Cyclosporine treatment for patients with CRF who developed pure red blood cell aplasia following EPO therapy.

Human recombinant erythropoietin is the main treatment for anemia in renal patients. Recently, there have been case reports of pure red blood cell aplasia (PRCA) developing in renal patients administered erythropoietin, probably because of neutralizing antibodies detected in all these patients. All reports were from the West, and most patients were treated with erythropoietin-alpha. Cyclosporine is an immunosuppressive agent used to treat a spectrum of autoimmune conditions. We report a series of Chinese renal patients who developed PRCA after treatment with erythropoietin-alpha, suggesting that this is a problem worldwide. They were treated successfully with cyclosporine and became transfusion independent.

Failed vaginal birth after a cesarean section: how risky is it? I. Maternal morbidity.

OBJECTIVE: Our purpose was to determine the maternal risks associated with failed attempt at vaginal birth after cesarean compared with elective repeat cesarean delivery or successful vaginal birth after cesarean. STUDY DESIGN: From 1989 to 1998 all patients attempting vaginal birth after cesarean and all patients undergoing repeat cesarean deliveries were reviewed. Data were extracted from a computerized obstetric database and from medical charts. The following three groups were defined: women who had successful vaginal birth after cesarean, women who had failed vaginal birth after cesarean, and women who underwent elective repeat cesarean. Criteria for the elective repeat cesarean group included no more than two previous low transverse or vertical incisions, fetus in cephalic or breech presentation, no previous uterine surgery, no active herpes, and adequate pelvis. Predictor variables included age, parity, type and number of previous incisions, reasons for repeat cesarean delivery, gestational age, and infant weight. Outcome variables included uterine rupture or dehiscence, hemorrhage >1000 mL, hemorrhage >2000 mL, need for transfusion, chorioamnionitis, endometritis, and length of hospital stay. The Student t test and the chi(2) test were used to compare categoric variables and means; maternal complications and factors associated with successful vaginal birth after cesarean were analyzed with multivariate logistic regression, allowing odds ratios, adjusted odds ratios, 95% confidence intervals, and P values to be calculated. RESULTS: A total of 29,255 patients were delivered during the study period, with 2450 having previously had cesarean delivery. Repeat cesarean deliveries were performed in 1461 women (5.0%), and 989 successful vaginal births after cesarean delivery occurred (3.4%). Charts were reviewed for 97.6% of all women who underwent repeat cesarean delivery and for 93% of all women who had vaginal birth after cesarean. Vaginal birth after cesarean was attempted by 1344 patients or 75% of all appropriate candidates. Vaginal birth after cesarean was successful in 921 women (69%) and unsuccessful in 424 women. Four hundred fifty-one patients undergoing cesarean delivery were deemed appropriate for vaginal birth after cesarean. Multiple gestations were excluded from analysis. Final groups included 431 repeat cesarean deliveries and 1324 attempted vaginal births after cesarean; in the latter group 908 were successful and 416 failed. The overall rate of uterine disruption was 1.1% of all women attempting labor; the rate of true rupture was 0.8%; and the rate of hysterectomy was 0.5%. Blood loss was lower (odds ratio, 0.5%; 95% confidence interval, 0.3-0.9) and chorioamnionitis was higher (odds ratio, 3.8%; 95% confidence interval, 2.3-6.4) in women who attempted vaginal births after cesarean. Compared with women who had successful vaginal births after cesarean, women who experienced failed vaginal births after cesarean had a rate of uterine rupture that was 8.9% (95% confidence interval, 1.9-42) higher, a rate of transfusion that was 3.9% (95% confidence interval, 1.1-13.3) higher, a rate of chorioamnionitis that was 1.5% (95% confidence interval, 1.1-2.1) higher, and a rate of endometritis that was 6.4% (95% confidence interval, 4.1-9.8) higher. CONCLUSION: Patients who experience failed vaginal birth after cesarean have higher risks of uterine disruption and infectious morbidity compared with patients who have successful vaginal birth after cesarean or elective repeat cesarean delivery. Because actual numbers of morbid events are small, caution should be exercised in interpreting results and counseling patients. More accurate prediction for safe, successful vaginal birth after cesarean delivery is needed.

Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs.

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score /= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population.

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

In vivo effects of chlorophyllin on the antitumour agent cyclophosphamide.

Cyclophosphamide (CP) is a potent antitumour agent used against many forms of cancer and against certain other diseases. Chlorophyllin (CHL), which is obtained by hydrolysis of chlorophyll to remove phytyl alcohol, is an efficient antimutagenic agent and has been used as a dietary supplement or to diminish the intensity of the discomforting side effects of CP therapy. We undertook to determine the antimutagenic effectiveness of CHL against CP in a mouse model and to determine whether the antitumour efficacy of CP was compromised in vivo by CHL treatment. Experiments utilised CHL administered either in drinking water (1%) for 2 days before treatment, or by gavage (200 mg/kg) 2 hr before treatment with CP (220 mg/kg). Urinary mutagenicity following CP treatment, as determined by the Salmonella/microsome assay, was decreased by both regimes of CHL co-treatment. Similarly, the increase in micronuclei in bone marrow polychromatic erythrocytes in response to CP was reduced by concomitant CHL treatment. In contrast, antitumour efficacy, as determined by growth delay of Colon 38 adenocarcinomas, was not diminished by CHL treatment. We conclude that CHL may have beneficial effects when used in combination with CP therapy.

Ethnic heterogeneity in the distribution of the OKT4 antigen on lymphocytes: studies in three black families.

Human T lymphocytes bear characteristic membrane antigens which allow for identification on these cells and their subpopulations with monoclonal antibody reagents directed against the specific cell-surface antigens. During a study of T lymphocyte subpopulations in a group of 41 infants from a high risk nursery, three of the seven black infants studied were found to be missing cells reactive with the monoclonal antibody OKT4 which identifies the helper-inducer subset of T cells. Immunological evaluation of these infants and study of their family members revealed that the OKT4 non-reactive lymphocytes reacted normally with another antibody, OKT4A, which also identifies the helper-inducer subset of T cells. The deficiency of the antigen recognized by the OKT4 antibody appeared not to reflect T cell immaturity and was not associated with obvious immunodeficiency. The OKT4 negative phenotype appeared to be transmitted in an autosomal recessive mode. Our studies suggest that heterozygosity for this phenotype is relatively common among the black population and that heterozygotes are not easily distinguishable from the random population on the basis of lymphocyte reactivity with the OKT4 monoclonal antibody.