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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 451 records · Page 25Linked to original sources

The significance of monocytes in glomeruli of human renal transplants.

A total of 50 biopsies from 42 renal transplants obtained during a 30-month period were studied for the presence of monocytes in the glomeruli using the nonspecific esterase reaction. Eleven biopsies from ten grafts were positive. Immune deposition was light or absent. The prognosis for the grafts containing glomerular monocytes was significantly worse during the six months after the biopsy than for those without such cells present.

Esterases↗

Transvenous high energy shock for ablating atrioventricular conduction in man. Observations on the histological effects.

Transvenous ablation of atrioventricular conduction by high energy shock through a pacing wire has been used as a method of controlling the ventricular response to rapid atrial arrhythmias. A patient in whom this technique successfully controlled refractory tachycardia was admitted with severe left ventricular impairment five months after the procedure and died. The heart was examined at necropsy. There was no sign of endocardial damage in the region of the atrioventricular node-His bundle. Histological sections failed to show any scarring, inflammation, or infiltration in the region of the atrioventricular node. On the contrary, there was no evidence of any surviving atrioventricular nodal tissue. The mechanism of this effect is not known. The lack of endocardial or myocardial damage further confirms the safety of this new method of controlling tachycardia.

Atrioventricular Node↗

Hyperkalaemia in diabetes mellitus--potential hazards of coexisting hyporeninaemic hypoaldosteronism.

Two patients with insulin-dependent diabetes mellitus (Type I), developed severe, life-threatening hyperkalaemia, the first following treatment with spironolactone, the second during treatment for staphylococcal septicaemia when glucose-induced hyperkalaemia occurred. Investigations demonstrated co-existing hyporeininaemic hypoaldosteronism. Prompt recognition of this combined hormone-deficiency syndrome led to appropriate treatment and recovery. The biochemical features and clinical importance of hyporeninaemic hypoaldosteronism are discussed.

Adult↗

Familial hypocalciuric hypercalcaemia: evidence for continued enhanced renal tubular reabsorption of calcium following total parathyroidectomy.

A patient with familial hypocalciuric hypercalcaemia (FHH) is reported. Seven years after total parathyroidectomy he remained hypocalcaemic, with biochemical evidence of hypoparathyroidism (enhanced renal tubular reabsorption of phosphate, low nephrogenic cyclic AMP excretion, and reduced serum concentration of 1,25-dihydroxycholecalciferol in the presence of normal renal function and normal serum 25-hydroxyvitamin D levels). Iv infusions of calcium were given before and 6 years after total parathyroidectomy. The renal tubular reabsorption of calcium was compared in these two situations. No difference was found. Before and after parathyroidectomy there was enhanced renal tubular reabsorption of calcium. It is concluded that the enhanced renal tubular reabsorption of calcium in FHH is independent of parathyroid hormone. Total parathyroidectomy corrects the hypercalcaemia in FHH by a reduction in the input of calcium into the extra-cellular fluid from gut and or bone perhaps as a result of reduced renal synthesis of 1,25-dihydroxycholecalciferol.

Adolescent↗

Impaired hearing in X-linked hypophosphataemic (vitamin-D-resistant) osteomalacia.

We assessed the hearing of 25 patients with X-linked hypophosphataemic osteomalacia. Twelve patients had subjective hearing loss and 2 had had episodic tinnitus, deafness, and vertigo similar to that in Ménière's disease. On pure-tone audiometry, 19 patients were shown to have sensorineural hearing loss, 3 of whom had evidence of an added conductive element. Tests were done to delineate sensory (cochlear) from neural deafness. Analysis of the stapedius reflex threshold, percentage speech discrimination score, tone decay, and loudness recruitment showed a disturbance of cochlear function. The possible mechanisms responsible for this dysfunction are discussed in the light of pathologic characteristics of familial hypophosphataemia and its extraosseous manifestations. Sensorineural hearing loss, a previously unrecognised complication of familial hypophosphataemic osteomalacia, occurs frequently.

Adolescent↗

Activation of the alternative complement pathway by isolated human glomerular basement membrane.

The capacity of isolated human glomerular basement membrane (GBM) to initiate surface activation of the human alternative complement pathway was defined by the deposition of C3b under circumstances in which the classical complement pathway was inoperative. The deposition of C3b from normal or C2-deficient serum was time- and magnesium-dependent, implying a role for the alternative pathway. Normal human serum rendered deficient in D did not sustain C3b deposition until its reconstitution with D, indicating an absolute requirement for a protein unique to the alternative pathway and essential to the cleavage activation of the C3 amplification convertase of that pathway. The capacity of the excess control proteins H and I to prevent C3b deposition onto GBM incubated in C2-deficient serum provided further evidence for the direct activation of the alternative pathway in this system. The use of radiolabeled monoclonal antibody to localize the deposited C3b afforded specificity and quantitation of about 100 ng of C3b/mg of GBM. Immunohistochemical analysis with a monoclonal antibody to detect C3b demonstrated its deposition to be confined to the epithelial surface of the GBM.

Antibodies, Monoclonal↗

Effect of glomerular basement membrane on the initiation of chemiluminescence and lysosomal enzyme release in human polymorphonuclear leucocytes: an in vitro model of glomerular disease.

The effect of glomerular basement membrane (GBM) on the stimulation of human polymorphonuclear leucocytes (PMNL) was investigated using the technique of chemiluminescence (CL). GBM, in the absence of serum, did not initiate CL of PMNL and neither did GBM preincubated with fresh human or rabbit serum. In contrast, GBM preincubated with rabbit anti-human GBM serum (anti-GBM), and then thoroughly washed, initiated an immediate and marked CL response. Heat inactivation of the anti-GBM only partially reduced the CL, suggesting that both Fc and C3b receptors on the PMNL were involved. The addition of fresh, but not heat-inactivated, human serum to PMNL incubated with untreated GBM resulted in a CL response after a short lag. Subsequent analysis of the serum by electrophoresis and immunofixation indicated that the GBM had activated complement. GBM preincubated with anti-GBM was found to elicit the selective release of lysosomal enzymes from PMNL, one of these enzymes degrading the collagen moiety of the GBM. Preincubation of GBM with the serum from a patient with Goodpasture's syndrome also initiated a CL response and a selective release of lysosomal enzymes from PMNL. These results provide additional evidence for imputing a role for PMNL in the pathogenesis of glomerulonephritis. Furthermore, the technique offers a useful in vitro model for the study of immunologically mediated glomerular disease.

Anti-Glomerular Basement Membrane Disease↗

Sleep architecture and REM sleep measures in prepubertal major depressives. Studies during recovery from the depressive episode in a drug-free state.

The sleep of 28 fully recovered, drug-free, prepubertal patients with major depressive disorder was recorded for three consecutive nights in the laboratory. Recovered depressives had significantly shorter first rapid eye movement period (REMP) latencies and a higher number of REMPs compared with themselves when depressed and with nondepressed neurotic and normal children. In addition, most sleep continuity measures improved considerably on recovery. We suggest that a short first REMP latency may be a marker of past episode or of trait in prepubertal major depressives.

Age Factors↗

Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered vitamin D3.

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24,25-dihydroxyvitamin D3 concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D3. Malabsorption of a standard dose of [3H]vitamin D3 was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D3 given to be calculated. Oral vitamin D3 400-4000 IU/day (effectively 400-1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.

Administration, Oral↗

Sleep architecture and REM sleep measures in prepubertal children with attention deficit disorder with hyperactivity.

A 2-night polysomnographic study of 9 rigorously assessed prepubertal children who fit Diagnostic Statistical Manual-III criteria for attention deficit disorder with hyperactivity (ADDH) and a contrast group of 11 control children is reported. Despite the fact that 57% of the ADDH group were reported to experience restless sleep on structured parental rating forms, they did not show any sleep architecture abnormalities on polysomnographic recordings when compared with the normals at baseline other than decreased rapid eye movement (REM) activity. Seven of the ADDH boys were restudied after 6 months of continuous methylphenidate therapy (mean daily dose of 34.4 +/- 14.0 mg or 1.4 +/- 0.7 mg/kg). Across and within (pre-post) group comparisons showed that methylphenidate therapy was associated with delayed sleep onset, lengthened sleep, and changes in certain REM sleep variables.

Arousal↗

Spindle characteristics in prepubertal major depressives during an episode and after sustained recovery: a controlled study.

In a previous publication, this group reported a dissociation between multiple sleep complaints and polysomnographic abnormalities in prepubertal major depressive children. Spindle activity has been thought by some to be a correlate of restorative sleep. On this basis, it was hypothesized that prepubertal depressives might exhibit differences in sleep spindle characteristics when compared with normal and psychiatric control groups, and with their former state during sustained recovery in a drug-free state. Further, it was thought that clinical complaints of disrupted sleep might be related to differences in spindle characteristics. Spindle frequency (Hz) was the only significant finding among the groups, but it was not specific to depressive disorder, since all psychiatric groups presented higher frequencies than did normal children. As expected, significant differences across halves of the sleep period time (SPT) were also found for the number of spindles, frequency (Hz), duration (ms), spindle density (rate), and the amount of stage 2 sleep (min). The presence or absence of sleep complaints had no bearing on spindle characteristics, thus indicating a lack of apparent relationship between the two. Upon recovery the depressives exhibited no changes across clinical state, and a cross-sectional comparison of the recovered data with the original control data gave results essentially identical to the first (active illness) comparisons. It is suggested that high spindle frequency may be a nonspecific correlate of emotional disorders in prepuberty, which, at least in depressives, does not change with clinical state.

Adolescent↗

Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function.

Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24,25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1,25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P less than 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 +/- 0.12 mmol/l GF, mean +/- SEM) and FHH (0.86 +/- 0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 +/- 16 mmol/l GF) which was significantly greater (P less than 0.0001) than the normal NcAMP (13.5 +/- 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.

24,25-Dihydroxyvitamin D 3↗

Studies on the glomerular filtration barrier and on the urinary excretion of basement membrane glycoproteins during the accelerated model of nephrotoxic serum nephritis.

A proliferative glomerulonephritis was induced in rats preimmunised with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-rat GBM IgG. All the rats developed a severe proteinuria within 2-5 days after the injection of anti-GBM IgG. At the same time, many mononuclear phagocytes infiltrated the glomeruli, the colloidal iron staining of the glomerular filtration barrier was altered, and the urinary excretion of laminin and of neutral proteinase strongly increased. However, the pattern and intensity of staining of different collagenous and non-collagenous BM glycoproteins were not modified, as shown by indirect immunofluorescence microscopy. The existence of a direct significant correlation between the proteinuria and the laminin urinary excretion, and between the latter and the urinary neutral proteinase activity suggests that lysosomal proteinase of mononuclear phagocytes may be involved in the damage of the GBM during the course of this experimental glomerulonephritis.

Animals↗