Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of99mTc-Sestamibi and23I-β-methyl-iodo-phenyl pentadecanoic acid

Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between -methyl-iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (65% of maximum activity), 2 = mildly decreased (45%–64%), 1 = moderately decreased (25%–44%), 0 = severely decreased (0%–24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct-related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001). Group III segments were associated with the absence of thrombolysis or PTCA (P < 0.001), with occlusion of the infarct-related artery (P < 0.001), with previous infarction in the same territory (P < 0.001) and with a- or dyskinesia in this territory (P < 0.001). These data could support the interpretation that areas in which the uptake of BMIPP is more decreased than that of Sestamibi (group I) are due to delayed recovery of fatty acid metabolism after reperfusion, whereas those with higher BMIPP than Sestamibi activity (group III) are accounted for by the enhanced metabolism induced by passive systolic wall stretch.     

Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and modified fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [¹²³I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are¹²³I-labelled IPPA and BMIPP. While [¹²³I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [¹²³I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [¹²³I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [¹²³I]IPPA and [¹²³I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.     

On the contractile function of protein phosphatases in isolated human coronary arteries

It is unknown whether protein phosphatases types 1 and 2A are present in and can regulate the tone of human vascular tissue. The expression and possible function of serine/threonine protein phosphatases (PP) type 1 (PP1) and type 2A (PP2A) were studied in isolated human coronary arteries. Catalytic subunits of PPI and PP2A were identified by means of phosphatase activity measurement in tissue homogenates, by separation of enriched extracts through affinity column chromatography, by immunoblotting with specific antibodies, by hybridization of mRNA with specific DNA probes and PCR of reverse transcribed mRNA. Based on these methods, the catalytic subunits of PP1(alpha,beta,gamma) and PP2A(alpha,beta) were identified. Appropriately, cantharidin, an inhibitor of PP1 and PP2A, increased basal tone of human isolated coronary artery rings with an EC50 of about 16 micromol/l by increasing the phosphorylation state of the regulatory light chains of myosin. In summary, PP1 and PP2A are expressed in human coronary arteries and they can alter vascular tone.     

Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.     

Analytic procedures for evaluating health care. Statistical control charts

The concern for quality of health care motivates evaluation programs designed to monitor the health care system, patient outcome, and provider expertise. An array of audit methods and instruments for evaluating professional and institutional performance has been developed. Although evaluation is viewed by many as the basis for accountability and improvement of health care, few are aware that most existing evaluation programs are really data-collecting systems. Very little if any, analysis of the data is done with the objective of optimizing the system. The "sampling with intervention" procedures often used to monitor the health care delivery system are primarily directed toward the individual patient while the system and provider continue to operate in the established mode. This article outlines analytic procedures for interpreting evaluation data generated by quality control and audit systems. Five common univariate statistical quality control charts are described.     

Doctor-patient relationships in fetal/infant death encounters.

A study of concerns of 100 middle-class mothers and fathers who had lost infants revealed that the death of an infant or fetus (through miscarriage) was viewed as devastating because of inadequate community recognition of the loss. The impact of these deaths and the lack of community support forces the parents to turn to their physicians from whom they attempt to seek counsel and comfort. Many physicians, unfortunately, are unable to meet the parent's needs because they cannot deal with death on the personal level, and/or their training militates against their accepting a shift in responsibility from "healer" to "counselor-consoler." Thus, an impasse often is reached in which the expectations of parents exceed the service that the physician is able or willing to render. This detracts from the physician's ability to fulfill adequately his role of provider of total care.