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Biomedical subjects

I Birchall

Publications and source records attributed to I Birchall.

15 recordsLinked to original sources

Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover.

BACKGROUND: The functions of urokinase in intestinal epithelia are unknown. AIMS: To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. METHODS: Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. RESULTS: From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. CONCLUSIONS: Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine.

Animals↗

Occult infection as a cause of hip pain in a patient with metastatic breast cancer.

A 39-year-old woman with breast cancer metastatic to bone presented with acute hip pain marginally responsive to escalating doses of opioid analgesics. Pathologic pelvic fractures were present and there were minimal clinical indicators of infection, but the severity and intractable nature of the pain prompted further investigation. Computed tomography revealed a pelvic abscess. Antibiotic therapy and drainage of the abscess resulted in markedly improved pain control, decreased analgesic requirements, and improved quality of life. We suggest that, in patients with malignancy, the diagnosis of occult infection should be aggressively pursued as a potentially reversible cause of intractable pain.

Abscess↗

Olfactory neuroblastoma: report of a case associated with inappropriate antidiuretic hormone secretion.

Esthesioneuroblastoma or olfactory neuroblastoma, is a rare tumour. It was first described by Berger et al. in 1924. Since then, approximately 250 cases have been reported. These neuroendocrine neoplasms are rarely associated with hormone excess syndromes. We report a case of olfactory neuroblastoma initially manifested with a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 27-year-old man. A literature review is briefly presented.

Esthesioneuroblastoma, Olfactory↗

Effect of dietary calcium on the development of hypertension and hypertensive vascular lesions in DOCA-salt and two-kidney, one clip hypertensive rats.

OBJECTIVE: To examine the effect of modest changes in dietary calcium on systolic blood pressure (SBP) and myocardial and renal vascular lesions in Sprague-Dawley rats. DESIGN: Regular- (0.4%, by weight), high- (0.8%) or low-calcium (0.24%) diets were fed to normotensive control, deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2-K, 1C) hypertensive rats for 8 weeks. METHODS: Tail-cuff SBP and metabolic balance were measured once a week. At the end of the study the kidneys and hearts were collected for histological study. RESULTS: Dietary calcium had no effect on SBP in the DOCA-salt rats, but loading with calcium accelerated the rise in SBP in 2-K,1C rats (P < 0.01, high- versus regular-calcium diet). The high-calcium diet reduced the percentage medial area of intramyocardial arteries in the DOCA-salt and 2-K,1C hypertensive rats. The DOCA-salt rats on the low-calcium diet had a higher renal vascular lesions score than those on the regular- or high-calcium diet (P < 0.05). CONCLUSIONS: A high-calcium diet appears to prevent intramyocardial vascular wall thickening in DOCA-salt and 2-K,1C hypertensive rats, and a low-calcium diet aggravates renal vascular lesions in DOCA-salt hypertensive rats. These effects are not related simply to changes in blood pressure.

Animals↗

Effect of dietary sodium chloride on the development of renal glomerular and vascular lesions in hypertensive rats.

1. The hypothesis that high levels of NaCl in the diet aggravates hypertension-associated renal vascular lesions was examined in unilaterally nephrectomized deoxycorticosterone acetate treated (DOCA) and two kidney one clip (2K1C) hypertensive rats, as well as normotensive controls. 2. High NaCl diet significantly increased systolic blood pressure (SBP) in DOCA rats, but had little effect on SBP in normal control rats, and did not affect the rise of SBP in 2K1C rats. 3. High NaCl diet was associated with a higher percentage of glomerular lesions and renal arterial and arteriolar lesions in DOCA and 2K1C rats (P < 0.05). 4. Thus high NaCl intake exacerbated renal arterial and arteriolar and glomerular lesions in both DOCA and 2K1C hypertensive rats. In 2K1C rats this effect may be in part independent of blood pressure.

Animals↗

Role of the renal medulla in adrenocorticotrophin-induced hypertension in rats.

OBJECTIVES: The mechanism of hypertension induced by adrenocorticotrophin (ACTH) remains unclear. The antihypertensive renomedullary lipids are vasodilators and it has been proposed that a deficiency of these lipids may contribute to the hypertension produced by destruction of the renal papilla. The aim of the present work was to study ACTH hypertension in both control and chemically renomedullectomized rats. METHODS: Renomedullectomy was produced by single intraperitoneal injection of 2-bromoethylamine (BEA) at 400 mg/kg. RESULTS: BEA-treated rats all developed increases in water intake and urine volume, with loss of papillae and medullary and cortical fibrosis. There was a significant correlation between papillary ablation and systolic blood pressure (SBP). SBP in renomedullectomized rats was higher after ACTH than sham injection, and higher than after ACTH injection in intact rats. CONCLUSION: Chemical renomedullectomy with BEA did not block or attenuate the onset or magnitude of ACTH hypertension in the rat.

Adrenocorticotropic Hormone↗

Morphology of renal parenchymal culture in collagen gels.

Explants of rabbit renal parenchyma have been grown in primary tissue culture suspended within hydrated collagen gels. Light and phase contrast microscopic analysis of the first 17 days in culture is described. Pieces of NZW rabbit renal parenchyma were suspended in collagen gels and bathed in supplemented RPMI 1640 medium and incubated at 37 degrees C in 5% CO2 in air. Tubules demonstrated a fine granularity by phase contrast microscopy and glomeruli appeared as red spheres. Blebs formed at the sides and ends of the explant and a monolayer outgrowth of tightly packed polygonal cells occurred from day 4. Histologically an immediate phase of necrosis was followed by regeneration whereby tubules became lined with a confluent epithelium composed of a single layer of flat to cuboidal-shaped cells sitting on an intact tubular basement membrane (TBM). Intraluminal casts of organized cellular debris as well as material presumed to be Tamm Horsfall protein were present. Glomeruli demonstrated collapsed capillary loops. The interstitium became widened by eosinophilic material. The tissue surface contained epithelial cells arranged in places into sac-like structures enclosing a space.

Animals↗

Caffeine potentiates the nephrotoxicity of mefenamic acid on the rat renal papilla.

The effect of caffeine given in combination with mefenamic acid on the renal papilla was studied. Sprague-Dawley rats were divided into four groups and gavage fed either control suspension, mefenamic acid, mefenamic acid and caffeine or caffeine alone for 4 months. Semiquantitative urinalysis was performed at 3 months and showed increased haematuria in the mefenamic acid and caffeine group. There were no significant differences in serum creatinine at sacrifice. Renal histology revealed more advanced papillary necrosis in rats gavage fed mefenamic acid and caffeine compared with all other groups (p less than 0.0001). Rats fed mefenamic acid alone showed more damage than control and caffeine-fed groups (p less than 0.0001, p less than 0.0002, respectively). This suggests that caffeine potentiates the nephrotoxicity of the non-steroidal anti-inflammatory drug, mefenamic acid, on the rat renal papilla. The mechanism of this potentiation by caffeine is yet to be defined.

Animals↗

Polymorphs infiltrate glomeruli in mesangial IgA glomerulonephritis.

During episodes of macroscopic hematuria, patients with IgA nephropathy commonly have polymorphonuclear neutrophils (PMNs) as well as fibrin and mononuclear cells in glomerular capillaries. We quantitated PMN and macrophage infiltration in glomeruli of 54 patients with IgA nephropathy in whom renal biopsies were obtained within 30 days of macroscopic hematuria. Control biopsies (N = 22) were from patients with IgA nephropathy and urinary erythrocyte counts below 50,000/ml. PMN monocyte/macrophages were quantitated using the monoclonal antibodies FMC10 and HAM56, respectively. In patients with heavy hematuria, 45.9 +/- 3.4% (mean +/- SE) of glomeruli were positive for PMNs (control 10.5 +/- 2.8%, P = 0.001) with a mean PMN count/glomerulus of 1.10 +/- 0.20 (control 0.13 +/- 0.03, P = less than 0.001). 65.6 +/- 9.7%. Of the glomeruli were positive for monocytes in the heavy hematuria group (control 40.0 +/- 8.4, P less than 0.05) with the mean monocyte count per glomerulus being 1.6 +/- 0.2 (control 0.6 +/- 0.1, P less than 0.01). We conclude that, in the acute phase of mesangial IgA nephropathy, PMN and monocytes are present and presumably participate in glomerular injury.

Biopsy↗

Chronic progressive renal lesions induced by lithium.

New Zealand white rabbits, eight fed lithium (Li) (50 to 250 mmole LiCl/kg food) and seven controls (C) had sequential open renal biopsies at zero, one, three, six, and 12 months. A distinctive histological lesion, consisting of cytoplasmic vacuolation and accumulation of glycogen in cells lining distal convoluted tubules and collecting ducts, was present in Li (one, three, six, and 12 months), but was absent in Li prior to lithium (zero months) and in C (zero, one, three, six, and 12 months). Histological changes of chronic focal interstitial nephropathy namely, interstitial fibrosis, (quantitated by point counting), tubular atrophy and cast formation (quantitated by digitization), and glomerular sclerosis (determined as the percent of sclerosed glomeruli) showed significant differences between Li and C from as early as one month (interstitial fibrosis, P less than 0.02; tubular atrophy, P less than 0.05; casts, P less than 0.05), and up to 12 months (glomerular sclerosis, P less than 0.05). Distal tubular dilatation and microcyst formation, (quantitated by digitization) was also marked in Li compared with C from one month (P less than 0.05). The degree of distal tubular dilatation and other changes of interstitial nephropathy tended to progress with duration of lithium exposure. Macroscopically, Li kidneys (12 months) were pale, granular, and exhibited microcysts. Raised blood urea (P less than 0.02) and serum creatinine levels (P less than 0.05) were also late features (12 months) of lithium-induced nephropathy. The data support the view that lithium induces chronic renal lesions. The precise relationship between the distinctive distal tubular lesion, distal tubular dilatation and focal interstitial nephropathy remains speculative.

Animals↗