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Biomedical subjects

H de Boer

Publications and source records attributed to H de Boer.

At least 19 recordsLinked to original sources
PubMed2006

Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptor.

Familial benign hypocalciuric hypercalcaemia (FHH) results from a heterozygous inactivating mutation of the calcium-sensing receptor (CaR) and is characterized by hypercalcaemia, hypocalciuria and inappropriately normal plasma levels of parathyroid hormone. In a minority of patients, a loss of function mutation of the CaR results in severe hypercalcaemia associated with complications for which no effective surgical or medical treatment is available. We investigated the effects of the calcimimetic agent cinacalcet, an allosteric modulator of the CaR, in a 26-year-old man presenting with hypercalcaemia due to a de novo inactivating mutation of the CaR. Complicating features were recurrent psychosis and progressive severe osteoporosis. A single dose of either 30 or 60 mg of cinacalcet resulted in a 63-88% decline in plasma parathyroid hormone levels within 2 h of administration of the agent, reverting to baseline levels after 12 h. Normalization of serum calcium was more gradual but sustained for up to 12 months of treatment with a maintenance twice-daily oral dose of 60+30 mg cinacalcet. In addition to its beneficial effects in primary and secondary hyperparathyroidism, cinacalcet may open new therapeutic avenues in the management of a subset of patients with severe hypercalcaemia due to inactivating mutations of the CaR.

Adult↗
PubMed2006

Glycaemic control without weight gain in insulin requiring type 2 diabetes: 1-year results of the GAME regimen.

INTRODUCTION: Weight gain appears to be unavoidable in patients with type 2 diabetes who are switched from oral agents to insulin therapy. Peripheral hyperinsulinism induced by the use of long-acting insulin may be the key to explain this adverse effect. AIM: The aim of this study was to investigate whether a regimen free of long-acting insulin can provide long-term glycaemic control without causing weight gain. PATIENTS AND METHODS: This is an uncontrolled, 1-year study comprising 58 patients with type 2 diabetes and secondary failure, age 30-75 years, BMI 25-35 kg/m(2), HbA1c > 7.5% and fasting C-peptide level > 0.3 mmol/l. All patients were treated with the GAME regimen, a combination of glimepiride administered at 20:00 hours for nocturnal glycaemic control, insulin aspart three times daily for meal-related glucose control and metformin. RESULTS: Seventy-one per cent of the patients were considered evaluable. HbA1c decreased from 10.0 +/- 0.3 to 7.4 +/- 0.1% (p < 0.001). Fifty-nine per cent reached HbA1c levels <or= 7.5%. Symptomatic nocturnal hypoglycaemia was not reported. Body weight tended to decrease during the first 3 months (-1.0 +/- 0.5 kg, p = 0.06), but then gradually rose to a value 0.8 +/- 0.5 kg higher than at baseline (p = 0.12). This is 4.4 +/- 0.6 kg less than predicted for conventional regimens employing long-acting insulin (p < 0.001). CONCLUSION: The GAME regimen provides long-term glycaemic control as well as stabilization of body weight in about 60% of type 2 patients presenting with secondary failure.

Adult↗
PubMed2005

Prevalence of epilepsy its treatment gap and knowledge, attitude and practice of its population in sub-urban Senegal an ILAE/IBE/WHO study.

A door-to-door survey was used to determine the prevalence of epilepsy among 4500 people within the Pikine Health District (population 480,000) Senegal. Prevalence was 14.2/1000, and 23.4% of all people with epilepsy had never received appropriate treatment. Figures for the prevalence had increased since a previous survey in 1989. In parallel a study of knowledge attitude and practice was performed in the same district. Salient findings were that: two-thirds of interviewees had at some time witnessed a seizure, 51% agreed when asked if epilepsy is caused by evil spirits, 35% said epilepsy is contagious, only about 18% said that traditional therapy is best, 60% would not mind their child to play with a child with epilepsy but only 32% would agree if their child would want to marry a person with epilepsy.

Adolescent↗
PubMed2005

Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism.

BACKGROUND: Morbid obesity is associated with increased estradiol production as a result of aromatase-dependent conversion of testosterone to estradiol. The elevated serum estradiol levels may inhibit pituitary LH secretion to such extent that hypogonadotropic hypogonadism can result. Normalization of the disturbed estradiol-testosterone balance may be beneficial to reverse the adverse effects of hypogonadism. AIM: To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism. PATIENTS AND METHODS: Ten severely obese men, mean age 48.2 +/- 2.3 (s.e.) years and body mass index 42.1 +/- 2.6 kg/m(2), were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week. RESULTS: Six weeks of treatment decreased serum estradiol from 120 +/- 20 to 70 +/- 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 +/- 0.8 to 14.8 +/- 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 +/- 1.0 to 23.8 +/- 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response. CONCLUSION: Short-term Letrozole treatment normalized serum testosterone levels in all obese men. The clinical significance of this intervention remains to be established in controlled, long-term studies.

Aromatase Inhibitors↗
PubMed2005

Diazoxide-mediated insulin suppression in obese men: a dose-response study.

BACKGROUND: It has been suggested that diazoxide (DZX)-mediated insulin suppression may be useful to promote weight loss in obese subjects. AIM: To assess the DZX-dose range that is safe to use in obese hyperinsulinaemic men. METHODS: Assessment of DZX efficacy and safety was based on plasma glucose and insulin responses to a standardized 500-kcal breakfast, taken on the sixth day of treatment. Basic information regarding the potential efficacy of DZX treatment was first evaluated in an open-label study in five non-obese men. Subsequently, a double-blind, randomized, placebo-controlled study was performed in 12 obese but otherwise healthy men, comparing placebo treatment with DZX in doses of 50, 75 and 100 mg three times daily for 6 days. RESULTS: In non-obese subjects, DZX 50 mg decreased peak insulin levels by +/-28% and raised peak glucose concentration from 7.1 +/- 0.6 to 7.8 +/- 0.6 mmol/l (p < 0.05). DZX 100 mg reduced peak insulin levels by 45% and caused a rise in peak glucose levels from 7.1 +/- 0.6 to 9.0 +/- 0.9 mmol/l (p < 0.05). In obese men, the 50 and 75 mg doses had no significant effects on glucose or insulin levels. DZX 100 mg reduced the peak insulin levels and insulin area under the curve by +/-20% (p < 0.05) but did not affect fasting or postprandial glucose levels. The relatively limited insulin-suppressive effects in obese subjects were attributed to the low plasma DZX levels that were achieved in this group. For comparable doses, plasma DZX levels were about 30% lower in obese than in non-obese men. Plasma DZX levels were highly dependent on dose (p < 0.001) and body weight (p < 0.001). Ninety-two percent of the total variability in DZX levels was explained by these two parameters. CONCLUSION: DZX-mediated insulin suppression is dose dependent in normal and in obese men. However, the efficacy of DZX is much less in obese than in non-obese subjects. This is attributed to weight-dependent differences in distribution volume that lead to markedly lower plasma DZX levels in obese subjects. Weight-adjusted doses will be needed to achieve biologically effective plasma DZX levels. Extrapolation of the data suggests that effective insulin suppression in obese men will at least require a daily dose of 3.2-4.2 mg/kg.

Adult↗
PubMed2004

Prevention of weight gain in type 2 diabetes requiring insulin treatment.

BACKGROUND: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds. AIM: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin. METHODS: In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1-2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control. RESULTS: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 +/- 0.3 mg/day (mean +/- standard error of the mean), and a total daily insulin dose of 24.1 +/- 2.6 IU. Fasting glucose levels decreased from 12.7 +/- 0.6 mmol/l to 8.1 +/- 0.3 mmol/l (p < 0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 +/- 0.4 to 7.7 +/- 0.2% (p < 0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 +/- 3.6 kg vs. 85.7 +/- 3.3 kg, p = 0.99). CONCLUSION: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.

Blood Glucose↗
PubMed2001

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Aged↗
PubMed1999

Feasibility of pacemaker therapy after dynamic cardiomyoplasty.

A 54-year-old man presented with total atrioventricular (AV) block 3 months after dynamic cardiomyoplasty was performed because of heart failure due to idiopathic dilated cardiomyopathy. Though the cardiomyostimulator acted as a back-up pacemaker, a DDDR pacemaker was implanted to optimize hemodynamics. During testing no cross-sensing or cross-stimulation between the pacemaker and the cardiomyostimulator was demonstrable. The synchronization delay, however, had to be adjusted.

Cardiomyoplasty↗
PubMed1999

Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency.

Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function. Thirty-eight men with childhood-onset GH deficiency were studied for a period of 3-5 yr. Measurements included anthropometry, computed tomographic scanning of abdomen and upper leg, bone densitometry, echo cardiography, and bicycle ergometry. The initial GH dose of 1-3 IU/m2 x day (9-27 microg/kg) was gradually tapered to 1.30+/-0.38 IU/m2 x day (11 g/kg), aiming at physiological insulin-like growth factor I levels. During the study, leg muscle mass progressively increased by 28.7% (P<0.001). Subcutaneous and intraabdominal fat decreased by 30.9% and 46.0%, respectively, after 1 yr (both P<0.001), but demonstrated a partial regain thereafter. Bone mineral density at the lumbar spine, femoral neck, and trochanter gradually increased by 9.6%, 11.1%, and 16.2%, respectively (all P<0.001). Left ventricular mass exceeded baseline values by 14.1% after 1 yr (P<0.001), but returned to pretreatment values thereafter. Stroke volume and cardiac output increased by 16.3% (P = 0.002) and 33.4% (P<0.001), respectively. Maximal work load increased from 189+/-30 to 232+/-41 watts (P<0.001). Thus, long term GH replacement is safe and beneficial. It improves cardiac performance without inducing left ventricular hypertrophy and progressively increases bone mineral density.

Adult↗
PubMed1998

Cognitive changes during growth hormone replacement in adult men.

The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.

Adult↗
PubMed1998

Intestinal calcium absorption and bone metabolism in young adult men with childhood-onset growth hormone deficiency.

Suboptimal growth hormone (GH) replacement therapy during childhood is a major cause of osteopenia in young adults with childhood-onset GH deficiency (CO-GHD). This is primarily attributed to reduced bone formation in childhood. It is currently not known whether GHD also has adverse effects on bone metabolism in adult life. To examine the impact of GHD on calcium and bone metabolism in adults, we evaluated 50 men with CO pituitary failure at a mean age of 28.2+/-4.5 years, i.e., 8.8+/-4.1 years after the discontinuation of previous GH treatment for short stature. Thirty-three patients had multiple pituitary hormone deficiencies (MPHD) for which they received conventional replacement therapy, seventeen patients had isolated GHD (IGHD), and forty-nine age-matched men served as controls. Intestinal calcium absorption, serum calcium concentration, serum phosphate levels, and renal calcium and phosphate excretion were normal in IGHD and MPHD patients. IGHD patients had marginally elevated serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen (ICTP: 5.0+/-1.2 vs. 4.2+/-1.2 microg/l, p < 0.05), but other indices of bone turnover were normal. In contrast, MPHD patients had reduced levels of the carboxy-terminal propeptide of type I procollagen (PICP: 137+/-76 vs. 179+/-72 microg/l, p < 0.01), elevated serum ICTP levels (6.0+/-3.8 vs. 4.2+/-1.2 microg/l, p < 0.001), and reduced serum 1,25-dihydroxyvitamin D levels (55.1+/-16.7 vs. 73.0+/-23.0 pmol/l, p < 0.001). Multivariate regression analysis showed that the serum levels of bone resorption and bone formation markers in MPHD patients were correlated with the hydrocortisone, thyroxine, and testosterone replacement doses. There was no relationship with serum insulin-like growth factor I concentration. Panhypopituitary adults receiving conventional hormone replacement therapy are at risk to develop osteopenia either caused by reduced bone formation or by increased bone resorption activity. Predominantly, these abnormalities result from nonoptimal thyroid, gonadal, or adrenal hormone replacement therapy. GHD is not an important factor. In adults, GHD does not adversely affect intestinal calcium absorption or bone formation activity. Bone resorption activity may be slightly higher than normal, but the abnormality is too small to expect substantial bone loss as a consequence of GHD.

Adult↗
PubMed1997

Growth hormone substitution in adult growth hormone-deficient men augments androgen effects on the skin.

OBJECTIVE: To assess whether growth hormone (GH) administration to adult GH-deficient men leads to increased sexual hair. The sexual hair scores are subnormal in these patients, even in the presence of normal serum androgen levels. PATIENTS: Forty-six adult men with childhood-onset of GH deficiency of whom 25 were androgen deficient and received replacement. DESIGN: Double-blind and placebo-controlled. Of the 46 patients, 33 started immediately with GH administration; the remaining 13 received placebo for the first 6 months followed by GH for the next 6 months. Sixty-one age-matched healthy men with normal height and serum concentrations of IGF-I served as a comparison group. MEASUREMENTS: Hair scores at 13 defined body regions were assessed before, and after 6 and 12 months of the intervention. At the same time levels of IGF-I, dehydroepiandrosterone sulphate, androstenedione, dihydrotestosterone (DHT), testosterone and sex hormone binding globulin (SHBG) were measured. From the latter two, the free androgen index (FAI) was calculated. RESULTS: Before GH administration, hair scores in the GH deficient patients were lower than in the comparison group. In the 33 men treated with GH from the beginning, there was an increase in hair scores after 6 months. The increase in hair scores was not seen during 6 months of placebo treatment. When the placebo group switched to GH administration, their hair scores had also significantly increased after 6 months of GH substitution therapy. Upon GH administration both levels of SHBG and testosterone/DHT declined while the FAI remained unchanged. CONCLUSION: GH substitution therapy to GH deficient men has an auxiliary effect on androgen action in the skin without an increase of the FAI.

Adult↗
PubMed1997

Guidelines for optimizing growth hormone replacement therapy in adults.

To minimize the rate of side-effects, a retrospective analysis of 28 studies of GH replacement therapy in adults indicates that the maintenance dose should usually not exceed 1.0 IU/m2/day (about 1.5-2.0 IU/day) in GHD patients 40-60 years old, or 1.5 IU/m2/day (about 2.5-3.0 IU/day) in GHD patients 20-40 years old. GHD women may tolerate, and in fact may need, higher replacement doses, though this issue requires further investigation. GH treatment should be started at a low dose, i.e. about 1.0 IU/day, and increased gradually, by about 0.5 IU per month, until the target dose is reached. In the absence of side-effects, the GH dose may be either too low, adequate, or too high. Measurement of GH-dependent serum markers provides the most promising approach to detect both GH depletion and excess, with serum IGF-I concentration the current method of choice. Clinical awareness of symptoms of GH excess remains important, however, particularly in patients with IGF-I levels in the high normal range.

Adult↗
PubMed1997

The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men.

We investigated the effects of GH on bone structure and turnover by histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28 +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had multiple pituitary hormone deficiencies. Patients were randomly assigned to four treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69, and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the subsequent 6 months. GH treatment resulted in an increase of cortical thickness from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume did not change. Bone formation variables increased significantly: osteoid surface increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25 +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased significantly (P = 0.001), whereas the resorption period, including reversal phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a stimulated bone turnover as a result of GH treatment and a shorter resorption and reversal time. The increased turnover did not result in an increased trabecular bone volume, but the cortical thickness increased significantly.

Adult↗
PubMed1996

Glycoalkaloids selectively permeabilize cholesterol containing biomembranes.

The effects of the glycoalkaloids alpha-solanine, alpha-chaconine and alpha-tomatine on different cell types were studied in order to investigate the membrane action of these compounds. Hemolysis of erythrocytes was compared to 6-carboxyfluorescein leakage from both ghosts and erythrocyte lipid vesicles, whereas leakage of enzymes from mitochondria and the apical and baso-lateral side of Caco-2 cells was determined. Furthermore, the effects of glycoalkaloids on the gap-junctional communication between Caco-2 cells was studied. From these experiments, it was found that glycoalkaloids specifically induced membrane disruptive effects of cholesterol containing membranes as was previously reported in model membrane studies. In addition, alpha-chaconine was found to selectively decrease gap-junctional intercellular communication. Furthermore, the glycoalkaloids were more potent in permeabilizing the outer membrane of mitochondria compared to digitonin at the low concentrations used.

Adenylate Kinase↗