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Biomedical subjects

M J Williams

Publications and source records attributed to M J Williams.

At least 73 records · Page 4Linked to original sources

Prognostic value of dobutamine echocardiography in patients with left ventricular dysfunction.

OBJECTIVES: This study sought to establish the prognostic implications of ischemic and viable myocardium identified by dobutamine echocardiography in patients with left ventricular dysfunction. BACKGROUND: Recent studies have suggested that in patients with viable myocardium identified by positron emission tomography, medical treatment is associated with recurrent cardiac events. Dobutamine echocardiography has been used to identify viable myocardium in patients with left ventricular dysfunction, but the prognostic significance of this test is undefined. METHODS: One hundred thirty-six consecutive patients (mean [+/- SD] age 67 +/- 7.9 years; 104 men) with moderate or severe left ventricular dysfunction (left ventricular ejection fraction 30 +/- 5%) undergoing dobutamine echocardiography were included in the study. Dobutamine was administered using a standard incremental protocol (5 to 40 micrograms/kg body weight per min intravenously in 3-min stages) with additional atropine (1 mg intravenously) as required. Standard body weight echocardiographic views were digitized on-line and compared using a side-by-side display. Viable myocardium was identified by enhancement of regional function at low dose (< 10 micrograms); scar was diagnosed by akinesia at rest or dyskinesia without change and ischemia as new or worsening dysfunction. One hundred thirty patients (95%) were followed up for 16 +/- 8 months after the original study for major cardiac events (cardiac death, myocardial infarction or severe unstable angina requiring late myocardial revascularization). RESULTS: No significant complications occurred during dobutamine echocardiography. Viable myocardium was detected in 26 patients (19%), ischemia in 23 (17%), both viability and ischemia in 13 (10%) and scar in 74 (54%). Of 108 patients treated medically, 46 had viable or ischemic myocardium, and 62 had scar only. There were no significant differences in age or other clinical characteristics, stress response, left ventricular dimensions and ejection fraction between the two groups. Cardiac events occurred in 26 medically treated patients (24%): 18 died of cardiac-related causes; 4 had a nonfatal myocardial infarction; and 4 had late revascularization because of unstable angina. The event rate was greater in patients with viable or ischemic myocardium than those with scar (43% vs. 8%, p = 0.01 by log-rank test). In a Cox regression model, the presence of viable or ischemic myocardium was found to predict subsequent events (relative risk 3.51, p = 0.02) independently of ejection fraction and age. CONCLUSIONS: Viable or ischemic myocardium detected at dobutamine echocardiography in patients with left ventricular dysfunction is associated with an adverse prognosis, independent of age and ejection fraction.

Aged↗

Prevalence and timing of regional myocardial dysfunction after rotational coronary atherectomy.

OBJECTIVES: This study aimed to evaluate the prevalence and time course of wall motion abnormalities associated with rotational coronary atherectomy. BACKGROUND: Although initial clinical studies found evidence of transient wall motion abnormalities after rotational coronary atherectomy, the prevalence and duration of these wall motion abnormalities are unknown. METHODS: Using simultaneous echocardiography, we prospectively evaluated 22 patients undergoing rotational atherectomy and compared their wall motion abnormalities with those of 10 patients undergoing coronary angioplasty alone. The extent of wall motion abnormality was quantified and plotted against time to produce curves of abnormal wall motion development and recovery for the two groups. RESULTS: The cumulative ischemic time was similar for the two groups ([mean +/- SD] 10.3 +/- 6 min for rotational atherectomy vs. 9.6 +/- 4.2 min for coronary angioplasty, p = 0.73). The rate of return to baseline function was significantly lower in the rotational atherectomy group than in the coronary angioplasty group (rotational atherectomy rate constant 0.069 +/- 0.079/min vs. coronary angioplasty rate constant 1.250 +/- 0.47/min, p = 0.0001). The mean time to recovery of baseline wall motion in the rotational atherectomy group (153 min, 95% confidence interval [CI] 6.5 to 3,600) was significantly longer than in the coronary angioplasty group (2.6 min, 95% CI 1.3 to 5.5, p = 0.0001). Rotational atherectomy burr time was longer in the patients who developed myocardial infarction than in those without myocardial infarction (4.7 +/- 2.4 vs. 3 +/- 1.4 min, p = 0.045). CONCLUSIONS: Transient wall motion abnormalities are common after rotational coronary atherectomy and have a longer duration than those observed after coronary angioplasty. This disparity may be a consequence of differences in the mechanisms by which rotational coronary atherectomy and coronary angioplasty produce their effect.

Aged↗

Dietary fat in relation to body fat and intraabdominal adipose tissue: a cross-sectional analysis.

Numerous studies report positive links between dietary fat and adiposity. However, the relation between fat intake and intraabdominal adipose tissue (IAAT), a risk factor for cardiovascular disease and diabetes, is not known. We therefore evaluated the association between dietary fat and adipose tissue stores in 135 white men aged 44 +/- 10 y (mean+/- SD: weight, 86 +/- 14 kg; body fat, 23 +/- 8%) and in 214 white women aged 45 +/- 14 y (weight, 64 +/- 12 kg; body fat, 33 +/- 10%). Dietary intake was estimated from 3-d food records, body composition from hydrostatic weighing, IAAT and subcutaneous abdominal adipose tissue (SCAAT) by computed tomography, and physical activity by using the Baecke Questionnaire. After adjustment for fat-free mass, sex, age, physical activity, and nonfat energy intake, fat intake was weakly correlated with fat mass, explaining only 2% of the variance (partial R2 = 0.018, P < 0.01). In a separate model that evaluated type of fat, saturated fat was positively related (partial R2 = 0.025, P < 0.01) to fat mass after adjustment for fat-free mass, sex, age, physical activity, and nonfat energy intake whereas polyunsaturated fat intake was negatively related (partial R2 = 0.007, P = 0.056). On the basis of partial correlation analyses, dietary fat was also associated with SCAAT adjusted for nonfat energy intake and IAAT (partial R2 = 0.014, P < 0.01), but not IAAT adjusted for nonfat energy intake and SCAAT. However, the association between dietary fat and adjusted SCAAT was not significant after further adjustment for sex, age, and physical activity. Thus, results of this cross-sectional analysis suggest that dietary fat independently plays a very minor role in increasing overall adiposity and does not specifically influence fat accretion in the intraabdominal region.

Adipose Tissue↗

Professor Struthers and the Tay whale.

Sir John Struthers was Professor of Anatomy in Aberdeen from 1863-1889. Some of his contributions, both locally and nationally are outlined, with a brief account of his early career. His interest in the anatomy of whales is noted and the saga of the Tay Whale and his involvement described in detail. Some of his other contributions are also recorded.

Anatomy, Comparative↗

Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women.

Intra-abdominal adipose tissue (IAF) seems to be the primary fat depot putting individuals at risk for cardiovascular disease (CVD). The purpose of this study was to determine IAF cut-points for identifying CVD risk in pre- and post-menopausal women. Age ranged from 18 to 77 y and percentage fat ranged from 9 to 48%. Computed tomography (CT), IAF, DEXA determined regional fat and blood lipid profiles were obtained on 220 Caucasian women. Student's t-tests were run to determine differences between pre- and post-menopausal women. Receiver-operating characteristic (ROC) analysis was used to develop IAF cut-points associated with elevated CVD risk. Post-menopausal women had higher percentage fat, greater proportion IAF and higher CVD risk. Menopausal status was not consistently independently related to CVD risk after adjusting for IAF, but IAF was after adjusting for menopausal status. The same cut-points for CVD risk were found with both 4- and 6-CVD risk factor analysis and for both pre- and post-menopausal as well as pooled data. 4-CVD risk factor analysis comprised cholesterol (C), HDL-C, systolic blood pressure and diastolic blood pressure. 6-CVD risk factor analysis comprised the 4-CVD risk factors plus triglycerides and cholesterol : HDL-C ratio. ROC L positive values indicate levels of IAF above which metabolic disturbances will be increased and were determined to be 110 cm2. ROC L negative values indicate levels of IAF below which CVD risk will not be affected and were determined to be 40 cm2. False positives were 3% and false negatives were 9%. ANOVA comparing women with IAF cross-sections less than 40 cm2, between 40 and 110 cm2 and more than 110 cm2 demonstrate large differences in CVD risk profile. It is suggested women who have IAF values above 110 cm2 are in jeopardy of possessing elevated CVD risk.

Abdomen↗

Intra-abdominal adipose tissue, physical activity and cardiovascular risk in pre- and post-menopausal women.

OBJECTIVE: Determine whether the independent inter-relationships between intra-abdominal adipose tissue (IAF) cardiovascular disease (CVD) risk, and physical activity (PA) support the hypothesis that the beneficial effect of PA of CVD risk is mediated through the effects of activity on IAF. DESIGN: Cross-sectional. SUBJECTS: 220 female Caucasian women 17-77 years old. MEASUREMENTS: Computed tomography IAF and subcutaneous abdominal adipose tissue (SAF), percent fat, CVD risk factors (blood lipids and blood pressure) and PA using the Baecke questionnaire. RESULTS: Zero-order correlations indicated that IAF, SAF, percent fat, age, menopausal status (MS), and all 4 of the PA indexes were consistently related to CVD risk. After adjusting for age, MS, SAF, and percent fat, IAF was negatively related to PA (r2 = 0.04), indicating that more active women had relatively small IAF compared to other fat depots. After adjusting for IAF, MS, and age none of the PA indexes were related to any of the CVD risk factors except cholesterol/HDL ratio (partial r2 = 0.02). However, after adjusting for PA, MS and age, IAF was related to all CVD risk factors except cholesterol (partial r2 = 0.03-0.23). CONCLUSION: These results support the hypothesis that PA may obtain at least part of its effect on CVD risk by reducing IAF.

Abdomen↗

Blood substitutes for transfusion.

Faced with an increased demand for blood products and a stable donor pool, different companies have developed products for oxygen carrying from hemoglobin, to fluorocarbon based compounds (the latter based on Teflon like products). There are several difficulties in showing efficacy of these compounds, and the reasons are discussed. In addition, various strategies for production of oxygen-carrying blood substitutes (OCBS) are noted as well as other applications for these compounds.

Blood Substitutes↗

Calpain cleavage of the cytoplasmic domain of the integrin beta 3 subunit.

The cytoplasmic domains of integrin beta subunits are involved in bidirectional transmembrane signaling. We report that the cytoplasmic domain of the integrin beta 3 subunit undergoes limited proteolysis by calpain, an intracellular calcium-dependent protease. Calpain cleavage occurs during platelet aggregation induced by agonists such as thrombin. Five cleavage sites have been identified. Four of these sites (C-terminal to Thr741, Tyr747, Phe754, and Tyr759) are utilized in intact platelets and flank two NXXY motifs (Asn744-Pro-Leu-Tyr747 and Asn756-Ile-Thr-Tyr759). The fifth site (Ala735) is accessible to calpain after EDTA treatment of the alpha IIb beta 3 heterodimer. The NXXY motif is critical to the bidirectional signaling functions of beta 3 integrins and their association with the cytoskeleton. Thus, calpain cleavage of the beta 3 cytoplasmic domain may provide a means to regulate integrin signaling functions.

Amino Acid Sequence↗

Time course of "warm-up" in stable angina.

Warm-up exercise can significantly reduce the severity of myocardial ischemia on exercise after a 10-minute rest, but this benefit is significantly less after a 30-minute rest. Further study is needed to clarify the mechanisms responsible for warm-up. The results of this study are consistent with a change in myocardial metabolism similar to ischemic preconditioning or a delayed increase in myocardial perfusion to the ischemic territory, which has returned toward baseline after 30 minutes.

Aged↗

Detection of synthetic protein isomers and conformers by electrospray mass spectrometry.

Electrospray mass spectrometry (ESMS) has been used to investigate the structural properties of a protein prepared by total chemical synthesis. Construction of an analog of the tenth type III module from fibronectin (10F3) by chemical ligation of the unprotected synthetic peptides 10F3(1-40) alpha COSH and BrAc (42-94) 10F3 was found to give two major products, both of which possessed a mass corresponding to the expected product, [(COS)40-41]10F3. Comparisons of the ESMS charge distributions obtained for these two synthetic products with that obtained for recombinant 10F3 suggested that one of the synthetic 10F3 analogs was correctly folded and the other was somehow misfolded. This was further confirmed by 1D and 2D NMR analysis. Exposure of the misfolded synthetic [(COS)40-41]10F3 to high pH and elevated temperature followed by analysis using liquid chromatography-mass spectrometry revealed a beta-ester linkage between residues Asn42 and Ser43, produced by an N-->O acyl shift rearrangement at Ser43, as the origin of the misfolding. ESMS was also used to measure the H-D exchange rates of labile protons within the synthetic and recombinant 10F3s. This application, which allows the number of slow exchanging backbone amides within a protein to be calculated, revealed clear differences in the H-bonding networks of the folded and unfolded synthetic protein modules. Replacement of Ser43 by an alanine was found to circumvent the N-->O acyl shift, and the resulting synthetic protein analogue, [Ala43, (COS)40-41]10F3, possessed identical structural properties to recombinant 10F3.

Amino Acid Sequence↗

Platelet adhesion receptors.

The response to vascular injury involves attachment and aggregation of platelets, coupled with initiation of the coagulation cascade. These inter-related processes ensure that the vessel injury is rapidly blocked with an aggregated clump of platelets that is then stabilized by a crosslinked fibrin matrix. Initial adherence relies on the ability of the platelet adhesion receptors to bind subendothelial matrix molecules. Platelet activation then results in the expression of high affinity integrin receptors on the cell surface that bind soluble ligands, allowing platelets to aggregate and form a haemostatic plug.

Blood Platelets↗

Improvement of transthoracic pulmonary venous flow Doppler signal with intravenous injection of sonicated albumin.

OBJECTIVES: This study was performed to determine whether intravenous injection of a sonicated albumin echocardiographic contrast agent (Albunex) improved the quality of the transthoracic pulmonary venous flow Doppler signal. BACKGROUND: Previous studies have shown that transesophageal echocardiography provides pulmonary venous flow Doppler signals superior in quality to those seen with transthoracic echocardiography, which are of limited quality in up to 25% of patients. METHODS: Twenty-one patients underwent transthoracic pulsed wave Doppler examination of pulmonary venous flow before, during and after two doses of Albunex ranging from 0.08 ml/kg (low dose) to 0.22 ml/kg (high dose). In addition, five patients underwent transesophageal examination of pulmonary venous flow before and after a 0.08-ml/kg dose of Albunex. The efficacy of the contrast injection was determined using a score that graded the quality of the three components of the pulmonary venous Doppler signal from 0 to 3 (0 = no visible signal; 3 = optimal signal). RESULTS: Albunex enhanced the quality of the pulmonary venous Doppler signal from baseline (score 3.9 +/- 1.8 [mean +/- SD]) and at both low (score 5.1 +/- 2.2, p < 0.05) and high doses (score 5.6 +/- 2, p < 0.001). Transthoracic pulmonary venous flow velocities were increased, and peak flow velocity ratios were unchanged, after injection of contrast agent. The contrast-enhanced variables showed good agreement with transesophageal flow velocities. CONCLUSIONS: Albunex improves the quality of the transthoracic pulmonary venous Doppler signal, thus allowing improved accuracy of measurement. This approach appears to be effective for increasing the quality of data obtained from the transthoracic examination.

Adult↗

Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women.

OBJECTIVES: This study compared the accuracy and cost implications of using exercise echocardiography and exercise electrocardiography for detection of coronary artery disease in women. BACKGROUND: The specificity of exercise electrocardiography in women is lower than in men. Exercise echocardiography accurately identifies coronary artery disease in women, but its utility in place of exercise electrocardiography is unclear. METHODS: One hundred sixty-one women without a previous Q wave infarction underwent exercise echocardiography and coronary angiography. Positive findings were a new or worsening wall motion abnormality on the exercise echocardiogram and ST segment depression > 0.1 mV at 0.08 s after the J point on the exercise electrocardiogram (ECG). RESULTS: Coronary artery stenosis > 50% diameter narrowing was present in 59 patients; the sensitivity (mean +/- SD) of exercise echocardiography was 80 +/- 3%. In 48 patients with an interpretable ECG, the sensitivity of exercise echocardiography was 81 +/- 4%, and that of the exercise ECG was 77 +/- 3% (p = 0.50). In 102 patients without coronary artery disease, the overall specificity of exercise echocardiography was 81 +/- 4%. In 70 patients with an interpretable ECG, the specificity of exercise echocardiography (80 +/- 3%) exceeded that of the exercise ECG (56 +/- 4%, p < 0.0004). The accuracy of exercise echocardiography was also greater than exercise electrocardiography (81 +/- 5% vs. 64 +/- 6%, p < 0.005). Exercise echocardiography stratified significantly more patients of intermediate (20% to 80%) pretest disease probability into the high (> 80%) or low (< 20%) posttest probability group. In women without a previous exercise ECG, the specificity of exercise echocardiography continued to exceed that of exercise electrocardiography (80 +/- 3% vs. 64 +/- 3%, p = 0.05). Exercise echocardiography had the best balance between accuracy and cost for the diagnosis of coronary artery disease in women. CONCLUSIONS: Exercise echocardiography is more specific than exercise electrocardiography for diagnosis of coronary artery disease in women and is a cost-effective approach to the diagnosis of coronary artery disease because of the avoidance of inappropriate angiography.

Adult↗

Atlantooccipital dislocation: a case report.

We report on a child who suffered an atlantooccipital dislocation and survived. The patient required tracheostomy and feeding gastrostomy due to retropharyngeal swelling from a traumatic pseudomeningocele. He later underwent fusion of his occiput to C3. The complications of such an injury and the anesthetic management are discussed.

Anesthesia↗

Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy.

OBJECTIVES: Cryosurgical ablation of the prostate represents a possibly efficacious method of treating prostate carcinoma in men failing radiation therapy. In addition to eradicating the disease, cryosurgery has the potential to avoid some of the morbidity associated with other treatment modalities. Therefore, a prospective Phase II trial was conducted to determine the safety and efficacy of cryosurgery following radiation therapy in men with local recurrence. METHODS: Cryosurgical ablation of the prostate was performed in men with prostate cancer previously treated by radiation therapy. All patients had biopsy-proven recurrent disease and no evidence of metastases. Initial follow-up occurred at approximately 3 months and included repeat biopsy and serum prostate-specific antigen (PSA) determinations. Biochemical disease-free survival defined as a PSA value less than 0.3 ng/mL was assessed using the Kaplan-Meier method. RESULTS: Thus far, 23 patients have been treated with cryosurgery with follow-up ranging between 12 and 23 months. Approximately 3 months after treatment, sextant biopsies revealed no cancer in 19 of 22 (86%) of the specimens; however, 10 of 22 (45%) showed small amounts of benign glandular tissue. The PSA at 3 months postoperatively declined in 18 of 22 (82%) patients but reached female levels in only 8 men (36%). Nineteen of 22 (86%) patients followed up a minimum of 1 year after cryotherapy have a PSA level equal to or greater than 0.3 ng/mL. Complications occurred in 100% of the patients with 12 of 22 (55%) requiring at least one transurethral resection of sloughed, necrotic tissue. CONCLUSIONS: Our preliminary results suggest that the current cryosurgical technique used in men failing radiation therapy has a low probability of biochemical cure and a high complication rate. Until more data are available, cryosurgery for men with locally recurrent disease after radiation therapy should be considered strictly experimental.

Aged↗