Subclinical trauma to perineum: a possible etiology of erectile dysfunction in young men

A substantial number of young men with erectile dysfunction have neither systemic disease nor a trauma in their history. We are familiar with impotence after major trauma but it is an unanswered question whether subclinical trauma may also induce arterial degeneration with subsequent erectile dysfunction. In a period of 36 months 129 patients underwent penile arteriography. After excluding those with major surgery, trauma or psychogenic impotence 91 angiograms were reevaluated. Special attention was paid to atherosclerotic and to focal occlusive arterial disease (> 50% stenosis) in the hypogastric-cavernous branch. 12 angiograms showed normal arteries, 59 typical atherosclerotic and 20 focal occlusive arterial disease. The mean age of patients with atherosclerosis was 53 +/- 8 years versus 35 +/- 14 years of those with focal lesions (p < 0.0001). 30% with focal arterial lesions were subject to subclinical trauma. 68% with atherosclerotic disease had clinical relevant atherosclerotic risk factors. Latency between onset of erectile dysfunction and presentation at the impotence clinic was 51 months in patients with focal lesions and 39 months in those with atherosclerotic disease (nonsignificant). We conclude that subclinical trauma of the hypogatric-cavernous arteries can induce focal arterial lesions with significant impairment of perfusion. This pathology may contribute to erectile dysfunction. These patients are significantly younger and they suffer from clinically evident impotence approximately 18 years earlier than patients whose impotence is clearly of atherosclerotic origin. Focal arterial lesions due to subclinical trauma are described for the first time as an etiology of erectile dysfunction. Further studies are needed to confirm these results.     

A logistic regression model when some events precede treatment: the effect of thrombolytic therapy for acute myocardial infarction on the risk of cardiac arrest

When outcomes occur in clinical trials before treatment can be given, neither intent-to-treat nor according-to-protocol analyses give optimal estimates of the treatment effect. A better approach employs a time-dependent variable for treatment. Intent-to-treat analyses are conservative, biasing against treatment; according-to-protocol analyses bias in favor of treatment. We show how to measure the effect of a time-dependent variable in a logistic regression using person-time intervals as units of measurement and describe appropriate methods for reporting model performance. The method is applied to develop a model to predict the probability that a patient with a myocardial infarction will have a sudden cardiac arrest within 48 hours of presentation to emergency medical services both when treated with thrombolysis and when not treated. We use a time-dependent treatment variable because many patients went into cardiac arrest while awaiting treatment. This technique has been programmed into an electrocardiograph for real-time use in an emergency department.     

T-cell large granular lymphocytic leukemia associated with pure red cell aplasia, successfully treated with cyclophosphamide

Authors report effective treatment of T-cell large granular lymphocyte (LGL) leukaemia and secondary pure cell aplasia with cyclophosphamide. The current classification of LGL proliferations is presented, with emphasis on the issues of diagnosis, clinical course and treatment. LGL proliferations are not so rare that previously thought and should be involved in the differential diagnosis of neutropenia, pure red cell aplasia, Felty's syndrome and vasculitis of unknown origin.     

Picrophilus gen. nov., fam. nov.: a novel aerobic, heterotrophic, thermoacidophilic genus and family comprising archaea capable of growth around pH 0

Two species belonging to a novel genus of archaea, designated Picrophilus oshimae and Picrophilus torridus, have been isolated from two different solfataric locations in northern Japan. One habitat harboring both organisms was a dry, extremely acidic soil (pH < 0.5) that was heated by solfataric gases to about 55 degrees C. In the laboratory both species grew heterotrophically on yeast extract and poorly on tryptone under aerobic conditions at temperatures between 45 and 65 degrees C; they grew optimally at 60 degrees C. The pH optimum was 0.7, but growth occurred even around pH 0. Under optimal conditions, the generation time was about 6 h, yielding densities of up to 10(10) cells per ml. The cells were surrounded by a highly filigreed regular tetragonal S-layer, and the core lipids of the membrane were mainly bis-phytanyltetraethers. The 16S rRNA sequences of the two species were about 3% different. The complete 16S rRNA sequence of P. oshimae was 9.3% different from that of the closest relative, Thermoplasma acidophilum. The morphology and physiological properties of the two species characterize Picrophilus as a novel genus that is a member of a novel family within the order Thermoplasmales.     

Use of magnesium sulphate in Scottish obstetric units

A case of sacrococcygeal teratoma is presented with characteristics of fetus-in-fetu. This pseudo-fetus presented a rudimentary single cavity heart, which beat at a different rate to that of the affected infant. X-ray examination showed no spinal column. This case confirms that fetus in fetu can be a remarkably complex, well-differentiated, highly organized teratoma.     

Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules

Studies on frequency and distribution pattern of TSH receptor (TSHR) and Gs alpha protein (gsp) mutations in toxic thyroid nodules (TTNs) reported conflicting results, most likely also related to the different screening methods applied and the investigation of only part of exon 10 of the TSHR. Therefore, we screened a consecutive series of 31 TTNs for both TSHR and gsp mutations by direct sequencing of exon 9 and the entire exon 10 of the TSHR gene and exons 7-10 of the gsp gene. Somatic TSHR mutations were identified in 15 of 31 TTNs. TSHR mutations were localized in the third intracellular loop (Asp619Gly and Ala623Val), the sixth transmembrane segment (Phe631Leu and Thr632Ile, Asp633Glu) and the second extracellular loop (Ile568Thr). One mutation was found in the extracellular TSHR domain (Ser281Asn). Two new TSHR mutations were identified. One involves codon 656 in the third extracellular loop (Val656Phe). The other new mutation is a 27-bp deletion in the third intracellular loop resulting in deletion of 9 amino acids at codons 613-621. Transient expression of the new TSHR mutations in COS-7 cells demonstrated their constitutive activity. No mutation was found in exons 7-10 of the gsp gene. This finding was confirmed by an allele-specific PCR for mutations in gsp codons 201 (Arg-->His, Cys) and 227 (Gln-->His, Arg). Our data indicate that constitutively activating TSHR mutations can be found in 48% of TTNs and thus currently represent the most frequent molecular mechanism known in the etiopathogenesis of TTNs. Moreover, the absence of gsp mutations in our series argues for an only minor role of these mutations in TTNs. Constitutive activation of the TSHR by a deletion in a region that might be involved in G protein coupling of the TSHR offers new insights into TSHR activation.     

The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and therapeutic implications

Multiple sclerosis (MS) remains a major challenge to basic and clinical research. Some of the pivotal immune mechanisms operating in this chronic inflammatory disease have recently been characterized but development of more satisfactory treatment still requires a better understanding of the pathogenesis and immunopathology of MS. Adhesion molecules are known to be of fundamental importance in autoimmune disease, and a variety of new therapeutic approaches to target them have emerged in the past few years; they should open new avenues to improve the outcome of this disabling disease.