Spinocerebellar ataxia and hypergonadotropic hypogonadism associated with familial sensorineural hearing loss

Cerebellar ataxia has been described as being associated with hypogonadism for almost 100 years. In the majority of cases, hypogonadism is hypogonadotropic. The association of cerebellar ataxia with hypergonadotropic hypogonadism is a rare genetic disorder with a recessive mode of inheritance. Cerebellar ataxia and hypogonadism can also occur associated with a large spectrum of additional clinical manifestations, including mental retardation, sensorineural deafness, choroidal dystrophy, ectodermal dysplasia and short stature, and polyneuropathy. We report the case of a woman with early-onset spinocerebellar ataxia, primary amenorrhea due to hypergonadotropic hypogonadism, and late-onset sensorineural hearing loss. Additional family members from the father's side are affected with late-onset hearing loss, suggesting a dominant mode of inheritance.     

Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients

BACKGROUND: In cardiac transplant recipients, long-term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients. METHODS: Forty-eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in-depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high-performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree. RESULTS: Forty-eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5+/-5.0 micromol/L, all patients had homocysteine levels above the upper range of normal (5-15 micromol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0+/-5.9 vs. 21.9+/-3.4 micromol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis. CONCLUSIONS: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy-lowering therapy in this patient population.     

Orofacial pain in young adults and associated childhood and adulthood factors: results of the population study, Wales, United Kingdom

Abstract – Objectives: The aim of the study was to investigate the prevalence of orofacial pain (OFP) among young adults (30–31 years old) and to determine the effect of childhood and adulthood risk factors on the occurrence of OFP. Methods: Prospective cohort study to investigate dental and social effects of malocclusion and effectiveness of orthodontic treatment was conducted in Wales, United Kingdom. At 20‐year follow‐up 337 subjects aged 30–31 participated (74% from previous follow‐up aged 19–20 and 33% from the baseline) and were asked about OFP. Results: The prevalence of OFP was 23% (95% CI: 19%, 28%). Childhood factors, socio‐demographic, lifestyle, health behavior factors, history of orthodontic treatment and tooth wear were not associated with OFP. Participants with OFP were more likely to report that their teeth did not fit together properly [odds ratio (OR) = 12.4, 95% CI: 2.7–56.5) and reported previous trauma to the jaws (2.3; 1.3–4.2). Both diurnal and nocturnal teeth clenching and grinding were significantly associated with OFP (3.1; 1.4–7.1). Participants with frequent headaches had increased risk of having OFP (3.7; 1.6–8.4) while having reported 4–10 types of pain in other parts of the body other than the head, was associated with OR = 9.2 (3.7–23.0). An increased tendency to have OFP was seen in those individuals with higher levels of psychological distress (2.3; 1.4–3.9), high score on Life Event Inventory (2.6; 1.3–5.3), depressive symptoms (2.2; 1.2–4.0) and stress (2.2; 1.2–4.0). High self‐esteem associated with lower risk of OFP (0.5; 0.3–0.9). Conclusions: This study shows that OFP is frequently reported by young adults aged 30–31 and supports a multifactorial etiology with factors from many domains, including local mechanical factors, psychological and co‐morbidities. However, none of the childhood factors considered in this study were associated with OFP in adulthood.     

Renal Arterial and Venous Endothelin in Hypertensive Patients with or Without Renal Artery Stenosis

Immunoreactive endothelin (ir-ET) levels were measured in the renal veins and aorta of 43 untreated hypertensive patients immediately before renal angiography. None of the patients used antihypertensive medication. Twenty-seven patients had renal artery stenosis, 17 of which were unilateral and 10 bilateral. Seven of the 17 patients with unilateral renal artery stenosis had an elevated renin ratio. Of the 16 patients with essential hypertension 6 had a unilateral small kidney with a normal blood supply. Although there was a trend towards higher levels of ir-ET in patients with renal artery stenosis, no significant differences in endothelin levels (venous or arterial) were found between different groups of patients or groups of kidneys. More than 75% of kidneys extracted endothelin, there being no significant differences between groups of kidneys. In conclusion, our data demonstrate that endothelin levels and renal endothelin extraction are comparable in essential hypertension and in hypertension associated with renal artery stenosis. Whereas renal uptake or endothelin is the rule, some kidneys, however, release this peptide irrespective of the presence or absence of renal artery stenosis.     

Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood

Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy- 6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/− 0.47, 3.44 +/− 0.25, and 1.20 +/− 0.10 mM +/− SEM on day 7; 1.16 +/− 0.13, 1.52 +/− 0.37, and 0.16 +/− 0.02 mM on day 21; and 0.67 +/− 0.09, 0.61 +/− 0.08, and 0.06 +/− 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/− 0.09, 1.46 +/− 0.18, and 2.11 +/− 0.04 mM; 2.10 +/− 0.05, 2.07 +/− 0.17, and 2.13 +/− 0.05 mM; and 1.42 +/− 0.13, 1.37 +/− 0.13, and 1.38 +/− 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds.     

Growth Hormone Treatment in Short Children with Chronic Renal Failure and after Renal Transplantation: Combined Data from European Clinical Trials

Growth retardation is common in children with chronic renal failure (CRF). To investigate the efficacy and safety of recombinant human growth hormone treatment in such children and in children after renal transplantation, 43 prepubertal children with CRF, and 30 prepubertal and 25 pubertal patients with a renal transplant were studied. Data are reported for 31, 26 and 17 of these patients, respectively. Median height velocity increased from 4.2 to 9.8 cm/year during the first year of treatment, and to 6.8 cm/year during the second year of treatment in the patients with CRF. In the prepubertal transplant group, median height velocity changed from 3.5 to 8.4 cm/year during the first year and to 5.4 cm/year during the second year. In the pubertal transplant group, median height velocity increased from 3.2 to 6.6 cm/year during the first year and was 4.5 cm/year during the second year. The gain in height SDS for the prepubertal children in both the CRF and transplant groups was approximately 1 SD over 2 years. Treatment was well tolerated, and renal function did not change significantly in any group.     

Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits

The transporter associated with antigen processing (TAP) supplies peptides into the lumen of the endoplasmic reticulum (ER) for binding by major histocompatibility complex (MHC) class I molecules. TAP comprises two polypeptides, TAP1 and TAP2, each a 'half-transporter' encoding a transmembrane domain and a nucleotide-binding domain. Immunoprecipitation of rat TAP1 and TAP2 expressed individually in the human TAP-deficient cell line, T2, revealed that both bound the endogenously expressed HLA-A2 and -B51 class I molecules. Using HLA-encoding recombinant vaccinia viruses HLA-A*2501, -B*2704, -B*3501 and -B*4402, alleles also associated with both TAP1 and TAP2. Thus, TAP1 and TAP2 do not appear to differ in their ability to interact with MHC class I alleles. Single TAP polypeptide subunits also formed MHC class I peptide-loading complexes, and their nucleotide-binding domains retained the ability to interact with ATP, and may permit the release of peptide-loaded MHC class I molecules in the absence of a peptide transport cycle. It is also demonstrated by chemical cross-linking that TAP2, but not TAP1, has the ability to form a homodimer complex both in whole cells and in detergent lysates. Together these data indicate that single TAP polypeptide subunits possess many of the features of the TAP heterodimer, demonstrating them to be useful models in the study of ATP-binding cassette (ABC) transporters.