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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 505 records · Page 28Linked to original sources

Reversible respiratory muscle weakness in hyperthyroidism.

Breathlessness is a common complaint in patients with hyperthyroidism, and respiratory failure requiring artificial ventilation, although rare, can occur. While a proximal myopathy is frequently recognized, diaphragm muscle function has not hitherto been studied in detail in thyrotoxicosis. The strength of the quadriceps femoris and respiratory muscles was therefore assessed in seven consecutive thyrotoxic patients, on presentation and during medical treatment, when euthyroid. Prior to therapy, reduced quadriceps muscle strength, vital capacity, and global expiratory and inspiratory muscle strength were found. Diaphragmatic weakness was present in one of four patients studied by measuring transdiaphragmatic pressures during maximal sniffs and during bilateral phrenic nerve stimulation at 1 Hz (twitch). After treatment, significant improvement occurred in quadriceps muscle strength, vital capacity, and global respiratory muscle strength. Sniff and twitch transdiaphragmatic pressures also increased significantly. These results indicate that respiratory muscle weakness occurs in hyperthyroidism and that such weakness is reversible with medical treatment. It is important to realize that respiratory muscles may be directly affected when assessing thyrotoxic patients with breathlessness, as severe involvement of the respiratory muscles may cause respiratory failure.

Chronic Disease↗

The measurement of inspiratory muscle strength by sniff esophageal, nasopharyngeal, and mouth pressures.

Sniff esophageal pressure (Pes) is a useful measurement of global inspiratory muscle strength, although it does require passage of an esophageal balloon. We investigated the relationship between nasopharyngeal pressure (Pnp) or pressure within the mouth (Pmo) and Pes during a maximal sniff from FRC without a noseclip. We measured Pes, Pnp, and Pmo simultaneously in 10 normal volunteers, and in 12 patients with inspiratory muscle weakness. In both groups, Pnp and Pmo were slightly less but very close to Pes. In normal volunteers, the mean ratio Pnp/Pes was 0.92 +/- 0.006 (mean +/- SE) and Pmo/Pes was 0.95 +/- 0.006. Regression analysis showed Pes = 4.57 + 1.05 Pnp (r = 0.995, p less than 0.001) and Pes = 0.74 + 1.05 Pmo (r = 0.994, p less than 0.001). Similar relationships between Pnp, Pmo, and Pes were found over a wide range of pressures generated by submaximal sniffs in normal subjects. In patients, the mean ratio Pnp/Pes was 0.90 +/- 0.02 and Pmo/Pes was 0.87 +/- 0.03. Regression analysis showed Pes = 5.12 + 1.0 Pnp (r = 0.949, p less than 0.001) and Pes = 11.2 + 0.882 Pmo (r = 0.936, p less than 0.001). We conclude that Pnp and Pmo predict Pes during a maximal sniff in both normal subjects and in patients with inspiratory muscle weakness. Sniff Pnp and/or Pmo may provide a useful and less invasive method of measuring maximal inspiratory pressures during a sniff.

Adult↗

Maximal relaxation rates of esophageal, nose, and mouth pressures during a sniff reflect inspiratory muscle fatigue.

Maximal relaxation rate (MRR, % pressure fall/10 msec) of the inspiratory muscles is reduced with fatigue. We have investigated whether MRR of esophageal pressure (Pes) generated by voluntary sniffs is decreased by fatigue, and whether sniff nasopharyngeal (Pnp) and mouth (Pmo) MRR reflect these changes. In 10 normal subjects, control MRR of sniff Pes correlated closely to Pnp MRR (r = 0.977, p less than 0.001) and Pmo MRR (r = 0.947, p less than 0.001). To produce inspiratory muscle fatigue, four highly motivated subjects breathed to exhaustion (3 to 6 min) through a high inspiratory resistance. MRR was determined from 10 sniffs for Pes, Pnp, and Pmo before fatigue, and at intervals up to 10 min after fatigue. The subjects showed a mean decrease in sniff Pes MRR of 33% (range, 20 to 42) immediately after fatigue, which returned exponentially to control values within 3 to 4 min. The mean changes in Pes MRR were reflected by similar changes in Pnp MRR, 32% (range, 18 to 43) and Pmo MRR, 33% (range, 21 to 42). Studies were repeated in the four subjects with closely similar results. We conclude that fatigue of the inspiratory muscles reduces MRR of sniff Pes, and that this is reflected in Pnp and Pmo. Sniff Pes, Pnp, and Pmo MRR measurements may provide a useful method for detecting and monitoring fatigue; Pnp and Pmo have the advantage of being less invasive.

Adult↗

Treatment of chemotherapy-induced neutropenia by subcutaneously administered granulocyte colony-stimulating factor with optimization of dose and duration of therapy.

In patients who have not received extensive prior chemotherapy or radiotherapy, it has been previously demonstrated that granulocyte colony-stimulating factor (G-CSF) abrogated the leukopenia following administration of melphalan (25 mg/m2). This study examined the necessity of a prechemotherapy period of G-CSF administration and the effect of varying the timing and duration of postchemotherapy G-CSF. Initially, patients received 0.3, 1.0, 3.0, and 10 micrograms/kg/d subcutaneously on days 1 to 5 and days 10 to 18. Melphalan was given on day 9. In the next portion of the study melphalan was administered on day 1 and G-CSF, 10 micrograms/kg/d, was administered by subcutaneous infusion on five schedules: (1) days 2 to 13; (2) days 8 to 13; (3) days 2 to 18; (4) days 8 to 18; (5) days -9 to -2 and 2 to 13. G-CSF produced a rapid and sustained elevation in neutrophil levels within 24 hours even when started 8 days after melphalan. This treatment was sufficient to abrogate the neutropenia in patients who had received no prior chemotherapy. It was not necessary to continue G-CSF for more than 7 days. G-CSF did not consistently alter the course of the thrombocytopenia that followed this dose of melphalan. G-CSF was well tolerated, although mild bone pain occurred and was reduced with acetaminophen. One of 22 patients developed cellulitis at an infusion site. We conclude that after melphalan chemotherapy, G-CSF may need to be given for only a short period to prevent chemotherapy-induced neutropenia, and that G-CSF induces a rapid rise in neutrophil levels even when started 8 days after melphalan administration.

Adult↗

Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients.

Cancer and Leukemia Group B (CALGB) accrued 1,745 patients with limited (LD) or extensive (ED) small-cell lung cancer (SCCL) to five separate trials between 1972 and 1986. We reviewed these data to evaluate the impact of pretreatment prognostic factors on outcome. In multivariate analysis, female gender was predictive of improved response (LD, P = .01; ED, P = .04) and survival (LD, P = .01; ED, P = .02). A performance status of 0 or 1 was associated with improved response rates in both subsets, but was statistically significant (P = .04) only for overall objective response in LD patients. Performance status was a highly significant predictor of survival in both LD and ED groups (P less than .001). Supraclavicular lymph node involvement, while still LD, had a borderline unfavorable impact on survival (P = .06) compared with a lesser extent of LD involvement. In ED patients, a decrease in survival rates was associated with an increased number of metastatic sites (P = .01). Changes in the patient population were noted with time: the percentage of women increased from 21% to greater than 35%; an increased number of metastatic sites was identified among ED patients; mean performance status improved for both LD and ED subsets. These trends reflect the changing demographics of lung cancer, improved lung cancer staging, and probably lead-time bias. Response rates, overall survival, and long-term (greater than 2-year) survival varied significantly among the five protocols, both before and after multivariate correction for identified prognostic variables. However, the changing character of the study population limits the ability to determine retrospectively how much improvements in therapy contributed to the positive changes in failure-free survival, overall survival, and long-term survival observed in our sequentially studied population.

Antineoplastic Combined Chemotherapy Protocols↗

Human bone microstructure studied by collagenase etching.

Bone samples from the iliac crest of patients with no signs of bone disorder were treated with collagenase to remove the collagen component and so allow detailed observation of the mineral hydroxyapatite. Both polished and unpolished surfaces were studied in the scanning electron microscope and they showed that the mineral component of bone is composed of small rounded units about 10 nm across which are fused together to form larger spheroidal units roughly 100 nm in diameter. In the unpolished surfaces these 100 nm units are seen to aggregate to form columns approximately parallel to their neighbours and with numerous interconnections forming a continuous mineral phase. The polished sections also show the hydroxyapatite as a continuous phase of contiguous spheroids and the holes from which the collagen fibres were removed are clearly revealed. Lamellations in the surface are interpreted as resulting from adjacent layers of collagen fibres having orientations approximately perpendicular to each other.

Bone and Bones↗

Color correspondence in apparent motion.

To maintain figural identity during motion perception, the visual system must match images over space and time. Correct matching requires a metric for identifying "corresponding" images, those representing the same physical object. To test whether matching is based on achromatic (black/white) polarity and chromatic (red/green) color, observers viewed an ambiguous motion display and judged the path of apparent motion. Matching preserved black/white identity regardless of whether frames were viewed binocularly or dichoptically. Red/green identity was also preserved, but coherence of motion depended in part on the number of frames in the motion sequence and on the background luminance. These results suggest that correspondence is computed by a weighted metric containing terms for image features coded early in visual processing.

Color Perception↗

Diaphragm strength in the shrinking lung syndrome of systemic lupus erythematosus.

The cause of the reduced lung volume in the 'shrinking lung' syndrome of systemic lupus erythematosus (SLE) was investigated in 12 patients with the condition. Nine patients described persistent episodes of pleuritic chest pain. Narrow section (3 mm) computed tomography of the thorax revealed no interstitial fibrosis or significant pleural disease. Assessment of diaphragmatic function using manoeuvres more reliable than the maximal occluded efforts previously used alone to assess respiratory muscle strength, showed that diaphragm strength was unequivocally normal in nine of 12 patients. In three, maximum transdiaphragmatic pressure was moderately reduced, but phrenic nerve stimulation demonstrated that this was due to incomplete activation of the diaphragm during a maximal voluntary effort, rather than to a primary abnormality of the diaphragm. Results of maximum lung recoil pressures and dynamic compliance, and analysis of the 12-s maximum voluntary ventilation, suggested a restriction in chest-wall expansion, although it was not possible to identify the underlying cause of this on the basis of our results. We conclude that the 'shrinking lung' syndrome of SLE is not explained by a primary abnormality of the diaphragm.

Adolescent↗

The effect of posture and abdominal binding on respiratory pressures.

We examined the effect of posture on the generation of respiratory pressures in 6 highly trained subjects. Transdiaphragmatic pressure was measured at FRC during bilateral percutaneous phrenic nerve stimulation (twitch Pdi) and maximal sniffs (sniff Pdi), with the abdomen bound and unbound. Maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures were measured with the abdomen unbound. Three postures were examined: seated (Se), semi-supine (30s), and supine (Su). Changes of posture did not significantly alter twitch Pdi. By contrast, sniff Pdi and static mouth pressures were significantly reduced in the Su posture. Abdominal binding significantly increased twitch Pdi only. We conclude that voluntary respiratory manoeuvres requiring activation, recruitment and coordination of different muscle groups are performed better in the Se position. We suggest that posture be standardised for serial comparative measurements of voluntary respiratory pressures in a given subject.

Abdomen↗

Infections in pediatric orthotopic heart transplant recipients.

The infectious complications of 31 orthotopic heart transplants in 27 patients performed between 1982 and 1987 were reviewed. Fifteen patients (56%) are alive 704 to 1829 days posttransplantation. Five of the 27 patients died within the first week posttransplantation of noninfectious causes. Infection occurred in 17 of the remaining 22 patients and was the major cause of death in 3 of the 12 fatalities. There were 10 proved and 4 probable bacterial infections. Three of the 10 proved bacterial infections were cases of sepsis with focal complications (two Pseudomonas aeruginosa, one Serratia marcescens) resulting in 2 deaths. The cases of sepsis occurred within 12 days of transplantation. There were 11 viral infections. Cytomegalovirus accounted for 7 of these including 1 fatal and 2 nonfatal episodes of disseminated disease. The mean time of onset of cytomegalovirus infection was 33 days. Two cases of fungal disease were identified at autopsy. One additional patient who received intense immunosuppression because of chronic rejection developed Pneumocystis carinii pneumonia. The most frequent site of infection was the lung with early pneumonias caused by Gram-negative bacteria and later episodes by viral (cytomegalovirus or respiratory syncytial virus) agents.

Adolescent↗

Respiratory muscle weakness and fatigue.

Respiratory muscle weakness can result from a variety of neuromuscular disorders, and it is now possible to identify different patterns of weakness and quantify the extent of this weakness using reliable, sensitive tests of respiratory muscle strength. However the quantification of respiratory muscle 'fatigue' has proved more difficult, and it is now recognized that there is unlikely to be one single index of fatigue, rather a whole sequence of changes that occur in response to loading. It is likely that in practice, a close interplay between respiratory pump capacity, demands on the pump and more especially, adaptive changes in respiratory drive, protect the respiratory muscles from overt peripheral contractile failure, and that the fall in tension following prolonged muscular activity involves many different closely inter-related processes. Investigation of these processes is likely to be more rewarding than attempts to develop a single 'test of fatigue', and may lead to an improved understanding of the role of respiratory muscle dysfunction in ventilatory failure.

Fatigue↗

Mortality from unintentional injuries in California, 1985.

In 1985 unintentional injuries were the fourth leading cause of death among California residents, causing 10,380 deaths. They were the leading cause of potential life lost, accounting for 278,109 years lost. This was more than twice the number of years lost due to heart disease and 1 1/2 times the number lost due to cancer. Motor vehicle traffic accidents were the leading cause of unintentional injury deaths, accounting for half (5,158) the deaths. The next two leading causes were poisoning (especially for men aged 25 to 44 years) and falls (especially among persons aged 75 and older). Drowning was second to motor vehicle accidents as a cause of death in children aged 1 to 14 years. California's age-adjusted injury mortality rates in 1985 were lower in coastal and urban counties than in inland and rural counties, and these rates were generally lower in counties having organized systems of trauma care.

Accidents↗

The effect of aminophylline on respiratory and limb muscle contractility in man.

The effect of oral aminophylline on respiratory muscle and quadriceps femoris strength was compared with placebo in five normal subjects. A double-blind randomized cross-over protocol, spanning 2-3 wks, was followed. Aminophylline was taken before both placebo and active drug periods to establish correct dosage, to allow tolerance to side-effects to develop, and to keep the two limbs of the study identical and double-blind. Maximal static inspiratory and expiratory mouth pressures at residual volume and total lung capacity, respectively, maximal sniff transdiaphragmatic pressure, maximal voluntary quadriceps femoris contraction force and theophylline levels were measured during placebo and active drug periods. For the group, there were no significant differences between respiratory or quadriceps muscle strength on aminophylline and on placebo although there was a tendency for greater values on aminophylline. Mean theophylline level was 14.6 mg.l-1 (range 8.4-25.0 mg.l-1). We conclude that aminophylline produces no enhancement of skeletal muscle strength, at therapeutic dosage in normal subjects.

Adult↗

Respiratory muscle rest.

The respiratory muscles have great reserves, and under normal circumstances, in a fit person, it is probably impossible to fatigue them by activity. However, respiratory muscle fatigue can be induced experimentally, and with the stress of pulmonary disability, or with impairment of muscle function due to neuromuscular disease or skeletal deformity. Respiratory muscle fatigue contributes to respiratory failure and clinical deterioration. Resting the respiratory muscles can allow time for recovery but requires complete or partial artificial ventilation. Whilst positive pressure ventilation has been carried out for many years in Intensive Care Units, this technique is difficult in the long-term. Recently there has been renewed interest in non-invasive ventilatory support. Nocturnal ventilation in an iron lung can cause long-term improvement in acute and chronic respiratory failure of patients with neuromuscular or skeletal abnormalities. Such patients may be maintained with devices at home, such as a pneumosuit, a cuirass, or positive pressure ventilation via the nose. In patients with chronic pulmonary disease respiratory muscle rest may be helpful during acute exacerbations. However, the value of rest in chronic respiratory failure of end-stage pulmonary patients is as yet unproven.

Humans↗

Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein.

HIV-1 encodes a potent trans-activator protein, tat, which is essential for viral gene expression. To study tat domains that function in trans-activation, we chemically synthesized the 86 amino acid tat protein (tat-86) and tat mutant peptides. Remarkably, tat-86 is rapidly taken up by cells, and produces a massive and specific stimulation of HIV-LTR-driven RNA synthesis. Mutant peptides of 21 to 41 amino acids exhibit significant activity. Only two regions are essential for trans-activation; we suggest that one represents an activation region and the other, a nucleic acid binding or nuclear targeting region. Amino acid substitutions within these regions greatly reduce trans-activation, demonstrating the functional significance of these domains. The N-terminal 37 amino acids and exon 2 are not essential. Thus, tat is similar to regulatory proteins of Ad E1A and BPV1 E5 oncogenes, requiring only small domains for autonomous function.

Amino Acid Sequence↗