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Biomedical subjects

David Hall

Publications and source records attributed to David Hall.

At least 19 recordsLinked to original sources

Contrasting signal transduction mechanisms in bacterial and eukaryotic gene transcription.

All known cell types use signal transduction systems to respond to an extracellular or intracellular event. The role of these systems can be to adapt to environmental changes or simply to maintain homeostasis. Cells detect and respond to stimuli in a number of ways. Here we review the mechanisms involved in the transmission of a signal from point of detection to site of action. In particular, a comparison is made between the signalling networks which function in gene transcription in bacterial and eukaryotic cells. Knowledge of the similarities between the systems found in the two types of cells can provide a better understanding of the function and origin of signalling components. In addition, the divergence evident can be exploited by molecules that modulate or disrupt the function of differential signalling mechanisms.

Animals↗

Clinal variation in phyB2, a candidate gene for day-length-induced growth cessation and bud set, across a latitudinal gradient in European aspen (Populus tremula).

The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short-day-induced bud set and growth cessation in Populus. We characterized patterns of DNA sequence variation at the putative candidate gene phyB2 in 4 populations of European aspen (Populus tremula) and scored single-nucleotide polymorphisms in an additional 12 populations collected along a latitudinal gradient in Sweden. We also measured bud set from a subset of these trees in a growth chamber experiment. Buds set showed significant clinal variation with latitude, explaining approximately 90% of the population variation in bud set. A sliding-window scan of phyB2 identified six putative regions with enhanced population differentiation and four SNPs showed significant clinal variation. The clinal variation at individual SNPs is suggestive of an adaptive response in phyB2 to local photoperiodic conditions. Three of four SNPs showing clinal variation were located in regions with excessive genetic differentiation, demonstrating that searching for regions of high genetic differentiation can be useful for identifying sites putatively involved in local adaptation.

Crosses, Genetic↗

Qualification discrepancies between urban and rural emergency department physicians.

The purpose of this study was to describe and compare the residency training and board certification credentials of physicians staffing rural and urban emergency departments (EDs) in the predominately rural states of the upper Midwest. EDs in Nebraska, North Dakota, and South Dakota with annual patient volumes greater than 10,000 met inclusion criteria for the study. ED administrators responded to surveys via mail, addressing physician training and board certification status and ED descriptive statistics. Thirty-four EDs met the inclusion criteria for the study with 26 responding (76%). ED physicians reported 50.6% American Board of Emergency Medicine (ABEM) certification and 33.1% residency training in Emergency Medicine (EM). Physicians staffing urban (metropolitan statistical area, MSA) EDs reported ABEM certification and residency training more frequently than those working in rural (non-MSA) EDs (65.2% vs. 30.8% and 48.3% vs. 12.3%, respectively). The results of this study reveal significant discrepancies between urban and rural EDs in physician board certification and residency training.

Certification↗

Non-elective Caesarean section: how long do we take to deliver?

This study measured the decision to delivery time intervals in non-elective caesarean sections and compared them to the 30-min interval suggested by international literature. It also evaluated fetal outcome. A 3-month prospective evaluation of all (n=178) non-elective caesarean sections was performed, using a structured time and data sheet, in a tertiary centre. Operations were divided into 'emergency', most pressing and 'urgent' where maternal or fetal compromise were not immediately life-threatening. The median interval for the 100 emergency cases was 48 min, and 59 min for the 78 urgent cases. Only 28 (15.7 per cent) of decision to delivery intervals were within 30 min. Twenty-two babies (12.4 per cent) had Apgar scores of below 7 at 5 min. Most decision to delivery intervals exceeded 30 min. It may be wiser to train staff to recognize and respond appropriately to emergencies than insisting on rigid decision to delivery intervals.

Apgar Score↗

Early onset severe pre-eclampsia: expectant management at a secondary hospital in close association with a tertiary institution.

OBJECTIVES: Early onset severe pre-eclampsia is ideally managed in a tertiary setting. We investigated the possibility of safe management at secondary level, in close co-operation with the tertiary centre. DESIGN: Prospective case series over 39 months. SETTING: Secondary referral centre. POPULATION: All women (n= 131) between 24 and 34 weeks of gestation with severe pre-eclampsia, where both mother and fetus were otherwise stable. METHODS: After admission, frequent intensive but non-invasive monitoring of mother and fetus was performed. Women were delivered on achieving 34 weeks, or if fetal distress or major maternal complications developed. Transfer to the tertiary centre was individualised. MAIN OUTCOME MEASURES: Prolongation of gestation, maternal complications, perinatal outcome and number of tertiary referrals. RESULTS: Most women [n= 116 (88.5%)] were managed entirely at the secondary hospital. Major maternal complications occurred in 44 (33.6%) cases with placental abruption (22.9%) the most common. One maternal death occurred and two women required intensive care admission. A mean of 11.6 days was gained before delivery with the mean delivery gestation being 31.8 weeks. The most frequent reason for delivery was fetal distress (55.2%). There were four intrauterine deaths. The perinatal mortality rate (> or =1000 g) was 44.4/1000, and the early neonatal mortality rate (> or =500 g) was 30.5/1000. CONCLUSIONS: The maternal and perinatal outcomes are comparable to those achieved by other tertiary units. This model of expectant management of early onset, severe pre-eclampsia is encouraging but requires close co-operation between secondary and tertiary institutions. Referrals to the tertiary centre were optimised, reducing their workload and costs, and patients were managed closer to their communities.

Adolescent↗

Are affluent, well-educated, career-orientated women knowledgeable users of the oral contraceptive pill?

OBJECTIVE: Studies have shown poor knowledge of oral contraceptives among women attending government health clinics and women in rural areas. Little is known about the level of contraceptive knowledge in educated, affluent, career-orientated women, although it could be expected that access to information would be greater. The study objective was to describe the profile, knowledge and understanding of oral contraceptive users in a private general practice in Johannesburg, South Africa. METHODS: Over a period of 3 months, all women attending a private general practice who were using an oral contraceptive were asked to complete an anonymous questionnaire. Informed written consent was obtained in all cases. RESULTS: Fifty-one women participated in the study. Most women were nulliparous (71%), held a tertiary educational qualification (80%), were employed (84%) and were not concerned about the cost of their pill (65%). Most respondents (86%) obtained their information from a doctor. However, only 12% of women were aware of the danger of extending the active pill-free interval. Less than half (49%) were aware that their pill was less effective if taken more than 12 hours late and only 31% of women knew that their pill was effective again after taking seven active tablets. CONCLUSIONS: Educated, affluent women attending a private general practice lacked basic knowledge of the oral contraceptive pill. Consultations by practitioners need to be improved.

Adolescent↗

Simple time-domain optical method for estimating the depth and concentration of a fluorescent inclusion in a turbid medium.

A simple time-domain optical method for estimating the depth and concentration of fluorescent inclusions in turbid media is described. We demonstrate direct depth estimation of a localized fluorescent object from the temporal position of the temporal point-spread function maximum. The depth estimation permits recovery of the fluorophore concentration, both of which are essential quantities for optical molecular imaging studies. Since the maximum is independent of the fluorophore concentration, excitation laser power, detector gain, and other system-dependent factors, this method ensures a robust and efficient approach.

Algorithms↗

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks. METHODS: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed. RESULTS: The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events. CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.

Acute Disease↗

Peripherally administered growth hormone increases brain dopaminergic activity and swimming in rainbow trout.

There is increasing evidence that growth hormone (GH) has important behavioral effects in fish, but the underlying mechanisms are not well understood. To investigate if peripherally administered GH influences the monoaminergic activity of the brain, and how this is correlated to behavior, juvenile rainbow trout were implanted intraperitoneally with ovine GH. Fish were either kept isolated or in groups of five. The physical activity and food intake of the isolated fish were observed after 1 and 7 days, when brains were also sampled. The content of serotonin, dopamine, and noradrenaline and their metabolites in hypothalamus, telencephalon, optic tectum, and brain stem was then analyzed. For fish kept isolated for 7 days following implant, GH increased swimming activity and the levels of the dopamine metabolite 3, 4-hydroxy-phenylacetic acid (DOPAC) were higher in all brain parts examined. In the optic tectum, the levels of the dopamine metabolite homovanillic acid (HVA) were lowered by the GH treatment. One-day GH implant did not affect behavior or monoamine levels of isolated fish. In the fish kept in groups, a 7-day GH implant increased the hypothalamic levels of DOPAC, but not in the other brain parts examined, which may indicate an effect on the brain dopaminergic system from social interactions. It can be concluded that peripherally administered GH may function as a neuromodulator, affecting the dopaminergic activity of the rainbow trout brain, and this is associated with increased swimming activity.

3,4-Dihydroxyphenylacetic Acid↗

Mortality after discharge from long-term psychiatric care in Scotland, 1977-94: a retrospective cohort study.

BACKGROUND: Recent United Kingdom strategies focus on preventable suicide deaths in former psychiatric in-patients, but natural causes of death, accidents and homicide may also be important. This study was intended to find the relative importance of natural and unnatural causes of death in people discharged from long-term psychiatric care in Scotland in 1977-1994. METHODS: People discharged alive from psychiatric hospitals in Scotland in 1977-94 after a stay of one year or longer were identified using routine hospital records. Computer record linkage was used to link hospital discharges to subsequent death records. Mortality was described using a person-years analysis, and compared to the general population rates. RESULTS: 6,776 people were discharged in the time period. 1,994 people (29%) died by the end of follow-up, 732 more deaths than expected. Deaths from suicide, homicide, accident and undetermined cause were increased, but accounted for only 197 of the excess deaths. Deaths from respiratory disease were four times higher than expected, and deaths from other causes, including cardiovascular disease, were also elevated. CONCLUSION: Suicide is an important cause of preventable mortality, but natural causes account for more excess deaths. Prevention activities should not focus only on unnatural causes of death.

Cardiovascular Diseases↗

A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1.

To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries.

Adult↗

An asymmetric synthesis of aza analogues of the tricyclic skeleton of daphnane and the ABC ring system of phorbol.

An asymmetric synthesis of aza analogues of the ABC ring system of phorbol and related compounds containing the 5-7-6-fused framework of daphnane involved construction of the central seven-membered ring by a regioselective reduction of a chiral imide and cyclization with trifluoromethanesulfonic acid. Subsequent demethylation and oxidative dearomatization of ring C afforded an enantiopure dienone 20 with the same relative and absolute configuration at the 9- and 10-positions of the phorbol skeleton.

Aza Compounds↗

Möbius bis and tris-spiroaromatic systems.

We propose that a general class of bis and tris-spiro 7-membered ring systems with a common atom X, of which there are a number of examples characterised crystallographically, can in fact be considered as spiroaromatic molecules in which each ring exhibits some degree of Möbius 4n pi-electron aromaticity. The aromaticity is probed as a function of the spiro-atom using ab initio calculations of the NICS(0) values, which indicate that the Möbius-aromaticity increases as the spiro-atom is changed e.g. from Al to P, and from e.g. P to As.

Journal Article↗

Birthweight and gestational age as predictors of outcome in preterm deliveries for severe pre-eclampsia.

The aim of this study was to compare the neonatal outcomes of babies with birthweights < 10th centile to those with birthweights > or = 10th centile with a gestational age of 28-34 weeks. This retrospective hospital-based study was performed at a tertiary referral centre. All women with early, severe pre-eclampsia, managed expectantly and who delivered a liveborn infant, over a 5-year period were included. The main outcome measures were birthweight within gestational age category, neonatal and infant deaths before discharge as well as neonatal intensive care. There were 136 and 190 babies in the < 10th and > or = 10th centile groups, respectively. No significant differences in outcome were noted in any of the gestational age categories. Thus within gestational age categories, birthweights < 10th centile did not predict a worse outcome in preterm deliveries for severe pre-eclampsia.

Adult↗