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Biomedical subjects

A M Meyers

Publications and source records attributed to A M Meyers.

At least 19 recordsLinked to original sources

Hereditary interstitial nephritis without basement membrane changes.

Hereditary interstitial nephritides are a heterogeneous group of disorders comprising medullary cystic disease, several varieties of Alport's syndrome and also one familial disorder with a distinct clinical syndrome and without characteristic ultrastructural glomerular basement membrane changes. Our family consisted of 11 members, 5 of which presented with renal dysfunction of varying degrees. Clinically, the affected siblings presented with long-standing hypertension, minimal proteinuria and no hematuria. All known causes of a secondary diffuse interstitial nephritis, Alport's syndrome and medullary cystic disease have been excluded. An HLA association is suggested between the affected and unaffected members of the family. Renal biopsy subsequently showed the typical features of a chronic interstitial nephritis without basement membrane changes.

Adult

IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes.

In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor alpha or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators.

Cells, Cultured

Effect of calcium supplement preparation containing small amounts of citrate on the absorption of aluminium in normal subjects and in renal failure patients.

It is well known that Al absorption is markedly enhanced by citrate. The aim of the study was to document whether low-dose citrate ingestion (4 g/day) contained in a well-known effervescent calcium supplement was sufficient to increase Al absorption in 16 normal volunteers and 15 subjects with stable chronic renal failure under conditions of either Ca carbonate or Al hydroxide supplementation. Serum and urine Al levels were measured using flameless atomic absorption spectrophotometry as previously described. After Ca carbonate plus Ca citrate ingestion, there was no rise over baseline (Ca Carbonate alone) serum or urine Al levels in either group. Ca carbonate and Al hydroxide taken together produced a significant rise in serum and urine Al levels in both groups. Maintaing Al hydroxide but substituting Ca citrate for the carbonate (same dose of elemental Ca) produced a further significant increment in serum Al (0.47 +/- 0.28-1.15 +/- 0.8 mumol/l; p < 0.001) and in urine Al(1.37 +/- 0.46-5.77 +/- 5.21 mumol/l; p < 0.001) in the chronic renal failure group as well as in serum Al (0.42 +/- 0.2-0.76 +/- 0.48 mumol/l; p < 0.001) and urine Al (2.70 +/- 1.24-8.24 +/- 3.96 mumol/l; p < 0.001 in the normal volunteer group. Due to decreased urine excretion, the increment in serum Al in the CRF group was significantly greater than in the normal subjects (p < 0.02). Thus small quantities of citrate present in effervescing Ca supplements can significantly enhance intestinal Al absorption even in normal subjects. All citrate-containing preparations are totally contra-indicated in chronic renal failure patients ingesting Al-containing compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Phosphorylation of endogenous protein in primate kidney. Effects of cyclic AMP.

1. Phosphorylation of endogenous proteins in response to cyclic AMP was assessed in membrane and cytosol from primate kidney. 2. Quantitative studies showed that cAMP significantly increased phosphorylation in baboon kidney membranes; in cytosol there was no effect. 3. Phosphorylation of specific proteins which had been electrophoretically separated showed that five major bands were intensified by cAMP in baboon membranes; in cytosol, three bands were intensified. Similar results were found in normal human kidney. 4. Photoaffinity labelling indicated that a 56 kDa band phosphorylated in cytosol may correspond to the regulatory subunit of type II cAMP-dependent protein kinase.

Affinity Labels

The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome.

The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%.

Adolescent

Hyperoxaluria in patients with recurrent calcium oxalate calculi: dietary and other risk factors.

The presence of mild hyperoxaluria in recurrent calcium oxalate stone formers is controversial. The aim of this study was to identify recurrent stone formers with mild hyperoxaluria and to classify them further by assessing their response to a low oxalate diet. In addition, the prevalence of other risk factors for stone formation in this group of patients was investigated. A total of 207 consecutive patients with recurrent renal calculi were screened and 40 (19%) were found to have mild hyperoxaluria. Of these, 18 (45%) responded to dietary oxalate restriction by normalising their urinary oxalate. The remaining 22 patients were classified as having idiopathic hyperoxaluria and were subdivided into those in whom urinary oxalate excretion was consistently elevated in all specimens measured and those in whom the elevation was intermittent in nature. Dietary oxalate restriction had a partially beneficial effect in lowering oxalate excretion in the patients with persistent hyperoxaluria. No difference in urinary oxalate excretion was found after dietary restriction in the patients with intermittent hyperoxaluria. Other risk factors, including dietary, absorptive and renal hypercalciuria and hypocitraturia, were documented, the prevalence of which (65%) was not significantly different from that (62.5%) found in 40 age- and sex-matched calcium stone formers without hyperoxaluria. The prevalence of hyperuricosuria was significantly greater in patients with hyperoxaluria when compared with stone controls. Further studies are required to elucidate the underlying mechanisms of hyperoxaluria in recurrent stone formers.

Calcium

Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease?

The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Microscopic polyarteritis--a treatable cause of rapidly progressive renal failure due to necrotising glomerulonephritis.

The clinical features of 25 patients with microscopic polyarteritis are reviewed. Major indications of disease were haematuria and proteinuria accompanied by significant renal dysfunction, which was rapidly progressive in the majority of patients. Unrewarding investigations aimed at defining a cause of haematuria that could be treated surgically only served to delay diagnosis, which could be promptly made by renal biopsy. Early institution of cyclophosphamide therapy led to ablation of the inflammatory process and stabilisation of renal function. In men, who were affected twice as often as women, there was a striking association with employment in the goldmining industry.

Adolescent

Prevalence of hypocitraturia and hypopyrophosphaturia in recurrent calcium stone formers: as isolated defects or associated with other metabolic abnormalities.

Several underlying metabolic abnormalities may be present in patients with recurrent calcium calculus disease (RCCD). The aim of this study was to determine the prevalence of deficiencies of 2 well-known potent inhibitors of crystal formation and growth, citrate and pyrophosphate, in the various metabolic subgroups and as single defects. In 107 patients with RCCD, urinary citrate was significantly decreased in all metabolic subgroups with 49% of patients having hypocitraturia (2.53 +/- 1.19 mmol/24 h) versus controls (3.44 +/- 0.96 mmol/24 h; p less than 0.001). Reduced pyrophosphate:creatinine ratios were present in all the patient subgroups, and 48% of all patients had reduced ratios (1.68 +/- 1.68 vs. 3.10 +/- 2.66 in controls; p less than 0.01). There was no correlation between citrate and pyrophosphate concentration. Isolated hypocitraturia was found in 11.2%, reduced pyrophosphate:creatinine ratios as the single defect in 11.2% and a combination of both in 12.1% of patients. Thus inhibitor defects play an important role in patients with RCCD and frequently occur as isolated biochemical defects.

Adolescent

Acute renal failure--10-year experience of the Johannesburg Hospital renal unit.

The 10-year experience of Johannesburg Hospital's renal unit in treating acute renal failure (ARF) is described; 290 patients were treated by haemodialysis--169 drawn from the surgical disciplines, 109 from the medical disciplines and 12 from obstetrics and gynaecology, suffering 55%, 41% and 33% mortality rates, respectively. The mortality rates were found to correlate strongly with the cumulative number of acute insults to renal function accruing as a result of the particular surgical or medical illness ('precipitating event') and culminating in ARF. Age was also shown to have a powerful influence on outcome, the survival rate falling steadily with each decade of life. A plea is made to limit the potential insults to renal function actively, particularly in the elderly, in an attempt to further reduce the high mortality rate with which ARF continues to be stubbornly associated.

Acute Kidney Injury

Renal retransplantation. The Johannesburg Hospital experience.

Between 1968 and 1985 108 renal retransplants were performed at Johannesburg Hospital; 102 patients received a second, 5 patients a third, and 1 patient a fourth kidney. The actuarial graft survival at 1 and 5 years is 52.8% and 40.5%. All retransplanted kidneys were obtained from cadaver donors. Factors that influence second graft survival are the period of survival of the previous graft, the use of cyclosporin A, the level of pre-sensitisation determined by preformed antibodies, the original disease (in particular diabetes and analgesic nephropathy) and the patient's sex. The results of retransplantation are not significantly different from those found in patients with first allografts; hence retransplantation is justified in those individuals whose previous donor kidney has ceased to function.

Adolescent

Outcome of renal transplants with impaired renal function at 6 months.

At 6 months after kidney transplantation 59 adults with impaired renal function were divided into three groups according to their serum creatinine level: group I 150-199 mumol/l; group II 200-299 mumol/l; and group III greater than or equal to 300 mumol/l. These patients were followed up for 5 years or to graft loss when it became apparent that the eventual outcome was related to the degree of renal impairment at 6 months. Age of donor and age of recipient did not have a bearing on the eventual outcome nor did the frequency of acute tubular necrosis or rejection episodes. Patients with severely impaired renal function with serum creatinine levels greater than or equal to 300 mumol/l have a poor outlook but there are no particular prognostic features on which to base a forecast for the individual patient.

Adolescent