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Biomedical subjects

P W Craswell

Publications and source records attributed to P W Craswell.

At least 19 recordsLinked to original sources

The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia.

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.

DNA↗

Patterns of lead excretion in patients with gout and chronic renal failure--a comparative German and Australian study.

The 6 day calcium EDTA lead excretion test was performed on German and Australian subjects with normal and impaired renal function, some of whom had gout, in order to determine if the pattern of results differed between the two countries. The German subjects lived around Heidelberg in an industrialized area where chronic lead nephropathy had not hitherto been thought to exist, while the Australian subjects were all from the State of Queensland where chronic lead nephropathy from the ingestion of lead paint during childhood continues to contribute to morbidity and mortality. Apart from the subjects with normal renal function, the German subjects consistently excreted less lead than the Queensland subjects and a strikingly consistent pattern was found: in both countries, subjects with a history of lead exposure, whether gouty or not, had greater EDTA lead excess values than subjects with gout but no lead exposure, these subjects in turn having greater EDTA lead excess values than subjects with neither gout nor lead exposure. In each country, the highest median EDTA lead excess occurred not in the group with gout and lead exposure, but in the group without gout and with lead exposure.

Australia↗

Chronic lead nephropathy.

Chronic lead nephropathy remains a cause of morbidity and mortality in Queensland, Australia, and in other parts of the industrial world. It is underdiagnosed because it is not considered in the differential diagnosis of chronic renal disease and because the established methods for estimating the body burden of lead are cumbersome, time consuming, and sometimes inaccurate.

Adult↗

Assessment of a two-step high-performance liquid chromatographic assay using dual-wavelength ultraviolet monitoring for 25-hydroxyergocalciferol and 25-hydroxycholecalciferol in human serum or plasma.

The technique of dual-wavelength monitoring was used to verify the purity of high-performance liquid chromatographic (HPLC) peaks quantified as 25-hydroxyergocalciferol and 25-hydroxycholecalciferol. The data obtained show the need for a second HPLC step prior to quantitation. Potential inaccuracy arising from inadvertent collection of radio-labelled decomposition products was assessed. Between-day coefficients of variation were 7.3, 5.0 and 3.6%, respectively for 11.3 (n = 12), 17.1 (n = 14), and 32.9 (n = 8) ng/ml of 25-hydroxycholecalciferol. For 25-hydroxyergocalciferol, these values were 6.4 and 3.8% for 11.1 (n = 12) and 20.1 (n = 8) ng/ml concentrations, respectively. Comparison of total 25-hydroxycalciferol with a competitive protein binding assay was made. The comparison produced a correlation coefficient (r) of 0.94 and a relationship of y = 1.03x + 3.3. Four of the samples contained more than 10 ng/ml of 25-hydroxyergocalciferol and the results are consistent with the reported 100% cross-reactivity of the competitive binding protein method for 25-hydroxyergocalciferol and 25-hydroxycholecalciferol. A simple regeneration procedure is also described which enables Sep-Pak C18 cartridges to be reused up to eighteen times. Samples may be stored at -18 degrees C for upto several months before assay and either serum or plasma may be used.

25-Hydroxyvitamin D 2↗

Chronic lead nephropathy in Queensland: alternative methods of diagnosis.

Indices of past lead absorption were measured and compared in patients with chronic renal failure from many causes, including some with chronic lead nephropathy. X-ray fluorescence (XRF) yielded finger bone lead concentrations by a new in vivo method. These correlated significantly with excess urinary lead following calcium di-sodium EDTA (ethylenediamine tetra-acetate) and erythrocyte lead concentration. Discriminant function analysis demonstrated that the patients in the study could be separated into two groups without any reference to the EDTA lead excretion test using the following variables, all of which contributed significantly to the discrimination. In order of importance, these were: a childhood history of acute lead poisoning, a history of gout, a family history of gout and detectable XRF finger bone lead. Although the XRF finger bone lead measurement is convenient and non-invasive, its lack of sensitivity (48%) limits its usefulness as a screening test for chronic lead nephropathy.

Aged↗

Chronic renal failure with gout: a marker of chronic lead poisoning.

EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with gout excreted significantly more excess lead chelate than those without gout. In the gout group 17 patients denied any childhood or industrial exposure to lead. They had a greater number of positive tests and excreted significantly more excess lead chelate than 14 patients with neither gout nor lead exposure. These results confirm that gout in the presence of chronic renal failure is a useful marker of chronic lead poisoning. Of 27 patients with positive lead mobilization tests, only 13 had elevated XRF finger bone lead concentrations (sensitivity 48%). Three of 15 patients with negative lead mobilization tests had elevated XRF finger bone lead concentrations (specificity 80%). Although the XRF finger bone lead test is a convenient noninvasive addition to the diagnostic evaluation of patients with chronic renal failure and gout, its application is limited due to the lack of sensitivity of the method.

Aged↗

Rapid progression of oxalosis-induced cardiomyopathy despite adequate haemodialysis.

Crystals of calcium oxalate (CaC2O4) were found at autopsy in the heart of a patient who, over a period of 11 months, appeared to receive adequate haemodialysis and yet died of rapidly progressive heart failure. Calcium oxalate crystals were not present in the kidneys which had been removed at the time of commencing haemodialysis. No secondary cause of oxalosis was evident. X-ray fluorescence analysis of the heart tissue revealed, as well as large amounts of calcium, excess strontium and markedly reduced amounts of potassium and rubidium.

Calcium Oxalate↗

Propranolol in pregnancy three year prospective study.

We compared propranolol with methyldopa in a randomized prospective study of 28 women with pregnancy associated hypertension. Both drugs were equally effective in controlling maternal hypertension. There was no significant difference in the birthweights of the babies in each group. However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia. The mean peak levels of propranolol, propranolol glucuronide, 4-hydroxypropranolol, and 4-hydroxypropranolol glucuronide were not significantly different in the first, second, third trimesters and at least 3 months post partum. The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels. Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk, being approximately 0.1% of the maternal dose.

Blood Pressure↗

Inhibition of DNA synthesis and alteration to DNA structure by the phenacetin analog p-aminophenol.

p-Aminophenol a structural analog and minor metabolite of phenacetin has previously been shown to be a potent nephrotoxic agent. In this report we have shown that p-aminophenol has a marked effect on DNA function and structure. DNA synthesis was inhibited in a dose-dependent manner in human lymphoblastoid cells after exposure to p-aminophenol. Results suggest that DNA synthesis is inhibited by the action of p-aminophenol on DNA structure. At low concentrations of p-aminophenol a reduction in the degree of supercoiling of cellular DNA is observed, as determined by sedimentation under neutral conditions. However at higher concentrations an increase in sedimentation of nucleoids (supercoiled molecules) is obtained which is indicative of an increased level of supercoiling or a more compact structural form of DNA due to folding or aggregation. The number of single strand breaks in DNA, when determined by sedimentation in alkaline sucrose gradients, increases with increasing dose of p-aminophenol. The increase in strand breakage observed at lower concentrations of p-aminophenol agrees with the reduced sedimentation rate obtained under neutral conditions. At higher concentrations of p-aminophenol the extent of breakage of DNA increases under alkaline conditions but an increase in sedimentation occurs under neutral conditions.

Aminophenols↗

Trace element abnormalities in chronic uremia.

We studied the elemental composition of autopsy tissue samples to characterize the trace element changes induced in various human tissues by uremia. Samples from the United States and Australia, including those from 120 uremic patients who had been on dialysis, 29 uremic patients who had not been on dialysis, and 64 control subjects, were analyzed by x-ray fluorescence. Tissues analyzed were aorta, bone, brain, heart, kidney, liver, lung, muscle, and spleen; elements measured included potassium, calcium, iron, copper, zinc, selenium, bromine, rubidium, strontium, molybdenum, cadmium, tin, and uranium. Uremic abnormalities that were statistically very significant were found, including increases of calcium, strontium, molybdenum, cadmium, and tin and decreases of potassium and rubidium. The distribution of iron, copper, and zinc are altered. We conclude that these abnormalities are primarily the result of the uremia and that, generally, they are neither greatly moderated nor exacerbated by the dialysis procedure.

Adolescent↗

Juvenile nephronophthisis and medullary cystic disease--the same disease (report of a large family with medullary cystic disease associated with gout and epilepsy).

A large family with medullary cystic disease is described to show that juvenile nephronophthisis and medullary cystic disease should not be differentiated by age of onset and type of inheritance. The age at diagnosis of six family members with medullary cystic disease ranged from 4-32 years, and age at death from renal failure or commencement of dialysis from 7-48 years. A mother of two children with renal failure in early childhood has histological evidence of medullary cystic disease with normal renal function. We suggest that juvenile nephronophthisis and medullary cystic disease are the same conditions and that the disease be classified as medullary cystic disease, autosomal dominant or recessive form. When undertaking genetic counselling in the parents of children with medullary cystic disease, we suggest that renal biopsy may need to be considered even if their renal function is normal. Three patients presented with gout, and the possibility of an association with medullary cystic disease should be considered when more than one member of a family develops gout. Two patients died of status epilepticus, and epilepsy is probably an added association of medullary cystic disease.

Adolescent↗

Hallucinogenic drug induced vasculitis.

A case of malignant hypertension in a 20-year-old man who self-administered various hallucinogenic drugs is described. Renal angiography showed arteritic changes with aneurysms in renal vessels and focal renal cortical infarction. A dramatic response in terms of resolution of arteritis occurred with prednisone therapy. The impressive use of minoxidil and labetalol in the initial control of the hypertension is also demonstrated.

Adolescent↗

Calcification in end-stage kidneys.

This study was carried out to determine the frequency and to quantitate the severity calcium-phosphate deposits in end-stage kidneys. In 57 of 59 end-stage kidneys obtained from patients with a variety of different renal diseases, calcium levels were greater than 2 standard deviations (SD) above control values. The mean calcium concentration was 157 +/- 24 mmol/kg dry defatted tissue in the end-stage kidneys as compared to 17 +/- 1 mmol/kg in the control kidneys. Histologically, calcium was deposited in the cortical tubular cells, basement membranes and interstitium. It would appear that calcification occurred during the course of renal failure rather thant terminally in that the kidney calcium concentration bore no relationship to the calcium X phosphate product, and the calcium concentration in the kidneys of uremic patients undergoing dialysis (144 +/- 23 mmol/kg) was no greater than that found in uremic patients not undergoing dialysis (188 +/- 62 mmol/kg). It is suggested that calcification may damage the diseased kidney accelerating the rate of renal functional deterioration.

Adolescent↗

Labetalol in the treatment of hypertensive renal patients.

The efficacy of labetalol in lowering blood pressure was assessed in 18 patients with chronic renal failure and hypertension. Before the start of labetalol therapy, all patients were receiving combined antihypertensive therapy, the most common being a beta-blocker and hydrallazine. Over the period of about four weeks labetalol was substituted for the prior therapy. 51Cr edetic acid (EDTA) estimations of glomerular filtration rate were performed before labetalol therapy, and then again after one and six months. Before the therapy with labetalol, 12 of the 18 patients had supine diastolic blood pressures of 100 mm Hg or more. At six months, 14 patients remained in the trial and, of these, only four had a supine diastolic blood pressure of 100 mm Hg or more. In the supine position there was a significant reduction of systolic, but not of diastolic, blood pressure. However, in the erect position there was a significant reduction both in systolic and in diastolic blood presure. Pulse rate did not vary significantly. Few side effects were encountered, transient postural dizziness being the most common side effect. Labetalol seems to be an effective substitute for the beta-blocker plus hydrallazine therapy. However, it is not as potent as minoxidil.

Adrenergic beta-Antagonists↗

Plasmapheresis in Goodpasture's syndrome with renal failure.

Four patients who presented with severe proliferative glomerulonephritis associated with linear deposition of IgG on the basement membrane have been treated by intermittent massive plasmapheresis. Two patients had all the features of Goodpasture's syndrome. In the other two cases, the characteristic renal lesion was present but there was no pulmonary involvement. In all cases, renal function improved after plasmapheresis while in two, renal function deteriorated after plasmapheresis was stopped. On of these patients responded to a second course of plasmapheresis but failed to respond to a third. This study supports previous reports of the value of plasmapheresis in patients with Goodpasture's syndrome and renal failure in whom recovery without plasmapheresis has not been recorded. The present study emphasizes the importance of continuing treatment for a period of weeks to permit prolonged remission. If treatment is withdrawn too early, rapid deterioration in renal function may result, and unless plasmapheresis is recommenced at once the renal failure may then prove irreversible.

Adolescent↗

Co-trimoxazole in chronic renal failure--a controlled experiment in Wistar rats.

Co-trimoxazole failed to cause a deterioration in renal function, as measured by pre- and posttreatment plasma urea levels, in groups of Wistar rats with either normal renal function or surgically induced chronic renal failure. In addition tubular necrosis was not produced. Co-trimoxazole does not appear to be extremely toxic to the Wistar rat kidney.

Animals↗