Characterization of seven low incidence blood group antigens carried by erythrocyte band 3 protein

Recent studies have demonstrated that band 3 carries antigens of the Diego blood group system and have elucidated the molecular basis of several previously unassigned low incidence and high incidence antigens. Because the available serological data suggested that band 3 may carry additional low incidence blood group antigens, we screened band 3 genomic DNA encoding the membrane domain of band 3 for single-strand conformational polymorphisms. We found that the putative first ectoplasmic loop of band 3 carries blood group antigen ELO, 432 Arg-->Trp; the third putative loop harbors antigens Vga (Van Vugt), 555 Tyr-->His, BOW 561 Pro-->Ser, Wu (Wulfsberg), 565 Gly-->Ala, and Bpa (Bishop), 569 Asn-->Lys; and the putative fourth ectoplasmic loop carries antigens Hga (Hughes), 656 Arg-->Cys, and Moa (Moen), 656 Arg-->His. We studied erythrocytes from carriers of five of these blood group antigens. We found similar levels of reticulocyte mRNA corresponding to the two band 3 gene alleles, normal content and glycosylation of band 3 in the red blood cell membrane, and normal band 3-mediated sulfate influx into red blood cells, suggesting that the mutations do not have major effect on band 3 structure and function. In addition to elucidating the molecular basis of seven low incidence blood group antigens, these results help to create a more accurate structural model of band 3.     

Growth of prepubertal children with inflammatory bowel disease

BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.     

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.     

Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.     

Alteration of oestradiol metabolism in myc oncogene-transfected mouse mammary epithelial cells

Targeted overexpression of the c-myc oncogene induces neoplastic transformation in immortalized, non-tumorigenic mouse mammary epithelial cells (MMEC). Experiments in the present study were conducted to examine whether cellular transformation induced by c-myc oncogene is associated with altered metabolism of 17beta-oestradiol (E2). The parental, MMEC and the stable c-myc transfectant (MMEC/myc3) cell lines were compared for major oestrogen metabolic pathways, namely E2 and E1 interconversion, and C2- and C16alpha-hydroxylation by both high-pressure liquid chromatography (HPLC) analysis and the 3H release assay using specifically labelled [C2-3H]E2 or [C16alpha-3H]E2. The reductive conversion of E1 to E2 was about 14-fold and 12-fold higher than the oxidative conversion of E2 to E1 in MMEC and MMEC/myc3 cells respectively. However, in MMEC/myc3 cells, both reductive and oxidative reactions were decreased by about 32% and 12% relative to those seen in the parental MMEC cells (P = 0.0028). The extent of C16alpha-hydroxylation was increased by 164.3% (P < 0.001), with a concomitant 48.4% decrease (P < 0.001) in C2-hydroxylation in MMEC/myc3 cells; this resulted in a fourfold increase in the C16alpha/C2 hydroxylation ratio in this cell line. Thus, a persistent c-myc expression, leading to aberrant hyperproliferation in vitro and tumorigenesis in vivo, is associated with an altered oestrogen metabolism. However, it remains unclear whether this represents a result of oncogene expression/activation or is rather a consequence of phenotypic transformation of the cells.     

Long-term follow-up study of vigabatrin in pretreated children with West syndrome

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with gram-positive bacteremia. In the patients with gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B.     

An epidemic of Malassezia pachydermatis in an intensive care nursery associated with colonization of health care workers' pet dogs

BACKGROUND: Malassezia species are lipophilic yeasts that are emerging as nosocomial pathogens, particularly in low-birth-weight neonates who receive lipid emulsions. When a cluster of patients with Malassezia pachydermatis infection was identified in an intensive care nursery, we initiated an investigation. METHODS: A case patient was defined as any infant in the intensive care nursery who had a positive culture for M. pachydermatis between October 17, 1993, and January 18, 1995. We conducted a cohort study to identify risk factors for colonization and infection with M. pachydermatis. We collected cultures from the infants and the health care workers and from the health care workers' pets, since this organism has been associated with otitis externa in dogs. RESULTS: Fifteen infants met the case definition: eight with bloodstream infections, two with urinary tract infections, one with meningitis, and four with asymptomatic colonization. The case patients were significantly more likely than the other infants to weigh 1300 g or less (15 of 65 vs. 0 of 419, P<0.001). In a multivariate analysis of infants weighing 1300 g or less, the independent risk factors for colonization or infection with M. pachydermatis were a greater severity of concomitant illness (odds ratio, 19.7; P=0.001), arterial catheterization for nine or more days (odds ratio, 29.5; P=0.027), and exposure to Nurse A (odds ratio, 74.7; P=0.004). In a point-prevalence survey, 9 additional infants, 1 health care worker, and 12 of the health care workers' pet dogs had positive cultures for M. pachydermatis. The isolates from all 15 case patients, the 9 additional colonized infants, 1 health care worker, and 3 of the 12 dogs had identical patterns of restriction-fragment-length polymorphisms. CONCLUSIONS: In this outbreak, it is likely that M. pachydermatis was introduced into the intensive care nursery on health care workers' hands after being colonized from pet dogs at home. The organism persisted in the nursery through patient-to-patient transmission.