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Biomedical subjects

M Pugh

Publications and source records attributed to M Pugh.

At least 19 recordsLinked to original sources
PubMed2005

Quality of care for NSAID users: development of an assessment tool.

OBJECTIVE: Assessments of NSAID use based on authoritative guidelines typically overlook patients' views and nuances of medical history. Our objective was to develop an assessment tool that incorporates these aspects, and technical items, for quality of care assessments in NSAID users. METHODS: Patients newly referred to a university hospital were interviewed by a nurse using an agreed template. A multidisciplinary group of rheumatologists, nurse specialists, primary care physicians and a pharmacist reviewed current guidance and systematic reviews on NSAID use, and a series of interview transcripts. The group agreed, by informal consensus, important determinants of effective and safe NSAID use. Technical aspects of medical care and items that reflected interpersonal care were included in an index for assessing quality of care for individual patients. Interview transcripts of 100 patients were scored by panel members and reliability of scores was tested by calculating weighted percentage agreement and the kappa statistic. RESULTS: Our final index had five domains: medical risk factors; steps taken to reduce risk; knowledge of adverse effects; NSAID dose; and cost efficiency. Each item was scored 0, 1 or 2. Scores were summed, giving a maximum of 10 (low scores indicating low quality). Intra-rater agreement was >90%; kappa was 0.47-0.87 for individual domains and 0.59 for overall score. Inter-rater agreement for overall score was 95%; kappa was 0.25-0.78 for domains and 0.48 for overall score. Patients with especially low scores were identified using the mode of scores for five assessors; obvious clinical concerns were identified, supporting index face validity. CONCLUSIONS: A simple index to evaluate quality of care for NSAID users based on a patient interview is described. This may be used by one or more assessors to examine care standards and highlight deficiencies in relation to NSAID use in practice.

Adolescent↗
PubMed2004

Functions of optic nerve glia: axoglial signalling in physiology and pathology.

An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

Adenosine Triphosphate↗
PubMed2001

Negative pressure pulmonary oedema after cryotherapy for tracheal obstruction.

We report a patient who suffered negative pressure pulmonary oedema because of tracheal obstruction after cryotherapy to granulation tissue in the trachea. The pathophysiology and clinical course of negative pressure pulmonary oedema is described. Though there are reports of negative pressure pulmonary oedema after airway obstruction, to our knowledge this is the first case reported after cryotherapy.

Aged↗
PubMed2001

The challenge of civil-military relations in international peace operations.

The relationship between military and civilian humanitarian organisations has developed in an increasingly integrative way. Military initiatives to institutionalise the relationship, since the interventions in Somalia and the Balkans, entail a dilution of humanitarian independence as was manifested in practice in Kosovo. Further, the state-centric foundations of military intervention run counter to the potential for humanitarian organisations to foster a cosmopolitan ethos that would not only preserve humanitarian principles but also contest statist assumptions about conflict, development and power.

Altruism↗
PubMed1999

The cutaneous vasoconstrictor response to venous stasis is normal in subjects with primary Raynaud's disease.

In control subjects and in subjects with primary Raynaud's disease, sudden sound or a mild cool stimulus evokes the pattern of alerting response that includes cutaneous vasoconstriction but vasodilatation in forearm muscle. In control subjects, response habituates on repetition of these stimuli both within experimental sessions and over successive days. However, in subjects with primary Raynaud's disease, the cutaneous vasoconstriction and the muscle vasodilatation persist. We have now tested whether a similar disparity exists for the cutaneous vasoconstriction evoked by venous stasis, a response considered to be a veno-arteriolar reflex mediated by sympathetic fibers, but not requiring transmission through the spinal cord. In 10 subjects with primary Raynaud's disease and in 10 matched controls, a sphygmomanometer cuff on the left arm was inflated to 40 mm Hg for 2 minutes, five times on each of three experimental sessions on days 1, 3, and 5. Cutaneous red cell flux (RCF) was recorded from the pulp and dorsum of the left index finger by using a laser Doppler meter; digital vascular conductance (DCVC) was computed as RCF divided by arterial pressure. The first venous stasis, in session 1, evoked a decrease in pulp and dorsum DCVC in the control and primary Raynaud's subjects. There were no differences between the groups in the magnitudes or durations of these responses. Within session 1, the magnitude of the decrease in DCVC diminished on repetition of venous stasis in the dorsum in controls and in the pulp in primary Raynaud's subjects. We propose these effects reflected the similar reductions in baseline DCVC over time; there was no change in the duration of the responses. Repetition of venous stasis had similar effects in both groups of subjects within sessions 2 and 3. Further, judging from the mean of the responses evoked in each Session the decreases evoked in pulp and dorsum DCVC by venous stasis were fully consistent in magnitude and duration over the three sessions in both groups. These results indicate that the direct constrictor influence of sympathetic fibers upon cutaneous blood vessels is similar in magnitude and similarly reproducible in controls and subjects with primary Raynaud's disease. This reinforces our view that the lack of habituation of the cutaneous vasoconstrictor component of the alerting response in subjects with primary Raynaud's disease reflects impairment of the central neural process of habituation, rather than a peripheral phenomenon, and that this lack of habituation predisposes these subjects to vasospasm.

Adult↗
PubMed1999

Cardiovascular responses evoked by mild cool stimuli in primary Raynaud's disease: the role of endothelin.

In control subjects and in subjects with primary Raynaud's disease, sudden sound evokes the pattern of the alerting response, which includes cutaneous vasoconstriction and vasodilatation in forearm muscle. However, whereas this pattern of response habituates on repetition of the sound stimulus in control subjects, both cutaneous vasoconstriction and muscle dilatation persist in subjects with primary Raynaud's disease. The aim of the present study was to test whether a similar disparity exists between control subjects and those with primary Raynaud's disease for the response to mild cool stimuli, and whether the cutaneous response is accompanied by the release of endothelin-1 (ET-1). In nine subjects with primary Raynaud's disease and in nine matched controls, the left hand was placed in cool water at 16 degrees C for 2 min five times on each of three experimental sessions on days 1, 3 and 5, with blood being taken from the venous drainage of the cooled hand before and at the end of the second session. In response to the first cool stimulus in Session 1, the subjects with primary Raynaud's disease showed a decrease in digital cutaneous vascular conductance (DCVC) in both the right and left hands, as indicated by a laser Doppler recording of erythrocyte (red cell) flux divided by arterial pressure, and six of the nine subjects showed an increase in forearm vascular conductance (FVC), as indicated by forearm blood flow measured by plethysmography divided by arterial pressure. On repetition of the stimulus in Session 1, there was no change in the magnitude of the increase in FVC, but the evoked decreases in DCVC became more prolonged in both the right and the left hand. Similar responses occurred in Sessions 2 and 3; in Session 2, the ET-1 concentration increased from a baseline value of 2.15+/-0.26 fM to 2.72+/-0.37 fM after five stimuli. There was no habituation of the increase in FVC over Sessions 1, 2 and 3, judging from the mean changes in each session. Control subjects also showed a decrease in DCVC in both hands, and in eight out of nine subjects there was an increase in FVC in response to the first cool stimulus in Session 1. However, on repetition of the stimulus in Session 1, the increase in FVC habituated, while there was no prolongation of the decrease in DCVC; in addition, the ET-1 concentration did not change in Session 2 in response to the stimulus (2.07+/-0.28 compared with 2.29+/-0.30 fM). Further, the increase in FVC habituated over the three sessions, such that there was a mean decrease in FVC in Session 3. These results indicate that, in subjects with primary Raynaud's disease, there is impairment of the ability of the central nervous system to allow habituation of the cardiovascular components of the alerting response evoked by mild cooling, as with the response to sound. We propose that persistence of the cutaneous vasoconstriction of the alerting response, coupled with increased release of ET-1 secondary to vasoconstriction, prolongs such vasoconstriction and eventually leads to vasospasm.

Adult↗
PubMed1998

Military intervention and humanitarian action: trends and issues.

An important trend in military doctrine for so-called 'peace support operations' has been to place them on a spectrum that includes coercion and enforcement. This paper focuses on British writers of doctrine as those responsible for driving the debate forward and forging a consensus among leading military powers. Their discourse is combat oriented, a fact reinforced by a trend towards strategic subcontracting to coalitions of the militarily willing and able. At the same time, there has been a move to institutionalise the involvement of military forces in relief, peace building and development activities. The overall emphasis is on stability and security to facilitate the delivery of humanitarian relief and to establish the conditions for peace-building processes. In the case of Bosnia, this involves conditionality and economic leverage. Although there is a long-established record of peace-keeping forces engaging in goodwill activities (with mixed results), the current trends contain contradictions that seem likely to contribute to the widely perceived erosion of classical humanitarian principles.

Altruism↗
PubMed1998

Lack of habituation of the pattern of cardiovascular response evoked by sound in subjects with primary Raynaud's disease.

1. The vasospasm of primary Raynaud's disease can be triggered by acute emotional stress. We have studied the pattern of cardiovascular response evoked by acute emotional stress, a sound stimulus of 90 dB, 2 kHz for 30 s, in eight subjects with primary Raynaud's disease and in eight age- and sex-matched controls, the sound being repeated five times on each of days 1, 3 and 5. 2. In controls, the first sound evoked the pattern of the alerting response that is characteristic of acute emotional stress: a rise in arterial pressure and heart rate, a decrease in vascular conductance in the cutaneous circulation of the digit, assessed by laser Doppler recording of erythrocyte (red cell) flux in the digit divided by arterial pressure, and an increase in forearm muscle vascular conductance, assessed from forearm blood flow recorded by venous occlusion plethysmography divided by arterial pressure. 3. In the subjects with primary Raynaud's disease, baselines of arterial pressure, digital cutaneous vascular conductance and forearm vascular conductance were not significantly different from those of the controls and they too showed the alerting response to the first sound, the magnitudes of the changes being comparable to those of the controls. 4. In both the controls and subjects with primary Raynaud's disease, the evoked responses were consistent on repetition of the sound on day 1. In contrast, judging from the means of the changes evoked on each day, the controls showed habituation of the individual components of the alerting response over days 1, 3 and 5, whereas the subjects with primary Raynaud's disease showed no habituation of either the forearm muscle vasodilatation or the digital vasoconstriction. Conversely, the decrease in digital cutaneous vascular conductance evoked by a single deep breath was fully reproducible in both controls and subjects with primary Raynaud's disease when tested at the beginning and end of each experimental day. 5. These results allow the novel conclusion that subjects with primary Raynaud's disease have an abnormality of the central neural modulation of the brain stem areas that integrate the cardiovascular components of the alerting response to acute emotional stress, such that habituation of the vasodilator and vasoconstrictor components of the response on repetition of the stimulus is impaired. We propose that such persistence of vasoconstrictor responses to stressful stimuli predisposes to vasospasm, particularly if neurally mediated vasoconstriction is reinforced by locally released vasoconstrictor factors.

Adult↗
PubMed1997

Should cardiac disease prevent autologous blood donation?

AIDS has created considerable concern among the public regarding being transfused with potentially infectious blood. However, autologous blood donations are still not maximally provided nor utilized. Significant heart disease disqualifies all allogeneic and most autologous blood donors (American Association of Blood Banks (AABB) Standards 1994). Disqualification is based on the widespread belief that donating blood could possibly be detrimental to their health. However, this belief has not been sufficiently documented. Sixty-eight donors (ages 14-84 years), all with histories of significant cardiac diseases, donated 111 units of whole blood (1-3 units). Twenty-eight patients donated 1 unit, 37 donated 2 units, and three patients donated 3 units. Fifty-nine patients had ischemic heart disease, and nine had valvular heart disease (five with mitral stenosis and four with mitral valve prolapse). No patient received erythropoietin, and only one received equal volume replacement with normal saline during donation. All these patients eagerly wished to donate in spite of being informed of the possible complications. No patient wishing to donate has been refused, and none has experienced any adverse consequences from donating. Forty-four patients underwent total hip/knee replacements. Only 56 units (50%) were transfused to 37 patients (54%). Although our experience is limited, it appears that many patients with histories of well established cardiac diseases can easily tolerate donating blood without compromising their health.

Adolescent↗
PubMed1997

DIC screening in the newborn.

Although reliable hemostasis screening in the newborn is difficult to obtain, the information gained from such testing is essential in differentiating the inherited from the acquired bleeding disorder. Sick infants are at risk for developing hemorrhage or thrombosis in response to a variety of diseases or injuries. Screening tests must be interpreted using appropriate normal ranges for term or preterm infants. Neonates are particularly susceptible to DIC because of their underdeveloped reticuloendothelial system and their tendency to develop acidosis, hypothermia, hypoxia, and shock. Bleeding is commonly the results of intravascular coagulation or decreased synthesis of clotting factors by the liver. Criteria based on clinical and laboratory findings have been determined in adults; however, these criteria are not necessarily applicable to neonates. A study reviewing 74 cases of newborns with suspected DIC reported that the most reliable diagnostic tests are the platelet count, D-dimer or FDP, PT, PTT, and fibrinogen. Whatever the test, the nurse's accurate assessment of the neonate, careful collection of blood, and reporting of abnormal results remain paramount in obtaining timely, appropriate care.

Adult↗
PubMed1996

Eastern cooperative group trial of interferon gamma in metastatic melanoma: an innovative study design.

IFN-gamma is a potent immunomodulator, which has activity against melanoma in vitro and in murine models. However, preclinical data suggests that the optimal therapeutic and immunomodulatory dose may not be the maximally tolerated clinical dose. We conducted a Phase II/III trial in good prognosis patients with metastatic melanoma to determine whether a therapeutic and immunomodulatory dose-response curve of IFN-gamma could be identified, and whether the two could be correlated. Ninety-eight patients with metastatic melanoma were randomized to one of seven dose levels of IFN-gamma ranging from 0.01 to 0.90 mg/m2. All patients were required to have s.c., skin, soft tissue, or nodal disease, although visceral disease was also allowed, and no more than one prior chemotherapy regimen. Patients received IFN-gamma as a 1-h i.v. infusion three times per week for at least 8 weeks or until progressive disease. Ninety-five patients were eligible for toxicity evaluation; 81 were eligible for tumor response. Four patients responded to therapy (response rate, 5%) at three dose levels: two patients at 0.01 mg/m2 and one each at 0.5 and 0.9 mg/m2. The duration of response ranged from 5 to 58 weeks. Toxicities were typical of IFNs and included flu-like constitutional symptoms. No dose-response relationship was identified for efficacy. A dose-response relationship for toxicity was observed only for fever and chills (p = 0.035) and hepatic toxicity (p = 0.034). IFN-gamma has minimal activity in metastatic melanoma, and a therapeutic dose-response curve could not be identified. Although potent dose-dependent effects on immunomodulation were identified (J. M. Kirkwood, J. Bryant, J. H. Schiller, M. M. Oken, E. C. Borden, and T. L. Whiteside. Immunomodulatory function of interferon gamma in patients with metastatic melanoma: results of a phase IIB trial in subjects with metastatic melanoma: ECOG Study E4987, submitted for publication), this biological activity does not translate into therapeutic activity in the metastatic disease setting in this trial.

Adult↗
PubMed1995

Changes in bone density in women starting hormone replacement therapy compared with those in women already established on hormone replacement therapy.

It is well established that hormone replacement therapy (HRT) will prevent postmenopausal loss of bone. However, it is not known to what extent HRT will continue to affect bone mineral density (BMD) in women established on HRT compared with those commencing treatment. We recruited 48 healthy early postmenopausal women into a prospective, comparative study. Twenty-nine women had never taken HRT (group A) whilst 19 women were already taking HRT (group B) (conjugated equine oestrogens, 0.625 mg daily; mean (+/- SD) years of use 2.2 (1.5) years). All of the women were started on, or switched to, micronized 17 beta-oestradiol (2 mg/day) continuously with dydrogesterone (10 mg/day) for the first 14 days of each cycle. BMD measurements were performed at the lumbar spine and proximal femur using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 and 24 months of treatment. Group A showed a significantly greater increase in lumbar spine BMD after 12 months (mean +/- SD) = 5.3 (4.6)%) compared with group B (mean +/- SD) = 2.1 (2.1)%) and 24 months of treatment (group A, mean (+/- SD) = 6.4 (5.2)%; group B, mean (+/- SD) = 2.3 (2.6)%; both p < 0.01) and 24 months of treatment (r = -0.05). These data demonstrate that HRT has the greatest effect on BMD when it is first administered, especially in those women with low BMD, but improvements may still be observed in women continuing HRT in the longer term.

Adult↗
PubMed1994

Gender- and race-specific effects of asthma and wheeze on level and growth of lung function in children in six U.S. cities.

The gender-and race-specific effects of asthma/wheeze on pulmonary function level and annual growth velocity were studied in a cohort of 10,792 white and 944 black children 6 to 18 yr of age, examined annually between 1974 and 1989 in six U.S. cities. In comparison with white boys who never reported asthma or wheeze, FEV1 levels were 5.7% lower and FEF 25-75 levels were 16.9% lower for white boys with a diagnosis of asthma who reported wheeze symptoms in the past year. White girls with asthma and wheeze had FEV1 levels that were 3.4% lower and FEF25-75 levels that were 13.6% lower than white girls with never-asthma/wheeze. Asthma with wheeze was associated with a greater percent deficit in FEV1 level in boys than in girls (p < 0.01) and, particularly in preadolescence, with a significant percent increment in FVC level (1.6%) for girls but not for boys. The diagnosis of asthma with or without wheeze in the past year was associated with a greater deficit in level of lung function than the reporting of wheeze symptoms in a child without the diagnosis of asthma. The prevalence of asthma and wheeze was higher among blacks, but no race differences were found in the effects of asthma or wheeze on level of FEV1 and FEF25-75. Compared with white adolescent female ever asthmatics with no medication use, FEV1 level was 5.8% lower for those with routine medication use and 7.8% lower for those with routine and additional medication use. Although white girls with wheeze but no diagnosis of asthma had slightly slower growth of FEV1 (0.3% per year) than did white girls without asthma or wheeze, children with asthma did not have slower annual growth in percent terms. In absolute terms, growth of FEV1 was 14.7 ml/yr and FEF25-75 was 47 ml/s/yr slower for asthmatic white boys with wheeze than for those without asthma; for girls with asthma and wheeze growth of FEF25-75 was 29 ml/s/yr slower. We conclude that in absolute terms, but not in percent terms, the pulmonary function deficits associated with asthma and wheeze increase throughout childhood. In the preadolescent and adolescent years, the mechanical properties of the lungs and the inflammatory process in asthmatics may differ by gender, leading to gender differences in their pulmonary function. We also conclude that lung function may not return to normal, even when asthmatics become asymptomatic.

Adolescent↗
PubMed1991

Case management of the anemic patient. Focus on hemodynamics.

Cardiac function of dialysis patients improves when severe anemia is corrected with Epoetin alfa. Direct clinical changes include a decrease in cardiothoracic ratio and diminished left ventricular size. Exercise-induced cardiac ischemia as noted by depression of the S-T segment on EKG is also reduced. Nephrology nurses must monitor hemodynamic changes, provide patient reeducation, and encourage patient compliance with medication regimens.

Adult↗