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Biomedical subjects

L P Hunt

Publications and source records attributed to L P Hunt.

At least 19 recordsLinked to original sources

Use of clinical risk factors to identify postmenopausal women with vertebral fractures.

INTRODUCTION AND HYPOTHESIS: Previous studies have been unable to identify risk factors for prevalent vertebral fractures (VF), which are suitable for use in selection strategies intended to target high-risk sub-groups for diagnostic assessment. However, these studies generally consisted of large epidemiology surveys based on questionnaires and were only able to evaluate a limited number of risk factors. Here, we investigated whether a stronger relationship exists with prevalent VF when conventional risk factors are combined with additional information obtained from detailed one-to-one assessment. METHODS: Women aged 65-75 registered at four geographically distinct GP practices were invited to participate (n=1,518), of whom 540 attended for assessment as follows: a questionnaire asking about risk factors for osteoporosis such as height loss compared to age 25 and history of non-vertebral fracture (NVF), the get-up-and-go test, Margolis back pain score, measurement of wall-tragus and rib-pelvis distances, and BMD as measured by the distal forearm BMD. A lateral thoraco-lumbar spine X-ray was obtained, which was subsequently scored for the presence of significant vertebral deformities. RESULTS: Of the 509 subjects who underwent spinal radiographs, 37 (7.3%) were found to have one or more VF. Following logistic regression analysis, the four most predictive clinical risk factors for prevalent VF were: height loss (P=0.006), past NVF (P=0.004), history of back pain (P=0.075) and age (P=0.05). BMD was also significantly associated with prevalent VF (P=0.002), but its inclusion did not affect associations with other variables. Factors elicited from detailed one-to-one assessment were not related to the risk of one or more prevalent VFs. The area under ROC curves derived from these regressions, which suggested that models for prevalent VF had modest predictive accuracy, were as follows: 0.68 (BMD), 0.74 (four clinical risk factors above) and 0.78 (clinical risk factors + BMD). Analyses were repeated in relation to the subgroup of 13 patients with two or more VFs, which revealed that in this instance, the Margolis back pain score and rib-pelvis distance were associated with the presence of multiple VFs (P=0.022 and 0.026, respectively). Moreover, the predictive value as reflected by the ROC curve area was improved: 0.80 (BMD), 0.88 (the four most predictive clinical risk factors consisting of the height loss, past NVF, Margolis back pain score and rib-pelvis distance) and 0.91 (clinical risk factors + BMD). CONCLUSIONS: Evaluation of additional risk factors from detailed one-to-one assessment does not improve the predictive value of risk factors for one or more prevalent vertebral deformities in postmenopausal women. However, the use of factors such as the Margolis back pain score and rib-pelvis distance may be helpful in identifying postmenopausal women at high risk of multiple prevalent VFs.

Aged↗

Pregnancy outcomes in women with or without placental malaria infection.

OBJECTIVE: To assess delivery outcomes in women with placental malaria who presented at public hospitals in Kisumu, a holoendemic region in western Kenya. METHODS: A cross-sectional study using both histology and molecular biology was conducted with 90 consecutive pregnant women who presented at 3 hospitals during a 2-week period. Data collectors completed standardized questionnaires using each patient's hospital record and physical examination results, and registered birth indices such as weight, head circumference, and weight-head ratio. Malaria infection of the placenta was assessed using a molecular biology approach (for genomic differences among parasite species) as well as histology techniques. Of the 5 histologic classes of placental infection, class 1 corresponds to active infection and class 4 to past infection; class 2 and 3 to active chronic infection; and class 5 to uninfected individuals. Plasmodium species typing was determined by polymerase chain reaction amplification of the parasite's genome. RESULTS: In newborns at term, low birth weight was directly associated with classes 2 and 4 of placental infection (P = 0.053 and P = 0.003, respectively), and differences in birth weight remained significant between the 5 classes (P < 0.001) even after adjusting for parity and mother's age. Plasmodium falciparum was the only detected parasite. CONCLUSIONS: In Kisumu, infection with P. falciparum is an important cause of low birth weight and morbidity when it is associated with histologic classes 2 and 4 of placental infection. Moreover, polymerase chain reaction assays should be supported by ministries of health as an ancillary method of collecting data for malaria control during pregnancy and providing a baseline for future interventions.

Adolescent↗

Characterisation of morbidity in a UK, hospital based, obesity clinic.

AIM: To identify clinical features which predict those most at risk of co-morbidities within an obesity clinic. METHODS: Children attending an obesity clinic had fasting glucose, insulin, and lipids measured prior to a standard oral glucose tolerance test (OGTT). History and examination established birth weight, family history of type 2 diabetes/obesity, pubertal status, and presence of acanthosis nigricans. Central and total fat mass was estimated by bio-impedance. RESULTS: Of the 126 children evaluated, 10.3% (n = 13) had impaired glucose tolerance (IGT); the majority (n = 11) of these would not have been identified on fasting glucose alone. Those with IGT were more likely to have a parental history of type 2 diabetes (relative risk 3.5). IGT was not associated with acanthosis nigricans. Twenty five per cent (n = 19) of those evaluated (n = 75) had evidence of the "metabolic syndrome" (MS). HDL cholesterol and triglyceride levels were related to insulin sensitivity (HOMA-R); HDL cholesterol was also related to birth weight SDS. We observed a trend for those with MS to have a lower birth weight SDS. The severity of obesity did not influence the likelihood of IGT or MS. CONCLUSIONS: Significant numbers of obese children have associated co-morbidities. Analysis of fasting blood glucose samples alone is not satisfactory to adequately evaluate glucose homoeostasis. The overall level of obesity does not predict co-morbidities. Special attention should be given to those with parental diabetes and a history of low birth weight who are more likely to have IGT and abnormal lipid profiles respectively.

Adolescent↗

Gram-negative bacteraemia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome.

Gram-negative infection is an important cause of morbidity and mortality after unrelated donor-bone marrow transplantation (UD-BMT). We performed a retrospective case-control study to examine the risk factors, prophylaxis, therapy and outcome of Gram-negative bacteraemia (GNB) in 428 patients undergoing UD-BMT. The incidence of GNB was 3.6% in children and 19% in adults. Of the adults, 11% developed GNB >60 days post UD-BMT. Predisposing risk factors for GNB included 'high-risk' disease status, chronic graft-versus-host disease and use of systemic steroids. Fever, a raised C-reactive protein (CRP) and hypotension were common findings at presentation. Patients were routinely given prophylactic ciprofloxacin: resistance to this antibiotic was seen in 33% of isolates. We identified an age-matched control group undergoing UD-BMT over the same time period as the study group. Gram-positive bacteraemia was significantly more common in cases than controls. Mortality from GNB was 17% in children and 24% in adults. We conclude that GNB is a common complication of UD-BMT with a high associated mortality. Patients should be educated further to present rapidly with symptoms suggestive of infection.

Adolescent↗

Widespread insecticide resistance in head lice to the over-the-counter pediculocides in England, and the emergence of carbaryl resistance.

BACKGROUND: Increasing resistance to insecticides used for the control of head lice infestation has been documented over the last decade. Treatment failure and tolerance to insecticides have been validated in a number of studies undertaken in several U.K. centres. OBJECTIVES: To establish the extent of insecticide resistance in head lice and acetylcholinesterase activity in the presence of carbaryl in head lice. METHODS: Head lice were collected from school children in four centres across England (Exmouth, Loughborough, Leeds and South Shields), and tested in their response to the insecticides permethrin, phenothrin, malathion and carbaryl. Data were compared with information collected in Bristol and Bath in 1998 and with susceptible body lice. The activity of louse acetylcholinesterase was measured with and without carbaryl in head lice collected in Bristol, Leeds, Loughborough and in body lice. The efficacy of a 1% carbaryl lotion was compared in children in Bristol and Leeds. RESULTS: Compared with body lice, head lice from all six centres were significantly different in their response (P < 0.0001) to permethrin, phenothrin and malathion after 2-h exposure tests. There were significant differences in louse acetylcholinesterase activity in body lice, and head lice collected in Loughborough and Bristol in the presence or absence of carbaryl (P < 0.001), indicating enzyme inhibition. However, the difference for lice from Leeds was not significant (P = 0.363) suggesting that the enzyme was resistant to carbaryl. Eighty-nine per cent of children treated in Leeds with carbaryl were cured compared with 100% in Bristol. CONCLUSIONS: The data suggest head lice resistance is present in many parts of England to over-the-counter products containing synthetic insecticides (permethrin, phenothrin and malathion). They further suggest that resistance is starting to develop to carbaryl in head lice in Leeds and that extensive use of this product would lead to significant resistance.

Acetylcholinesterase↗

Biological versus chronological ageing of oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment.

BACKGROUND: The present study addresses the issue of biological ageing of the oocyte (as indicated by basal serum FSH levels) versus chronological ageing. METHODS: 1019 infertile but ovulating women were studied in their first cycle of IVF treatment. A series of logistic regression models were developed to assess statistical significance of effects of age and FSH on implantation rates and live babies born. RESULTS: The number of oocytes retrieved and embryos available for transfer declined with increasing age and basal serum FSH concentrations. Fertilizing ability of oocytes increased with advancing age but was not affected by FSH concentrations. Although the number of oocytes or embryos available for transfer had no independent effect on implantation rates, the implanting ability of fertilized oocytes (embryos) was inversely related to increasing age and independently to FSH. The chance of a baby being born, however, was determined more by age than by serum FSH. CONCLUSIONS: Ovarian ageing affecting oocyte quality and fecundity can occur independently of chronological age. This has important practical implications whereby serum basal FSH measurement may be a valuable prognostic index, though chronological age remains important.

Adult↗

Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Adult↗

Expected contribution to serum oestradiol from individual ovarian follicles in unstimulated cycles.

Data relating serum oestradiol concentration to follicle size in unstimulated cycles are lacking. We provide precise data on serum concentrations expected for any follicle diameter (FD) in the mid- to late follicular phase. Infertile women (n = 35) with apparently normal ovulatory cycles were studied in detail in 128 unstimulated monofollicular cycles leading to IVF. Using mathematical modelling to account for repeated cycles in the same woman, the relationship between serum oestradiol and FD was explored and reference ranges for serum oestradiol at individual FD were calculated. Serum oestradiol concentrations [number of patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In 'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for each size of follicle the oestradiol distribution was skewed. Functional oocyte competence varied in apparently normal ovulatory cycles and was correlated with pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide limits for maturing follicles of any given diameter prior to the onset of the LH surge.

Estradiol↗

Sensorineural hearing loss and prematurity.

OBJECTIVE: To elucidate clinical antecedents of sensorineural hearing loss (SNHL) in very preterm infants. DESIGN: Case-control study. SUBJECTS: Fifteen children < 33 weeks' gestation with significant SNHL born between 1 January 1990 and 31 December 1994, detected within 9 months of birth, and 30 matched control children. METHODOLOGY: Perinatal variables in the two groups were compared using non-parametric tests and conditional logistic regression (EGRET). RESULTS: Median birth weight for the index group was 960 g (range 600-2914 g) compared with 1026 g (range 410-2814 g) for controls. Children with SNHL had longer periods of intubation, ventilation, oxygen treatment, and acidosis, and more frequent treatment with dopamine or frusemide. Neither peak nor trough aminoglycoside levels, nor duration of jaundice or level of bilirubin varied between groups. However, SNHL was more likely if peak bilirubin levels coexisted with netilmicin use (odds ratio (95% confidence interval) 14.2 (1.8 to 113.6)) or if acidosis occurred when bilirubin levels were over 200 micromol/l (OR 8.0 (0.9 to 71.6). Frusemide use in the face of high serum creatinine levels (OR 8.9 (1.1 to 74.5)) or netilmicin treatment (OR 5.0 (0.99 to 24.8)) was also associated with SNHL. At 12 months of age, seven of 15 children with SNHL had evidence of cerebral palsy compared with two of 30 controls (OR 12.3 (2.1 to 71)). CONCLUSIONS: Preterm children with SNHL required more intensive care in the perinatal period and developed more neurological complications than controls. Among very preterm babies, the coexistence of risk factors for hearing loss may be more important than the individual factors themselves.

Aminoglycosides↗

Nursing at the forefront.

The Government sees nurses at the forefront of the drive for improvement in healthcare delivery. In this article, Lord Hunt, the Government spokesperson on nursing, spells out the role that nurses are expected to play in this process. Clinical governance has undoubtedly already been mentioned if not enacted in your Trust, and maybe some of you have applied for the discretionary points now on offer. Whatever the outcome of these and other strategies, the future is going to be different for perioperative nurses, whether we like it or not. Your views, as ever, are welcome....

Education, Nursing↗

Effect of time post mortem on the concentration of endotoxin in rat organs: implications for sudden infant death syndrome (SIDS).

The aim of the study was to test the following hypotheses: (i) that endotoxin injected 40 min prior to death can be detected in rat organs post mortem and (ii) that endotoxin levels do not change with increasing time post mortem. Rats were injected with or without endotoxin in buffered saline, 40 min prior to being killed. Endotoxin levels in rat organs were assessed using a Limulus amoebocyte assay. The effect of storage time post mortem was assessed by following various storage regimes at 25 degrees C and 8 degrees C. Significant differences (P = < 0.001) in endotoxin levels of all samples tested were found between rats injected with and without endotoxin. A significant increase in detectable endotoxin was observed between 0 h and 6 h post mortem in rats injected with or without endotoxin. No difference in detectable endotoxin levels in the kidney, liver and spleen was observed from 30 h to 102 h post mortem in rats injected with or without endotoxin. In rats injected with endotoxin, detectable endotoxin levels in the heart were raised between 0 h and 6 h, 6 h and 54 h, and 30 h and 78 h. Endotoxin injected into rats 40 min prior to death can be detected post mortem. For rats injected with saline or endotoxin prior to death levels in the kidney, liver and spleen were not affected by storage at 8 degrees C for 30-102 h, after initial storage at room temperature for 6 h. Levels of endotoxin detected in the hearts of rats injected with saline were not affected by storage up to 102 h. In rats injected with endotoxin prior to death, detectable levels in the heart were significantly affected by increasing time in storage.

Animals↗

Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia.

The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected only after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD-), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P <.001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).

Adolescent↗

Cytomegalovirus infection in recipients of related and unrelated donor bone marrow transplants: no evidence of increased incidence in patients receiving unrelated donor grafts.

Recent reports suggest an increased incidence of cytomegalovirus (CMV) infection in recipients of unrelated donor (UD) bone marrow transplantation (BMT). In this study we have collated the incidence of CMV infection and disease in sequential UD (n = 119) and related donor (RD; n = 79) BMT performed in a single institution over a 7-year period. Low-risk patients (CMV seronegative recipient and donor) accounted for 51% of UD BMT (n = 61) and 62% of RD BMT (n=49), with CMV excretion documented in one RD BMT only. The remaining high-risk patients received identical prophylaxis regimens with aciclovir and intravenous immunoglobulin (IVIG). Two groups consisting of 58 UD BMT (median age 9.0 years, range 0.7-45.3 years) and 30 RD BMT (median age 13.6 years. range 1.6-47.6 years) were analysed. CMV reactivation/re-infection was documented in 15 UD BMT (26%) and 10 RD BMT (33%) (P = 0.72), and CMV disease in four UD BMT (8%) and four RD BMT (13%) (P = 0.533). In this series the risk of CMV excretion and disease following UD BMT was similar to that following RD BMT.

Acyclovir↗

Comparison between two prospective studies of cardiovascular disease carried out amongst renal replacement patients in UK and Italy.

The data on 256 non-diabetic patients entering renal replacement therapy (RRT) in Manchester between 1 January 1983 and 31 December 1986 were compared with those on 84 non-diabetic patients entering RRT in Milan between 1 January 1983 and 31 December 1988. In each unit, patients had been studied prospectively and the findings were entered on the same database for this report. At the end of the study, 68% of patients were alive in each centre and in each 16% had died from cardiovascular disease. 11% of Manchester and 18% of the Milan patients developed angina. The data do not support the view that there is a differential risk for cardiovascular disease in the Northern and Southern parts of Europe and it may be advisable to study the matter prospectively in a larger patient cohort.

Adolescent↗

Social disadvantage, family composition, and diabetes mellitus: prevalence and outcome.

OBJECTIVE: To investigate the relation between social disadvantage and family composition on diabetes prevalence and diabetes care outcome. DESIGN: Retrospective audit in the south west of England of 801 children with diabetes mellitus. MAIN OUTCOME MEASURES: Prevalence of diabetes in relation to the Townsend index. Admissions to hospital with diabetes related problems, glycated haemoglobin, time spent in hospital, outpatient attendance rates. RESULTS: There was no association between social status and diabetes prevalence. Social deprivation increased the likelihood of admission for hypoglycaemia. Children living with a single parent were more likely to be admitted to hospital with a diabetes related problem and stay in hospital longer. Having either a parent with diabetes or a single parent increased the rates of clinic non-attendance. No association was identified between medium term diabetes control and either social disadvantage or single parent status. CONCLUSIONS: Social disadvantage has no effect on diabetes prevalence and little on diabetes outcome in childhood. Family structure and parental diabetes have adverse effects on some aspects of diabetes outcome.

Adolescent↗