Quantitative relationship between global left ventricular thallium uptake and blood flow: effects of propranolol, ouabain, dipyridamole, and coronary artery occlusion

The quantitative relationship between fractional myocardial thallium uptake and radioactive microsphere-determined flow was studied in 33 open chest dogs under baseline conditions during increased coronary flow (dipyridamole), decreased coronary flow (propranolol and coronary artery stenosis), inhibition of Na-K ATPase (ouabain), and regional infarction. Myocardial contents of thallium and microspheres were compared in left ventricular (LV) biopsies taken 5, 10, 15, 30, and 60 min after thallium injection, expressed as fractions of injected dose. Maximal LV thallium uptake occurred 10 min after injection and the 10-min values were therefore used for subsequent comparisons. Combining all dogs, fractional LV thallium content (% injected dose) correlated well with fractional LV blood flow (% cardiac output) (r = 0.95). However, for fractional LV flows in the low, normal, or moderately elevated range (LV flow/cardiac output less than 9%), thallium content consistently exceeded flow by about 15%. This relationship was not altered by ouabain or regional ischemia or infarction. For greatly elevated fractional LV flows (greater than 9%), thallium content was not significantly different from flow. To explain these differences, myocardial and systemic extraction fractions for thallium were determined in eight dogs with a dual tracer method. At baseline, myocardial extraction fraction was significantly greater than systemic (88 +/- 0.4% compared with 75 +/- 1%, p less than 0.001). During dipyridamole, myocardial extraction fraction decreased and myocardial and systemic values were no longer significantly different (82 +/- 1% compared with 79 +/- 1%). These results show that the fraction of injected thallium dose taken up by the LV myocardium exceeds the delivered fraction of cardiac output over a wide range of LV flows, and is not altered by ouabain-induced inhibition of sodium-potassium ATPase or regional myocardial infarction. This difference is explained by a greater myocardial than systemic extraction fraction for thallium. During high LV flows produced by dipyridamole, fractional LV thallium uptake and flow become similar as myocardial and systemic extraction fractions equalize.     

Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection.

OBJECTIVE: To determine whether adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest and improved cardioprotection. Cold crystalloid cardioplegia with adenosine, procaine and magnesium (A) was compared with standard cold crystalloid hyperkalemic cardioplegia (K). METHODS: Sixteen pigs were randomized to receive either cold K (n=8) or A (n=8), where hyperkalemia was substituted with 1.2 mM adenosine. The cold (6 degrees C) cardioplegia was given intermittently and antegradely, with an aortic cross-clamp time of 1 h. Hemodynamic data was continuously measured and pressure-volume conductance catheters were used to determine global left ventricular systolic and diastolic function. Coronary flow and O2 content differences allowed determination of left ventricular energetics. Blood samples, and left ventricular microdialysis were used to measure parameters of ischemia. Measurements were done at 1 and 2 h after cross-clamp release. RESULTS: Mean arterial pressure was reduced with 55 mmHg (standard deviation, SD: 19) in the K group versus 30 mmHg (SD: 14) in the A group 2 h after cross-clamp release (p=0.030). Left ventricular contractility expressed as slope of the preload recruitable stroke work index (Mw) was reduced to 53% (SD: 14) in the K group versus 78% (SD: 23) in the A group 2h after cross-clamp release (p=0.046). Reduction of maximum of first derivate of pressure with respect to time (dP/dtmax) was 804 mmHg/s (SD: 189) in the K group versus 538 mmHg/s (SD: 184) in the A group (p=0.033). The slope of the myocardial oxygen consumption-pressure volume area was at 2 h reperfusion increased from 1.37 (SD: 0.64) to 2.86 (SD: 1.27) in the K group, whereas no shift was detected in the A group (p=0.019). Cardiac troponin T measured in the coronary sinus 1 h after cross-clamp release was 1.25 microg/l (SD: 0.64) in the K group versus 0.73 microg/l (SD: 0.31) in the A group (p=0.046). CONCLUSION: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest, improves post cardioplegic left ventricular systolic function and efficiency, and attenuates myocardial cell damage.     

Mechanical restitution curves: a possible load independent assessment of contractile function.

OBJECTIVE: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload. METHODS: Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm. RESULTS: Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways). CONCLUSIONS: We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.     

Tobacco smoking: a major risk factor for loss of teeth in three 70-year-old cohorts

Oral health was examined in a random sample of 1377 people in three 70-year-old cohorts studied within 5-yr intervals. During the studied period 1971-1983 the prevalence of toothlessness decreased from 52 to 34%. Toothlessness in men was more common in smokers, 48%, and ex-smokers, 32%, than in non-smokers, 20%. Eichner's index was used as a measurement of dental invalidity. This index showed a worse dental state among smokers and ex-smokers compared to non-smokers. Multivariate analyses indicated that tobacco smoking was a major independent risk factor for tooth loss in elderly men.     

The cost-effectiveness of rehabilitation in the home: a study of Swedish elderly.

OBJECTIVES. To investigate whether care of elderly and disabled patients could be more cost-effective after a short-term hospital stay, we examined the impact of a primary home care intervention program on functional status, use and costs of care after 6 months. METHODS. When clinically ready for discharge from the hospital, chronically ill patients with dependence in one to five functions in personal activities of daily living were randomized to physician-led primary home care with a 24-hour service, and the controls were offered ordinary care. Physical, cognitive, social, and medical functions were assessed in 110 team subjects and 73 controls. Data regarding inpatient days and outpatient visits were collected and converted to costs. RESULTS. Team patients demonstrated better instrumental activities of daily living and outdoor walking and significantly fewer diagnoses and drugs at 6 months. They used less inpatient and more outpatient care compared with the control patients. Significant cost reductions were found in the team group. CONCLUSIONS. This primary home care intervention program is cost-effective, at least for a selection of patients at risk for long-term hospital care.     

Arginine-vasopressin analogues with high antidiuretic/vasopressor selectivity. Synthesis, biological activity, and receptor binding affinity of arginine-vasopressin analogues with substitutions in positions 1, 2, 4, 7, and 8

In a search for more selective agonists of arginine-vasopressin (AVP), 10 analogues of [Sar7]- and [MeLa7]AVP with additional substitutions in positions 1 (beta-mercaptopropionic acid), 2 (phenylalanine), 4 (valine), or 8 (D-arginine) were synthesized and tested for antidiuretic and vasopressor activities. All analogues are characterized by a relatively high antidiuretic activity and by a sharp decrease in pressor activity. Their antidiuretic/vasopressor (A/P) selectivities were 2-3 orders higher (except for peptides 2 and 3) than that of the parent hormone. The additivity of the effects of changes in positions 1, 2, 4, and 8 combined with the sarcosine or N-methylalanine substitutions in position 7 on the biological activity is observed. Binding affinities of AVP analogues to plasma membranes from bovine kidney inner medulla and from rat liver containing specific vasopressin receptors were also determined. Generally, these analogues retained high binding affinities to renal vasopressin receptors, and on the other hand they are characterized by a large decrease in binding affinities to hepatic vasopressin receptors, which share characteristics with vasopressor receptors.     

Curriculum factors influencing knowledge of communication skills among medical students

Background  

Communication training builds on the assumption that understanding of the concepts related to professional communication facilitates the training. We know little about whether students' knowledge of clinical communication skills is affected by their attendance of communication training courses, or to what degree other elements of the clinical training or curriculum design also play a role. The aim of this study was to determine which elements of the curriculum influence acquisition of knowledge regarding clinical communication skills by medical students.     

Renal transplant function after ten years of cyclosporine.

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.     

Effects of a Broad-spectrum Behavioral Medicine Treatment Program on Children with Refractory Epileptic Seizures: An 8-Year Follow-Up

We present an 8 year follow-up on a group of children with refractory epileptic seizures who participated in the early 1980s in a controlled group study on the effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures. In the original study, 18 children were divided into three groups: behavior modification group, attention control group, and control group. The purpose was to investigate the effects of a learning-based treatment program superimposed on a regular medical treatment program. Also, the effects of professional attention were evaluated. At the 10 week and 1 year follow-ups, only the group receiving the behavior modification intervention had a significantly reduced rate of seizure index. The present study investigates these same children 8 years later using the same methods of investigation for an additional 10 week period. The results indicate that a significant reduction in seizures was obtained only for the behavior modification group at the 8 year follow-up.