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Biomedical subjects

J Clarke

Publications and source records attributed to J Clarke.

At least 145 records · Page 8Linked to original sources
PubMed1997

High bicarbonate dialysate in haemodialysis patients: effects on acidosis and nutritional status.

BACKGROUND: Metabolic acidosis adversely affects both protein and bone metabolism in patients with chronic renal failure, and could also affect morbidity and mortality. This trial aimed to investigate the effects of different dialysate bicarbonate concentrations on control of acid base balance, and nutritional status. METHODS: Forty-six stable haemodialysis patients were dialysed using LowBic. (30 mmol/l) or HighBic. (40 mmol/l) bicarbonate dialysate in a single blind double crossover trial, of two consecutive six-month periods. Blood gas analysis, anthropometric indices and dialysis dose were measured, in addition to biochemical indices. RESULTS: Predialysis 'arterial' plasma pH values were significantly higher when using the HighBic. dialysate (LowBic. 7.38 +/- 0.05, HighBic. 7.43 +/- 0.04, P < 0.001), as was predialysis serum total CO2 at all times during the study (P < 0.01). Kt/V, (LowBic. 1.27 +/- 0.19, HighBic. 1.27 +/- 0.25), urea generation rates (UGR) (LowBic. 1.99 +/- 0.77, HighBic. 1.92 +/- 0.77 mmol/min), and normalized protein catabolic rate (NPCR) (LowBic. 1.04 +/- 0.26, HighBic. 0.99 +/- 0.28 g/kg/day) did not differ, and values of parathroid hormone (PTH) were comparable. Triceps skinfold thickness (TSF) showed a significant change (LowBic. 14.8 +/- 6.9-11.8 +/- 5.5, HighBic. 14.9 +/- 6.3-15.8 +/- 6.4 mm, P < 0.05) which was reversed following dialysate change (HighBic. 11.8 +/- 5.5-13.3 +/- 7.2, LowBic. 15.8 +/- 6.4-13.8 +/- 6.7 mm, P < 0.05). No differences in mid upper arm circumference were found. CONCLUSIONS: Bicarbonate dialysate concentrations of 40 mmol/l were safe, well tolerated, and produced better control of acidosis, with an increase in TSF, compared to a bicarbonate concentration of 30 mmol/l.

Acidosis↗
PubMed1997

The effects of smoking outside workplaces on non-regular smokers.

The introduction of workplace smoking bans has resulted in smokers smoking outside their workplaces (exiled smoking). Social identity theory postulates that this may cause antagonism between smokers and non-smokers, or where non-smokers were friends with smokers, pressure on non-smokers to smoke. This study examines perceptions and beliefs about exiled smoking in 166 non-smoking workers. They saw smokers as having a work benefit not available to them, but otherwise they were generally not drawn to the activity. Half had joined smokers outside for breaks, but of these only one-third had ever smoked. Those would smoked reported that they did not have a regular pattern of joining the same group of smokers. Although it may provide a conduit for susceptible non-smokers to take up smoking, exiled smoking does not appear to influence those who are not otherwise vulnerable.

Adult↗
PubMed1997

Quinine--acute self-poisoning and ocular toxicity.

Quinine is widely prescribed as a treatment for nocturnal leg cramps. In acute overdosage, it may lead to significant ocular problems. This study reveals that some 30 patients were discharged from Greater Glasgow Health Board hospitals between 1988 and 1992 following acute self-poisoning with quinine. Six of these subjects had severe visual problems, two being registered as blind and another three as partially sighted. These observations, combined with the doubtful clinical efficacy of quinine, suggest that its continued widespread use should be reappraised.

Adolescent↗
PubMed1997

Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb.

Anteroposterior polarity in the vertebrate limb is thought to be regulated in response to signals derived from a specialized region of distal posterior mesenchyme, the zone of polarizing activity. Sonic Hedgehog (Shh) is expressed in the zone of polarizing activity and appears to mediate the action of the zone of polarizing activity. Here we have manipulated Shh signal in the limb to assess whether it acts as a long-range signal to directly pattern all the digits. Firstly, we demonstrate that alterations in digit development are dependent upon the dose of Shh applied. DiI-labeling experiments indicate that cells giving rise to the extra digits lie within a 300 microm radius of a Shh bead and that the most posterior digits come from cells that lie very close to the bead. A response to Shh involves a 12-16 hour period in which no irreversible changes in digit pattern occur. Increasing the time of exposure to Shh leads to specification of additional digits, firstly digit 2, then 3, then 4. Cell marking experiments demonstrate that cells giving rise to posterior digits are first specified as anterior digits and later adopt a more posterior character. To monitor the direct range of Shh signalling, we developed sensitive assays for localizing Shh by attaching alkaline phosphatase to Shh and introducing cells expressing these forms into the limb bud. These experiments demonstrate that long-range diffusion across the anteroposterior axis of the limb is possible. However, despite a dramatic difference in their diffusibility in the limb mesenchyme, the two forms of alkaline phosphatase-tagged Shh proteins share similar polarizing activity. Moreover, Shh-N (aminoterminal peptide of Shh)-coated beads and Shh-expressing cells also exhibit similar patterning activity despite a significant difference in the diffusibility of Shh from these two sources. Finally, we demonstrate that when Shh-N is attached to an integral membrane protein, cells transfected with this anchored signal also induce mirror-image pattern duplications in a dose-dependent fashion similar to the zone of polarizing activity itself. These data suggest that it is unlikely that Shh itself signals digit formation at a distance. Beads soaked in Shh-N do not induce Shh in anterior limb mesenchyme ruling out direct propagation of a Shh signal. However, Shh induces dose-dependent expression of Bmp genes in anterior mesenchyme at the start of the promotion phase. Taken together, these results argue that the dose-dependent effects of Shh in the regulation of anteroposterior pattern in the limb may be mediated by some other signal(s). BMPs are plausible candidates.

Animals↗
PubMed1997

Absence of bradycardic response to apnea and hypoxia in heart transplant recipients with obstructive sleep apnea.

In patients with obstructive sleep apnea, the vagal stimulation caused by inspiration against the upper airway obstruction results in sinus bradycardia during the apnea followed by a reflex tachycardia at apnea termination. We report on five heart transplant recipients with obstructive sleep apnea who demonstrated no change in baseline heart rate in spite of marked hemoglobin oxygen desaturation, presumably on account of parasympathetic denervation of the allograft. Heart transplant recipients with obstructive sleep apnea may be at an increased risk of development of potentially fatal ventricular arrhythmias if the allograft is unable to respond appropriately to hypoxia. Should cardiac parasympathetic reinnervation occur, prospective polysomnography may be a marker for this process in these patients.

Bradycardia↗
PubMed1997

Well-being at the end of life: Part 1. A research agenda for psychosocial and spiritual aspects of care from the patient's perspective.

This article reviews the scientific literature concerning psychosocial and spiritual aspects of palliative care for the patient with cancer. It discusses 4 separate areas: the continuum of care, communication, spiritual and psychological issues, and psychotherapeutic and behavioural management of physical symptoms. Most of the research could be classified as fundamental according to the Cancer Control Framework of the National Cancer Institute of Canada. In some areas, even fundamental research was lacking. There is a need for clearer and more relevant definitions of the desired outcomes of interventions and also for the development of appropriate quantitative and qualitative methods. We must determine which interventions can be initiated earlier in the disease trajectory and can provide benefit at the palliative phase. Given the burden of suffering that palliative care aims to address, relatively little research in this area has been conducted.

Humans↗
PubMed1996

Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function oxidase activity in streptozotocin-diabetic rats.

The effect of vitamin C supplementation on hepatic cytochrome P450 expression was investigated in streptozotocin (STZ) diabetic male Wistar Albino rats. STZ-treated rats displayed the usual characteristics of diabetes including; hyperphagia, polydipsia, decreased body weight gain and also the increased expression and activity of hepatic CYP1A, 2B, 2E and 4A proteins. Vitamin C administration in drinking water (2% w/v) was associated with significant decreases in the levels of hyperglycaemia (P < 0.05), glycosylated haemoglobin (P < 0.05), hyperlipidaemia (P < 0.001), and hyperketonaemia (P < 0.001) associated with STZ-diabetes. Vitamin C-treatment selectively reduced the activity and expression of CYP2E proteins (P < 0.001). These effects on CYP2E expression may be mediated by the reduced levels of circulating ketone bodies, however, a direct effect on CYP2E expression in diabetes cannot be discounted.

Animals↗
PubMed1996

Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans.

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.

Amino Acid Sequence↗
PubMed1996

Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.

Angiogenesis is a key process in tumor growth and metastasis and is a major independent prognostic factor in breast cancer. A range of cytokines stimulate the tumor neovasculature, and tumor-associated macrophages have been shown recently to produce several important angiogenic factors. We have quantified macrophage infiltration using Chalkley count morphometry in a series of invasive breast carcinomas to investigate the relationship between tumor-associated macrophage infiltration and tumor angiogenesis, and prognosis. There was a significant positive correlation between high vascular grade and increased macrophage index (P = 0.03), and a strong relationship was observed between increased macrophage counts and reduced relapse-free survival (P = 0.006) and reduced overall survival (P = 0.004) as an independent prognostic variable. These data indicate a role for macrophages in angiogenesis and prognosis in breast cancer and that this cell type may represent an important target for immunoinhibitory therapy in breast cancer.

Breast Neoplasms↗