-releasing hormone agonist (GnRHa)/FSH protocol for ovulation induction. This difference was not predictable by parameters monitored through the cycles.

Massive lymphocytic infiltration of uterine leiomyomas associated with GnRH agonist treatment.

AIMS: To report two unusual cases of massive lymphocytic infiltration of uterine leiomyomas, following GnRH agonist treatment. Previous reports have described a variety of alterations in leiomyoma histology following such therapy. METHODS AND RESULTS: These cases were studied using haematoxylin and eosin stains, and immunohistochemistry for B and T-cell markers (CD20/CD79a and CD3/UCHL-1) was performed. Leiomyomas were heavily infiltrated predominantly by mature lymphocytes of T-cell phenotype. Associated myocyte degenerative changes were present. CONCLUSIONS: Massive lymphocytic infiltration of leiomyomas may occur as a result of GnRH agonist treatment, although the mechanism is unclear.

Rapid determination of dissolved organic phosphorus in soil leachates and runoff waters by flow injection analysis with on-line photo-oxidation.

A rapid method suitable for the determination of dissolved organic phosphorus (DOP) in soil leachates and runoff waters is presented. The flow injection (FI) manifold contains an in-line PTFE reaction coil wrapped around a low power UV lamp and is based on the spectrophotometric determination of dissolved reactive phosphorus (DRP) and mineralised DOP at 690 nm after reduction of phosphomolybdate to molybdenum blue with tin(II) chloride. The linear range was 0-1.5 mg 1(-1) PO(4)-P, with a detection limit (3 s) of 7 mug 1(-1) and a sample throughput of 40 h(-1). Tolerance to potential matrix interferences in soil pore waters, particularly Al(III), Si(IV), Fe(II) and Fe(III), was achieved using a combination of on-line sample pre-treatment by a strong acid ion exchange column, low photoreactor pH and acid induced control of the kinetics of the molybdenum blue reaction. The results obtained with this manifold were in good agreement with those obtained by a batch spectrophotometric reference method.

Investigation of the fetal pulmonary inflammatory reaction in chorioamnionitis, using an in situ Y chromosome marker.

Chorioamnionitis is a frequent finding in the placenta in second-trimester premature labor. Seventy-six archival perinatal and fetal autopsies between 15 and 28 weeks of gestation with a morphologic diagnosis of chorioamnionitis were reviewed. Of the 76 cases, 52 (68%) had inflammatory cells in the lungs, which is higher than the reported incidence of clinical infection in neonates with chorioamnionitis. In 23 cases there were peribronchial lymphocytic hyperplasia and neutrophils in the airspaces, in 8 there was a lesser degree of interstitial inflammation as well as luminal neutrophils, and in 21 (40%) there were neutrophils in the airspaces only. To determine whether the neutrophils in the airspaces in the latter were maternal or fetal in origin, the lung sections of seven male fetuses in the group were examined by in situ hybridization for the Y repeat probe pHY 2.1, together with appropriate controls. Two of the tests were technical failures. The remaining five, and the positive controls, showed positivity for pHY 2.1 in 70-86% of luminal neutrophils. We conclude that luminal neutrophils in fetal lungs in this situation are fetal in origin.

Testicular seminoma in a patient with pineal germinoma.

A case is reported of a 30 year old man with a testicular seminoma. He had presented 16 years previously with a pineal germinoma, followed two years later by intracranial metastases. This is an unusual occurrence of double pathology in the germ cell line.

Isoprenaline-induced and constitutive members of a proline-rich protein sub-group from mouse parotid glands studied with monoclonal antibody NAL1.

Members of the proline-rich protein (PRP) family of mouse parotid glands were analysed before and after stimulation with the beta-agonist isoprenaline by using a monoclonal antibody raised against the induced PRP A3(0) (GP-27). Antibody NAL1 reacted strongly with isoprenaline-induced B-type PRP precursors and their salivary counterparts, but not against the A-type PRPs A1(0) (Gp-66) and A2(0) (GP-45) or human salivary proteins, and it is likely that NAL1 recognizes a proline-rich repeat variant unique to this group of rodent PRPs. PRP-related antigens were observed in the parotid glands (N1(0) and N2(0] and saliva of normal mice. The antigens were located immunocytochemically in secretory granules of parotid acinar cells of both normal and isoprenaline-stimulated mice. The total amount of PRP antigens increased 16-fold from 2.5 to 40% of parotid protein after 10 days of isoprenaline treatment, as estimated by enzyme-linked immunosorbent assay. Immunoblotting showed that new PRP species appeared during the period of increase. After treatment with isoprenaline, B-type PRPs appeared first, followed by A3(0) and another member of the family. These results show that the mouse PRP family is larger than previously thought and can be divided immunologically into sub-groups. That a subset of PRPs are produced in the normal mouse indicates that there is differential beta-adrenergic regulation within the family, and also has implications for the role of PRPs in the normal maintenance of healthy dentition and other processes.