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Biomedical subjects

C C Evans

Publications and source records attributed to C C Evans.

At least 19 recordsLinked to original sources

Altered hemodynamics in transgenic mice harboring mutant tropomyosin linked to hypertrophic cardiomyopathy.

We used transgenic (TG) mice overexpressing mutant alpha-tropomyosin [alpha-Tm(Asp175Asn)], linked to familial hypertrophic cardiomyopathy (FHC), to test the hypothesis that this mutation impairs cardiac function by altering the sensitivity of myofilaments to Ca(2+). Left ventricular (LV) pressure was measured in anesthetized nontransgenic (NTG) and TG mice. In control conditions, LV relaxation was 6,970 +/- 297 mmHg/s in NTG and 5,624 +/- 392 mmHg/s in TG mice (P < 0.05). During beta-adrenergic stimulation, the rate of relaxation increased to 8,411 +/- 323 mmHg/s in NTG and to 6,080 +/- 413 mmHg/s in TG mice (P < 0.05). We measured the pCa-force relationship (pCa = -log [Ca(2+)]) in skinned fiber bundles from LV papillary muscles of NTG and TG hearts. In control conditions, the Ca(2+) concentration producing 50% maximal force (pCa(50)) was 5.77 +/- 0.02 in NTG and 5.84 +/- 0.01 in TG myofilament bundles (P < 0.05). After protein kinase A-dependent phosphorylation, the pCa(50) was 5.71 +/- 0.01 in NTG and 5.77 +/- 0. 02 in TG myofilament bundles (P < 0.05). Our results indicate that mutant alpha-Tm(Asp175Asn) increases myofilament Ca(2+)-sensitivity, which results in decreased relaxation rate and blunted response to beta-adrenergic stimulation.

Actin Cytoskeleton↗

Correlation between myofilament response to Ca2+ and altered dynamics of contraction and relaxation in transgenic cardiac cells that express beta-tropomyosin.

We compared the dynamics of the contraction and relaxation of single myocytes isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-beta-Tm) mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared with NTG controls, TG-beta-Tm myocytes showed significantly reduced maximal rates of contraction and relaxation with no change in the extent of shortening. This result indicated that the depression in contraction dynamics determined in TG-beta-Tm isolated hearts is intrinsic to the cells. To further investigate the effect of Tm isoform switching on myofilament activity and regulation, we measured myofilament force and ATPase rate as functions of pCa (-log of [Ca2+]). Compared with controls, force generated by myofilaments from TG-beta-Tm hearts and myofibrillar ATPase activity were both more sensitive to Ca2+. However, the shift in pCa50 (half-maximally activating pCa) caused by changing sarcomere length from 1.8 to 2.4 microm was not significantly different between NTG and TG-beta-Tm fiber preparations. To test directly whether isoform switching affected the economy of contraction, force versus ATPase rate relationships were measured in detergent-extracted fiber bundles. In both NTG and TG-beta-Tm preparations, force and ATPase rate were linear and identically correlated, which indicated that crossbridge turnover was unaffected by Tm isoform switching. However, detergent extracted fibers from TG-beta-Tm demonstrated significantly less maximum tension and ATPase activity than NTG controls. Our results provide the first evidence that the Tm isoform population modulates the dynamics of contraction and relaxation of single myocytes by a mechanism that does not alter the rate-limiting step of crossbridge detachment. Our results also indicate that differences in sarcomere-length dependence of activation between cardiac and skeletal muscle are not likely due to differences in the isoform population of Tm.

Actin Cytoskeleton↗

Epithelioid haemangioendothelioma.

Epithelioid haemangioendothelioma is a rare pulmonary neoplasm with less than 40 cases described world wide. We describe the only case to have presented with hypertrophic pulmonary osteoarthropathy who has been treated with azathioprine and has remained alive and well with no deterioration in pulmonary function since being diagnosed 16 years ago. The progression of the chest radiograph and spiral CT appearances of this rare neoplasm are described, and current views regarding the cellular origin of the neoplasm, its cytological appearance, clinical presentation and prognosis are discussed.

Adult↗

Sternocostoclavicular hyperostosis presenting with thoracic sinus formation.

Sternocostoclavicular hyperostosis (SCCH) is a condition which is well described in the Japanese literature but is rare in Western Europe. It is characterised by pain and swelling in the upper anterior part of the chest, which tends to be progressive. A patient is described with bilateral chronic discharging sinuses over the anterior ends of the clavicles in whom the diagnosis appeared to be one of SCCH.

Aged↗

Essayists, essays, and hosts: Daniel Hale Williams Medical Reading Club.

The 66-year-old Daniel Hale Williams Medical Reading Club is an independent reading club comprised of 65 physicians in the metropolitan Washington, DC, area. Members representing all specialty fields meet six times a year for dinner and fellowship, to consider topics of common interest to the profession, and to hear a prepared lecture given by a featured essayist. Club members take turns as hosts for each meeting. This article gives a historical list of these meetings, naming the essayist and the topic, the hosts, and the site of the meetings.

District of Columbia↗

Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux.

BACKGROUND: An association between asthma and gastro-oesophageal reflux is well recognised but the underlying mechanism is unclear. One suggestion is that gastric juice is aspirated into the tracheal and upper airways but detection of these events is difficult and involves radioisotopic studies. A new method of making direct measurements of tracheal and oesophageal pH over a 24 hour period is described, together with its application to patients with asthma. METHODS: The technique involves insertion of simultaneous tracheal and oesophageal pH probes under general anaesthesia. Continuous monitoring of pH over a 24 hour period is possible, permitting comparison with peak flow readings during wakefulness and at night should the patient be disturbed. Representative data from four patients with asthma (mean FEV1 62% predicted) and symptomatic gastro-oesophageal reflux, together with data from three non-asthmatics, is presented. RESULTS: Thirty seven episodes of gastro-oesophageal reflux lasting more than five minutes were recorded. Of these, five were closely followed by a fall in tracheal pH from a mean (SE) of 7.1 (0.2) to 4.1 (0.4) and a fall in peak expiratory flow (PEFR) of 84 (16) l/min. When gastro-oesophageal reflux occurred without tracheal aspiration the fall in PEFR was 8 (4) l/min. CONCLUSIONS: This new technique was well tolerated and allowed quantitation of the number, duration, and timing of episodes of tracheal micro-aspiration. Unlike acid reflux without aspiration, these events appear to be related to significant acute changes in lung function in asthmatic patients. Further studies with this new method may elucidate the role of gastro-oesophageal reflux in asthma.

Asthma↗

Twenty-four-hour tracheal pH monitoring--a simple and non-hazardous investigation.

Prolonged oesophageal pH monitoring is commonly used in the investigation of gastro-oesophageal reflux. In contrast, tracheal pH monitoring is virtually unknown. We report a simple technique of measuring tracheal pH where the pH probe is inserted under local anaesthetic and can be left in position for 24 h to allow prolonged monitoring. Ten control individuals were studied. All completed the study without complication. One patient with mixed connective tissue disease, failed hiatal hernia repair and subsequent recurrent aspiration pneumonia was studied, on and off ranitidine, using simultaneous tracheal and oesophageal pH monitoring. This method showed evidence of gastro-oesophageal reflux and tracheal aspiration off treatment. When repeated with the patient taking ranitidine, the frequency of significant gastro-oesophageal reflux was reduced and no episodes of tracheal acid aspiration were recorded. Prolonged tracheal pH monitoring is a simple and non-hazardous technique. It is sensitive in detecting tracheal aspiration and may be more sensitive than pre-existing radiolabelled isotope techniques.

Esophagus↗

Simultaneous tracheal and esophageal pH monitoring: investigating reflux-associated asthma.

Aspiration of gastric acid into the trachea may cause asthma in some patients who have gastroesophageal reflux. Antireflux surgery has been advocated for such patients, but lack of an objective test for acid aspiration makes patient selection difficult. We report a new technique for demonstrating acid aspiration, simultaneous tracheal and esophageal pH monitoring. Tracheal pH was measured with a 1.0-mm pH electrode introduced through the cricothyroid membrane under bronchoscopic vision. A standard esophageal pH electrode was placed in the usual position. Tracheal and esophageal pH were monitored over a 24-hour period. Peak expiratory flow rate was measured hourly while the patient was awake. We present data obtained in 3 patients with severe asthma and symptomatic gastroesophageal reflux. All 3 patients demonstrated a decrease in tracheal pH to less than 5.5, coinciding with a decrease in esophageal pH to less than 4.0. The test was repeated after antireflux operation and showed that significant decreases in esophageal pH no longer lowered tracheal pH. Asthmatic symptoms were improved, and medication was reduced in 2 of the 3 patients.

Adult↗

Lung cancer in elderly patients: the role of induced sputum production to obtain a cytological diagnosis.

A single induced sputum sample using hypertonic saline and a ward nebulizer was obtained from 24/26 (92%) patients prior to fibreoptic bronchoscopy for suspected bronchial carcinoma. In 11 of the 19 patients later found to have bronchial carcinoma, positive cytology was found in the induced sputum sample (58% sensitivity), with no false positives (100% specificity). These results are higher than those reported for ordinary sputum samples. They suggest a possible role for this technique in diagnosing bronchial carcinoma in elderly patients in whom bronchoscopy may be considered hazardous, or where this facility is not readily available.

Aged↗

The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.

The case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.

Adult↗

Three cases of alpha-1-antitrypsin deficiency in the elderly.

We report three elderly patients who presented with increasing dyspnoea on exertion and radiological evidence of basal bullous emphysema. On further investigation they were found to have alpha-1-antitrypsin deficiency. We emphasize that alpha-1-antitrypsin deficiency can present much later than is usually the case especially if the patient is a life-long non-smoker.

Aged↗

Endoscopic bougie and balloon dilatation of multiple bronchial stenoses: 10 year follow up.

This paper reports 10 year follow up data on four patients who underwent mechanical dilatation of multiple bronchial stenoses (sarcoidosis two cases, berylliosis one case, idiopathic stenoses one case). Two patients enjoyed symptomatic and physiological improvement during the nine years before they presented with a recurrence of stenosis. The other two had recurrences sooner, and improved only slightly after they had started prednisolone treatment.

Adult↗