Etiology of troponin I elevation in patients with congestive heart failure and low clinical suspicion of myocardial infarction

BACKGROUND: Increased troponin I (TnI) has been detected in congestive heart failure (CHF) patients. We demonstrate that occurrence of LVH, and systolic and diastolic blood pressure values (SBP and DBP, respectively) correlate with increasing levels of serum TnI in a selected CHF population. METHODS: Our team reviewed the medical records of 40 consecutive patients admitted with CHF symptoms, low clinical suspicion of myocardial infarction (MI), and serum TnI measured upon admission. Twenty numerical and categorical parameters were screened. Patients were divided in to seven non-exclusive groups by increasing cutoff values of serum TnI (0, 0.1, 0.2, 0.3, 0.4, 0.6, and 1.5 ng/ml). In each group the average value of numerical parameters and the occurrence of categorical ones were calculated. The correlation between these values and the seven TnI cutoffs were analyzed. RESULTS: Occurrence of electrocardiographic left ventricular hypertrophy (ECG-LVH), and average values of SBP and DBP significantly correlated with the TnI cutoffs by means of multiple regression analysis (P = 0.001, 0.02 and 0.007, respectively). CONCLUSION: ECG-LVH and values of SBP and DBP significantly correlate with increasing cutoff levels of serum TnI in hospitalized patients with CHF and low clinical suspicion of MI.     

N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy

Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.     

Uncoupling of social zeitgebers and diurnal cortisol secretion in clinical depression

Daily activities (zeitgebers) such as waking, eating, and exercising, done alone or in the presence of others, may help to entrain biological rhythms. To examine whether the relationship between zeitgebers and biological rhythms is altered in depression, this study tracked daily activity and cortisol secretion in 50 depressed and 50 control participants using a daily diary methodology. The groups reported similar levels of regular daily activities. Among control participants, regular daily activities were associated with a normative decline in cortisol secretion. Among depressed participants, daily activities and cortisol secretion were unrelated, consistent with the hypothesis that these activities are less able to entrain diurnal rhythms. This lack of social entrainment may underlie some of the circadian disturbances in depression.     

Hypertension management and control in primary care: a study of 20 practices in 14 states

STUDY OBJECTIVE: To describe the management and control of hypertension in primary care practice. DESIGN: Retrospective medical record review. SETTING: Twenty primary care practices in 14 states. PATIENTS: Thirteen thousand forty-seven patients with hypertension. MEASUREMENTS AND MAIN RESULTS: Diagnoses, drugs prescribed, and blood pressure readings were extracted from the electronic medical record at each practice in the study. For patients with hypertension and comorbid diagnoses, the most recent blood pressure and antihypertensive drugs prescribed were determined. Analyses assessed the blood pressure control rates and the association between control and demographic variables, frequency of visits to the practice site, and pharmacologic treatment patterns. Among the 20 practices in the study, 13,047 patients had received a diagnosis of hypertension and their blood pressures had been measured within the previous 12 months. One third of the patients had comorbid coronary heart disease, diabetes mellitus, heart failure, and/or renal insufficiency. The most recent blood pressure reading was below 140/90 in half the patients. Control was associated with age 60 years or younger, female sex, more than one visit to the practice, more than one comorbidity, and type of practice (p<0.01, logistic regression). Wide variability was noted among practices in the use of multiagent antihypertensive therapy, and in antihypertensive therapy by drug class. Among patients without comorbidity treated with one drug, systolic blood pressure did not differ significantly by drug class. Diastolic blood pressure was slightly lower in patients prescribed thiazide diuretics than in those prescribed angiotensin receptor blockers (p=0.03, analysis of covariance). CONCLUSION: Blood pressure control in primary care practice can be much better than reports usually indicate. Good control in this study was not due to specific drug choice, but instead may have been due to regular monitoring of blood pressure and motivation of the practice to improve patient care.     

Accuracy of methods to estimate ionized and "corrected" serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support

BACKGROUND: The purpose of this study was to determine the accuracy of 22 published methods to estimate serum ionized calcium (iCa) and "corrected" total serum calcium (totCa) concentrations in critically ill, multiple trauma patients. Seven of these formulas estimated iCa and 15 were directed toward predicting a "corrected" totCa. METHODS: Adult patients admitted to the trauma intensive care unit who received specialized nutrition support were consecutively recruited for study. Patients who received blood products, i.v. calcium, or therapeutic doses of heparin within 24 hours before the laboratory measurements or had a history of cancer, bone disease, parathyroid disease, hyperphosphatemia (> or = 6 mg/dL), hyperbilirubinemia (> 3.5 mg/dL), or renal failure requiring dialysis were excluded. The 22 published methods were analyzed for sensitivity, specificity, percentage false negatives, and percentage false positives for predicting hypocalcemia or hypercalcemia. RESULTS: One hundred patients were studied 4.9 +/- 3.3 days postinjury and were receiving enteral nutrition (n = 81), parenteral nutrition (n = 18), or both (n = 1) at the time of study. Twenty-one patients were hypocalcemic (iCa < or = 1.12 mmol/L) and 6 were hypercalcemic (iCa > or = 1.32 mmol/L). The mean sensitivity of the 22 methods for assessing hypocalcemia was 25% +/- 32% and the specificity was 90% +/- 18%. Although the average percentage of false positives for assessing hypocalcemia was 10% +/- 18%, the mean percentage of false negatives was inordinately high at 75% +/- 32%. The most common method for determination of "corrected" totCa concentration ["corrected" calcium = totCa + (0.8 x (4-serum albumin concentration))] had a sensitivity of only 5%. The McLean-Hastings nomogram method, the most common method for estimating serum iCa concentration, had a sensitivity of 67% but unfortunately also had a significant false-positive rate of 27%. Serum totCa correlated modestly with iCa (r2 = .334, p < .001). Those patients with a serum albumin < or = 2 g/dL (n = 43) had a significantly higher prevalence of hypocalcemia than those with a higher serum albumin concentration (37% incidence of hypocalcemia vs 10%, respectively, p < .002). CONCLUSIONS: Aberrations in calcium homeostasis are frequent (27%) in postresuscitative critically ill multiple trauma patients. Methods for predicting hypocalcemia lack sensitivity and are often associated with an unacceptable rate of false negatives. Predictive methods for estimating ionized or corrected serum concentrations should not be used. Direct measurement of serum iCa concentration is indicated for assessing calcium status for this population.     

Nursing at ground zero: experiences during and after September 11 World Trade Center attack

The purpose of this study is to discover shared perceptions, feelings, and common experiences of nurses after the September 11th World Trade Center terrorist attack through interpretive analysis of narrative stories of seventeen nurses. Six themes and one constitutive pattern describe the experiences: (a) Loss of a symbol and regaining new meaning, (b) Disaster without patients, (c) Coordinating with and without organizations, (d) Rediscovering the pride in nursing, (e) Traumatic Stress, and (f) Preparing for the future. The constitutive pattern is that nursing enables a humanitarian disaster response.     

Measuring sensitivity moment-by-moment: microanalytic look at the transmission of attachment

Meta-analyses have indicated that the mediating power of sensitivity in the transmission of attachment across generations is not nearly as great as would be predicted by attachment theory (van IJzendoorn, 1995; De Wolff & van IJzendoorn, 1997). To make sense of these findings, the author suggests that current measures of sensitivity should be expanded to include the assessment of mother-infant behavior on a micro-behavioral level. This paper reviews evidence for two central propositions: (1) The internal working model of mothers is expressed in subtle, fine-grained interactive behaviors with their infants, and (2) infants perceive and remember these behaviors in the form of interactional expectancies. Following these propositions, hypothesized representational micromodels for each major attachment organization are then offered, based on the Parallel Distributed Processing (PDP) approach to information processing. In closing, this paper presents some of the most pressing unresolved issues for attachment researchers as they seek to empirically identify the mechanisms by which attachment is transmitted across generations.     

Adverse effects from inappropriate medication administration via a jejunostomy feeding tube.

Numerous complications can arise when administering medications to patients receiving continuous enteral feeding. We report a case of a patient who could not be fed by mouth and was receiving continuous jejunal enteral feeding who had an adverse event associated with inappropriate administration of a medication via his jejunostomy tube. He had taken an extended-release niacin product before hospitalization for type IIb hyperlipidemia. The patient was inappropriately given a single dose of 750 mg of niacin as the short-acting tablets that were crushed and administered via the jejunostomy tube. He experienced severe cutaneous flushing, a feeling of warmth, itching, nausea, and emesis. He was noted to have "prickly heat" to the forehead, according to the nursing notes. A discussion of problems and guidelines for medication administration in adult patients receiving continuous tube feeding is provided.