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Biomedical subjects

J Halse

Publications and source records attributed to J Halse.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Early kidney transplantation may prevent aluminium-related bone disease.

In uraemia patients aluminium (Al) accumulation in bone leads to low turn-over bone disease. Al-related bone disease causes bone pain, non-traumatic fractures and hypercalcaemia, and does not respond to treatment with vitamin D compounds. Al-contaminated dialysate and ingestion of Al-containing phosphate binding agents are the main risk factors for bone Al accumulation. Studies of selected patients have indicated that Al-related bone disease ameliorates after successful kidney transplantation, but systematic studies of bone Al have not been reported. In a prospective study we investigated the effect of successful kidney transplantation on bone Al and clinical bone disease.

Adrenal Cortex Hormones↗

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↗

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↗

[Are prosecuted parents allowed the benefit of the doubt in cases of child abuse?].

The justified campaign against child abuse has unfortunately had a side effect. It has ruined the lives of some innocent parents of children with undiagnosed osteogenesis imperfecta. For 15 years, Colin Paterson and co-workers have studied a large number of patients with type IV of osteogenesis imperfecta, and have found that more than 50 per cent of them have normal radiographs of the bones at the time of the first fracture. Paterson and co-workers have also found that fractures of the ribs and skull are by no means uncommon in osteogenesis imperfecta type IV. These important observations should help, in the future, to prevent prosecution of innocent parents of children with osteogenesis imperfecta type IV, provided that the observations are not overlooked by pediatricians.

Child↗

The early effects of aluminium deposition and dialysis on bone in chronic renal failure: a cross-sectional bone-histomorphometric study.

Renal osteodystrophy and aluminium deposition in bone were studied in 19 predialysis and 65 short-term dialysis patients at kidney transplantation during a 1-year period by means of histomorphometric analysis of bone biopsies. All but three patients on dialysis had histological bone disease at transplantation. Hyperparathyroidism was more pronounced in predialysis patients, while the prevalence of stainable bone aluminium (aluminium-positive bone) was greater in dialysis patients (77% versus 37%; P less than 0.05). Aluminium even accumulated in bone with high turnover, while extensive aluminium deposition was associated with delayed mineralisation, hyperosteoidosis, and less fibrosis. Aluminium-stained bone surface was correlated with intake of phosphate binders in non-dialysed patients and with dialysis duration in dialysed patients. All patients dialysed for more than 17 months had aluminium-positive bone. Dialysis patients with aluminium-positive bone had less bone volume and were older than those with aluminium-negative bone. Four patients, all with aluminium-stained bone surface greater than 45% and a dialysis duration exceeding 2 years, had symptomatic bone disease. Our policy of early kidney transplantation may have prevented manifest aluminium-related bone disease in a number of other patients.

Adolescent↗

A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects.

Twenty-six acromegalic patients were randomized to treatment with either SMS 201-995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201-995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly.

Acromegaly↗

[Normocalcemic primary hyperparathyroidism. Skeletal scintigraphy findings indicated a metastatic malignant disease].

The article reports a patient with skeletal pain were radionuclide skeletal images (100 MBq 99mTc-methylenediphosphonate) suggested a metastatic neoplastic lesion as the underlying cause. Further examination revealed that the patient suffered from normocalcemic primary hyperparathyroidism, and after removal of an adenoma of the parathyroid gland the images normalised and the skeletal pain disappeared.

Adenoma↗

Bone remodeling in predialysis chronic renal failure: how does the choice of index for mineralizing surface influence the interpretation?

To study how calculating bone dynamics with different indices of mineralizing surface (MS) may influence the interpretation of bone remodeling in chronic renal failure (CRF) and to discuss which of three often used indices may be closest to the true MS, we compared bone histomorphometry in predialysis patients with moderate (se-creatinine less than 400 mumol/liter) and advanced CRF. All were double-labeled with tetracycline and had no stainable bone aluminum. Bone dynamics were calculated with MS = double-labeled (dLS) + single-labeled surface (sLS), MS = dLS + sLS/2, and MS = dLS. As sLS was twice that of dLS in both groups and the label interval was only 10 days, most single labels were probably double labels, but unseparable due to wide and unsharp labels resulting from high rather than low bone turnover. Bone volume was the same in both groups, while osteoid and resorption indices, sLS, and bone formation rate (with MS = dLS + sLS) were increased in advanced CRF. dLS + sLS is higher than the true MS, but more representative for MS than dLS + sLS/2, with the true value between these two indices. Bone resorption, osteoid formation, and mineralization remain in balance even in advanced CRF. Osteomalacia is hardly the consequence of CRF alone.

Adult↗

Null cell adenomas of the pituitary gland. An immunohistochemical study.

Fourteen null cell adenomas of the pituitary gland were examined immunohistochemically with antisera against three general neuroendocrine markers and 22 hormones. All cases showed positive immunostaining for neuron-specific enolase, ten cases for synaptophysin, and six cases expressed chromogranin immunoreactivity. Hormone immunoreactivity was detected in a few cells in ten of the 14 cases studied and the number of hormones demonstrated in each case was one or two. Thyroid-stimulating hormone was detected in five of the 14 cases, gastrin in four, beta-endorphin in two, calcitonin gene related peptide in one, prolactin in one, and follicle-stimulating hormone in one.

Adenoma↗