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PubMed2004

Does the storage time of transfused red blood cells influence regional or global indexes of tissue oxygenation in anemic critically ill patients?

OBJECTIVE: To determine whether transfusion of red cells either < or =5 days or > or =20 days from donation alters tonometric indexes of gastric mucosal oxygenation or global oxygenation parameters in euvolemic anemic critically ill patients without ongoing hemorrhage. The a priori hypothesis was that stored red cells worsen gastric oxygenation. DESIGN: Prospective, double-blind, randomized study. SETTING: A 12-bed general medical/surgical intensive care unit in a Scottish teaching hospital. PATIENTS: Ventilated euvolemic anemic (mean +/- sd hemoglobin, 85.8 +/- 8.4 g/L) critically ill patients with significant organ failure, but no evidence of hemorrhage. INTERVENTIONS: After baseline measurements, patients were randomized to receive two units of leukodepleted red cells that were either < or =5 days (ten patients) or > or =20 days (12 patients) after donation according to a standardized protocol. MEASUREMENTS AND MAIN RESULTS: Changes in gastric to arterial Pco2 gap (Pg-Paco2 gap), gastric intramucosal pH, arterial pH, arterial base excess, and arterial lactate concentrations were measured during baseline (2.5 hrs), during transfusion (3 hrs), and for 5 hrs after transfusion. Mean age of red cells stored < or =5 days was 2 days (first and third quartile, 2, 2.25; range, 2-3); red cells stored >/=20 days had a mean age of 28 days (first and third quartile, 27, 31; range, 22-32). Hemoglobin concentration increased by 15.0 g/L and 16.6 g/L, respectively, in the fresh and stored groups (p =.62). There were no significant differences between the groups either using treatment-by-time analysis or comparing the pre- and posttransfusion periods either for Pg-Paco2 gap (mean difference, 0.03 kPa; 95% confidence limits, -1.66, 1.72) or gastric intramucosal pH (mean difference, 0.015 pH units; 95% confidence limits, -0.054, 0.084). The mean change within each group from the pre- to posttransfusion period for Pg-Paco2 gap and gastric intramucosal pH, respectively, was 0.56 kPa (95% confidence limits, -0.68, 1.79) and -0.018 pH units (95% confidence limits, -0.069, 0.032) for "fresh" red cells and 0.52 kPa (95% confidence limits, -0.6, 1.64) and -0.033 pH units (95% confidence limits, -0.080, 0.129) for "stored" red cells. There was no statistically or clinically significant improvement in any other oxygenation index during the measurement period for either group compared to baseline values. CONCLUSIONS: Transfusion of stored leukodepleted red cells to euvolemic, anemic, critically ill patients has no clinically significant adverse effects on gastric tonometry or global indexes of tissue oxygenation. These findings do not support the use of fresh red cells in critically ill patients.

Adult↗
PubMed2002

Early identification of patients with an acute coronary syndrome as assessed by dispatchers and the ambulance crew.

This study was performed to evaluate the possibility of early identification of patients with an acute coronary syndrome who are transported by ambulance. All patients in the community of Göteborg who were transported by ambulance over a period of 3 months owing to symptoms raising any suspicion of an acute coronary syndrome were studied. In all 930 cases that were included in the survey, 130 (14%) had a final diagnosis of acute myocardial infarction (AMI) and 276 (30%) had a final diagnosis of an acute coronary syndrome. Independent risk indicators for development of AMI were: male sex (odds ratio 1.70; 95% confidence limits 1.02-2.84), cold and clammy on admission of the ambulance crew (odds ratio 2.07; 95% confidence limits 1.23-3.49) and showing electrocardiogram (ECG) signs of myocardial ischemia on admission to the emergency department (odds ratio 8.78; 95%confidence limits 5.28-14.61). Independent predictors for development of an acute coronary syndrome were: male sex (odds ratio 1.97; 95% confidence limits 1.30-2.99), a history of angina pectoris (odds ratio 3.41; 95% confidence limits 2.24-5.26), cold and clammy on admission of the ambulance crew (odds ratio 1.95; 95% confidence limits 1.21-3.15), and ECG signs of myocardial ischemia on admission to the emergency department (odds ratio 5.55; 95% confidence limits 3.63-8.58). Among patients seen by the ambulance crew with symptoms raising any suspicion of an acute coronary syndrome, predictors for that diagnosis included male sex, a history of angina pectoris, patients being cold and clammy on admission of the ambulance crew, and ECG signs of myocardial ischemia on admission to the emergency department.

Acute Disease↗
PubMed2004

Relationship between world-ranking and Olympic performance of swimmers.

Coaches believe world-ranking lists are a reliable tool for predicting international swimming performance. To examine the relationship between world-ranking and Olympic performance, we modelled world-ranking time and best time from the 2000 Olympic Games for 407 top-50 world-ranked swimmers. Analysis of log-transformed times yielded within-athlete and between-athlete coefficients of variation (CV) and percent changes in performance from world-rankings to Olympics. Variations and performance progressions were compared across sex, stroke, distance, nation and medal status. The within-athlete coefficient of variation of performance for all swimmers was 0.8% (95% confidence limits: 0.7 to 0.9%). Females were slightly less consistent, although not substantially different to males (ratio of female/male within-athlete CV: 1.1; 95% confidence limits: 1.0 to 1.2) and had a wider range of talent (ratio of female/male between-athlete CV: 1.2; 95% confidence limits: 1.1 to 1.4). Swimmers from Australia (AUS) were more consistent than those from the United States (USA) and other nations (OTHER) (ratio of within-athlete CV, USA/AUS: 1.5; 95% confidence limits: 1.0 to 2.2; OTHER/ AUS: 1.6; 95% confidence limits: 1.2 to 2.1). Most Olympic medallists (87%) had a top-10 world-ranking. Overall performance time at the Olympics was slower than world-ranking time by 0.3% (95% confidence limits: 0.2 to 0.4%), medallists improved by 0.6% (95% confidence limits: 0.4 to 0.9%) and non-medallists swam 0.6% slower (95% confidence limits: 0.5 to 0.7%). We conclude that a top-10 ranked swimmer who can improve performance time by 0.6%, equivalent to 0.13 s in the men's 50-m freestyle, will substantially increase their chance of an Olympic medal (the difference between first and fourth place).

Achievement↗
PubMed1992

Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment.

Capillary permeability was investigated in 32 Thai patients aged 14-49 years who had acute falciparum malaria with use of three distinct techniques: quantitation of the urinary albumin/creatinine ratio (ACR), estimation of the transcapillary escape rate of radiolabeled albumin (TER), and retinal photography/fluorescein angiography. Fourteen patients had uncomplicated infections and 18 were severe cases. The severely ill patients had significantly higher ACRs (median, 4.8 mg/mmol; 95% confidence limits, 2.4-19.9 mg/mmol) and TERs (median, 8.3%/h; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 6.2-13.2%/h) than the uncomplicated cases (ACR: median, 2.1 mg/mmol; 95% confidence limits, 1.0-8.8 mg/mmol; TER: median, 5.9%/h; 95% confidence limits, 3.8-10.6%/h; P = .014 and .042). Both variables were significantly associated with biochemical indices of disease severity including total serum bilirubin levels (rs greater than or equal to 0.398, P less than .025 in each case), but there were no significant differences between ACRs and TERs among comatose and noncomatose patients with severe infections (P greater than or equal to .08). Retinopathy (hemorrhages, cotton-wool spots, capillary nonperfusion, and/or extravasation of fluorescein) was found in eight severely ill patients and in two uncomplicated cases. Fluorescein leakage was evident in six patients. Although fluorescein leakage had the strongest parametric correlation with the presence of coma relative to both ACR and TER in the full patient series (r = 0.58, P less than .01), multiple linear regression analysis indicated that concentrations of plasma lactate (t = 2.998, P = .006) and serum creatinine (t = 2.200, P = .036) were the factors responsible for this association. These data do not support a role for tissue edema in the pathogenesis of cerebral malaria but reveal an association between markers of disease severity and a generalized increase in systemic capillary permeability.

Adolescent↗
PubMed1999

Recovery of LV contractility in man is enhanced by preischemic administration of enflurane.

BACKGROUND: Volatile anesthetics enhance postischemic functional recovery in animal models; this effect has not been investigated in man. METHODS: Twenty-two patients undergoing coronary surgery were randomized to enflurane administration (0.5% to 2%) for 5 minutes to reduce systolic blood pressure by 20% to 25% immediately before cardioplegic arrest. Left ventricular contractility was assessed by pressure-area relations using echocardiographic automated border detection during inflow occlusion before and after cardiopulmonary bypass. Linear regression analysis in 16 patients with paired data sets assessed changes in contractility. RESULTS: The relation was highly linear (r = 0.95+/-0.02). A change of slope versus the change in x intercept was detected in controls (mean difference, 16.1 mm Hg/cm2, 95% confidence limits, 5.9 to 26.3; 2.2 cm2, 95% confidence limits, -1.1 to 5.5; p = 0.007), which was different from those of treated patients (mean difference, 0.7 mm Hg/cm2, 95% confidence limits, -2.2 to 3.7; -0.06 cm2, 95% confidence limits, -1.6 to 1.5; p > 0.2). Analysis of covariance in the overall group confirmed a significant effect of treatment (p = 0.002). CONCLUSIONS: Enflurane enhances postischemic functional recovery, possibly through pharmacologic preconditioning of myocardium.

Aged↗
PubMed1994

Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen hospital.

The adult patients of somatic departments of a Copenhagen hospital were screened on a randomly selected day during a 14 day period by interviewers who examined them using a structured questionnaire regarding life-style. A patient was considered having an alcohol problem if one or more of the following criteria was fulfilled: (1) a self-reported daily alcohol consumption for at least 2 years of at least 60 g of ethanol in men and 36 g in women, (2) a Michigan Alcoholism Screening Test (MAST) score of or above 5, (3) an alcohol-related discharge diagnosis. In total, 692 patients fulfilled the entry criteria, but 181 patients (26.2%) had to be excluded owing to predefined exclusion criteria (terminal illness, dementia, etc.), and 74 patients (14.5%) refused to participate. Among the 437 interviewed patients, 125 patients (28.6%; 95%-confidence limits 24.4-33.1%) fulfilled one or more of the diagnostic criteria for an alcohol problem. Only 14 patients (3.2%; 95%-confidence limits 1.8-5.3%) had an alcohol-related discharge diagnosis. The prevalence of patients with alcohol problems was significantly (P < 0.05) higher among male patients (82 of 171 men (48.0%; 95%-confidence limits 40.3-55.7%)) than among female patients (43 of 266 women (16.2%; 95%-confidence limits 12.0-21.2%)). The prevalence of patients with alcohol problems was 32.4% (95%-confidence limits 25.5-39.8%) in internal medicine departments, 28.5% (95%-confidence limits 21.3-36.6%) in surgical departments, and of female patients 22.2% (95%-confidence limits 13.7-32.8%) in the department of gynaecology and obstetrics.

Adolescent↗
PubMed2002

Predictors of outcome after the Fontan operation: is hypoplastic left heart syndrome still a risk factor?

OBJECTIVE: This study was undertaken to evaluate factors contributing to a decrease in early mortality and morbidity after the Fontan procedure between January 1, 1992, and December 31, 1999. METHODS: Outcomes evaluated were early survival, duration of pleural effusions, and duration of hospitalization. Potential predictors evaluated included anatomic diagnosis, presence of a common atrioventricular valve, preoperative pulmonary artery pressure, type of Fontan operation, type of intentional right-to-left shunt or baffle fenestration, and use of modified ultrafiltration. RESULTS: The modified Fontan procedure was performed in 332 patients at a median age of 22 months (range, 11-380 months) and a median weight of 11 kg (range, 5.8-120 kg). Prior stage I reconstructive surgery for classic or variant hypoplastic left heart syndrome had been performed in 205 (53%) of 332 patients, and 318 (96%) had undergone an interim superior cavopulmonary connection. A lateral-tunnel Fontan operation was performed in 281 patients, and an extracardiac conduit Fontan operation was performed in 51 patients. An intentional right-to-left shunt was created in 298 (90%) patients. Between 1992 and 1999, the outcome after the modified Fontan operation improved significantly. Overall mortality was 6.6% (22/332), with only 2 deaths since 1994. Morbidity was also reduced, with a decreased duration of pleural effusions and decreased hospital stay. In a multivariable analysis of the entire cohort, only the presence of a common atrioventricular valve (odds ratio, 7.64; 95% confidence limits, 2.07-28.14; P =.0002) and increased preoperative pulmonary artery pressure (odds ratio, 1.46/1 mm Hg increase; 95% confidence limits, 1.2-1.78; P <.001) increased the risk of early death, whereas use of a single-punch fenestration in a lateral-tunnel Fontan (odds ratio, 0.06; 95% confidence limits, 0.01-0.65; P =.02) and use of modified ultrafiltration (odds ratio, 0.14; 95% confidence limits, 0.03-0.72; P =.019) decreased the risk of death. The risk of prolonged pleural effusions (>3 days) was increased in patients with hypoplastic left heart syndrome (odds ratio, 1.73; 95% confidence limits, 1.07-2.81; P =.03) and was decreased by use of a single-punch fenestration in a lateral-tunnel Fontan operation (odds ratio, 0.17; 95% confidence limits, 0.07-0.4; P <.001), as well as by the use of modified ultrafiltration (odds ratio, 0.25; 95% confidence limits, 0.15-0.40; P <.01). CONCLUSIONS: In a contemporary series of Fontan operations performed largely in patients with hypoplastic left heart syndrome or variants, systemic ventricle morphology had no effect on mortality. Some patient characteristics, however, continue to influence outcome. The decrease in mortality and morbidity in the current era is attributed to changes in management strategies, specifically the use of modified ultrafiltration and baffle fenestration.

Cohort Studies↗
PubMedDate not supplied

Laboratory and therapeutic control in the Thrombosis Centre Rotterdam using chromogenic prothrombin time tests.

Growing interest is observed in chromogenic substrate assays, because of their better precision, performance and possibilities for automation. Applied to a Cobas Bio centrifugal analyzer, we compared Nycotest-Chrom (N-test) and Thromboquant-PT (Tbq) with Thrombotest (TT). Precision tests were performed with samples from 4 plasma pools: normal (45 sec), low (100 sec), middle (150 sec) and high (200 sec) segments of the therapeutic range of TT. N-test had the best precision profile in both intraassay and interassay determinations compared with Tbq. Both chromogenic substrate assays were better than TT in this respect. By orthogonal regression a provisional therapeutic range was calculated from 312 determinations and later adjusted in a confirmation experiment with natural logarithm regression in 946 determinations. Compared with a TT range of 105-180 sec, the therapeutic ranges were 71-120 sec for N-test and 63-103 sec for Tbq. In a clinical therapeutic control phase, 110 patients were randomized in equal proportions to two groups A and B. Every 2 weeks for a period of 16 weeks, blood samples were tested for N-test, Tbq and TT. In group A, dose adjustment was based on N-test, and in group B on Tbq. The monitoring physician was blinded for Tbq and TT in group A and for N-test and TT in group B. No differences were found between the groups for mean TT, N-test, Tbq or mean dosage, nor differences were found in complication rate. A definite therapeutic range was complied using sensitivity/specificity curves together with their 95% confidence limits. Given TT 105-180 sec, the therapeutic range of N-test is from 80 (95% confidence limits: 77-82) to 110 (95% confidence limits: 108-115) sec, and of Tbq from 68 (95% confidence limits: 66-71) to 95 (95% confidence limits: 91-98) sec. It was concluded that the two chromogenic substrate assays performed equally safe in the monitoring of patients on oral anticoagulant therapy, despite differences in diagnostic correspondence with the reference TT.

Administration, Oral↗
PubMed1992

Repair of hypoplastic or interrupted aortic arch via sternotomy.

Herein we describe our experience with repair of interrupted aortic arch and coarctation plus hypoplastic aortic arch in 55 consecutive infants (1984 to 1990). Median age at operation was 6 days and median weight 3.1 kg. Associated severe intracardiac anomalies were the rule. All patients had significant congestive cardiac failure, and the majority required prostaglandin E1 resuscitation and inotropic support (with or without ventilation) before the operation. All operations were performed via sternotomy with core cooling and circulatory arrest. Isolated myocardial perfusion was used in 13 patients during arch repair. A complete intracardiac (biventricular) repair was performed except in patients expected to require a Fontan operation as definitive treatment. The operative mortality overall was 14.5% (confidence limits 10% to 22%). For arch repair plus biventricular intracardiac repair, the operative mortality was 9% (confidence limits 5% to 15%), and for arch repair plus palliative intracardiac repair, 40% (confidence limits 22% to 60%). The mortality in the isolated myocardial perfusion group was 0% (confidence limits 0% to 14%), which may be related to reduced myocardial ischemic time (p less than 0.05). Actuarial survival was 75% (confidence limits 65% to 83%) at 12 months, with no subsequent deaths over 1294 patient-months (mean 28 months) of follow-up. Actuarial freedom from recurrent arch obstruction was 69% (confidence limits 48% to 85%) at 46 months' follow-up. Primary repair of interrupted aortic arch and coarctation plus hypoplastic arch compares favorably with a staged approach and is recommended even when complex intracardiac anatomy is present.

Aorta, Thoracic↗
PubMed1997

Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients.

PURPOSE: To evaluate single photon emission computed tomographic (SPECT) imaging of regional cerebral blood flow in the diagnosis of Alzheimer disease (AD) and the differential diagnosis of the dementias. MATERIALS AND METHODS: Regional cerebral blood flow SPECT was performed with inhaled xenon-133 in 261 patients and with injected technetium-99m hexamethyl-propyleneamine oxime (HMPAO) in 162 patients with possible dementia. In 16 patients, both agents were used in 1 day. SPECT images obtained in elderly healthy control subjects (with Xe-133 in 15, with Tc-99m HMPAO in 14) were available. In each patient without AD, further classification of disease was attempted. Histopathologic correlation was available in 54 patients (with autopsy in 51, with biopsy in three). RESULTS: SPECT diagnoses were true-positive in 37, true-negative in eight, false-positive in three, and false-negative in six patients. Sensitivity was 86% (37 of 43; 95% confidence limits = .72, .95); specificity, 73% (eight of 11; confidence limits = .39, .94); positive predictive value, 92% (37 of 40; confidence limits = .80, .98); and negative predictive value, 57% (eight of 14; confidence limits = .29, .82). CONCLUSION: Regional cerebral blood flow SPECT may assist in the early and late diagnoses of AD and in the differential-diagnosis of the dementias when there is a complicated or confusing clinical picture.

Aged↗
PubMed2002

Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity.

The anticonvulsant effect of cannabinoids has been shown to be mediated through activation of the cannabinoid CB(1) receptor. This study was initiated to evaluate the effects of endogenously occurring cannabinoids (endocannabinoids) on seizure severity and threshold. The anticonvulsant effect of the endocannabinoid, arachidonylethanolamine (anandamide), was evaluated in the maximal electroshock seizure model using male CF-1 mice and was found to be a fully efficacious anticonvulsant (ED(50)=50 mg/kg i.p.). The metabolically stable analog of anandamide, (R)-(20-cyano-16,16-dimetyldocosa-cis-5,8,11,14-tetraenoyl)-1'-hydroxy-2'-propylamine (O-1812), was also determined to be a potent anticonvulsant in the maximal electroshock model (ED(50)=1.5 mg/kg i.p.). Furthermore, pretreatment with the cannabinoid CB(1) receptor specific antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) completely abolished the anticonvulsant effect of anandamide as well as O-1812 (P< or =0.01, Fisher exact test), indicating a cannabinoid CB(1) receptor-mediated anticonvulsant mechanism for both endocannabinoid compounds. Additionally, the influence of cannabinoid CB(1) receptor endogenous tone on maximal seizure threshold was assessed using SR141716A alone. Our data show that SR141716A (10 mg/kg i.p.) significantly reduced maximal seizure threshold (CC(50)=14.27 mA) compared to vehicle-treated animals (CC(50)=17.57 mA) (potency ratio=1.23, lower confidence limit=1.06, upper confidence limit=1.43), indicating the presence of an endogenous cannabinoid tone that modulates seizure activity. These data demonstrate that anandamide and its analog, O-1812, are anticonvulsant in a whole animal model and further implicate the cannabinoid CB(1) receptor as a major endogenous site of seizure modulation.

Animals↗
PubMed2002

Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention.

The aim of the present study was to evaluate the recently defined simple insulin sensitivity check index QUICKI (Katz et al. 2000) for insulin resistance diagnostics in common clinical and epidemiological practice. Both the QUICKI (1/log insulin + log glycemia in mg/dL) and HOMA (insulin * glycemia in micromol/L/22.5) indexes were calculated from fasting values in 259 adult healthy volunteers and patients, and in 47 healthy and obese children of prepubertal age of both sexes. In adults, a fall in the QUICKI index (mean +/- SEM in healthy subjects = 0.366 +/- 0.029) as well as an increase in the HOMA index (in healthy subjects 1.57 +/- 0.87) corresponded to metabolic and clinical manifestations of insulin resistance in various groups of outpatients. The QUICKI index had lower dispersion variances and the 95% confidence limits displayed a higher discrimination capacity. Patients with glucose intolerance or diabetes, hyperlipidemia typical for insulin resistance, or with combination of these metabolic disorders were characterized by QUICKI index values that were significantly lower than those of healthy volunteers. The QUICKI index in healthy prepubertal children indicated a higher insulin resistance compared to adults (mean 0.339 +/- 0.020); an increase in the QUICKI index in obese children with BMI over 25 was not significant, although obese children showed a significant increase of serum leptin and triglycerides and a decrease of HDL-cholesterol. Adult patients with QUICKI index below 0.357 (which is at the lower limit of 95% confidence limits in healthy persons) represented a group with typical manifestations of metabolic syndrome, differing in these parameters significantly from the group of patients of comparable age with a QUICKI index greater than 0.357. The present study suggests suitability of the QUICKI index for diagnosis of insulin resistance in clinical and epidemiological practice. However, a normal QUICKI index range needs to be established for each laboratory with an appropriate control group because of significant interlaboratory variations in insulin determinations and/or possible differences in various populations.

Adult↗
PubMed1994

Unilateral nephrectomy 24 hours after bilateral kidney irradiation reduces damage to the function and structure of the remaining kidney.

The effect of unilateral nephrectomy 24 h after irradiation on renal function and death with renal insufficiency as well as histopathological changes in the kidney was assessed. Single doses totaling 8-18 Gy were given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hematocrit.(Hct). Histological damage was quantified by two parameters: kidney area and number of surviving tubule cells along the renal capsule. The number of glomeruli was scored as an indication of the number of nephrons. Changes in the two functional parameters did not appear sooner after irradiation in the nephrectomized mice than in the non-nephrectomized mice. Rather, less impairment of function was measured by both parameters in the nephrectomized mice but only after radiation doses greater than 12 Gy. The LD50 at 424 days after irradiation was also higher in the nephrectomized mice than that in the mice receiving only irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 11.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreement with the data on function. Unilateral nephrectomy alone induced a 10% increase in size of the contralateral kidney. The dose-response curve for the kidney area from nephrectomized mice was parallel to and displaced above that for non-nephrectomized mice, indicating that the increase in renal mass occurred independent of and was not compromised by radiation. Unilateral nephrectomy alone induced no increase in the number of proximal tubules in the contralateral kidney. However, tubule survival was higher in nephrectomized mice given doses greater than 12 Gy compared with mice receiving only radiation. Fitting the tubule survival data by maximum likelihood analysis gave D0's of 6.7 Gv (95% confidence limits = 6.3, 7.1 Gy) and 3.7 Gy (95% confidence limits = 3.5, 3.8 Gy) for the irradiated nephrectomized mice and irradiated mice, respectively. However, the number of glomeruli was the same for both groups, suggesting that the number of the nephrons did not change. These data suggest that the improvement in renal function in mice nephrectomized 24 h after irradiation of both kidneys compared to those receiving only irradiation was due to tubule hyperplasia and not renal hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.

We investigated the pharmacokinetics of bromocriptine and octreotide, both individually and in combination, in 12 patients with active acromegaly. The pharmacodynamics of the drugs were assessed by 12-h profiles of GH secretion and insulin-like growth factor-I (IGF-I) measurements. During the 42-day study period, bromocriptine was administered for 28 days (from day 8; 5 mg, orally, twice daily) and octreotide (200 micrograms, sc, twice daily) from days 15-42. IGF-I levels, 12-h GH, and plasma bromocriptine and octreotide profiles were obtained on days 0, 14, 28, and 42. During bromocriptine treatment, both the area under the GH day curves (AUC) and mean IGF-I decreased to 64% (95% confidence limits, 43-72% and 48-82%, respectively) of initial values. During octreotide treatment, the respective values were 23% (18-30%) and 32% (21-36%), which were greater decreases than those during bromocriptine treatment [36% (95% confidence limits, 32-54%) for AUC for GH and 50% (95% confidence limits, 34-58%) for IGF-I]. With combined treatment, the AUC for GH was reduced to 16% (12-21%) and that of IGF-I to 25% (16-27%) of initial values. This combination was more effective than bromocriptine [25% (95% confidence limits, 22-37%) for AUC for GH and 39% (95% confidence limits, 25-43%) for IGF-I] and octreotide alone [78% (95% confidence limits, 53-89%) for AUC for GH and 78% (95% confidence limits, 57-98%) for IGF-I]. The pharmacokinetic parameters of octreotide were unchanged by the coadministration of bromocriptine. The bioavailability of bromocriptine increased by approximately 40% when bromocriptine was administered together with octreotide compared with administration alone (P < 0.01). Bromocriptine disposition parameters were unaltered. In conclusion, treatment of acromegalics with a combination of octreotide and bromocriptine increases the bioavailability of bromocriptine and reduces both GH and IGF-I levels more effectively than treatment with either drug alone. This presents the possibility of less frequent drug administrations, lower doses of octreotide, and, consequently, lower treatment costs.

Acromegaly↗
PubMed1990

Estimation of the joint risk for multiple-compound exposure based on single-compound experiments.

In the absence of data from multiple-compound exposure experiments, the health risk from exposure to a mixture of chemical carcinogens is generally based on the results of the individual single-compound experiments. A procedure to obtain an upper confidence limit on the total risk is proposed under the assumption that total risk for the mixture is additive. It is shown that the current practice of simply summing the individual upper-confidence-limit risk estimates as the upper-confidence-limit estimate on the total excess risk of the mixture may overestimate the true upper bound. In general, if the individual upper-confidence-limit risk estimates are on the same order of magnitude, the proposed method gives a smaller upper-confidence-limit risk estimate than the estimate based on summing the individual upper-confidence-limit estimates; the difference increases as the number of carcinogenic components increases.

Animals↗
PubMed1986

Non-Hodgkin's lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment: a case-control study.

A previous case-control study which used the occupational information available on the New Zealand Cancer Registry found that agricultural workers were at increased risk of developing non-Hodgkin's lymphoma. The findings are now presented for the second phase of the study which entailed interviewing 83 cases of non-Hodgkin's lymphoma registered under code 202 of the International Classification of Diseases together with 168 controls with other types of cancer and 228 general population controls. The findings for the two control groups were similar, and there were no significant differences between cases and controls regarding potential exposure to phenoxy-herbicides (odds ratio = 1.4, 90% confidence limits 0.7-2.5, p = 0.26) or chlorophenols (odds ratio = 1.3, 90% confidence limits 0.6-2.7, p = 0.39). The odds ratio for fencing work, necessitating exposure to several potential risk factors including arsenic and sodium pentachlorophenate was 2.0 (90% confidence limits 1.3-3.0, p = 0.01). The odds ratio for employment in a meat works, necessitating potential exposure to 2, 4, 6-trichlorophenol and zoonotic viruses, was 1.8 (90% confidence limits 1.1-3.1, p = 0.04). There was a significant statistical interaction between the risks associated with these two activities, the odds ratio for involvement in both activities compared with involvement in neither being 5.7 (90% confidence limits 2.3-14.3, p = 0.03).

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1990

Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II)

The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled multicenter trial. Eight hundred seventy-eight patients started treatment with verapamil, 360 mg/day, and 897 patients with placebo. Treatment started in the second week after admission and continued for up to 18 months (mean 16 months). Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group. The 18-month mortality rates were 11.1 and 13.8% (p = 0.11, hazard ratio, 0.80; 95% confidence limits, 0.61 to 1.05), and major event rates 18.0 and 21.6% (p = 0.03, hazard ratio, 0.80; 95% confidence limits, 0.64 to 0.99) in the verapamil and placebo groups, respectively. In patients without heart failure in the coronary care unit the mortality rates were 7.7% in the verapamil group and 11.8% in the placebo group (p = 0.02, hazard ratio, 0.64; 95% confidence limits, 0.44 to 0.94), and major event rates 14.6 and 19.7% (p = 0.01, hazard ratio 0.70; 95% confidence limits (0.52 to 0.93). In patients with heart failure the mortality rates were 17.9 and 17.5% (p = 0.79, hazard ratio, 1.05; 95% confidence limits, 0.72 to 1.54), and major event rates 24.9 and 24.9% (p = 1.0, hazard ratio 0.98; 95% confidence limits 0.72 to 1.39). Long-term treatment with verapamil after an acute myocardial infarction caused a significant reduction in major events, and the positive effect was found in patients without heart failure.

Aged↗
PubMed1994

Surgical treatment of aortic coarctation in infants younger than three months: 1985 to 1990. Success of extended end-to-end arch aortoplasty.

There remains controversy regarding the appropriate surgical treatment of coarctation of the aorta in infants. In 1985 we introduced the extended end-to-end repair into our practice and now wish to present a review of our recent experience. One hundred fifty-one infants younger than 3 months of age underwent repair of coarctation between 1985 and 1990. In 25% and 33% of the patients, there was hypoplasia of the isthmus and of the transverse arch, respectively. Surgical procedures were as follows: subclavian flap angioplasty in 15 patients, resection with a traditional end-to-end anastomosis in 43, and resection with an extended end-to-end anastomosis into the arch in 77. In 30 patients, the extension was proximal to the origin of the left carotid artery (radically extended end-to-end anastomosis). Other procedures were used in 16 patients. Mortality (13 early and 12 late deaths) was related on multivariate analysis to the presence of an associated major heart defect, preoperative resuscitation, and direct postoperative gradient over the arch. This immediate postoperative gradient was significantly lower after both extended and radically extended end-to-end anastomosis if there was a hypoplastic isthmus, and after radically extended end-to-end anastomosis if the transverse arch was hypoplastic. Actuarial freedom from recoarctation at 4 years was 57% (confidence limits 28% to 78%) after subclavian flap angioplasty, 77% (confidence limits 60% to 87%) after end-to-end anastomosis, 83% (confidence limits 66% to 92%) after extended end-to-end anastomosis and 96% (confidence limits 77% to 100%) after radically extended end-to-end anastomosis. We conclude that the extended end-to-end anastomosis and radical end-to-end anastomosis appear to offer the best prognosis for all infants with coarctation. The technique can be applied successfully to almost all types of arch anomalies.

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