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Biomedical subjects

N Fineberg

Publications and source records attributed to N Fineberg.

At least 19 recordsLinked to original sources

Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.

BACKGROUND: Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies. OBJECTIVE: To describe the prevalence and severity of hyperglycemia on hospital admission among acute ischemic stroke patients, to examine the independent relationship of admission hyperglycemia to all-cause mortality, and to document the inpatient management of hyperglycemia. METHODS: Patients hospitalized with acute ischemic stroke at one hospital from July 1993 to June 1998 (n = 656) were identified. Demographic data, diagnoses, and blood glucose (BG) values were retrieved from the electronic medical record system. Admission stroke severity, fingerstick BG results, and new diabetes diagnoses were obtained by chart review. Hyperglycemia was defined as admitting random serum BG > or = 130 mg/dL. Hazard ratios (HR) for 30-day, 1-year, and 6-year mortality were calculated using multivariable Cox regression models. RESULTS: Hyperglycemia at admission to hospital was present in 40% of patients with acute stroke. Patients with hyperglycemia were more often women and more likely to have prior diagnoses of diabetes and heart failure. Almost all of these patients remained hyperglycemic during their hospital stay (mean BG = 206 mg/dL), and 43% received no inpatient hypoglycemic drugs. Hyperglycemic patients had longer hospital stay (7 vs 6 days, p = 0.015) and higher inpatient hospital charges ($6,611 vs $5,262, p < 0.001). Hyperglycemia independently increased the risk for death at 30 days (HR 1.87, p < or = 0.01), 1 year (HR 1.75, p < or = 0.01), and 6 years after stroke (HR 1.41, p </= 0.01). CONCLUSIONS: Admitting hyperglycemia was common among patients with acute ischemic stroke and was associated with increased short- and long-term mortality and with increased inpatient charges. Inpatient blood glucose management was suboptimal in this hospital. A trial of intensive treatment of hyperglycemia should be considered.

Acute Disease↗

HbA1c measurement improves the detection of type 2 diabetes in high-risk individuals with nondiagnostic levels of fasting plasma glucose: the Early Diabetes Intervention Program (EDIP).

OBJECTIVE: Whereas new diagnostic criteria based on a fasting plasma glucose (FPG) of > 126 mg/dl (7.8 mmol/l) have improved the detection of diabetes, multiple reports indicate that many people with diabetes diagnosed by 2-h oral glucose tolerance test (OGTT) glucose measurements > or = 11.1 mmol/l (200 mg/dl) would remain undiagnosed based on this FPG criteria. Thus, improved methods to detect diabetes are particularly needed for high-risk individuals. We evaluated whether the combination of FPG and HbA1c measurements enhanced detection of diabetes in those individuals at risk for diabetes with nondiagnostic or minimally elevated FPG. RESEARCH DESIGN AND METHODS: We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP). RESULTS: Of 244 high-risk subjects studied by FPG measurements and OGTT, 24% of the individuals with FPG levels of 5.5-6.0 mmol/l (100-109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals with FPG levels of 6.1-6.9 mmol/l (110-125 mg/dl) had OGTT-diagnosed diabetes. In the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0 mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0 mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels > or = 7.0 mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort with type 2 diabetes. CONCLUSIONS: Diagnostic criteria based on FPG criteria are relatively insensitive in the detection of early type 2 diabetes in at-risk subjects. HbA1c measurement improves the sensitivity of screening in high-risk individuals.

Biomarkers↗

Prospective study correlating fibrinopeptide A, troponin I, myoglobin, and myosin light chain levels with early and late ischemic events in consecutive patients presenting to the emergency department with chest pain.

BACKGROUND: Although thrombus formation plays a major role in acute coronary syndromes, few studies have evaluated a thrombus marker in risk stratification of patients with chest pain. Furthermore, the relation between markers that reflect myocardial injury and thrombus formation that may predict events in a heterogeneous patient population is unknown. This study correlated markers of thrombus and myocardial injury with early and late ischemic events in consecutive patients with chest pain. METHODS AND RESULTS: Serum troponin I (TnI), myoglobin, and myosin light chain levels were obtained from 247 patients and urinary fibrinopeptide A (FPA) from 178 of the 247. By multivariate analysis, patients with an elevated FPA level were 4.82 times more likely to die or have myocardial infarction, unstable angina, and coronary revascularization at 1 week (P=0.002, 95% CI 1.78, 13.03), whereas those with an elevated TnI (>0.2 ng/mL) were 9.41 times more likely (P<0.001, 95% CI 2.84, 31.17). At 6 months (excluding the index event), an elevated FPA level was an independent predictor of events, with an odds ratio of 9.57 (P<0.001, C1 3.29, 27.8), and was the only marker to predict a shorter event-free survival (P<0.001). The other markers did not independently correlate with cardiac events, although MLC incrementally increased early predictive accuracy in combination with the FPA and TnI. CONCLUSIONS: Elevated FPA and TnI correlated with cardiac events during the initial week in patients presenting to the Emergency Department with chest pain. FPA predicted adverse events and a shorter event-free survival at 6 months.

Aged↗

Long-term follow-up of patients requiring intravenous amiodarone to suppress hemodynamically destabilizing ventricular arrhythmias.

BACKGROUND: Intravenous amiodarone is effective for the acute suppression of recurrent hemodynamically destabilizing ventricular arrhythmias. There are no follow-up data on patients undergoing long-term therapy with intravenous amiodarone. The objective of this investigation was to evaluate long-term outcome. METHODS AND RESULTS: We reviewed the clinical courses of 245 patients given intravenous amiodarone for sustained ventricular tachyarrhythmias. Of the 107 survivors (84% men; mean age 64 years) released from the hospital taking oral amiodarone, 41 were discharged with an empiric prescription for oral amiodarone. For 64 patients a decision regarding further therapy was based on results of an electrophysiologic study. Two patients were treated empirically with oral amiodarone and an implantable cardioverter defibrillator. Clinical variables and survival curves were the same for the empirically treated group and the group whose treatment was based on electrophysiologic findings (P =.89). Survival at 6, 12, and 18 months was 88%, 81% and 71%, respectively, for empirically treated patients, and 83%, 80% and 73%, respectively, for patients whose therapy was directed with an electrophysiologic study. Of the 64 patients who underwent electrophysiologic studies, 33 received an implantable cardioverter defibrillator. The Kaplan-Meier survival curves for patients with and patients without an implantable cardioverter defibrillator were similar (P =.46). CONCLUSIONS: Patients for whom recurrent ventricular tachycardia and fibrillation are suppressed with intravenous amiodarone and who are discharged receiving oral amiodarone have an 80% 1-year survival rate. Although not randomized, our data suggested that among such patients, electrophysiologic testing, implantation of a cardioverter defibrillator, or both may not be necessary. Ascertaining the best management strategy for these patients will require a prospective randomized trial.

Aged↗

Nutrition management of type 2 diabetes by primary care physicians: reported use and barriers.

A survey was mailed to a probability sample of primary care physicians in Indiana to assess their use of and barriers to nutritional therapy for patients with type 2 diabetes. Most (62%) primary care physicians reported referring their type 2 diabetes patients for nutrition counseling, while 38% reported providing counseling themselves. Patient-centered barriers were most frequently cited as reasons for poor effectiveness of nutrition therapy. This differs from previous research that cites system-level factors as barriers.

Counseling↗

Establishment of a clinically correlated human pericardial fluid bank: evaluation of intrapericardial diagnostic potential.

The development of a clinically correlated human pericardial fluid bank and database is described. A unique feature of this registry is the availability of a large number of pericardial fluid samples for testing with respect to multiple factors and for correlation with angiographic findings and clinical syndromes expressed by the patients. The collection of data at the present time comprises frozen pericardial fluid samples obtained from patients who have undergone cardiac surgery; and historical, clinical, and laboratory data obtained from the patient records. Nearly 400 samples have been stored and analyzed thus far, with sample entry continuing. This registry is designed to evaluate the local factors that play a role in mediating or reflecting myocardial or coronary responses. Pathophysiologic processes of particular interest include restenosis, plaque ruptures, and angiogenesis. Study of the pericardial fluid bank should lead to enhanced understanding of molecular mechanisms, as well as to the explanation for the reasons underlying interpatient variability in these processes. It is further anticipated that this information might provide a foundation for the diagnostic use of pericardial fluid to individualize therapies targeting angiogenesis or plaque physiology.

Coronary Angiography↗

Increased thrombin activity correlates with increased ischemic event rate after percutaneous transluminal coronary angioplasty: lack of efficacy of locally delivered urokinase.

BACKGROUND: Angiographic thrombus is associated with increased coronary occlusion and restenosis rates after angioplasty. Administration of intracoronary urokinase decreases the incidence of thrombus but is associated with an increased periprocedural event rate, including stroke and myocardial infarction. An alternative approach is to deliver the agent directly into the arterial wall, thereby reducing the thrombotic substrate in the absence of a systemic effect of the delivered agent. OBJECTIVE: This randomized, double-blind, prospective study correlated intracardiac fibrinopeptide A levels with the ischemic events after angioplasty and evaluated whether locally administered urokinase could reduce the event rate. METHODS: Fifty-four patients with acute coronary syndromes were randomly assigned to local delivery of urokinase or saline. Levels of fibrinopeptide A, a marker of thrombin activity, were obtained before and after administration of heparin, after 2 balloon inflations, and at the end of the procedure in 43 patients and were correlated with ischemic events within the 6-month follow-up period (death, myocardial infarction, or recurrent ischemia). RESULTS: Multivariant analysis revealed that an elevated fibrinopeptide A level before angioplasty significantly correlated with an increased likelihood of an adverse event over the 6-month clinical follow-up. A postangioplasty reduction in the fibrinopeptide A level was noted in control patients (P <.001), but not after local urokinase administration, and the final fibrinopeptide A level was higher in the urokinase group (P =.02). Urokinase had no effect on the procedural results. On follow-up more patients receiving urokinase (13 of 27) had ischemic events than did control patients (6 of 25, P =.04). Most events were recurrent ischemia caused by restenosis. CONCLUSIONS: Heparin-resistant thrombin activity, as evidenced by an increased fibrinopeptide A level correlates with ischemic events on long-term follow-up. Local delivery of urokinase increased the event rate.

Angina, Unstable↗

Clinical utility of troponin T levels and echocardiography in the emergency department.

We investigated the clinical utility of cardiac troponin T (TnT) and echocardiography in the emergency department to predict subsequent in-hospital diagnosis and adverse cardiac events. TnT is a cardiac-specific protein released during cell injury such as that following acute myocardial inFarction (MI). Unlike creatine kinase-MB isoenzymes, TnT is increased in a subset of patients with unstable angina, and these may be at higher risk for subsequent cardiac events. Echocardiography is a useful noninvasive imaging technique for the assessment of ischemic heart disease in acute care settings because of its mobility and rapid results. Serial TnT determinations and echocardiographic images were prospectively evaluated in 100 patients with chest discomfort and admitted to the hospital. Serum was obtained for CKMB and TnT on presentation to the emergency department and 4, 8, 16 and 24 hours later. TnT was considered increased when at values greater than 0.1 microg/L. Echocardiograms were recorded on videotape in the emergency department and images reviewed in a blinded fashion for wall-motion abnormalities. When available, current echocardiographic results were compared with previous results to determine whether a new wall-motion abnormality was present. Of the 100 patients (57 men, 43 women), TnT was increased in 21 of 21 with acute MI and 15 of 41 with unstable angina. One of the 38 patients with stable angina had an increased TnT value and died 5 months later of a noncardiac cause. Ninety percent of patients who sustained acute MI had a TnT increase detected within 4 hours of presentation. Fifteen of 18 patients with acute MI and 9 of 37 patients with unstable angina had a new wall-motion abnormality on echocardiography. The combination of TnT levels with echocardiography yielded a positive predictive value of 84% and a negative predictive value of 90% for adverse cardiac events in the follow-up population, which was more accurate than either test analyzed separately. TnT and echocardiography are useful tests in emergency department triage of unstable coronary syndromes. Both tests are predictive of discharge diagnosis and follow-up events. However, the combined utility of TnT levels and echocardiographic imaging is a more powerful predictor of adverse cardiac events than isolated results.

Angina, Unstable↗

Evaluation of patterns of perfusion and metabolism in dobutamine-responsive myocardium.

OBJECTIVES: We investigated the patterns of perfusion and metabolism in dysfunctional myocardium whose contractility improved with dobutamine. BACKGROUND: Clinical studies have suggested that dobutamine echocardiography can identify hibernating myocardium, but laboratory studies suggest that reduced perfusion limits the response to dobutamine. METHODS: Twenty-five patients with coronary disease and ventricular dysfunction underwent low (5 and 10 micrograms/kg body weight per min) and high dose (maximum of 50 micrograms/kg per min) dobutamine echocardiography and positron emission tomography (PET) using nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left ventricular segments. RESULTS: Perfusion and metabolism were normal in 56.4%, mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake) in 14.5% of dysfunctional segments viable on PET. Wall motion improved with dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose), and 86 of these (97%) were viable on PET. Improvement in wall motion with dobutamine was more common in segments with normal perfusion and metabolism (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and those with mismatch (32%, p = 0.03). All the segments with a biphasic response were supplied by vessels with > or = 70% stenosis, and 88% had normal perfusion and metabolism. CONCLUSIONS: The majority of viable segments with rest dysfunction had normal perfusion and metabolism, suggesting that myocardial stunning was common. Improvement of wall motion at low and high doses of dobutamine was highly correlated with myocardial viability on PET and was more common in myocardium with normal perfusion. A biphasic response to dobutamine identified segments with normal perfusion and metabolism supplied by severely diseased vessels.

Ammonia↗

Gestational diabetes: should it be added to the syndrome of insulin resistance?

OBJECTIVE: The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance). RESEARCH DESIGN AND METHODS: On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test > or = 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied. RESULTS: GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), beta-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting beta-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM. CONCLUSIONS: Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.

Adolescent↗

Controlled portions of presweetened cereals present no glycemic penalty in persons with insulin-dependent diabetes mellitus.

OBJECTIVE: To determine metabolic responses to commercially sweetened flaked corn cereal, unsweetened flaked corn cereal, glucose, and sucrose in teenagers and young adults with insulin-dependent diabetes mellitus (IDDM). DESIGN: A crossover design in which each subject consumed test meals in random order on 4 separate days at least 72 hours apart. SETTING: The inpatient setting of the General Clinical Research Center of the Indiana University Medical Center Hospital. SUBJECTS: Sixteen males and eight females, aged 14 to 25 years, with IDDM. INTERVENTIONS: After fasting overnight, each subject underwent challenge tests with 50 g carbohydrate per 1.73 m2 of body surface area from sweetened flaked corn cereal, unsweetened flaked corn cereal, sucrose, and glucose. All subjects were maintained on continuous intravenous infusion of insulin overnight (euglycemic goal = 3.9 to 6.7 mmol/L), with a constant basal insulin dose infused before and throughout a 3-hour postprandial period. MAIN OUTCOME MEASURES: Plasma glucose, free insulin, triglycerides, and free fatty acid levels measured at baseline and 15, 30, 45, 60, 90, 120, 150, and 180 minutes after meals. STATISTICAL ANALYSES PERFORMED: Comparisons among the four meals were made using two-way repeated measures analyses of variance followed by the Newman-Keuls multiple comparison procedure to identify specific differences among meals. The areas under the response curves were compared using one-way repeated measures analysis of covariance, adjusted for baseline values. RESULTS: The response to glucose for the area under the 3-hour blood glucose response curve was significantly greater than the response to sucrose (P = .006 by repeated measures analysis of variance); the areas for the two cereals (not significantly different from one another) were between the glucose and sucrose areas. At 3 hours, glycemia differed significantly among three of the meals: unsweetened flaked corn cereal > sweetened flaked corn cereal > sucrose (P < .001). Glucose at 3 hours was greater than sucrose (P < .001). There were no significant differences for free insulin, triglycerides, or free fatty acids. APPLICATIONS: Equivalent gram amounts of carbohydrate as presweetened breakfast cereals are not detrimental to persons with IDDM compared with unsweetened cereals. Therefore, presweetened cereals can be used in the correct portion sizes and based on the number of carbohydrate or starch servings in a person's diabetic meal plan.

Adolescent↗

Refining treatment approaches in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has emerged as a common but frequently hidden psychiatric disorder which inflicts an intolerable burden on sufferers and demands effective management. For many years, however, OCD was considered treatment resistant and it is only in the past 15 years that effective therapy has become available. The discovery that the symptoms of OCD could be controlled with clomipramine, but not with other tricyclic antidepressants, was a crucial step in the development of effective management of the condition. The ability of clomipramine to treat OCD derives from its potency as an inhibitor of serotonin reuptake. Serotonin reuptake inhibition has become the fundamental requirement for the pharmacological management of OCD. In the past decade selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective in the management of OCD. Meta-analysis comparing the efficacy of clomipramine and SSRIs initially suggest that clomipramine is more effective than SSRIs, but changes in the clinical characteristics of trial populations over time indicate that the meta-analyses may be misleading. In the few direct comparisons of SSRIs and clomipramine, the two treatments have in fact proved equally effective. Attention is now shifting to the impact side effects on efficacy, a particularly important consideration for OCD patients who require long-term medication but are frequently reluctant to take drugs. The limited data available suggest that SSRIs are better tolerated than clomipramine and are therefore more likely to lead to a favourable treatment outcome.

Clomipramine↗

Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: effects on restenosis and implications for catheter-based drug delivery.

OBJECTIVES: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. BACKGROUND: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. METHODS: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). RESULTS: Delivery of efficiency was 0.01% and intramural retention < 24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicine resulted in toxicity to the adjacent musculature. CONCLUSIONS: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

Animals↗

Vascular injury, repair, and restenosis after percutaneous transluminal angioplasty in the atherosclerotic rabbit.

BACKGROUND: Several nonatherosclerotic animal models of restenosis exist and are used for the evaluation of the vascular response to angioplasty-induced injury. However, few studies have evaluated the response of an atherosclerotic vessel to angioplasty. The present study examined the radiographic, histological, immunohistochemical, and morphometric responses over time of atherosclerotic rabbit femoral arteries after percutaneous transluminal angioplasty (PTA). METHODS AND RESULTS: Rabbits (n = 94) underwent arterial dissection and were fed a hypercholesterolemic diet for 3 weeks, and then PTA was performed. Arteries were obtained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused radial stretching of the artery, medial compression, intramural hemorrhage, injury to normal arterial segments, and dissection within the intima and media. Thrombus filled and cellular accumulation repaired the dissection. Peak smooth muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after angioplasty, generally at the dissection but also in normal sections of the artery. Adventitial injury and subsequent adventitial cellular proliferation and collagen production were observed. A rapid decrease in the radiographic minimal luminal diameter was noted at 3 days, resulting from vascular recoil or thrombus filling the dissection. At 7 to 14 days, only 24% to 33% of the luminal loss was accounted for by an increase in the intimal area, and 22% to 28% of the intima was neointima. CONCLUSIONS: Restenosis in an atherosclerotic artery results from a variable combination of intimal proliferation, vascular remodeling/wound contraction, and recoil of the normal section of the artery. The variability of an atherosclerotic artery to PTA injury results from variable dissection, thrombus formation, and cellular response to injury as well as variable scar contraction and elastic recoil.

Angioplasty, Balloon↗

Symptom-limited arm exercise increases detection of ischemia during dipyridamole tomographic thallium stress testing in patients with coronary artery disease.

Exercise combined with dipyridamole during thallium stress testing in patients with coronary artery disease (CAD) increases the frequency of angina and ischemic ST changes in the electrocardiogram. Evidence for an increase in thallium abnormalities has been inconclusive. We prospectively examined 54 consecutive patients who underwent coronary angiography and tomographic thallium with dipyridamole (0.57 mg/kg) alone and combined with symptom-limited dynamic arm exercise. Most patients presented with a history of chest pain and 49 had angiographic evidence of significant coronary stenosis (50% diameter narrowing). Thallium abnormalities were scored blindly by consensus. The number of abnormal segments (total and ischemic) and indexes of left ventricular dysfunction, such as increased lung uptake or ischemic dilation, were compared in the 49 patients with CAD. During arm exercise more patients had evidence of ischemia (39 vs 30; p < 0.001), and the number of ischemic segments increased significantly from 1.3 +/- 1.5 to 2.5 +/- 2.2 (p < 0.001). There was also a significant increase in the indexes of left ventricular dysfunction, ischemic dilation (10 vs 4 patients; p < 0.03) and increased lung uptake (16 vs 5 patients; p < 0.001). Patients who exercised had increased thallium evidence of extent and severity of ischemia and more frequent indexes of left ventricular dysfunction. Thus, symptom-limited arm exercise improves detection of extent and severity of ischemia in patients with CAD undergoing dipyridamole thallium stress testing.

Aged↗

Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized boys.

Fifty boys, hospitalized on a school-age and an adolescent unit in an intermediate length psychiatric hospital, were studied while off psychoactive medication to determine how serum dopamine beta hydroxylase (DBH) activity varies with different childhood maltreatment experiences. Childhood maltreatment was categorized according to onset (before 36 months old, between 36-72 months old and over 72 months old). Childhood maltreatment groups were compared with a group of psychiatrically hospitalized boys who had neither been abused nor neglected. Boys who were younger than 72 months at age of onset of maltreatment had significantly lower DBH activity than those who had experienced maltreatment later in childhood and those who had not been subjected to abuse or neglect. This difference appeared attributable to the DBH activity of school age (but not adolescent) boys who had been abused/neglected before 72 months. Boys with a principal diagnosis of conduct disorder solitary aggressive type had lower DBH activity than boys without this diagnosis regardless of whether or not they had been maltreated. Low serum DBH may be a biological sequela of maltreatment early in life that correlates with the development of conduct disorder solitary aggressive type in boys.

Adolescent↗

Length of stay of acute psychiatric inpatients: an exponential model.

We examined the length of stay of inpatients admitted to a psychiatric unit in central London. The commonest length of stay (mode) was less than 1 week. In general, subsequent weeks showed successively fewer discharges, so that the distribution curve of the number of patients by length of stay showed a smooth decline. Analyzing the first 13 weeks of stay, the distribution curve corresponded very closely to a theoretical exponential decay curve. This has implications for recording the average length of stay and thus for comparing one hospital unit with another. It may also have implications for planning for acute psychiatric services. A plea is made for using the median rather than the mean for recording the average length of admission for some purposes.

Acute Disease↗

Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.

Blood Glucose↗