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PubMedDate not supplied

Virus-inactivated factor VIII concentrate prevents postoperative bleeding in a patient with von Willebrand's disease.

A patient with von Willebrand's disease underwent cholecystectomy after replacement therapy with a factor VIII concentrate that had been sterilized by treatment with tri(n-butyl)phosphate and Tween 80. The patient received 53 units of factor VIII per kg of body weight prior to operation. In addition, a total of 280 units of factor VIII per kg was infused within 10 days after operation. This replacement regimen prevented excessive bleeding during surgery and supported normal hemostasis during the postoperative period. Analysis of the multimeric pattern and the functional assay of von Willebrand factor in factor VIII concentrates indicated that the procedures utilized for virus inactivation had no significant deleterious effect upon the quality of von Willebrand factor molecules.

Adult↗
PubMed2001

The growth hormone (GH)-insulin-like growth factor axis during testosterone replacement therapy in GH-treated hypopituitary males.

Several studies suggest a direct effect of sex steroids on insulin-like growth factor-I (IGF-I) production. Oestrogen has been hypothesized directly to inhibit hepatic IGF-I production, but the role of androgens is not clarified. We aimed to investigate whether testosterone exerts a pituitary-independent effect on IGF-I and related parameters. Eight adult hypopituitary men (39.9 +/- 5.7 years) receiving growth hormone (GH) and testosterone replacement therapy (250 mg testosterone enantate every fourth week) participated in this prospective study. Frequent blood samples were drawn over a 5 week period in relation to two testosterone injections. Mean baseline IGF-I levels were 352 +/- 135 microg/L, and they remained unaltered during the study period (analysis of variance (ANOVA), P = 0.88). Free IGF-I levels did not change either (ANOVA, P = 0.35). Serum IGF binding protein-3 (IGFBP-3) and acid-labile subunit decreased (ANOVA, P = 0.04 and P = 0.02 respectively) but post hoc analysis did not reveal a particular difference between days. IGFBP-1 increased following testosterone administration (ANOVA, P = 0.05), whereas GH binding protein levels tended to decrease following testosterone administration (ANOVA, P = 0.08). Prostate-specific antigen tended slightly to increase after each testosterone injection (ANOVA, P = 0.08, post hoc, NS). We conclude that major changes in total IGF-I are not induced during conventional intramuscular testosterone replacement in GH-treated hypopituitary males, suggesting that testosterone effects on IGF-I are likely to be secondary to a stimulation of endogenous GH release.

Adult↗
PubMed1995

[Incidence of birth injuries to newborn infants in relation to birth weight. An analysis of the Hessen perinatal study].

There has been a decrease in the incidence of obstetric traumas in single newborn in vertex presentation weighing more than 2.499 g between 1983 and 1992, in Hessian hospitals, the drop in incidence being from 0.70% to 0.33%. The rate of injuries depends on the birth weight. During the perinatal analysis period of 10 years the average rate of injuries is 0.47% in the birth weight range between 2.500-3.999 g, in the range between 4.000 and 4.499 g 1.61% and in the birth weight group above 4.499g 3.39%. These differences are statistically highly significant. During the ten years under report, 1.908 infant injuries at birth were recorded. 70% of these infants were in the 2.500-3.999 g range and only 6.7% in the weight group beyond 4.999 g. There are no comparable data in literature. The drop in the rate of injuries compared to 1983 is represented by a factor of 2.5 in the 2.500-3.999 g birth weight range, by 1.5 in the 4.000-4.499 g range and by 1.8 in the group over 4.999 g. We do not intend to artificially construct a connection, but during the report period there was an increase in the rate of Caesarean sections in cases of vertex presentation and single births, in all weight groups. If in any particular case the birth weight is estimated to be higher than 4.499 g according to sonographic examination, this does not imply that Caesarean section must be performed, since that would be associated with increased maternal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Injuries↗
PubMed2007

Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia.

BACKGROUND: Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients. METHODS: We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid-lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4 weeks, and returned for a final visit after a 4-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for fat content were performed throughout the study. RESULTS: All patients tolerated titration to the highest dose, 1.0 mg per kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL) cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline (P<0.001 for both comparisons). Kinetic studies showed a marked reduction in the production of apolipoprotein B. The most serious adverse events were elevation of liver aminotransferase levels and accumulation of hepatic fat, which at the highest dose ranged from less than 10% to more than 40%. CONCLUSIONS: Inhibition of the microsomal triglyceride transfer protein by BMS-201038 resulted in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, owing to reduced production of apolipoprotein B. However, the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation.

Adolescent↗
PubMed2003

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland.

Melatonin is produced nocturnally by the pineal gland and is a neurochemical representation of time. It regulates neuroendocrine target tissues through G-protein-coupled receptors, of which MT(1) is the predominant subtype. These receptors are transiently expressed in several fetal and neonatal tissues, suggesting distinct roles for melatonin in development and that specific developmental cues define time windows for melatonin sensitivity. We have investigated MT(1) gene expression in the rat pituitary gland. MT(1) mRNA is confined to the pars tuberalis region of the adult pituitary, but in neonates extends into the ventral pars distalis and colocalizes with luteinizing hormone beta-subunit (LH beta) expression. This accounts for the well documented transient sensitivity of rat gonadotrophs to melatonin in the neonatal period. Analysis of an upstream fragment of the rat MT(1) gene revealed multiple putative response elements for the transcription factor pituitary homeobox-1 (Pitx-1), which is expressed in the anterior pituitary from Rathke's pouch formation. A Pitx-1 expression vector potently stimulated expression of both MT(1)-luciferase and LH beta-luciferase reporter constructs in COS-7 cells. Interestingly, transcription factors that synergize with Pitx-1 to trans-activate gonadotroph-associated genes did not potentiate Pitx-1-induced MT(1)-luciferase activity. Moreover, the transcription factor, early growth response factor-1, which is induced by gonadotrophin-releasing hormone (GnRH) and trans-activates LH beta expression, attenuated Pitx-1-induced MT(1)-luciferase activity. Finally, pituitary MT(1) gene expression was 4-fold higher in hypogonadal (hpg) mice, which do not synthesize GnRH, than in their wild-type littermates. These data suggest that establishment of a mature hypothalamic GnRH input drives the postnatal decline in pituitary MT(1) gene expression.

Animals↗
PubMed1977

Presence of a putative 15S precursor to beta-globin mRNA but not to alpha-globin mRNA in Friend cells.

Dimethyl sulfoxide-induced Friend cells were labeled for periods of 5-60 min. The denatured RNA was fractionated by sucrose gradient centrifugation and the distribution of alpha- and beta-globin-specific [(3)H]RNA was determined by hybridization to hybrid plasmids containing mouse alpha- and beta-globin DNA, respectively. After 5 min of labeling, a 15S peak of beta-globin-specific (but not alpha-globin-specific) [(3)H]RNA was detected, next to an equal amount of 10S beta-globin [(3)H]RNA. With increasing periods of labeling, the amount of 15S beta-globin [(3)H]RNA remained constant but the amount 10S beta-globin [(3)H]RNA increased steadily. alpha-Globin-specific [(3)H]RNA sedimented at 11 S after 5 min of labeling and at 9.5 S after longer labeling periods. Analysis of 15S globin-specific [(3)H]RNA purified by the poly(dC)-cDNA method [Curtis, P. J. & Weissmann, C. (1976) J. Mol. Biol. 106, 1061-1075] showed oligonucleotides characteristic of beta-globin mRNA but not of alpha-globin mRNA, as well as about 20 new oligonucleotides. Our results suggest that 10S beta-globin mRNA arises via a 15S precursor that has a half-life of 5 min or less; 9.5S alpha-globin mRNA may be derived from an 11S precursor.

Animals↗
PubMed2003

The epidemiology of head injuries in Sweden from 1987 to 2000.

The purpose of the present study was to evaluate the variability in the annual head injury incidence rate in Sweden from 1987 to 2000. It was hypothesized that the annual incidence rate would decrease over time due to a variety of primary preventive strategies that have been introduced in Swedish society. We used the Hospital Discharge Register at the National Board for Health and Welfare and head injury codes 800-804, and 850-854 from ICD9 system and S2.0-S2.9, and S6.0-S6.9 codes from ICD-10 system. We evaluated the patterns of age, gender, external cause of injury (E-code), type of injury, length of hospital stay, and trends over time. Head injuries due to transportation collision were reduced over the 14-year period analysis. Falls persisted as the dominant cause of head injury. Overall, men had 2.1 times the incidence of head injury compared to women. There was a decline in younger ages experiencing a head injury over this interval, while the number of head injuries among elderly people increased over time. Concussion was about three times more frequent than fractures. Hematoma and diffuse or focal contusions had a much lower incidence rate than concussion. Concussions and fractures decreased over time. Diffuse or focal injuries showed a steady rate of occurrence over the study interval while hematoma increased. Although length of hospital stay varied widely from zero to more than 50 days, 73.6% of hospital days were confined to two days or less. The incidence rate is stable over this time frame. While head injuries attributable to transportation accidents decreased, falls made up an increasing proportion of head injuries. Since we observed an increase in head injuries among elderly, primary prevention strategies may need to be targeted at this age group, and at preventing falls.

Accidental Falls↗
PubMed1988

The effect of the preceding day's protein intake on basal metabolic rates in young adults.

1. Changes in basal metabolic rates (BMR), following alterations in the preceding day's dietary protein (8.6, 11.5 and 14.0% of energy) were studied in eight, young, healthy adults over 4 d. 2. Results showed a significant training effect, with BMR values 4.8% lower on day 4 of the study period. Analysis of the results by ANOVA revealed a significant interaction between subjects and diets (P less than 0.005), a significant difference between subjects but no differences in BMR due to the protein content of the diets. 3. Mean coefficient of variation (CV) for intra- and inter-individual differences in BMR from day-to-day was of the order of 4 and 9% respectively. 4. Changes in protein content of the preceding day's diet do not influence variations in BMR which appear to be random in nature with a true CV of 3.8%.

Adult↗
PubMed1998

Hypnosis enhances recall memory: a test of forced and non-forced conditions.

Visual memory recall in hypnosis was investigated. To address criterion shift problems in previous studies, both forced and non-forced recall procedures were used. Previous methodological weaknesses with regard to hypnotizability and hypnotic depth were also addressed. Over 300 volunteers were screened for hypnotizability using the Harvard Group Scale of Hypnotic Susceptibility: Form A (Shor & Orne, 1962). Final high and low hypnotizability groups were selected using the Stanford Hypnotic Susceptibility Scale: Form C (Weitzenhoffer & Hilgard, 1962). Participants in each hypnotizability group were randomly assigned to either forced or non-forced recall conditions and to hypnosis or waking conditions. Participants were shown 60 slides of line drawings and then tested immediately in 3 recall periods. Analysis of variance results showed that those exposed to hypnosis and to a forced recall procedure were significantly more confident of their responses to correct items than those exposed to a non-forced recall procedure or a waking condition. Participants exposed to hypnosis and forced recall procedures recalled more correct items than those exposed to a waking condition. The findings support the hypermnesic effects of hypnosis when participants are required to provide a fixed number of responses.

Adult↗
PubMed1986

The autodecomposition of radiolabeled human growth hormone.

Human growth hormone (hGH) was radiolabeled with 125I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric 125I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf-life and repurification schedule of radioiodinated polypeptides.

Drug Stability↗
PubMed1989

Changes in limb striking pattern: effects of speed and accuracy.

This study investigated the changes in an arm striking pattern as a result of practice and the effects of speed and accuracy requirements on such changes. The task was to strike a baseball-size foam ball from a batting tee adjusted to the height of each subject's iliac crest. Ten righthanded subjects, initially displaying an inefficient striking pattern, volunteered for this study. All subjects performed the task according to the following conditions: (1) speed, (2) accuracy, and (3) speed and accuracy. Each subject completed 10 trials in each condition (randomly ordered) for five consecutive days. A high-speed camera (64 fps) was used to photograph subjects' striking patterns for each condition over the 5-day period. Analysis of variance of joint angles at arm reversal and contact and velocity of hand relative to the glenohumeral axis at contact revealed that subjects initially constrained limb segments to act in a unitary fashion; then, with practice, a more efficient pattern was developed. The requirement of speed was found to enhance a change in limb configuration, whereas the requirement of accuracy, and subsequent reduction in speed, impeded the development of a more efficient striking pattern. Analysis of radial error revealed no differences in accuracies to the target by either condition or day of practice. A graphic analysis of segmental angular momentum versus relative time showed that joint angle changes allowed subjects to transfer angular momentum and thereby increase the velocity of the hand at contact.

Acceleration↗
PubMed2000

Biological removal of gaseous ammonia in biofilters: space travel and earth-based applications.

Gaseous NH3 removal was studied in laboratory-scale biofilters (14-L reactor volume) containing perlite inoculated with a nitrifying enrichment culture. These biofilters received 6 L/min of airflow with inlet NH3 concentrations of 20 or 50 ppm, and removed more than 99.99% of the NH3 for the period of operation (101, 102 days). Comparison between an active reactor and an autoclaved control indicated that NH3 removal resulted from nitrification directly, as well as from enhanced absorption resulting from acidity produced by nitrification. Spatial distribution studies (20 ppm only) after 8 days of operation showed that nearly 95% of the NH3 could be accounted for in the lower 25% of the biofilter matrix, proximate to the port of entry. Periodic analysis of the biofilter material (20 and 50 ppm) showed accumulation of the nitrification product NO3- early in the operation, but later both NO2- and NO3- accumulated. Additionally, the N-mass balance accountability dropped from near 100% early in the experiments to approximately 95 and 75% for the 20- and 50-ppm biofilters, respectively. A partial contributing factor to this drop in mass balance accountability was the production of NO and N2O, which were detected in the biofilter exhaust.

Air Pollution↗
PubMed2005

Psychosocial benefits of solitary reminiscence writing: an exploratory study.

Claims have been made that reminiscence has benefits for older people's psychological well-being, and that writing memories may be a therapeutic process. This paper describes an exploratory study in which five nursing home residents engaged in a process of writing their memories by themselves, in a series of booklets containing memory prompts and photographs, over a period of four weeks. Each completed booklet was typed up by researchers and returned to participants the following week, with a bound copy provided to participants at the end of the study period. Analysis focuses on two sets of data: an in-depth case study of one participant, and a thematic analysis of field notes, researcher reflections, and the written material produced by the other study participants. The case study revealed three main themes: views on the past; sharing the past; and confidence in writing about the past. The field note analysis indicated the presence of four themes: proof and maintenance of skills; psychological or internal processes; social contact; and pleasure in reminiscence. The writing was seen as cathartic and provided a meaningful purpose, an opportunity to exercise writing skills and memory, and a focus for participants to share key stories with others. This exploratory study suggests that there is potential in using solitary writing within a reminiscence framework to improve psychological well-being in older people. However, caution should be exercised when encouraging older people to write their stories. Issues of confidentiality, audience, support, and appropriateness of the activity for the individual need consideration.

Aged↗
PubMed1986

Short-term studies on the in vivo metabolism of N-oxides of nicotine in rats.

This study was designed to examine the in vivo reduction of the N-oxidation products of nicotine metabolism in rats. Male Fischer-344 rats were divided into one control and three experimental groups (n = 20). Each treatment group received either 0.02% trans-nicotine N'-oxide, 0.02% cis-nicotine N'-oxide, or 0.02% nicotine N,N'-dioxide in drinking water for 3 wk. After 7 d of metabolite administration, plasma nicotine levels in the trans-nicotine N'-oxide group rose to twice that of the cis-nicotine N'-oxide or nicotine N,N'-dioxide group. Plasma cotinine [1-methyl-5-(3-pyridinyl)-2-pyrrolidinone] concentrations reached maximum levels during wk 1 in the cis-nicotine N'-oxide and nicotine N,N'-dioxide groups but continued to increase for another 7 d in the trans-nicotine N'-oxide group. At d 15 and again at d 21, rats from each group (n = 10) were placed in metabolism chambers and given 50 ml tap water over a 24-h period. Analysis of urine obtained from a metabolism-chamber study conducted after 15 d of consumption revealed concentrations of nicotine in the trans-nicotine N'-oxide group that were 3 times higher than cis-nicotine N'-oxide-treated animals. Urinary cotinine levels were similar in all three groups. Results from a second chamber study (d 21) showed similar urinary nicotine and cotinine values in all treatment groups. Plasma total triiodothyronine (TT3) concentrations were reduced in all treatment groups during the first week. Plasma total thyronine (TT4) concentrations were reduced (p less than 0.05) in the trans-nicotine N'-oxide and cis-nicotine N'-oxide treatment groups during the first week. Plasma total thyronine (TT4) concentrations cis-nicotine N'-oxide is presented. An analytical method for separation of nicotine, cotinine, and cis- and trans-nicotine N'-oxide, as well as cis- and trans-nicotine N,N'-dioxide, is also outlined.

Age Factors↗
PubMed2006

A comparison of vasopressin and glucagon in beta-blocker induced toxicity.

OBJECTIVE: We compared the efficacy of vasopressin and glucagon in a porcine model of beta-blocker toxicity. Our primary outcome was survival over 4 hours. METHODS: Sixteen pigs received a 1-mg/ kg bolus of propranolol IV followed by continuous infusion at 0.25 mg/kg/minute. Toxicity was defined as a 25% decrease in the product of heart rate (HR) and mean arterial pressure (MAP), at which point 20 mL/kg normal saline was rapidly infused. Each pig was randomly assigned to receive either vasopressin or glucagon after the saline bolus. The vasopressin group received a continuous infusion at 0.0028 U/kg/minute, titrated up to a maximum of 0.014 U/ kg/minute. The glucagon group received a 0.05-mg/kg bolus followed by continuous infusion at 0.15 mg/kg/hour. The HR, MAP, systolic BP (SBP), cardiac output (CO), glucose, and pH were monitored for 4 hours from toxicity or until death. RESULTS: One pig survived at 4 hours (vasopressin group). Analysis of the 4-hour Kaplan-Meier survival curves found no differences between the groups (log-rank test 0.059, p = 0.81). No overall differences were identified in MAP, systolic BP, cardiac output, glucose, pH, or HR. However, over the first hour MAP and SBP were significantly higher in the vasopressin group (p = 0.004, p = 0.006, respectively). CONCLUSION: In this beta-blocker toxicity model, there were no differences in the survival curves between vasopressin- and glucagon-treated pigs during a 4-hour analysis period. No overall differences were noted in MAP, systolic BP, CO, HR, pH, or glucose levels, although vasopressin treatment yielded higher MAP and systolic BP early in resuscitation.

Adrenergic beta-Antagonists↗
PubMed2006

Secondary structure of a KCNE cytoplasmic domain.

Type I transmembrane KCNE peptides contain a conserved C-terminal cytoplasmic domain that abuts the transmembrane segment. In KCNE1, this region is required for modulation of KCNQ1 K(+) channels to afford the slowly activating cardiac I(Ks) current. We utilized alanine/leucine scanning to determine whether this region possesses any secondary structure and to identify the KCNE1 residues that face the KCNQ1 channel complex. Helical periodicity analysis of the mutation-induced perturbations in voltage activation and deactivation kinetics of KCNQ1-KCNE1 complexes defined that the KCNE1 C terminus is alpha-helical when split in half at a conserved proline residue. This helical rendering assigns all known long QT mutations in the KCNE1 C-terminal domain as protein facing. The identification of a secondary structure within the KCNE1 C-terminal domain provides a structural scaffold to map protein-protein interactions with the pore-forming KCNQ1 subunit as well as the cytoplasmic regulatory proteins anchored to KCNQ1-KCNE complexes.

Amino Acid Sequence↗
PubMed2005

Safety and immunogenicity of glycoprotein D-adjuvant genital herpes vaccine.

BACKGROUND: Two previous trials have suggested that a herpes simplex virus (HSV) type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and 3'-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides protection against genital herpes disease in women with no preexisting HSV antibody. METHODS: The safety and immunogenicity of this vaccine were evaluated in a large, multicenter, double-blind, randomized, placebo-controlled trial. The effects of sex and preexisting HSV immunity were sought. RESULTS: When solicited symptoms that continued after the initial 4 days of observation were excluded, the incidence of unsolicited symptoms occurring during the 7 months after vaccination (the primary analysis period) was 22.1% in vaccine recipients and 21.9% in placebo recipients. Significant increases in the number of local and systemic symptoms were found in vaccine recipients within 4 days after vaccination. However, most symptoms were mild to moderate in severity and were short lived. Women reported symptoms more frequently than did men, but preexisting immunity had little effect. The vaccine induced higher titers of HSV gD antibody on enzyme-linked immunosorbent assays than did natural infection with HSV. CONCLUSION: The vaccine was generally safe, well tolerated, and immunogenic.

Adjuvants, Immunologic↗
PubMed2003

Resistance in Enterobacteriaceae: results of a multicenter surveillance study, 1995-2000.

OBJECTIVES: To assess changes over time in susceptibility of Enterobacteriaceae from patients in ICUs, compare susceptibility rates of isolates from patients in ICUs with those from inpatients outside ICUs, and explore phenotypic patterns of cross-resistance and co-resistance. DESIGN: From 1995 to 2000, centers participating in the ICU Surveillance Study tested 100 to 200 consecutive nosocomial gram-negative bacilli by broth microdilution. SETTING: Each year, 42 to 97 U.S. hospitals tested isolates. RESULTS: In all years, imipenem was the most potent agent tested, followed by amikacin and ertapenem. Extended-spectrum beta-lactam and monobactam agents had good activity against Escherichia coli and Klebsiella species, but limited activity against Enterobacter species. Susceptibility to imipenem and amikacin did not fluctuate during the analysis period, whereas susceptibility to ceftazidime, ceftriaxone, and ciprofloxacin decreased 2% to 5%. The decline was most pronounced for susceptibility of Escherichia coli to ciprofloxacin: 98.7% of ICU isolates were susceptible in 1995 versus 93.2% in 2000. Susceptibility of ICU isolates was lower than that of non-ICU isolates, except for ciprofloxacin, for which the reverse was true. Cross-resistance was common among extended-spectrum cephalosporins and penicillins, but uncommon between imipenem and ertapenem. Only imipenem and ertapenem remained highly active against Enterobacteriaceae with a phenotype suggesting possible production of an extended-spectrum beta-lactamase and those with a phenotype suggesting possible Amp C hyperproduction. CONCLUSIONS: Imipenem was the most active agent against nosocomial Enterobacteriaceae. Susceptibility to ciprofloxacin decreased from 1995 to 2000, particularly in Escherichia coli, and, in contrast to other agents, was lower among non-ICU isolates.

Cross Infection↗