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Biomedical subjects

D Bell

Publications and source records attributed to D Bell.

At least 109 records · Page 6Linked to original sources
PubMed1995

Phase II study of high dose epirubicin in combination with cyclophosphamide in patients with advanced breast cancer.

BACKGROUND: Combination chemotherapy for metastatic breast cancer will palliate symptoms in the majority of patients but only a small percentage will have prolonged survival. Higher doses of doxorubicin lead to increased response rates in breast cancer and early studies have shown that epirubicin could be tolerated in higher doses with less relative toxicity than doxorubicin. AIMS: This study was initiated to assess the dose of epirubicin that could be tolerated by escalating its dose while maintaining a fixed dose of cyclophosphamide. Simultaneously tumour response rate, spectrum of toxicities, duration of response and overall survival in patients with metastatic breast cancer were assessed. METHODS: Patients with metastatic breast cancer commenced chemotherapy with a starting dose of epirubicin of 120 milligram per metre squared (mg/m2) and cyclophosphamide 600 mg/m2. The dose of epirubicin was to be escalated or reduced depending on toxicity. RESULTS: Forty female patients were entered into this study and three patients withdrew because of toxicity. Overall tumour response rate was 75% with 27.5% of patients obtaining a complete response. Median time to progressive disease was 35 weeks and median overall survival was 48 weeks, with median survival for complete responders being 103 weeks. Thirty-one (77%) patients completed five or more courses of treatment. Haematological toxicity was the main side effect and 70% of patients required a dose reduction. No patients were eligible for a dose escalation. One patient died as a consequence of neutropenic sepsis. Four (10%) patients had treatment ceased because of decrease in left ventricular ejection fraction and one patient died as a consequence of heart failure. Four patients remain alive. CONCLUSIONS: High dose epirubicin combined with cyclophosphamide is an effective treatment regimen for metastatic breast cancer obtaining higher overall response rates with increased percentage complete responses compared to conventional dose chemotherapy. Although toxicity was increased, high dose chemotherapy was well tolerated and mortality associated with treatment was not increased. No dose escalations of epirubicin were possible and a dose of 90 mg/m2 of epirubicin would be the maximum dose when used in combination with cyclophosphamide. Further trials are required to determine the influence of this high dose therapy on survival duration and whether comparable benefits can be achieved with shorter durations of therapy.

Adenocarcinoma↗
PubMed1995

Vestibular function test anomalies in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described. Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis rotation (EVA) gains at the higher frequencies tested. As a group, the average gain of EVA was significantly lower than normals in the 0.1 - 1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s. Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.

Adult↗
PubMed1995

Effect of triazolam on responses to a cold-water immersion in humans.

Managing alertness of soldiers during sustained operations is a source of serious concern for military unit commanders. A frequently employed strategy is to induce sleep before an operation, especially operations requiring prolonged travel. Sleep-inducing drugs could have an action on thermoregulation through their effect on alertness and a possible direct effect on the brain. The goal of this study was therefore to evaluate the effect of a commonly prescribed triazolam (Halcion) on thermoregulatory responses to cold-water immersion. Eight subjects were immersed twice in 18 degrees C water for up to 90 min in the morning; once after ingesting 0.25 mg triazolam (TRZ) the prior evening, and again after placebo (PLB) treatment. There were no significant differences between trials for mean duration of the immersion, the change in rectal temperature and mean skin temperature. Total metabolic heat production was similar for both conditions: 767 +/- 107 vs. 781 +/- 105 kj.m-2 for TRZ and PLB, respectively. The results should be considered in light of a large variation among the subjects in sensitivity to TRZ, which was unrelated to biometrical characteristics such as surface area-to-mass ratio, lean body mass, % body fat, and physical fitness. Although not statistically significant, there was a trend for a smaller increase in plasma free fatty acid and glycerol concentrations after water immersion with TRZ. The results suggest that the ingestion of a single dose of triazolam 11 h prior to a cold-water immersion is not likely to accelerate the rate of onset of hypothermia. Individual sensitivity, however, may predispose some sensitive subjects to negative effects in this regard.

Adipose Tissue↗
PubMed1994

Use of the cyclic AMP antagonist, Rp-cAMPS, to distinguish between cyclic AMP-dependent and cyclic AMP-independent contractile responses in rat ventricular cardiomyocytes.

Conventional inhibitors of cyclic AMP-dependent protein kinase lack membrane-permeability or selectivity, or both. The Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate, Rp-cAMPS, is a novel membrane-permeable antagonist of cyclic AMP. We have assessed the ability of this compound to distinguish between cyclic AMP-dependent and cyclic AMP-independent contractile responses elicited in ventricular cardiomyocytes isolated from the hearts of adult rats. Cardiomyocytes were stimulated to contract at 0.5 Hz in the presence of calcium ion (2 mM) and adenosine deaminase (5 units/ml). Contractile shortening was expressed as maximum shortening relative to prestimulus cell length (delta L%). In the presence of a maximally-effective concentration of isoprenaline (100 nM), which acts by a cyclic AMP-dependent mechanism, Rp-cAMPS inhibited the contractile response in a concentration-dependent and time-dependent manner. Following preincubation for 30 min with Rp-cAMPS (100 microM), the contractile response to isoprenaline (100 nM) was 14% of that elicited in the absence of this inhibitor. An incubation time of 30 min was chosen for all subsequent studies. Rp-cAMPS (< or = 200 microM) inhibited the contractile response to isoprenaline (100 nM) significantly and in a concentration-dependent manner, but failed to inhibit the contractile responses elicited by phenylephrine (2 microM) and calcium ion (7 mM) which act by cyclic AMP-independent mechanisms. In the presence of Rp-cAMPs (200 microM), the contractile response to isoprenaline (100 nM) was 24% of that in the absence of inhibitor. Rp-cAMPS was used subsequently to investigate the contractile-coupling mechanisms associated with some novel inotropic agents. Rp-cAMPS (< or = 200 microM) also inhibited the contractile responses to secretin (20 nM) and VIP (20 nM) significantly. In the presence of Rp-cAMPS (200 microM), the contractile response elicited by secretin (20 nM) was 19% of that in the absence of inhibitor, while that elicited by VIP (20 nM) was abolished completely. Rp-cAMPS (< or = 200 microM) failed to inhibit the contractile response elicited by CGRP (1 nM). In summary, Rp-cAMPS is a membrane-permeable, selective antagonist of cyclic AMP in ventricular cardiomyocytes and can be used, in conjunction with the bioassay of the intracellular accumulation of cyclic AMP, to distinguish between cyclic AMP-dependent and cyclic AMP-independent contractile coupling mechanisms in these cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Deaminase↗
PubMed1994

A reproducible method for identification of human genomic DNA autonomously replicating sequences.

We demonstrate a method for the isolation of autonomously replicating sequences from pools of clones obtained from genomic DNA libraries constructed using affinity purification of cruciform DNA. The selection of autonomously replicating sequences was based on their differential ability to replicate as episomes after transfection of pools of plasmid clones into human HeLa cells. Two separate libraries containing affinity-purified cruciform DNA were used, one prepared from DNA of log phase primary human genital fibroblasts and the other prepared from DNA of log phase SW48 colon adenocarcinoma cells. Representative samples of the entire phage libraries were converted to phagemid clones by filamentous helper phage-mediated mass excision to produce pBluescript libraries in Escherichia coli. Clones were grown up individually and the bacteria pooled into groups of 48 for recovery of plasmid DNA. Plasmid pools of 48 independent clones (120 micrograms total) were then transfected by calcium phosphate coprecipitation onto log phase HeLa cells, which were allowed to grow for 3 days before recovery of plasmid by Hirt lysis. The recovery of plasmid from each transfection was estimated to range from 10 to 60 ng. DpnI digestion was then used to digest plasmids which had not been replicated and therefore retained a bacterial methylation pattern which was sensitive to digestion. We estimated from agarose electrophoresis gels that 40-200 pg of recovered plasmid DNA per transfected pool of DNA was resistant to DpnI and therefore was capable of transforming competent E. coli cells. The DpnI-resistant fraction yielded from one to seven independent clones from each pool, with genomic DNA inserts ranging in size from 0.35 to 3.4 kb.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗
PubMed1994

Carotid body tumor associated with hyperparathyroidism.

Hyperparathyroidism in association with carotid body tumor is a rare combination. A common embryologic cellular origin was postulated previously to explain this unusual occurrence. We report a case of left carotid body tumor and left inferior parathyroid adenoma. We believe this to be the sixth reported case in the literature with this combination.

Adenoma↗
PubMed1994

Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man.

1. Oral creatine supplementation has been shown to increase muscle creatine and phosphocreatine concentrations with consequent benefits on performance during short-term maximal exercise. However, recently there have been anecdotal reports that creatine supplementation can also influence the pattern of substrate utilization and improve performance during more prolonged, submaximal exercise, which, based on recent experimental evidence, may have some scientific justification. 2. Eight men performed a continuous incremental exercise test running at 10 km/h on a motorized treadmill at predetermined workloads from 50% to 90% of maximal oxygen uptake, before and after 5 days of creatine supplementation (4 x 5 g daily). Exercise was performed for 6 min at each workload to achieve a steady state, and respiratory gas exchange and blood lactate concentrations were measured during the last 30 s at each workload. Measurements were also made at 5-min intervals for the first 15 min of recovery. 3. The results showed no measurable effect of creatine supplementation on respiratory gas exchange and blood lactate concentrations during either incremental submaximal exercise or recovery. This suggests that creatine supplementation does not influence substrate utilization during and after this type of exercise.

Adult↗
PubMed1994

Delayed presentation: dislocation of the proximal tibiofibular joint after knee dislocation.

Attention is brought to a unique case of an anterior dislocation of the proximal tibiofibular joint detected 1 month following closed reduction of a posterior knee dislocation. Open reduction and internal fixation were necessary to achieve a stable proximal tibiofibular joint. Additional attention should be paid to the proximal tibiofibular joint when evaluating acute or chronic knee dislocation.

Accidents, Traffic↗
PubMed1994

Secretin and vasoactive intestinal peptide are potent stimulants of cellular contraction and accumulation of cyclic AMP in rat ventricular cardiomyocytes.

Although secretin and vasoactive intestinal peptide (VIP) stimulate production of the second-messenger substance cyclic AMP and exert a positive inotropic action on rat ventricle in vitro, a direct action of these peptides on cardiomyocytes has not been established. In contrast to hearts of other mammalian species, which possess VIP-preferring receptors, rat heart is unique in that the existence of a "relatively nonselective receptor" at which both secretin and VIP may bind has been proposed. We wished to define the receptor(s) for secretin and VIP present on rat ventricular cardiomyocytes using a homogeneous suspension of viable cells. With adenosine deaminase 5 U/ml and the phosphodiesterase (PDE) inhibitor isobutyl methylxanthine (IBMX) 1 mM, both secretin and VIP increased intracellular levels of cyclic AMP maximally and concentration dependently after 5 min: EC50 values were 8 and 58 nM, respectively. At maximally effective concentrations, secretin 1 microM increased intracellular levels of cyclic AMP fourfold above basal levels, whereas a 1.6-fold increase was induced by VIP 10 microM. Maximum changes in cell length (dL) of isolated cardiomyocytes during electrically stimulated (0.5 Hz) contractions were determined in the presence of adenosine deaminase 2.5 U/ml. Under these conditions, both secretin and VIP produced a concentration-dependent positive contractile response that became maximal 5 min after addition of the peptide. Secretin 50 nM increased the amplitude of cellular contractions maximally to a value 37% greater than that obtained without peptide. VIP 20 nM increased the amplitude of cellular contractions maximally to a value 19% greater than that obtained without peptide. The EC50 values were 470 and 700 pM for VIP and secretin, respectively. The selective antagonist at VIP-preferring receptors, 4-Cl DPhe-6 Leu-17 VIP 10 microM did not antagonise the actions of VIP. In the presence of the selective antagonist at receptors for secretin, secretin 7-27 > or = 10 microM, the concentration dependence of the effect of secretin on accumulation of cellular cyclic AMP and contractile amplitude displayed a rightward parallel shift: the pA2 value for secretin 7-27 was 4.96. Secretin 7-27 also induced a rightward parallel shift of the concentration dependence of the actions of VIP. VIP 10 microM was additive with low concentrations of secretin (< 10 nM) in stimulating production of cyclic AMP but antagonised this response at higher concentrations of secretin (> 10 nM). Similarly, VIP 2 and 20 nM enhanced the contractile response to low concentrations of secretin (< 1 nM), but antagonised the response at higher concentrations of secretin (> 1 nM).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Calcitonin gene-related peptide stimulates a positive contractile response in rat ventricular cardiomyocytes.

Calcitonin gene-related peptide (CGRP) elicits marked positive inotropic and chronotropic actions in the atria of several mammals. The second-messenger substance cyclic AMP and activation of L-type calcium channels have been implicated in these actions, but CGRP failed consistently to stimulate a contractile response in ventricular tissue obtained from various mammals. We assessed the actions of CGRP using isolated ventricular cardiomyocytes obtained from adult rats. Maximum changes in cell length (dL) of isolated cardiomyocytes during electrically stimulated (0.5 Hz) contractions were determined with adenosine deaminase (2.5 U/ml). In these conditions, CGRP produced a potent concentration-dependent positive contractile response that became maximal 4 min after initial stimulation. CGRP increased amplitude of cellular contractions maximally at a 1-nM concentration to a value 21.4% greater than that obtained without peptide. The EC50 value for the response was 31 pM. At concentrations greater than 1 nM, amplitude of the cellular contractile response decreased rapidly. The CGRP2-selective agonist, [cys ACM2,7] CGRP, increased the amplitude of cellular contractions maximally at 500 nM to a value 19.8% greater than that obtained without peptide. EC50 for this response was 6 nM. Salmon calcitonin (< or = 100 nM) did not elicit a significant contractile response. The fragment, CGRP8-37, a selective antagonist at the CGRP1 receptor subtype, while devoid of agonist activity, was a potent competitive antagonist of the positive contractile action of CGRP (pA2 value = 7.95). CGRP, present at maximally effective concentration (1 nM), when combined with isoprenaline ISO 100 pM-1 microM, elicited a greater increase in contractile amplitude than that elicited by ISO 100 pM-1 microM without CGRP. CGRP 1 nM combined with low concentrations of extracellular calcium ion < or = 4 mM produced a greater increase in contractile amplitude than that elicited by calcium ion < or = 4 mM without CGRP, but this additive effect was abolished in the presence of higher concentrations of extracellular calcium ion (> 4 mM). The cyclic AMP antagonist, Rp-cyclic AMPS (< or = 200 microM), did not inhibit the contractile response to CGRP 1 nM, but inhibited the contractile responses to ISO 100 nM and secretin 20 nM significantly and in a concentration-dependent manner. Diltiazem < or = 1 microM, a selective antagonist of L-type calcium channels, also failed to inhibit the contractile response to CGRP 1 nM but inhibited the contractile responses to ISO 100 nM and secretin 20 nM significantly and in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

An evaluation of drug injection behaviors and HIV infection. National AIDS Research Consortium.

This paper investigates domains of drug injection behavior and the association of derived factors to HIV serostatus. Two sets of data were randomly selected and matched from a national data set of over 40,000 drug injectors. One set was HIV seropositive and the other HIV seronegative heterosexual injectors. Samples were matched to control for the effects of race/ethnicity, gender, and age on serostatus. Factor analysis was used to investigate relationships among drug injection behaviors. Four independent factors were found. Two factors were found to be statistically related to HIV serostatus in high seroprevalence areas. None of the needle use factors was found to be significantly associated with serostatus in low seroprevalence areas.

Adult↗
PubMed1994

The value of serum C-reactive protein levels as a marker of sepsis in intensive care unit patients.

A one-year prospective study was carried out to assess the value of routine serum C-reactive protein (CRP) measurement in the early diagnosis of infection in ICU patients of a District General Hospital. Ninety-one patients were included in the study. Sixty-eight patients yielded 28 proved and 77 suspected episodes of infection. Control data were drawn from 23 uninfected ICU patients. Both absolute values and percentage rates of change were examined for the following variables: serum CRP, maximum daily temperature and peripheral white blood cell count. Neither absolute CRP levels nor rates of change in CRP were found to relate significantly to proved infection. In the group in whom infection was suspected but not proved, absolute CRP levels were higher than controls on the day before the suspected infection (p = 0.019), but were not significantly raised on the day of infection nor the day after. The only significant rises in CRP (> 25%) were found in the suspected infection group from the day before to the day of infection, when compared with controls (p = 0.04). Traditional markers of infection--maximum temperature and peripheral white blood cell count--were significantly associated with infection. Maximum temperature was significantly higher in both proved and suspected infection on the day before infection (p = 0.000 and 0.001), and on the day of infection (p = 0.025 and 0.03), compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1994

Quality of life at three months following admission to intensive and coronary care units.

OBJECTIVE: Measurement of quality of life three months following critical illness, to assess impact on health expectations. DESIGN: Continuous quantitative study of patients admitted to a combined intensive and coronary care unit during a nine-month period. Questionnaires giving baseline information were completed soon after admission, and postal questionnaires incorporating the Nottingham Health Profile were sent to surviving patients three months following discharge from the unit. SETTING: District General Hospital. SUBJECTS: ICU sample included 60 patients, male n = 31, female n = 29. Twenty-nine patients received surgical treatment, 31 patients received medical treatment. Coronary Care Unit (CCU) sample included 112 patients, male n = 74, female n = 38. Fifty-four patients admitted following acute myocardial infarction (MI), 58 patients non-MI admission. MEASUREMENTS AND MAIN RESULTS: Hospital mortality for ICU patients was 31%, increasing to 34% at three months. Hospital mortality for CCU patients was 14%, increasing to 19% at three months. Significant differences in mean NHP scores between ICU and CCU patients were noted with higher CCU scores in the areas of sleep (p = 0.04), and social isolation (p = 0.01). Within the ICU group surgical patients had a higher mean NHP score in the area of pain (p = 0.02). There were no significant differences in the scores of male and female ICU patients. Within the CCU group non-MI patients had significantly higher mean scores than MI patients in the areas of energy (p = 0.007), pain (p = 0.04), emotion (p = 0.05), social isolation (p = 0.01) and physical ability (p = 0.003). Female CCU patients had higher mean NHP scores than male patients with significant differences in the areas of pain (p = 0.04), sleep (p = 0.009) and physical ability (p = 0.006). CONCLUSION: ICU patient quality of life three months after admission compares favourably with a corresponding group of CCU patients, particularly in areas of sleep and social isolation. CCU patients' general functional status deteriorated significantly compared to their pre-admission status. Critical illness is a costly area of medicine, but the results suggest that outcomes are beneficial in terms of quality of life for those surviving acute illness.

Activities of Daily Living↗