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New insight into the mechanism of cardiovascular dysfunction in the elderly: transfer function analysis.

This study sought to test the hypothesis that alterations in the relationships between (i) mean arterial pressure (MAP) and heart rate (HR), (ii) cardiac output (CO) and MAP, and (iii) total peripheral resistance (TPR) and MAP variability contribute to the diminished dynamic control of cardiovascular function with advanced age. Six-minute hemodynamic data were continuously recorded in 11 elderly (70 +/- 2 years) and 11 young (26 +/- 1 year) healthy volunteers under supine resting condition and during lower body negative pressure-induced orthostatic challenge. The data were converted using fast Fourier transform, and the ratio of cross-spectra to auto-spectra between two signals (i.e., MAP-HR, CO-MAP, TPR-MAP) was computed for transfer function analysis. In the low-frequency ranges (LF; 0.04-0.14 Hz) and high-frequency ranges (0.15-0.30 Hz), the gain and coherence of the transfer function describing the relationship between MAP-HR signals were significantly greater in younger than in older adults. The phase degree was significantly >0 in both groups under all conditions, suggesting that the MAP variability preceded the HR variability. In contrast, the coherence between CO-MAP signals in both age groups was <0.5, indicating that the beat-to-beat MAP variability was not significantly related to the CO signals. However, the transfer function gain and coherence of TPR-MAP signals were significantly greater in the young group (coherence >/=0.5 in the LF range), suggesting a more effective dynamic vasomotor control. In conclusion, the oscillations in CO-MAP signals are not significantly synchronized or not related in a simply linear fashion in both age groups. The MAP variability is more related to the oscillation of TPR signals in the young group only. Advanced age not only diminishes MAP-HR transfer function gain, but also weakens its coherence. Thus, alterations in the relationship between MAP-HR variability and TPR-MAP variability may significantly contribute to the diminished dynamic control of cardiovascular function manifest in the elderly.

Adult↗

Predicting residue contacts using pragmatic correlated mutations method: reducing the false positives.

BACKGROUND: Predicting residues' contacts using primary amino acid sequence alone is an important task that can guide 3D structure modeling and can verify the quality of the predicted 3D structures. The correlated mutations (CM) method serves as the most promising approach and it has been used to predict amino acids pairs that are distant in the primary sequence but form contacts in the native 3D structure of homologous proteins. RESULTS: Here we report a new implementation of the CM method with an added set of selection rules (filters). The parameters of the algorithm were optimized against fifteen high resolution crystal structures with optimization criterion that maximized the confidentiality of the predictions. The optimization resulted in a true positive ratio (TPR) of 0.08 for the CM without filters and a TPR of 0.14 for the CM with filters. The protocol was further benchmarked against 65 high resolution structures that were not included in the optimization test. The benchmarking resulted in a TPR of 0.07 for the CM without filters and to a TPR of 0.09 for the CM with filters. CONCLUSION: Thus, the inclusion of selection rules resulted to an overall improvement of 30%. In addition, the pair-wise comparison of TPR for each protein without and with filters resulted in an average improvement of 1.7. The methodology was implemented into a web server http://www.ces.clemson.edu/compbio/recon that is freely available to the public. The purpose of this implementation is to provide the 3D structure predictors with a tool that can help with ranking alternative models by satisfying the largest number of predicted contacts, as well as it can provide a confidence score for contacts in cases where structure is known.

Algorithms↗

Effects of norepinephrine infusion on systemic hemodynamics and plasma 6-keto-prostaglandin F1 alpha in normotensive subjects and patients with essential hypertension.

Altered prostacyclin metabolism may underlie essential hypertension. In this study, responses of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha: a stable metabolite of prostacyclin) to infused norepinephrine (NE) were compared in 14 normotensive subjects (NT) and 20 untreated patients with essential hypertension (EH). In addition, changes in systemic hemodynamics following NE-infusion were compared with changes in plasma 6-keto-PGF1 alpha. The subjects were all hospitalized and placed on a diet containing 6-8 g of salt per day. Blood pressure was recorded directly through the brachial artery, cardiac output (CO) was determined with the dye-dilution technique using cuvette and total peripheral vascular resistance (TPR) was calculated before and 60 min after NE-infusion. Arterial plasma 6-keto-PGF1 alpha was also determined before and after NE-infusion. The rate of NE-infusion was adjusted to elevate mean arterial pressure (MAP) by 10-15%. Plasma 6-keto-PGF1 alpha was radioimmunoassayed. Elevation of MAP was 13.0 +/- 1.2 (SE) in NTs and 11.7 +/- 1.4% in EHs. After NE-infusion, CO and TPR both significantly increased in NTs, while only CO increased significantly in EHs. Changes in CO and TPR were both significantly different between the two groups (p less than 0.01). Initial plasma 6-keto-PGF1 alpha was reduced in EHs as compared with NTs (174 +/- 15 vs 295 +/- 41 pg/ml, p less than 0.02). However, during NE-infusion, the increase in plasma 6-keto-PGF1 alpha was greater in EHs than in NTs (p less than 0.01). There was a significant negative correlation between changes in TPR and plasma PG (r = -0.36, p less than 0.05). The results indicate that responses of systemic hemodynamics and plasma 6-keto-PGF1 alpha to infused NE are different in the NT and EH groups, and that the absence of changes in TPR in EHs may be related to a marked increase in circulating prostacyclin. These findings, together with the reduced initial levels of plasma 6-keto-PGF1 alpha in EHs, probably represent altered prostacyclin metabolism in essential hypertension.

6-Ketoprostaglandin F1 alpha↗

Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism. A randomized controlled multicenter trial.

Four centers participated in a double-blind study in which 53 patients with angiographically documented acute massive pulmonary embolism (baseline Miller index > or = 17/34 and mean pulmonary artery pressure > or = 20 mm Hg) were randomly assigned to treatment with either 0.6 mg/kg bolus injection of alteplase over 15 min with a maximum dose of 50 mg (bolus group; n = 36), or 100 mg of alteplase over 2 h (2-h group; n = 17). The primary objective was to compare the rapidity of resolution of pulmonary embolism as judged by the change in total pulmonary resistance (TPR) over the initial first hour. Further objectives were to evaluate the changes in TPR over the next 11 h and the degree of lung scan resolution at 20 to 28 h. At 1 h, TPR decreased by 29 +/- 17 percent in the bolus group and by 36 +/- 16 percent in the 2-h group (mean +/- SD; p = 0.19). Continuous monitoring of TPR revealed that this variable improved in both groups without significant intergroup differences over the 12-h study period, although TPR decreased initially faster in the 2-h group. At 20 to 28 h, the absolute improvements in the lung scan perfusion defect were 14 +/- 12 percent in the bolus group compared with 13 +/- 9 percent in the 2-h group, with no significant intergroup differences. Major bleeding occurred in one patient of the 2-h group (6 percent) and in three patients of the bolus group (8 percent) (p > 0.5). Four patients (three from the bolus group and one from the 2-h group) may have experienced recurrent pulmonary embolism during the hospital stay. Neither death nor intracranial bleeding occurred.

Acute Disease↗

Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2.

The aryl hydrocarbon receptor (AhR) is a ligand-inducible transcription factor that mediates biological responses to halogenated aromatic hydrocarbons. The unliganded AhR is a cytoplasmic, tetrameric complex consisting of the AhR ligand-binding subunit, a dimer of hsp90, and the hepatitis B virus X-associated protein 2 (XAP2). The role of XAP2 as a member of the AhR core complex is poorly understood. XAP2 shares significant homology with the immunophilins FKBP12 and FKBP52, including a highly conserved, C-terminal, tetratricopeptide repeat (TPR) domain. XAP2 forms a complex with hsp90 and the AhR but can also bind to both independently. This binding is mediated by the conserved TPR domain. Single-point mutations in this region are sufficient to disrupt the association of XAP2 with both the AhR and hsp90 in cells. Cotransfection of the AhR and XAP2 in COS-1 cells results in increased AhR levels compared with cells transfected with the AhR alone. In contrast, coexpression of the AhR with the TPR containing proteins FKBP52, protein phosphatase 5 (PP5), or XAP2 TPR-mutants deficient in binding to the AhR and hsp90 does not affect AhR levels and coexpression of the AhR with the TPR domain of PP5 results in AhR down-regulation. These results demonstrate that XAP2 is apparently unique among hsp90-binding proteins in its ability to enhance AhR levels. A yellow fluorescent protein (YFP)-XAP2-FLAG was constructed and biochemically characterized, and no loss of function was detected. YFP-XAP2-FLAG was transiently transfected into NIH 3T3 and was found to localize in both the nucleus and the cytoplasm when visualized by fluorescence microscopy. Treatment of Hepa-1 cells with the hsp90-binding benzoquinone ansamycin, geldanamycin, and the macrocyclic antifungal compound radicicol resulted in AhR but not XAP2 or FKBP52 turnover. Taken together, these results suggest that XAP2/hsp90 and FKBP52/hsp90 complexes are similar yet exhibit unique functional specificity.

Amino Acid Motifs↗

Screening tests for urinary tract infection in children: A meta-analysis.

OBJECTIVE: To review systematically and to summarize the existing literature regarding performance of rapid diagnostic tests for urinary tract infection (UTI) in children. DESIGN: Systematic review and meta-analysis. METHODS: Published articles reporting the performance of urine dipstick tests (leukocyte esterase [LE] and/or nitrite), Gram stain, or microscopic analysis of spun or unspun urine in the diagnosis of UTI in children </=12 years of age. Articles were identified through a comprehensive MEDLINE search, and those articles meeting a priori inclusion criteria were selected. Eligibility criteria included the use of urine culture as the reference standard, independent comparison of urine culture with the results of one of the screening tests, definition of positive screening test results provided, only pediatric patients included or evaluable separately, and both gold standard and screening test performed on all patients. For each test, heterogeneity of reported sensitivity and specificity of all studies was determined. The subgroups of studies with similar definitions of UTI and age of study subjects were analyzed separately to account for some of the differences in reported results. When significant unexplained heterogeneity among studies precluded simple combining of results, a summary receiver-operator characteristic curve was fitted for each screening test, from which pooled estimates of true-positive rate (TPR; ie, sensitivity) and false-positive rate (FPR; 1-specificity) were calculated. PRIMARY RESULTS: A total of 1489 titles were identified by the MEDLINE search; 26 articles met all criteria for inclusion. There was significant heterogeneity among studies for nearly all tests for both TPR and FPR, which was explained only partially by the stringency of the definition of UTI or age of subjects studied. Based on the pooled estimates, the presence of any bacteria on Gram stain on an uncentrifuged urine specimen had the best combination of sensitivity (0.93) and FPR (0.05). Urine dipstick tests performed nearly as well, with a sensitivity of 0.88 for the the presence of either LE or nitrite and an FPR of 0.04 for the presence of both LE and nitrite. Pyuria had lower TPR and higher FPR: for presence of >5 white blood cells/high-power field in a centrifuged urine sample, the TPR was 0.67 and the FPR was 0.21, whereas for >10 white blood cells per mm(3) in uncentrifuged urine, the TPR was 0.77 and the FPR was 0.11. CONCLUSIONS: Both Gram stain and dipstick analysis for nitrite and LE perform similarly in detecting UTI in children and are superior to microscopic analysis for pyuria.

Bacteriuria↗

Systemic and regional haemodynamic effects of 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT, in the anaesthetised rat.

The present experiment was performed to investigate the haemodynamic effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) in the anaesthetised normotensive rat. DOI (1-300 micrograms/kg i.v.) increased mean arterial pressure (MAP), total peripheral resistance (TPR) and decreased cardiac output (CO) and heart rate (HR). DOI increased all vascular resistances investigated (hindquarters, mesenteric and renal). Alpha-methyl-5-HT (10-300 micrograms/kg i.v.) dose-dependently increased MAP, TPR, all regional vascular resistances and decreased CO and HR. The bradycardia induced by alpha-methyl-5-HT was suppressed by bivagotomy. Both DOI and alpha-methyl-5-HT were more effective on renal vascular bed than hindquarters and mesenteric vascular beds. The effects of DOI and alpha-methyl-5-HT were antagonised by spiperone (10 or 100 micrograms/kg i.v.) and LY 53857 (10 micrograms/kg i.v.). Intracerebroventricular administration of DOI (100 micrograms/kg) increased MAP, TPR, regional vascular resistances and did not change HR and CO. Pretreatment with xylamidine (10 micrograms/kg i.v.), a selective peripheral 5-HT2 receptor antagonist, blocked i.v. and i.c.v. effects of DOI. These results suggest that: 1) the increase in MAP induced by DOI and alpha-methyl-5-HT is due to an increase in TPR. All regional vascular beds and in particular the renal vascular bed participate in the increase of TPR. 2) Peripheral--and may be--central 5-HT2 receptors seem to be implicated in the control of regional vascular resistances. 3) Cardiac effects of alpha-methyl-5-HT are baroreflexly-mediated whereas those of DOI are--at least in part--centrally mediated.

Amphetamines↗

Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients.

AIM AND BACKGROUND: Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia. PATIENTS AND METHODS: Eleven RTRs whose serum phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively, were included in this study. None of the patients received drugs altering phosphate metabolism and they did not change their routine diets. Urinary phosphate excretion and tubular phosphate reabsorption (TPR) were calculated before and 3 weeks after dipyridamole treatment. RESULTS: The mean levels of serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 +/- 0.46 mg/dl, 7,187.5 +/- 1,833.49 mg/day and -2.78 +/- 0.62, respectively. After treatment, the mean levels of serum-urine phosphate and TPR were 2.73 +/- 0.46 mg/dl, 4,845.27 +/- 1,138.99 mg/day and -1.48 +/- 0.80, respectively. Serum and urine phosphate levels and TPR were found to be significantly different before and after dipyridamole therapy (p < 0.05). CONCLUSION: Short-term dipyridamole therapy increased TPR and serum phosphate levels and decreased urinary phosphate excretion. We did not observe negative effect on renal functions in these cases. Although the number of the cases included in this study is small, dipyridamole is an effective choice in management of hypophosphatemic RTRs.

Administration, Oral↗

Cardiac and peripheral vascular responses to head-up tilt during whole body thermal stress.

During acute orthostatic stress, neurally mediated control of cardiac output (CO) and total peripheral vascular resistance (TPR) play an important role in the maintenance of systemic blood pressure. To examine the influence of thermal stress on the CO and TPR responses to orthostatic stress, 10 healthy male volunteers were exposed to normothermic control conditions followed by whole-body thermal stress produced by a cold or hot water-perfused suit during 5 min-70 degrees head-up tilt (HUT). HUT increased mean arterial pressure (MAP) by 3% of the pre-tilt value during normothermic control and cooling, whereas it decreased MAP by 4% of the pre-tilt value during heating. HUT decreased CO by 16-17% of the pre-tilt value under each thermal condition. The increase of TPR during HUT was exaggerated during cooling and inhibited during heating compared to normothermic control. Tilt-induced decrease of skin blood flow was greater during heating than cooling. These results suggest that the smaller increase of TPR rather than the CO change is responsible for the decreased MAP during acute orthostatic stress in hyperthermic humans. The contribution of skin vascular constriction to TPR changes during HUT is increased during heating and decreased during cooling.

Adult↗

Acute hemodynamic effects of ethanol in conscious spontaneously hypertensive and normotensive rats.

This study investigated the differential hemodynamic effects of small to high doses of ethanol in conscious age-matched spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Changes evoked by ethanol (0.25, 0.5, or 1 g/kg, i.v.) or equal volume of saline in mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were followed for 90 min in the two rat strains. The baseline MAP (163 +/- 4 vs. 113 +/- 2 mm Hg) of SHRs was significantly (p < 0.05) higher, compared with WKYs due mainly to the presence of an elevated TPR 13.82 +/- 0.12 vs. 2.51 +/- 0.09 mm Hg/ml/min/100 g, p < 0.05) in SHRs. In both rat strains, all doses of ethanol produced immediate increases in MAP at 1 min, after which the MAP responses varied and depended on the rat strain and dose of ethanol used. In WKYs, 0.25 g/kg ethanol had no effect on MAP, but caused significant decreases in CO and SV and increased HR. Ethanol (0.5 and 1 g/kg) produced a short-lived (10 min) and dose-related increase in MAP. The higher dose (1 g/kg) of ethanol elicited significant (p < 0.05) increases in TPR that were counterbalanced by concomitant decreases in CO and SV. In SHRs, the two higher doses (0.5 and 1 g/kg) of ethanol elicited significant (p < 0.05) decreases and increases in MAP, respectively, compared with control (saline-treated) values. The pressor response to the 1 g/kg dose of ethanol was associated with an increase in TPR that achieved a statistical significance (p < 0.05) at 50 and 80 min after ethanol administration. HR was significantly (p < 0.05) reduced by the two higher doses of ethanol, whereas SV and CO were not changed. Blood ethanol concentrations measured 10, 30, and 60 min after ethanol administration were similar in SHRs and WKYs. These findings suggest that acute administration of ethanol to conscious rats elicits hemodynamic responses that are strain- and dose-dependent. In contrast to a short-lived and dose-related pressor response in WKYs, ethanol (0.5 and 1 g/kg) elicited opposite and longer lasting effects on MAP (decreases and increases, respectively) in SHRs. In both rat strains, the pressor response to the higher dose of ethanol was associated with an increase in TPR; an effect that was compromised by a concomitant decrease in CO in WKYs but not SHRs.

Animals↗

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats.

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

Animals↗

The effect of the teaching physician rule on residency education.

BACKGROUND AND OBJECTIVES: In 1996, the Health Care Finance Administration implemented the Teaching Physician Rule (TPR) to clarify the responsibilities of attending physicians when they are supervising residents and billing Medicare for that service. We measured some of the effects of the TPR on family practice residency training. METHODS: After pilot testing, a questionnaire was mailed to the directors of all family practice residency programs in the United States. The directors were asked to provide a similar questionnaire to a senior resident. RESULTS: Of 449 residency directors, 310 (69%) responded. Eighty percent of residencies apply the TPR to at least some patient encounters. Residency directors reported that the TPR had an overall negative effect on their residency. Residents reported a more negative impression of the rule than did the directors. On average, residency directors reported that the mandated level of supervision in the outpatient setting increased faculty attending time by .24 FTE. CONCLUSIONS: The TPR was perceived by residency directors and senior residents to have some negative effect on family practice residency programs, at least in part by increasing the need for more faculty time for supervision.

Family Practice↗

Impairment of cardiovascular and vasomotor responses during tilt table simulation of "push-pull' maneuvers.

BACKGROUND: Numerous studies have shown that tolerance to positive acceleration (+Gz) is impaired subsequent to an exposure of less than +1 Gz. HYPOTHESIS: Vasodilation induced by antecedent negative Gz (-Gz) exposure delays sympathetic vasoconstriction during subsequent +Gz, further reducing G-tolerance. METHODS: There were 20 subjects tested on an electronic tilt table, and exposed to the following randomized head-up tilt (HUT) and head-down tilt (HDT) conditions: +75 degrees HUT for 60 s, followed by transition to either 0 degrees (supine) HDT, or -25 degrees HDT, or -45 degrees HDT for 7 or 15 s at tilt rate of 45 degrees x s(-1). This was followed by HUT, divided into three periods: HUT1 (approximately 3-10 s), HUT2 (approximately 15-22 s), and HUT3 (approximately 27-35 s). Systolic blood pressure (SBP) was normalized to heart and head-levels. Stroke volume (SV) was estimated using impedance cardiography; forearm blood flow (FBF) estimated by venous occlusion plethysmography and forearm vascular resistance (FVR) was calculated from FBF and SBP. Total peripheral resistance (TPR) was estimated by MAP/(SV*HR). RESULTS: Heart-level SBP decreased significantly during HDT for both HDT durations (p < 0.01). SBP increased significantly at head-level during HDT (p < 0.001). During HUT1 heart and head-level SBP decreased for all conditions (p < 0.001), recovering to baseline levels by HUT2. TPR decreased significantly for all HDT conditions (p < 0.001), with this decrease related to the degree of HDT angle (p < 0.05). During HUT1, TPR remained depressed below baseline. At HUT2, TPR remained decreased for the -45 degrees/7-s condition only (p < 0.01). FBF decreased significantly during HDT (p < 0.02), with the magnitude related to the HDT angle. FBF remained elevated during HUT1 (p < 0.01). FVR decreased as a function of HDT angle during HDT (p < 0.001), with the decrease persisting into the HUT1 phase (p < 0.01). By the HUT2 and HUT3 periods, FVR were above baseline levels for the -45 degrees HDT condition (p < 0.01). CONCLUSION: These results confirm in humans the delayed recovery of peripheral vascular resistance observed in animal studies when -Gz precedes +Gz. Since SV recovered to baseline levels during the "pull" phase (HUT1-3), with TPR and forearm vascular resistance remaining depressed, baroreflex-mediated peripheral vascular control is delayed. This delay at higher subsequent +Gz levels is dangerous for the military pilot, since symptoms of G-intolerance due to delay in head-level BP recovery will ensue at lower absolute +Gz levels during push-pull type maneuvers.

Acceleration↗

Do we need all three criteria for the diagnostic separation of pleural fluid into transudates and exudates? An appraisal of the traditional criteria.

BACKGROUND: Classification of pleural effusions into transudates and exudates is based on pleural fluid absolute lactic dehydrogenase value (FLDH), fluid to serum ratio of LDH (LDHR) and fluid to serum ratio of total protein (TPR) used in a parallel combination strategy. Combining multiple tests in a parallel strategy to improve diagnostic accuracy is useful only if the pair-wise correlation of the individual tests is less than 0.75. So far, this concept has not been tested in patients with pleural effusions. MATERIAL/METHODS: Biochemical data from our 200-patient series with a known cause of pleural effusion were included in this study. Correlation between the three possible combinations of tests was determined. RESULTS: There were 116 males and 84 females. The mean age was 62+/-1.1 years (mean+/-SEM). Of the 200 effusions, 156 were exudates and 44 were transudates. There was a significant correlation between FLDH and LDHR (r=0.93, p<0.00). However, the correlation between FLDH and TPR (r=0.27) and TPR and LDHR (r=0.22) was not significant. CONCLUSIONS: The operative mechanism for LDHR and FLDH used in the classification of transudate and exudates appears to be similar, and therefore unsuitable for a parallel combination strategy in the diagnostic separation of pleural effusion. FLDH and TPR have a dissimilar operating mechanism, and can therefore be combined in this process. Therefore, the diagnostic separation of pleural effusion can be done cost effectively by utilizing FLDH and TPR alone, as the cost for estimating serum LDH is eliminated in this approach.

Aged↗

Circadian relations among cardiovascular variables of young adults.

Every 4 hours for 24 hours, 14 clinically healthy young individuals (6 women and 8 men), 26 +/- 4 years of age, measured systolic (S) and diastolic (D) blood pressure (BP) by sphygmomanometer and heart rate by ECG and did impedance cardiography under usual living conditions. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated. Time series of SBP, DBP, HR, SV, CO and TPR were analyzed by single and population-mean cosinor. A circadian cardiovascular rhythm is demonstrated by rejection of the zero amplitude assumption in the population-mean cosinor test for SBP, DBP, HR, SV, CO and TPR (P < 0.01). TPR peaks around 0400 (-61 degrees from local midnight), in antiphase with all other variables, their acrophase occurring around 1600 (-240 degrees). A circadian rhythm of statistical significance or of borderline statistical significance is found for all variables except TPR in women. Circadian rhythm characteristics were otherwise mostly similar in men and women with a statistically significant gender difference found by parameter tests only for the MESOR and amplitude of SBP.

Adult↗

[Cardiovascular hemodynamics in patients with essential hypertension during multi-stage exercise].

We investigated cardiovascular hemodynamics in patients with essential hypertension at rest and during exercise. Eight patients with borderline hypertension (Group B), 18 patients with sustained hypertension, and 10 normotensive subjects (Group N) were studied. Patients with sustained hypertension were categorized in two groups; 10 patients without cardiac hypertrophy (Group NH), and eight patients with cardiac hypertrophy (Group HH). To assess the cardiovascular hemodynamics, M-mode echocardiograms, electrocardiograms and carotid pulses were recorded during multistage exercise using a supine bicycle ergometer. Blood pressure was measured simultaneously by the cuff method. At rest, isovolumic relaxation times (IRT) in Groups NH and HH were significantly prolonged as compared with that of Group N. The IRT of Group HH was significantly prolonged as compared with that of Group NH (Group N: 0.06 +/- 0.01 sec, Group B: 0.07 +/- 0.01 sec, Group NH: 0.08 +/- 0.02 sec, Group HH: 0.09 +/- 0.01 sec, respectively). Only the atrial filling fraction of Group HH was significantly increased over that of Group N (Group N: 25.6 +/- 12.1%, Group B; 30.0 +/- 8.1%, Group NH: 27.9 +/- 11.3%, and Group HH: 41.4 +/- 13.1%, respectively). The total peripheral vascular resistance (TPR) in Groups NH and HH was significantly increased over that of Group N (Group N: 1600 +/- 224 dyne/sec/cm-5, Group B: 1704 +/- 465 dyne/sec/cm-5, Group NH: 2370 +/- 608 dyne/sec/cm-5, and Group HH: 3290 +/- 1598 dyne/sec/cm-5, respectively). There was no significant difference in the cardiac index, ejection fraction or heart rate among all groups at rest and during exercise. However, the difference between TPR at rest and TPR at a load of 75 watt (delta TPR) was increased in Groups NH and Group HH over Group N (Group N: 558 +/- 166 dyne/sec/cm-5, Group B: 614 +/- 336 dyne/sec/cm-5, Group NH: 883 +/- 415 dyne/sec/cm-5, and Group HH: 1306 +/- 774 dyne/sec/cm-5, respectively). From these findings, we concluded that there is early diastolic left ventricular dysfunction in Groups NH and HH, and that the degree is more distinct in Group HH. It seems that systolic left ventricular function of both groups is normal during moderate exercise loads, and marked reduction of the TPR in both groups during exercise may be caused by marked peripheral vascular dilatation.

Adult↗

[The effect on barbiturates on hemodynamics during extracorporeal circulation: thiopental versus methohexital].

We studied the effects of thiopentone (3 vs 6 mg/kg) and methohexitone (1 vs 2 mg/kg) on TPR during hypertensive episodes (m BP greater than 80 mmHg) under the conditions of ECC and hypothermia: T led to an initial shortlasting increase of TPR up to 114% and 125% from baseline for the dosages tested. This was followed by a decrease to 67% and 56% respectively. After 5 min TPR returned to control. The effect of M on TPR is less pronounced (maximum reduction of 35%) but of longer duration. In contrast to thiopentone we did not observe a biphasic course of TPR following administration of methohexitone.

Anesthesia↗

Short-term therapy of severe hypertension. Hemodynamic correlates of the antihypertensive response in man.

Ten severely hypertensive patients were randomized into five treatment groups: vasodilators; vasodilators plus diuretics; sympatholytics; sympatholytics plus diuretics; and sympatholytics, diuretics, and vasodialtors. Cardiac index was measured daily by echocardiography, and total peripheral resistance (TPR) calculated. Plasma renin activity (PRA) and creatinine clearance (CCR) were measured every other day. There was no difference in antihypertensive response. Seven patients, whose initial TPR was high, responded to treatment with a fall in TPR, regardless of regimen. Three patients with a high pretreatment cardiac index responded with a fall in cardiac index. Changes in TPR or cardiac index were not related to changes in CCR. There was no correlation between PRA and either blood pressure or TPR. It is concluded that the pretreatment hemodynamic status of severely hypertensive patients is the major determinant of the hemodynamic response to antihypertensive therapy.

Adolescent↗