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Biomedical subjects

M R Rose

Publications and source records attributed to M R Rose.

At least 19 recordsLinked to original sources
PubMed2006

Evolution of late-life fecundity in Drosophila melanogaster.

Late-life fecundity has been shown to plateau at late ages in Drosophila analogously to late-life mortality rates. In this study, we test an evolutionary theory of late life based on the declining force of natural selection that can explain the occurrence of these late-life plateaus in Drosophila. We also examine the viability of eggs laid by late-age females and test a population genetic mechanism that may be involved in the evolution of late-life fecundity: antagonistic pleiotropy. Together these experiments demonstrate that (i) fecundity plateaus at late ages, (ii) plateaus evolve according to the age at which the force of natural selection acting on fecundity reaches zero, (iii) eggs laid by females in late life are viable and (iv) antagonistic pleiotropy is involved in the evolution of late-life fecundity. This study further supports the evolutionary theory of late life based on the age-specific force of natural selection.

Aging↗
PubMed2004

Evaluation of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

OBJECTIVES: To determine whether Gulf War veterans with neuromuscular symptoms that included weakness and fatigue had either 1) objective correlates for muscle weakness or fatigue; or 2) any etiologic explanation for such symptoms; and if so, 3) whether such objective measures or etiologic mechanisms were specific to Gulf War service. METHODS: Forty-nine ill Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill) were compared with 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic troops who were not deployed to the Gulf (Era-ill). Quantitative myometry was used to objectively measure weakness and fatigue. Subjects had an ischemic forearm exercise test, a subanaerobic bicycle exercise test, and a muscle biopsy. RESULTS: Quantitative strength and fatigue measures did not correlate with self-perception of weakness or fatigue for any of our groups. No specific muscle biopsy abnormalities were found. There was no defect of adenylate deaminase or glycogenolysis found. Gulf-ill subjects did find the subanaerobic bicycle exercise more effortful and generated significantly higher plasma lactate concentrations compared with Gulf-well subjects. CONCLUSION: Because complaints of weakness and fatigue in unwell servicemen do not correlate with actual weakness or fatigue, explanations for these symptoms must lie outside of the neuromuscular system. Increased lactate production during subanaerobic bicycle exercise reflects mitochondrial inefficiency, but it is unclear whether this reflects mitochondrial damage sustained during Gulf War service or inactivity secondary to ill health.

Biopsy↗
PubMed2004

Drug treatment for facioscapulohumeral muscular dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy is a progressive muscle disease which has no agreed treatment. Early suggestions that corticosteroids might be helpful were not supported by a subsequent open label study. The beta 2 adrenergic agonist albuterol, also known as salbutamol, is known to have anabolic effects which might be beneficial for facioscapulohumeral muscular dystrophy. Creatine has been used as a muscle performance enhancer by athletes and it might be helpful in muscular dystrophies including facioscapulohumeral muscular dystrophy. OBJECTIVES: The objective of the review was to determine whether there is any drug treatment which alters the progression of facioscapulohumeral muscular dystrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group specialised register (searched August 2003), MEDLINE (January 1966 to August 2003) and EMBASE (January 1980 to August 2003) for any references to facioscapulohumeral muscular dystrophy. Abstracts from the major neurological meetings and trial bibliographies were also searched for further references to trials. Experts were contacted for information regarding unpublished trials or trials in progress. SELECTION CRITERIA: We included all randomised or quasi-randomised trials of any drug treatment for facioscapulohumeral muscular dystrophy, in adults with a recognised diagnosis of facioscapulohumeral muscular dystrophy. Trials had to include an assessment of muscle strength at one year. DATA COLLECTION AND ANALYSIS: All identified trials were independently assessed by both reviewers to ensure that they fulfilled the selection criteria and were then rated for their quality. Trial data were extracted and entered by one reviewer and checked by the other. If appropriate data existed a weighted treatment effect was to be calculated across trials using the Cochrane statistical package, Review Manager. The results were to have been expressed as relative risks and 95% confidence intervals and risk differences and 95% confidence intervals for dichotomous outcomes, and weighted mean differences and 95% confidence intervals for continuous outcomes. MAIN RESULTS: Two published high quality randomised controlled trials fulfilled the selection criteria. One compared creatine supplementation with placebo and the other compared high and low-dose albuterol with placebo. A further unpublished randomised controlled trial of albuterol in facioscapulohumeral muscular dystrophy was identified. The creatine trial showed a non-significant difference in favour of creatine. The albuterol trial showed no significant difference in muscle strength at one year but some secondary measures such as lean body mass and handgrip strength did improve. REVIEWERS' CONCLUSIONS: There is no evidence from randomised controlled trials to support any drug treatment for facioscapulohumeral muscular dystrophy but only two randomised controlled trials have been published.

Adrenergic beta-Agonists↗
PubMed2003

Scapular fixation in muscular dystrophy.

BACKGROUND: Winging of the scapula is caused by weakness of the thoracoscapular muscles, which allows the scapula to lift off the chest wall during shoulder movements. In facioscapulohumeral muscular dystrophy (and occasionally in other muscular dystrophies) there is selective weakness of the thoracoscapular muscles which may spare other shoulder muscles such as the deltoid muscle. This imbalance results in significant winging and loss of shoulder function. Historically, a number of different surgical and non-surgical interventions have been used to achieve scapular stability. This review examines the evidence available for the use of all scapular fixation techniques in muscular dystrophy, especially facioscapulohumeral muscular dystrophy. OBJECTIVES: To examine the evidence for the relative efficacy of scapular fixation techniques in muscular dystrophy (especially fascioscapulohumeral muscular dystrophy) in improving upper limb function. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (search updated March 2003) for randomised trials and other reports, and made enquiries from authors of trials and other experts in the field. SELECTION CRITERIA: All reports of scapular fixation for muscular dystrophy, including quasi-randomised or randomised controlled trials, comparing any form of scapular fixation (surgical and non-surgical) in people (of all ages and of all severity) with scapular winging due to muscular dystrophy. Our primary outcome measure was objective improvement in shoulder abduction. Our secondary outcome measures were: patient-perceived improvement in performance of activities of daily living, cosmetic results, subjective improvement in pain and proportion of patients with significant postoperative complications. DATA COLLECTION AND ANALYSIS: We collated and summarised studies on the treatment of scapular winging in muscular dystrophy. MAIN RESULTS: No randomised trials were identified. We therefore present a review of the non-randomised literature available. REVIEWER'S CONCLUSIONS: Operative interventions appear to produce significant benefits, though these have to be balanced against postoperative immobilisation, need for physiotherapy and potential complications. We conclude that a randomised trial would be difficult, but a register of cases and the use of a standardised assessment protocol would allow more accurate comparison of the disparate techniques.

Humans↗
PubMed2002

Neurophysiologic analysis of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

BACKGROUND: UK veterans who were deployed to the Gulf in 1990 to 1991 reported higher prevalence of neuromuscular symptoms. OBJECTIVE: To investigate whether these Gulf War-related symptoms were associated with objective evidence of neuromuscular dysfunction. METHODS: Forty-nine Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill), 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic veterans who were not deployed to the Gulf (Era-ill) underwent detailed neurophysiologic assessment: nerve conduction studies, quantitative sensory and autonomic testing, and concentric needle and single-fiber electromyography (EMG). RESULTS: Nerve conduction studies detected carpal tunnel syndrome in two Gulf-ill, two Gulf-well, one Bosnia-ill, and three Era-ill veterans. Ulnar neuropathy was detected in one Gulf-ill and two Era-ill veterans. However, results of detailed nerve conduction studies of the Gulf-ill veterans were comparable with results observed in the other three groups. Quantitative sensory and autonomic assessments also failed to show any specific abnormalities in the Gulf-ill group. Similarly, quantitative assessment of concentric needle and single-fiber EMG detected no chronic denervation or myopathic changes or any abnormalities of neuromuscular transmission in the Gulf-ill veterans. CONCLUSION: Gulf War-related neuromuscular symptoms are not associated with specific impairments of peripheral nerves, neuromuscular junctions, or skeletal muscles.

Adult↗
PubMed2002

Intravenous immunoglobulin in neurological disease: a specialist review.

Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2).

Drug Costs↗
PubMed2001

A prospective natural history study of inclusion body myositis: implications for clinical trials.

Eleven patients with untreated inclusion body myositis (IBM) were prospectively studied during a 6-month period that included muscle strength, lean body mass, and muscle mass measurements. There was an overall quantifiable mean decline in percent of predicted normal muscle strength of 4% from baseline in a 6-month period, but one third of patients showed no change or slight improvements in strength. Short-term treatment trials in IBM will require large numbers of patients to detect slowing, arrest, or even slight improvement in muscle strength.

Aged↗
PubMed2001

Perspective: reverse evolution.

For some time, the reversibility of evolution was primarily discussed in terms of comparative patterns. Only recently has this problem been studied using experimental evolution over shorter evolutionary time frames. This has raised questions of definition, experimental procedure, and the hypotheses being tested. Experimental evolution has provided evidence for multiple population genetic mechanisms in reverse evolution, including pleiotropy and mutation accumulation. It has also pointed to genetic factors that might prevent reverse evolution, such as a lack of genetic variability, epistasis, and differential genotype-by-environment interactions. The main focus of this perspective is on laboratory studies and their relevance to the genetics of reverse evolution. We discuss reverse evolution experiments with Drosophila, bacterial, and viral populations. Field studies of the reverse evolution of melanism in the peppered moth are also reviewed.

Animals↗
PubMed2000

Ageing and immortality.

The concept of the force of natural selection was developed to explain the evolution of ageing. After ageing, however, comes a period in which mortality rates plateau and some individual organisms could, in theory, live forever. This late-life immortality has no presently agreed upon explanation. Two main theories have been offered. The first is heterogeneity within ageing cohorts, such that only extremely robust individuals survive ageing. This theory can be tested by comparisons of more and less robust cohorts. It can also be tested by fitting survival data to its models. The second theory is that late-life plateaus in mortality reflect the inevitable late-life plateau in the force of natural selection. This theory can be tested by changing the force of natural selection in evolving laboratory populations, particularly the age at which the force plateaus. This area of research has great potential for elucidating the overall structure of life-history evolution, particularly the interrelationship between the three life-history phases of development, ageing and immortality.

Aging↗
PubMed2000

Variation in the reversibility of evolution.

How reversible is adaptive evolution? Studies of microbes give mixed answers to this question. Reverse evolution has been little studied in sexual populations, even though the population genetics of sexual populations may be quite different. In the present study, 25 diverged replicated populations of Drosophila melanogaster are returned to a common ancestral environment for 50 generations. Here we show that reverse evolution back to the ancestral state occurs, but is not universal, instead depending on previous evolutionary history and the character studied. Hybrid populations showed no greater tendency to undergo successful reverse evolution, suggesting that insufficient genetic variation was not the factor limiting reverse evolution. Adaptive reverse evolution is a contingent process which occurs with only 50 generations of sexual reproduction.

Adaptation, Physiological↗
PubMed2000

Postponed aging and desiccation resistance in Drosophila melanogaster.

Studies with the fruit fly, Drosophila melanogaster, have repeatedly shown that selection for postponed reproduction leads to increases in mean life span and increased stress resistance; including increased resistance to desiccation, starvation and ethanol vapors. We show that desiccation resistance declines with age in both short- and long-lived flies suggesting that desiccation resistance may serve as a useful biomarker for aging-related declines in physiological performance. We examined the physical basis of desiccation resistance in five replicate populations selected for postponed reproduction and five replicate control populations. The variables examined were water content, rates of water loss during desiccation, and water content at time of death due to desiccation. In the absence of desiccation stress, both the flies exhibiting postponed senescence and their controls maintained constant water content throughout their lifetimes. In the presence of desiccation stress, the short-lived flies showed significantly higher rates of water loss at all ages than did the long-lived flies. Flies from the two treatments did not differ in water content at death. Our results indicate that water loss rates are the major determinant of desiccation resistance. Water loss rates are under genetic control and covary with age in populations with genetically-determined postponed senescence.

Aging↗
PubMed2000

Testing the heterogeneity theory of late-life mortality plateaus by using cohorts of Drosophila melanogaster.

Variation among individuals in robustness has been posed as a general explanation for the lack of increase in late-life mortality rates. Here, we test corollaries of this heterogeneity theory. One is that populations that have undergone strong laboratory selection for differentiated stress resistance should show significant differences in their late-life mortality schedules. To test this corollary, we employed 40 410 flies from three groups of Drosophila melanogaster populations that differ substantially in their resistance to starvation. No significant differences between these groups were found for late-life mortality. Another corollary of the heterogeneity theory is that there should be late-life plateaus in stress resistance that coincide with the plateau stage of the mortality curve. In 20 994 flies from six replicate outbred laboratory populations, we measured mortality rates every other day and starvation and desiccation resistance every 7 days. Both male and female starvation and desiccation resistance clearly decreased with time overall. There was no late-life plateau in male desiccation resistance. A late-life plateau in male starvation resistance may exist, however. Together, these two experiments generally constitute evidence against heterogeneity as a major contributor to the phenomenon of late-life mortality plateaus.

Animals↗
PubMed2000

Increased hsp22 RNA levels in Drosophila lines genetically selected for increased longevity.

RNAs for the small heat shock protein (hsp) genes hsp22 and hsp23 are induced during Drosophila aging, suggesting that these genes might have specific functions at late ages. To determine if hsp22 and hsp23 gene expression might correlate with life span, RNA levels for these and additional genes were analyzed throughout the adult life span in a set of five outbred "O" lines, which have been genetically selected for increased longevity, and in five matched control "B" lines. Control ribosomal protein genes rp49 and AP3/RpPO RNA levels were similar in O and B lines. In contrast, hsp22 RNA levels were twofold-tenfold higher in all five O lines relative to all five B lines, while hsp23 exhibited a smaller but significant increase. Thus increased hsp22 and hsp23 RNA levels correlate with the increased life span and increased stress resistance of the genetically selected O lines.

Animals↗
PubMed1999

The dropped head plus syndrome: quantitation of response to corticosteroids.

Severe neck extensor weakness causes the dropped head syndrome and is a disabling symptom of many specific disorders. When a diagnosis cannot be established, it has been considered a manifestation of a restricted noninflammatory myopathy. A 44-year-old man presenting with dropped head and subsequent severe limb weakness did not respond to a first trial of corticosteroids but responded well to a subsequent prolonged trial of azathioprine followed by prednisone. The decision to persist with the second trial of treatment was prompted by documented sequential increases in lean body and muscle mass, and an improvement in the quantitative myometry score which preceded clinically obvious improvement. While mechanical damage to overstretched cervical paraspinal muscles is thought to preclude a response to treatment, cases of unexplained dropped head syndrome may merit consideration of prolonged immunosuppressant treatment.

Adrenal Cortex Hormones↗
PubMed1999

Genetics of aging in Drosophila.

The genetics of aging in Drosophila are reviewed under the separate headings of population genetics, physiological genetics, and molecular genetics. However, connections between these sub-fields are brought forward for discussion.

Aging↗
PubMed1999

The effects of nutritional manipulation and laboratory selection on lifespan in Drosophila melanogaster.

There are parallels between the effects of laboratory selection and nutritional manipulation on the expression of lifespan and other fitness-related characters in Drosophila melanogaster. However, little is known about the effects of laboratory selection and nutritional manipulation when applied simultaneously. Given that D. melanogaster is one of the major model organisms for testing theories of aging, simultaneous application of laboratory selection and nutritional manipulation is of considerable interest. To that end we developed six groups of five fold replicated populations selected for either early or late fertility. Each of these groups was maintained on either high- or low-nutrition diets. Comparisons among the groups showed that nutrition is neutral in selecting for lifespan. Moreover, the dietary-restriction response can be broken by simultaneous selection and nutritional manipulation. Finally, characters that respond in a parallel manner under selection or nutritional manipulation may not when the two are applied simultaneously.

Animal Nutritional Physiological Phenomena↗