Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study

Summary We enrolled children with acute lymphoblastic leukemia (ALL) in a Pediatric Oncology Group (POG) pilot study to monitor erythrocyte (RBC) methotrexate (MTX) and folate (F) levels before and during treatment. The mean value for RBCF at diagnosis was 0.86±0.46 nmol/ml RBC in the 214 patients who achieved remission and 1.21±0.74 nmol/ml RBC in the 10 patients who did not (P=0.020). Folate levels tended to increase during remission induction, but they dropped following an intensive consolidation with methotrexate to levels that were sustained throughout chemotherapy treatment. Methotrexate levels reached mean values of approximately 0.15 nmol/ml RBC at the end of an intensive methotrexate consolidation, then fell to levels that were sustained throughout maintenance therapy. There was a weak correlation between improved event-free survival and higher RBCMTX levels after consolidation, but no correlation was found between improved survival and the level of RBCMTX or RBCF during maintenance therapy. A larger study with more complete data is needed to determine whether RBCMTX or RBCF might be useful in predicting event-free survival in patients with ALL.This work was supported in part by grants from the National Cancer Institute and the National Institute of Health (CA-30969, CA-28476, CA29139, CA-159-89, and CA-33587)     

Psychiatric hospitalization: treatment or triage?

We examined the outcome of active duty psychiatric inpatients (N = 101) 2 years after admission. Most patients were young with minor diagnoses (adjustment disorders), yet only 20% were still on active duty 2 years later. This compared poorly with national retention rates for all lengths of time in service (p < 0.0001). Longer time in service and low severity of diagnosis predicted a better outcome. We discuss implications of these findings.     

Fetal calf serum stimulates 'autoreactive' T-cell hybridomas

During attempts to generate Sendai virus-specific T-cell hybridomas, a number of autoreactive T-cell hybridomas were produced. These hybrids secrete IL-2 in response to class II-positive syngeneic cells in the absence of added Sendai virus. Class II molecules on the stimulator cells are involved since monoclonal anti-class II antibodies block the reaction, and mapping studies using recombinant mouse strains show the response is class II restricted. Hybridomas adapted to grow in serum-free medium do not respond to syngeneic cells in the absence of serum; however, addition of fetal calf serum (FCS) restores the response. The component of FCS responsible for the stimulation of the hybridomas has been partially purified and characterized, and its mode of action investigated. These findings suggest that the putative 'autoreactive' T-cell hybridomas reported by others may be specific for a component of the culture medium rather than being truly self-reactive.     

Communication between psychiatrists and general practitioners: what style of letters do psychiatrists prefer?

This study investigated the style of referral letter that psychiatrists would like to receive from general practitioners. Ninety psychiatrists in Edinburgh were asked to answer a brief questionnaire about their preferences and select one of six sample letters presented to them. The most popular letter was one page in length and contained two or three headings.     

Structure and diversity of class I antigen presenting molecules in the mouse

Sequence comparisons among class I genes provide insight into the nature and origins of diversity in the human and mouse MHC. The profiles of diversity among alleles and between different loci indicate that genetic interactions among class I genes generate sequence diversity in both species. Humans and mice differ in the extent that sequence transfer occurs between loci. In mice, sequences encoding the antigen binding domain show little evidence of locus specificity. A series of mouse class I mutants have been analyzed, providing strong evidence that interlocus gene conversion plays a significant role in the exchange of sequences among class I genes. A similar process is suspected in human class I and both mouse and human class II genes. However, the transfer of sequence among genes in these groups appears to occur predominantly between alleles and only to a minor extent between loci.     

Direct detection of infectious HIV-1 in blood using a centrifugation-indicator cell assay

Plasma HIV RNA is a useful surrogate marker for predicting HIV-1 disease progression in infected individuals but provides no information regarding the infectious viral titer. Traditional assays of infectious HIV-1 are, however, time consuming, insensitive, use non-standardized reagents and are subject to selection bias introduced by prolonged cultivation. In this pilot study infectious HIV-1 was detected directly in patient plasma using the indicator line HeLa-CD4-CCR5-LTR/beta-gal in a centrifugation-culture method. Replication competent HIV-1 was identified within 2 days of tissue culture inoculation in six (26%) of 23 plasma specimens. The capability of a new cell line, MT4-CCR5-tat, to amplify plasma HIV-1 was also tested. HIV was cultivated from ten (71%) of 14 specimens using MT4-CCR5-tat cells before titering the virus with the indicator cell assay. Using these stable cell lines in refined versions of this assay it may be feasible to develop rapid, simple methods for titering infectious plasma HIV-1 and for testing the susceptibility of the virus to antiretroviral drugs.     

Is communication improving between general practitioners and psychiatrists?

General practitioners and psychiatrists communicate mainly by letter. To ascertain the most important items of information that should be included in these letters ("key items") questionnaires were sent to 80 general practitioners and 80 psychiatrists. A total of 120 referral letters sent to psychiatric clinics in 1973 and 1983 were studied, together with the psychiatrists' replies, and these were rated for the inclusion of "key items." General practitioners' letters contain less information about the family but more about psychiatric history than they did a decade ago. Overall, psychiatrists' letters have not changed. Registrars, however, now include noticeably more "key items" than they did 10 years ago, but their letters remain twice the length of those written by consultants. It is suggested that letter writing skills are vital to good patient management and should be taught to postgraduate trainees in general practice and psychiatry.     

Determination of prostaglandin E1 in plasma with picogram per millilitre sensitivity by double antibody extraction and column switching high-performance liquid chromatography

Prostaglandin E(1) (PGE(1)) is a vaso- and arteriodilator that is used for the experimental treatment of a variety of vascular diseases. A high-performance liquid chromatography (HPLC) method was developed for the purpose of quantifying PGE(1) in the plasma of patients undergoing constant infusion therapy. Plasma (0.5 ml) was extracted with a double antibody precipitation technique and the PGE(1)-immunoprecipitate was isolated and washed by repeated resuspension and centrifugation. PGE(1) was recovered from the precipitate by extraction with acetonitrile and derivatized with panacyl bromide for determination on a heteromodel column switching HPLC system with fluorescence detection. The content of PGE(1) in immunoextracts was determined by HPLC peak height comparison against a standard curve of PGE(1) peak height vs amount derivatized. The result was corrected for the plasma extraction efficiency (determined with radiolabelled PGE(1)) to obtain the plasma concentration. Standard curves were linear from 25 to 400 pg (r > 0.99) and the y-intercepts were not significantly different from zero (p < 0.05). The immunoextraction recovery from six human donors was 63.5 +/- 2.0% (S.D., n = 18). The quantification limit of the method was 50 pg ml(-1) (signal-to-noise ratio 3:1), at which the estimated assay relative standard deviation was 18%. The utility of the method for the measurement of PGE(1) plasma levels during constant intravenous infusion was demonstrated in a dog study.