The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex

BACKGROUND AND METHODS. Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS. Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS. The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.     

Frequent attenders in secondary care: a 3-year follow-up study of patients with medically unexplained symptoms

BACKGROUND: There are few longitudinal studies of patients with medically unexplained symptoms. The aim of this study was to investigate outcome in frequent attenders in secondary care who present repeatedly with medically unexplained symptoms. METHOD: Forty-eight patients presenting with medically unexplained symptoms, from a sample of 61, participated in a 3-year follow-up study. Psychiatric morbidity, functional impairment and use of services were evaluated. RESULTS: At follow-up there was a high prevalence of psychiatric morbidity with 69% having at least one psychiatric diagnosis. The sample continued to be high users of a range of health services and substantial functional impairment was reported. CONCLUSION: In this group of frequent attenders with medically unexplained symptoms outcome as measured by psychiatric morbidity, service use and functional impairment remained poor after 3 years.     

Immunohistochemical renin study of DES-induced renal tumor in the Syrian hamster

Diethylstilbestrol (DES) treatment of a male Syrian hamster resulted in the development of a renal tumor and its widely scattered scrosal metastases. Cells in both the primary tumor and metastatic nodules contained secretory granules. The tumors were transplanted serially into DES-supported and non-DES-supported host hamsters until DES-independent tumors developed. Rabbit antiserum to mouse salivary renin and rabbit antiserum to rat kidney resin were reacted with sections of the primary tumor, metastatic nodules, and all transport tumors. The sections were stained by the PAP and Vector-ABC-AP procedures. Renin-positive material was observed in all tumors. Plasma renin activity (PRA) was determined for the host hamsters carrying the renal tumor transplants and compared to the PRA values that had been determined for normal non-DES-treated male and female hamsters. It was found that the average PRA values of host hamsters carrying the tumor transplants were significantly higher than the normal PRA ralues.     

Operative morbidity and reproductive outcome in secondary myomectomy: a prospective cohort study

BACKGROUND: This prospective study was designed to evaluate the operative morbidity and reproductive outcome in patients who had secondary myomectomy for recurrent symptomatic uterine fibroids. METHODS: A total of 58 women were subjected to a secondary myomectomy via the abdominal route. The operative morbidity such as blood loss, presence of adhesions and febrile index were estimated and the pregnancy outcome over a 2-4 year period of follow-up. RESULTS: The mean age and standard deviation (+/- SD) of the women was 35 (+/- 2.4) years. Nineteen patients (33%) had a postoperative temperature vertical line 100 degrees F and the estimated blood loss ranged from 159-2500 ml (median 700 ml). Seven patients (12%) required blood transfusion and one had a hysterectomy due to haemorrhage. Nine women (15.5%) became pregnant but only five (56%) had live births. Those with successful pregnancies tended to be younger with a mean age of 31.8 (+/- 2.6) years versus 35 (+/- 1.8) years, (P = 0.08, non-significant) and had fewer uterine leiomyomata; median with range values, 2 (1-6) versus 7 (6-15). The variables which best predicted the postoperative likelihood of pregnancy were; age, presence of tubal adhesions and the number of uterine fibroids. CONCLUSION: This prospective study showed a high operative morbidity and a poor fertility outcome after a repeat myomectomy. The factors affecting successful outcome in a logistic regression model were age, tubal adhesions and number of uterine fibroids.     

Simple procedure for assessing relative quantities of neutral and acidic sugars in mucin glycoproteins: its use in assessing cyclical changes in cervical mucins.

A simple histochemical procedure for assessing relative amounts of neutral and acidic sugars in mucin glycoproteins, and its application in the study of cyclical changes of human cervical mucins, is described. This procedure, the saponification/selective periodate oxidation/borohydride reduction/alcian blue pH 2.5/periodic acid Schiff (KOH/PA*/Bh/Ab 2.5/PAS) method, uses a selective oxidation step to remove the PAS positivity of sialic acid; thus only neutral sugars stain positively with PAS, and acidic sugars (O-sulphate esters and carboxyl groups) stain with alcian blue. This differs from the KOH/Ab/PAS technique which stains sialic acid residues with both alcian blue and PAS. Applying the KOH/PA*/Bh/Ab 2.5/PAS technique to the study of cyclical changes of human cervical mucins, a decreased neutral:acidic sugar ratio in the secretory phase mucins compared with those of the proliferative phase was found. This difference was not seen with KOH/Ab/PAS staining in the same cases. The techniques and reagents used in this procedure can be easily applied in a clinical histopathology laboratory.     

Immunoglobulin concentrations in children receiving treatment for acute lymphoblastic leukaemia

As part of a wider survey of infections and defence mechanisms, concentrations of serum immunoglobulins IgG, IgA, and IgM were measured regularly by single radial immunodiffusion in a group of children receiving treatment for acute lymphoblastic leukaemia while in their first remission. IgM concentrations were often markedly raised at diagnosis, and IgG and IgA concentrations both began falling within one month of diagnosis. Four months after diagnosis all three had fallen significantly, but this tendency stopped after six months. Only IgG partially recovered, and non returned to pretreatment concentrations even in children followed for two years. The results suggest that vincristine and prednisone are the major factors that initiated the fall in IgG and IgA. Lowered IgM concentrations may have been due to cranial irradiation or continuous maintenance treatment, or both.     

Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.