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Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1995

Optimizing the use of cyclosporine in renal transplantation.

OBJECTIVE: To review the existing data on the use of cyclosporine (CsA) in kidney transplantation, particularly with respect to therapeutic drug monitoring. DATA SOURCES: A literature search was conducted of applicable articles related to therapeutic drug monitoring of cyclosporine in renal transplantation. Previous consensus guidelines were examined. Discussions on issues related to this topic convened in Toronto, ON, on June 15-16, 1994. DATA SYNTHESIS: The literature was analyzed to examine patient factors and drug interactions affecting CsA concentrations, the effect of CsA concentrations on patient outcome, current methods of analysis, pharmacodynamic monitoring, and new immunosuppressants. CONCLUSIONS: CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving short-term patient and graft survival. The rate of graft loss after the first year (primarily due to chronic rejection) has remained largely unchanged. Sandimmune Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are underway to determine its effectiveness and safety. Indications for therapeutic drug monitoring for CsA are provided.

Cyclosporine↗
PubMed1995

Cyclosporin A: analytical methodology and factors affecting therapeutic drug monitoring.

The majority of centres measuring cyclosporine have followed the advice of previous consensus meetings. Although most measurements are made using assays with a high specificity for the parent compound, there are still some between-method differences that can be attributed to methodological variables, such as antibody specificity and assay calibration. With experience of cyclosporine therapeutic drug monitoring (TDM) now spanning 15 years, it would be reasonable to infer that the subject is incapable of growth. However, continued interest in the pharmacokinetics of cyclosporine, the introduction of a new formulation of the drug, and the development of new immunosuppressive agents all combine to emphasise the still incomplete extent of our knowledge in this field.

Cyclosporine↗
PubMed1995

Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms.

BACKGROUND: Some patients with angina pectoris and normal coronary arteriograms have reduced coronary flow reserve and abnormal endothelium dependent vasodilator responses. Endothelin-1 (ET-1), a potent vasoconstrictor, is an important modulator of microvascular function and may also have algogenic properties. METHOD: Plasma ET-1 was measured in peripheral venous blood in 40 patients (30 women) (mean (SD) age 56 (8) years) with angina and normal coronary arteriograms and 21 normal controls (17 women) (mean (SD) age 53 (7) years). Patients with systemic hypertension, left ventricular hypertrophy, or coronary spasm were excluded. Plasma ET-1 was measured using radioimmunoassay. RESULTS: Thirty five patients had > or = 1 mm ST segment depression during exercise. Left bundle branch block was present in four patients at rest and in one during exercise. Mean (SD) (range) concentration of ET-1 (pg/ml) was higher in patients than in controls (3.84 (1.25) (1.97-7.42) v 2.88 (0.71) (1.57-4.48) P < 0.0001). In patients with "high" (> control mean (one SD)) ET-1 concentrations (n = 23), the time to onset of chest pain during exercise was significantly shorter (6.21 (3.9) v 9.03 (3.9) min; p = 0.01) than in patients with "low" ET-1 concentrations. Of the five patients with left bundle branch block, four had plasma ET-1 concentration > 4.0 pg/ml. CONCLUSION: Plasma endothelin is raised in patients with angina and normal coronary arteriograms and is consistent with the demonstration of endothelial dysfunction in such patients. The association between "high" plasma ET-1 and an earlier onset of chest pain during exercise suggests that endothelin may also have a role in the genesis of chest pain in patients with normal coronary arteries.

Adult↗
PubMed1995

[The diagnosis of myocardial damage during coronary angioplasty by the analysis of the isoforms of the enzyme creatine kinase MB].

BACKGROUND: The existence of myocardial damage during percutaneous transluminal coronary angioplasty (PTCA) is controversial. Mild elevations in creatine kinase (CK) activity and its isoenzyme MB (CKMB) in patients who underwent PTCA have been reported. However, other authors failed to confirm these elevations. The low sensitivity of total CK and CKMB activity for the detection of myocardial damage in different settings other than myocardial infarction might account for the controversial findings. Measurement of CKMB isoforms has been shown to have a higher sensitivity than the assessment of CK or CKMB activity for early diagnosis of myocardial infarction. Its sensitivity for the diagnosis of myocardial damage in settings other than infarction is not well described. OBJECTIVES: The aim of our study was two-fold: 1) to assess the incidence of myocardial damage after PTCA and 2) to compare the sensitivity of total CK and CKMB activity and measurement of CKMB isoforms for the detection of myocardial damage. METHODS: 14 patients (11 men and 3 women) with chronic stable angina underwent PTCA. Two electrocardiographic leads were monitored from the beginning of the procedure until 30 minutes after the PTCA. ST segment shifts of at least 1 mm, lasting for more than 1 minute, were considered indicative of myocardial ischemia. The duration of ischemic episodes was measured from the onset of the ST shift until its return to baseline. Total ischemic time, in minutes, was the sum of the duration of every ischemic episode. Blood samples were drawn before PTCA and serially during the first 24 hours post PTCA. CK (normal < 200 U/l) and CKMB (normal < 14 U/l) activities were measured. The CKMB isoforms were separated by electrophoresis, measured by densitometric scanning and their ratio calculated (CKMB2/CKMB1 normal < 1.5). RESULTS: Vessels which underwent PTCA were: the left anterior descending artery (LDA) in 5 patients, the circumflex coronary artery (Cx) in 3 patients, right coronary artery (RCA) in 3 patients, LDA and Cx in 1 patient and Cx and RCA in 2 cases. Eleven patients underwent balloon dilatation, 1 underwent atherectomy (Rotablator) and two patients had treatment with both Rotablator and balloon angioplasty. Ischemic ST segment shifts were found in ten patients and the median of total ischemic time was 13.5 minutes (interquartile range: 2-15 minutes). Total CK and CKMB activities were within the normal range in every patient whereas in 7 patients (50%) the peak ratio CKMB2/CKMB1 was above the normal range. There were no differences in age, sex, number of vessels or lesions treated or in the time of balloon inflation between patients with and without abnormal CKMB2/CKMB1 peak. However, the ischemic time was significantly higher in patients with CKMB2/CKMB1 > 1.5 (median 15 vs 0 minutes; p = 0.023). CONCLUSIONS: Myocardial damage during PTCA is not an uncommon finding. The CKMB isoforms are more sensitive markers of myocardial damage during PTCA than total CK or CKMB activities.

Aged↗
PubMed1994

Comparison of two strategies for myocardial management during coronary artery operations.

Despite the current trend for using blood cardioplegia, ventricular fibrillation with intermittent ischemia is still used as a strategy to manage the myocardium with impressive results. These two methods of myocardial management were compared in 40 patients undergoing elective coronary artery operations using creatine kinase MB isoforms and troponin T assays. Each patient was randomized to have either cold blood cardioplegia (n = 20) or ventricular fibrillation with intermittent ischemia (n = 20) for myocardial management during the construction of distal anastomoses. Until recently, the comparison of different methods of myocardial management has been hindered by the lack of a specific and sensitive marker of myocardial damage. Analysis of creatine kinase MB isoforms (MB2, cardiac tissue form; MB1, plasma-modified form) and cardiac-specific troponin T (a structural protein) has been shown to improve the sensitivity for the detection of myocardial damage. There were no significant differences between the two groups in age, sex ratio, extent of disease, or left ventricular function. Blood samples for analysis were collected before cross-clamp application and at time intervals up to 48 hours after. Median peak creatine kinase MB2 activity was found to be significantly higher in the blood cardioplegia group compared with ventricular fibrillation (26.5 U/L versus 19.5 U/L, respectively, p = 0.04). Although median peak troponin T concentration was higher in the blood cardioplegia group, the difference failed to reach significance (2.2 ng/mL versus 1.6 ng/mL, p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Neutrophil elastase and obliterative bronchiolitis.

Bronchoalveolar lavage levels of elastase were assayed to determine the timing and magnitude of elevations in elastase relative to both fibrosis, as indicated by hyaluronate (HA) levels, and decline in FEV1 characteristic of the clinical syndrome of obliterative bronchiolitis (OB). Samples were collected from 48 heart-lung or single lung transplant recipients. Regression analysis was performed and demonstrated that high levels of elastase occurred with active decline in lung function and in association with high levels of HA. This study suggested that intense neutrophil elastase release occurs concurrent with the development of OB and may contribute to the destruction of bronchiolar architecture.

Adolescent↗