Mutagenicity studies with N-acetyl-l-aspartic acid

Analytical studies have reported that N-acetyl-l-aspartic acid (NAA) is present at low concentrations in many foods. The current studies were conducted to assess the mutagenicity of NAA using standard OECD guideline in vitro bacterial and in vivo mammalian mutagenicity studies. For comparison and control data, mutagenicity studies were also conducted with its constituent amino acid l-aspartate (ASP) because NAA is metabolized to ASP. The combination of an in vitro method for assessing point mutations in bacteria and an in vivo method to assess clastogenicity in an animal model provided adequate evidence for mutagenicity hazard assessment of NAA. No evidence of mutagenicity was observed in either test system with either NAA or ASP. The results from the current studies demonstrate that the presence of NAA in foods is not likely to represent a risk for mutagenicity.     

Bivariate modeling of interobserver agreement coefficients

Many studies of interobserver agreement yield outcome measures on more than one binary trait. For example, Becker et al. (Int. J. Psychiatry Med. 2002; 32(3):271-283) reported on a study of depression and anxiety as two outcome measures obtained on 173 patients evaluated by two screening instruments, the first using a Patient Health Questionnaire and the second employing a Structured Clinical Interview. In this case, although inferences on each trait separately are usually of main interest, a question that also arises is whether or not the level of interobserver agreement can be regarded as stable across the two traits. In this paper, we develop the required methodology and provide an illustrative example.     

Pathways to distress: The multiple determinants of depression,hopelessness, and the desire for hastened death in metastatic cancer patients

We tested a model in which psychosocial and disease-related variables act as multiple protective and risk factors for psychological distress in patients with metastatic cancer. We hypothesized that depression and hopelessness constitute common pathways of distress, which mediate the effects of psychosocial and disease-related factors on the desire for hastened death. This model was tested on a cross-sectional sample of 406 patients with metastatic gastrointestinal or lung cancer recruited at outpatient clinics of a Toronto cancer hospital, using structural equation modeling. The results supported the model. High disease burden, insecure attachment, low self-esteem, and younger age were risk factors for depression. Low spiritual well-being was a risk factor for hopelessness. Depression and hopelessness were found to be mutually reinforcing, but distinct constructs. Both depression and hopelessness independently predicted the desire for hastened death, and mediated the effects of psychosocial and disease-related variables on this outcome. The identified risk factors support a holistic approach to palliative care in patients with metastatic cancer, which attends to physical, psychological, and spiritual factors to prevent and treat distress in patients with advanced disease.     

Mutations in the nebulin gene can cause severe congenital nemaline myopathy

Previously, we reported results indicating that nebulin was the gene causing the typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the identification of mutations in the nebulin gene in seven offspring of five families affected by the severe congenital form of nemaline myopathy. One pregnancy was terminated on the grounds of foetal abnormality, while six affected infants died at ages ranging from the first day of life to 19 months. Only three of the six neonates were able to establish spontaneous respiration. Three had arthrogryposis. In three of the five families, the mutations were located in exon 184. These mutations are predicted to cause absence of the C-terminal part of nebulin.     

The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy

We report the coverage, safety, and logistics of a school-based typhoid fever immunization campaign that took place in Hue City, central Vietnam; a typhoid fever endemic area. A cluster-randomized evaluation-blinded controlled trial was designed where 68 schools (cluster) were randomly allocated the single dose Vi polysaccharide vaccine (Typherix) or the active control hepatitis A vaccine (Havrix). A safety surveillance system was implemented. A total of 32,267 children were immunized with a coverage of 57.5%. Strong predictors for vaccination were attending primary schools, peri-urban location of the school, and low family income. Human resources were mainly schoolteachers and the campaign was completed in about 1 month. Most adverse events reported were mild. Safe injection and safe sharp-waste disposal practices were followed. A typhoid fever school-based immunization campaign was safe and logistically possible. Coverage was moderate and can be interpreted as the minimum that could have been achievable because individual written informed consent procedures were sought for the first time in Hue City and the trial nature of the campaign. The lessons learned, together with cost-effectiveness results to be obtained by the end of follow-up period, will hopefully accelerate the introduction of Vi typhoid fever vaccine in Vietnam.     

Whipple disease and non-Hodgkin lymphoma

6 years ago a 60-year-old man had been suffering from chronic diarrhea, weight loss and epigastric pain. Some years before he had developed joint pain, symmetric at both hands and feet. Duodenal biopsy and PCR reaction revealed Whipple's disease. Treatment with Co-trimoxazole for more than 21 months achieved remission. 6 years after diagnosis of Whipple's disease the patient presented with multilocal lymphadenopathy. Malignant Non-Hodgkin-Lymphoma (Centrocytom) stage PS IV b was diagnosed. COP-chemotherapy (Vincristine, Cyclophosphamide, Prednisone) achieved partial remission up to now. Whether the appearance of the malignant lymphoma is a consequence of Whipple's disease or a second neoplastic disease remains to be answered by further epidemiological studies.     

Combination treatment of IFNalpha2b and ribavirin in patients with chronic hepatitis C and persistently normal ALTs

Combination therapy of interferon-_2b and ribavirin was prospectively evaluated in 20 patients with chronic replicative hepatitis and persistently normal ALTs. Patients with normal ALTs on three or more occasions within 6 months received interferon-_2b 3 MU three times a week with ribavirin 1000–1200 mg everyday for 12 months and had a follow-up of 6 months. HCV genotype 1 was found in 16, and HCV genotype 2 or 3 in 4 patients. No patient experienced an ALT elevation during therapy. Ten of 20 patients (50%) cleared virus at the end of treatment. In an intent-to-treat analysis, a sustained virological response (SR) was achieved in 8 of 20 patients (40%). Nonresponse occurred in 5 patients. Relapse and breakthrough were seen in 2 patients each. Treatment was discontinued in 3 patients due to side effects. Interferon (IFN) ribavirin combination therapy is effective in patients with normal ALTs and appears superior to IFN monotherapy.     

Combination of line immunoassays Mikrogen recomLine CMV IgG and recomLine CMV IgG Avidity helps to date the onset of CMV primary infection

CMV IgG avidity assays are widely used and can be helpful in pregnant women to date the onset of CMV primary infection; however, these tests are not standardized and sometimes give inconclusive results. We evaluated the performances of Mikrogen recomLine CMV IgG and IgG Avidity compared to the VIDAS CMV IgG Avidity. On a first sample set of 89 sequential sera collected from 40 women with precisely determined onset of CMV primary infection, the combination of Mikrogen recomLine CMV IgG and IgG Avidity showed an accurate interpretation in 83.1% (74/89), an incorrect result in 4.5% (4/89), and an inconclusive result in 12.4% (11/89) and showed a better sensitivity to diagnose infections <14?weeks compared to VIDAS (85.9% vs. 76.9%). On a second sample set of 89 sera with an intermediate VIDAS CMV IgG Avidity, the combination of line immunoassays provided additional information on the time of infection in 79% (70/89) of the samples. This combination of line assays is useful as additional confirmatory testing and can help to date more precisely the onset of CMV primary infection.     

Cholestatic liver diseases from child to adult: the diversity of MDR3 disease

The phospholipidfloppase MDR3 (gene symbol: ABCB4) is expressed in the canalicular membrane of hepatocytes and mediates the biliary excretion of phosphatidylcholine, which is required for the formation of mixed micelles in bile. Several mutations of ABCB4 have been identified, which cause cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 3 (PFIC-3), intrahepatic cholestasis of pregnancy (ICP) and the low phospholipid associated cholelithiasis syndrome (LPAC). Here, we report on four new (S1076N; L 23Hfs16X; c.286 + 1G > A; Q 1181E) and one known (S27G) MDR3 mutations in eight patients of three families. The patients presented with a wide spectrum of liver diseases. The clinical presentation and decisive laboratory findings or the association to a trend-setting family history led to the identification of the genetic background in these patients. Even the same mutation may be associated with varying disease progression.