Development of chicken antibodies to bovine interferon alpha

We have developed chicken polyclonal antibody to bovine interferon alpha (IFNalpha). Five hundred microg of recombinant bovine IFNalpha suspended with complete Freund's adjuvant was used in the first immunization round. A suspension of the same amount of IFNalpha and incomplete Freund's adjuvant was used for all subsequent boosters. The antibody was purified from egg yolks using polyethylene glycol precipitation. The first reactive antibody appeared several weeks after the first immunization. The antibody is specific for IFNalpha in immunoblotting, it is also useful in ELISA and immunohistochemistry. This method provides a fast, cheap and efficient alternative to development of monoclonal antibodies to conserved mammalian antigens.     

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.     

Prostatic central zone volume, lower urinary tract symptom severity and peak urinary flow rates in community dwelling men

PURPOSE: Previous studies have suggested that central zone prostatic volume may be more strongly correlated with lower urinary tract symptom severity and peak urinary flow rates than total prostatic volume. We determine whether prostatic central zone volume and central zone index volume correlate better with these measures than total prostate volume in an age stratified, community based random sample of healthy white men. MATERIALS AND METHODS: A cohort of 474 men were randomly selected from the 2,115 community dwelling men, 40 to 79 years old, who participated in the Olmsted County study of urinary symptoms and health status among men. All men had undergone transrectal ultrasound of the prostate. The total prostate and hypoechoic central zone volumes were caliper measured by 1 operator on static ultrasounds from baseline. Volumes were calculated with the prolate ellipsoid formula. The operator was blinded to clinical information and outcome. The associations between total prostate volume and central zone index (central zone volume/total volume), and American Urological Association (AUA) symptom index and peak urinary flow rates, respectively, were quantified with the Spearman rank correlation coefficient and least squares regression models. RESULTS: There was a moderately strong correlation between patient age and central zone volume (rs 0.54, p <0.001), total prostate volume (rs 0.45, p <0.001) and central zone index (rs 0.38, p <0.001). The AUA symptom index and peak flow rates correlated less strongly with central zone volume (rs 0.17, p = 0.001 and rs -0.20, p <0.001, respectively) and total volume (rs 0.16, p <0.001 and rs -0.16, p <0.001, respectively). Central zone index weakly correlated with AUA symptom index (rs 0.08, p = 0.103) and peak urinary flow rate (rs -0.08, p = 0.0823). In regression models predicting AUA symptom index and peak flow rates central zone volume added little information after accounting for age and total prostatic volume in predicting AUA symptom index (p = 0.55) and peak flow rate (p = 0.84). CONCLUSIONS: Central zone volume measured from static images optimized for total prostate volume no more closely correlated with lower urinary tract symptom severity or peak urinary flow rates than total prostate volume. Thus, the potentially greater imprecision in measuring central zone volume may not be offset by gains in strength of association with lower urinary tract symptom severity or peak urinary flow rates.     

Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.     

Biometric changes in the eyes of Norwegian university students--a three-year longitudinal study

PURPOSE: The aim of this study was to investigate the changes in biometric measurements and corresponding refractive errors during a three-year period among university students exposed to high educational demands. METHODS: A three-year longitudinal cohort study was performed among 149 Norwegian engineering students (79 females and 70 males, mean age 20.6+/-1.2 years) measuring their refraction and ocular dimensions at the beginning and at the end of the period. The examinations included refraction, keratometry, and A-scan ultrasonographic measurements of the ocular components, all made in cycloplegia. RESULTS: After three years the mean refractive change was -0.52+/-0.45 D (p<0.05), which was accompanied by a change in lens thickness of 0.07+/-0.10 mm (p<0.05), and a vitreous chamber elongation of 0.27+/-0.30 mm (p<0.05). The results refer to the right eye. Stratification of the sample based on their initial refraction (myopes, emmetropes, and hyperopes) showed refractive change towards myopia for all subgroups as well as a significant increase in lens thickness and vitreous chamber depth. No significant three-year change in anterior chamber depth or corneal curvature was found in any of the groups. For all groups, vitreous chamber elongation gave a notable dioptric change in myopic direction. CONCLUSIONS: A shift in refraction towards myopia after puberty is accompanied by vitreous chamber elongation which can explain the dioptric change in myopic direction.     

The clinical effect and the effect on serum IgG antibodies to peripheral nerve tissue of plasma exchange in patients with Guillain-Barré syndrome

Summary The mixed haemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with the Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange were examined in 18 patients. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after plasma exchange. Before the exchange antibodies were detected in sera from 11 of the patients. These patients showed clinical improvement during the treatment. After plasma exchange, antibodies were detected in sera from only two of the patients. The seven patients without detectable antibodies showed no clinical improvement.

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Zusammenfassung Bei 18 Patienten mit Guillain-Barré Syndrom, die einem therapeutischen Plasmaaustausch (PA) unterzogen wurden, wurde das Serum mit Hilfe einer gemischten Hämagglutinations-Technik auf IgG-Antikörper (IgG-AK) gegen peripheres Nervengewebe untersucht. Einfluß der PA auf den klinischen Zustand und Titerverlauf wurden verglichen: Bei 11 Patienten wurden IgG-AK gefunden; sie zeigten unter der PA eine klinisch verifizierte Besserung, die in einigen Fällen auch elektromyographisch gesichert werden konnte; nach Beendigung der PA waren nur noch in 2 Fällen IgG-AK nach-weisbar. Bei den restlichen 7 Patienten fehlten IgG-AK; bei ihnen war die PA ohne Effekt.

     

Serum concentrations of thyrotropin, thyroid hormones and thyroid hormone-binding proteins during acute and recovery stages of idiopathic respiratory distress syndrome.

A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3--5. After that period an increase in thyroid hormone levels occurred. The serum T2 increased to the level of healthy prematures by day 6--10, whereas the serum T4 increased to normal levels by day 21--30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T4/TBG ratios were low during recovery from IRDS.     

Pharmacokinetics of a single oral dose of muzolimine in cardiac failure

Summary The pharmacokinetics of a new high ceiling diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The -phase (distribution phase) lasted until 12–16 h after administration and the mean t_1/2 was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t_1/2 was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T_1/2 was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min^–1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.