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Biomedical subjects

J Halse

Publications and source records attributed to J Halse.

At least 19 recordsLinked to original sources

The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese.

BACKGROUND: Contradicting results have been published regarding the effect of conjugated linoleic acid (CLA) on insulin resistance. However, only a few studies have used the euglycemic hyperinsulinemic clamp method, which is considered the standard for measuring insulin resistance. OBJECTIVE: To evaluate if CLA as a mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the insulin resistance in healthy overweight and obese male and female adults. DESIGN: The main study was a randomized, double-blind, placebo-controlled trial with change in body composition as primary end point comprising 118 subjects receiving supplementation with either placebo (olive oil) or CLA (Clarinol) for 6 months. A sub-population of 49 subjects agreed additionally to participate in an euglycemic hyperinsulinemic clamp study at baseline and after 6 months of supplementation with study drug. The primary outcome was the change in glucose uptake (M) as measured by the hyperinsulinemic euglycemic glucose clamp method. Secondary outcomes were the correlates between insulin resistance and changes in body composition or blood chemistry parameters. Forty-one subjects completed the clamp test at both time points. RESULTS: The median M of the CLA group was 11.0 mg min(-1) lean body mass (lbm)(-1) (n=24) at baseline, 10.3 mg min(-1) lbm(-1) (n=24) after 6 months, and the median difference was +0.21 mg min(-1) lbm(-1) (n=24). The median M of placebo group was 8.4 mg min(-1) lbm(-1) at baseline and 9.3 mg min(-1) lbm(-1) after 6 months and the median difference was -0.22 mg min(-1) lbm(-1) (n=17). No significant (P<0.05) differences were found within groups or between groups. Likewise, the glucose uptake insulin concentration ratio during clamp (M/I) was independent of treatment and time. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index derived from fasting glucose and insulin were also independent of treatment and time, and HOMA for the clamp population (n=49) corresponded well with HOMA for the per protocol population (n=83). Correlation analysis showed that changes in M were inversely correlated to changes in glucohemoglobin (P=0.002), but did not correlate with changes in either glucose, insulin, insulin c-peptide, leptin, adiponectin or percent body fat. CONCLUSIONS: CLA does not affect glucose metabolism or insulin sensitivity in a population of overweight or obese volunteers.

Adolescent↗

Body composition analysis by dual X-ray absorptiometry: in vivo and in vitro comparison of three different fan-beam instruments.

BACKGROUND: Dual X-ray absorptiometry (DXA) is the preferred method for measuring body composition in clinical practice, but interchange between devices may pose problems with the interpretation of results. OBJECTIVE: To establish conversion equations for body composition variables between three fan-beam DXA systems. METHODS: Body composition was assessed in 21 subjects using Lunar Expert (Expert), Lunar Prodigy (Prodigy) and Hologic Delphi W (Delphi). Weekly measurements of Hologic whole body phantom 164 were performed. RESULTS: There were no significant differences between DXA-measured means of body weight, fat mass and lean body mass. Bland-Altman analysis revealed that Lunar Expert increasingly overestimated fat mass with increasing total mass (p<0.001) relative to Delphi and Prodigy, while Delphi produced a constant underestimation of fat mass. Correlations between scale weights and DXA-measured body weights, and between DXA-measured body weights and the sum of fat masses, lean body masses and bone mineral contents (BMC) between the three instruments, were excellent (Rsqr 0.998-0.910; p<0.001). Conversion factors to Prodigy for Expert and Delphi were respectively 1.003 and 1.011 for total body mass, 0.954 and 1.079 for fat mass, 1.018 and 0.967 for lean body mass and 1.049 and 1.136 for BMC (Rsqr 0.999-0.991; p<0.001). Standard error of estimate (SEE) for the slopes ranged from 0.20% to 2.10%. Phantom studies revealed stable instrument function with CV% commonly<2%, except for lean mass for Delphi (5.5%). CONCLUSIONS: Despite the significant differences in measurement of body composition between DXA fan-beam instruments, clinically relevant conversion factors can be established.

Absorptiometry, Photon↗

Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease.

OBJECTIVE: To study the influence of underweight, body composition and vitamin D deficiency on bone mineral density in patients with advanced pulmonary disease. DESIGN: Cross-sectional study with time span for inclusion set at 5 years. SETTING: The clinical work and biochemical analyses were carried out at Rikshospitalet University Hospital, Norway. Analyses for vitamin D metabolites and bone markers were carried out at Aker University Hospital, and bone measurements at Clinic of Osteoporosis. SUBJECTS: Seventy-one candidates for lung transplantation (63% chronic obstructive pulmonary disease, 42 underweight and 29 normal weight) were included. MAIN OUTCOME MEASURES: Body composition, bone mineral density at lumbar spine and femur neck, serum concentration of calcidiol and vitamin D intake. RESULTS: Subnormal calcidiol levels were present in 52% of the underweight patients and 69% of the normal-weight patients. The resulting models of linear regression showed that for the lumbar spine T scores model, the total variation of 16.7% was explained by group (underweight/normal weight), sex and age. For the femur neck T scores model, the total variation of 20.4% was explained by the interaction of underweight and vitamin D deficiency (with borderline significance) and by arm muscle circumference percentage of standard. In patients with normal calcidiol levels, the median intake of vitamin D was 17 microg in the underweight patients and 11 microg in the normal-weight patients. CONCLUSIONS: Vitamin D deficiency was common in both underweight and normal-weight patients, but only in the underweight patients, an association between vitamin D deficiency and reduced femur neck T scores was indicated.

Adult↗

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.

Blood Glucose↗

The Sp1 binding site polymorphism in the collagen type I alpha 1 (COLIA1) gene is not associated with bone mineral density in healthy children, adolescents, and young adults.

Up to 85% of the variance in bone mineral density (BMD) is genetically determined. A putative candidate gene involved in the regulation of bone mass is the COLIA1 gene encoding type I collagen, which is the major protein of bone. We examined possible allelic influences of a G to T COLIA1 gene polymorphism in a recognition site for the transcription factor Sp1 on: (i) gain of forearm BMD using single photon absorptiometry (SPA); and (ii), BMD of the forearm, spine, hip, and whole body with dual X-ray absorptiometry (DXA). At baseline, 269 healthy boys and girls aged 8.2-16.5 years were eligible for the study. Forearm BMD measurements obtained at baseline and after 3.8+/-0.1 years (+/-s.d.) were used to calculate the annual percentage change in BMD. Calcium intake and physical activity were determined by a detailed questionnaire at baseline and after 1 year. Essentially no significant differences in forearm BMD gain or in BMD assessed at the forearm, spine, and whole body were observed among the three COLIA1 genotypes. In conclusion, the data indicate that the polymorphism at the Sp1 site in the COLIA1 gene is not associated with BMD or gain of forearm BMD in healthy boys and girls.

Adolescent↗

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↗