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Biomedical subjects

H Mulder

Publications and source records attributed to H Mulder.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparative prospective, double-blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of Paget's disease of bone.

OBJECTIVE: To compare the efficacy and safety of tiludronate and etidronate at the same dosage (400 mg/day) for the treatment of active Paget's disease of bone. METHODS: We studied 234 patients with radiologic lesions characteristic of Paget's disease of bone and serum alkaline phosphatase (AP) concentrations at least twice the upper limit of normal, in a prospective, randomized, double-blind, multicenter clinical trial lasting 6 months. Patients were randomly allocated into 1 of 3 treatment groups: tiludronate for 3 months followed by placebo for 3 months, tiludronate for 6 months, or etidronate for 6 months. Serum AP levels and urinary hydroxyproline excretion were measured at baseline and after 3 months and 6 months. Patients with a reduction of at least 50% in the serum AP concentration were considered to be responders. RESULTS: After 3 months, the proportion of responders was higher in the tiludronate group (57.4%) than in the etidronate group (13.9%) (P < 0.0001). In the etidronate group, this percentage was lower among patients who had received previous treatment with a bisphosphonate (2.3%) than among those who had not (28.6%) (P < 0.01). Previous bisphosphonate treatment was not associated with response in the tiludronate group. After 6 months, the proportion of responders did not differ between the 2 tiludronate groups (60.3% and 70.1%), but was lower in the etidronate group (25.3%) (P < 0.0001). There was a higher proportion of patients with treatment-resistant disease (< 25% reduction of serum AP) in the etidronate group (51.9%) than in the tiludronate 3-month group (17.9%) or the tiludronate 6-month group (19.5%) (P < 0.0001). Gastrointestinal disturbances were more common, and occurred earlier, with tiludronate, but they were mostly mild, requiring no treatment. CONCLUSION: Tiludronate at 400 mg/day for 3 months or 6 months is more effective than the same dosage of etidronate for 6 months in the treatment of Paget's disease.

Adult↗
PubMed1995

Non-parallelism of islet amyloid polypeptide (amylin) and insulin gene expression in rats islets following dexamethasone treatment.

Islet amyloid polypeptide (IAPP), a novel islet hormone candidate, has been reported to be over-expressed relative to insulin in rats following dexamethasone treatment. In order to investigate the expression of IAPP and insulin following dexamethasone treatment of rats for 12 days, we applied in situ hybridization and immunocytochemistry, allowing us to evaluate islet changes in gene expression and morphology. Tissue concentrations of IAPP and insulin were measured by radioimmunoassay. A low dose of dexamethasone (0.2 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 249 +/- 13% and 150 +/- 24% of controls, respectively (p < 0.001 and p < 0.01). A high dose of dexamethasone (2.0 mg/kg daily) increased the islet levels of IAPP and insulin mRNA to 490 +/- 13% and 203 +/- 9% of controls, respectively (p < 0.001 and p < 0.001). The pancreatic concentration of IAPP increased more than that of insulin (p < 0.05). Morphometric analysis revealed that dexamethasone treatment induced both hyperplasia and hypertrophy of insulin cells. Changes in the cellular localization of IAPP and insulin mRNA were not observed. Thus, we conclude that the increased level of IAPP mRNA is due to both an increase at the cellular level as well as hyperplasia/hypertrophy of insulin cells. In contrast, the increased level of insulin mRNA appears to be due to hyperplasia/hypertrophy of insulin cells, since insulin gene expression decreased at the cellular level (p < 0.001 vs controls). These observations provide further evidence that IAPP and insulin gene expression are regulated in a non-parallel fashion, which may be relevant to the pathogenesis of non-insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1995

Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis.

PURPOSE: To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis. PATIENTS AND METHODS: Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times. RESULTS: Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03). CONCLUSIONS: Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses.

Absorptiometry, Photon↗
PubMed1995

A series of carcinoid tumours of the breast.

Eight patients with a carcinoid tumour of the breast were treated between 1985 and 1992. All were reviewed for their history, physical examination, mammographic and ultrasound features. Staining methods according to Grimelius, with H&E and Neurone Specific Enolase were repeated, and all were positive. In only one patient was a positive axillary lymph node found. No recurrences were seen during follow-up. In agreement with the available literature there seems to be a less aggressive behaviour of carcinoid tumours of the breast in patients over 65 years of age. When a carcinoid tumour is suspected in this age group, the diagnosis can be confirmed by (immuno)histological analysis of a needle biopsy. If the diagnosis of carcinoid is confirmed, a limited operation, without an axillary lymph node dissection, may be considered.

Aged↗
PubMed1995

Islet amyloid polypeptide (amylin) is expressed in sensory neurons.

Islet amyloid polypeptide (IAPP) or amylin is a hormone candidate predominantly expressed in insulin cells. A role for IAPP in the regulation of glucose homeostasis and the development of non-insulin-dependent diabetes mellitus has been proposed. IAPP is structurally related to the sensory neuropeptide calcitonin gene-related peptide. In the present study, using in situ hybridization, immunocytochemistry, and immunochemistry, the expression of IAPP in sensory neurons in the rat was investigated. IAPP was expressed in a population of small- to medium-sized nerve cell bodies in dorsal root ganglia from all levels and in the jugular-nodose and trigeminal ganglion; IAPP-expressing nerve cell bodies constituted a subpopulation of those expressing calcitonin gene-related peptide. In addition, IAPP-like immunoreactivity occurred in nerve cell bodies storing substance P and pituitary adenylate cyclase-activating polypeptide. IAPP-immunoreactive nerve fibers were encountered in the dorsal horns of the spinal cord, and to a lesser extent in peripheral tissues receiving sensory innervation; IAPP-immunoreactive fibers constituted a subpopulation of those containing calcitonin gene-related peptide and/or substance P. The immunochemical determinations demonstrated a low level of IAPP-like immunoreactivity in the dorsal root ganglia and spinal cord, which chromatographically coeluted with authentic rat IAPP. We conclude that IAPP is expressed in sensory neurons, thus being a novel sensory neuropeptide candidate for which a physiological role remains to be identified.

Amyloid↗
PubMed1994

Localization of hormone-sensitive lipase to rat Sertoli cells and its expression in developing and degenerating testes.

Using in situ hybridization, hormone-sensitive lipase was found to be expressed in a stage-dependent manner in Sertoli cells of rat testis. No expression was found in Leydig cells but expression in spermatids could not be excluded. These results suggest a role for hormone-sensitive lipase in the metabolism of lipid droplets in Sertoli cells, in contrast to its previously proposed function in steroid biosynthesis. The expression of testicular hormone-sensitive lipase mRNA and protein, both larger in size compared to other tissues, coincided with the onset of spermatogenesis and was dependent on scrotal localization of the testis, suggesting a temperature-dependent, pretranslational regulation of expression.

Animals↗
PubMed1994

Islet amyloid polypeptide is expressed in endocrine cells of the gastric mucosa in the rat and mouse.

BACKGROUND/AIMS: Islet amyloid polypeptide (IAPP) or amylin is a novel islet hormone candidate with a suggested role in the regulation of glucose homeostasis and the pathogenesis of non-insulin dependent diabetes mellitus. Occurrence of IAPP in the gastrointestinal tract of rats and humans has also been shown. The expression of IAPP in the stomach of the rat and mouse and the possible colocalization of IAPP and known gastric hormones were investigated in this study. METHODS: In situ hybridization, immunofluorescence, and combined in situ hybridization and immunocytochemistry were used. RESULTS: IAPP messenger RNA and IAPP-like immunoreactivity were shown in the same endocrine cells in the antrum and fundus of the rat and in the antrum of the mouse. IAPP was expressed in a major population of somatostatin-immunoreactive cells as well as in small populations of gastrin- and peptide YY-immunoreactive cells. CONCLUSIONS: Our results establish the synthesis and storage of IAPP in gastric endocrine cells in the rat and mouse. The extensive colocalization of IAPP with somatostatin and to a lesser extent with gastrin and peptide YY suggests that IAPP may modulate endocrine activity in the gastric mucosa in a paracrine and/or autocrine mode.

Amyloid↗
PubMed1994

NOS-containing neurons in the rat gut and coeliac ganglia.

Nitric oxide (NO) is considered an important inhibitory neurotransmitter in the gut. Nitric oxide synthase (NOS)-containing neurons were visualized by immunocytochemistry using antibodies against neuronal NOS in the oesophagus, the gastrointestinal tract and the coeliac ganglion of rat. NOS-containing nerve cell bodies were numerous in the myenteric but fewer in the submucous ganglia all along the gut. Synthesis of NOS in enteric nerve cell bodies was confirmed by in situ hybridization, demonstrating the presence of NOS mRNA. Varicose nerve fibers formed extensive networks in the circular smooth muscle and the myenteric ganglia. The pyloric sphincter contained abundant NOS-containing nerve fibers. NOS-containing nerve terminals were frequently found around the Brunner glands in the duodenum; scattered nerve terminals occurred in the gastric and colonic mucosa and around blood vessels in the submucosa all along the gut. The neuronal cell bodies in the coeliac ganglion were non-immunoreactive but frequently surrounded by baskets of NOS-immunoreactive nerve fibers. Double staining for NOS and neuropeptides in oesophagus, stomach and small and large intestine revealed that a small subpopulation of the NOS-containing nerve cell bodies stored in addition vasoactive intestinal peptide (VIP), and in oesophagus, stomach and small intestine also neuropeptide Y (NPY). However, NOS-containing nerve terminals, particularly those in the circular muscle of the gut, frequently contained VIP throughout the gut; in the oesophagus, stomach and the small intestine they contained also NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Pituitary adenylate cyclase activating polypeptide expression in sensory neurons.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel vasoactive intestinal peptide (VIP)-like peptide isolated from ovine hypothalami. The presence of PACAP-like immunoreactivity was recently demonstrated in nerve cell bodies of sensory ganglia in the rat. Since PACAP belongs to a large family of chemically related neuropeptides, we have, in the present study, tried to establish the synthesis of PACAP in neurons of sensory ganglia, using in situ hybridization with a 35S-labelled oligonucleotide probe complementary to PACAP mRNA. The expression of PACAP was compared to that of calcitonin gene-related peptide (CGRP) using a radiolabelled CGRP oligonucleotide probe. The PACAP probe labelled small to medium-sized neurons in the trigeminal ganglion and dorsal root ganglia at different levels, indicating the presence of PACAP mRNA. The CGRP probe labelled nerve cell bodies of varying size, outnumbering those labelled by the PACAP probe. In dorsal root ganglia, cells expressing PACAP constituted c. 10% and those expressing CGRP 46% of the total number of nerve cell bodies. Expression of PACAP was seen in a small subpopulation of cells expressing CGRP. We conclude that PACAP is synthesized in a subpopulation of neurons of sensory ganglia in the rat. Therefore, the recently described effects of PACAP--cutaneous vasodilation, potentiation of oedema formation and depression of nociceptive spinal reflexes--may be physiological and related to neurogenic inflammation and modulation of pain transmission.

Animals↗
PubMed1994

Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss.

We conducted a prospective study of etidronate's effects on corticosteroid-induced bone loss in postmenopausal women with temporal arteritis for whom high-dose prednisone therapy was indicated. Group A (n = 10) received etidronate (400 mg/day for 2 weeks, then 11 weeks off etidronate; four cycles total) and prednisone: Group B (n = 10) received only prednisone. Vertebral bone mineral density (BMD) was measured blinded by dual X-ray absorptiometry. At 3, 6 and 12 months, vertebral BMD was significantly (P < 0.01) increased in Group A and decreased in Group B, based on mean actual and percent changes in BMD and mean changes in BMD Z-score from baseline. Between-group comparisons were also significant (P < 0.002) at each time point. No adverse events related to etidronate treatment were reported. Our results suggest that corticosteroid-induced bone loss may be prevented by instituting intermittent cyclical etidronate therapy when high-dose prednisone therapy is begun. Further research into bisphosphonate use in corticosteroid-induced bone loss (with larger patient populations, longer follow-up and fracture assessment) is warranted.

Adrenal Cortex Hormones↗
PubMed1994

Prader-Willi-like phenotype in fragile X syndrome.

A 3-year-old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical-cytogenetic-molecular grounds, Prader-Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR-1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader-Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader-Willi syndrome is negative. Clinical behavior can be of help.

Body Weight↗
PubMed1993

Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study.

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.

Amyloid↗
PubMed1993

Calcitonin-testosterone interrelationship. A classic feedback system?

Calcitonin infusion in pharmacological doses reduces the serum concentration of testosterone, LH and FSH, probably by acting at the hypothalamic level. This fact, in combination with the well-known calcitonin stimulating effect of testosterone, suggests that calcitonin and testosterone are possibly acting as a classic negative feedback system.

Adult↗
PubMed1992

Normocalcemia with persistent increase of parathyroid hormone: a prospective study.

Twelve patients were followed up for 3 months after parathyroidectomy. Serial measurements of serum parathyroid hormone (PTH), calcium, and phosphate were made. Four patients had an increased serum PTH postoperatively, which was already apparent by the third postoperative day. All patients became normocalcemic. Their hyperparathyroid-like phosphate parameters indicated that we were dealing with a biologically active PTH. Using preoperative biochemical parameters it was impossible to predict which patients would have an increased PTH postparathyroidectomy (PTX). Probably the patients with high PTH post-PTX had higher parathyroid volumes. In our opinion after PTX, a normocalcemic high PTH situation should be avoided by 3 1/2 parathyroid gland extirpation in all cases.

Aged↗
PubMed1992

Pectus excavatum. A clinical study with long-term postoperative follow-up.

Between 1972 and 1987, 192 patients have been operated upon for pectus excavatum of which 152 patients were included in the study (79%). Mean age at operation was 15.3 +/- 5.5 years; 117 were male. Mean follow-up was 8.1 +/- 3.6 years. The deformity was noted before the age of 5 in 90%. Type I symmetrical and localized deformity was seen in 33.2%, type II symmetrical but diffuse depression in 23.7% and type III localized or diffuse asymmetrical deformity in 43.1%. It was considered severe in 68.9%, fair in 16.9% and mild in 14.2%. There were significantly more asymmetrical defects in the older age groups. The operation consisted of subperichondral chondrectomy, transverse sternotomy and division of the intercostal bundles at the outer limit of the chondrectomy and suturing the edge of this broad sheet of muscle and perichondrium to the anterior surface of the chest wall more laterally and under tension, elevating and stabilizing the sternum. Results were satisfactory in 83.6% (excellent 44.1%, good 39.5%). Results were not significantly influenced by age, sex, severity, type, symmetry, the extent of cartilage resection or follow-up. Results were inversely influenced by the occurrence of wound problems. The optimal age for operation is considered to be between 5 and 10 years. Both physical as well as psychological cosmetic factors may serve as an indication for operation.

Adolescent↗
PubMed1992

Assignment of the aspartylglucosaminidase gene (AGA) to 4q33----q35 based on decreased activity in a girl with a 46,XX,del(4)(q33) karyotype.

Aspartylglucosaminuria (AGU) is a recessive autosomally inherited lysosomal storage disorder due to deficiency of the enzyme aspartylglucosaminidase (AGA). The structural gene for this human enzyme (AGA) has been assigned to the region 4q21----qter. We determined the AGA activity in cultured fibroblasts of a girl with a 46,XX,del(4)(q33) karyotype. The results indicate that the girl is a hemizygote for AGA, permitting the assignment of human AGA to the region 4q33----qter.

Aspartylglucosaminuria↗