Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor

Fanconi anemia (FA) is a condition that induces susceptibility to bone marrow failure, myelodysplastic syndrome (MDS), and leukemia. We report on a high incidence of expanding clonal aberrations with partial trisomies and tetrasomies of chromosome 3q in bone marrow cells of 18 of 53 FA patients analyzed, detected by conventional and molecular cytogenetics. To determine the clinical relevance of these findings, we compared the cytogenetic data, the morphologic features of the bone marrow, and the clinical course of these patients with those of 35 FA patients without clonal aberrations of 3q. The 2 groups did not differ significantly with respect to age, sex, or complementation group. There was a significant survival advantage of patients without abnormalities of chromosome 3q. Even more pronounced was the risk assessment of patients with gains of 3q material with respect to the development of morphologic MDS and acute myeloid leukemia (AML). Thus, our data from 18 patients with 3q aberrations reveal that gains of 3q are strongly associated with a poor prognosis and represent an adverse risk factor in FA.     

Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma,results of a phase II single center study

The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin’s lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m², days 1 and 8), vinorelbine (30 mg/m², days 1 and 8) and prednisone (100 mg/day, days 1–8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.     

Experimental calibration of a two-stage prism-grating system for measuring cell velocity

A new optical system for the measurement of the erythrocyte velocity in microvessels is extensively applied for the first time. It is based on the projection of the erythrocyte image onto two photodiodes through a prism grating. The differential signal of the photodiodes is proportional to the velocity. The system is comparable to those of M. Anliker, M. Casty, P. Friedli, R. Kubli, and H. Keller ((1977). Noninvasive measurement of blood flow. In “Cardiovascular Flow Dynamics and Measurement” (N. H. Hwang and N. Normann, eds.), pp. 43–88. Univ. Park Press, Baltimore) and D. W. Slaaf, J. P. S. M. Rood, G. J. Tangelder, and T. Arts ((1979). Microvasc. Res.17, S173). It measures an instantaneous velocity. The system is calibrated by a velocity which is constant over the total measuring field and by a known flow rate and profile. Concerning applicability and results the device is compared to the two-slit methods, the laser-Doppler-anemometry and high-speed cinematography.     

Intracardiac echocardiography: an ideal guiding tool for device closure of interatrial communications.

BACKGROUND: This study sought to evaluate safety and radiation exposure when using intracardiac echocardiography (ICE) in comparison to transesophageal echocardiography (TEE) in order to guide transcatheter closure of interatrial communications. METHODS: Eighty patients (44 males, 36 females, mean age 46, SD 13 years) undergoing device closure of atrial septal defect (n=12) or patent foramen ovale (n=68) had the procedure guided by ICE (n=50, group 1) or TEE (n=30, group 2). In group 1, all procedural stages were completely guided by ICE, including imaging of the interatrial communication during balloon sizing, device unfolding and release, and during the final check for adequate positioning. In group 2, exclusive implantation of devices was guided by use of TEE. RESULTS: Especially, the spatial relationship between device and cardiac structures (e.g. the ascending aorta, the interatrial septum and the superior vena cava) was accurately demonstrated in group 1. Image resolution provided by ICE was superior to that of TEE. No severe complications, including any related to ICE, were seen. Fluoroscopy time (FT) and procedure time (PT) were shorter in group 1 than in group 2 (FT: 5.5+/-1.5 min vs. 9.3+/-1.6 min, P<0.0001; PT: 31.9+/-4.6 min vs. 38.8+/-5.8 min, P<0.01). Neither sedation nor anesthesia was required in group 1. CONCLUSIONS: ICE is a safe tool to guide device closure of interatrial communications. For the patient, procedural stress and radiation exposure are negligible. ICE can be considered the guiding tool of choice for device closure, particularly when long or repeated echocardiographic viewing is required.     

A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency

Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.     

Sex differences in risk factor control of treated hypertensives: a national primary healthcare-based study in Sweden.

BACKGROUND: To evaluate potential sex differences, this study aimed to investigate blood pressure and lipid control and other risk factors for cardiovascular disease in treated hypertensive (tHT) patients from primary healthcare. DESIGN AND METHODS: This cross-sectional survey of tHT patients was carried out between 2002 and 2005 by 264 primary care physicians from Sweden who consecutively recruited 6537 tHT patients (48% men and 52% women) from medical records. RESULTS: tHT men more often reached the treatment goal for systolic/diastolic blood pressure, less than 140/90 mmHg, than tHT women (30 vs. 26%, P<0.01). Men had lower systolic blood pressure than women, however, women had lower diastolic blood pressure and higher pulse pressure. More tHT women had total cholesterol>or=5.0 mmol/l than corresponding men (75 vs. 64% P<0.001). Men more often had diabetes (25 vs. 20% P<0.001), left ventricular hypertrophy (20 vs. 16% P<0.001), and microalbuminuria (24 vs. 16% P<0.001). Women were more often treated with diuretics (64 vs. 48%) and beta-receptor blockers (54 vs. 51%), and men more often treated with angiotensin-converting enzyme inhibitors (27 vs. 18%), calcium channel blockers (34 vs. 26%), and lipid-lowering drugs (34 vs. 29%). CONCLUSION: A need still exists for more intensified treatment of elevated blood pressure and hypercholesterolemia, especially in women. In hypertensives of both sexes, smoking and other risk factors also need to be addressed to reduce the risk of cardiovascular disease.     

Discriminant analysis of factors distinguishing patients with functional dyspepsia from patients with duodenal ulcer

Patients with duodenal ulcer or functional dyspepsia do not differ on dyspeptic symptoms. The aim of the present study was to test the hypothesis that functional dyspepsia and duodenal ulcer are two different diagnostic entities by examining the discriminating power of several anamnestic, biological, and psychosocial variables. Ninety-four patients with duodenal ulcer and 86 patients with functional dyspepsia were included. Anamnestic data, global assessment,Helicobacter pylori status, blood group, Lewis^a+ phenotype, and several measures of psychological distress and somatic complaints were registered. Compared to patients with functional dyspepsia, the duodenal ulcer patients were more often infected byHelicobacter pylori and had their stomach discomfort more often relieved by eating. Compared to patients with duodenal ulcer, patients with functional dyspepsia had higher scores of depression, trait anxiety, general psychopathology and different somatic complaints (called somatization). They were also less satisfied with the health care system, their disorder had a greater negative impact on their quality of life, and their global assessment of own health was poorer. Discriminant analysis including age, smoking,Helicobacter pylori status, global assessment, and somatic complaint classified 86.1% of the patients correctly (77.9% of the patients with functional dyspepsia and 93.6% of the patients with duodenal ulcer). It is concluded that duodenal ulcer and functional dyspepsia are two separate diagnostic entities. Patients with duodenal ulcer are older, smoke more often, and almost all are infected withHelicobacter pylori, while patients with functional dyspepsia are characterized by somatization and a negative assessment of their own health.