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The Nottingham System: objective assessment of facial nerve function in the clinic.

The House-Brackmann is the most widely accepted system for the clinical assessment of facial nerve function. It is, however, being subjective and discontinuous, prone to interobserver variation. The need for an objective system persists. The Nottingham System is described and compared to the Burres-Fisch system in a study of 29 subjects with varying degrees of facial nerve function, ranging from normal to total paralysis. Within-group component of variance analysis was 7% for the Nottingham System compared to 26% for the Burres-Fisch system. Bland and Altmans' analysis showed the Burres-Fisch system to be biased, overestimating small percentage scores, and underestimating large ones. The Nottingham System proved unbiased. The Nottingham System is recommended as an accurate objective continuous grading system for the rapid assessment of facial nerve function in the clinic.

Adolescent↗

Validation of geometric methods for estimating segmental myocardial motion of the left ventricle at cineangiography.

Functional myocardial changes which result from ischemia are typically local rather than total. For assessing such regional changes quantitatively, left ventricular angiography has been used. The ventricular image has been divided into several components which can be measured individually. In order to test the validity of such methods, left ventricles of 5 dogs were labeled with endocardial tantalum markers and the segmental myocardial motion was estimated using cineangiography. Variance analysis of beat to beat measurements of total ejection fractions was performed. Total ejection fraction demonstrated the least variation with an average 3.5 per cent, segmental myocardial shortening 15 and regional stroke volumes 13 to 18 per cent. Intermethodologic variation with different regional volume measurements was 11 to 13 per cent. Regional stroke volume calculations showed large methodologic variations in beat to beat analysis. Conclusions and clinical decisions based on such measurements should be drawn with caution.

Animals↗

Comparison of results with CO2 laser and traditional surgical treatment of stage I malignant melanoma.

The follow-up data on 39 cases of stage I malignant melanoma treated with CO2 laser are compared to those of an analogous group of cases treated by traditional surgical methods and selected for their clinical and pathologic similarities with the laser-treated group. The findings were expressed in terms of tumor-free time and were evaluated by variance analysis. The data showed that traditional methods gave better results. CO2 laser surgery requires longer healing time, which may have a negative effect on the course of the disease.

Evaluation Studies as Topic↗

Serum copper and ceruloplasmin in early and in advanced hepatocellular carcinoma: diagnostic and prognostic relevance.

To evaluate the prognostic value of serum copper (S-Cu) and ceruloplasmin and their pathophysiologic significance in human hepatocellular carcinoma (HCC), we studied 49 patients with HCC (20 of which were submitted to partial hepatectomy) compared with 110 patients with liver cirrhosis. In HCC both S-Cu and ceruloplasmin were higher than in cirrhosis; moreover, S-Cu was correlated with the extension of HCC, evaluated by instrumental data and by surgical inspection. In cirrhotic patients, mean S-Cu was 122.9 micrograms/dl (SD, 29.3), in early HCC, 153.0 micrograms/dl (SD, 34.5), and in advanced HCC, 193.1 micrograms/dl (SD, 37.7). Variance analysis gave F = 59.4. In HCC patients S-Cu was positively correlated with ceruloplasmin and with fibrinogen. Survival, evaluated by Mantel's test stratified for surgical therapy, was longer in patients with S-Cu levels lower than 175 micrograms/dl and in those at an earlier stage. We therefore conclude that S-Cu has a relevant diagnostic value in detecting HCC also in early stage and allows prognostic evaluation as regards survival.

Adolescent↗

Steroid and antihistamines modulate RANTES release in cultured peripheral blood mononuclear cells of atopic patients.

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (antihistamines) (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by the mini-Wright procedure. PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that the steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.

Journal Article↗

The impact of micronized purified flavonoid fraction on the treatment of acute haemorrhoidal episodes.

OBJECTIVE: To evaluate the efficacy and the tolerability of micronized purified flavonoid fraction (MPFF) on symptoms and signs of acute haemorrhoidal disease (HD). RESEARCH DESIGN AND METHODS: Patients experiencing an acute HD episode for less than 48 h were enrolled in this randomized, double-blind, placebo-controlled study (n = 90 in two hospital-based study centres in Beijing). One group received MPFF, six tablets per day for 4 days followed by four tablets per day for 3 days and the other a placebo. Symptoms and signs of HD were assessed by blinded observers at day 0 (D0), day 4 (D4), and day 7 (D7) on a 4-point severity grading scale (from 1 = absent to 4 = severe). A two-way variance analysis was performed for comparison between groups. RESULTS: Forty-nine patients (49) in the MPFF group and 41 in the placebo group (mean age 43.2 years [range 18-76 years]), percentage of male gender 54.4%, mean time from onset of acute episode 45.3 h (range 16-48 h) were included in this analysis. No significant differences between groups were seen at baseline in terms of age, gender, and frequency and intensity of symptoms, except for oedema, whose frequency and severity was significantly greater in the MPFF group (p = 0.024). During the 7-day treatment, there was a significant difference in favour of MPFF in the evolution of pain and oedema (p < or = 0.001 at D7) and in bleeding (p = 0.021 at D4, and p = 0.047 at D7). The appreciation of global efficacy by patients (p = 0.007) or investigators (p = 0.006) also favoured MPFF. Blood pressure, heart rate and laboratory parameters remained within normal ranges and were not modified during the study in either group. No patient had to stop the treatment owing to adverse events and only one patient reported gastrointestinal discomfort. CONCLUSION: MPFF significantly reduced the extent of pain and bleeding in the selected subjects of this study with acute haemorrhoids. The tolerability was similar in patients receiving MPFF to that in patients receiving a placebo during the 7-day duration of the treatment.MPFF can be considered an effective and well-tolerated agent in the treatment of acute episodes of haemorrhoids.

Acute Disease↗

Extracting biological information from DNA arrays: an unexpected link between arginine and methionine metabolism in Bacillus subtilis.

BACKGROUND: In global gene expression profiling experiments, variation in the expression of genes of interest can often be hidden by general noise. To determine how biologically significant variation can be distinguished under such conditions we have analyzed the differences in gene expression when Bacillus subtilis is grown either on methionine or on methylthioribose as sulfur source. RESULTS: An unexpected link between arginine metabolism and sulfur metabolism was discovered, enabling us to identify a high-affinity arginine transport system encoded by the yqiXYZ genes. In addition, we tentatively identified a methionine/methionine sulfoxide transport system which is encoded by the operon ytmIJKLMhisP and is presumably used in the degradation of methionine sulfoxide to methane sulfonate for sulfur recycling. Experimental parameters resulting in systematic biases in gene expression were also uncovered. In particular, we found that the late competence operons comE, comF and comG were associated with subtle variations in growth conditions. CONCLUSIONS: Using variance analysis it is possible to distinguish between systematic biases and relevant gene-expression variation in transcriptome experiments. Co-variation of metabolic gene expression pathways was thus uncovered linking nitrogen and sulfur metabolism in B. subtilis.

Arginine↗

Inositol and glucocorticoid in the development of lung stability in male and female rabbit fetuses.

Inasmuch as inositol affects the development of lung surfactant, and exogenous glucocorticoids accelerate fetal lung maturation, a possible interaction of the two substances on alveolar stability of preterm rabbit fetuses of 28 days gestation was investigated. On days 26 and 27 of gestation inositol or glucose were added to the diet of does treated with betamethasone (0.2 mg/kg intramuscularly on days 26 and 27). Inositol increased lung-thorax compliance of paralyzed fetuses at all insufflation pressures studied (from 16 to 22.5 and 30 cm H2O and back to 22.5, and 16 cm H2O). At a ventilation pressure of 30 cm H2O, lung-thorax compliance of fetuses treated with inositol plus betamethasone was more than doubled as compared with controls (1.2 +/- 0.6 versus 0.5 +/- 0.2 ml/kg x cm H2O; p less than 0.001). Inositol alone had no detectable effect on compliance, whereas betamethasone tended to increase compliance (p = 0.05). According to variance analysis, the effect of inositol was statistically significant only among the males. Inositol prevented the glucocorticoid-induced decrease in lung protein and, to a lesser extent, the decrease in DNA. Inositol did not further increase the lavageable surfactant pool of the glucocorticoid-treated, ventilated fetuses, although the area occupied by lamellar bodies within type II cells was increased after inositol plus betamethasone. According to the present study, inositol modifies the physiologic and biochemical response of the immature fetal lung to a pharmacologic dose of exogenous glucocorticoid.

Animals↗

Presence of insulin-renin-aldosterone-potassium interrelationship in normal subjects, disrupted in chronic hemodialysis patients.

The factors regulating aldosterone secretion in normals and in patients on chronic hemodialysis were studied by the determination of the circadian rhythm of plasma aldosterone, renin, cortisol, insulin, potassium, sodium, and glucose. Four normal volunteers and eight normotensive patients on regular dialysis treatment (RDT) were studied during prolonged recumbency on low sodium diet. A definite circadian rhythm for renin could not be demonstrated in RDT patients. The significant simple and multiple correlation coefficients found in normal subjects suggest that insulin participates in the regulation of aldosterone together with the other known factors: ACTH, renin, and potassium. In chronic renal failure, however, when basal conditions were maintained during prolonged recumbency, the correlations of insulin and renin with aldosterone were not found, suggesting that in this condition aldosterone secretion is controlled by ACTH and potassium. As a direct influence of insulin on aldosterone could not be demonstrated by multiple variance analysis, it seems that insulin is related to aldosterone indirectly through renin and/or potassium. The presence of significant correlations between insulin-potassium and potassium-aldosterone in RDT patients, without a significant insulin-aldosterone correlation, suggest that in the normals insulin participates in aldosterone regulation through renin secretion and not through potassium. A correlation between potassium and renin was not found in normals or in RDT patients.

Adult↗

Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats.

Earlier data showed that men fasted for 38 h had a reduced rate of chlorzoxazone metabolism, suggesting a decreased level of cytochrome P450 2E1 (CYP2E1). In contrast, the level of CYP2E1 in fasted rats had been shown to be elevated. In this study, we have investigated whether chlorzoxazone metabolism in fasted rats was changed by determining the pharmacokinetics of chlorzoxazone and its metabolite, 6-hydroxychlorzoxazone (6-OHCZ), as a CYP2E1 probe, and by measuring liver CYP2E1 using immunoblot techniques. Chlorzoxazone was administered by gavage (50 mg kg(-1)) or intravenously (25 mg kg(-1)) to control (nine for oral and three for intravenous) and 24 h-fasted (nine for oral and four for intravenous) male Sprague-Dawley rats. Following sampling of blood through a jugular vein cannula, chlorzoxazone and 6-OHCZ plasma concentrations were measured by HPLC with UV detection. Pharmacokinetic parameters for chlorzoxazone and 6-OHCZ in each treatment group were determined by model fitting and non-compartmental analysis. In parallel with the increased liver CYP2E1 level, the elimination of chlorzoxazone and 6-OHCZ was significantly increased in fasted rats in the oral and the intravenous study. A multiple analysis of variance covariance analysis and a multiple regression analysis revealed a significant correlation between 1/t(1/2) and CYP2E1 level and aniline hydroxylase activity. However, the correlation between 1/t(1/2) and pentoxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase and erythromycin N-demethylase was not significant. Therefore the contribution of other P450s to chlorzoxazone metabolism seemed to be minor in the concentration range that we tested. In conclusion, fasting rats for 24 h caused a measurable induction of CYP2E1, which produced a significant increase in the rate of chlorzoxazone metabolism and elimination.

Administration, Oral↗

Relationship between serum lipoprotein(a) concentrations and coronary vasomotion in coronary spastic angina.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) concentrations are reported to impair endothelium-dependent vasodilatation of the epicardial coronary artery. However, the effects on vasomotor abnormalities in coronary spastic angina (CSA) have not been thoroughly investigated. METHODS AND RESULTS: In the present study 80 sites of spasm (spastic sites) without significant organic stenosis (% diameter stenosis <50%) were assessed in 80 patients with CSA diagnosed by intracoronary ergonovine (EM) test. Spastic sites were divided into 2 groups: Group 1 included 30 sites provoked by the full dose (=50 microg) of EM, and Group 2 included 50 sites provoked with less than 50 microg (34.7+/-8.2 microg). Control subjects (n=22) did not show coronary spasm with the EM test. Serum Lp(a) concentrations were measured in all patients. Group 2 had a significantly greater basal coronary artery tone in the spastic sites than Group 1 (p<0.001). Lp(a) level in Group 2 was significantly higher compared with both the control group and Group 1 (p<0.05 by analysis of variance). Multivariate analysis confirmed that only serum Lp(a) concentration was associated with low-dose EM spasm provocation. CONCLUSIONS: Serum Lp(a) concentration could be a marker for high disease activity in CSA.

Adult↗

The preflight evaluation. A comparison of the hypoxia inhalation test with hypobaric exposure.

STUDY OBJECTIVES: We sought to compare arterial oxygen partial pressure (PaO2) relationships between a 15.1% hypoxia inhalation test (HIT) at sea level and a hypobaric chamber exposure equivalent to 2,438 m (8,000 feet) of altitude above sea level in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects. DESIGN: Comparison of physiologic variables before and during intervention. SETTING: A referral-based pulmonary disease clinic at a US Army medical center in a metropolitan area. SUBJECTS: The study included three groups: group 1, 15 patients, 3 women and 12 men, with COPD (forced expiratory volume in the first second [FEV1, mean +/- SD], 41 +/- 14% of predicted); group 2, 9 healthy men; and group 3, 18 men with COPD (FEV1, 31 +/- 10% of predicted) previously reported in detail. INTERVENTIONS: We evaluated each group at sea level followed by one of two different types of hypoxic exposures. Group 1 received exposure to 15.1% oxygen at sea level, the HIT. Groups 2 and 3 received hypobaric chamber exposure equivalent to 2,438 m (8,000 feet) above sea level. MEASUREMENTS AND MAIN RESULTS: For all three groups combined, the arterial oxygen tension at sea level (PaO2SL) explained significant variability in PaO2 during hypoxic exposure according to the following formula: PaO2 during exposure = 0.417 (PaO2SL)] + 17.802 (n = 42; r = 0.756; p < 0.001). Neither the type of hypoxic exposure (HIT vs hypobaric), status as patient vs control, sex, nor age explained significant variability in PaO2 during hypoxia exposure after inclusion of PaO2SL as a covariate in analysis of variance. Subsequent analysis revealed that forced expiratory spirometric variables FEV1 and FEV1 to FVC ratio served as second order covariates with PaO2SL to improve description of PaO2 during hypoxia exposure for the combined samples (n = 42; p < 0.05). Analysis of residuals from regression analysis revealed approximately normal distribution. CONCLUSIONS: The PaO2 relationships did not differ between the 15.1% HIT at sea level and hypobaric exposures of 2,438 m (8,000 feet) above sea level. Normal subjects and patients with COPD formed a single relationship. The present study extends descriptive models to a larger range of subjects. Regression models have definable accuracy in predicting PaO2 during hypoxia exposure that increases with inclusion of spirometric variables.

Adult↗

Trace element concentrations and superoxide dismutase and catalase activities in benign and malignant larynx tumors.

The plasma and erythrocyte levels of zinc, copper, and magnesium and the activities of red-cell copper-zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) were determined in patients with benign and malignant tumors of the larynx. Blood samples from patients and healthy controls were drawn using heparinized tubes. The erythrocyte Cu/Zn-SOD and CAT activities were determined spectrophotometrically and the zinc, copper, and magnesium concentrations were determined in erythrocyte and plasma by atomic absorption spectrometry. Variance analysis was employed in the statistical evaluation of the findings. There was a significant increase in red-cell Cu/Zn-SOD activity in the subjects with malignant and benign tumors compared to controls (p<0.001). The CAT activity increased only in the benign tumor group (p<0.01). The plasma zinc concentrations were significantly lower in the malignant tumor group (p<0.05) and significantly higher in the benign tumor group (p<0.01). The erythrocyte copper concentrations were significantly lower in both benign and malignant tumor groups (p<0.001). The plasma copper and magnesium and the erythrocyte magnesium concentrations did not show significant differences relative to controls (p>0.05). The increases in the activities of SOD and CAT activities and the changes in trace elements concentrations can indicate the presence of increased reactive oxygen species that might play a part in the pathogenesis larynx tumors.

Adult↗

Validity of hair mineral testing.

The variance of testing was compared between the College of American Pathologists clinical survey and that of a recent review about hair mineral testing. The review suggested that the accuracy of hair mineral testing was unreliable. In general, there was a greater range of variance in the College of American Pathologists testing results. These latter results are based on laboratory testing and are used as a "yardstick" to determine if a laboratory passes or fails that analyte and are considered a "gold standard." An extract, which resulted from a method that avoided the washing step, was compared among five laboratories. Very good precision resulted, indicating that the varied washing steps used by the laboratories in a recent review were probably the source of much variance. Analysis of hair analysis seemed to yield important information in several historical or forensic cases involving Ludwig von Beethoven, Napoleon Bonaparte, ex-US-presidents Zachary Taylor and Andrew Jackson, and Charles Hall, an Arctic explorer. Several elements that were reviewed, including arsenic, cadmium, cobalt, germanium, lead, lithium, manganese, mercury, nickel, and thallium, showed relationships between body burden, dosage, and exposure or toxicity. Evidence of toxicity could not be found by measuring hair aluminum or vanadium. Chromium, selenium, and zinc seemed to have nutritional value. Ratios of hair elements with clinical importance could not be found.

Famous Persons↗

The effect of heparinized blood exchange transfusion on endotoxin induced disseminated intravascular coagulation (DIC).

Sepsis of the newborn induced by gram negative bacteria, especially E. coli is often accompanied by a severe coagulation disorder. It can be treated by blood exchange transfusion (ET) with heparinized blood. In this study the hematological effect obtained by the exchange transfusion was investigated in rabbits after induction of a generalized Shwartzman reaction by two spaced injections of endotoxin (75 microgram/kg) 24 hrs. apart. Three groups of 6 animals each were investigated: group I: without endotoxin but with ET (controls); group II: endotoxin without ET; group III: endotoxin with ET. Fibrinogen, soluble fibrin monomer complexes (SFMC), fibrin(ogen) degradation products (FDP), platelet- and leukocyte counts and urine volume (ml/hr) were estimated. In group II a decline in the fibrinogen level, and in platelet and leukocyte count, as well as an increase in SFMC and FDP could be observed from 6 hrs. on after the second endotoxin injection. In group III 6 hrs. after the second endotoxin injection, exchange transfusion with heparinized blood was performed. Variance analysis showed significant differences in all parameters, except in the urine volumes after exchange transfusion between group III and group II. By exchange transfusion an approach of the values towards the values of the controls could be recognized. The findings indicate, that by blood exchange transfusion the hematological consequences of the endotoxin induced DIC can be corrected, while the dysfunction of the kidneys can be improved only slightly.

Animals↗

Study on propolis quality from China and Uruguay.

The composition, bacteriostatic and ROO*-scavenging potential activities of fifteen propolis samples from various botanic and geographic origins were determined to obtain objective information related to propolis quality. Variance analysis showed significant differences (p < or = 0.05) in the contents of polyphenols, flavonoids and active components between fresh and aged propolis. The state of the product (fresh or aged) could be differentiate by using flavonoid pattern and biological activities. A minimum propolis concentration of 80 microg/ml was required inhibit Bacillus subtilis and Staphylococcus aureus while 800 microg/ml was required to inhibit Escherichia coli using fresh propolis. Aged propolis inhibit B. subtilis and S. aureus at concentration of 100 microg/ml and E. coli at 1000 microg/ml. A minimum flavonoids percentage of 18 g/100 g and a maximum ROO*-scavenging potential activity of 4.3 microg/ml were determined in fresh propolis. Flavonoids levels in aged propolis were approximately 20% lower than in fresh propolis. A maximum flavonoids percentage of 19.8 g/100 g and a ROO*-scavenging potential activity between 5.7 to 6.4 microg/ml in aged propolis were quantified. Another objective was to assess the use of ROO*-scavenging potential activity in propolis quality.

Bacillus subtilis↗

Pharmacological properties of GABAA receptors in rat hypothalamic neurons expressing the epsilon-subunit.

The pharmacological properties and functional role of native GABA(A) receptors (GABA(A)Rs) were investigated in rat hypothalamic neurons expressing the epsilon-subunit with the help of whole-cell patch-clamp recording and single-cell reverse transcription-PCR. Two cell groups were identified: histaminergic tuberomamillary and orexinergic/hypocretinergic neurons. Approximately 25% of histaminergic and 70% of orexinergic neurons contained mRNA encoding for the epsilon-subunit. Double-immunofluorescence staining revealed a somatic localization of this protein in these two neuronal groups. Constitutive activity, diazepam modulation, fast desensitization of maximal currents, and activation by propofol (6-98 microm) of GABA(A)Rs did not correlate with epsilon-subunit expression. Propofol at 3-12 microm potentiated GABA-mediated currents similarly in all neurons. However, noise variance analysis of GABA-mediated currents enhanced by propofol revealed a significant difference between epsilon-positive and epsilon-negative neurons. The former displayed no difference between control and potentiated responses, and, in the latter, noise was decreased in the presence of propofol. Spontaneous IPSCs recorded in cultured hypothalamic neurons were prolonged in the presence of propofol in all epsilon-negative neurons, whereas propofol-resistant IPSCs were recorded in epsilon-positive cells. The infrequent expression of the epsilon-subunit may be a key factor in the recently discovered central role of the tuberomamillary nucleus in anesthesia.

Anesthetics, Intravenous↗

In vitro effect of human growth hormone on lymphocyte transformation and lymphocyte growth factors secretion.

Cultures of human blood peripheral lymphocytes were performed in the presence or absence of human growth hormone, and also of phytohemagglutinin and normal human serum 10%. After incubation for 48 h, the supernatants were tested for their ability to promote the uptake of [3H]thymidine into lectin-activated lymphocytes. Supernatants from lymphocyte-free control samples, treated in the same manner, were assayed under the same experimental conditions. Variance analysis of the different dose-response relationships was performed. The results of these in vitro experiments confirm that physiological levels of GH inhibit the lectin-induced lymphoproliferation and that lymphocytes secrete an 'activity' able to stimulate the incorporation of [3H]thymidine into lectin activated lymphocytes. Furthermore we show that: 1) Secretion of this lymphocyte-stimulating activity is increased by physiological levels of GH; 2) This lymphocytic secretion is not radioimmunoassayable IGF-I; 3) Using fast protein liquid chromatography (FPLC), this activity appears in fractions with various molecular weights.

Adult↗