Hepatitis in fatal infectious mononucleosis

A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.     

Content and psychometric evaluations of questionnaires for assessing physical function in people with neck disorders: a systematic review of the literature

Purpose: The purpose was to investigate how physical function is assessed in people with musculoskeletal disorders (MSD) in the neck. Specifically, we aimed to determine: (1) Which questionnaires are used to assess physical function in people with MSD in the neck? (2) What do those questionnaires measure? (3) What are the measurement properties of the questionnaires?

Materials and methods: A systematic review was performed to identify questionnaires and psychometric evaluations. The content of the questionnaires was categorized according to the International Classification of Function, Disability and Health, and the psychometric properties were quality-rated using the COnsensus-based Standards for the selection of health Measurement INstruments checklist.

Results: Ten questionnaires and 32 articles evaluating measurement properties were analyzed. Most questionnaires covered only the components body functions and activity and participation, more often activity participation than body function. Internal consistency was adequate in most questionnaires, whereas responsiveness was generally low. Neck Disability Index was most evaluated, but the evaluations of all questionnaires tended to cover most properties in the checklist.

Conclusions: The questionnaires differed substantially in items and extent to which their psychometric properties had been evaluated. Focus of measurement was on activities in daily life rather than physical function as such.

• Implications for Rehabilitation

• To provide early diagnostics and effective treatment for patients with neck disorders, valid and reliable instruments that measure relevant aspects of the disorders are needed.

• This paper presents an overview of content and quality of questionnaires used to assess physical function in neck disorders, which may facilitate informed decisions about which measurement instruments to use when evaluating the course of neck disorders.

• Most of the questionnaires need more testing to judge the quality, however the NDI was the most frequently tested questionnaire.

• The COnsensus-based Standards for the selection of health Measurement INstruments checklist is a useful tool in relation to psychometric testing of questionnaires, but clear definitions of interpretation of the quality criteria in each study would enhance comparability of results.

     

Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study

Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m², with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m² under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.     

Pancreatic elastase 1 after pancreatic transplantation.

Human pancreatic elastase 1 (E1) is a novel pancreas-specific proteinase that has not yet been investigated after pancreatic transplantation (PTx). Using a recently developed E1 ELISA, we studied the E1 serum curves in 36 type I diabetic patients subjected to PTx with enteric exocrine diversion from the pretransplant value up to 8 years after transplantation (n = 731 samples). A characteristical pattern was observed: following PTx, E1 rose above the normal range to a peak within 6 days and then gradually fell to stabilize after 4-6 weeks at an elevated level (10 ng/ml) for approximately 1 year. Two to 8 years after PTx, E1 levels were still slightly elevated (1-6 ng/ml) in 14/20 patients. During 24 acute rejection episodes, E1 was found not be a sensitive rejection marker during the early postoperative period because of its slow decline from the peak level. However, increasing E1 levels in seven patients more than 2 months after PTx were associated with a variety of lesions to the pancreatic graft, thus suggesting a useful marker indicating exocrine graft damage late after PTx. The slightly elevated levels even years after PTx are most probably due to the non-portal venous drainage of the pancreatic graft.     

Specific detection of Entamoeba histolytica DNA by hemolysin gene targeted PCR

Diagnostic differentiation of pathogenic Entamoeba histolytica from non-pathogenic Entamoeba dispar is of great clinical importance. We have developed and evaluated a new polymerase chain reaction (PCR) assay (haemo-PCR) based on the novel E. histolytica hemolysin gene HLY6. The specificity of this assay was confirmed by analyzing different Entamoeba species, faeces samples, human and bacterial DNA, and digestion of amplification products with appropriate restriction enzymes. The sensitivity was confirmed by serial dilutions of E. histolytica HM-1:IMSS DNA in the excess of human DNA. Totally, 45 clinical samples were analyzed by the haemo-PCR assay including amoebic liver abscess (ALA) fluids from 23 patients suspected for amoebiasis, four faeces samples containing E. histolytica and E. dispar, and positive and negative controls. The results were compared with those obtained with PCRs for cystein-rich surface protein (P30) and small subunit ribosomal RNA (ssu rRNA) genes. The haemo-PCR gave a positive result in 18 (89%) ALA fluids compared with 14 (77%) and five (28%) by PCR for p30, and ssu rRNA, respectively. PCR products were obtained only from specimens containing E. histolytica DNA. The haemo-PCR assay was therefore found to be a valuable diagnostic tool for identification of E. histolytica infections both in faeces and ALA samples.     

Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.