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Biomedical subjects

J Halse

Publications and source records attributed to J Halse.

At least 19 recordsLinked to original sources

Pattern of cancer in Indian patients hospitalized in Durban, South Africa.

In emigrants from less to more developed countries, consequent changes in environmental factors are associated, inter alia, with changes in occurrences of the chronic diseases of lifestyle. In South Africa, most immigrants from India arrived in the early 1900s. To learn of the current pattern of cancer in the descendants of these people, enquiries were made on several series of patients admitted to RK Khan Hospital in Durban. The results were then compared with those of patients admitted to Ambojogai Hospital, North West India, the ancestral home of the majority of South African Indians. The most prominent differences were the lower percentages in South African Indians in respect of cancers of the mouth/pharynx in both sexes and of cervical cancer, and their considerably higher percentages, principally in the cases of stomach cancer in both sexes, of prostate cancer in males and of breast cancer in females. Discussion of risk factors indicates that in such populations there could be some control over the rises in some cancers, and on reductions in others. However, endeavours at prevention are hindered not only by the lack of knowledge prevailing, but also by their general indifference; likewise, this is the case with western populations.

Diet

Sandostatin LAR in acromegalic patients: long-term treatment.

We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a stable and consistent suppression of GH and insulin-like growth factor (IGF-I) during the entire study period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients. The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9 patients and to between 500-1000 micrograms/L in the remaining 5 patients. Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious additional effect on GH suppression, but provided a further decrease in IGF-I levels. Forty milligrams of the drug had no additional effect on GH or IGF-I compared to 30 mg. Acromegalic signs and symptoms improved during treatment. Although the fluctuations of daily mean octreotide levels were high, dosage increments caused an increase in the average serum concentration in the individual patient. Pituitary tumor size reduction was seen in all previously untreated patients (n = 4). We found only minor changes in glucose metabolism (oral glucose tolerance test and hemoglobin A1C) during treatment, but no biologically relevant changes in thyroid function (TSH, T3, and free T4). One patient developed asymptomatic gallstones, and another acquired vitamin B12 deficiency during treatment. The drug is well tolerated during long term treatment. Sandostatin LAR may well be the future medical treatment of choice for acromegalic patients.

Acromegaly

Lack of relationship between vitamin D receptor genotype and forearm bone gain in healthy children, adolescents, and young adults.

Recent studies have suggested that genetic effects on bone mineral density (BMD) are related to allelic variation in the vitamin D receptor (VDR) gene. We examined 1) allelic influences of the VDR gene on BMD of the forearm, spine, hip, and whole body; and 2) allelic influences of the VDR gene on forearm BMD gain. Two hundred and seventy-three healthy boys and girls, aged 8.2-16.5 yr, at baseline were eligible. Forearm BMD was assessed with single photon absorptiometry at baseline. BMD gain was calculated as the annual percent change in BMD measured by single photon absorptiometry from the baseline and after 3.8 +/- 0.1 (+/-SD) yr. Calcium intake and physical activity were assessed by a detailed questionnaire at baseline and after 1 yr. VDR alleles were determined by BsaMI endonuclease restriction fragment analysis after PCR amplification. No significant differences in forearm BMD gain or in BMD assessed at the forearm, spine, hip, and whole body were observed among the three VDR genotypes. These findings did not change after adjusting for environmental factors such as calcium intake and physical activity or age, weight, height, and changes in weight and height during the observation period. In conclusion, our data do not support the idea that VDR genotypes are related to BMD gain or to BMD at the forearm, hip, spine, and whole body in healthy boys and girls, aged 8-21 yr. VDR genotyping is probably of little use for the detection of individuals who would benefit from increased calcium and physical activity to increase their peak bone densities.

Absorptiometry, Photon

Predialysis calcitriol administration: effects on pre- and post-transplant renal osteodystrophy.

Twins with parallel loss of kidney function and moderate hyperparathyroid bone disease were participants in a double-blind study where twin A was given placebo and twin B calcitriol. After 8 months. A's bone disease had not improved, while B's bone had normalized. Thereafter, both received calcitriol until kidney transplantation 11 months later, when both had normal bone structure. Two years after transplantation, both twins had hyperparathyroid bone disease, but A had more pronounced changes. This report illustrates our findings in larger series: When started early in the course of renal failure, calcitriol can reverse pre-transplant hyperparathyroid bone disease and also influence post-transplant bone disease.

Calcitriol

X chromosome inactivation pattern in female carriers of X linked hypophosphataemic rickets.

X linked hypophosphataemia (XLH) results from an abnormality of renal tubular phosphate reabsorption. The disorder is inherited as an X linked dominant trait and the gene has been mapped to Xp22.1-p22.2. A candidate gene (PEX) has recently been isolated. The most striking clinical features are growth retardation and skeletal abnormalities. As expected for X linked dominant disorders, females are less affected. However, such a gene dosage effect does not exist for renal phosphate reabsorption. Preferential X chromosome inactivation has been proposed as a possible explanation for this lack of gene dosage. We have examined the X inactivation pattern in peripheral blood cells from 12 females belonging to seven families with XLH using PCR analysis at the androgen receptor locus. The X inactivation pattern in these patients did not differ significantly from the pattern in 30 healthy females. The X inactivation pattern in peripheral blood cells does not necessarily reflect the X inactivation pattern in renal cells. However, the finding of a normal distribution of X inactivation in peripheral blood cells indicates that the similarity in the renal handling of phosphate in male and female patients is not related to a ubiquitous preferential X inactivation.

Adult

[Osteoporosis drugs prescribed on blue forms!].

The National Insurance Administration, through the system of blue prescription forms, refunds part of the cost of drugs used to treat a number of chronic diseases. To obtain a refund, the indication for prescribing the drug must be included in the list of diagnoses which entitle a refund through the system. The list is a long one, and costs are refunded for prophylactic drugs (e.g. against hypertension and hypercholesterolemia), drugs to alleviate symptoms (e.g. for certain skin diseases and heart failure) and curative measures. The qualitative criteria for a refund, over and above the diagnosis, are not precisely defined, and doctors are free to choose the drug they prefer, regardless of price. The authors discuss whether the list of diagnoses should be extended to include osteoporosis, and recommend that doctors should be able to prescribe the relevant preventive and palliative drugs on a blue form. Many think that this refund system is a good initiative.

Aged

Autonomous hyperparathyroidism in X-linked hypophosphataemia.

Four patients with familial hypophosphataemic rickets developed significant hypercalcaemia which persisted after discontinuation of vitamin D therapy. They had increased PTH levels and were operated for hyperparathyroidism at the ages of 18, 20, 24 and 45 years, respectively. Three of the patients had previously received phosphate treatment and one patient developed hyperparathyroidism 7 years after treatment with calcitriol. Histological evaluation revealed different degrees of parathyroid hyperplasia in all patients, with persistently increased PTH and/or calcium levels after surgery. The possibility of autonomous hyperparathyroidism should be evaluated in the follow-up of patients with X-linked hypophosphataemic rickets.

Adult

Sandostatin LAR in acromegalic patients: a dose-range study.

Sandostatin LAR is a sustained release formulation of octreotide that has been developed by microencapsulating the drug with biodegradable poly(lactide-glycolide)-glucose. We have investigated the efficacy and tolerability of Sandostatin LAR given as a single dose im to patients with active acromegaly who showed good GH suppression during a 2- to 4-week pretreatment period with octreotide given sc. Two double blind studies were performed. Initially, 14 patients were randomized and observed over 42 days after a single im injection of 3, 6, 9, or 12 mg Sandostatin LAR. In the second study, 15 patients were randomized and observed over 60 days after a single im injection of either 20 or 30 mg Sandostatin LAR. Assessments of 12-h GH and octreotide profiles and adverse events were made on day -14 (during treatment with Sandostatin, sc); day 0 (off treatment after wash-out period); days 1, 7, 14, 21, 28, 35, and 42; and, for study 2, also on days 49 and 60 after the im injection. Only injections of 20 or 30 mg were followed by a suppression of basal GH and insulin-like growth factor I to levels comparable to those seen during sc treatment. The suppression of mean GH to less than 5 micrograms/L lasted for 4 weeks in the group receiving 20 mg and for at least 6 weeks in those given 30 mg Sandostatin LAR. The pharmacokinetic profile fitted a biphasic drug release model previously described for peptides in similar drug delivery systems. Serum concentrations correlated with the im administered dose. Suppression of GH and insulin-like growth factor I was achieved at serum octreotide concentrations exceeding approximately 600 ng/L. Tolerability was good. Sandostatin LAR holds promise as a valuable drug for the treatment of acromegaly. The results of ongoing long term studies will provide further necessary knowledge of the drug.

Acromegaly

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.

Adult

[Idiopathic osteoporosis in middle-aged men--a "new" disease?].

Idiopathic osteoporosis is uncommon in middle-aged men. We discuss nine otherwise healthy men aged from 35 to 57 years, eight of whom were shown to be osteoporotic when subjected to detailed investigation because of back pain. None had suffered fractures of the appendicular skeleton as adults. All had an ordinary life style and ate a normal diet. Lumbar spine bone density was greatly reduced in all nine patients, while six of them showed normal values for cortical bone density in the forearm. Bone histomorphometry showed high turnover of bone tissue, with high bone resorption and lower than average bone formation. Serum osteocalcin levels were low in all nine patients, but alkaline phosphatase was higher than the upper normal limit in six of them. The etiology of the disease is unknown, but the pathogenesis is a result of disparity between formation and resorption of bone tissue. Unidentified environmental factors may be one of the reasons for the appearance of idiopathic osteoporosis as a "new" disease among middle-aged men.

Adult

Fracture strength prediction in rat femoral shaft and neck by single photon absorptiometry of the femoral shaft.

The bone mineral content (BMC) and bone mineral density (BMD) of the femoral midshaft from 15 skeletally mature male rats were measured by Single Photon Absorptiometry (SPA), and comparisons made to fracture strength of the femoral diaphysis and the femoral neck. In stepwise regression the factors contributing significantly to the ultimate bending moment of the shaft were BMC and femoral length. BMC correlated strongly with the ultimate bending moment of the femoral diaphysis (r2 = 0.63, P < 0.01). The correlation between BMC and ultimate moment of the femoral neck was moderate (r2 = 0.51, P < 0.01). The correlations between BMD and mechanical parameters were lower than the corresponding values for BMC, with a significant result only for the bending moment of the femoral diaphysis (r2 = 0.48, P < 0.01). In conclusion, BMC rather than BMD, is most predictive for fracture strength of the femur in rats.

Absorptiometry, Photon

A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.

We investigated the pharmacokinetics of bromocriptine and octreotide, both individually and in combination, in 12 patients with active acromegaly. The pharmacodynamics of the drugs were assessed by 12-h profiles of GH secretion and insulin-like growth factor-I (IGF-I) measurements. During the 42-day study period, bromocriptine was administered for 28 days (from day 8; 5 mg, orally, twice daily) and octreotide (200 micrograms, sc, twice daily) from days 15-42. IGF-I levels, 12-h GH, and plasma bromocriptine and octreotide profiles were obtained on days 0, 14, 28, and 42. During bromocriptine treatment, both the area under the GH day curves (AUC) and mean IGF-I decreased to 64% (95% confidence limits, 43-72% and 48-82%, respectively) of initial values. During octreotide treatment, the respective values were 23% (18-30%) and 32% (21-36%), which were greater decreases than those during bromocriptine treatment [36% (95% confidence limits, 32-54%) for AUC for GH and 50% (95% confidence limits, 34-58%) for IGF-I]. With combined treatment, the AUC for GH was reduced to 16% (12-21%) and that of IGF-I to 25% (16-27%) of initial values. This combination was more effective than bromocriptine [25% (95% confidence limits, 22-37%) for AUC for GH and 39% (95% confidence limits, 25-43%) for IGF-I] and octreotide alone [78% (95% confidence limits, 53-89%) for AUC for GH and 78% (95% confidence limits, 57-98%) for IGF-I]. The pharmacokinetic parameters of octreotide were unchanged by the coadministration of bromocriptine. The bioavailability of bromocriptine increased by approximately 40% when bromocriptine was administered together with octreotide compared with administration alone (P < 0.01). Bromocriptine disposition parameters were unaltered. In conclusion, treatment of acromegalics with a combination of octreotide and bromocriptine increases the bioavailability of bromocriptine and reduces both GH and IGF-I levels more effectively than treatment with either drug alone. This presents the possibility of less frequent drug administrations, lower doses of octreotide, and, consequently, lower treatment costs.

Acromegaly

The neuronal regulation of fracture healing. Effects of sciatic nerve resection in rat tibia.

The effect of sciatic nerve resection on tibial fracture healing was studied in rats 25 days post-trauma. To prevent differences in loading between sham-operated and nerve-resected animals the fractured limbs were cast-immobilized. On radiograms 8 of 11 fractures in the sham-operated animals showed very little callus formation in contrast to only 1 of 8 fractures in the group with nerve resection. Measured by single-photon absorptiometry, animals with sciatic nerve resection had a higher bone mineral content than the sham-operated animals. However, the mechanical strength in three-point cantilever bending was not better in the nerve-resected rats, implying a defective organization of the large callus. These results suggest neural regulation plays a role in the type of fracture healing, primary or secondary, and in the amount and quality of the callus.

Animals

Chronic renal failure: diagnostic measures before parathyroidectomy.

To investigate whether conventional criteria suffice to differentiate between hyperparathyroid and aluminum (Al)-related bone disease, we obtained bone biopsies from 7 patients with chronic renal failure (CRF) at the time of PTX and 3.5-36 months later. All had hypercalcemia and elevated mid-region parathyroid hormone levels and 3 had bone pain at PTX. Bone histomorphometry revealed that 5 patients had hyperparathyroid bone disease at PTX, while 2 had osteomalacia and skeletal Al deposits. Retrospective determination of intact PTH showed normal levels at PTX in the latter two. PTX effectively reduced all indices of parathyroid hyperactivity, but the two patients with Al-related bone lesions did not improve clinically nor histologically after PTX. Intact PTH and/or bone biopsy prior to PTX could have deterred surgery in those with Al-related bone disease.

Aluminum

[Bone mineral density and occurrence of fractures in 66-year old women in Oslo].

During 1991 we examined 196 randomly chosen females born in 1925 and resident in Oslo. 40% had suffered fractures of the appendicular skeleton, most commonly of the forearm and the ankles, after the menopause. Results from bone mineral density measurements of the lumbar spine (L2-4) and the femoral neck were not significantly lower, while results from the distal 1/3 of the forearm site were significantly lower, among participants with fractures than among participants without fractures. The values for bone mineral density obtained from these three sites corresponded with the values reported from other countries. Biochemical indices of calcium metabolism were similar in fracture and non-fracture subjects. Age at menopause, weight, height and demographic characteristics were also similar in the two groups. We conclude that low bone mineral density cannot be the sole explanation of the very high prevalence of fractures among female residents of Oslo found in the present and previous studies.

Adult

[Endocrine disorders in adolescents and young adults].

Evaluation of 158 patients younger than 25 years-of-age who had been hospitalized in a specialized adult endocrine department during an 11 year-period, brought to light specific endocrine problems connected both to pediatrics and internal medicine. There is need for close collaboration between pediatricians, as experts on disturbances in growth and pubertal development, and internists, with experience of diagnosing rare endocrinological disorders. Such collaboration might also improve the follow-up of young patients into adulthood.

Adolescent