Search

Twenty-eight patients with symptomatic Paget's disease of bone were treated with synthetic salmon calcitonin for periods of 9 to 42 months (average, 23 months). Serum alkaline phosphatase concentration and urinary hydroxyproline excretion, which had been elevated before treatment, were decreased by calcitonin treatment in all patients, and some decrease was sustained in 23 in association with variable decreases in pain, heat and stiffness of major joints. Improvement was sustained further in approximately half of these patients; the other half had partial return of symptoms. Calcium absorption was increased in 9 of 10 patients studied; the increase did not correlate with plasma concentrations of parathyroid hormone. The mean endogenous fecal calcium excretion was decreased significantly but there was no significant change in mean urinary calcium excretion. Mean accretion rate of calcium to bone, studied in 10 patients, was decreased by 35% after 6 months of treatment and by a further 23% 1 year later. There was no consistent effect of calcitonin treatment on bone mineral mass. No serious adverse effects of treatment such as allergic reactions were observed. Calcitonin appears to be effective initially in most patients with Paget's disease of bone, but with long-term treatment resistance may be acquired.

Surveys of nephrologists in Canada indicate that the incidence of analgesic nephropathy has decreased by about 50% in less than a decade in association with the removal of phenacetin from the market and restrictions on the availability analgesic mixtures containing acetaminophen and acetylsalicylic acid. The number of patients presenting with end-stage renal disease attributed to analgesics has shown a similar drop. These decreases have occurred in spite of increased consumption of acetaminophen as a single analgesic. Analgesic nephropathy should not be expected to disappear, however, since there is evidence that the drugs still in use have the potential to cause renal damage.

Long-term anticonvulsant drug therapy may lead to abnormalities of calcium metabolism resulting in osteomalacia. The prevalence and severity of altered calcium metabolism was studied in an adult outpatient population of persons with epilepsy receiving anticonvulsant therapy for a minimum of 2 years. Assessment of calcium metabolism was based on serum concentrations of calcium, phosphorus, alkaline phosphatase and 25-hydroxycholecalciferol and of plasma parathyroid hormone, intestinal absorption of isotopic calcium and skeletal bone mineral mass as determined by in vivo neutron activation or x-ray photodensitometry.Thirty-nine patients who had been receiving anticonvulsant therapy for an average of 20 years were studied; none had clinical evidence of metabolic bone disease. Decreased serum calcium concentration was noted in 10%, decreased serum phosphorus concentration in 10% and elevated serum alkaline phosphatase concentration in 44%. The mean serum 25-hydroxycholecalciferol concentration was significantly lower (P < 0.001) than in a control group (11.6 v. 19.6 mg/mL). None of 18 patients studied had an increased plasma concentration of parathyroid hormone, and only 1 of 17 patients had decreased intestinal absorption of isotopic calcium. Bone mineral mass was decreased in 44% of 32 patients studied.It was concluded that long-term treatment with anticonvulsant drugs leads to mild abnormalities of calcium metabolism and decreased bone mineral mass in a substantial percentage of adult outpatients with epilepsy. These abnormalities probably predispose the patients to the development of clinically significant metabolic bone disease.

The propensity of urine to promote calcium stone formation was compared in 64 patients with recurrent idiopathic calcium nephrolithiasis and 30 healthy individuals without such a history. The rates of excretion of urine crystalloids, the urine saturation with brushite (CaHPO4-2H2O), the ability of the urine to calcify collagen in vitro, and the concentration of urine inhibitors of collagen calcification were measured. The patients had a reduced urine citrate excretion rate in addition to an increased urine calcium excretion rate, while the rates for urine magnesium, phosphate, uric acid and oxalate were not significantly different in the two groups of subjects. The urine concentration of magnesium, phosphate and uric acid was decreased in the patients because of the higher urine volume. The urine creatinine excretion rate correlated with the rates of excretion of urine calcium, magnesium, phosphate, uric acid and oxalate in both groups, which suggested that increased lean body mass, possibly associated with greater food intake, may be an important determinant of crystalloid excretion. The urine of the patients was significantly more saturated with brushite than the urine of the control subjects and resulted in greater collagen calcification when incubated in vitro. The urine concentration of inhibitors of collagen calcification, however, was not significantly different in the two groups. Thus, the urine of patients with recurrent idiopathic calcium nephrolithiasis is more highly saturated with brushite, largely as a result of an increased urine calcium excretion rate, and contains a lower concentration of magnesium and citrate, substances that tend to prevent the precipitation and growth of crystals in urine.

Forty-six patients who underwent renal artery repair for presumptive renovascular hypertension are presented. Preoperative investigation included a rapid sequence IVP, a high quality angiogram and split function studies, as well as renin assays of renal venous blood in the more recent cases. Atherosclerosis was the causative pathological lesion in 60% of the patients, with fibromuscular dysplasia or miscellaneous causes of stenosis accounting for the remaining 40%.Surgical correction was usually obtained by bypass grafting (57%). Hypertension was cured or significantly improved in 36 patients (78%).Optimal results are dependent upon complete preoperative investigation and surgical repair of all the stenotic areas.

To clarify further the beneficial effect of thiazide diuretics on recurrent calcium nephrolithiasis, the effect of short-term hydrochlorothiazide therapy on urine saturation with brushite (CaHPO(4).2H(2)O), in vitro collagen calcification by urine, and urinary inhibitors of calcification was studied.In 22 patients with idiopathic calcium oxalate/phosphate stones the urine calcium excretion decreased, the urine magnesium excretion increased and the urine magnesium/calcium ratio increased significantly (P < 0.001) during hydrochlorothiazide therapy. Supersaturation of the urine with brushite, which was present in 19 of the 22 patients, was reduced significantly (P < 0.001) in all during thiazide therapy, and to the undersaturated range in 16. The ability of urine to calcify collagen in vitro also decreased significantly (P < 0.001) during thiazide therapy, a change that correlated significantly (r = 0.4513, P < 0.05) with the decrease in brushite saturation. The concentration of urinary inhibitors of calcification, as determined with an in vitro collagen calcification system, was decreased significantly (P < 0.01) by thiazide therapy.It was concluded that, in addition to decreasing urine calcium excretion and increasing urine magnesium excretion, thiazide diuretics decrease the urinary brushite saturation and thus may prevent spontaneous nucleation or crystal growth, or both, of calcium phosphate. The ability of thiazides to decrease collagen calcification in vitro suggests that they may also prevent crystal growth on a nidus of organic matrix. Thiazides do not appear to act by increasing the excretion of urinary inhibitors of calcification.

In the 6 1/2 years ending June 1977, 210 patients with abdominal aortic aneurysms underwent operation at Toronto Western Hospital; 160 aneurysms (76%) were unruptured and 50 (24%) were ruptured. In the patients with unruptured aneurysms the mean age was 68 years; the oldest was 91, and 12 were more than 80 years of age. The overall hospital mortality was 5.6%. Death in hospital occurred in 1 (1.2%) of the 83 asymptomatic patients, 4 (7.4%) of the 54 symptomatic patients and 4 (17.0%) of the 23 patients for whom operation was considered urgent. In the patients with ruptured aneurysms the mean age was 71 years; the oldest was 90, and five were more than 80 years of age. The overall hospital mortality was 54%. The morbidity and mortality were analysed; in particular the reasons for the markedly variable hazard of operations for the three categories of unruptured aneurysm were sought. The surgical literature is confusing because of the interchanging use of the words unruptured, elective and symptomless. The current philosophy management and technique of operation in a large cardiovascular surgery service with many trainees are presented and a plea is made for a standardized and simplified operation, always performed with three assistants helping the operating surgeon.

Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without such a history to examine the factors that predispose normocalciuric patients to stone formation. The urine calcium excretion rate was higher in the normocalciuric patients than in the control subjects (227 v. 183 mg/24 h; P less than 0.01), but the urine calcium concentration was not significantly different. The urine magnesium and citrate excretion rates and concentrations were lower in the normocalciuric patients than in the control subjects (P less than 0.001), while the urine uric acid and oxalate excretion rates and concentrations and the urine saturation with brushite (CaHPO4-2H2O) were not significantly different. These results suggest the importance of slight increases in the urine calcium excretion rate together with decreased urine magnesium and citrate excretion rates in normocalciuric persons with recurrent calcium stone formation. The urine of the hypercalciuric patients was more highly saturated with brushite than the urine of the normocalciuric patients and the control subjects, and the excretion rates of uric acid and oxalate were increased in the hypercalciuric patients. The hypercalciuric patients had a higher urine creatinine excretion rate than the normocalciuric patients and a higher daily urine volume than the control subjects, which suggests that differences in lean body mass or fluid and food intake, or both, may be important determinants of these differences in crystalloid excretion. As in the normocalciuric patients, the urine citrate excretion rate and concentration were decreased in the hypercalciuric patients compared with the control subjects.

The authors review their experience with 29 patients who were operated upon for renal artery stenosis and had been followed up for longer than one year postoperatively. The preoperative assessment should include an aortogram and split-function test. A bypass prosthesis was the most useful operative technique. One year following surgery 40% were cured, 40% significantly improved and 20% unchanged. The results in patients with a longer follow-up (to seven years) were similar.A plea is made for more frequent preoperative renal biopsies and a greater willingness to perform bilateral repairs at the time of the initial operation.

Amyl nitrite was administered on two occasions to a patient with muscular subaortic stenosis, to ascertain if selective peripheral vasodilatation would affect the degree of obstruction to left ventricular outflow in this condition. On each occasion there was a marked increase in the systolic pressure gradient across the left ventricular outflow tract prior to the onset of reflex tachycardia. Following the second amyl nitrite inhalation, the systolic cross-sectional area of the left ventricular outflow tract decreased to 1.0 sq. cm., from the control value of 2.6 sq. cm. It is believed that the increased degree of muscular subaortic stenosis, following peripheral vasodilatation, could be secondary to a decrease in the systolic size of the whole left ventricle, or to a selective decrease in the physical size of the left ventricular outflow tract.

Twenty-five patients with impending death from myocardial infarction were treated with assisted circulation. Of these, 19 had suffered cardiac arrest from which they could not be resuscitated and six were in severe, intractable and expectedly terminal cardiogenic shock.All patients were treated by venoarterial bypass employing a bubble oxygenator. Assistance was continued for an average duration of one hour and 45 minutes at a flow rate between two and four litres per minute. The patients all showed improved cerebral, pulmonary and renal function and acid-base values returned to normal.Five patients survived for at least one month and two were improved; hence 28% of these otherwise terminal patients were helped by this technique of assisted circulation.

Two cases of primary hyperparathyroidism due to single parathyroid adenomas presented with the additional feature of hyperchloremic acidosis. The defect in urinary acidification responsible was not of the distal or gradient-limited type since both patients could lower urine pH adequately. However, there was a defect of bicarbonate reabsorption, an abnormality referred to as the proximal or rate-limited type of renal tubular acidosis. It is suggested that this defect represents an exaggeration of the physiological effect of parathormone on bicarbonate reabsorption and may be responsible for the frequent finding of hyperchloremia in association with primary hyperparathyroidism as well as for the urinary bicarbonate-wasting associated with a variety of causes of secondary hyperparathyroidism.

Fecal and salivary sodium and potassium concentrations were measured in 22 hypertensive patients with hypokalemia who were undergoing investigation for primary aldosteronism due to an adrenocortical adenoma (Conn's syndrome). Of eight patients with a high aldosterone secretion rate, five had clearly low fecal Na/K ratios, (including all four patients with Conn's syndrome), in three the ratios were equivocal. Of 14 patients with hypertension and a normal aldosterone secretion rate, none had a sufficiently low fecal Na/K ratio strongly to suggest hyperaldosteronism, although two were borderline. Salivary electrolyte concentrations were not as consistent an indicator of mineralocorticoid hormone excess. Estimation of fecal sodium and potassium concentrations may be useful in the diagnosis of mineralocorticoid hormone excess and in assessing the results of therapy.

Data concerning 351 patients with analgesic nephropathy was obtained by a survey of Canadian nephrologists and suggested an incidence of at least 20, and of perhaps 50 cases per million population. Renal function at the time of diagnosis (as judged by serum creatinine level) was normal in 15%, mildly to moderately impaired in 59%, and severely impaired in 26% of cases. Follow-up serum creatinine level in 222 cases showed that renal function became worse in 42% of cases, with terminal renal failure developing in one-half of these patients. However, significant improvement in kidney function was observed in 25% of patients. Cessation of analgesic abuse considerably increased the likelihood of improvement in renal function.