Gas chromatographic method for the determination of valproic acid in human plasma.

A gas chromatographic method has been developed for the routine monitoring of valproic acid (VPA) in human plasma samples. Two compounds, 2-ethylpentanoic acid (EPA) and 2-propylhexanoic acid (PHA), were synthesized and evaluated as internal standards together with cyclohexane carboxylic acid (CHCA), a commonly employed internal standard. Crystalline barium salts of VPA, EPA, and PHA were prepared, which enabled preparation of standard solutions of high accuracy for use in calibration experiments and in daily intra-laboratory quality control tests. The extraction scheme was designed on the basis of the solvent partitioning properties of VPA. Solvent transfers are required in the extraction scheme, but solvent evaporations are not. Studies were made of the performances of EPA, PHA, and CHCA as internal standards in the VPA assay at different lifetimes of the 10% SP-1000 chromatography column. As judged by these studies, EPA or CHCA is a better choice than PHA as an internal standard, provided that certain guidelines are followed in the use of CHCA.     

The effects of renal transplantation on peripheral blood dendritic cells

Recent advances allow accurate quantification of peripheral blood (PB) myeloid and plasmacytoid dendritic cell (DC) populations (mDC and pDC, respectively), although the response to renal transplantation (RT) remains unknown. Using flow cytometry, PBDC levels were quantified in patients with end stage renal disease (ESRD) undergoing RT. PBDC levels were significantly reduced in ESRD patients pre-RT compared to healthy controls, with further reduction noted immediately following a hemodialysis session. RT resulted in a dramatic decrease in both subsets, with a greater reduction of pDC levels. Both subset levels were significantly lower than in control patients undergoing abdominal surgery without RT. Subgroup analysis revealed significantly greater mDC reduction in RT recipients receiving anti-lymphocyte therapy, with preferential binding of antibody preparation to this subset. Samples from later time points revealed a gradual return of PBDC levels back to pre-transplant values concurrent with overall reduction of immunosuppression (IS). Finally, PBDC levels were significantly reduced in patients with BK virus nephropathy compared to recipients with stable graft function, despite lower overall IS. Our findings suggest that PBDC levels reflect the degree of IS in renal allograft recipients. Furthermore, PBDC monitoring may represent a novel strategy to predict important outcomes such as acute rejection, long-term graft loss and infectious complications.     

Genetic studies in the Amish community

The Amish community was established in Pennsylvania, Ohio and Indiana. They form a distinct and biologically isolated community by virtue of their strong cultural and religious beliefs. This paper outlines aspects of the Amish culture and reviews some of the recent genetic studies that have been undertaken in this community.     

Cross-sectional and longitudinal evaluations of an endurance training program.

A comparison of the cardiorespiratory responses obtained using both a longitudinal and cross-sectional evaluation of an endurance training program was made in two groups of 60 young male military personnel. Both groups were initially tested (T1) and then retested 6 months later (T2). At T1, Group I was a sample of personnel not participating in a training program while Group II had undergone a 5-month endurance program (2-4 mile run/day). At T2, Groups I and II had been participating in the program for 6 and 11 months, respectively. Testing consisted of sub-maximal and maximal determinations of VO2, VE and heart rate (HR) using an interrupted treadmill test. VO2 max was 11% greater in Group II compared to Group I at T1 and increased 10% in Group I at T2. Similar results were also seen for HR submax, HR max and VE max. These results show that similar values indicative of an improved level of cardiorespiratory fitness can be obtained using either a cross-sectional or longitudinal design when relatively homogeneous groups are studied.     

Parental reactions to children with congenital heart disease

Informal discussions with 260 families of children with congenital heart disease are reported. Parents raised questions concerning etiology, timing of the diagnosis, pathophysiology and symptomatology, and need for restriction. Depending upon the stage and seriousness of the disease, common parental behavior was observed. A psychological process similar to mourning is required at the time of diagnosis and at the time of corrective surgery in order to promote the family's adaptation to the child with congenital heart disease. Management suggestions are included.This study was supported in part by Grant #3990530 from the Mary Duke Biddle Fund and Grant #MH 08045-13 Psychiatry G.P. Special Training.     

Mixed mesenchymal and neuroectodermal tumor of the cerebellum

Summary An unusual cerebellar tumor composed of mixed mesenchymal and neuroectodermal elements in a 44 year old man is reported. The mesenchymal element is well-differentiated adipose tissue, whereas the neuroectodermal components exhibit a variety of medulloblastomatous, astrocytomatous, oligodendrogliomatous and ependymomatous areas. A possible origin of such unusual mixed neoplasms is briefly discussed.     

characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak

A monkeypox outbreak occurred in the United States in 2003. Patient's sera were sent to the Centers for Disease Control and Prevention as a part of outbreak response measures. Clinical and epidemiologic information was abstracted from the case investigation forms. Serum samples from patients were tested by using an immunoglobulin M (IgM)-capture and an IgG enzyme-linked immunosorbent assay ELISA against Orthopoxvirus antigen. The detection of antiviral IgG and IgM antibodies and the kinetics of the antiviral IgG and IgM antibody responses were evaluated. Patients were classified as confirmed, probable, or suspect cases or were excluded as cases based on laboratory test results and epidemiologic and clinical criteria. A total of 37 confirmed case patients with monkeypox were identified, and 116 patients were excluded as case patients based on molecular testing or insufficient epidemiology and clinical data to warrant classification as a suspect or probable case. Of 37 confirmed case patients, 36 had a known history (presence or absence) of smallpox vaccination. Of those, 29 of the 36 either had or developed an IgG response, while 34 of the 36 developed an IgM response, regardless of vaccination status. Serum collected > or =5 days for IgM detection or serum collected > or =8 days after rash onset for IgG detection was most efficient for the detection of monkeypox virus infection. IgM ELISA detects recent infection with orthopoxviruses and, in this case, recent infection with monkeypox virus. In addition, analysis of paired sera for IgG and IgM detected seroconversion, another indicator of recent infection. The ELISA results correlated with the virologic PCR and viral culture results, indicating its diagnostic capabilities for monkeypox and potentially other orthopoxvirus infections due to zoonotic transmission or bioterrorism events.