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Biomedical subjects

J Halse

Publications and source records attributed to J Halse.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

[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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

[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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

[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↗
PubMed1993

[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↗
PubMed1993

Long-term treatment of macroprolactinomas with CV 205-502.

The long-term efficacy and tolerability of CV 205-502, a non-ergot dopamine agonist with D-2 receptor affinity, were studied for up to 36 months in 16 patients with macroprolactinomas. Prolactin values were reduced in all cases, becoming either normalized or suppressed in 12. The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects. Concomitantly we observed improvement in gonadal function, galactorrhea, headache, libido and general well-being. Adverse reactions were experienced by 15 patients during dosage increment and caused one patient to discontinue the medication. Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205-502, sufficient to normalize PRL levels in three. Two patients experienced serious adverse events, causing the discontinuation of treatment in one case. In eight patients treatment with CV 205-502 and bromocriptine could be compared. Three patients responded better to CV 205-502 than to bromocriptine treatment. Only one patient preferred bromocriptine to CV 205-502 for long-term treatment. We conclude that CV 205-502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas. CV 205-502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed.

Adult↗
PubMed1993

PTH-stimulated adenylate cyclase activity and bone histomorphometry in iliac crest biopsies in the evaluation of uremic patients: a pilot study with the use of artificial intelligence.

Iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (pHPT) were investigated. It appeared that serum 1,25- and 24,25-(OH)2-D3 correlated inversely with basal adenylate cyclase (AC) activity and relative PTH-stimulated AC, respectively. Net PTH-elicited AC (dPTH-AC) activation hence reflected individual vitamin D status. The combination variable serum PTH (s-PTH) x dPTH-AC x [H+] correlated well with resorption surface (RS) in both normals, patients with pHPT or subjects with uremia, while s-PTH, dPTH-AC activity or pH as single variables were only marginally related to RS. For all subjects analyzed, osteoid volume (OV) correlated positively with serum alkaline phosphatase but negatively with serum 1,25-(OH)2-D3. OV showed no correlation with dPTH-AC, while the relationship between OV and s-PTH was strong, suggesting that PTH stimulates osteoid deposition via some signalling pathway other than cAMP. In normals, OV was inversely proportional to s-PTH, due to homologous desensitization of this signalling system. Furthermore, s-PTH was negatively correlated with urine cAMP due to homologous desensitization of the effect of PTH on the kidney 25-(OH)-D3 1 alpha-hydroxylase. This phenomenon was absent in uremic patients. Evaluation of variables by artificial intelligence showed that the prototype uremic patient exhibited serum creatinine > 900 microM, RS > 0.12, pH between 7.15 and 7.34 and s-PTH x dPTH-AC x [H+] between 0.5 and 3.7 units with the distinguishability index 'very good' (< 5% overlap) towards normals. Average similarity of uremic patients with the prototype for normal subjects was only 22%. Cluster analysis of all the variables was conducted for comparison and yielded less clinically relevant information. Hence, emulation done by the expert system was superior and clearly indicates that present treatment modalities restore normal bone turnover only to a minor degree or not at all.

Adenylyl Cyclases↗
PubMed1992

Aluminum metabolism and bone histology after kidney transplantation: a one-year follow-up study.

Parathyroid activity, bone aluminum (Al) metabolism, bone histology, and clinical bone disease were studied in 55 successfully grafted kidney recipients at transplantation (Tx) and after 1 yr of immunosuppression with a low dose corticosteroid and a high dose cyclosporin-A regimen. Symptoms of Al-related bone disease disappeared after Tx. Serum Al and stainable bone Al decreased. The rate of Al removal from the bone surfaces was independent of graft function (creatinine range, 62-415 mumol/L) and bone turnover. Osteoblast activity and bone formation rate increased, while mineralization lag time normalized. Indices of bone resorption remained elevated, indicating persisting hyperparathyroidism. Eighteen percent of the recipients had posttransplant hypercalcemia, most likely caused by incomplete involution of hyperplastic parathyroid glands, while 53% had normocalcemic hyperparathyroidism related to impaired graft function. Cortical thickness decreased, while cancellous bone volume remained stable after Tx; both indices correlated significantly at follow-up with their respective values at Tx. None of 46 radiologically examined recipients had aseptic bone necrosis 1 yr after Tx.

Adolescent↗
PubMed1992

Pretransplant parathyroidectomy in renal failure: effects on bone histology and aluminum deposits during dialysis and after kidney transplantation.

Using repeat bone biopsies, we studied whether 1) subtotal parathyroidectomy (PTX) enhances aluminum (Al) deposition in bone and 2) whether pretransplant PTX affects Al removal from bone after kidney transplantation. Twenty-four kidney graft recipients, 10 subjected to PTX 9-44 months prior to transplantation and 14 controls matched for dialysis duration, had bone biopsies taken at transplantation. Serum calcium and parathyroid hormone levels had decreased after PTX in all 10. At transplantation, eroded bone surface was lower in PTX-recipients, while extent of Al-stained bone surface and prevalence of symptomatic Al-related bone disease were similar in both groups (PTX: 2/10; non-PTX: 4/14). Hence, PTX did not enhance accumulation of stainable bone Al nor increase prevalence of clinical bone disease during dialysis. Fourteen (7 PTX) recipients with functioning grafts had a second biopsy 12 months after transplantation. Symptomatic Al-related bone disease was cured regardless of pretransplant PTX, and Al-stained surface had decreased in all but one (PTX) recipient.

Adult↗