Biomedical subjects
Publications and source records attributed to H Mulder.
The disappearance of a drug induced SLE syndrome in a 43 year old man, was described. He replaced antihypertensive agent hydralazine by an other vasodilating agent cadralazine.
The basal and calcium-stimulated calcitonin response was measured in 10 patients with giant cell arteritis before and 1, 3 and 6 wk after the start of daily treatment with 60 mg of prednisone. The study shows that plasma calcitonin level in response to a calcium injection is increased after 1 wk treatment with prednisone. Later on the calcitonin secretion capacity diminishes significantly compared to the initial level. The phylogenetic old calcitonin system first tries to prevent the occurrence of the process of osteoporosis. Moreover, exhaustion of this system later contributes to the process of steroid osteoporosis.
The lateral capsular sign is a simple radiographic finding visible on routine anteroposterior knee x-ray near the tibial articular surface at the lateral point of the lateral tibial plateau. The lateral capsular sign is a flake of bone superior and posterior to the insertion of the iliotibial tract, and represents an avulsion of the meniscotibial portion of the lateral capsular ligament. A positive lateral capsular sign implies disruption of the lateral capsule and a tear of the anterior cruciate ligament. These findings are illustrated by clinical examples.
The effect of continuous infusion of calcitonin on serum osteocalcin concentration was studied in 14 patients with Paget's disease. In all patients serum osteocalcin was initially increased. Within 24 h calcitonin gradually reduced serum osteocalcin, a marker of osteoblastic activity. This means that inhibition of the function of the osteoclasts by calcitonin results in an inhibition of the osteoblasts within 24 h in patients with Paget's disease.
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In 24 patients with hyperthyroidism (15 with Graves' disease and 9 with toxic nodular goitre), serum beta 2-microglobulin (beta 2-m) levels were measured prior to and during 6 wk of treatment with carbimazole. The same schedule was followed in 7 patients with hypothyroidism, but their treatment consisted of levothyroxin in increasing doses. In 16 of the patients with hyperthyroidism, beta 2-m was initially found to be increased. In all these patients an increased beta 2-m declined to normal or near-normal levels. The patients with hypothyroidism had a normal medium serum beta 2-m. During substitution there was a tendency for the serum beta 2-m to decline. Indirect arguments are stated for the hypothesis that both in Graves' disease and in toxic nodular goitre activated T-lymphocytes are modulated in their function by carbimazole acting as an immunosuppressing agent. Moreover, we conclude that thyroid hormone levels are not directly responsible for the increased serum beta 2-m concentrations in hyperthyroidism.
The interaction between testosterone and calcitonin secretion capacity was studied in 9 patients with prostatic cancer. Treatment with the antiandrogenic agent cyproterone acetate resulted in an expected decrease in serum testosterone but an unexpected and unexplained increase in calcitonin secretion capacity. The previous statement that a positive correlation between sex hormones and calcitonin secretion capacity can be recognized probably requires revision. This unexpected effect of cyproterone acetate had possible additive beneficial advantages for treatment, such as bone mass sparing and its analgesic effect.
We studied the effects of furosemide on plasma renin and plasma aldosterone in 8 patients with mild to moderate congestive heart failure. In particular, we tried to correlate these effects with changes in plasma electrolyte concentrations and with the diuretic response on furosemide. We concluded that the diuretic response in patients with congestive heart failure is not dependent on the initial serum renin nor on the initial serum aldosterone concentration. The diuretic response did not correlate either with the changes in serum renin and/or serum aldosterone concentration. Serum renin and serum aldosterone correlated mutually before and after intravenous furosemide. We confirmed the inverse correlation between serum sodium and serum renin. SeNa and SeK correlated at all times with serum aldosterone; SeCl correlated with serum aldosterone only before intravenous furosemide administration. Indirect evidence could be provided that in patients with congestive heart failure a decreased renal blood flow is present, using the urinary beta 2-microglobulin concentration. Aldosterone has again, indirectly, proved to be integrated in the renal magnesium handling.
Previous studies have suggested that sex steroids, including both oestrogen and testosterone, influence calcitonin secretion. However, a negative effect of gonadotrophins on calcitonin has not been excluded. Twelve men with infertility and low-normal serum levels of testosterone were studied before and during tamoxifen therapy. Increases in the serum levels of LH, FSH, testosterone and calcitonin were observed after treatment. Our findings suggest that testosterone has a direct influence on calcitonin secretion.
Patients (859) from six countries were randomized into an endoscopically controlled double-blind trial. The objective of this study was to compare the efficacy and safety of nizatidine 300 mg nocte with ranitidine 300 mg nocte in the therapy of duodenal ulceration. Patients fulfilling the entry criteria and completing the protocol numbered 777 (388 nizatidine, 389 ranitidine). Endoscopy was performed on entry and at 4-week intervals (up to 8 weeks) until the ulcer healed, except in Germany where endoscopy was also performed after 14 days. Both groups appeared well matched for population demographics, duodenal ulcer history, previous therapy and pre-study symptomatology. Overall healing rates in the nizatidine group compared favourably with the ranitidine group at 4 weeks (nizatidine 81%, ranitidine 80%) and 8 weeks (nizatidine 92%, ranitidine 93%). Data from Germany alone showed similar ulcer healing rates after 2 weeks therapy (nizatidine 60%, ranitidine 64%). Although there were no differences between or within the treatment groups, overall ulcer healing was significantly impaired (p less than 0.05 or less) in patients with a large ulcer (greater than 15 mm), a family history of peptic ulcer disease, verified disease or greater than 5 years duration, or heavy smokers (greater than 20 cigarettes/day). Age did not influence healing. Overall healing rates were significantly influenced by country of patient origin, being higher in Germany, and lower in Belgium (p less than 0.001). After 2 weeks therapy, about 60% of the nizatidine and ranitidine treated patients were pain free, while 4 weeks therapy was associated with relief of all symptoms in 72% of patients and relief of night pain in more than 90%. Antacid consumption reduced at a similar rapid rate during the study. Events were reported equally in both treatment groups, events compatible with peptic ulcer disease predominating. Events associated with study termination appeared related to documented disease or protocol violations. Monitoring of laboratory data suggested no significant haematological or biochemical abnormalities in the nizatidine group. Nizatidine 300 mg nocte appears to be as effective as ranitidine 300 mg nocte in both ulcer healing and symptomatic response.
Two hundred and seventy five patients from six countries were randomized into an endoscopically controlled, eight-week, double-blind, study. The objective of this investigation was to compare the efficacy and safety of nizatidine, administered as either a single (300 mg nocte) or twice daily (150 mg B.D.) dose, with ranitidine 150 mg twice daily, in the therapy of benign gastric ulceration. Two hundred and fifty-two patients fulfilled entry criteria and completed the protocol (80 nizatidine 150 mg B.D.; 89 nizatidine 300 mg nocte; 83 ranitidine 150 mg B.D.). Endoscopy was performed on entry and at four-week intervals until the ulcer healed. The diagnosis of benign ulceration was always supported by endoscopic histology and/or cytology. On entry into the study, both groups appeared well matched (i.e. for population demographics, duodenal ulcer history, previous therapy and pre-study symptomatology), except for epigastric day pain which was significantly less in the ranitidine group (p = 0.020). Overall gastric ulcer healing rates were similar in the three groups at four weeks (nizatidine B.D. 66.2%: nizatidine nocte 65.2%: ranitidine B.D. 63%) and at eight weeks (nizatidine B.D. 90%: nizatidine nocte 86.5%: ranitidine B.D. 86.7%). Healing was not consistently influenced by country of origin or smoking. After four weeks of therapy, 66% (nocte dose) to 68% (B.D. dose) of nizatidine treated patients were symptom free, while 93% (nocte dose) to 95% (B.D. dose) were free of night pain. Events were similar in the three treatment groups, and the majority were gastro-intestinal.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (delta nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 +/- 4.68 nmol/100 ml glomerular filtrate vs 29.52 +/- 25.62 nmol/100 ml glomerular filtrate; P less than 0.005). In the group of patients with primary hyperparathyroidism delta nephrogenous cAMP was 13.41 +/- 7.54 nmol/100 ml glomerular filtrate (P less than 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 +/- 10.74 nmol/100 ml glomerular filtrate (P less than 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 +/- 0.10 vs 0.22 +/- 0.09 mmol/l and 0.09 +/- vs 0.22 +/- 0.09 mmol/l; P less than 0.025 and P less than 0.005, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
The effect has been studied of continuous infusion of calcitonin in 14 hypercalcemic patients and 5 patients with Paget's disease of the bones. In all hypercalcemic patients but one, a good serum calcium lowering effect was obtained. In all subjects there was a significant decrease of serum beta 2 microglobulin concentration during calcitonin infusion (4.1 +/- 3.4 vs 2.9 +/- 2.5 mg . l-1; P less than 0.01). Especially in patients with an initial increased serum beta 2 microglobulin, a pronounced decrement of this serum beta 2 microglobulin was achieved. Moreover, a positive correlation was found between the drop in serum calcium concentration and the serum beta 2 microglobulin concentration before calcitonin infusion (r = 0.83; P less than or equal to 0.01). Urinary beta 2 microglobulin excretion did not change significantly during calcitonin infusion. These results led to the speculation that the serum calcium lowering effect of calcitonin is not only the result of the direct antiosteoclastic effect of this hormone but that some immunologic modulating effect of calcitonin on the monocyte macrophage system of the bones is contributory to this hypocalcemic effect of calcitonin.
To determine the frequency of coexisting thyroid gland lesions, a consecutive series of 30 patients operated upon for primary hyperparathyroidism were studied. Lesions of the thyroid gland were found in 21 (70 per cent) patients. It is known that patients undergoing surgical treatment for a disease of the parathyroid or thyroid gland should be carefully evaluated both preoperatively and intraoperatively for abnormalities in the other gland or glands to recognize coexistent disease and treat it in one single procedure. The results of this study has lead to the appreciation of the value of a scintiscan of the thyroid gland prior to operations upon the parathyroid gland. All of the patients with an abnormal scintiscan had coexisting pathologic findings of the thyroid gland. These results suggest that it is quite helpful in evaluating the thyroid gland prior to parathyroid gland operations.
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