Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overnight monitoring using pulse oximeter was performed on 10 patients with Duchenne muscular dystrophy (mean age, 22; mean %FVC, 26.6%; mean PaCO2, 54.1 Torr; mean PaO2 76.6 Torr). At the same time, spinal deformity and obesity were examined. In 4 patients, the measurement of the chest and abdominal wall movements were performed by using a respisomnograph. In 5 patients, nocturnal desaturation below 95% occurred despite normal daylight blood gas tension. In the other 5 patients with hypercapnea of over 50 Torr, nocturnal desaturation below 85% occurred, and 3 patients required oxygen supplementation treatment using a low concentration of oxygen. In 4 patients with hypercapnea over 50 Torr, cuirass-assisted respirators were used and they prevented mild nocturnal desaturation, but did not have much effect on severe nocturnal desaturation. Nocturnal desaturation was associated not only with hypopnea and hypoventilation, but with normal chest and abdominal wall movement using cuirass-assisted respirators. It seemed that desaturation with normal respiratory pattern can be attributed to ventilation-perfusion mismatching. The severity of the desaturation did not always correlate to the spinal deformity and the obesity.
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PMID:[Nocturnal hypoxia and treatment in the patients with Duchenne muscular dystrophy]. 237 59

Malignant limb-girdle muscular dystrophy was first described by Miyoshi and co-workers in 1966, and has clinical features similar to Duchenne muscular dystrophy but is inherited through an autosomal recessive trait. This paper describes a patient with malignant limb-girdle muscular dystrophy with complete deficiency of adhalin (50 kDa dystrophin-associated glycoprotein (DAG)) in skeletal muscle. The patient was an 11-year-old Japanese girl whose parents were cousin. She learned to walk at one year and 3 months of age. Her gait became unsteady at 3 years of age, and motor dysfunction in the lower extremities progressed thereafter. At 8 years of age, she had difficulty in standing up from a sitting position, but could walk without assistance. At 11 years, she could walk with support, but could not stand up without assistance. Her intelligence was normal. Muscle atrophy was not apparent due to obesity, but her calves appeared hypertrophic. She had generalized muscle weakness, predominantly in the pelvic girdle muscle. Muscle tone was slightly hypotonic, and deep tendon reflexes of the legs were absent or hypoactive. Her sensory system appeared normal. Serum creatine kinase level was elevated to 30 times above the upper limit of the normal range in the patient and normal in her parents. EMG showed a mild myopathic pattern. CT scan of muscle revealed marked low density in the upper legs and mild in the lower legs. Muscle histology showed muscle fiber necrosis with a small number of regenerating fibers. Opaque fibers were occasionally observed, but not as many as in Duchenne type. Fiber splitting was seen frequently.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Complete deficiency of adhalin (50 kDa DAG) in skeletal muscle of malignant limb-girdle muscular dystrophy]. 778 Dec 37

A specific-weight chart and simple clinical tools are sufficient to obtain an accurate diagnosis of undernutrition or obesity among patients with Duchenne muscular dystrophy (DMD). The authors collected weight-for-age measures from a sample of 252 boys and anthropometric data from 109 of those boys with DMD. The data confirm the accuracy of the DMD ideal-weight chart previously proposed by Griffiths and Edwards (1988). Obesity may occur from the age of seven years; its prevalence seems to reach 54 per cent by the age of 13 years. Undernutrition occurs after the age of 14 years, involving 54 per cent of boys at about 18 years of age. Obese boys show a centralized body-fat distribution, in agreement with other obese populations.
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PMID:Nutritional assessment in Duchenne muscular dystrophy. 825 88

The high prevalence of obesity at an early stage of Duchenne muscular dystrophy (DMD) could result not solely from reduced physical activity, but may also involve low resting energy expenditure (REE), abnormal nutrient utilization, or overfeeding. We hypothesized that the dramatic muscle mass loss in DMD should reduce the REE. REE was measured by indirect calorimetry in 13 9-13-y-old DMD boys (5 obese, 8 nonobese) and 9 male age-matched controls. Muscle mass was estimated from 3-d creatinine excretion in urine. Daily energy intake was estimated from 7-d diet records. In the nonobese DMD group (NODMD) the muscle mass was reduced by 71%, and the REE was 13% lower than in controls (47.5 versus 54.6 kcal.h-1, p < 0.05). Postabsorptive respiratory quotients appeared higher in both DMD groups than in the controls; however, the difference was significant only for the NODMD group (0.88 versus 0.83, p < 0.05). Respiratory quotients were not different between the two DMD groups. Diet records were not contributive in revealing a different dietary behavior between groups. Our results suggest that: 1) muscle mass loss in DMD is associated with a low REE, 2) low postabsorptive fat utilization might occur at an early stage of the disease, and 3) obesity is not associated with an increase in fat utilization in DMD. This study warrants further research to test low REE and low fat utilization as risk factors in developing obesity in DMD.
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PMID:Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. 879 42

Many anticipate that application of findings in molecular genetics will help to achieve greater precision in defining high-risk populations that may benefit from chemopreventive interventions. We must recognize, however, that genetic susceptibility, environmental factors, and complex gene-environment interactions are all likely to be risk determinants for most cancers. Cohort studies of twins and cancer indicate that having "identical" genes is generally not a very accurate predictor of cancer incidence. Data from twin studies support the suggestion that environmental factors such as tobacco use significantly influence cancer risk. The complexities of the genetic contribution to disease risk are exemplified by the development of Duchenne muscular dystrophy in only one of monozygotic twin girls, hypothesized to be the result of X chromosome inactivation, with the distribution patterns of the X chromosome being skewed to the female X in the manifesting twin and to the male X in the normal twin. Evidence from transgenic and genetic-environmental studies in animals support the possibility of genetic-environmental interactions. Calorie restriction modifies tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D diet increases prepolyp hyperplasia formation in Apc-mutated mice; and calorie restriction early in life influences development of obesity in the genetically obese Zucker rat (fafa). Such environmental modulation of gene expression suggests that chemoprevention has the potential to reduce risk for both environmentally and genetically determined cancers. In view of the growing research efforts in chemoprevention, the NCI has developed a Prevention Trials Decision Network (PTDN) to formalize the evaluation and approval process for large-scale chemoprevention trials. The PTDN addresses large trial prioritization and the associated issues of minority recruitment and retention; identification and validation of biomarkers as intermediate endpoints for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDN's decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scale testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power.
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PMID:Cancer risk factors for selecting cohorts for large-scale chemoprevention trials. 902 95

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy, denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.
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PMID:[Clinical relevance of myosin isoforms in the diaphragm]. 1093 18

Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5mg/kg/dose). This total dose is twice as high as the daily low dosage prednisone regimen (0.75 mg/kg/day). Twenty boys (8.0+/-1.2 years) were treated. Historical control groups included 18 untreated boys (6.1+/-1.6 years) and four boys (7.3+/-0.6 years) treated with daily prednisone. Strength (using a hand-held manometer and grip meter) and timed functional testing were measured. There was an improvement in upper extremity strength for 95% of boys (n=20) at 6 months using quantitative strength testing. Improvement in lower extremity strength occurred in all boys with antigravity quadriceps strength (17/17). The improvement (P=0.001 for proximal upper extremities; P=0.002 for grip; and P<0.0001 for proximal lower extremities) was significant compared to untreated boys. Sixteen boys were treated continuously for more than 12 months (22+/-1.5 months). Of these, 15 remained significantly stronger than prior to treatment and 8/16 showed additional gains in strength after six months of treatment. Six boys were on the weekly prednisolone 2 years or longer without interruption. All six had upper and lower extremity strength at follow-up that was as good or better than at baseline. Functional testing improved in boys less than 8 years without contractures. Three boys without antigravity quadriceps strength at the start of treatment lost the ability to walk unassisted within 6 months. Eight other boys lost the ability to ambulate unassisted between 12 and 24 months of treatment. In each, progressive contractures developed. Linear growth was maintained in all boys on weekly treatment. Obesity rates did not differ from untreated boys. Twice weekly prednisone improved strength over 6-12 months in the majority of boys, but did not slow contracture development. Sustained benefit beyond 12 months is possible with fewer side effects compared to daily prednisone.
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PMID:High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. 1246 46

An open controlled trial of 0.75 mg/Kg/day prednisolone was conducted at a stage when the patients had started falling several times in a day and stopped on their attaining a chair bound stage, thus minimising the total period of steroid therapy. Out of the 67 DMD patients enrolled in this study, 44 were put on prednisolone therapy and 23 served as controls. All patients were followed-up at two-monthly intervals for two years and thereafter they continued to take their respective medications till their chair-bound stage; then the drug was gradually withdrawn. In the treatment group 24 patients could not continue the trial because of adverse effects - 14 due to excessive obesity, 3 due to measles, 4 due to pulmonary tuberculosis, 2 due to recurrent throat and chest infection and 1 due to an unexplained high leukocyte count. Of the remaining 20 patients in the treatment group, steroid therapy was stopped in 5 patients as there was no improvement in power in six months. Fifteen patients in the treatment group and 19 patients in the control group could be followed regularly for 2 years and then up to chair-bound stage. Outcome parameters included fall frequency, peak expiratory flow rate, limb muscle power, ability to lift weights, time taken in getting up from squatting position, walking 9 metres and climbing 13 stairs. Maximum improvement was noted between 2 and 4 months while mild improvement in some parameters continued up to six months. All parameters remained stabilised for 1 year or so, after which there was slight deterioration. Deterioration at 2 years was, however, less than the natural course of events noted in control patients. Prednisolone treated patients and controls became chair bound at the mean age of 169 +/- 9 and 132 +/- 8 months respectively. Till the ideal stage of the disease and the type or dosage of starting steroid therapy is defined by specially designed studies, 0.75 mg/Kg/day prednisolone therapy may be started in DMD patients at the stage of frequent falls ( > 10 / day) on walking or increased get-up time ( > 10 s) as observed while testing Gowers' sign; this improves muscle power and timing of motor performance within 2-4 months of onset of therapy in about 75% of those who tolerate this therapy, with a possible gain of approximately 3 years in terms of independent walking.
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PMID:Prednisolone in Duchenne muscular dystrophy with imminent loss of ambulation. 1678 14

Mechanical ventilation has become an important treatment option in chronic ventilatory failure. There are different diseases which lead to ventilatory failure and to home mechanical ventilation (HMV). A primary loss of in- and expiratory muscle strength is the reason for respiratory deterioration in neuromuscular disease. In most of these diseases ventilatory failure develops because of the progressive character of muscular damage. Initially, ventilatory failure can be found during night-time. In the case of hypercapnia at daytime, life expectancy is strongly reduced, especially in amyotrophic lateral sclerosis and Duchenne muscular dystrophy. HMV leads to a prolongation of life and to an increase in quality of life, if bulbar involvement is not severe. Impressive clinical improvements under HMV have been found in restrictive disorders of the rib cage like kyphoscoliosis or posttuberculosis sequelae, with an increase of quality of life, walking distance and a decrease in pulmonary hypertension. Only few data are published about long-term results of HMV in Obesity Hypoventilation. In terms of retrospective analyses of clinical data HMV seems to improve survival in this population. Some patients only need CPAP treatment, but most patients have to be treated with ventilatory support. The application of HMV in patients with chronic ventilatory failure due to chronic obstructive pulmonary disease (COPD) is growing, but there are controversial results in randomised clinical trials. Analysis of these data suggest better results of HMV in patients with severe hypercapnia, with the application of higher effective ventilatory pressure and a ventilator mode with a significant reduction in the work of breathing. Under such conditions HMV leads to a reduction of hypercapnia, an improvement in sleep quality, walking distance and quality of life, but until now there is no evidence in reduction of mortality in COPD.
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PMID:[Mechanical ventilation in chronic ventilatory insufficiency]. 1762 Feb 31

Duchenne muscular dystrophy yields pervasive and progressive muscle mass loss. In the current measures relating to the monitoring of disease progression the following are relevant (i): the type of scale used, (ii) the clinical significance of the attribute being measured and (iii) the mathematical properties of the data provided. The high prevalence of obesity at an early stage of this pathology could result not only from reduced physical activity, but also from low resting energy expenditure, abnormal nutrient utilization or overfeeding. This muscle weakness may be attenuated by regular low-intensity exercise. However, there is a critical lack of data to support appropriate exercise prescription. Because inappropriate activity may exacerbate the dystrophic process, a systematic analysis of muscle function to determine potential exercise load thresholds to avoid injury in dystrophic mice and dogs, and then in humans is recommended.
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PMID:Duchenne muscle activity evaluation and muscle function preservation: is it possible a prophylactic strategy? 1803 91


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