Effect of inspired O2 on cardiopulmonary and metabolic responses to exercise in man.
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Biomedical subjects
Publications and source records attributed to R H Edwards.
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Almost all methods of measuring residual volume of urine in the bladder of patients undergoing urologic assessment are biased to an unknown extent. The authors describe the application of an unbiased stereologic technique for estimating the volume of bladder urine known as the Cavalieri method. The method requires imaging of a series of systematic (ie, equally spaced) parallel sections through the bladder. Such data can be conveniently obtained with magnetic resonance (MR) imaging. If sampling begins at a position randomly chosen within the distance corresponding to the section interval, bladder volume is estimated without bias as the sum of the areas of the bladder sections on the images multiplied by the section interval. Computer-aided point-counting techniques represent an efficient means of obtaining the required section area estimates. Optimum sectioning and point counting densities for estimating bladder volume were established by analyzing detailed data sets obtained in five volunteers. It was shown that if an average of only 20 points were counted in each of only five systematic sections through the bladder, the volume of bladder urine was estimated with a coefficient of error of about 5%. By studying these five volunteers and an additional 13 with MR imaging and the Cavalieri method, the authors showed that the difference between the volume of urine in the bladder before and after micturition is unbiased (ie, shows no systematic difference) with respect to the volume of urine voided by the subjects.
Muscle breakdown and repair were measured by metabolic balance techniques in a patient with polymyositis who was being treated with prednisolone and azathioprine. Changes in body muscle mass that had been estimated from nitrogen and phosphorus balances correlated with antropometric assessments of thigh muscle mass and quadriceps strength. Decline in muscle strength was associated with a net rate of muscle breakdown of 148 g/day. Recovery was associated with a net rate of muscle repair of up to 100 g/day. Early reduction in corticosteroid treatment appeared to enhance the rate of repair. Changes in the isometric contraction force of the quadriceps muscle (but not in clinical symptoms, plasma creatine kinase [CK] or erythrocyte sedimentation rate [ESR] were found to reliably indicate whether the muscle was in a state of breakdown or repair. Treatment of the individual patient may be quantitatively monitored by metabolic balance studies or, more simply, by measurement of muscle strength.
Over 1,000 needle biopsies have been carried out at University College Hospital in London. Needle biopsy has been used by us for histochemical and electron microscopic examination of muscle during the diagnosis and treatment of neuropathic and myopathic disorders, for the diagnosis of mitochondrial myopathies, to study the course of recovery in polymyositis, and for investigations into muscle changes in systemic lupus erythematosus (SLE) and other autoimmune conditions. We have developed a microprocessor system for the measurement of muscle fiber areas, and needle biopsy specimens provide suitable material for such measurements. We have also used needle biopsy specimens for studies of protein turnover using stable isotopes and for trace metal and electrolyte analyses. Needle biopsy is safe and rapid. As the patient usually experiences only minimal discomfort and there is no permanent scar, repeat biopsies are well tolerated allowing follow-up studies after treatment.
31P nuclear magnetic resonance (NMR) was used to investigate the resting energy metabolism of the calf muscle in boys with Duchenne's muscular dystrophy. Reductions in the phosphocreatine/adenosine triphosphate (PCr/ATP) and the PCr/Pi ratios were found, but ATP as a fraction of the total mobile phosphorus signal was not reduced, and intracellular pH was normal in the Duchenne muscle. Attempts at quantitation of the NMR signal suggested that the reduced total phosphorus signal seen in the Duchenne muscle was a result of muscle fiber loss only and that the muscle fiber ATP concentration was probably normal in the diseased tissue. An exercise study in one 7-year-old boy with Duchenne's dystrophy demonstrated that the muscle had a normal ability to break down and resynthesize phosphocreatine. Presented here are the first reported trials of the effects of two putative therapeutic agents on energy metabolism determined by NMR in Duchenne's muscular dystrophy.
Fourteen patients with liver cirrhosis of differing severity participated in a one-dimensional chemical shift imaging 31P MRS study of the liver. Patients were divided into two groups according to the severity of their liver disease using Child's classification and the aminopyrine breath test (AB test). Seven normal volunteers without liver disease acted as controls. The phosphomonester (PME) peak in normal subjects was 4.77% (95% confidence interval, CI: 4.11-5.42) of total phosphorus. The PME peak was significantly elevated in both mild cirrhosis [5.80% (95% CI: 5.46-6.14), p = 0.0051, vs normal subjects] and severe cirrhosis [9.64% (95% CI: 8.71-10.57), p = 0.0002, vs normal subjects and p = 0.001, vs mild cirrhosis]. There was a significant negative linear correlation (r = 0.88, p < 0.01) of PME with the percentage dose of 14CO2 excreted over 2 h in the AB test. pH values in patients with mild cirrhosis [7.45 (95% CI: 7.35-7.55)] but not severe cirrhosis [7.36 (95% CI: 7.25-7.47)] were significantly elevated (p = 0.04) compared to normal subjects [7.29 (95% CI: 7.17-7.41)]. Comparison of the peak area of PME at TR = 0.5 s against that using TR = 5.0 s in cirrhotic liver suggested no reduction in T1 of phosphorus metabolites in cirrhosis. A relationship between the severity of liver cirrhosis and a relative increase in PME was demonstrated and this was not due to a reduction of T1. This study highlights the clinical potential of 31P MRS as a non-invasive means of assessing the severity of liver cirrhosis.
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We have examined the anatomy and fibre type composition of the human adductor pollicis in muscles taken post mortem. Histochemical staining of muscle fibres showed that type I fibres predominated in all cases with a mean occurrence of 80%. This composition is similar to that of the soleus muscle and unlike that of the quadriceps which has approximately equal proportions of the two fibre types. Comparing the contractile characteristics, however, the adductor pollicis has similar properties to the quadriceps and both are quite distinct from those of the slowly contracting soleus muscle. The lack of correlation between fibre composition, as revealed by histochemical staining, and contractile properties in these muscles must mean that fibres of the same type from different muscles do not necessarily have the same contractile speed. The results also suggest that the type I fibres of the human adductor pollicis are faster than those of both the soleus and quadriceps muscles.
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Nerve growth factor (NGF) has a crucial role in the development of sensory and sympathetic neurones. However, although it can affect other neural cell types under certain experimental conditions, no biological role has been convincingly demonstrated elsewhere in the nervous system. The 5' end of the mouse NGF gene contains several relatively short exons. The NGF messenger RNA contains two in-frame initiator methionine codons; the second precedes the signal peptide sequence. Studies of the translation of other eukaryotic mRNAs indicate that the first AUG is preferred, suggesting that the signal for secretion might be ambiguous. We have analysed the NGF mRNA species from various cell types, some of which (clonal myoblast and fibroblast cell lines) are known to secrete NGF, to search for different NGF transcripts. One pathway of RNA splicing generates the transcript already described from a submaxillary gland complementary DNA clone. We demonstrate here that there is another splicing pathway, leading to a shorter transcript that lacks the second exon. This short transcript is the major form in most other mouse tissues and in the tissues of several other species, but both transcripts are usually present. In the short transcript, the initiator methionine is immediately upstream from a signal peptide-like sequence whereas in the long transcript the first methionine is 62 amino acids upstream from the signal peptide-like sequences. This may result in a different cellular localization of the NGF or alter the biological activity of the NGF precursor.