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Biomedical subjects

J Lea

Publications and source records attributed to J Lea.

At least 19 recordsLinked to original sources
PubMed2004

Prognostic factors in brain metastases: can we determine patients who do not benefit from whole-brain radiotherapy?

AIMS: Whole-brain radiotherapy (WBRT) is a standard treatment recommendation for patients with brain metastases. The goal of treatment is symptom control, which in the short run can be often achieved by steroids. Patients with a short life expectancy may not derive benefit from the addition of radiation. The ability to identify this group would aid the decision of whether to recommend WBRT. MATERIALS AND METHODS: Data on all patients referred for WBRT to palliative radiotherapy teams at two comprehensive cancer centres were prospectively collected over a 2-year period. The most frequent radiation dose and fractionation was 2000 cGy in 5 fractions over 1 week. Multivariate logistic regression analysis using forward stepwise selection process was used to develop a prediction model for early death (before 8 weeks). The variables considered were sex, performance status, primary disease, weight loss, age, time from primary diagnosis to brain metastases diagnosis, number of metastatic sites and Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) status. RESULTS: Two hundred and seventy-five patients with brain metastases were assessed. The median follow-up was 19 weeks, and estimated median overall survival was 5.3 months. Multivariate regression revealed Eastern Cooperative Oncology Group (ECOG) performance status and number of metastatic sites to be significant predictors of early death. The odds ratios were 2.38 (95% confidence interval [CI] 1.77-3.19) and 1.39 (95% CI 1.07-1.81), respectively. Sixty-eight per cent of patients could be correctly classified; however, 55% would have been incorrectly predicted to die early. CONCLUSIONS: Poor performance status and number of metastatic sites are useful predictors of early death. A regression model was highly predictive overall, but this was primarily due to a high negative predictive value of 86%. The ability to predict patients who would die early (positive predictive value) was only 45%. Thus, despite the understanding that we are over-treating a subset of patients, further research is required to identify patients who do not require radiotherapy.

Adult↗
PubMed2001

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Adrenergic beta-Antagonists↗
PubMed2001

Structure of three high voltage-activated calcium channel alpha1 subunits from Schistosoma mansoni.

Voltage-gated calcium (Ca2+) channels contribute to impulse propagation in excitable cells and also regulate intracellular levels of Ca2+. High voltage-activated (HVA) Ca2+ channels are heteromultimeric membrane proteins. The pore-forming, voltage-sensing subunit is the alpha1 subunit. We have cloned 3 HVA Ca2+ channel alpha1 subunit cDNAs from Schistosoma mansoni. One of these sequences most closely resembles the L-type class of HVA alpha1 subunits. The other two sequences are most closely related to non L-type alpha1 subunits. These schistosome alpha1 subunits have many of the features common to HVA Ca2+ channels, but also have distinct structural motifs. Analysis of the structural and functional properties of schistosome Ca2+ channel subunits may provide information about these critical components of excitable cells.

Amino Acid Sequence↗
PubMed2000

Reproductive stage and history affect the phonotactic preferences of female midwife toads, Alytes muletensis.

We investigated whether the reproductive stage or reproductive history of females affects their preferences for male calls that differ in frequency. We repeatedly tested gravid female midwife toads prior to and immediately after mating, and during ovulation. When females were ovulating they were much more consistent in their choice of call than when they were gravid but not ovulating. When females had recently mated they still showed positive phonotaxis, but did not reliably discriminate between alternative calls. This study is the first to test gravid female anurans repeatedly at different stages in their reproductive cycle (ovulating or not; pre- and postmating). It highlights the need to treat with caution the results from population-based preference studies in which individuals are tested only once, and in which variation in reproductive state is not taken into account. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1995

Maintenance of stellite and tungsten carbide saw tips: respiratory health and exposure-response evaluations.

OBJECTIVE: To study exposure to cobalt and chromium in saw maintenance rooms and test respiratory health among saw filers at lumber mills. Hard-metal lung disease is associated with cobalt in the manufacture of tungsten carbide tools; recently it has also been reported among tool maintenance workers. Lumber mills often use saws tipped with tungsten carbide or with a newer alloy, stellite (containing more cobalt, as well as chromium). METHODS: A cross sectional study of 118 saw filers at eight lumber mills was carried out that included a standardised questionnaire, spirometry, personal air sampling, and examination of tasks every 10 minutes (by observation). Comparison data were from a study of bus mechanics tested with similar methods. RESULTS AND CONCLUSION: Cobalt exposure was associated with tungsten carbide grinding but not with stellite grinding. Chromium exposure was associated mainly with stellite welding. Saw filers had a twofold increase in phlegm and wheeze (P < 0.01) and a threefold increase in cough, phlegm, and wheeze related to work (P < 0.001), but no increase in breathlessness. Stellite welding was associated with a significant increase in nasal symptoms and cough related to work and a small decrease in airflow (forced expiratory volume in one second/forced vital capacity (FEV1/FVC%), P < 0.05). Saw filers wet grinding with tungsten carbide had significant reductions in forced expiratory lung volumes (FEV1 and FVC, P < 0.05) and were significantly more likely to have FEV1 and FVC values in the abnormal range. Cobalt exposure (in wet grinding) and duration of work that involved tungsten carbide grinding were both associated with significant reductions in FEV1 and FVC. Average cobalt exposures in this study were about 5 micrograms/m3, well below the currently accepted permissible concentration, which suggests that the current workplace limit for cobalt may be too high.

Adult↗
PubMed1992

Predictors of infection in chronic lymphocytic leukaemia (CLL).

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001).

Aged↗
PubMed1991

Hypogammaglobulinaemia in low grade B cell tumours; significance and therapy.

Bacterial infection is an important cause of morbidity and mortality in patients with B-cell tumors; this is related to their secondary hypogammaglobulinaemia. Two studies of intravenous replacement therapy [IVIg] have been performed in such patients: a crossover study over two years and a randomised, multicentre study over one year. Both involved infusions of IVIg [400 mg/Kg] or an equivalent volume of saline every three weeks for one year. In both studies, serious bacterial infections were considerably reduced by IVIg. Viral and fungal infections were uncommon. In the crossover study bacterial infections were more frequent in periods in which patients serum IgG levels were below the normal range [less than 6.4 g/l]. The sites of bacterial infection were similar in these studies to those in previously published reports, namely respiratory tract, skin, urinary tract and blood. There were a few mild adverse reactions which were related to the rate of infusion, but no serious toxic effects. Haematological parameters were not significantly changed by IVIg at this dose and disease progression did not appear to be changed.

Agammaglobulinemia↗
PubMed1989

Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors.

A randomized crossover study of prophylactic immunoglobulin (IgG) therapy was performed in patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin's lymphoma (NHL). Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously (IV) every 3 weeks for 1 year. They were then switched to the alternative preparation for another year. The number of serious bacterial infections was significantly less (P = .001; Mainland's cross-over method) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L (P = .046; Fisher's exact test).

Aged↗
PubMed1980

Chromosome studies of children with specific speech and language delay.

Among 88 children with speech and language problems from whom chromosome results were obtained, four were identified with a chromosome anomaly. Three had sex chromosome aneuploidy and had developmental problems, particularly with articulation. The fourth child had low-grade trisomy 21 in blood, with minimal signs of Down's syndrome but with bilateral conductive hearing loss. It is suggested that delay in speech development is one facet of the developmental problems that may be significant in later behavioural problems in adolescent and adult males with X and Y aneuploidy.

Adolescent↗
PubMed1978

Ultrasound placental site in relation to bloody taps in midtrimester amniocentesis.

In an unselected, consecutive series of 137 midtrimester amniocenteses for prenatal genetic diagnosis, it was found that the incidence of blood contamination of amniotic fluid samples was similar regardless of placental site as determined by ultrasound localization. Three (5.8%) patients with anterior placental location versus 5 (9.1%) patients with posterior placentas had gross blood in the amniotic fluid by visual inspection. These results support the view that placental penetration during amniocentesis is not the major cause of bloody taps. Ultrasound studies done prior to midtrimester amniocentesis should, perhaps, be more specifically evaluated in relation to pregnancy information obtained rather than solely as an aid to improve technical performance of amniocentesis.

Amniocentesis↗
PubMed1976

Screening for intrauterine growth retardation using the ultrasound biparietal diameter.

Fifteen hundred patients were scanned to predict fetal age and weight by biparietal diameter measurement. three hundred eleven patients had more than one scan. Forty-three small for gestational age (SGA) babies were ultimately delivered in this population. Prenatal ultrasound screening criteria for grouping into appropriate for gestational age (AGA) or small for gestational age (SGA) categories were: a) only an absolute biparietal diameter below the third percentile for the reference Rochester region population; b) only delta BPD calculated as less than 50 percent of the mean growth rate for the reference population; and c) a combination of these two factors. Intrauterine growth retardation was most accurately determined when an absolutely small biparietal diameter was found (at the time of the last ultrasound examination) in a woman with accurate gestational age assessment. Least accurate was the prediction based on one biparietal diameter measurement in a woman with poor clinical dates. A 50 percent false positive detection rate and poor sensitivity to intrauterine growth retardation were found using ultrasound biparietal diameter measurements as a screening test in this manner.

Cephalometry↗