Search PubMed⌕ Search

Biomedical subjects

A J Howie

Publications and source records attributed to A J Howie.

At least 109 records · Page 6Linked to original sources

A simple method for assessment of glomerular size and its use in the study of kidneys in acromegaly and compensatory renal enlargement.

As measurement of absolute glomerular size is difficult we developed a method of assessing glomerular size that was simple and practical and could be used to compare the kidneys in different groups of patients. Using a semi-automatic image analyser, the cross-sectional area of 100 randomly-selected glomeruli, outlined by Bowman's capsule, was measured on sections of kidneys taken at necropsy. The mean of the logarithms of the largest 25 areas was calculated. The method was applied to compare control kidneys (53) with the kidneys in acromegalics (20), in patients with one kidney (10) and in patients with asymmetrical kidneys (12). Kidneys were heavier in the three test groups than in controls. Glomerular sizes were similar in controls and in acromegalics but were larger in single and disparate kidneys. There was a relationship between glomerular size and kidney weight within the control group and across the four groups taken together. This only partly accounted for the observed differences in glomerular size between the groups. Histological comparison of the acromegalic and single kidneys showed more global glomerulosclerosis in single kidneys and also segmental lesions, mainly at the glomerular hilum, only in the single kidneys. These findings show that renal enlargement occurs in acromegaly and in single and disparate kidneys but is accompanied by markedly different glomerular features. This implies different mechanisms for the renal enlargement. The method of assessing glomerular size is useful in the study of these and other conditions affecting the kidney.

Acromegaly↗

Reactive oxygen products in heterologous anti-glomerular basement membrane nephritis in rats.

The effect of 'scavengers' of reactive oxygen products (ROPs) was studied in the heterologous phase of anti-glomerular basement (anti-GBM) nephritis induced in rats. Glomerulonephritis was induced by the intravenous administration of sheep anti-GBM antibody (5 mg/100 g) to rats on day 0. The intraperitoneal administration of superoxide dismutase (SOD) 30 mg/kg/day or 150 mg/kg/day leads to a significant reduction in proteinuria on day 1 and also on day 3 in animals given SOD 30 mg/kg/day. Proteinuria was not significantly reduced by the intraperitoneal administration of inactivated SOD (150 mg/kg/day). In rats given polyethylene glycol coupled catalase (PEG-catalase) intraperitoneally at a dose of 10,000 iu/kg/day and 100,000 iu/kg/day proteinuria was lower than in rats with unmodified anti-GBM nephritis. These differences were significant on day 1 (P less than 0.05) in rats given PEG-catalase 100,000 iu/kg/day and on days 3 and 5 in rats treated with either dose of PEG-catalase (P less than 0.01). These data suggest a role for superoxide anion and hydrogen peroxide, or a product of their interaction such as hydroxyl radical, in glomerular injury induced by anti-GBM antibody.

Animals↗

Changes at the glomerulo-tubular junction in renal transplants.

We studied by microscopy 377 biopsies, nephrectomies, and necropsy kidneys from 123 human renal transplants. We discovered two common abnormalities of the renal corpuscle, both affecting the glomerulo-tubular junction. Adhesion of the tip of the glomerular tuft to the origin of the tubule, as reported in various non-transplant glomerulopathies, was seen in 197 specimens (52 per cent). This change was common in material showing acute or chronic vascular rejection and glomerulopathy, and was almost universal in transplants that had been in place for over 1 year. Another change at the glomerulo-tubular junction, not previously highlighted, consisted of an infiltrate of lymphocytes or neutrophil polymorphs into the epithelium at the tubular origin. This change was seen in 145 specimens (38 per cent) and was associated with cellular rejection and ascending infection. These changes are of importance because they show two responses of the kidney to injury that involve the glomerulo-tubular junction and thus suggest that this part of the kidney has some specific properties that have been largely neglected up to now.

Cell Adhesion↗

Lymphoid aggregates in bone marrow: study of eventual outcome.

The practical importance of finding a morphologically benign lymphoid aggregate in the bone marrow of patients without known lymphoproliferative disease was assessed in 786 consecutive patients who had had 951 iliac crest bone marrow biopsies performed. Of these, 430 patients known to have lymphoproliferative disease at the time of biopsy were excluded. Of 356 patients, 86 (aggregate group) had at least one lymphoid aggregate in their biopsy specimen biopsy specimen (82 morphologically benign, three suspicious, and one malignant). Another 86 patients without aggregates (control group) were matched by age and sex. Both groups were followed up until death, or for a mean of 21.9 and 22.9 months, respectively, to assess their outcome. Eighteen (22%) of the 82 patients with morphologically benign lymphoid aggregates were later proved to have lymphoproliferative disease compared with none of the 86 control patients. Another 12 patients in the aggregate group and seven in the control group were suspected of having a lymphoproliferative disease on clinical grounds, so that altogether 30 (37%) and seven (8%), respectively, developed confirmed or suspected lymphoproliferative disease. In both cases the differences were highly significant (p less than 0.001). It is suggested that lymphoid aggregates in clinical biopsy material may not be a physiological finding and should alert pathologists or haematologists to the possibility of lymphoproliferative disease.

Adult↗

Tamm-Horsfall protein outside the kidney.

Tamm-Horsfall protein is the main protein in normal urine and readily precipitates. Previously there has been little study of the protein outside the kidney. An antiserum to the protein was used in an immunohistological investigation of human tissues. No Tamm-Horsfall protein was detected in normal organs other than the kidney. The protein was detected outside the kidney in abnormal organs in three general sites: (i) in ulcers of epithelial surfaces exposed to urine, (ii) deep in the wall of a bladder that had had previous surgery and (iii) in lymph nodes at the hilum of kidneys that had been obstructed or contained extra-tubular deposits of the protein. There was little evidence of a cellular response to the deposits of Tamm-Horsfall protein. The antiserum to Tamm-Horsfall protein is a good immunohistological marker of extravasated urine and is useful in the study of such conditions as fistulas of the urinary tract, operations on the urinary tract and reflux of urine into lymphatics and lymph nodes.

Female↗

The role of superoxide anion and hydrogen peroxide in glomerular injury induced by puromycin aminonucleoside in rats.

1. The nephrotic syndrome was induced in inbred female Wistar rats by the intravenous injection of puromycin aminonucleoside (PA) (5 mg/100 g body weight). 2. One group (n = 12) received superoxide dismutase (SOD) (15 mg/kg body weight), a second group (n = 12) received polyethylene glycol coupled catalase (PEG-catalase) (5000 i.u./kg body weight) and the third (n = 9) saline (150 mmol/l NaCl) via the intraperitoneal route, in addition to the PA. 3. SOD and PEG-catalase reduced the 24 h urine protein on days 8 and 15 compared with unmodified puromycin treated animals and this difference was significant on day 15 for SOD (P less than 0.05) and for PEG-catalase (P less than 0.01). Glomerular filtration rate, as measured by the creatinine clearance, was lower in the PEG-catalase group but did not differ significantly from the saline treated group. 4. These data suggest that superoxide anion and hydrogen peroxide, or their reaction products, are involved in the glomerular injury of puromycin nephropathy.

Animals↗

Rheumatoid arthritis and IgA nephropathy.

We describe four patients with seropositive rheumatoid arthritis who developed proteinuria and microscopic haematuria. Renal biopsy demonstrated a mesangial proliferative glomerulonephritis with mesangial deposits of IgA. These data suggest a possible causal relationship between rheumatoid arthritis and IgA nephropathy.

Adult↗

Polyarteritis and the kidney.

We report data on 43 patients with polyarteritis affecting the kidneys. The majority (41 patients) had renal histological evidence of microscopic polyarteritis. Although most patients (30 of 43) had significant renal impairment at the time of diagnosis (serum creatinine greater than 250 mumol/l) only five had a symptom, macroscopic haematuria, that directed attention to the kidneys. In the majority of patients in whom data was available there was rapid deterioration in renal function between presentation and diagnosis. Renal function at diagnosis was worse in patients aged over 50 of whom 20 out of 29 had a serum creatinine greater than 500 mumol/l compared with only four of 14 patients aged less than 50. The prognosis was worse in patients over 50 (41 per cent died), in patients with a serum creatinine higher than 500 mumol/l (54 per cent died) and in patients treated with intravenous methylprednisolone, (four also had intravenous cyclophosphamide) (38 per cent died). The major cause of death was sepsis and the actuarial one-year survival was 62 per cent. These results suggest that our approach to treatment should be modified towards lessening immunosuppression in older patients and in patients with renal failure at diagnosis.

Adult↗

The glomerular tip lesion: a steroid responsive nephrotic syndrome.

The glomerular tip nephropathy is a cause of the nephrotic syndrome and has distinct pathological features. Glomerular tufts appear normal on light microscopy except for a segmental lesion invariably present in all glomeruli at the origin of the proximal tubule. Data on twenty adults whose renal biopsies demonstrated this lesion and who were followed for a mean of 7.4 years are analyzed. Eighteen patients were treated with steroids; ten of these had complete remission of proteinuria and seven a significant reduction of their proteinuria. Ten patients had moderately impaired renal function (serum creatinine greater than 120 mumol/l) at presentation, eight received steroids and achieved a reduction in serum creatinine. The prognosis was good, with no patient developing chronic renal failure requiring dialysis.

Adult↗

Non-steroidal anti-inflammatory drugs and renal failure.

In 3 years seventeen patients presented to one unit with renal failure associated with the use of non-steroidal anti-inflammatory drugs (NSAID). Seven patients presented with acute renal failure, in four due to acute tubular necrosis and in three to acute interstitial nephritis; all recovered when NSAID treatment was stopped. Four patients presented with symptomless renal impairment discovered during routine follow-up in a rheumatology clinic; again all improved on withdrawal of NSAID. The remaining six patients presented with chronic renal failure, a disorder not previously associated with NSAID treatment. The pattern of renal disease associated with NSAID may be more extensive than has previously been recognised. A history of NSAID use should be sought in all patients presenting with unexplained renal failure.

Acute Kidney Injury↗

Epithelial membrane antigen in normal and proteinuric glomeruli and in damaged proximal tubules.

Epithelial membrane antigen was detected in normal glomeruli by a polyclonal antiserum to the antigen and by the monoclonal antibodies Ca 1, DAKO-EMA and HMFG 2, but not HMFG 1, using an indirect immunoperoxidase method. The antigen was in the form of a thin ring or collar at the junction of glomerulus and tubule. In a series of 47 renal biopsies from patients with proteinuria, the antigen could still be seen in glomeruli, provided that there were adequate numbers of glomeruli in the sections. The main object of study was the glomerular tip lesion, in which tip adhesions were seen to be just adjacent to the patch of epithelial membrane antigen. This suggested that the antigen may be important in pathogenesis of the lesion. Normal proximal tubules did not express epithelial membrane antigen but it was detected on the luminal border of acutely damaged proximal tubules. Thus the distribution of epithelial membrane antigen in the kidney is more complex than was previously thought.

Antigens, Surface↗

Changes at the glomerular tip: a feature of membranous nephropathy and other disorders associated with proteinuria.

Renal biopsies and post-mortem kidneys were examined for segmental lesions at glomerular tips, consisting of adhesion of the tuft to Bowman's capsule with an area of intra-capillary foam cells or hyaline material or sclerosed material. Of 72 consecutive renal biopsies showing membranous nephropathy, 46 (64 per cent) had tip changes. Such changes were correlated with the presence of acute tubular damage and with later stages of the nephropathy, but otherwise seemed unrelated to any particular clinical or pathological feature. Fourteen other patients were identified whose renal biopsies showed tip changes in glomeruli that had segmental or global mesangial hypercellularity not of a well-recognized type such as IgA nephropathy. These patients had persistent proteinuria unresponsive to steroids. Tip changes were also seen in several miscellaneous conditions including IgA nephropathy and diabetic glomerulosclerosis. These findings demonstrate that tip changes are seen in many disorders of the kidney associated with proteinuria and represent a previously unrecognized common response of the glomerulus to some insult, the glomerular tip lesion, as originally defined, is distinguished by the apparent normality of tufts except for the tip changes and can be regarded as presumed minimal change nephropathy plus tip changes and when tip changes are seen, the most important factor determining the prognosis is the condition of the rest of the glomerular tuft.

Female↗

Necropsy study of infarcts of prostate and prostatic urethra.

A prospective study of 100 prostate glands taken at necropsy showed evidence of vascular disorders in 14. In 12 cases there was oedema, haemorrhage, or necrosis of the anterior wall of the prostatic urethra, and in two there was more extensive central infarction. There had been a period of hypotension in all 14 cases, at least 12 had had urethral catheterisation, and seven had had an operation within a month of death, four of which were for repairs of ruptured aortic aneurysm. Affected glands were the same size as a group of unaffected glands. We suggest that the prostatic urethra is at risk of ischaemia in hypotensive patients with a urethral catheter. This may be a contributory factor in urethral strictures after cardiovascular surgery.

Aged↗