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Biomedical subjects

P Burckhardt

Publications and source records attributed to P Burckhardt.

At least 91 records · Page 5Linked to original sources

Treatment of bone metastases from breast cancer and myeloma with pamidronate.

28 patients with progressing painful bone metastases (18 breast cancer, 9 myeloma and 1 low grade lymphoma) received pamidronate 60 mg by 24 h continuous infusion for at least 2 courses (range 2-12). In patients urinary calcium and hydroxyproline excretion significantly decreased in relation to diminution of bone resorption. 9 of 18 breast cancer patients and 8 of 9 evaluable patients with myeloma had symptomatic improvement. Sclerotic areas of previously lytic lesions appeared in 8 breast cancer patients and in 1 myeloma patient. Transient fever developed in 1 patient and local phlebitis in 2. Among the 28 patients, 15 did not receive any anticancer treatment or have any change of the anticancer therapy during pamidronate administration. Of 7 with breast cancer, 4 had an improvement of symptoms and 4 sclerosis on radiographs. Impressive control of symptoms was the major feature of 8 myeloma patients, but only 1 had radiographic sclerosis.

Adult↗

[Calcium in the prevention and treatment of osteoporosis].

Calcium intake improves the development of bone mass in adolescence and the preservation of bone mass in adulthood, slows down the postmenopausal bone loss and improves bone density also later on. These are recent data obtained from prospective studies. They justify dietary supervision of adolescents, of women during pregnancy, lactation, and after menopause, and of elderly persons of both sexes. They also justify the prescription of about 500 mg of calcium in the case of calcium-poor nutrition in these groups. Above all, they document the necessity of the simultaneous prescription of at least 500 mg of calcium in the treatment of osteoporosis with estrogens, fluor, calcitonin and bisphosphonates.

Adolescent↗

Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1-bisphosphonate.

Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.

Aged↗

Response to retreatment of malignant hypercalcemia with the bisphosphonate AHPrBP (APD): respective role of kidney and bone.

Malignant hypercalcemia is caused by both increased bone resorption and enhanced tubular reabsorption of calcium. First, the response to an infusion of APD was compared in two groups of patients: 23 with breast cancer versus 20 with squamous cell cancer. The decrease in plasma calcium was smaller in the latter group (p less than 0.05 at day 14), due to increased tubular reabsorption of calcium (TmCa/GFR 2.20 +/- 0.05 versus 2.58 +/- 0.06 mmol/liter; p less than 0.001), whereas the degree of bone resorption reflected by urinary hydroxyproline was identical. Therefore, at a given initial plasma calcium level, the type of tumor (on which TmCA/GFR depends) seems to be a determinant for the effectiveness of the treatment. Second, the response to the initial treatment was compared with that to a second treatment with the same dose in 12 patients whose malignant hypercalcemia relapsed. Within 9 days, plasma calcium decreased from 3.46 +/- 0.10 to 2.50 +/- 0.10 mmol/liter after the first course, but only from 3.37 +/- 0.08 to 2.79 +/- 0.09 mmol/liter after the second course (p less than 0.01). TmCa/GFR was similar before the first and the second treatment and did not vary during the days following the infusion of APD. Initial urinary hydroxyproline was slightly but not significantly higher before the second treatment. It dropped following both APD courses, but to a lesser extent after the second treatment, reflecting higher bone resorption or possible resistance to bisphosphonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone and Bones↗

Calciotropic hormones and the aging bone.

The aging of bone is conditioned by intrinsic and extrinsic factors. The decrease of bone density, of cortical and of trabecular bone volume with age goes along with an increase of interstitial trabecular bone (Courpron, 1981), in addition to other intrinsic structural changes. Interstitial bone has a lower cellularity and a lower metabolic activity than the bone tissue which is closer to the trabecular surface. This increase of interstitial bone serves as an example for the supposed decrease of bone cellularity, cellular activity, and hormonal receptors with age in bone. Therefore, the "playground" for calciotropic hormones is reduced in advanced age, independently from the hormonal changes which will be discussed thereafter. The relative role of this decrease of the target organ with age is not yet fully understood. The process of aging can interfere with each step of calcium metabolism from calcium intake and absorption, vitamin D intake and absorption to vitamin D production, hydrolysation and action, as well as to secretion and action of calciotropic hormones such as PTH, calcitonine, and gonadal steroids.

Aging↗

[Microbiological findings of 97 cases of acute pyelonephritis].

To optimize the therapeutic approach to acute pyelonephritis (PNA), the medical records of 89 patients (73 women and 16 men) hospitalized with diagnosis of PNA between January 1984 and 1987 have been studied. According to routine bacteriological urinalysis, gram-negatives were found in more than 92% (E. coli in 79%, Proteus in 6%). Gram-positives were found in only 8%. The gram-negatives (n = 82) showed resistance to amoxicillin in 36%, to amoxicillin/clavulanic acid in 17%, to cotrimoxazole in 18%, and to ceftriaxone in 1%. No resistance to netilmicin or norfloxacin was found. These results justify treatment with norfloxacin or ceftriaxone instead of amoxicillin, amoxicillin/clavulanic acid or cotrimoxazole for gram-negatives. Among the 7 cases with gram-positives, resistance was found to amoxicillin/clavulanic acid, cotrimoxazole and also netilmicin, and to norfloxacin, ceftriaxone and amoxicillin. Therefore, an initial therapy using the association amoxicillin-netilmicin is recommended in PNA.

Acute Disease↗

[The various forms of osteoporosis and their treatment].

Age-associated bone loss is transiently accelerated by the menopause and can lower bone mass below the threshold of mechanical resistance. The appearance of fractures allows the clinical diagnosis of osteoporosis (OP). In addition to age and menopause, major causal factors of OP are low peak bone mass in young adults for genetic or nutritional reasons, and inadequate nutrition in advanced age. Endocrine and digestive diseases, corticotherapy, physical inactivity and low body weight are among other additional causes sometimes calling for specific treatment. Postmenopausal OP predominantly involves trabecular bone, leading to vertebral fractures as early as the age of about 60. Men are 6 times less frequently involved. Age-related bone loss also involves cortical bone and causes fracture of the proximal femur at the age of about 80 in both sexes. Fracture of the forearm chiefly affects women after the menopause. Absorptiometry allows quantitative evaluation of demineralization, diagnosis of "osteopenia" in the absence of fractures, and monitoring of follow-up. It permits few conclusions regarding parts of the skeleton other than those measured. Lumbar and femoral absorptiometry is the most useful, followed by that of the forearm. The clinical relevance of laboratory tests is still debated. Treatment consists either of drugs stimulating bone formation (fluoride, possibly anabolic steroids), or of drugs inhibiting bone resorption (calcitonin, possibly bisphosphonates, or estrogens in postmenopausal women, whenever possible in combination with progestational agents), associated with calcium and vitamin D (according to age and cause of OP), together with physiotherapy if necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A single infusion of Pamidronate (APD) in Paget's disease of bone].

Bisphosphonates are strong inhibitors of bone resorption and have become the treatment of choice of Paget's disease of bone. Second generation compounds such as amino-hydroxypropylene bisphosphonate (Pamidronate or APD) have not been found to impair bone mineralization, but to induce sustained remission of Paget's disease after short or medium courses. Gastrointestinal side effects may limit compliance. Therefore, 11 patients with mild but symptomatic Paget's disease of bone were treated with APD administered as a single intravenous infusion of 60 mg over 24 hours. The follow-up, with clinical and biochemical evaluations, was between 6 months and one year. Clinical improvement and normalization of biochemical parameters were observed in all patients. On average, plasma alkaline phosphatase activity fell progressively and significantly from 256 +/- 29 U/l (means +/- SEM) to 97 +/- 6 U/l after 6 months and to 102 +/- 11 U/l after one year (normal less than 120 U/l). Urinary excretion of hydroxy-proline decreased within 7 days to normal (from 4.3 +/- 0.5 mumol/lGF to 1.7 +/- 0.2 mumol/lGF, normal less than 2.2). Thereafter it remained within the normal range until one year later (1.8 +/- 0.2 mumol/lGF after 6 months and 1.9 +/- 0.3 mumol/lGF after 1 year). Side effects were negligible, with only a transient increase in body temperature in 2 patients. When bone scintigraphy was repeated after 6 months it revealed a marked decrease in the activity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Treatment of tumor-induced osteolysis by APD.

Bisphosphonates, associated with rehydration, became the treatment of choice of malignant hypercalcemia when it became apparent that these compounds normalized plasma calcium in most cases within a few days and with almost no side effects, and that their effect was prolonged. Dichloromethylene bisphosphonate and aminobisphosphonate, especially APD, were shown to inhibit bone resorption with no noticeable inhibition of bone formation, and were highly effective in the long-term treatment of Paget's disease. APD was used in almost 300 patients with malignant hypercalcemia published in the literature and has been used in the medical clinic at Lausanne for several years. When given to 14 patients with malignant hypercalcemia at the dose of 25 mg/day until plasma calcium became normal for two consecutive days, APD had to be given for 4-11 days, severe hypercalcemia needing longer treatment than mild hypercalcemia (Adami et al. 1982). When given for a fixed period of 6 days, again plasma calcium normalized in all patients, whether APD was given i.v. (30 mg/day, ten patients) or orally (1200 mg/day, ten patients) (Adami et al. 1985). Further shortening of the treatment to one single infusion given over 24 h did not decrease the efficacy, as long as high enough doses were given (Blomqvist 1986). For severe hypercalcemia of above 3.5 mmol/liter 60-90 mg had to be given, while 30-45 mg was sufficient in milder cases (Body 1984). Otherwise, mild, transient, and asymptomatic hypocalcemia could occur. Normalization of plasma calcium went along with clinical improvement, sometimes even with correction of coma. Renal function was improved, even when the initial plasma creatinine levels were up to twice normal. Hypercalcemia could reoccur, but the duration of the effect of APD (1 week to several months) depended among other things on the dose administered. The decrease in plasma calcium was accompanied by a decrease in urinary calcium and hydroxyproline, both showing inhibition of bone resorption. In the case of recurrency, the treatment could be repeated with almost unaltered efficacy, except in end-stage cancer disease. When given to 13 normocalcemic patients with bone metastases from breast cancer, hydroxyproline and urinary calcium again decreased. Bone pains and radiologic signs of metastatic bone resorption also showed significant improvement, although these latter effects could also be explained by the antitumoral treatment, in this uncontrolled open trial.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The peak bone mass concept.

Peak bone mass (PBM), i.e. the bone mass developed after growth in early adult life, is a major determinant for bone mass in the senescence, resp. for the risk of osteoporosis. Individual differences among young adults are so important that a person with a high PBM has a relatively low risk for osteoporosis, even if its annual bone loss is fast. PBM is conditioned by genetic, hormonal, and nutritional factors, and by physical activity, the latter two offering possible impact for preventive measures. Preservation of PBM through the early, resp. premenopausal life, can be favoured by adequate nutrition and physical activity, both together being capable of postponing the appearance of osteoporosis by several years. But various parts of the skeleton decrease constantly through life, starting already in the twenties; even when absorptiometry shows no loss of bone density until menopause, resp. during early adult life, there is a constant decrease of the mechanical properties of the bone with age. Therefore, the development of an optimal PBM is probably more effective in preventing osteoporosis than the measures for preservation of bone.

Adolescent↗

Short and long term results of a progressive reintroduction of carbohydrates (PRCH) after a protein-sparing modified fast (PSMF).

Most studies report on a more than 50 percent weight regain 2-3 years after PSMF. We studied the effect of a progressive reintroduction of carbohydrates (PRCH) after a PSMF diet based on natural foods which delivered 800-1200 kcal, 1.2-1.4 g protein/kg of ideal weight, less than 40 g CHO/day. Among 1270 outpatients between 1981-1985, 87 (18M, 69F, age 41.3 +/- 13.8, BMI 32.9 +/- 5.1) followed both PSMF and PRCH. Follow-up was obtained for 57 patients, 1/3 by direct examination, 2/3 by letter. Weight remained stable during PRCH, in opposition to other reports. Best results during PRCH were found in patients with optimal compliance to PSMF, as measured by rate of weight loss (r = 0.284). Only about 40 percent of the obtained weight loss was regained 39.5 months after the treatment. Progressive reintroduction of carbohydrates prevents the expected weight regain after PSMF and even seems to have a positive effect on long term weight maintenance.

Adult↗

[Drug treatment of obesity].

Anorectic agents constitute the most widely used supportive drug treatment in obesity as well as that most often prescribed. A large number of substances have been proposed for this purpose, and some have been found to be reasonably effective, while others exhibiting side effects which forbid their use, as thyroid hormones and diuretic agents. There are other substances with properties that might justify their use, such as ballast preparations, some antidepressive agents, and a few compounds acting principally on the gastrointestinal tract. Of current interest are substances furthering thermogenesis, but for the time being these remain in the realm of pure research. The anorectic agents usually available bring about a weight loss of about 0.5 lb (0.230 kg) per week more than prescription of a placebo, though only over a limited period of time. Once the drug is discontinued, weight regain is the rule and it appears even that association of an anorectic agent to behavioural therapy might have an unfavourable effect on maintenance of the weight loss. Their use is therefore difficult to justify except in the rare cases where a short-term reduction in weight is desired or in patients suffering from an illness linked to their overweight. Differences in eating habits observed with amphetamines compared with fenfluramine and its dextrorotatory isomer dexfenfluramine suggest that these compounds could play a supportive role in the management of obese patients along with the dietetic training and changes in eating habits which are still fundamental to the medical treatment of obesity.

Antidepressive Agents↗

[Treatment of neoplastic hypercalcemia using single-infusion diphosphonate].

40 patients with malignant hypercalcemia were treated with a single dose of APD, a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose response in man, the patients were divided into four groups receiving 30, 45, 60 or 90 mg respectively as 24-hour infusion. Initial plasma calcium was similar in all groups except that receiving 90 mg, some of whose patients had higher initial values. All patients responded to APD with a rapid decrease of plasma calcium concentration from 3.44 +/- 0.10 mmol/l at day 0 to 2.33 +/- 0.06 at day 6, p less than 0.001). Plasma calcium became normal within 4 to 6 days in all patients but 6, all from the group receiving the low doses of APD (30 or 45 mg). Slight and asymptomatic hypocalcemia occurred in only 2 patients of the low dose groups, but in 6 of the high dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 2 months in 6 patients of group 30 mg, in 5 patients of group 45 mg, in 1 patient of group 60 mg and in 2 patients of group 90 mg, whereas mortality was almost identical in the 4 groups. When retreated with a single dose of APD, all patients again showed normalization of calcemia. In all groups plasma phosphate, plasma creatinine and urinary calcium excretion decreased significantly. Clinical improvement was observed in all patients, with minimal side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[So-called "renal" idiopathic hypercalciuria most often has a dietary origin].

Among renal stone formers with idiopathic hypercalciuria, patients who remain hypercalciuric despite low calcium intake have often been regarded as having a primary renal leak of calcium, i.e. renal hypercalciuria. However, at any given intake of calcium, dietary factors other than calcium can generate hypercalciuria, e.g. high intakes of sodium, of animal protein or of carbohydrates, or obesity itself. Thus, the incidence of renal hypercalciuria among stone formers has probably been overestimated. To address this issue, the aforementioned dietary and/or metabolic factors have been evaluated in 51 stone formers with idiopathic hypercalciuria refractory (i.e. U-Ca. V greater than 250 mg/24 h) to 5 days on low calcium intake (max. 400 mg/day). In 15 patients (all had U-Na. V greater than 200 mmol/24 h), U-Ca.V was within the 95% confidence limits of a nomogram U-Ca.V versus U-Na.V, suggesting that their idiopathic hypercalciuria was related, at least in part, to the high sodium intake. 7 patients had severe hyperuricosuria (greater than 1 g/24 h) suggesting high animal protein intake. 20 patients were obese (greater than 120% ideal weight) with (7 cases) or without (13 cases) concomitant fasting hyperinsulinemia (greater than 18 microU/ml). In addition, a careful retrospective analysis of intravenous pyelograms disclosed medullary sponge kidneys in 8 cases which had remained undiagnosed so far; in one of them histological confirmation was obtained after surgical removal of a renal pole and a radiologico-histological comparison. Thus, only 14 out of 51 patients had an otherwise unexplained idiopathic hypercalciuria on low calcium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget's disease of bone.

PURPOSE: Disabling pain, skeletal deformity, or risk of joint involvement characterize Paget's disease of bone. Because the disease often affects the elderly, for whom compliance is a problem, we investigated therapy with a single intravenous infusion of amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD). PATIENTS AND METHODS: Eleven patients with mild but symptomatic Paget's disease and one patient with very severe disease were treated with AHPrBP administered as a single intravenous infusion of 60 mg over 24 hours. Follow-up with clinical and biochemical evaluations was performed over six months for all patients, and over one year for seven patients. RESULTS: Clinical improvement and normalization of biochemical parameters were observed in all patients except one with extremely severe disease. On average, plasma alkaline phosphatase activity fell progressively and significantly from 256 +/- 29 U/liter (mean +/- SEM) to 97 +/- 6 U/liter after six months, and to 102 +/- 11 U/liter after one year (normal: less than 120 U/liter). Urinary excretion of hydroxyproline decreased within seven days to normal (from 4.3 +/- 0.5 mumol/liter of glomerular filtrate [lGF] to 1.7 +/- 0.2 mumol/lGF; normal: 2.2 mumol/lGF). Thereafter, it remained within the normal range until one year (1.8 +/- 0.2 mumol/lGF after six months and 1.9 +/- 0.3 mumol/lGF after one year). Side effects were negligible. Two patients noted only a transient increase in body temperature. When bone scintigraphy was repeated after six months, it revealed a marked decrease of the activity of the disease. CONCLUSION: Due to the important and sustained inhibition of bone resorption induced by AHPrBP, a single infusion of 60 mg of the bisphosphonate leads to a rapid decline in activity and a long-standing remission of moderate Paget's disease, without significant side effects.

Aged↗