N S Fineberg's research while affiliated with Indiana University-Purdue University Indianapolis and other places

Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies. 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. 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. 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). 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.

The authors performed this study to determine whether exposure of renal calculi to radiographic contrast material has an effect on the attenuation values at computed tomography (CT) performed with varying collimation widths. Renal calculi (23 stones of various composition) were scanned with 1-, 3-, and 10-mm collimation. Stones were then exposed to a solution of radiographic contrast material for 5 minutes, washed with water, and rescanned 36 hours later. The reproducibility of the CT attenuation measurements on different days was evaluated by obtaining measurements in a subset of 16 renal stones on 4 different days. There was no statistically significant change in attenuation after contrast material exposure at narrow collimation. At wider collimation, statistically significant increases were noted in both attenuation and standard deviation. A small amount of variability between readings was noted on different days, with a minimal increase in attenuation each day. Correlation between readings remained very high. Exposure of stones to a radiographic contrast material had a statistically significant effect on CT attenuation values only at wide collimation. This may be related to technical factors including volume averaging. Absence of an effect at narrow collimation suggests that the attenuation values of renal stones do not significantly change after exposure to contrast material.

We have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified in kidney sections from male and female mice (strain 129) aged one day to eight months and this parameter was correlated with changes in renal histopathology. Aprt heterozygous and wild-type mice were used as controls. Following anesthesia, the left kidney was removed and immediately frozen in dry ice. Unstained cryosections were examined by polarized light to determine total area of birefringent particles. The right kidney was perfused and embedded in plastic, and stained sections were viewed by light microscopy to examine the histopathology and to determine the location of the birefringent particles. A pathological score was assigned to the histological findings. The scores from the right kidney were compared with crystal/particle area in the left kidney, and the data were analyzed using two-way analysis of variance. The chemical composition of the particles was determined by x-ray diffraction analysis. Several stone fragments from the bladder were also examined by scanning electron microscopy (SEM). Crystals were detected in kidney sections from one- to two-day-old Aprt knockout mice. The crystal burden remained low in both sexes throughout the study except in males at the 120- to 240-day period. Furthermore, there was a substantial degree of renal pathology, primarily seen as interstitial fibrosis, in those males with a very high level of stone formation. The crystalline material was identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM indicated that the crystals were spherical, with a diameter of 10 to 20 microm. Tissue staining and fixation procedures dramatically reduced the amount of birefringent material in kidney sections. Aprt heterozygotes of both sexes had low levels of crystalline material in the kidneys and no pathology. Birefringent material or pathological changes were not seen in kidneys from wild-type mice. Both male and female Aprt knockout mice accumulate DHA. However, the area occupied by DHA crystals was significantly greater in 120- to 240-day-old males compared with the females of similar age. Also, substantial renal pathology was detected in kidneys of male mice that had very high levels of stone material.

We set out to evaluate changes in arterial oxygen tension (PaO2) when weaning neonates from inhaled nitric oxide (INO). We reviewed the records of 505 prospectively collected INO weaning attempts on 84 neonates with hypoxic respiratory failure. PaO2 values before and 30 min after weaning attempts were recorded. Relationships between change in PaO2 and decreases in INO concentrations were investigated using regression analysis and ANOVA. PaO2 decreased (−18.7 ± 1.8 torr; P < 0.001); when weaning INO. A stepwise decline in PaO2 was observed weaning INO from 40 ppm. The greatest decline occurred when INO was discontinued (−42.1 ± 4.1 torr). Forward stepwise multiple regression using variables with significant relationships to the decline in PaO2 identified the specific dose reduction 7(P < 0.001), the prewean PaO2 (P < 0.001), and surfactant therapy (P = 0.018) as the variables best describing the change in PaO2(P = 0.004, r = 0.51). In conclusion, a graded decline in PaO2 occurs when reducing INO. INO should be weaned to less than 1 ppm before discontinuing its use. Prior surfactant treatment appears to enhance the oxygenation reserve when weaning INO. Pediatr Pulmonol. 2001; 32:14–19.

To assess the out-of-hospital cardiac arrest (OHCA) survival advantage after providing police with automated external defibrillators (AEDs) in rural and suburban Indiana. An observational evaluation was conducted in six Indiana counties (population: 464,741) before (retrospective) and after (prospective) training and equipping police with AEDs. The primary outcome evaluated was survival to hospital discharge for all cases of ventricular tachycardia/ventricular fibrillation (VT/VF) OHCA. Other factors evaluated include age, gender, race, arrest location, witnessed arrest, bystander cardiopulmonary resuscitation, response intervals, and survival to discharge for all OHCAs. Results are reported using chi-square, Student's t-test, and logistic regression. Police were equipped with 112 AEDs, increasing total defibrillator capability by 43.2%. During the study period, AED-equipped police responded prior to emergency medical services (EMS) in 26 of 388 cases (6.7%). The time intervals from 911 call-to-scene and 911 call-to-shock were shortened by 1.6 minutes (95% confidence interval [95% CI] = 0.0 to 3.1, p = 0.05) and 4.8 minutes (95% CI = 1.3 to 8.3, p = 0.008), respectively, with police response as compared with EMS response. Survival to hospital discharge for VT/VF OHCA was 15.0% (3/20) in cases in which police responded first and 10.0% (16/160) in cases in which EMS responded first (relative risk [RR] 0.63, 95% CI = 0.17 to 2.39, p = 0.45). Survival to hospital discharge for VT/VF OHCA did not improve from the prestudy period (16/204, 7.8%) to after police AED availability (19/180, 10.6%) (RR 0.72, 95% CI = 0.36 to 1.45, p = 0.38). Out-of-hospital cardiac arrest survival in suburban and rural Indiana did not improve after police were equipped with AEDs, likely related to poor police response.

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. We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP). 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. 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.

Although factors such as age, blood pressure, and its responsiveness to changes in sodium balance and extracellular fluid volume status (salt sensitivity) are associated with an increased risk of end-organ disease and cardiovascular events in hypertensive subjects, no such relationship with mortality has been demonstrated for salt sensitivity in normotensive subjects. We conducted long-term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago. We ascertained the status of 596 subjects (85% of the total population), 123 (21%) of whom had died. The following initial measurements were significantly (P<0.002) associated with subjects who had died compared with subjects known to be alive: age at study, pulse pressure, systolic, diastolic, and mean arterial pressures, hypertension, salt sensitivity, baseline renin levels, and body mass index (but not body weight). A stepwise logistic regression found the following independent predictors of death (odds ratio, 95% CI): age at initial study (1.08, 1.06 to 1.10), baseline blood pressure (1.03, 1.01 to 1.04), sodium sensitivity (1.73, 1.02 to 2.94), and male gender (1.91, 1.15 to 3.17). When survival curves were examined, normotensive salt-sensitive subjects aged >25 years when initially studied were found to have a cumulative mortality similar to that of hypertensive subjects, whereas salt-resistant normotensive subjects had increased survival (P:<0.001). These observations provide unique evidence of a relationship between salt sensitivity and mortality that is independent of elevated blood pressure.