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.     

PAPULAR-PURPURIC GLOVES-AND-SOCKS SYNDROME

Background and Objective. Papular-purpuric gloves-and-socks syndrome (PPGSS) is a recently described dermatosis in which human parvovirus B19 (HPV B19) has been implicated as etiologic agent; however, it is suspected that PPGSS may be caused by various agents. This study was designed to survey the general characteristics of PPGSS and to determine the role of HPV B19 in its etiology. Methods. We analyzed data from 21 patients and examined serum samples from three new cases for various viruses. Results. The PPGSS displays a striking uniform clinical pattern. Histologic and immunofluorescence findings are nonspecific. Seroconversion of HPV B19 was reported in six cases and confirmed in two of our patients. In only one case was a possible causative role of Coxsackie virus B6 suggested consistently. Conclusions. The PPGSS represents a distinctive dermatosis and a manifestation of HPV B19 infection. Unlike erythema infectiosum, anti-HPV B19 antibodies seem to develop later after onset of the skin eruption and while viremia is still present.     

Self-reported level of and factors influencing the compliance to desferrioxamine therapy in multitransfused thalassaemias

Aim: To analyse the self‐reported degree of and factors influencing the compliance to desferrioxamine (DFO) therapy in children with transfusion‐dependent thalassaemia major in Malaysia. Methods: A cross‐sectional study was conducted on all children with thalassaemia major on DFO attending Likas Hospital, Sabah, in September 2008. Patients or carer‐providers were interviewed to report on the degree of compliance as either highly (administering >90% of DFO), moderately (51–90%), poorly (1%–50%) or non‐compliant (0%) to DFO in the preceding month. The latest serum ferritin levels were noted. Results: The median (range) age at first blood transfusion of these 139 (73 males, median (range) age at interview: 9.0 years (2–16 years)) patients were 1.0 year (2 months to 10 years). The median (range) duration of regular DFO therapy was 2 years (2 months to 10 years). Forty‐three (31%) of the patients reported themselves to be highly compliant, 70 (50%) moderately and 26 (19%) poorly or non‐compliant. Multivariate analysis showed that a lower family income negatively affected the degree of compliance, while family support positively affected the degree of compliance to DFO. No correlation existed between self‐reported degree of compliance and latest serum ferritin level (6444 ± µmol/L; P = 0.186). Conclusion: The self‐reported compliance to DFO therapy was moderate in this cohort of patients with thalassaemia major in Malaysia. The serum ferritin level was high, possibly because of the relatively short duration of DFO therapy and compliance. Oral iron chelator should be considered to improve the compliance to iron chelation.     

Incidence and Predictors of Permanent Pacemaker Requirement after Transcatheter Aortic Valve Implantation with a Self‐Expanding Bioprosthesis

Background: Previous reports have suggested the occurrence of cardiac conduction disorders and permanent pacemaker (PPM) requirement after transcatheter aortic valve implantation (TAVI). Based on a single‐center experience, we aim to assess the incidence of postprocedural conduction disorders, need for PPM, and its determinants after TAVI with a self‐expanding bioprosthesis. Methods: From August 2007 to October 2009, 32 consecutive patients underwent TAVI with the Medtronic CoreValve (MCV) System (Medtronic Inc., Minneapolis, MN, USA). Three patients paced at baseline and two cases of procedure‐related mortality were excluded. We analyzed the 12‐lead electrocardiogram at baseline, immediately after procedure and at discharge. Requirements for PPM were documented and potential clinical, electrophysiological, echocardiographic, and procedural predictors of PPM requirement were studied. Results: After TAVI, eight patients (29.6%) required PPM implantation due to high‐grade atrioventricular (AV) block. The prevalence of left bundle branch block increased from 13.8% to 57.7% directly after implantation (P = 0.001). Need for PPM was correlated to the depth of prosthesis implantation (r = 0.590; P = 0.001). At a cutoff point of 10.1 mm, the likelihood of pacemaker could be predicted with 87.5% sensitivity and 74% specificity and a receiver operator characteristic curve area of 0.86 ± 0.07 (P = 0.003). Of the seven patients with preexisting right bundle branch block (RBBB), four (57.1%) required PPM implantation after TAVI. Conclusions: High‐grade AV block requiring PPM implantation is a common complication following TAVI and could be predicted by a deeper implantation of the prosthesis. Patients with preexisting RBBB also seem to be at risk for the development of high‐grade AV block and subsequent pacemaker implantation. (PACE 2010; 1364–1372)     

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.     

Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas

LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)- associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV- LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non- Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV- associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.     

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.