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Biomedical subjects

A G Maciver

Publications and source records attributed to A G Maciver.

14 recordsLinked to original sources

Wegener's granulomatosis involving the urogenital tract.

OBJECTIVE: To report eight cases of limited Wegener's granulomatosis (WG) affecting the urogenital tract (testis, ureter, bladder, urethra and penis) and to emphasize the importance of the anti-neutrophil cytoplasm antibody (ANCA) test in establishing the diagnosis. PATIENTS AND METHODS: Eight patients (six men and two women, aged 41-77 years) were diagnosed with WG, based on their previous medical history, the ANCA test and by biopsy. RESULTS: In each case, there were difficulties and delay in establishing the diagnosis of WG and starting appropriate treatment. The ANCA test was positive in seven cases and helped in establishing the diagnosis, in conjunction with the confirmation of vasculitis and granulomata by biopsy. CONCLUSION: We advocate ANCA testing in patients presenting with limited urogenital disease in association with a past or present relevant history of arthritis, skin vasculitis and/or biopsies showing necrosis or non-specific inflammation.

Adult

Clinical features and outcome of patients with thin and ultrathin glomerular membranes.

There is considerable disagreement regarding the natural history of renal disease associated with thin glomerular basement membranes (TGBM). We followed 43 patients (19 male), mean age 41.6 years (range 19-73) for a mean of 88 months (48-140). TGBM was recognized in adults when glomerular basement membrane thickness, measured from multiple sites in electronmicrographs of renal biopsy tissue as the harmonic mean, was < 320 nm. At presentation, 95% had microscopic haematuria, 12% macroscopic haematuria, 14% loin pain, 28% proteinuria, and 14% hypertension. There was no difference in GBM width between the sexes (male 258 nm vs. female 251 nm) but there was a significant negative correlation between age and GBM width (r = -0.53, p < 0.001), with older patients having the thinnest membranes. Twenty six patients had ultrathin GBM (< 270 nm), of whom 54% had 3+ haematuria vs. 12% of the group with BM > 270 nm (p < 0.01). In the ultrathin group, 71% had loss of anionic charge from the GBM, vs. 17% in those with membranes which were thin but > 270 nm (p < 0.05). Proteinuria occurred more frequently in those with GBM > 270 nm, 65% vs. 8% in the ultrathin group (p < 0.01). Thin GBM were associated with a benign prognosis, as after a mean follow-up of 85 months (48-140), there was no significant change in either serum creatinine or mean arterial blood pressure. Patients with ultrathin GBM had greater loss of GBM anionic charge, which might result in both an alteration of flow characteristics within the glomerular capillaries and also increased fragility of the glomerular basement membrane with likelihood of rupture and resultant macroscopic haematuria.

Adult

Aortic valve disease in patients with Wegener's granulomatosis.

Wegener's granulomatosis usually affects the upper and lower respiratory tract as well as the kidney. Cardiac involvement is rare, although electrocardiographic abnormalities, coronary artery vasculitis, cardiac arrhythmias, and myocardial infarction have been described. We report two cases of aortic valve disease associated with Wegener's granulomatosis that were progressive despite clinical remission of Wegener's disease in both patients. One patient has undergone successful valve replacement and the other is currently awaiting surgery. Aortic valve histopathology showed myxoid degeneration that was most likely due to previously active vasculitis affecting the vessels of the aortic wall and valvular necrosis with subsequent progressive degeneration of the cusps.

Adult

Do mesangial immune complex deposits affect the renal prognosis in membranous glomerulonephritis?

Patients with rheumatoid arthritis who develop membranous glomerulonephritis associated with gold or penicillamine therapy have been shown to get better when the drugs are discontinued, whereas up to 50% of patients with idiopathic membranous glomerulonephritis develop renal failure. A feature of the lesion in rheumatoid disease is the presence of mesangial immune complex deposits in addition to the basement membrane deposits of classical idiopathic membranous glomerulonephritis. To determine whether the presence of mesangial immune complexes indicates a different renal outcome in membranous glomerulonephritis we studied 3 groups: group A 10 patients with rheumatoid arthritis and drug induced membranous glomerulonephritis with mesangial immune complex deposits, group B 14 patients with idiopathic membranous glomerulonephritis with additional mesangial immune complex deposits and group C 25 patients having classic idiopathic membranous glomerulonephritis with deposits solely in the glomerular basement membrane. After median follow up of 72 months, nephrotic range proteinuria resolved in all cases in group A after drug withdrawal, 93% of group B, but only 60% of group C (groups A + B vs C, X2 = 7.8, p < 0.01). Serum creatinine remains less than 500 mumol/l in all patients in group A, 93% of group B, but only 64% of group C (groups A + B vs C, X2 = 7.6, p < 0.01). Mesangial immune complex deposits were predominantly of the IgM isotype in both the rheumatoid and idiopathic membranous group. The presence of mesangial immune complex deposits suggests either a different pathogenesis or host responsiveness to that found in classic idiopathic membranous glomerulonephritis, and predicts a more favourable renal outcome.

Adult

C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.

Adult

An immunohistological study of granulomatous prostatitis.

Granulomatous prostatitis may result from tuberculosis and fungal infection and has been described following prostatic surgery. In most cases, however, the aetiology is unknown, although it may be due to a reaction to extravasated or altered prostatic secretions. We have investigated cells (macrophages, lymphocytes), serum proteins (fibrinogen, alpha 1-antitrypsin) and prostatic epithelial products (prostatic-specific antigen and prostatic acid phosphatase) in diffuse granulomatous prostatitis (3 cases), focal periacinar prostatic granulomas (9) and focal prostatic infarcts (5), using an immunohistological technique. T-lymphocytes and macrophages are present in diffuse and focal granulomatous prostatitis, but few B-lymphocytes occur. Fibrinogen-related antigen is absent from granulomas, but a small amount is present within infarcts, whereas plentiful alpha 1-antitrypsin was detected both in granulomas and infarcts. Significant reduction in prostatic-specific antigen and acid phosphatase reactivity occurs in granulomatous prostatitis. This suggests that cytokines derived from activated macrophages and T-lymphocytes may be exerting a cell regulatory effect and altering cell secretions, as well as causing destruction of the prostatic epithelium.

Acid Phosphatase

Monoclonal antibodies that recognize different membrane proteins that are deficient in Rhnull human erythrocytes. One group of antibodies reacts with a variety of cells and tissues whereas the other group is erythroid-specific.

1. Rhnull human erythrocytes lack all of the antigens of the Rh and LW blood group systems and have abnormal shape and an increased osmotic fragility. In this paper two murine monoclonal antibodies raised against intact human erythrocytes were used to investigate further the abnormalities in these cells. BRIC 125 reacts weakly with Rhnull erythrocytes and BRIC 69 does not react at all. The results showed that BRIC 125 reacts with a component of Mr 47,000-52,000 which has a substantial content of N-glycans. In contrast, BRIC 69 reacted with a band of Mr 31,000 together with a very diffuse band of Mr 35,000-52,000. Treatment of BRIC 69 immunoprecipitates with endoglycosidase F/peptidyl-N-glycosidase F resulted in the loss of both BRIC 69 reactive components and the appearance of a new band of Mr similar to that of the Rh(D) polypeptide. 2. BRIC 125 had a broad reactivity with cells in peripheral blood, whereas the reactivity of BRIC 69 was confined to erythrocytes. BRIC 125, but not BRIC 69, reacted with human kidney tissue and bound to endothelium in peritubular capillaries, arteries and veins as well as the epithelial tissue of distal tubules. BRIC 125 stained haemopoietic cells, foetal hepatocytes and megakaryocytes in foetal liver and sinusoidal cells, hepatocytes and portal tracts in adult liver. In contrast, BRIC 69 reactivity was confined to haemopoietic cells in foetal liver. The BRIC 125 epitope has a wide tissue distribution, suggesting the occurrence of a related group of polypeptides which have a general functional role on cell surfaces. 3. Rhnull erythrocytes are deficient in at least four different membrane polypeptides.

Antibodies, Monoclonal

Zollinger-Ellison syndrome in a child: medical treatment with cimetidine.

A 12-year-old boy presented with intestinal obstruction associated with duodenal and oesophageal ulceration. At laparotomy he was found to have an islet cell tumour in the right lobe of the liver. Gastroenterostomy was performed. Raised levels of serum gastrin were detected. Treatment with cimetidine has produced satisfactory control of his symptoms for 16 months, and is an acceptable alternative to total gastrectomy in childhood.

Child

Quantitative liver imaging using 131-I Rose Bengal as an index of liver function and prognosis.

A technique for assessing quantitatively hepatic function by direct measurement of liver parenchymal cell uptake of 131I Rose Bengal using a scintillation camera with a digital store and retrieval system is described. Ninety-four studies were performed on 84 patients with a variety of hepatic disorders over a two-year period, the diagnosis in each case being established by liver biopsy or laparotomy. The results were compared with the clinical, biochemical and histological assessment of the patients. A good correlation was found between the half-time for hepatic uptake of 131I Rose Bengal and the histological changes, as well as with clinical prognosis measured in terms of clinical improvement or deterioration to death. The rate of liver uptake was found to be a better index than the clearance of radioisotope from the blood and was superior to conventional biochemical investigations in both icteric and anicteric patients. The test was not shown to be of clinical value in discriminating between intra- and extrahepatic causes of jaundice. It is suggested that this technique may provide a safe and sensitive method for assessing the severity of liver dysfunction and also for monitoring clinical progress, especially in situations where liver biopsy may be unreliable or hazardous.

Biopsy

The secretory immunoglobulin system in urothelial neoplasia.

The role of the secretory immunoglobulin system in urinary tract neoplasia has been investigated by staining formalin-fixed, paraffin-wax embedded sections of normal and abnormal urinary tract epithelium for secretory component (SC), IgA and J (joining) chain. Normal mucosa contains IgA with J chain and SC as a thin superficial layer on surface umbrella cells and in small amounts in the cytoplasm of intermediate cells. Inflamed mucosa is infiltrated by many IgA and J chain positive plasma cells in the lamina propria and there is IgA, SC and J chain in the cytoplasm of the second layer of the epithelium as much as in surface umbrella cells. Epithelium with moderate to severe dysplasia and invasive transitional cell carcinoma is almost always negative, containing only occasional cells with cytoplasmic IgA, J chain and SC, whilst surface staining is entirely absent.

Humans