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PubMed1998

Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome.

IKs channels are voltage dependent and K+ selective. They influence cardiac action potential duration through their contribution to myocyte repolarization. Assembled from minK and KvLQT1 subunits, IKs channels are notable for a heteromeric ion conduction pathway in which both subunit types contribute to pore formation. This study was undertaken to assess the effects of minK on pore function. We first characterized the properties of wild-type human IKs channels and channels formed only of KvLQT1 subunits. Channels were expressed in Xenopus laevis oocytes or Chinese hamster ovary cells and currents recorded in excised membrane patches or whole-cell mode. Unitary conductance estimates were dependent on bandwidth due to rapid channel "flicker." At 25 kHz in symmetrical 100-mM KCl, the single-channel conductance of IKs channels was approximately 16 pS (corresponding to approximately 0.8 pA at 50 mV) as judged by noise-variance analysis; this was fourfold greater than the estimated conductance of homomeric KvLQT1 channels. Mutant IKs channels formed with D76N and S74L minK subunits are associated with long QT syndrome. When compared with wild type, mutant channels showed lower unitary currents and diminished open probabilities with only minor changes in ion permeabilities. Apparently, the mutations altered single-channel currents at a site in the pore distinct from the ion selectivity apparatus. Patients carrying these mutant minK genes are expected to manifest decreased K+ flux through IKs channels due to lowered single-channel conductance and altered gating.

Animals↗
PubMed2006

Risk of collateral damage to endourologic tools by holmium:YAG laser energy.

BACKGROUND AND PURPOSE: Today, the holmium:YAG laser is the gold standard in endourologic stone treatment because of its high efficacy. However, guidewires and stone-extraction tools often are close to the fiber and may be damaged accidentally by the laser. The aim of our study was to evaluate the duration of laser application required to disrupt wires at different energy settings. MATERIALS AND METHODS: Two standard wires (0.035-inch guidewire and 0.025-inch hydrophilic Terumo wire) and two baskets (1.9F Nitinol tipless and 3F stone extraction) were investigated. We used a holmium:YAG laser (Auriga; Wavelight Laser Technologie AG, Erlangen, Germany) and two fibers (230 and 365 microm) at 800 and 2000 mJ and a 5-Hz pulse rate. The laser was brought into direct contact with the wires. RESULTS: The average time required for transection was 55 to 103 seconds for a safety wire. The Terumo wire broke after 20 to 40 seconds of direct laser application; 15 to 34 seconds was required for a Dormia basket. Thin Nitinol basket wires were disrupted after only 1 to 4 seconds. One- and two-factorial variance analysis showed a high degree of significance (P < 0.0001) of the energy level and type of wire. CONCLUSION: The disruption of stone-extraction tools occurs in a remarkably short time with laser exposure, especially in case of Nitinol baskets, whereas guidewires are more resistant. Attention should be paid to avoiding contact of laser energy with wires and baskets during stone fragmentation.

Aluminum↗
PubMed2005

Importance of the intraoperative identification of the external branch of the superior laryngeal nerve during thyroidectomy: electromyographic evaluation.

OBJECTIVE: To establish the frequency and degree of postthyroidectomy injury of the external branch of the superior laryngeal nerve (EBSLN) by means of electromyography and to assess whether intraoperative identification of the nerve and the presence of malignancy influence morbidity. PATIENTS AND METHODS: Prospective, randomized, blind study. Comparison of 100 superior thyroid poles subjected to surgery because of benign and malignant disease, divided in three groups: G1, thyroidectomies, without searching for the EBSLN; G2, thyroidectomies, searching for the EBSLN; G3, Control, lobes, contralateral to the lobectomy, not surgically manipulated. The electromyographic function of the EBSLN was assessed in all cases, classifying the degree of injury and clinically assessing its function. Central tendency measures were used, as well as X (2) and multiple variance analysis. RESULTS: In G1, with 50 dissections of the superior pole, 25 injuries were found in 15 patients (10 bilateral and 5 unilateral). In G2, EBSLN injury was found after 13 explorations of the superior pole in 8 patients (5 bilateral and 3 unilateral). G3 patients did not present EBSLN injury. X (2) among groups and degree of injury revealed that intraoperative identification of the EBSLN decreases its injury. No evidence were found that injury frequency is increased by the presence of thyroid malignancy, extracapsular infiltration, or size of tumor. Clinical manifestations of hoarseness were present in 14% of G1 patients and 8% of G2 patients. DISCUSSION: The rate of EBSLN injury increased when not exploring and/or identifying it expressly. The presence of cancer, extracapsular extension, or size of the thyroid tumor exerted no influence on the frequency of injury; localization of the nerve was the only factor affecting injury. Hoarseness correlated with the degree of injury. CONCLUSION: EBSLN must be localized expressly to decrease the risk of injury.

Adolescent↗
PubMed2006

Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients.

INTRODUCTION: Angiogenesis has been correlated with increased invasion and metastases in a variety of human neoplasms. Inadequate inhibition of the growth of tumor microvessels by anticancer agents may result in treatment failure, rated clinically as progressive or stable disease. We designed this trial to investigate the modification of the vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-gamma) in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan. MATERIALS AND METHODS: Forty-five metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF and IFN-gamma during the treatment with cetuximab (initial dose of 400 mg/m(2), followed by weekly infusions of 250 mg/m(2)) plus weekly irinotecan (90 mg/m(2)). The circulating levels of the cytokines were assessed at the following time points: just before and at 1, 21, 50 and 92 days after the start of cetuximab plus irinotecan treatment. RESULTS: Basal serum VEGF median levels were significantly decreased just at the first day (after the first treatment infusion (P = 0.016). The VEGF persisted at the following time points reaching the highest statistical significance 92 days after the first infusion (P < 0.0001). On the contrary, IFN-gamma values showed a statistical significant increase one day after the first infusion (P < 0.0001). This effect persisted 21 days after the treatment start (P = 0.001), but was no more evident at the following time points. Moreover, a linear regression model with variance analysis showed a significant negative correlation between VEGF and IFN-gamma values 1, 21 and 50 days after the treatment beginning (P = 0.002, 0.001 and 0.047, respectively). CONCLUSIONS: This study suggests that a cetuximab may induce a modulation of VEGF circulating levels. The reduction of VEGF serum levels is a sudden and long lasting phenomenon. Moreover, in our study we identified a IFN-gamma increase, even if the specific role of this behavior remains to be investigated.

Adult↗
PubMed1986

An indirect approach for the study of the elastic modulus of the brachial artery in patients with essential hypertension.

An indirect approach for the study of the changes in the incremental circumferential modulus (E) of the brachial artery after arteriolar vasodilatation was undertaken in patients with sustained essential hypertension. The product of E and the thickness (h) of the arterial wall was evaluated by means of the Moens-Korteweg equation using determinations of brachioradial pulse wave velocity and brachial artery diameter with pulsed Doppler methods. In three homogeneous groups of patients with hypertension the Eh product was studied after vasodilatation caused either by nitrendipine, a calcium entry blocking agent, or by medroxalol, an alpha and beta blocking agent, or by isosorbid dinitrate. The three drugs caused similar reductions in blood pressure and increases in arterial diameter and hence decreases in wall thickness. Variance analysis for multigroups indicated that the decrease in Eh after vasodilatation was significant for nitrendipine but not for medroxalol and isosorbid dinitrate. Covariance analysis showed that for any level in Eh product the decrease in Eh was higher for nitrendipine than for isosorbid dinitrate and medroxalol. Since the three drugs had comparable mechanical and geometrical effects, the study provided evidence that, in men with essential hypertension, the smooth muscle tone of the brachial artery was significantly more sensitive to calcium inhibition than to autonomic blockade, causing a more important decrease in elastic modulus.

Adult↗
PubMed1988

Cooling down unstable angina with high dosage of isosorbide dinitrate (ISDN) continuously infused.

The aim of this study was to explore the capability of isosorbide dinitrate (ISDN) infusion to quench the 'hot phase' of unstable angina, a real cardiological emergency. Fifteen patients consecutively admitted to CCU because of angina at rest, with at least 4 ischaemic attacks per day, resistant to the usual therapy with oral and/or topical nitrates and calcium-antagonists, were included in the study. During ischaemia the electrocardiogram showed ST-segment elevation in 7 patients, ST-segment depression in 4, an alternation of ST-segment elevation and depression in 3 and pseudonormalization of a basally negative T wave in 1 patient. History of exertional angina with variable degrees of effort was reported in 6 patients and 9 had an old myocardial infarction. Coronary arteriography performed in 10 patients showed a significant stenosis of 1, 2 and 3 vessels in 5, 2 and 3 patients, respectively. ISDN infusion was started at 1.0 mg h-1, and was increased stepwise when persistence of ischaemic episodes had to be faced. The mean dosage infused was 3.5 mg h-1 (range 1.00-12). The mean duration of intravenous therapy was 8.3 days (range 2-25). Eleven of the 15 patients (73%) showed an effective decrease in the number of ischaemic episodes during ISDN infusion, as assessed by regression and variance analysis. After discharge (mean follow-up 59 months, range 2-96), 7 patients were free from ischaemic attacks, 3 underwent coronary by-pass surgery, 2 complained of some attacks and 3 died (2 because of sudden death three years after this study). In conclusion, ISDN infusion--individually tailored for dosage and duration--can be effective in 'cooling down' the storm of ischaemic episodes in unstable angina. An effective intravenous therapy with nitrates can represent, in some patients, a temporal remedy on the way to elective coronary bypass surgery and/or towards elective PTCA. Furthermore, in a sizeable number of patients with unstable angina, this approach can attain a complete abolishment of the ischaemic attacks.

Adult↗
PubMed1996

Computation of the full likelihood function for estimating variance at a quantitative trait locus.

The proportion of alleles identical by descent (IBD) determines the genetic covariance between relatives, and thus is crucial in estimating genetic variances of quantitative trait loci (QTL). However, IBD proportions at QTL are unobservable and must be inferred from marker information. The conventional method of QTL variance analysis maximizes the likelihood function by replacing the missing IBDs by their conditional expectations (the expectation method), while in fact the full likelihood function should take into account the conditional distribution of IBDs (the distribution method). The distribution method for families of more than two sibs has not been obvious because there are n(n - 1)/2 IBD variables in a family of size n, forming an n x n symmetrical matrix. In this paper, I use four binary variables, where each indicates the event that an allele from one of the four grandparents has passed to the individual. The IBD proportion between any two sibs is then expressed as a function of the indicators. Subsequently, the joint distribution of the IBD matrix is derived from the distribution of the indicator variables. Given the joint distribution of the unknown IBDs, a method to compute the full likelihood function is developed for families of arbitrary sizes.

Alleles↗
PubMed1993

Identification and measurement of productive behaviors in senile dementia of the Alzheimer type.

Caregivers of 106 individuals with senile dementia of the Alzheimer type (SDAT) were administered the Functional Behavior Profile (FBP) as part of a caregiver assessment battery. Three factors--task performance, problem solving, and social interaction--accounted for 70.6% of the variance. Analysis yielded a reliable and valid assessment that documents the observable productive behaviors of a person with SDAT. Significant differences across the stages of the disease were observed. The FBP can serve as a guide for individualized caregiving strategies by helping the caregiver focus on the presence of productive behaviors useful in managing the impaired person.

Aged↗
PubMed1996

Potential cardioembolic sources of stroke in patients less than 60 years of age.

Minor potential cardioembolic sources of stroke such as atrial septal aneurysm or patent foramen ovale are important risk factors for cryptogenic stroke. We aimed to determine the prevalence of these abnormalities through an exhaustive aetiological work-up. One hundred and eighteen stroke patients under 60 years of age, who had no evidence of a significant cardiac source of embolism, were classified into four groups following transoesophageal echocardiography and assessment of cervical arteries. Group A comprised 30 patients (25.4%) who had an arteriopathy, probably related to stroke without any cardiac abnormality; group B, had only a potential cardiac source; group C, nine (7.6%) had an obvious arterial source of stroke and incidental cardiac abnormalities; group D, 30 (25.4%) had neither cardiac or arterial source. Data were analysed with the Chi-square test to compare risk factors between groups, and variance analysis was used to compare age between groups. Significance was assessed as P < 0.05. Fisher's exact test was used to test the association between arterial septal aneurysm and patient foramen ovale. In groups B and D atrial septal aneurysm represented 56.8% of the cardiac abnormalities and was diagnosed in 35.4% of the 79 patients who had an unexplained stroke, and a patent foramen ovale was found in 34.1% of the patients. According to Fisher's exact test, atrial septal aneurysm was significantly associated with patent foramen ovale (P < < 0.001). On this basis, one fourth of the patients might be said to have had a truly cryptogenic stroke as the aetiological work-up failed to demonstrate any source of stroke. Comparison between groups showed that in 23% of the patients in whom an arterial source was detected, there was also a potential cardioembolic source (group C), vs 62% in patients who had no arterial source (groups B and D) (P = 0.0007). Our study confirmed the strong association between atrial septal aneurysm, patent foramen ovale and stroke. Although there was a lower incidence of cardiac risk factors for stroke in patients who had cervical artery disease, we suggest that all patients who have a stroke without evidence of a major cardiac source should undergo transoesophageal echocardiography, in order to ensure a better prevention.

Adult↗
PubMed1995

Comparative biomechanical stability of titanium bone fixation systems in metacarpal fractures.

The biomechanical properties of apex bending and torsional rigidity of 11 different titanium mini- and microplates (Leibinger and Synthes) were examined to evaluate the effects of plate design and thickness and screw size and design. Two hundred sixteen fresh-frozen human cadaveric metacarpal bones underwent a midshaft transverse osteotomy followed by application of one of the following plates: Synthes 1.5-mm and 2.0-mm five-hole linear plates; Leibinger linear 1.2-mm 5-hole, 1.7-mm 4-hole, 2.3-mm 4-hole plates; or Leibinger three-dimensional 1.2-mm 4-hole, 1.2-mm 8-hole, 1.7-mm 4-hole, 1.7-mm 8-hole, 2.3-mm 4-hole, and 2.3-mm 8-hole plates. The specimens were subjected to a three-point bending test with apex dorsal or apex volar loading or torsional loading. Analysis of variance statistical analysis revealed that increasing plate thickness and, more significantly, three-dimensional design were associated with increased rigidity.

Biomechanical Phenomena↗
PubMed1996

Biomechanical testing of titanium self-tapping versus pretapped lag screw fixation of spiral metacarpal fractures.

Biomechanical tests of torsional loading and cantilevered bending were used to study the effects of varying screw size design of five different titanium miniscrews and microscrews in a metacarpal spiral oblique fracture model. Sixty-six fresh frozen human cadaveric metacarpal bones were subjected to torsional loading until failure, producing a spiral oblique fracture. The randomized fractured metacarpal bones were then repaired utilizing two 1.2-mm, 1.7-mm, or 2.3-mm self-tapping Leibinger lag screws; and 1.5-mm or 2.0-mm pretapped Synthes lag screws. Following repair, the specimens were then subjected to cantilevered bending or torsional loading. Failure torque and bending loads were then used to calculate failure stresses at the midshaft for torsional loading or at the proximal screw for cantilevered bending. Analysis of variance statistical analysis revealed that within the cortical thickness of bone studied, no significant difference in shear stress or axial stress was observed with increasing screw diameter and screw design.

Biomechanical Phenomena↗
PubMed1991

High density cAMP-gated channels at the ciliary membrane in the olfactory receptor cell.

Spatial distribution of the cAMP-gated channel was investigated in amphibian olfactory receptor cells. Low doses of cAMP applied to the cytoplasmic side of a membrane patch excised from cilia produced single channel activity of unitary conductance 28pS. Variance analysis showed that the ciliary membrane contained 920 cAMP gated-channels/microns2 in the newt and 2400 channels/microns2 in the toad. In contrast, the membrane of the dendrite and cell body contained only 2 cAMP-gated channels/microns2 (newt) and 6 channels/microns2 (toad). Thus, there is a high density of cAMP-gated channels in the cilia where olfactory transduction is thought to take place.

Animals↗
PubMed2000

Rotational malalignment of the femoral component in total knee arthroplasty.

Ligamentous balancing is a crucial part of total knee arthroplasty. To ensure proper kinematics, balance must be achieved in flexion and extension. Failure to do so may result in limited range of motion, premature polyethylene wear, or patellofemoral tracking problems. Balancing in extension is dependent on the type and extent of correctional ligamentous release. Flexion balance is dependent on proper femoral rotation. There are two methods to determine femoral rotation. In the classic method, the knee is tensed in flexion after ligamentous release in extension. The anteroposterior cut then is made parallel to the cut tibial surface. Alternatively, the anteroposterior cut can be based off fixed femoral landmarks. The purpose of the current study was to determine the variance between balancing the flexion gap with the classic method versus the technique of using fixed femoral landmarks to determine rotation. One hundred consecutive posterior stabilized knee arthroplasties were performed using the classic method. The resected posterior condyles in each case were measured. The actual difference between the resected condyles using the classic method was compared with the calculated difference of resected bone using bony landmarks to determine rotation. A variance analysis then was performed. Compared with classically balanced knees, rotational errors of at least 3 degrees occurred in 45 % of patients when rotation was determined from fixed bony landmarks. These patients had trapezoidal rather than rectangular flexion gaps. Such errors may have implications regarding polyethylene wear, range of motion, and long-term clinical results.

Arthroplasty, Replacement, Knee↗
PubMed1997

Radon in residences: influences of geological and housing characteristics.

222Rn is a radioactive gas emitted during the decay of 238U. 222Rn is a recognized lung carcinogen in humans and a common indoor air contaminant. This paper describes the results of research undertaken in 894 residences of the Province of Quebec (Canada), in which one of the objectives was to evaluate the influence of geological and housing characteristics on 222Rn levels. After a random selection of homes, 222Rn concentrations were measured with alpha track detectors in the basement and the main bedroom during two consecutive 6-mo periods. Geological subsoil characteristics were determined from various sources (e.g., geological maps, databanks on uranium sampling in lake and stream sediments), and housing characteristics were documented with a questionnaire. Statistical variance analysis of data indicates that geological factors only explain 5% and 4.5% of the variations in 222Rn concentrations, respectively, in the basement and on the first floor. When variables relative to housing characteristics are added, the analysis explains only 18% and 15% of the variations in 222Rn concentrations in the basement and on the first floor. These results illustrate the difficulties in predicting 222Rn concentrations in homes.

Air Pollutants, Radioactive↗
PubMed1998

Alcohol intake and blood pressure: the importance of time elapsed since last drink.

BACKGROUND: A positive association of chronic exposure to alcoholic beverages with blood pressure and the prevalence of hypertension has been described in epidemiological surveys, but the influence of time elapsed since last ingestion in this setting was not demonstrated. DESIGN: A cross-sectional, population-based survey. METHODS: In total 1089 adults from Porto Alegre, randomly selected from a population-based, multi-stage probability sample, were interviewed at home. The average daily alcohol intake of each subject was calculated taking into account the concentration of ethanol in the beverages (distilled or fermented beverages), and the time elapsed between the last ingestion of ethanol and the moment of blood pressure determination. Standardized sitting blood pressure and anthropometric parameters were collected. The magnitude and shape of the associations were analyzed considering blood pressure as a continuous variable and the prevalence of arbitrarily defined hypertension. Simple and multiple linear regression models, including models to identify nonlinear associations, with quadratic and cubic terms of the amount of alcohol consumed, were employed. Blood pressure means were compared by analysis of variance and analysis of covariance. The association between hypertension and exposure to ethanol was analyzed through logistic regression models, controlling for various potential confounders. RESULTS: Positive nonlinear associations of the amount of alcohol consumed with blood pressure and the prevalence of hypertension (> or = 160/95 mmHg) were found, independent of age, years of education, smoking, and use of oral contraceptive and antihypertensive drugs. The consumption of 30 g/day ethanol was associated with increases of 1.5 and 2.3 mmHg in diastolic and systolic blood pressures, respectively, for men, and 2.1 and 3.2 mmHg, respectively, for women. The prevalence of hypertension was higher among those ingesting more than 30 g/day (odds ratio = 2.9, P < 0.01). The time elapsed between the last ingestion and blood pressure measurement was independently associated with the prevalence of hypertension. Men with last consumption of alcohol 13-23 h prior to measurement had odds of being hypertensive 2.6 (confidence interval 1.3-5.0) greater than did subjects who had consumed alcoholic beverages 24 h and more before the blood pressure determination. For men, systolic and diastolic blood pressures were lower during the first 3 h after ingestion and increased afterward. Frequency of consumption and type of beverage consumed were not independently associated with level of blood pressure. CONCLUSION: A time-dependent association between alcohol consumption and effects on blood pressure, demonstrated in experimental studies, was found for free-living individuals selected at random.

Adolescent↗
PubMed2003

Microalbuminuria, a parameter independent of metabolic influences in hypertensive men.

OBJECTIVE: To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. DESIGN: Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. MAIN OUTCOME MEASURES: Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. RESULTS: HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. CONCLUSIONS: Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.

Adult↗
PubMed1995

Evaluating the effectiveness of case management plans.

Case management plans have been used as a strategy for quality improvement and cost containment of healthcare. The authors discuss the methods used for evaluating the effectiveness of these plans. Variance analysis and measuring expected outcomes of care are the main themes. The authors also present one hospital approach to outcomes management that can be used by healthcare administrators to evaluate patient-care outcomes.

Clinical Protocols↗
PubMed1999

Diet and chronic constipation in children: the role of fiber.

BACKGROUND: Chronic constipation is one of the most common disorders in Western countries and despite numerous clinical, pathophysiologic, and epidemiologic studies its cause is still unclear. Several hypotheses have been proposed and according to experimental studies and clinical observation, fiber intake could play a role in its pathogenesis. The purpose of this case-control study was to examine the possible correlation of idiopathic chronic constipation in children and dietary intake, particularly fiber intake. METHODS: A randomized sample of children (291 children with constipation and 1602 controls) aged 2 to 14 years was taken from three of the 52 counties of Greece. Stratification was performed on the basis of urban, rural, or suburban location and socioeconomic status. The nutritional data were obtained from a 3-day dietary record and a dietary history. Statistical analysis was performed with multivariate tests, multivariate analysis of variance, discriminant analysis, and chi-square analysis according to the characteristics of the correlated variables. RESULTS: Constipated children had a lower caloric and nutrient intake (p < 0.001), lower body weight/height (p < 0.001), and higher prevalence of reported anorexia (p < 0.001). Discriminant analysis indicated that dietary fiber alone was independently negatively correlated with chronic constipation, despite the age and the age of onset of constipation. Relative risk also had a negative correlation with fiber intake (p < 0.001). Of the main fiber fractions only cellulose and pentose were independently correlated with chronic constipation. CONCLUSIONS: Lack of fiber may play an important role in the etiology of chronic idiopathic constipation in children.

Adolescent↗