Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions.

BACKGROUND: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. RESULTS: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.

Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study.

OBJECTIVE: To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis (MS). METHODS: Patients aged 18-65 years with a diagnosis of MS, a stable disability level < or =6 on the Kurtzke extended disability status scale (EDSS), and a mean score >4 on the fatigue severity scale (FSS) were eligible for the 9 week, single blind, phase 2, two centre study. Exclusion criteria included a diagnosis of narcolepsy, sleep apnoea, or clinically significant major systemic disease and recent use of medications affecting fatigue. All patients, who remained blinded for the treatment regimen, received placebo during weeks 1-2, 200 mg/day modafinil during weeks 3-4, 400 mg/day modafinil during weeks 5-6, and placebo during weeks 7-9. Safety was evaluated by unblinded investigators. Efficacy was evaluated by self rating scales, using the FSS, the modified fatigue impact scale (MFIS), a visual analogue scale for fatigue (VAS-F), and the Epworth sleepiness scale (ESS). Adverse events were recorded. RESULTS: Seventy two patients (MS type: 74% relapsing-remitting; 7% primary progressive; 19% secondary progressive) received treatment. After treatment with 200 mg/day modafinil for 2 weeks, a significant improvement in fatigue versus placebo run in was demonstrated. Mean scores after treatment with 200 mg/day modafinil were: FSS, 4.7 versus 5.5 for placebo (p<0.001); MFIS, 37.7 versus 44.7 (p<0.001); and VAS-F, 5.4 versus 4.5 (p=0.003). Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in. Mean ESS scores were significantly improved (p<0.001) with 200 mg/day modafinil (7.2) and 400 mg/day (7.0) versus the score at baseline (9.5). Serious adverse events were not found at either dose. The most common adverse events were headache, nausea, and aesthenia. Sixty five patients (90%) completed the study. CONCLUSIONS: These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS.

Wilson's disease: copper unfettered.

Wilson's disease is a rare autosomal recessive inherited disorder of copper metabolism. Hepatic excretion of copper is impaired due to mutation of the gene for a copper-transporting adenosine triphosphatase, ATP7B. Copper accumulation in liver, brain, and other tissues may cause a wide spectrum of hepatic, neuropsychiatric, and other clinical manifestations. The diagnosis may be supported by measurement of serum ceruloplasmin, urinary copper excretion, and hepatic copper content as well as by detection of Kayser-Fleischer rings. Several treatments are available to increase urinary excretion and decrease intestinal absorption of copper.

Anonymity, neutrality, and confidentiality in the actual methods of Sigmund Freud: a review of 43 cases, 1907-1939.

OBJECTIVE: The aim of this historical study was to examine the methods actually used by Sigmund Freud in his practice of psychoanalysis in his mature years (1907-1939) and to assess the relationship between these methods and Freud's published recommendations concerning anonymity, neutrality, and confidentiality. METHOD: The authors used both published and unpublished sources, including reports or autobiographies by analysands, letters by analysands, interviews of analysands, letters by Freud, published works by Freud, and clinical records of subsequent treatment. RESULTS: Information concerning Freud's actual methods was found in 43 cases, including 10 clinical psychoanalyses, 19 didactic analyses, and 14 with combined clinical and didactic purposes. These 43 cases probably encompassed a majority of Freud's psychoanalytic hours during these years. Deviations from Freud's recommendations were found to the following extent: for anonymity, 43 cases (100%); for neutrality, 37 cases (86%); for confidentiality, 23 cases (53%). In addition, there were significant extra-analytic relations between Freud and 31 of these analysands (72%). CONCLUSIONS: These results show a substantial disparity between Freud's recommendations and his actual methods. Freud's prescribed method, as defined by his recommendations, was not tested or used in his practice. Freud's actual method was never explicitly described in his writings and cannot be replicated.

Respiratory dysfunction in muscular dystrophy and other myopathies.

Respiratory muscle weakness occurs in a wide spectrum of acute and chronic myopathic disorders, and may cause a restrictive ventilatory defect and life-threatening ventilatory failure. Therapeutic intervention is based on a thorough knowledge of the course of each disease and meticulous monitoring of respiratory function. Comprehensive management of patients with myopathic disorders requires an understanding of the pathophysiology and specific manifestations of respiratory involvement in each disease.

Immunosuppressive treatment of motor neuron syndromes. Attempts to distinguish a treatable disorder.

OBJECTIVE: To determine if response to immunosuppressive treatment in motor neuron syndromes could be predicted on the basis of clinical features, anti-GM1 antibodies, or conduction block. DESIGN: Prospective, uncontrolled, treatment trial using prednisone for 4 months followed by intravenous cyclophosphamide (3 g/m2) continued orally for 6 months. SETTING: All patients were referred to university hospital medical centers. PATIENTS: Sixty-five patients with motor neuron syndromes were treated with prednisone; 11 patients had elevated GM1 antibody titers, and 11 patients had conduction block. Forty-five patients received cyclophosphamide, eight of whom had elevated GM1 antibodies and 10 had conduction block. RESULTS: One patient responded to prednisone, and five patients responded to cyclophosphamide treatment. Only patients with a lower motor neuron syndrome and conduction block improved with either treatment. Response to treatment did not correlate with GM1 antibodies. CONCLUSIONS: GM1 antibodies did not serve as a marker for improvement in patients with motor neuron syndrome treated with immunosuppressive drugs. Patients with amyotrophic lateral sclerosis failed to improve irrespective of laboratory findings.

Mononuclear cell analysis of muscle biopsies in prednisone- and azathioprine-treated Duchenne muscular dystrophy.

Prednisone improves strength and function in patients with Duchenne dystrophy. Although the mechanism of this effect is uncertain, prior studies suggested that the benefit might result from immunosuppressive effects on T lymphocytes invading muscle. A recent randomized, double-blind, controlled trial of prednisone and azathioprine demonstrated that azathioprine had no effect in Duchenne dystrophy, raising questions about the role of immunosuppression in mediating clinical improvement. The goal of this current study was to compare the effects of prednisone and azathioprine on mononuclear infiltrates from biopsies performed at the end of the controlled clinical trial (reported separately in the article by Griggs et al on page 520). We studied 14 patients from the prednisone group (0.75 mg/kg/d), 10 from the combination therapy group (prednisone 0.3 mg/kg/d and azathioprine 2.5 mg/kg/d), and 13 from the azathioprine group (2.5 mg/kg/d), and used monoclonal antibodies for cell typing. There were no significant differences between the groups for total T cells, T-cell subsets, B cells, natural killer cells, total mononuclear cells, necrotic muscle fibers, or fibers focally invaded by mononuclear cells. These data indicate that azathioprine decreases mononuclear subsets infiltrating muscle to a similar degree as does prednisone, although azathioprine-treated patients do not show a clinical improvement. This implies that immunosuppressive actions on cellular infiltrates in muscle are probably not the primary mechanism of prednisone-induced clinical improvement.

Opacity versus counterprojection: an analytic intervention explored.

A peculiarly effective intervention by the author's psychoanalyst is explored and discussed in terms of its implicitly expressive properties. It is placed in the context of the classical concept of opacity and more flexible Sullivanian ideas, as expanded and clarified by Havens.

Ipsilateral acoustic-reflex adaptation testing for detection of facial-nerve pathology: three case studies.

Abnormal acoustic-reflex adaptation monitored in the same ear for both contralaterally and ipsilaterally presented tonal activators is reported in three cases. One case had Bell's palsy, whereas the other two cases had no clinically observable evidence of seventh-nerve involvement. These cases show that the existence of abnormal acoustic-reflex adaptation in the absence of Bell's palsy does not necessarily implicate the presence of eighth-nerve pathology.

Influenza A infection simulating pulmonary embolism.

The diagnosis of pulmonary embolism is generally established when the patient has characteristic pulmonary perfusion abnormalities in the setting of an appropriate clinical history and with no concurrent cardiopulmonary disease on chest x-ray film. The initial evaluation, including positive pulmonary perfusion scan, of four young black women suggested the diagnosis of pulmonary emboli. A syndrome of respiratory tract viral infection then developed, and further evaluation by angiography and perfusion scans contradicted the diagnoses of pulmonary emboli. Each patient had substantial convalescent-phase complement-fixation titers to influenza A. Thus, if reliance is placed in pulmonary perfusion scans, an erroneous diagnosis of pulmonary emboli may be made for patients with influenza A.

Haemophilus parainfluenzae and influenzae endocarditis: a review of forty cases.

Two cases of bacterial endocarditis caused by Haemophilus parainfluenzae are reported with a review of 33 other cases of H. parainfluenzae endocarditis and 5 cases of H. influenzae endocarditis. Although H. parainfluenzae is usually considered a non-pathogenic microorganism, this review firmly establishes its role as a causative agent in endocarditis. Furthermore, several clinical features were noted which were atypical when compared to findings usually present in patients with bacterial endocarditis. The mean age of the patients was only 27 years. Over 60% of the patients had no identifiable predisposing illness, an unexpected finding in view of the low degree of pathogenicity associated with this microorganism. Polymicrobial bacteremia, usually with viridans streptococci, was found in 11% of patients. Major arterial emboli were documented in 57% of patients, an incidence unchanged from the pre-antibiotic era. Diagnosis of the disease is dependent upon an awareness of the fastidious cultural requirements necessary for isolation of Haemophilus species. Culture media must contain a source of X and V factors. Mortality from H. parainfluenzae endocarditis has been reduced from 100 per cent prior to 1940 to about 12 per cent by use of appropriate antimicrobial agents. Awareness that Haemophilus species can cause bacterial endocarditis is important because the diagnosis is dependent upon utilization of special culture methods and the patient may not respond to some of the empiric regimens used for treating bacterial endocarditis. It should be especially considered as a possible cause of "culture-negative" or "abacteremic" endocarditis.