[Fatal complications of a single infusion of mithramycin].
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Biomedical subjects
Publications and source records attributed to A Baglin.
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Terminal chronic renal failure was discovered in a patient who had received CCNU 1 940 mg/m2 during the previous two years. The renal function was normal before treatment, and there was no evidence of other causes of renal failure. The clinical picture was identical with that observed in patients receiving such treatment and recently published. This case emphasizes the need for limiting the dose of nitrosyl-urea compounds to 1 200 mg/m2 and for monitoring the renal function very closely during and towards the end of the treatment.
1 The pharmacokinetics of atenolol, after 200 mg orally, were studied in 18 patients with terminal renal insufficiency (creatinine clearance less than 5 ml/min), of whom twelve were being treated by chronic dialysis. 2 The peak plasma level, 1.59 +/- 0.43 mg/l, was reached in 4.7 +/- 2.1 h. 3 Without dialysis treatment, the apparent plasma half-life of atenolol was greatly increased (73.4 +/- 28.8 /). During dialysis, it dropped to 7.5 +/- 3.7 h but returned to 51.2 +/- 17.3 h after dialysis. The plasma atenolol plot was a rising slope for a few hours after the end of dialysis. 4 Renal clearance of atenolol was very low (4.6 +/- 1.5 ml/min). 5 Plasma clearance during dialysis was 42.6 +/- 21.3 ml/min for a mean blood flow-rate of 236 +/- 25 ml/min through a cuprophane membrane dialyser. 6 These results suggest that dosage should be modified for these patients.
Pathophysiology of diabetic microangiopathy is unclear, but hyperglycemia is admitted as an important factor. In three patients having microangiopathy with lesions very similar to those of diabetes (one nodular glomerulosclerosis, two retinopathies), glucose tolerance was found normal. Such cases, already reported, but rather rare, raise the question of the validity of tests currently used in the diagnosis of diabetes, of the importance of hyperglycemia compared to others factors (specially genetic) in the occurrence of microangiopathy, and of the specificity of these lesions.
The effects of dopamine on renal excretory function were studied in 20 patients with chronic renal failure (plasma creatinine higher than 30 mg/i). Effects were marked at a dose of 2 micrograms/kg/mn and were no greater at a dose of 5 micrograms/kg/mn (10 subjects in each case). In general, creatinine clearance increased by 28%, urea excretion by 45%, urine output by 77% and urinary sodium output by 164%. In ten patiens with terminal renal failure (plasma creatinine greater than 100 mg/i), the effects of dopamine were maintained. In these individuals, furosemide (250 mg by single intravenous injection) resulted in a higher total urine and urinary sodium output but had a less favourable effect upon creatinine.
The increase in total body sodium and hyperactivity of the renin-angiotensin system plays a major part in hypertension in patients underdoing chronic dialysis. After sodium depletion most patients become normotensive. Their hypertension seems to be due to sodium overload but it is favoured by insufficient inhibition of renin secretion. Some renin hypertensive, hypersecretion of renin is the main factor in these cases but its effect is aggravated by the sodium overload. Other factors may play a role as suggested by the studies of hypertensive patients after bilateral nephrectomy. However, their roles and mechanisms are unknown at present.
In three of these four cases of malignant tumour of the adrenal cortex, a prolonged fever and a major inflammatory syndrome were the presenting features. The precise diagnosis was made before surgery only once. In two cases, it was a surgical discovery (one patient operated upon with a false diagnosis and another with no precise diagnosis). In the last case, the malignant tumour of the cortex was discovered at autopsy. The chief characteristics of these tumours are reviewed: rare ; presenting with chest pain, a mass in the hypochondrium, metastases, or general symptoms, possibly high and prolonged fever. The prognosis is gloomy, the majority of patients dying the six months which follow the operation.
A 21-year-old man suffered severe (up to 15.5 mg%) and prolonged (7 months) hypercalcaemia as a result of immobilisation following severe trauma. During the period of hypercalcaemia, plasma parathormone and calcitonin levels were undetectable. A study using radioactive calcium revealed a very marked increase in bone resorption, a moderate increase in accretion and virtually no intestinal absorption. Iliac biopsy revealed dense calcification front and there was no osteoid substance. This hypercalcaemia appeared to be due to increased bone resorption, while the synthesis of osteoid substance seemed to be insufficient to permit an equivalent increase in calcium accretion.
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The results of radio-immunoassay of parathormone in peripheral venous blood (using an anti-serum preferentially recognising fragments from the carboxyl-terminal pole) were compared with those of blood calcium measured on the same day in 33 cases of primary hyperparathyroidism. In the 28 patients with hypercalcaemia, PTH was invariably high (27 cases) or at the upper limit of normal (1 case). In the 5 patients with normal blood calcium levels, it was normal in 3 cases. It is thus important to take blood calcium levels into account in the interpretation of PTH estimation, that latter being more valid during a hypercalcaemic phase.
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In a patient suffering from obstructive cardiomyopathy (IHSS), the onset of septicaemia due to staphylococus aureus was accompanied: 1. by the appearance of massive mitral incompetence and of cardiac failure; 2. by a marked reduction in the left intra-ventricular pressure gradient; 3. by acute reversible renal failure (interstitial nephritis); 4. by a glomerulonephritis with immune complexes deposits. After the septicaemia had been treated, replacement of the mitral valve by a disc prosthesis of Lillehei was carried out. Twenty months after the operation, the patient was completely asymptomatic, and catheterisation showed that the left intra-venticular pressure gradient had disappeared, as had the haemodynamic signs of cardiac failure.
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Multisite cervico-mediastinal venous blood samples were collected fort the estimation of parathormone before operation in twenty four patients subsequently confirmed at surgery to have primary hyperparathyroidism. The examination made it possible to lateralise a single (single adenoma: 18 cases) or predominant lesion (multiple adenomas or hyperplasia: 6 cases), in 15 of them (62%). In patients with a single adenoma, exact lateralisation was obtained in 12 out of 18 cases (9 had selective samples with 7 accurate lateralisations). This lengthy and costly examination is essentially of value in localisation and should be used essentially in patients with virtually definite primary hyperparathyroidism and in whom the responsible lesion has not been discovered at exploratory operation.
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