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Biomedical subjects

M Pike

Publications and source records attributed to M Pike.

At least 19 recordsLinked to original sources
PubMed2004

Glucocorticoid corticosteroids for Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is the most common muscular dystrophy of childhood. This incurable disease is characterised by muscle wasting and loss of walking ability leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is one of the major aims of treatment. OBJECTIVES: The aim of this review was to assess whether glucocorticoid corticosteroids stabilize or improve muscle strength and walking in boys with DMD. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised register (October 2003) using the term 'Duchenne muscular dystrophy'. We also searched MEDLINE (January 1966 to October 2003), EMBASE (January 1980 to October 2003), CINAHL and LILACS (January 1982 to October 2003). We wrote to authors of published studies and other experts in this disease to help identify other trials, checked the references in the identified trials and handsearched the abstracts of relevant journals. SELECTION CRITERIA: Types of studies: randomised or quasi-randomised trials. TYPES OF PARTICIPANTS: all patients with a definite diagnosis of Duchenne muscular dystrophy. Types of interventions: glucocorticoids such as prednisone, prednisolone, deflazacort or others, with a minimum treatment period of three months. PRIMARY OUTCOME MEASURE: prolongation of walking (independent walking without long leg calipers). SECONDARY OUTCOME MEASURES: strength outcome measures, manual muscle strength testing using Medical Research Council strength scores, functional outcome measures and adverse events. DATA COLLECTION AND ANALYSIS: We identified five randomised controlled trials that met the inclusion criteria for our review. Two reviewers independently selected the trials for the review and assessed methodological quality. Data extraction and inputting were double-checked. MAIN RESULTS PRIMARY OUTCOME MEASURE: data from one small study used prolongation of walking as an outcome measure and did not show significant benefit. SECONDARY OUTCOME MEASURES: The meta-analysis of the results from three randomised controlled trials showed that glucocorticoid corticosteroids improved muscle strength and function over six months. Improvements were seen in time taken to rise from the floor (Gowers' time), nine metres walking time, four-stair climbing time, ability to lift weights, leg function grade and forced vital capacity. One randomised controlled trial showed that glucocorticoid corticosteroids stabilize muscle strength and function for up to two years. The most effective prednisolone regime appears to be 0.75 mg/kg/day. Not enough data were available to compare efficacy of prednisone with deflazacort.Adverse effects: Excessive weight gain, behavioural abnormalities, cushingoid appearance and excessive hair growth were all more common with glucocorticoid corticosteroids than placebo. Long-term adverse effects of glucocorticoid therapy could not be evaluated because of the short-term duration of the randomised studies.Non-randomised studies: a number of non-randomised studies with important efficacy and adverse effects data are tabulated and discussed. REVIEWERS' CONCLUSIONS: There is evidence from randomised controlled studies that glucocorticoid corticosteroid therapy in Duchenne muscular dystrophy improves muscle strength and function in the short-term (six months to two years). The most effective prednisolone regime appears to be 0.75 mg/kg/day. In the short term, adverse effects were significantly more common but not clinically severe. Long-term benefits and hazards of glucocorticoid treatment cannot be evaluated from the currently published randomised studies. Non-randomised studies support the conclusions of functional benefits but also indicate clinically significant adverse effects of long-term treatment. These benefits and adverse effects have implications for future research studies and clinical practice.

Adrenal Cortex Hormones↗
PubMed2003

Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National Case-Control Study of Cervical Cancer.

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20-44 years from the UK National Case-Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of sexual partners, and, independently, to age at first intercourse. The risk of both types of cervical cancer increased with increasing duration of use of oral contraceptives, and this effect was most marked in current and recent users of oral contraceptives. The risk of squamous cell carcinoma was associated with high parity and the risk of both squamous cell and adenocarcinoma increased with early age at first birth. Long duration smoking (20 or more years) was associated with a two-fold increase in the risk of squamous cell carcinoma, but smoking was not associated with the risk of adenocarcinoma. Further studies are needed to confirm the suggestion from this and other studies of differences in risk related to smoking between squamous cell and adenocarcinomas of the cervix.

Adenocarcinoma↗
PubMed2001

Pharmacokinetics and pharmacodynamics of recombinant FGF-2 in a phase I trial in coronary artery disease.

Fibroblast growth factor-2 (FGF-2) is a heparin-binding protein capable of inducing angiogenesis in multiple animal models of chronic ischemia. The pharmacokinetics and pharmacodynamics of a single dose of recombinant FGF-2 (rFGF-2) administered by intracoronary or intravenous infusion were evaluated in a Phase I trial in 66 patients with severe coronary artery disease. rFGF-2 displayed biphasic elimination with a mean studywide distribution t1/2 of 21 minutes and a mean apparent terminal elimination t1/2 of 7.6 hours. Systemic exposure to rFGF-2 was comparable following intracoronary or intravenous administration. Peak plasma concentration and area under the concentration-time curve increased proportionally with dose, indicating linear pharmacokinetics over the dose range examined (0.33 to 48.0 micrograms/kg). Greater systemic exposure was observed when heparin was administered closer to rFGF-2 infusion, consistent with slower clearance of heparin/rFGF-2 complexes. Infusion of rFGF-2 was associated with changes in acute hemodynamics. While a clear PK/PD dose-response relationship was not established, a trend toward hypotension and tachycardia with higher rFGF-2 doses was observed.

Adult↗
PubMed2000

Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease.

BACKGROUND: We report the effects of the administration of recombinant fibroblast growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon emission computed tomography imaging in humans with advanced coronary disease. METHODS AND RESULTS: A total of 59 patients with coronary disease that was not amenable to mechanical revascularization underwent intracoronary (n=45) or intravenous (n=14) administration of rFGF-2 in ascending doses. Changes in perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF-2 administration. In this uncontrolled study, perfusion scans were analyzed by 2 observers who were blinded to patient identity and test sequence; scans were displayed in random order, with scans from nonstudy patients randomly interspersed to enhance blinding. Combining all dose groups, a reduction occurred in the per-segment reversibility score (reflecting the magnitude of inducible ischemia) from 1.7+/-0.4 at baseline to 1.1+/-0.6 at day 29 (P:<0.001), 1.2+/-0.7 at day 57 (P:<0.001), and 1.1+/-0.7 at day 180 (P:<0.001). The 37 patients with evidence of resting hypoperfusion had evidence of improved resting perfusion: their per-segment rest perfusion score of 1.5+/-0. 5 at baseline decreased to 1.0+/-0.8 at day 29 (P:<0.001), 1.0+/-0.8 at day 57 (P:=0.003), and 1.1+/-0.9 at day 180 (P:=0.11). CONCLUSIONS: These preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis.

Coronary Disease↗
PubMed2000

Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary.

The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.

Angiogenesis Inducing Agents↗
PubMed2000

Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a phase I open-label dose escalation study.

OBJECTIVES: Evaluate the safety, tolerability and preliminary efficacy of intracoronary (IC) basic fibroblast growth factor (bFGF, FGF-2). BACKGROUND: FGF-2 is a heparin-binding growth factor capable of inducing functionally significant angiogenesis in animal models of myocardial ischemia. METHODS: Phase I, open-label dose-escalation study of FGF-2 administered as a single 20-min infusion in patients with ischemic heart disease not amenable to treatment with CABG or PTCA. RESULTS: Fifty-two patients enrolled in this study received IC FGF-2 (0.33 to 48 microg/kg). Hypotension was dose-dependent and dose-limiting, with 36 microg/kg being the maximally tolerated dose. Four patients died and four patients had non-Q-wave myocardial infarctions. Laboratory parameters and retinal examinations showed mild and mainly transient changes during the 6-month follow-up. There was an improvement in quality of life as assessed by Seattle Angina Questionnaire and improvement in exercise tolerance as assessed by treadmill exercise testing (510+/-24 s at baseline, 561+/-26 s at day 29 [p = 0.023], 609+/-26 s at day 57 (p < 0.001), and 633+/-24 s at day 180 (p < 0.001), overall p < 0.001). Magnetic resonance (MR) imaging showed increased regional wall thickening (baseline: 34+/-1.7%, day 29: 38.7+/-1.9% [p = 0.006], day 57: 41.4+/-1.9% [p < 0.001], and day 180: 42.0+/-2.3% [p < 0.001], overall p = 0.001) and a reduction in the extent of the ischemic area at all time points compared with baseline. CONCLUSIONS: Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 microk/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of the study.

Aged↗
PubMed1999

Spinal cord insults in the prenatal, perinatal, and neonatal periods.

We investigated the features of children with spinal cord insults (SCI) occurring in the pre-, peri-, and neonatal periods by sending 340 questionnaires to all paediatric neurologists, paediatric urologists, and neonatologists in the UK and Ireland. We requested information about timing, nature, and level of SCI in their patients; family and maternal history; pregnancy, delivery, and neonatal period; clinical presentation, imaging, laboratory studies, and outcome. Two-hundred and sixty-one questionnaires were returned with data on 58 patients with SCI. Seven out of the 58 children with SCI had pure dysraphic cord syndromes and were excluded. Fifty-one patients (33 males, 17 females, one unknown), born between 1972 and 1996, remained. Clinical presentations included severe respiratory failure (N=20; five of whom died neonatally) and hypotonia or weakness recognized either during the neonatal period (N=12) or after 28 days (N=10). Data on clinical presentation were not given in nine cases. Lesions were cervical (N=22) and thoraco-lumbar (N=29). SCI was ascribed to ischaemia (N=12), trauma (N=4), and other associated underlying conditions (N=11), whilst the aetiology was unknown in 24 cases. Mean gestational age (36.2 weeks) and birthweight (2.6 kg) were lower than previously reported with the lowest figures associated with thoraco-lumbar and ischaemic lesions. More males were affected by lesions than females and the incidence of preterm delivery, multiple pregnancy, breech presentation, forceps delivery, and caesarean delivery were higher than average. Forceps delivery was associated with cervical lesions. Outcome data were given in 47 children, nine of whom died either neonatally or within the first 20 months of life. Motor disability ranged from a complete recovery in one out of 40 to paraparesis in 26 out of 40, and tetraparesis in 13 out of 40 patients: 17 out of 39 were ambulant. Sphincter dysfunction was present in 22 out of 38 patients and scoliosis in 16 out of 37. Learning difficulties were present in 10 out of 39, behavioural problems in five out of 39 and seizures in four out of 39 patients. SCI in the pre-, peri-, and neonatal periods are rare but probably under-diagnosed and are heterogeneous in aetiology, presentation, and outcome. Boys appear to be more susceptible than girls.

Female↗
PubMed1998

Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study.

Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (P<0.01) increase in the ratio of choline-containing compounds to N-acetylaspartate (Cho/NA) in the left cerebellum in boys with DMD compared with control boys. There was no change in the creatine/NA ratio and a significant increase (P=0.03) in the Cho/creatine ratio, suggesting that the change in Cho/NA ratio was due to an increase in choline-containing compounds; this increase has been previously observed in the brain of the murine model of DMD, the mdx mouse. No significant changes were observed in spectra obtained from left frontal lobe in DMD compared to controls. We also observed a significant association between Cho/NA in the left cerebellum, and the performance of DMD boys on the Matrix Analogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.

Age Factors↗
PubMed1998

Challenges of establishing a nursing center in rural eastern Oregon.

The success of the center, in fact its very existence, is the result of cooperation among many persons and agencies. Financial gifts, loans and grants have given the clinic a three-year time period to learn valuable lessons on how to organize for self-sufficiency. Staff have learned how to market to increase patient visit and have obtained Federal Rural Health Clinic status which will increase revenues substantially. Nurse Practitioners are learning appropriate visit coding and hold regular brainstorming meetings to develop creative business opportunities to assure financial stability. As a result of these experiences, the NP faculty have been able to design learning experiences for the nurse practitioner students which introduce them to entrepreneurial realities. Challenges are being met by the NPs in this rural practice which require vigor, creativity, and vigilance. Once the center reaches the level of self-sufficiency, it is the intent of the community to build a facility which can support a significant increase in patient load and still have room for other social and health services to operate within the facility. Bridges to the medical community are being strengthened through better communication and more community involvement. Educating the public and the medical community about the role of nurse practitioners and the broad base of nursing centers is a continual challenge for both faculty and students at the School of Nursing.

Community Health Centers↗
PubMed1996

Cataracts, motor system disorder, short stature, learning difficulties, and skeletal abnormalities: a new syndrome?

We present a 4-generation family in which affected individuals have cataracts, a motor neuronopathy with upper motor neuron signs, short stature, developmental delay, and skeletal abnormalities. An additional symptom is weakness during pregnancy which resolves after delivery. The condition is inherited in an autosomal dominant manner. The manifestations and inheritance are not found in any previously described conditions. We consider that this is a new syndrome.

Abnormalities, Multiple↗
PubMed1996

Episcleral plaque thermoradiotherapy of posterior uveal melanomas.

Episcleral plaque radiotherapy is a widely applied treatment for selected patients with uveal melanomas. This treatment is well tolerated but may produce severe late radiation complications resulting in decreased visual acuity that reduces the attractiveness of conservative therapy. The purpose of this study was to access if the addition of episcleral hyperthermia decreases late radiation complications through radiation dose reduction while maintaining high incidence of local tumor control. In a 3-year period, episcleral plaque thermoradiotherapy was given to 25 patients with uveal melanoma in a Phase I study. The mean tumor height was 6.2 mm and the mean tumor basal area was 173 mm(2). The mean radiation dose given to the tumor apex was 72.2 Gy and the mean hyperthermia temperature, given once for 45 min, was 43.5 degrees C. Of the 25 patients treated, 22 (88%) showed tumor height reduction, 2 (8%) showed no change, and 1 (4%) had an increase in tumor height. At the last follow-up (range, 20-68 months; mean, 31.2 months), a 43% mean tumor height reduction was recorded (p = 0.0002). Of the 22 patients initially showing tumor regression, 2 (9%) had subsequent tumor progression. At least ambulatory vision (>5/200) was maintained by 20 (80%) patients. Severe complications, including hemorrhagic retinal detachment and a large vitreous hemorrhage, were seen in 2 (8%) patients early in this Phase I study. The treatment program was well tolerated by the study patients. Severe late treatment toxicity was sharply reduced by limiting the mean scleral temperature to < or equal to 44 degrees C. This study employing 30% lower radiation doses, showed tumor regression in the majority of patients. Longer follow-up is needed to assess long-term treatment efficacy and late treatment complications.

Adolescent↗
PubMed1996

Interleukin-2 promotes the motility of dendritic cells and their accumulation in lung and skin.

Dendritic cells (DC) play a critical role as antigen-presenting cells in vivo. It has previously been shown that DC accumulate in the lung in response to parenteral injections of IFN-gamma. In the current paper, we report that rat DC express the interleukin-2 receptor (IL-2R) alpha-chain (OX-39) and display enhanced motility in response to IL-2 in Boyden chamber and video time-lapse microscopy assays. Increased motility was specifically inhibited by pretreating DC with OX-39 (anti-IL-2R) but not OX-22 (anti-CD45RC), an isotype-matched murine monoclonal antibody. The intratracheal injection of IL-2 increased the number of OX-6+ dendritic cells located around pulmonary venules and in the lung interstitium. When IL-2 was injected into the footpad of the rat. DC were increased around dermal venules at 24 h. This effect was blocked by the parenteral injection of anti-OX-39. We conclude that IL-2 is a potent enhancer of DC motility and may cooperate with other T helper(h)-1 proinflammatory cytokines in attracting DC to sites of inflammation.

Animals↗
PubMed1995

Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study.

Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.

Adenosine Triphosphate↗