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Biomedical subjects

B Keymeulen

Publications and source records attributed to B Keymeulen.

33 records · Page 2Linked to original sources

111In-octreotide scintigraphy: a tool to select patients with endocrine pancreatic tumors for octreotide treatment?

The results of octreotide scintigraphy, performed in two patients with malignant endocrine pancreatic tumors, were compared with the effect of somatostatin-14 and its analogue octreotide on hormonal levels and clinical outcome. Radiolabeled octreotide failed to demonstrate any tumor localisation in a patient with a malignant insulinoma. Nevertheless, IV injection of somatostatin and octreotide resulted in a significant decrease in peripheral insulin levels. Moreover in this patient, chronic treatment with a high dose of octreotide subcutaneously was able to transiently lower the incidence of hypoglycemic events. In a second patient with metastatic PP-oma, 111In-octreotide disclosed a pancreatic tumor in the tail of the pancreas and metastatic supraclavicular lymph nodes. In this patient IV administration of somatostatin and octreotide inhibited the hormonal secretion of the tumor but subcutaneous injection of octreotide induced hardly any decrease in plasma PP levels and failed to affect tumor growth. These observations find a possible reason for this in the heterogeneous affinity of the somatostatin receptors in endocrine pancreatic tumors. They indicate that octreotide scintigraphy alone should not be used to select patients with neuroendocrine tumors who can benefit from chronic treatment with the somatostatin analogue.

Adult↗

Regional cerebral hypoperfusion in long-term type 1 (insulin-dependent) diabetic patients: relation to hypoglycaemic events.

Regional distribution of cerebral blood flow was determined semi-quantitatively with 99Tcm-HMPAO brain SPET under basal conditions in Type 1 (insulin-dependent) diabetic patients of recent onset and longer disease duration, and related to metabolic control and history of hypoglycaemic events. Long-term diabetic patients showed significantly more alterations in regional cerebral blood flow than diabetics of recent onset and healthy controls. Regional hypoperfusion, predominantly localized in the fronto-temporal cortex, was almost exclusively observed in patients with long-term diabetes. The latter finding was related to lower HbA1c levels (i.e. better metabolic control) and to the frequency of impending hypoglycaemia, but not to age of the patient, duration of diabetes or to chronic diabetes complications. The incidence of hypoperfusion was comparable in patient groups with or without a medical history of hypoglycaemic coma. However, regions of hypoperfusion were larger in the patients who had experienced hypoglycaemic coma. It is concluded that regional cerebral hypoperfusion in long-term Type 1 (insulin-dependent) diabetics, as evidenced by HMPAO-SPET can be related to the frequency and degree of hypoglycaemic events and to tight metabolic control, which is however at the expense of an increased risk of recurrent hypoglycaemia.

Adult↗

Proliferation and hypertrophy of liver cells surrounding islet grafts in diabetic recipient rats.

The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 +/- 72 microns 2 in diabetic islet recipients vs. 382 +/- 42 microns 2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 +/- 1.1 g to 13.8 +/- 2.2 g on posttransplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular nutrients. Progressive revascularization of the implant sites and overall metabolic normalization are thought to explain the return of a normal liver histology by the third week after transplantation. In conclusion, intraportal islet grafts exert profound effects on the liver of diabetic rat recipients. The morphological features of the implant sites may serve as markers for the function of the islet grafts as well as for the adaptive capacity of the recipient liver.

Animals↗

Progressive diaphyseal dysplasia (Camurati-Engelmann's disease). Improvement of clinical signs and of bone scintigraphy during pregnancy.

The case of a woman suffering from progressive diaphyseal dysplasia is presented. Characteristic symptoms of crippling pain in both legs, severe aching in both forearms, and episodic temporofrontal and occipital headache were only partially regulated by corticosteroid treatment. However, pregnancy resulted in a progressive disappearance of these symptoms, allowing withdrawal of steroid treatment. Tc-99m MDP scintigraphy performed immediately after delivery showed a decrease of the intense uptake in the forearms, tibiae, and skull, which had been documented prior to pregnancy. However, widespread pain recurred within 6 weeks after delivery, accompanied by a recurrence of multiple severely hyperactive foci on bone scintigraphy. Alterations of immune modulated processes and changes in bone mineral homeostasis and in endogenous cortisol metabolism during pregnancy can be considered as possible explanations for the temporary improvement in clinical and scintigraphic signs of progressive diaphyseal dysplasia in this patient.

Adult↗

Immunointervention in type 1 (insulin-dependent) diabetes mellitus.

The hitherto identified hallmarks of the autoimmune aspects in Type 1 diabetes are reviewed. Their implication in the disclosure of the pre-clinical phase of the disease is put forward. The possible delineation of this pre-diabetic phase can lead to an early immunotherapeutic approach. The effect of immunomodulation by agents such as azathioprine, cyclosporin A and nicotinamide in newly diagnosed diabetes and the use of some of these drugs in clinical trials on pre-diabetic individuals are discussed.

Animals↗

Type 1 (insulin-dependent) diabetes mellitus: an autoimmune, predictable and preventable disease? Lessons from national registries and new challenges to clinical biology.

Type 1 (insulin-dependent) diabetes mellitus is a frequent chronic disease that affects children as well as adults. The disease keeps a life-long burden on patients, their environment and society. Although still incompletely understood, its pathogenesis becomes progressively unravelled. Autoimmune phenomena play an important role, be it as underlying cause or as consequence or innocent bystanders of another primary event. Much of the present knowledge on environmental and genetic triggers for the slow islet beta-cell destruction culminating in clinically overt disease has been acquired through national diabetes registries. The latter represent confidential data- and blood sample banks that collect epidemiological, clinical and biological information from as many new cases as possible within a given area. These registries operate along international guidelines and offer a worldwide framework for optimizing prediction of clinically overt disease in individuals at risk by means of specialized clinical biological tests, carried out in reference laboratories under international quality control surveillance. Better understanding of pathogenesis and predictability of Type 1 diabetes also creates perspectives for disease prevention. Collaborative efforts of national registries provide the methodology of choice to assess the effectiveness of proposed pharmacological or immunological interventions. Several international trials are being contemplated for the near future. Clinical biology will play an important role for selection of the subjects and their further monitoring.

Adolescent↗

Semiquantitative analysis of cerebral blood flow by means of 99Tcm-HMPAO SPECT in individuals before and after a high altitude Himalayan expedition.

Nine members of the 'Belgian Tibet Expedition 1991' underwent a 99Tcm-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission computed tomographic study before and after their stay at high altitude. Cerebral and cerebellar activity were analysed in three circumference profiles, representing the lower, middle and upper transaxial sections of the brain. The count value of each volume element (VE) was normalized to the maximum cerebellar value. In order to compare individual regional cerebral blood flow (rCBF) before and after the expedition, the relative differences in rCBF were calculated for each VE as: rel delta (%) = 100 x (value after expedition - value before expedition)/value before expedition. In 4/9 cases regional rel delta values were negative in most cortical regions; in 3/9 individuals nonsignificant changes were found and 2/9 climbers showed a positive rel delta value in most cortical regions. For the group as a whole there was (1) a mean decrease of 1.7% in global cortical CBF and (2) a significantly (P < 0.01) diminished rCBF was observed in both temporal and the left frontotemporal areas.

Adult↗

The effect of insulin treatment on function of intraportally grafted islets in streptozotocin-diabetic rats.

This study examines whether a 10-week period of daily insulin injections following intraportal islet transplantation improves the metabolic state in streptozotocin-diabetic recipients of a suboptimal number of beta cells. In recipients receiving 0.5 million beta cells, insulin treatment increased the number of animals with normal basal glycemia (from 2/6 to 7/8) and normal serum fructosamine (from 1/6 to 6/8). However, during the four weeks following a 10-week insulin regimen, this beneficial effect was lost and no differences were noticed in glucose tolerance curves and hepatic insulin reserves of insulin-treated and untreated recipients. In recipients receiving 1.1 million beta cells, administration of insulin did not influence the number of animals with normal basal glycemia (7/7 in both groups) or with normal serum fructosamine (5/7 versus 4 to 6/7) during the period of treatment or during the subsequent 4 weeks; prior insulin treatment did not improve glucose tolerance curves but reduced the hepatic insulin reserves by one-third. It is concluded that insulin injections can improve the metabolic state in recipients of an insufficient islet mass but do not enhance the metabolic capacity or insulin reserves of a hepatic islet implant. The reduced hepatic insulin content in one group of insulin-treated recipients raises the possibility that supplements of insulin injections reduce the size of grafted insulin reserves.

Animals↗

Hepatic artery aneurysm. Case reports with review of the literature.

Two cases of hepatic artery aneurysm are reported. The first presented as obstructive jaundice, the second as an upper gastrointestinal bleeding. The diagnosis was made by performing ultrasound, CT-scan and angiography. In both cases surgery was the treatment. However, in some cases, interventional angiography with embolisation of the affected vessel offers an alternative treatment.

Aged↗

Effect of donor islet mass on metabolic normalization in streptozotocin-diabetic rats.

The effect of donor islet mass on the metabolic normalization in streptozotocin-diabetic rats was examined by comparing normal control rats with two transplant groups receiving 800 or 2,000 islets intraportally, i.e. grafts containing respectively, 0.8 or 2 million Beta cells at 70% purity. After transplantation, basal glycaemia and daily urine volumes normalized in all recipients and remained normal in both groups over the 20-week follow-up period. After intragastric glucose challenge, the 800-islet group exceeded the normal range of glycaemia at all tested time points (0-120 min) whereas the 2,000-islet group exhibited higher glycaemia only at 15 and 30 min; no deterioration in glucose tolerance occurred during the 20-week follow-up. Both transplant groups presented lower serum fructosamine levels than diabetic control rats, normal levels being maintained only in the 2000-islet group. At post-transplantation week 21, both recipient groups exhibited the same body weight as age-matched normal control rats, but their serum triglyceride levels were significantly higher. Hepatic insulin contents were comparable to the insulin contents of the grafts at the time of implantation, representing 16 or 40% of the pancreatic insulin content in the age-matched control rats. Although islet grafts with 0.8 million Beta cells can restore basal glycaemia in adult streptozotocin-diabetic rats, implants of 2 million Beta cells are necessary to correct other parameters of glucose homeostasis. The present data indicate the need of determining the number of grafted Beta cells in studies on the metabolic outcome of islet cell transplantation. DNA content and percentage of Beta cells in the graft are proposed as useful parameters.

Analysis of Variance↗

Detection of autoantibodies against islet amyloid polypeptide in human serum. Lack of association with type 1 (insulin-dependent) diabetes mellitus, or with conditions favouring amyloid deposition in islets. The Belgian Diabetes Registry.

A radiobinding assay for the detection of autoantibodies against islet amyloid polypeptide was developed, analytically validated, and--in parallel with a similar assay for the detection of autoantibodies against insulin--applied to sera from recent-onset Type 1 (insulin-dependent) diabetic patients and from age- and sex-matched control subjects. There was no difference in islet amyloid polypeptide autoantibody titres between patient groups and matched control subjects, nor within subject groups according to age. At onset of Type 1 diabetes, elevated islet amyloid polypeptide-autoantibody levels (> 97th percentile of control subjects) were only detected in 1 of 30 patients aged 0-19 years and in 2 of 35 patients aged 20-39 years. By contrast, insulin autoantibodies were frequently demonstrated, in particular at onset of diabetes under age 20 (0-19 years: 18 of 30 patients; 20-39 years: 10 of 35 patients; p < 0.01 vs matched control subjects). Islet amyloid polypeptide autoantibodies were not detectable in 3 insulinoma patients nor in 37 patients (aged 33-70 years) with Type 2 diabetes (vs 1 of 40 in matched control subjects). In positive serum, adsorption onto protein A-Sepharose removed islet amyloid polypeptide binding activity, hereby confirming its antibody nature. In conclusion, Type 1 diabetes is associated with an age-dependent autoantibody reaction against insulin but not against islet amyloid polypeptide. Conditions associated with amyloid deposition in islets (Type 2 diabetes, insulinoma and ageing) do not favour the formation of autoantibodies against islet amyloid polypeptide.

Adolescent↗

Kingella kingae, a rare cause of bacterial meningitis.

A male adolescent with a history of pharyngitis developed meningitis due to Kingella kingae. This is a Gram-negative coccobacillus belonging to the family of Neisseriaceae. It is a rarely reported human pathogen, from which only 2 cases of meningitis have been described up to the present day. Our patient developed ophthalmoplegia, suggestive of basal meningitis. He was treated with penicillin G and recovered completely.

Adolescent↗

[Prevention of type 1 diabetes: interventions in mice and in humans].

Prevention of type 1 diabetes mellitus is a major challenge in health care research, but until the present day we have not succeeded in achieving this goal. Thanks to the availability of good animal models of type 1 diabetes, our insight in the pathogenesis has grown, and new possibilities of intervention have emerged. In the coming years, major advances in prevention of type 1 diabetes are to be expected.

Animals↗