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Acemetacin in the long-term therapy of rheumatoid arthritis.

An open label study was carried out to assess the long-term use of acemetacin in patients suffering from rheumatoid arthritis. One hundred and two patients were treated with acemetacin, some patients for up to a 12-month period. Analysis of efficacy showed that acemetacin therapy was associated with statistically significant sustained improvements in the target variables of duration of morning stiffness, Ritchie articular index and left and right grip strength. With regard to tolerability, a number of adverse events were recorded but were generally reported as either mild or moderate. In total, 28,988 patient days' treatment with acemetacin were completed and acemetacin proved an effective and well-tolerated long-term therapy in patients with rheumatoid arthritis.

Adolescent↗

Dose-effect relationships of trauma to symptoms of depression and post-traumatic stress disorder among Cambodian survivors of mass violence.

BACKGROUND: The dose-effect relationships of cumulative trauma to the psychiatric symptoms of major depression and post-traumatic stress disorder (PTSD) in a community study of Cambodian survivors of mass violence were evaluated. METHOD: In 1990, a survey of 1000 households was conducted in a Thai refugee camp (Site 2) using a multi-stage random sampling design. Trauma history and psychiatric symptoms were assessed for two time periods. Analysis used linear dose-response regression modelling. RESULTS: 993 Cambodian adults reported a mean of 14 Pol Pot era trauma events and 1.3 trauma events during the past year. Symptom categories of depression, PTSD, dissociative and culturally dependent symptoms exhibited strong dose-effect responses with the exception of avoidance. All symptom categories, except avoidant symptoms, were highly correlated. CONCLUSIONS: Cumulative trauma continued to affect psychiatric symptom levels a decade after the original trauma events. The diagnostic validity of PTSD criteria, with the notable exception of avoidance, was supported. Inclusion of dissociative and culturally dependent symptoms increased the cultural sensitivity of PTSD.

Adolescent↗

Reversal of vitamin-D2-induced hypercalciuria by chlorothiazide.

To test the effects of chlorothiazide on vitamin-D2-induced hypercalciuria, we carried out 17 metabolic studies lasting 12 days each in adult Sprague-Dawley male rats. Three groups were studied: (A) control rats receiving only the vitamin-D2 vehicle; (B) vitamin-D2-treated rats receiving 50 IU/day; and (C) rats treated in the same manner as group B with the addition of chlorothiazide 20 mg/day for the last 6 days of the study. Urine was collected during the last 3 days, and a blood sample was obtained at the end of each study period. Analysis of the data showed that there were no significant differences between the groups in changes of serum calcium concentration (A, 6.1 +/- 0.1 mg/dl; B, 6.1 +/- 0.2 mg/dl; C, 6.0 +/- 0.2 mg/dl), serum creatinine concentration (A, 0.5 +/- 0.07 mg/dl; B, 0.52 +/- 0.08 mg/dl; C, 0.48 +/- 0.04 mg/dl), and creatinine clearance (A, 4.8 +/- 0.7 ml/min/kg; B, 5.2 +/- 1.2 ml/min/kg; C, 4.9 +/- 0.5 ml/min/kg). The administration of vitamin-D2 significantly increased the urinary calcium excretion from 6.7 +/- 1.0 mg/kg/day to 19.5 +/- 9.7 mg/kg/day (p less than 0.02), but the calciuria was inhibited in group C rats by the addition of chlorothiazide, which restored urinary calcium excretion to 6.8 +/- 2.5 mg/kg/day (p less than 0.02). Evaluation of the ratio of calcium/creatinine excretion (A, 0.19 +/- 0.03; B, 0.53 +/- 0.25; C, 0.20 +/- 0.07) and calcium/sodium excretion (A, 0.22 +/- 0.05; B, 0.48 +/- 0.25; C, 0.19 +/- 0.04) further confirmed these effects of vitamin-D2 and chlorothiazide on urine calcium excretion. We conclude that in rats conventional doses of vitamin-D2 consistently induce marked hypercalciuria, even without hypercalcemia, and that this hypercalciuria can be effectively prevented by chlorothiazide.

Animals↗

Effect of racemic epinephrine on ventilatory function in the neonate postextubation.

The use of nebulized racemic epinephrine to improve ventilatory function in the newborn postextubation was studied. Forty-five infants intubated for more than 3 days were randomized to receive racemic epinephrine by nebulization immediately postextubation or to receive only warmed, humidified gas. Measurements of air flow, esophageal pressure, tidal volume, respiratory rate, and heart rate were made before treatment and every 10 min for 1 h after treatment. Resistance was calculated from recorded data. Changes from baseline values were calculated for each time period. Analysis of variance of these variables for treatment, sex, and time main effects and their interactions, with appropriate adjustments for covariables, was performed. Although some sex interactions were seen, there were no significant time effects or interactions. This study provides no evidence that using nebulized racemic epinephrine in infants postextubation improves ventilatory function.

Administration, Inhalation↗

Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span.

GH participates in growth, metabolism, and cellular differentiation. To study these roles, we previously generated two different dwarf mouse lines, one expressing a GH antagonist (GHA) and the other having a disrupted GH receptor and binding protein gene (GHR -/-). In this study we compared the two dwarf lines in the same genetic background (C57BL/6J). One of the most striking differences between the mouse lines was their weight gain profile after weaning. The weights of the GHA dwarfs gradually approached controls over time, but the weights of the GHR -/- dwarfs remained low throughout the analysis period. Additionally, fasting insulin and glucose levels were reduced in the GHR -/- mice but normal in the GHA mice. IGF-I and IGF binding protein 3 (IGFBP-3) levels were significantly reduced, but by different degrees, in both mouse lines, but IGFBP-1 and -4 levels were reduced and IGFBP-2 levels increased in GHR -/- mice but unaltered in GHA mice. Finally, life span was significantly extended for the GHR -/- mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes.

Animals↗

E-domain peptide of rat proinsulin-like growth factor-II: validation of a radioimmunoassay and measurement in culture medium and rat serum.

We recently discovered a peptide derived from the carboxyl-terminal portion of the E-domain of rat proinsulin-like growth factor II (pro-IGF-II) in medium conditioned by BRL-3A rat liver cells. This peptide begins at residue 117 in the pro-IGF-II sequence. To measure physiological concentrations of this peptide in serum, we established an RIA for a synthetic peptide [rat pro-IGF-II-(117-156); E-domain peptide] corresponding to the carboxyl-terminal 40-amino acids of rat pro-IGF-II. The 41-residue peptide [Tyr116]pro-IGF-II-(117-156) was also synthesized and iodinated for use as tracer. Using polyclonal antibodies, we established a standard curve that measured as little as 25 pg/tube. Tracer was not displaced by insulin, human (h) IGF-I, hIGF-II, pro-hIGF-I-(71-105), rat GH, mouse EGF, ACTH, bovine PTH, ovine FSH, TRH, or LHRH under our assay conditions. However, a synthetic analog of the E-domain peptide [Phe117]pro-IGF-II-(118-156) showed displacement similar to that of the synthetic E-domain peptide. Serial dilutions of either culture medium or rat serum exhibited displacement parallel to the standard curve. Measurement of E-domain peptide in serum-free medium conditioned by BRL-3A rat liver cells showed a time-related increase in E-peptide concentration over a 72-h period. Analysis of E-peptide immunoreactivity from conditioned medium after gel filtration chromatography in 1 M acetic acid revealed a single peak which had a mol wt (determined by Western blot) identical to that of the synthetic E-peptide standard. The concentration of immunoreactive E-domain peptide levels in serum of 5-day-old rat pups was 30-40 times higher than concentrations in the serum of adult rats. Gel filtration chromatography of adult rat serum in 1 M acetic acid revealed a single major peak of immunoreactivity eluting at a position similar to the elution position of the E-domain peptide from BRL-3A rat liver cell-conditioned medium. The RIA described here should prove useful for measurement of the somatic output of E-domain peptide under different physiological conditions.

Animals↗

Transforming growth factor-beta promotes differentiation of ovarian thecal-interstitial cells but inhibits androgen production.

Evidence that transforming growth factor-beta (TGF beta) is produced by thecal-interstitial cells (TIC) has suggested the hypothesis that TGF beta may be an autocrine regulator of TIC function. The purpose of these studies is to begin to test this hypothesis. In the present experiments we tested the effects of TGF beta on steroid production by TIC isolated from the ovaries of hypophysectomized immature rats by Percoll gradient centrifugation. When TIC (10(4) viable cells/well) were cultured in serum-free medium (0.2 ml in 96-well plates), low amounts of androsterone (less than 4 ng/ml) were produced at 2, 4, and 6 days. TGF beta (0.01-100 ng/ml) did not change basal androsterone production. Treatment with LH (50 ng/ml) stimulated a 100-fold increase in androsterone at 2 days and 60-fold increases at 4 and 6 days. Concomitant treatment with TGF beta (10 ng/ml) caused a 65% inhibition (ED50 = 2.3 +/- 0.7 ng/ml) of androsterone production at each time period. Analysis of key steroid metabolites demonstrated that androsterone and androstenedione were inhibited equally, while progesterone was significantly increased (ED50 = 1.2 +/- 0.2 ng/ml). Time-course studies revealed that TGF beta alone did not alter progesterone production at 2 days, but markedly increased progesterone (10-fold) above control levels at 4 and 6 days. Dose-response experiments showed that TGF beta did not alter the sensitivity of the TIC to LH stimulation, indicating that LH activation of the intracellular signaling pathway was not blocked by TGF beta. Treatment with insulin-like growth factor-I (IGF-I) together with LH caused a synergistic increase in androsterone production. The synergistic stimulation of LH action by IGF-I could be blocked by TGF beta. Interestingly, TIC were more sensitive to TGF beta in the presence of IGF-I (ED50 = 0.18 +/- 0.04 ng/ml). In contrast, TGF beta enhanced progesterone production only at the highest dose of TGF beta (10 ng/ml). To further elucidate the mechanism of TGF beta action, the effects of TGF beta on the TIC content of 17 alpha-hydroxylase/C17-20 lyase (P450(17)alpha) and cholesterol side-chain cleavage (P450scc) were analyzed by immunoblotting. TGF beta alone or in combination with LH stimulated an increase in P450scc content, but did not alter P450(17 alpha content. These results lead us to conclude that 1) the TIC are targets for TGF beta; 2) IGF-I increases the sensitivity of TIC to TGF beta action; and 3) TGF beta acts directly on TIC to stimulate progesterone while inhibiting androgen production.

Androgens↗

Controlled study of nimodipine in aneurysm patients treated early after subarachnoid hemorrhage.

We enrolled 75 consecutive patients admitted with subarachnoid hemorrhages in a randomized, double-blind, placebo-controlled trial to determine the effect of early intervention with nimodipine on outcome and cerebral blood flow. The cardioprotective effect of nimodipine was assessed by measuring the electrocardiographic changes over the first 3 days of drug treatment. There was a mild lowering of the mean cerebral blood flow in the nimodipine-treated group over the 21-day period. Analysis of the continuous electrocardiographic traces showed no difference between the nimodipine and placebo groups in the frequency or type of abnormality detected. At 3 months, 4 of the 38 patients receiving nimodipine had died, compared with 10 of the 37 placebo-receiving patients. Of the 50 eligible patients who had a proven cerebral aneurysm, 1 patient (4%) on nimodipine died compared with 6 (24%) receiving placebo (0.01 less than P less than 0.05, chi 2 test; approximate 95% confidence interval for mortality difference, 0.4% to 39.6%). We conclude that nimodipine does not increase the cerebral blood flow or protect the heart after a subarachnoid hemorrhage. There were no side effects from nimodipine. The trend toward improved outcome should be verified in a larger series of patients.

Adolescent↗

The effects of enforced activity on ventilation, circulation and blood acid-base balance in the semi-terrestrial anuran, Bufo marinus.

Strenuous exercise results in a marked blood acid-base disturbance which is accompanied by large increases in ventilation rate, heart rate and mean arterial blood pressure. Recovery to normal resting values follows an exponential time course with a half-time of approximately 2 h for all parameters except Pa, CO2 and ventilation rate. The latter return to normal by 30 min following the exercise period. Analysis reveals that there is initially a large discrepancy between the quantity of metabolic acids buffered in the blood and the blood lactate levels. The significance of this finding is discussed. Significant changes in the concentrations of chloride, bicarbonate and lactate, in both plasma and erythrocytes, accompany the blood acid-base disturbance. Chloride and bicarbonate appear to be passively distributed between the two compartments according to a Gibbs-Donnan equilibrium whereas lactate only slowly permeates the erythrocyte.

Acid-Base Equilibrium↗

Evaluation of variation of acteoside and three major flavonoids in wild and cultivated Scutellaria baicalensis roots by micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (MEKC) conditions were developed to analyze the constituents of Scutellariae Radix (SR) and Scutellaria baicalensis roots. Using the MEKC method, the major flavonoid constituents of baicalin, baicalein and wogonin of wild and cultivated S. baicalensis roots were compared. In a preliminary comparison of electropherogram, one special peak was found in a wild sample but not in a 2-year-cultivated one. The compound corresponding to the peak was isolated and identified as a phenylethanoid glycoside, acteoside, by comparing the 1H- and 13C-NMR spectral data with that of the authentic compound. This is the first time acteoside has been isolated from the Scutellaria genus. It could only be found in SR derived from wild S. baicalensis roots and 4-year-cultivated plants, but not in plant materials cultivated for 3 years. Applying the MEKC method established in this study, rapid and simultaneous determinations of acteoside together with 3 flavonoids in samples were achieved. The method can thus be used for the quality control of SR in a shorter analysis period than HPLC.

Chromatography, High Pressure Liquid↗

A randomized control trial of post-operative care following endoscopic sinus surgery: debridement versus no debridement.

Endoscopic sinus surgery (ESS) has undergone exponential growth worldwide in the last decade. It is now accepted as a safe and effective means of treating sinonasal disease. The purpose of this study was to determine whether post-operative debridement is necessary after ESS. Seventeen patients undergoing bilateral primary ESS were randomized to receive debridement of either the left or right ethmoid cavity. All patients included in the study had symmetrical disease. Saline douches and all other concomitant treatments were delivered bilaterally. Outcome measures were based on regular symptom scores and surgeons' semi-quantitative assessment of the debrided and non-debrided cavities, over a three-month period. Analysis of adhesion rates, healing and symptom scores showed no statistically significant difference between the two groups. In conclusion, this study did not demonstrate significant benefit from post-operative ESS cavity debridement, at least with regard to cavity healing. This should be considered a pilot study and therefore limited conclusions can be drawn. Further work is needed to determine the optimum post-operative care for ESS.

Adolescent↗

The treatment of dissociative identity disorder with cognitive analytic therapy: experimental evidence of sudden gains.

The central aim of this study was to assess the effectiveness of cognitive analytic therapy (CAT) with a patient presenting with DID. The methodology employed an A/B single case experimental design with six-months continuous follow-up in seven experimental measures. A and B represent the assessment of seven dissociative experimental variables under two conditions: baseline (A) and treatment (B). Treatment consisted of 24 sessions of CAT with four follow-up sessions, which is standard within the CAT model for personality disorder patients. A battery of measures of general psychological functioning was also completed at assessment, termination, and follow-up. During treatment the intensity of a range of dissociative symptoms was observed to be reduced, with sudden gains evident due to specific CAT interventions in specific dissociative symptoms. The long-term effectiveness of the intervention was established by the illustration of either continued stability or continued improvement in experimental variables across the follow-up period. Analysis of the general measures illustrates clinically significant change across a variety of robust psychometric measures. The study illustrates the utility of single-case approaches with dissociative disorders and the potential for utilizing CAT generally with such presentations.

Adult↗

A comparison of reported levels and expression of anger in everyday and driving situations.

Incidents of road rage are frequently reported in the media, yet despite claims that aggression on congested roads is a serious social problem, little empirical research has explored the question of whether people really do become more aggressive behind the wheel. This study compares levels and expression of anger in everyday and driving situations with the aim of testing some of the commonly held beliefs about aggression on the roads. A survey questionnaire presented 15 short scenarios describing frustrating situations and included a measure of anger and three levels of expression, outward, displaced, and suppressed. The questionnaire was posted on the Internet and received 226 responses during a 3-month period. Analysis revealed that people were no more likely to report experiencing anger while driving than in non-driving situations. However, the expression of anger did differ in the two contexts. In response to the driving scenarios, respondents were significantly more likely to report displacing their anger than in non-driving situations. Those individuals who reported high levels of anger were also more likely to be outwardly aggressive while driving than they were in non-driving situations. Although males and females reported very similar levels of anger, their expression of anger did differ. For females, the largest difference is between outwardly expressing anger and the other two forms, displacing and suppressing, whereas for men, the differences between these three forms are more alike. The paper concludes with a discussion of the practical implications of these findings.

Activities of Daily Living↗

Structural studies on the core oligosaccharide of Phenylobacterium immobile strain K2 lipopolysaccharide. Chemical synthesis of 3-hydroxy-5c-dodecenoic acid.

The fatty acid composition of the bound lipids of 17 strains from Phenylobacterium immobile was investigated. Ester-linked 3-hydroxy-5c-dodecenoic acid was found to be the major substituent in the lipopolysaccharide. Therefore the occurrence of this unusual acid can be taken as a useful marker for the determination of P. immobile by simple fatty acid analysis. Lipid A backbone was found to consist of 2,3-diamino-2,3-dideoxy-D-glucose, which up to this time has only been detected in group I of purple nonsulfur bacteria and their non-phototrophic relatives. A convenient chemical synthesis for 3-hydroxy-5c-dodecenoic acid is described. The polysaccharide region of P. immobile strain K2 lipopolysaccharide was investigated. The methods used included gel filtration procedures, methylation analysis, periodate oxidation, Smith degradation, oxidation with chromium trioxide and enzymic degradations of the isolated oligosaccharide. We found that strain K2 has a rough-type lipopolysaccharide, devoid of an O-specific side chain. For the core oligosaccharide the following structure is proposed: (Formula: see text) beta-D-Glcp(1-3)-L-alpha-D-Hep rho(1-3)-L-alpha-D-Hep rho(1-3-L-alpha-D-Hep rho(1-4/5)dOclA.

Carbohydrate Conformation↗

Differences between males and females in the seasonality of birth and month of clinical onset of disease in children with type 1 diabetes mellitus in Ireland.

The aim was to study the monthly rhythm of birth and clinical onset in 303 children with type 1 diabetes mellitus (DM1) aged 0-15 years (156 males, 147 females) born between 1980 and 1996 in Ireland and compare to 951,717 infants born in the general population during the same period. Analysis was performed using the cosine fit for rhythm and t-test between the seasons of the year. Whereas the males showed a rhythmic pattern of month of birth, peaking in the summer (p < 0.05), similar to that in the general population, the females showed no seasonal differences in either month of birth or month of onset. A mirror image pattern, nadir in spring and summer (p < 0.01), was observed in month of clinical onset, also only in males. If we assume a viral infectious etiology of DMI, females seem to be less susceptible than males to the environmental infectious influences.

Adolescent↗

Failure to diagnose congenital heart disease in infancy.

OBJECTIVE: To identify factors that predict failure to diagnose congenital heart disease in newborns. DESIGN: All fatal cases in the Baltimore-Washington Infant Study were compiled. The Baltimore-Washington Infant Study includes 4390 cases of infants with congenital cardiovascular malformations identified in a population-based study between 1981 and 1989 in the Baltimore-Washington metropolitan area. Death occurred in 800 such infants in the first year of life. In 76 of these infants, death occurred before diagnosis of heart disease. These cases were identified by community search of autopsy records. Their characteristics are compared with those of infants who died after a cardiac diagnosis was made. RESULTS: Infant characteristics (birth weight, gestational age, intrauterine growth retardation, and chromosomal anomaly) are associated with death of infants with congenital cardiovascular malformations and with death of such infants before diagnosis. Diagnoses of coarctation of the aorta, Ebstein's anomaly, atrial septal defect, and truncus arteriosus are overrepresented in infants found by community search, particularly in those infants without associated malformations. Paternal education is associated with failure to diagnose congenital heart disease in life but other sociodemographic characteristics of the infant's family are not. CONCLUSIONS: Diagnosis of congenital cardiovascular malformations requires close observation in the neonatal period. Analysis of age at death of infants with undiagnosed congenital cardiovascular malformation suggests that such infants may be at risk if discharged within the first 2 days of life.

Age Distribution↗

[Monitoring and evaluating actions implemented to confront AIDS in Brazil: civil society's participation].

The United Nations Declaration of Commitment on HIV/AIDS recommends that governments conduct periodic analysis of actions undertaken in confronting the HIV/AIDS epidemic that involve civil society's participation. Specific instruments and mechanisms should be created towards this end. This paper examines some of the responses of the Brazilian government to this recommendation. Analysis contemplates the Declaration's proposals as to civil society's participation in monitoring and evaluating such actions and their adequacy with respect to Brazilian reality. The limitations and potentials of MONITORAIDS, the matrix of indicators created by Brazil's Programa Nacional de DST/Aids [National Program for STD/AIDS] to monitor the epidemic are discussed. Results indicate that MONITORAIDS's complexity hampers its use by the conjunction of actors involved in the struggle against AIDS. The establishment of mechanisms that facilitate the appropriation of this system by all those committed to confronting the epidemic in Brazil is suggested.

Acquired Immunodeficiency Syndrome↗

[Sexually transmitted diseases in adolescence: study of risk factors].

Sexually transmitted diseases are frequent in adolescence and facilitates HIV contamination. The early age limit of the first sexual intercourse, the diversity of partners, the habit of not using condoms and illicit drug abuse are pointed out as risk factors for sexual transmitted disease. We interviewed 356 adolescents who sought medical attendance at the Adolescent Health Study Center of The State University of Rio de Janeiro between August/2001 and July/2002 regarding their sexuality and to identify risk behaviors. Periodical analysis and chi-square tests were performed on the collected data. We observed statistically significant correlations between Sexual transmitted diseases and the variables of: slow learning, alcohol, tobacco and drug abuse, sexual abuse and the habit of not using condoms during sexual intercourse. The results indicate multiple Sexually transmitted disease risk behaviors in adolescence, and the failure to use condoms is the factor which is most possibly influenced by programs run by health workers.

Adolescent↗