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D R Marsh

Publications and source records attributed to D R Marsh.

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Strength and aerobic training attenuate muscle wasting and improve resistance to the development of disability with aging.

By the age of 50 yrs old, humans become aware that they are losing muscle strength (mass) and endurance (mitochondria). A frequent symptom of neuromuscular disorders is muscle weakness (Walton, 1988). We define the aging-associated muscle wasting as a progressive neuromuscular syndrome that will lower the quality of life in the elderly by (1) decreasing the ability to lift loads (progressing to difficulty arising from a chair), and (2) decreasing endurance (leading to an inability to perform the activities of daily living, which increases health care costs). Campion (1994) states that the most successful outcome would be for the very elderly to take control of the last stage of their life and make it worth living. To obtain this goal, prevention of muscle wasting is an absolute requirement. Muscle mass and motor unit number, activation, and synchronization are highly related to strength; both decrease with aging (Rodgers and Evans, 1993). Resistance-training is the best way to increase muscle mass, neural coordination, and strength. Mitochondrial concentration is highly related to endurance capacity in young and old (Holloszy and Coyle, 1984). Both muscle contractile and mitochondrial protein decrease with aging in sedentary humans (reviewed by Rodgers and Evans, 1993). Endurance training, which is the best exercise to increase/maintain mitochondrial concentration with aging, has generally resulted in relatively small functional benefits to nursing home patients (Fiatarone et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

No effect of aging on skeletal muscle insulin-like growth factor mRNAs.

This study examined the hypothesis that during aging insulin-like growth factor (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the gastrocnemius muscle of growing animals (3 mo) would be downregulated in a coordinated manner with muscle size during aging-associated atrophy. As indicated by muscle wet weight and total protein content, the gastrocnemius muscle was growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not have an effect on IGFBP-5 mRNA concentration. We conclude that the aging-associated atrophy of skeletal muscle is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.

Aging

Quality of data in the Manchester orthopaedic database.

OBJECTIVE: To determine the completeness and accuracy of data in a computerised clinical information system (Manchester orthopaedic database) in comparison with the data available through the Hospital Activity Analysis. DESIGN: Retrospective review of case notes, computer data, and Hospital Activity Analysis data. SETTING: Orthopaedic unit in a district general hospital in Manchester. SUBJECTS: 200 random patient records distributed through the period of use of the computer system (1 October 1988 to 31 March 1990) and 121 records for random admissions between 1 April 1989 and 31 March 1990, 71 of which were included in the previous sample. MAIN OUTCOME MEASURES: Conformity of the computer record key words and Hospital Activity Analysis codes to an ideal key word record and ideal code record drawn up by one investigator from the clinical notes; overall quality (completeness times accuracy). RESULTS: Overall completeness of the data in the orthopaedic database was 62% and the accuracy was 96%. Completeness improved after feedback to doctors on the use of key words in regular audit meetings. Completeness was higher in inpatient than outpatient records (69.9% v 53.7%, p less than 0.001) and when a new key word was required compared with missing and incorrect key words (both p less than 0.001). Completeness was lower when the key word was required of a senior registrar (p less than 0.05). Accuracy was not significantly different. The completeness of Hospital Activity Analysis data was 90.5% and accuracy 69.5%. Thus the overall data quality was similar in both systems. CONCLUSIONS: Even in a system designed for simple and efficient data capture, compliance by users was poor. Accuracy was high, suggesting that users understood the principles of data entry. Completeness of data capture can be improved by providing feedback to users on use of the system and performance. Improvements in future versions of the software should improve performance.

Abstracting and Indexing

Effect of hindlimb unweighting on anaerobic metabolism in rat skeletal muscle.

Female Sprague-Dawley rats (250 g) were hindlimb suspended for 14 days, and the effects of hindlimb unweighting (HU) on skeletal muscle anaerobic metabolism were investigated and compared with nonsuspended controls (C). Soleus (SOL), plantaris (PL), and red and white portions of the gastrocnemius (RG, WG) were sampled from resting and stimulated limbs. Muscle atrophy after HU was 46% in SOL, 22% in PL, and 24% in the gastrocnemius compared with nonsuspended C animals. The muscles innervated by the sciatic nerve were stimulated to contract with an occluded circulation for 60 s with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1.0 Hz. Peak tension development by the gastrocnemius-PL-SOL muscle group was similar in HU and C animals (13.0 +/- 1.2, 12.2 +/- 0.8 N/g wet muscle). Occlusion of the circulation before stimulation created a predominantly anaerobic environment, and in situ glycogenolysis and glycolysis were estimated from accumulations of glycolytic intermediates. Total glycogenolysis and glycolysis were higher in the RG muscle of HU animals (74.6 +/- 3.3, 58.1 +/- 1.1) relative to C (57.1 +/- 4.6, 46.1 +/- 2.9 mumol glucosyl units/g dry muscle). Consequently, total anaerobic ATP production was also increased (HU, 251.3 +/- 1.1; C, 204.6 +/- 8.9 mumol ATP/g dry muscle). Total ATP production, glycogenolysis, and glycolysis were unaffected by HU in SOL, PL, and WG muscles. The enhanced glycolytic activity in RG after HU may be attributed to a shift in the metabolic profile from oxidative to glycolytic in the fast oxidative-glycolytic fiber population.

Adenosine Triphosphate

Glycolysis is predominant source of myocardial ATP production immediately after birth.

Glycolytic flux, as well as glucose, fatty acid, and lactate oxidation, was determined in isolated working hearts obtained from 1- and 7-day-old rabbits. One-day-old rabbit hearts were perfused via the inferior cava against a constant aortic and pulmonary arterial afterload, whereas hearts from 7-day-old rabbits were perfused via the left atria against a constant aortic afterload. Hearts were perfused with buffer containing 100 microU/ml insulin and either 1) 11 mM [U-14C/2-3H]glucose, 0.4 mM palmitate, 2 mM lactate; 2) 11 mM glucose, 0.4 mM [1-14C]palmitate, 2 mM lactate; or 3) 11 mM glucose, 0.4 mM palmitate, 2 mM [U-14C]lactate. Glycolytic rates (measured as 3H2O production) were high in 1-day-old hearts but decreased by 7 days (from 2,730 +/- 280 to 580 +/- 80 nmol.min-1.g dry wt-1). Rates of glucose oxidation (measured as 14CO2 production) were lower in both 1- and 7-day-old hearts (59 +/- 4.4 and 23 +/- 2 nmol.min-1.g dry wt-1). Palmitate oxidation rates were low in 1-day-old hearts but dramatically increased by 7 days (22.6 +/- 5.6 and 305 +/- 33 nmol oxidized.min-1.g dry wt-1, respectively). In contrast, lactate was readily oxidized by both 1- and 7-day-old hearts (169 +/- 14 and 456 +/- 52 nmol.min-1.g dry wt-1, respectively). In 1-day-old hearts, 44% of steady-state ATP production from exogenous sources were derived from glycolysis, whereas 18, 13, and 25% were derived from glucose, palmitate, and lactate oxidation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Anaerobic energy provision in aged skeletal muscle during tetanic stimulation.

The effect of age on skeletal muscle anaerobic energy metabolism was investigated in adult (11 mo) and aged (25 mo) Fischer 344 rats. Hindlimb skeletal muscles innervated by the sciatic nerve were stimulated to contract with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1 Hz for 60 s, with an occluded circulation. Soleus, plantaris, and red and white gastrocnemius (WG) were sampled from control and stimulated limbs. All muscle masses were reduced with age (9-13%). Peak isometric tensions, normalized per gram of wet muscle, were lower throughout the stimulation in the aged animals (28%). The potential for anaerobic ATP provision was unaltered with age in all muscles, because resting high-energy phosphates and glycogen contents were similar to adult values. Anaerobic ATP provision during stimulation was unaltered by aging in soleus, plantaris, and red gastrocnemius muscles. In the WG, containing mainly fast glycolytic (FG) fibers, ATP and phosphocreatine contents were depleted less in aged muscle. In situ glycogenolysis and glycolysis were 90.0 +/- 4.8 and 69.3 +/- 2.6 mumol/g dry muscle (dm) in adult WG and reduced to 62.3 +/- 6.9 and 51.5 +/- 5.5 mumol/g dm, respectively, in aged WG. Consequently, total anaerobic ATP provision was lower in aged WG (224.5 +/- 20.9 mumol/g dm) vs. adult (292.6 +/- 7.6 mumol/g dm) WG muscle. In summary, the decreased tetanic tension production in aged animals was associated with a decreased anaerobic energy production in FG fibers. Reduced high-energy phosphate use and a greater energy charge potential after stimulation suggested that the energy demand was reduced in aged FG fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Glycogen content has no effect on skeletal muscle glycogenolysis during short-term tetanic stimulation.

The effect of skeletal muscle glycogen content on in situ glycogenolysis during short-term tetanic electrical stimulation was examined. Rats were randomly assigned to one of three conditions: normal (N, stimulated only), supercompensated (S, stimulated 21 h after a 3-h swim), and fasted (F, stimulated after a 20-h fast). Before stimulation, glycogen contents in the white (WG) and red gastrocnemius (RG) and soleus (SOL) muscles were increased by 13-25% in S and decreased by 15-27% in F compared with N. Hindlimb blood flow was occluded 60 s before stimulation to produce a predominantly anaerobic environment. Muscles were stimulated with trains of supramaximal impulses (100 ms at 80 Hz) at a rate of 1 Hz for 60 s. Muscle glycogenolysis was measured from the decrease in glycogen content and estimated from the accumulation of glycolytic intermediates in the closed system. The resting glycogen content had no effect on measured or estimated glycogenolysis in all muscles studied. Average glycogenolysis in the WG, RG, and SOL muscles was 98.4 +/- 4.3, 60.9 +/- 4.0, and 11.2 +/- 3.6 mumol glucosyl U/g dry muscle, respectively. Hindlimb tension production was similar across conditions. The results suggest that in vivo glycogen phosphorylase activity in skeletal muscle is not regulated by the content of its substrate glycogen (range 80-165 mumol/g) during short-term tetanic stimulation in an anaerobic environment.

Adenosine Triphosphate

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

Adrenal Cortex Hormones

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Asthma

Use of a wheel aesthesiometer for testing sensibility in the hand. Results in patients with carpal tunnel syndrome.

Tests of spatial discrimination were performed on the hands of patients with carpal tunnel syndrome, before and after surgical decompression. Impairment of sensibility and its recovery after treatment were better demonstrated by a new instrument, the wheel aesthesiometer, than by the moving two-point discrimination test. The psychophysics of the new test and the nature of the sensory impairment in carpal tunnel syndrome are discussed.

Carpal Tunnel Syndrome

Midazolam in conservative dentistry. A cross-over trial.

In a double-blind trial, 50 patients were randomly allocated to receive up to 0.29 mg/kg diazepam (Valium 5 mg/ml) or 0.14 mg/kg of midazolam (midazolam hydrochloride 5 mg/ml) intravenously at a first session of conservative dentistry, the alternative being administered at the second session. Good operating conditions were reported under each sedative and no important physiological differences were observed. Most patients failed to return to 'street fitness' 30 minutes after either session of treatment. Previous reports of reduced incidence of venous thrombophlebitis with midazolam were not convincingly confirmed in this trial, but data quality was poor. For about half the patients, the amnesic effect was stronger following midazolam.

Adolescent