Search PubMed⌕ Search

Biomedical subjects

J E Shaw

Publications and source records attributed to J E Shaw.

At least 37 records · Page 2Linked to original sources
PubMed1999

Functional overlap between the mec-8 gene and five sym genes in Caenorhabditis elegans.

Earlier work showed that the Caenorhabditis elegans gene mec-8 encodes a regulator of alternative RNA splicing and that mec-8 null mutants have defects in sensory neurons and body muscle attachment but are generally viable and fertile. We have used a genetic screen to identify five mutations in four genes, sym-1-sym-4, that are synthetically lethal with mec-8 loss-of-function mutations. The phenotypes of sym single mutants are essentially wild type. mec-8; sym-1 embryos arrest during embryonic elongation and exhibit defects in the attachment of body muscle to extracellular cuticle. sym-1 can encode a protein containing a signal sequence and 15 contiguous leucine-rich repeats. A fusion of sym-1 and the gene for green fluorescent protein rescued the synthetic lethality of mec-8; sym-1 mutants; the fusion protein was secreted from the apical hypodermal surface of the embryo. We propose that SYM-1 helps to attach body muscle to the extracellular cuticle and that another gene that is dependent upon mec-8 for pre-mRNA processing overlaps functionally with sym-1. RNA-mediated interference experiments indicated that a close relative of sym-1 functionally overlaps both sym-1 and mec-8 in affecting muscle attachment. sym-2, sym-3, and sym-4 appear to provide additional functions that are essential in the absence of mec-8(+).

Alleles↗
PubMed1999

A rural cancer outreach program lowers patient care costs and benefits both the rural hospitals and sponsoring academic medical center.

The Rural Cancer Outreach Program (RCOP) between two rural hospitals and the Medical College of Virginia's Massey Cancer Center (MCC) was developed to bring state-of-the-art cancer care to medically underserved rural patients. The financial impact of the RCOP on both the rural hospitals and the MCC was analyzed. Pre- and post-RCOP financial data were collected on 1,745 cancer patients treated at the participating centers, two rural community hospitals and the MCC. The main outcome measures were costs (estimated reimbursement from all sources), revenues, contribution margins and profit (or loss) of the program. The RCOP may have enhanced access to cancer care for rural patients at less cost to society. The net annual cost per patient fell from $10,233 to $3,862 associated with more use of outpatient services, more efficient use of resources, and the shift to a less expensive locus of care. The cost for each rural patient admitted to the Medical College of Virginia fell by more than 40 percent compared with only an 8 percent decrease for all other cancer patients. The rural hospitals experienced rapid growth of their programs to more than 200 new patients yearly, and the RCOP generated significant profits for them. MCC benefited from increased referrals from RCOP service areas by 330 percent for cancer patients and by 9 percent for non-cancer patients during the same time period. While it did not generate a major profit for the MCC, the RCOP generated enough revenue to cover costs of the program. The RCOP had a positive financial impact on the rural and academic medical center hospitals, provided state-of-the-art care near home for rural patients and was associated with lower overall cancer treatment costs.

Academic Medical Centers↗
PubMed1999

Innexin-3 forms connexin-like intercellular channels.

Innexins comprise a large family of genes that are believed to encode invertebrate gap junction channel-forming proteins. However, only two Drosophila innexins have been directly tested for the ability to form intercellular channels and only one of those was active. Here we tested the ability of Caenorhabditis elegans family members INX-3 and EAT-5 to form intercellular channels between paired Xenopus oocytes. We show that expression of INX-3 but not EAT-5, induces electrical coupling between the oocyte pairs. In addition, analysis of INX-3 voltage and pH gating reveals a striking degree of conservation in the functional properties of connexin and innnexin channels. These data strongly support the idea that innexin genes encode intercellular channels.

Animals↗
PubMed1999

Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius?

OBJECTIVE: To determine if impaired fasting glucose (IFG; fasting plasma glucose level 6.1-6.9 mmol/l) can predict future type 2 diabetes as accurately as does impaired glucose tolerance (IGT; 2-h plasma glucose level 7.8-11.0 mmol/l). RESEARCH DESIGN AND METHODS: A longitudinal population-based study was performed with surveys in 1987 and 1992 on the island of Mauritius, assessing diabetes status by the oral glucose tolerance test. A total of 3,717 subjects took part in both surveys. Of these subjects, 3,229 were not diabetic in 1987 and formed the basis of this study. RESULTS: At baseline, there were 607 subjects with IGT and 266 subjects with IFG. There were 297 subjects who developed diabetes by 1992. For predicting progression to type 2 diabetes, the sensitivity, specificity, and positive predictive values were 26, 94, and 29% for IFG and 50, 84, and 24% for IGT, respectively. Only 26% of subjects that progressed to type 2 diabetes were predicted by their IFG values, but a further 35% could be identified by also considering IGT. The sensitivities were 24% for IFG and 37% for IGT in men and 26% for IFG and 66% for IGT in women, respectively. CONCLUSIONS: These data demonstrate the higher sensitivity of IGT over IFG for predicting progression to type 2 diabetes. Screening by the criteria for IFG alone would identify fewer people who subsequently progress to type 2 diabetes than would the oral glucose tolerance test.

Adult↗
PubMed1999

Impact of new diagnostic criteria for diabetes on different populations.

OBJECTIVE: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified. RESEARCH DESIGN AND METHODS: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals. RESULTS: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values. CONCLUSIONS: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.

Adult↗
PubMed1998

Does peripheral neuropathy invariably accompany nephropathy in type 1 diabetes mellitus?

In patients with Type 1 diabetes mellitus complicated by diabetic nephropathy and retinopathy, it is usually believed that significant neuropathy is almost universal, but few studies have directly addressed this. This study assessed neuropathy in 91 such subjects, using vibration perception thresholds (VPT) and the neuropathy disability score (NDS). A total of 34% of subjects had no neuropathy on age adjusted VPT (z score) and 26% had no neuropathy on NDS. The severity of neuropathy as measured by VPT z score was related to increasing glycated haemoglobin (P = 0.02) and male sex (P = 0.03), and NDS was independently associated with age (P < 0.0001) and HbA1c (P = 0.003). These factors together accounted for only 12 and 31% of the total variance in VPT z score and NDS, respectively. In conclusion, the study has shown that a significant proportion of patients with diabetic nephropathy are free of neuropathy, but the full explanation for their protection from neuropathy is unclear.

Adult↗
PubMed1998

Diabetic neuropathy in Mauritius: prevalence and risk factors.

The study of diabetic neuropathy has been primarily in Europids, despite the high prevalence of diabetes in other populations. We set out to ascertain the prevalence of diabetic neuropathy and its risk factors in the island nation of Mauritius. Population surveys were carried out in 1987 and 1992 in Mauritius to establish the prevalence of Type 2 diabetes. In the second survey, vibration perception threshold (VPT) was also measured at the great toe in 847 subjects with diabetes, 204 subjects with impaired glucose tolerance and 127 subjects with normal glucose tolerance. Neuropathy was defined as levels of VPT exceeding the mean plus 2 standard deviations defined separately for three age groups of Mauritian non-diabetic subjects. Risk factors for neuropathy were identified cross sectionally from the 1992 data, and longitudinally from the 1987 data. Neuropathy was detected in 8.3% of the 847 diabetic subjects (12.7%) of those with known diabetes, and 3.6% of those with newly diagnosed diabetes). Logistic regression identified diabetes duration (odds ratio [95% CI]; 1.08 [1.04-1.13] per year, P=0.0002), treatment with insulin or oral hypoglycaemic agents (2.63 [1.36-5.09], P=0.004) and greater height (1.36 [1.19-1.57] per 5 cm, P < 0.001) as risk factors for neuropathy, in the cross sectional analysis. In the longitudinal analysis, diabetes duration (1.11 [1.05-1.18] per year, P=0.001), fasting glucose (1.12 [1.03-1.22] per mmol/l, P=0.01) and height (1.23 [1.03-1.45] per 5 cm, P=0.02) were associated with neuropathy. A lower 2-h plasma insulin was also associated with neuropathy in the longitudinal analysis. The prevalence of diabetic neuropathy in Mauritius is the lowest reported for any population, but the risk factors associated with it are similar to those previously found.

Adult↗
PubMed1998

UNC-115, a conserved protein with predicted LIM and actin-binding domains, mediates axon guidance in C. elegans.

Axon guidance receptors modulate the growth cone cytoskeleton through signaling pathways that are not well understood. Here, we describe the C. elegans unc-115 gene, which encodes a candidate cytoskeletal linker protein that acts in axon guidance. unc-115 mutants have defects in a subset of axons, particularly as the affected axons change environments during outgrowth. The unc-115 gene encodes a putative actin-binding protein that is similar to the human actin-binding protein abLIM/limatin; it has a villin headpiece domain and three LIM domains that could mediate protein interactions. unc-115 is expressed in neurons during their development and is required cell-autonomously in certain neurons for normal axon guidance. We propose that UNC-115 modulates the growth cone actin cytoskeleton in response to signals received by growth cone receptors.

Amino Acid Sequence↗
PubMed1998

Analysis of osm-6, a gene that affects sensory cilium structure and sensory neuron function in Caenorhabditis elegans.

Mutation in the Caenorhabditis elegans gene osm-6 was previously shown to result in defects in the ultrastructure of sensory cilia and defects in chemosensory and mechanosensory behaviors. We have cloned osm-6 by transposon tagging and transformation rescue and have identified molecular lesions associated with five osm-6 mutations. The osm-6 gene encodes a protein that is 40% identical in amino acid sequence to a predicted mammalian protein of unknown function. We fused osm-6 with the gene for green fluorescent protein (GFP); the fusion gene rescued the osm-6 mutant phenotype and showed accumulation of GFP in ciliated sensory neurons exclusively. The OSM-6::GFP protein was localized to cytoplasm, including processes and dendritic endings where sensory cilia are situated. Mutations in other genes known to cause ciliary defects led to changes in the appearance of OSM-6::GFP in dendritic endings or, in the case of daf-19, reduced OSM-6::GFP accumulation. We conclude from an analysis of genetic mosaics that osm-6 acts cell autonomously in affecting cilium structure.

Alleles↗
PubMed1998

An analysis of dynamic forces transmitted through the foot in diabetic neuropathy.

OBJECTIVE: Biomechanical studies in diabetic neuropathy have clearly demonstrated abnormal foot pressures, but information on other aspects of gait is limited. This study aimed to investigate and describe the forces transmitted through the foot during walking in diabetic subjects with varying degrees of peripheral neuropathy and to determine if abnormalities in these forces might contribute to the risk of plantar ulceration. RESEARCH DESIGN AND METHODS: Subjects from the following groups were included: healthy control subjects (C); diabetic control subjects (D); subjects with diabetic neuropathy (DN); subjects with previous neuropathic ulceration (DNU); and subjects with Charcot neuro-arthropathy (CH). Gait analysis was performed as subjects walked over a Kistler force plate. Peak forces were measured (as percent body weight) in the vertical and horizontal planes. Comparisons were made between all of the groups and between each diabetic group and a healthy control group matched for walking speed. RESULTS: There were 181 subjects studied. In comparison with that of the speed-matched controls, the mean peak vertical force was higher in each of the diabetic groups, especially in the most neuropathic subjects (DNU, 113 vs. 110%, P < 0.01). This increase was entirely due to higher forces during heel contact (DNU, 111 vs. 106%, P < 0.001). The single peak force occurred during heel strike (rather than during foot push-off) in 23-38% of footsteps of healthy and diabetic control subjects but in 53-73% of footsteps of neuropathic subjects. There was also a trend for higher peak medial forces (CH, 6.2 vs. 5.5%, P < 0.05). CONCLUSIONS: Diabetic neuropathy is associated with a change in the time pattern of the forces transmitted through the foot and an increase in the vertical forces through the heel. The magnitude of the changes is small in absolute terms, but these changes may contribute to the risk of plantar foot ulceration.

Adult↗
PubMed1997

A randomised controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating.

The treatment of gustatory sweating in diabetes mellitus is usually with oral anti-cholinergic drugs, but these frequently lead to unacceptable side effects. Glycopyrrolate is an anti-muscarinic agent that can be applied topically and is efficacious in gustatory sweating occurring in other conditions. In a double-blind placebo-controlled crossover study, we assessed the value of glycopyrrolate in 13 diabetic patients with gustatory sweating. Sweating was measured by a sweat challenge, and diaries recorded by the patients throughout the 2 weeks of each treatment period. Compared to placebo, glycopyrrolate reduced the sweat response to a challenge by 82% (p < 0.01). The frequency of episodes of gustatory sweating during the treatment period was also reduced by 51% (p < 0.01), with a nearly 100% reduction in the frequency of episodes of severe sweating (p < 0.01). In conclusion, topically applied glycopyrrolate is a very effective treatment in reducing both the severity and frequency of diabetic gustatory sweating.

Administration, Topical↗
PubMed1997

Poor vision as a contributory factor in diabetic neuro-arthropathy.

Two patients with longstanding insulin-dependent diabetes mellitus (IDDM) complicated by neuropathy, nephropathy and retinopathy leading to poor vision each developed a swollen and relatively painless foot. The previous day, both had been walking over uneven ground. At initial presentation, no X-ray was taken of the foot in case one and no action was taken over an undisplaced navicular fracture in case two. A few weeks later, a midfoot Charcot had developed in both cases. Poor vision may increase the risk of injury to the feet and may be an important risk factor for Charcot neuro-arthropathy. Plain radiographs are an important investigation for the swollen insensitive foot, even in the absence of pain.

Adult↗
PubMed1997

The mechanism of plantar unloading in total contact casts: implications for design and clinical use.

Although the total contact cast (TCC) has been shown to be an extremely effective treatment for the healing of plantar ulcers in diabetic patients, little is known about the biomechanics of its action. In this study, plantar pressure and ground reaction force measurements were obtained from over 750 foot contacts as five subjects with known elevated plantar forefoot pressures walked barefoot, in a padded cast shoe, and a TCC. Peak plantar pressures in the forefoot were markedly reduced in the cast compared with both barefoot and shoe walking (reductions of 75% and 86% respectively, P < 0.05). Peak plantar pressures in the heel were not, however, significantly different between the shoe and the TCC, and the longer duration of heel loading resulted in an impulse that was more than twice as great in the cast compared with the shoe (P < 0.05). An analysis of load distribution indicated that the mechanisms by which the TCC achieves forefoot unloading are (1) transfer of approximately 30% of the load from the leg directly to the cast wall, (2) greater proportionate load sharing by the heel, and (3) removal of a load-bearing surface from the metatarsal heads because of the "cavity" created by the soft foam covering the forefoot. These results point out some of the "essential design features" of the TCC (which are different from what had been previously supposed), support the use of the TCC for healing plantar ulcers in the forefoot, but raise questions about its utility in the healing of plantar ulcers on the heel.

Adult↗
PubMed1997

Radical radiotherapy for carcinoma of the uterine cervix using external beam radiotherapy and a single line source brachytherapy technique: the Clatterbridge technique.

At the Clatterbridge Centre for Oncology, a single line source brachytherapy technique using the Selectron (Nucletron) low dose rate remote afterloading equipment has been developed for use in conjunction with homogenous whole pelvis external beam radiotherapy in the radical treatment of carcinoma of the cervix. The technique incorporates several modifications aimed at reducing treatment related morbidity while maintaining satisfactory local tumour control and cure rates. A flexible dose prescription system has been devised to allow individualization of the brachytherapy isodose distribution according to the clinical findings and the estimated normal tissue doses. Modifications of source loading distributions are carried out to limit the point "A" dose rate to a narrow range to take into account the dose rate effect on the risk of complications. Source loading distributions are also modified according to the estimated normal tissue doses in order to respect normal tissue tolerance. This paper describes the technique and its underlying principles.

Brachytherapy↗
PubMed1997

The pathogenesis of diabetic foot problems: an overview.

Foot ulceration and lower limb amputation are still common complications of diabetes. Diabetic peripheral neuropathy and peripheral vascular disease are the most important etiologic factors, but there is a complex interplay between these abnormalities and a number of other contributory factors, such as altered foot pressures, limited joint mobility, glycemic control, ethnic background, and cardiovascular parameters. Identification of patients at high risk of ulceration is nevertheless simple, and education of such patients can achieve a major reduction in amputation and ulceration rates.

Arthropathy, Neurogenic↗
PubMed1997

How long does it take to get a "do not resuscitate" order?

UNLABELLED: Less than 50% of physicians know the resuscitation wishes of their patients and only a small fraction of patients have completed "do not resuscitate" (DNR) orders before death. One of the common reasons given by physicians is that the process of "getting a DNR" takes too long, and some authorities have suggested that additional reimbursement is needed. The purpose of this study is to assess how long the DNR education and consent process actually takes in practice. Our study group was a convenience sample of consecutive patients seen by experienced oncologists in a community and academic practice setting. Physicians were asked to record the time spent in DNR discussions with patients, the outcomes, and their comments. DNR orders were obtained on 16 of 22 patients with a single interview lasting a mean time of 16 minutes. Additional DNR orders were obtained on two more patients after a second interview of 6 patients, mean time 17.5 minutes. After a third interview of 4 patients, mean time 23 minutes, only 2 of 22 patients would not allow DNR orders. Of these two, one died intubated in the intensive care unit and the other underwent continued unsuccessful induction therapy for acute leukemia before dying. CONCLUSION: DNR orders can be obtained on nearly all patients within the time frame of an inpatient or outpatient visit. Time is not the main obstacle to DNR discussions, and additional reimbursement for additional time is not necessary. A small subset of patients continue to refuse DNR orders. Physician and patient reluctance to broach the subject may be a bigger impediment than time.

Adolescent↗