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Biomedical subjects

M Rush

Publications and source records attributed to M Rush.

At least 19 recordsLinked to original sources
PubMed1997

Changing patterns of case ascertainment and trends in meningococcal disease in England and Wales.

We have reviewed data on meningococcal disease routinely collected in England and Wales from 1989 to 1995 to illustrate and explain changing patterns and guide future surveillance. Statutory notifications of meningococcal meningitis and septicaemia, laboratory confirmed infections, and death registrations coded as meningococcal disease were analysed in terms of their numbers, the age of cases, season of the report, and (if available) site of isolation, serogroup, and serotype. Case fatality rates were estimated for clinically diagnosed and culture confirmed cases. The number of cases notified each year, in particular those notified as septicaemia, rose significantly over the period (p < 0.0001) but there was no net change in the number of culture confirmed cases. Case fatality rates estimated from routine data fell, most markedly for cases notified as septicaemia, but the true case fatality rate of culture confirmed cases did not change between 1993 and 1995. These data suggest that reporting practice changed between 1989 and 1995 and that the ascertainment of clinically diagnosed disease improved, particularly for meningococcal septicaemia. Late in 1995, reports from all data sources increased and the age distribution of both notified and laboratory confirmed cases changed. These changes were accompanied by an increase in the proportion of infections due to Neisseria meningitidis of serogroup C and a significant increase in serotype C2a infections (p < 0.0001). Continuing efforts to reconcile data from several sources will be needed to ensure that routine data can be interpreted accurately to provide evidence for the development of future vaccination policy and to monitor vaccination programmes. In addition, the role of non-culture diagnosis will be crucial in enhancing surveillance based on clinical diagnoses.

Adolescent↗
PubMed1995

A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines.

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria/tetanus/pertussis (DTP) vaccination and febrile convulsion, and between measles/mumps/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an increased relative incidence for convulsions 0-3 days after DTP vaccination. The effect was limited to the third dose of vaccine for which the attributable risk (all ages) was 1 in 12,500 doses. Completion of vaccination by 4 months instead of 10 months after the change in the UK to an accelerated immunisation schedule may have resulted in a 4-fold decrease in febrile convulsions attributable to DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR vaccination were attributable to the measles component of the vaccine (risk 1 in 3000 doses). An excess of admissions for a convulsion 15-35 days after MMR vaccination was found only for vaccines containing the Urabe mumps strain (1 in 2600 Urabe doses). There was a causal association between MMR vaccination and ITP resulting in admission 15-35 days subsequently; there was no evidence of a mumps strain-specific effect. The estimated absolute risk of 1 in 24,000 doses was 5 times that calculated from cases passively reported by clinicians. This finding emphasises the need for active surveillance of adverse events. The record linkage method that we used is an effective way to identify vaccine-attributable adverse events.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines.

Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12-18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain (39/266, 15% vs 39/204, 19%, p = 0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27/3 rubella strain and the potential for elimination of rubella with a single dose strategy.

Antibodies, Viral↗
PubMed1995

Antibody responses and reactions to the whole cell pertussis component of a combined diphtheria/tetanus/pertussis vaccine given at school entry.

To measure the clinical effect of adding a whole cell pertussis component to diphtheria/tetanus vaccine (DT) given as a pre-school booster, 190 children aged 4-5 years were randomised by a double-blind method to receive either diphtheria/tetanus/pertussis (DTP) or DT vaccine in a 1:1 ratio at selected clinics in England. The geometric mean antibody titres to each of the three pertussis antigens were at least sixfold higher in the DTP than the DT vaccine group and equalled or exceeded those in infants immediately after primary immunisation with DTP vaccine. There were no significant differences between DTP and DT vaccinated children in their diphtheria and tetanus antitoxin levels. The frequency of large local reactions and systemic symptoms such as crying and a disturbed night was 2-3-fold higher in the DTP vaccinees than in the DT vaccinees. Medication was given to 44% of DTP and 23% of DT vaccinees (p = 0.006). Although the change to whole cell DTP vaccine at school entry would result in good pertussis antibody titres, the 2-3-fold increase in reactogenicity that would be caused may be unacceptable at a time when whooping cough is not circulating widely. Evaluation of acellular DTP vaccines given as a pre-school booster in children vaccinated under the accelerated schedule is planned.

Antibody Formation↗
PubMed1995

Adverse events and antibody response to accelerated immunisation in term and preterm infants.

A study was performed to compare adverse events and antibody response in term and preterm children vaccinated with diphtheria, tetanus, and pertussis vaccine at 2, 3, and 4 months of age. A total of 124 children were recruited and grouped according to gestational age: 37 weeks or more (n = 52), 34 to 36 weeks (n = 40), and less than 34 weeks (n = 32). Study nurses followed up children 24 hours after each vaccination to record temperature, redness, and swelling at the injection site and any systemic symptoms. Proportions of children experiencing adverse events did not differ between groups. Blood samples were obtained six weeks after the vaccination course at which time all children had protective levels of diphtheria and tetanus antitoxins. Geometric mean antibody titres (95% confidence interval) to pertussis toxin were 2754 (2042 to 3715), 5495 (4074 to 7413), and 3690 (2951 to 4677), to filamentous haemagglutinin were 541 (282 to 1023), 951 (537 to 1698), and 614 (426 to 1023), and to agglutinogens 2 and 3 were 12,106 (6918 to 21,380), 21,330 (13,183 to 34,674), and 22,387 (15,136 to 33,113) in children born at a gestational age of less than 34 weeks, 34 to 36 weeks, and 37 weeks or more respectively. These findings support the current recommendations that preterm children are vaccinated at chronological age according to the national schedule.

Age Factors↗
PubMed1995

Contrast-enhanced transcranial imaging. Results of an American phase-two study.

BACKGROUND AND PURPOSE: Pulsed color Doppler imaging of cerebrovascular structures permits rapid visual identification of the intracranial vessels. In some patients, however, the clinical utility of transcranial ultrasound examinations is limited by poor tissue penetration and inadequate imaging of vessels. This phase-two clinical trial evaluates whether administration of an echocontrast agent in such ultrasound-refractory patients enhances image acquisition enough to yield meaningful diagnostic impressions. METHODS: This is a phase-two clinical trial of safety and efficacy of the "galactose/palmitic acid-based microbubble preparation" Levovist injection (Berlex Laboratories). Thirty subjects with clinical indications for cerebrovascular imaging but refractory to transcranial Doppler studies were enrolled in a nonrandomized, single-center study. Echocontrast agent was administered intravenously in a tiered-dose protocol. Safety was determined by clinical and laboratory monitoring for 18 to 24 hours. Efficacy of contrast enhancement was determined by comparisons between each patient's precontrast (control) and postcontrast images. RESULTS: No significant patient discomfort, side effects, or adverse reactions occurred that were due to the intravenous administration of the echocontrast agent. Optimal image enhancement was obtained using the 300-mg/mL concentration (3 g bolus) of contrast. Visualization of both individual arterial segments and/or the entire circle of Willis was demonstrated. Clinical confidence of diagnostic impressions was achieved in 77% (23/30) of subjects. CONCLUSIONS: The transpulmonary ultrasound contrast agent (Levovist injection) was easily administered and found to be safe in the 30 patients studied and increased the diagnostic utility of transcranial ultrasound in 77% of the patients studied.

Adult↗
PubMed1994

The epidemiology of measles in England and Wales: rationale for the 1994 national vaccination campaign.

An epidemic of between 100,000 and 200,000 cases of measles during 1995 has been predicted in England and Wales. This prediction was based on epidemiological evidence from several sources. Notifications of measles to the Office of Population Censuses and Surveys have risen in 1994, with a high proportion of cases in children aged over 10 years. An increase in the incidence of measles was seen in data from other sources, including laboratory reports of confirmed infections and consultations with general practitioners for new episodes of measles. Antibody tests were performed on saliva and serum from notified cases in several districts. Over three quarters of the notified cases in 1994 that were confirmed occurred in children of school age. The proportion of children aged 7 to 14 years who were susceptible to measles, obtained from studies of the age specific prevalence of antibody, rose from 6.0% (146/2453) in 1986 and 1987 to 9.2% (144/1565) in 1991. Mathematical modelling has predicted that the level of susceptibility anticipated in the school age population in 1995 would have been sufficient to allow a resurgence of measles. Over half of the cases in the resulting epidemic would have occurred in people aged at least 10 years and, because mortality is higher in this older age group, between 30 and 60 deaths would have occurred. A mass campaign to immunise all children of school age is expected to cause an immediate reduction in disease transmission and prevent a substantial toll of morbidity and mortality.

Adolescent↗
PubMed1994

Age specific antibody prevalence to parvovirus B19: how many women are infected in pregnancy?

Infection with parvovirus B19 is an important cause of late fetal mortality in the second trimester, and many infections in pregnancy remain undiagnosed. A serological survey stratified by age has been used to estimate the incidence of maternal infection with parvovirus B19 in pregnancy. Serum remaining from specimens submitted for diagnosis from 6864 people of all ages to seven public health laboratories in England was tested for antibody to parvovirus B19. The antibody prevalence rose with age to 45% at 10 years and 60% to 70% in adults. The age specific force of infection was highest in children aged less than 10 years and lowest in adults. Maternal infection with parvovirus B19 is estimated to occur in approximately one pregnancy in 400. It has been estimated that fetal death occurs in 9% of these cases, which suggests that parvovirus B19 may cause more than 150 fetal deaths in England and Wales each year. Testing for evidence of recent infection with parvovirus B19 should be considered for unexplained cases of fetal hydrops in the second trimester, especially in years of parvovirus B19 epidemics.

Adolescent↗
PubMed1994

Overexpression of heat shock protein (hsp) 70 associated with abnormal p53 expression in cancer of the pancreas.

Heat shock proteins (hsp) are involved in degradation or chaperoning nascent and abnormal proteins to various subcellular locations. p53 tumour suppressor gene overexpression and mutation occur frequently in pancreatic cancers. Mutant p53 proteins produced in cancers of other sites have been found to form complexes with hsp 70. Consequently, binding to hsp 70 may be used to indicate the presence of mutant p53 proteins. The presence of hsp 70 was investigated by immunohistochemistry in core biopsies of 42 adenocarcinomas of the pancreas (well differentiated, N = 1 and moderate to poorly differentiated, N = 41). Four cases of islet cell tumours were included in the study. These neoplasias were compared with biopsies of chronic pancreatitis (N = 9) and normal pancreas (N = 5). The majority of adenocarcinomas, 24/42 (57%), showed expression of both hsp 70 and p53. None of the islet cell tumours or cases of chronic pancreatitis showed p53 and hsp 70 coexpression. Only 1 (20%) of the normal pancreas showed concurrent nuclear immunostaining for p53 and cytoplasmic immunostaining for hsp 70. The high proportion of pancreatic adenocarcinoma showing immunoreactivity for both hsp 70 and p53 may indicate high mutation rate of the p53 gene in this tumour. Further studies using molecular techniques are required to elucidate the nature of both hsp and p53 genes in pancreatic cancers.

Adult↗
PubMed1990

Clinically isolated mandibular relapse in childhood acute leukemia.

With improved methods for preventing extramedullary relapse in the leptomeninges and gonads, the problem of clinically isolated relapse at other sites has become more significant. The authors report here two children with acute leukemia who developed mandibular relapse while in complete hematologic remission. One had been off chemotherapy for acute lymphoid leukemia for 2.5 years. The other child is apparently the first patient with promyeloid morphologic features to experience relapse at this site. Both children are in second complete remission and off treatment after local radiation therapy and second courses of chemotherapy. Review of these two and five previously reported isolated mandibular relapses in childhood leukemia indicate that they are usually delayed until after cessation of therapy. Treatment with radiation and combination chemotherapy can result in long remission and possibly cure.

Child, Preschool↗
PubMed1989

Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia.

To test the hypothesis that spironolactone-hydrochlorothiazide (Aldactazide) will improve urine output and lung function in infants with bronchopulmonary dysplasia, we studied 21 hospitalized, spontaneously breathing, oxygen-dependent infants with chronic bronchopulmonary dysplasia. Infants were randomly assigned to receive either a 1:1 mixture of spironolactone and hydrochlorothiazide orally (n = 12) (3 mg/kg/day of both compounds) or no treatment (n = 9) for 6 to 8 days each. Dynamic lung compliance, total pulmonary resistance, and hemoglobin oxygen saturation were measured on the first and last days of each study period. Fluid intake and urine output were measured each day. Although the treatment significantly increased urine output, neither lung mechanics nor oxygenation were improved by the drug. The magnitude of the diuresis achieved with spironolactone-hydrochlorothiazide treatment was comparable to the diuresis achieved in a previous study of furosemide treatment (J Pediatr 1986:109;1034-9). Statistical analysis indicated that a type II error was an unlikely explanation for our failure to detect a beneficial effect. In three patients, doubling the oral dose did not improve lung mechanics or oxygenation. We speculate that diuresis per se is not responsible for lung function improvement during treatment with other drugs with diuretic properties.

Bronchopulmonary Dysplasia↗
PubMed1987

Cloned extrachromosomal circular DNA copies of the human transposable element THE-1 are related predominantly to a single type of family member.

The 2300 base-pair transposon-like human element, THE-1, has been identified in the extrachromosomal circular DNA of the established human cell line HeLa as a relatively homogeneous population of covalently closed 1900 base-pair molecules. THE-1, which has been classified tentatively as a retroviral-like transposable element (a retrotransposon), is present in the extrachromosomal circular DNA of African green monkey (BSC-1) and human lymphoblastoid (Jurkat) cell lines. The 1900 base-pair extrachromosomal elements isolated and cloned from HeLa cells (1) appear to contain only THE-1-specific nucleotide sequences, (2) are circularized versions of the linear chromosomal sequence, and (3) are related predominantly to a single, or single type of, family member.

Autoradiography↗
PubMed1987

Isolated gonadotropin-releasing hormone neurons harvested from adult male rats secrete biologically active neuropeptide in a regular repetitive manner.

Immunochemical treatments for the recovery of viable GnRH neurons from adult male rats have previously been described by this laboratory. In the present report, efforts were made to limit cellular adhesion, as well as the proteolytic and mechanical damage which occurred during isolation of the neurons, in order to determine if such damage may account for failure of the isolated cells to exhibit spontaneous neuropeptide release. These modifications prevented the loss of assayable GnRH during the isolation process, and neurons recovered from individual rats in this study contained 10.7 +/- 2.5 ng GnRH. Further, all isolated neuronal preparations exhibited spontaneous peptide release which continued in a regular repetitive manner. When maintained in closed chambers, these preparations released 105 +/- 42 pg/ml biologically active GnRH at 18.9 +/- 0.4-min intervals. In contrast, GnRH release from heterologous preparations was characterized by erratic low level pulses. The results from this work suggest that independent neuroendocrine properties of GnRH neurons may be responsible for tonic gonadotropin secretion in castrated adult male rats and that the erratic patterns of gonadotropin release in gonadally intact males may be related, in part, to coupling between GnRH neurons and unidentified neuronal factors.

Animals↗
PubMed1986

Osteoblastic insufficiency is responsible for maintenance of osteopenia after loss of ovarian function in experimental beagle dogs.

Bone loss developing after cessation of ovarian function in humans represents a major health problem. To establish the value of ovariohysterectomy in female beagle dogs as a model for bone loss and to study static and dynamic parameters of bone associated with the negative bone balance occurring after cessation of ovarian function, we performed iliac crest bone biopsies before and 4 months after ovariohysterectomy in eight beagle dogs and in five sham-operated controls. Cessation of ovarian function was documented by an increase in serum levels of LH 4 weeks after ovariohysterectomy. There was no change in serum calcium, phosphorus, and creatinine during the 4 months of the study. Cancellous bone mass and trabecular mean wall thickness decreased significantly after ovariohysterectomy (P less than 0.01). In addition, the number of osteoblasts was increased and the bone formation rate per osteoblast, that is, the activity of bone-forming cells, was decreased (P less than 0.01). Parameters of bone resorption were not significantly altered in the animals with ovariohysterectomy. No changes in histomorphometric parameters of bone structure, formation or resorption were observed in the sham-operated controls. These data indicate that ovariohysterectomy in beagle dogs may serve as a useful model for bone loss associated with cessation of ovarian function. Osteoblastic insufficiency appears to play a major role in the maintenance of bone loss occurring after ovariohysterectomy in beagle dogs.

Amenorrhea↗
PubMed1985

Duplex scanning with continuous wave Doppler for carotid disease.

Duplex scanning with the use of continuous wave Doppler instrumentation was used for the evaluation of carotid disease and compared to angiography. In twenty such patients 100% accuracy for diagnosis of total occlusion by Duplex scanning with continuous wave Doppler, was obtained. The sensitivity for those patients with 50%-99% stenosis was 92% and for those patients with 20%-49% stenosis was 75%. The overall accuracy for this diagnostic test for all groups of stenosis was 85%. This compares favorably with other noninvasive vascular techniques and is felt to be an accurate and useful technique for the detection of carotid stenosis. Several advantages of this technique are pointed out.

Angiography↗