Immediate ultrastructural effects of endothelin-1 on rabbit basilar artery

Summary In this study intra-arterial Endothelin-1 was applied to rabbit basilar arteries and morphological findings were compared between two groups who were either perfusion fixed or immersion fixed. We planned to establish the quantitative dimension of the drug-induced morphological alterations, independent of the fixation technique's effect.There was an abundance of collagenous fibres deposited among the smooth muscle cells which was not observed in control arteries and after immersion fixation. These degenerative changes are similar to the finding following subarachnoid haemorrhage. The only fixation-related difference was the fact that lamina elastica interna was not corrugated in the perfusion fixation group.It is concluded that, the observed changes in the connective tissue of the arterial wall alter the passive elastic properties and so affect the degree of the response to the vasoactive messengers.     

Human lymphocyte antigens (HLA) and Graves' disease in Turkey

To evaluate the association of HLA types with Turkish patients with Graves' disease, HLA typing, clinical findings, and thyroid antibodies were correlated. The HLA types, clinical findings (ophthalmopathy and age at onset), and thyroid stimulating hormone (TSH) receptor (TRAb) and antithyroid microsomal antibodies (MAb) were analyzed. Seventy Turkish patients with Graves' disease and 306 control subjects were assessed. Serological HLA typing was performed in HLA A, B, C, DR, and DQ loci. There was a significantly increased prevalence of HLA B8, B49, DR3, DR4, and DR10 in Graves' disease. The association of Graves' disease with HLA DR3 was found to be less strong than previously described. The HLA DR4 antigen may contribute to the predisposition of Graves' disease in Turkey. The results suggest that HLA B7, B13, DR7, DQw2, and DQw3 may confer a protective effect for Graves' disease in Turkey. Patients carrying HLA B12, B18, and B44 haplotypes had a tendency to develop the disease at a later age. The difference from the other studies may be the result of the selection of the controls; in part, of the variability in serological typing reagents; and, also, of the rather weak HLA associations with the disease.This study was presented in part at the Annual Meeting of the National Endocrinology and Diabetes Association, Bursa, Turkey, May 25–28, 1992.     

Recent experience with Moyamoya disease in Turkey

A series of moyamoya patients is presented. Angiographic findings, outcome of revascularization surgery and a young case with moyamoya disease and hyperphosphatemia are reported. Thirteen patients (6 males and 7 females; age range 2–50 years) were included in the study group. Findings of the patients at presentation were intracranial haemorrhage in two adult cases and sequelae of cerebral ischemia in the rest of the group. One young girl had hyperphosphataemia. Angiography showed distal internal carotid or proximal anterior and middle cerebral artery stenosis, unique collaterals, microaneurysm of the posterior lateral choroidal artery and flow-related changes in the posterior circulation. In 3 patients, encephalo-duro-arterio-synangiosis (EDAS) and burrholes were performed at surgery. Follow-up angiograms of these patients showed revascularization. Moyamoya, a rare but potentially devastating disease, must be addressed as a cause of haemorrhagic and ischaemic cerebral events. Received: 19 January 1999; Revised: 14 April 1999; Accepted: 17 May 1999     

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.     

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.     

Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis

Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments.     

Morphometric Measurements of the Cranium in Patients with Chiari Type I Malformation and Comparison with the Normal Population

Summary. Summary.   Background: To determine the degree of development of the posterior fossa and signs of occipital dysplasia in patients with Chiari type I malformation by morphometric measurements.   Methods: In 22 patients with Chiari type I malformation, distance, surface area and angle values reflecting the degree of development of the posterior fossa were measured and compared with the measurements of 21 normal subjects.   Findings: In patients with Chiari type I malformation, the depth of the posterior fossa, the length of the clivus reflecting development of the basi-occiput and Klaus' index were significantly shorter than in normal subjects (p<0.001, p=0.007, and p<0.001, respectively). The ratios of the depth of the posterior fossa to the height of the supratentorial region and Twining's line reflecting anteroposterior distance of the posterior fossa were also significantly smaller in the Chiari group (p<0.001 for both). In sagittal section, the surface area of the bony part of the posterior fossa and the ratio of this area to the area of the supratentorial region were significantly smaller than in normal subjects (p=0.038 and p=0.002, respectively). The angle measurements of the cranial base (basal angle, Boogard's angle and nasion-basion-opisthion angle) showed that there was an evident tendency for platibasia in the Chiari group (p=0.04, p=0.004, p<0.001, respectively). In addition, it was shown by measuring tentorium-twining's line angle that the tentorium was steeper in the Chiari group than normal subjects.   Interpretation: These results support the opinion, which claims the existence of underdevelopment of the occipital bone and posterior fossa in patients with Chiari type I malformation.     

Case of disseminated Langerhans' cell histiocytosis presenting with sclerosing cholangitis

Langerhans' cell histiocytosis is an uncommon disorder of childhood with a wide clinical spectrum. Although liver involvement is common in the disseminated form, presentation with hepatic disfunction is unusual. We describe an 18-month-old girl who presented with intrahepatic cholestasis. The patient was shown to have Langerhans' cell histiocytosis with sclerosing cholangitis by liver biopsy and skin biopsy showing S-100, CD1a positivity, and Birbeck granules by electron microscopy.     

Single-voxel MR spectroscopy and diffusion-weighted MRI in two patients with <Emphasis Type="SmallCaps">l</Emphasis>-2-hydroxyglutaric aciduria

l-2-Hydroxyglutaric aciduria is a rare inherited, neurometabolic disorder. The underlying metabolic defect and the pathophysiology of l-2-hydroxyglutaric aciduria have not yet been defined. We present MR spectroscopy and cranial MR imaging findings, including diffusion-weighted sequences in two male siblings (aged 10 and 12 years). MR spectroscopy revealed a multiplet at 2.10–2.50 ppm and two broad peaks at 0.9–1.6 ppm. The multiplet at 2.10–2.50 ppm might have been created by elevated glutamate and glutamine or l-2-hydroxyglutaric acid itself, which has a similar chemical structure to glutamate. Diffusion-weighted images demonstrated increased diffusion of water molecules in the white-matter lesions.     

Determination of endothelial function and early atherosclerotic changes in healthy obese women

The aim of this study was to determine the associations between vascular endothelial function, intima-media thickness (IMT) of the common carotid artery and anthropometric/metabolic parameters in healthy obese women without obesity-related metabolic complications and age-matched healthy lean controls. Twenty-four obese [body mass index (BMI) > 30 kg/m2; age 31.4 +/- 7.4 yr] and 14 lean (BMI < 24 kg/m2; age 30.5 +/- 7.2 yr) women were studied. All of the subjects had normolipemia. Insulin resistance was calculated according to the homeostasis model assessment (HOMA) formula. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. IMT of the common carotid artery was calculated from high-resolution ultrasound imaging of the two common carotid arteries. Obese and lean women were matched with respect to age, smoking status, blood pressure, glucose, insulin concentrations and HOMA. IMT of common carotid artery was significantly higher (0.56 +/- 0.09 vs 0.45 +/- 0.06 mm, p < 0.001) and FMD (percentage of change from baseline) was significantly lower (13.3 +/- 6.5% vs 25.2 +/- 13.9%,p < 0.001) in the obese subjects. Lipid profile, blood pressure, indirect measurement of insulin resistance, leptin concentrations and anthropometric parameters did not predict the FMD or IMT in the obese and lean groups. It is concluded that even in healthy obese women with a normal metabolic profile, deterioration in endothelial function and early atherosclerotic changes are evident compared with healthy lean counterparts. Some undetermined factors in our study other than obesity-related well-known risk factors could be responsible for this observation.