Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.     

What Motivates Participation and Dropout Among Low‐Income Urban Families of Color in a Prevention Intervention?*

Low‐income urban parents of color enrolled in a parent training study were interviewed to understand what motivated their participation and what led 30% of them to subsequently drop out. Most enrolled because they wanted to be better parents. Most dropped out because of time and schedule constraints. Retention was higher when parents' motivations for participation matched program goals. Program location and qualities of the recruiter were cited most often as important; financial compensation was cited least often as important.     

Neonatal rectal colonization with Malassezia furfur

Malassezia furfur and Candida albicans are fungal pathogens which have been recognized with increasing frequency as agents of mortality and serious morbidity in neonatal intensive care unit patients. A longitudinal study of oral, rectal and umbilical colonization by these organisms of newborns admitted to a neonatal intensive care unit within 24 h of birth was undertaken. Of 71 infants followed for a minimum of 10 days, 24 were colonized with M furfur and 12 with C albicans during the first 10 days of life. The lower gastrointestinal tract was found to be the most common colonization site for both organisms. Statistically significant (P<0.05) inverse associations were demonstrated between gestational age and risk of colonization with either organism at any site, and between birthweight or gestational age and risk of rectal colonization with either organism. Antibiotics were associated with a relative risk colonization of 4.06 (P=0.06) with either organism at any site. It is concluded that M furfur and C albicans are common colonizing organisms in a neonatal intensive care unit setting and are most frequently harboured in the lower gastrointestinal tract. M furfur, recently implicated as a systemic pathogen in this population, has not been previously recognized as a gastrointestinal commensal organism. The relationship between colonization and invasive fungal disease, and potential roles for preventive strategies, remain to be elucidated.     

Head injury mortality in two centers with different emergency medical services and intensive care

The authors report data collected prospectively on 551 cases of head injury in New Delhi, India, and 822 cases in Charlottesville, Virginia. The mortality rate, adjusted for initial severity of injury, was 11.0% in New Delhi versus 7.2% in Charlottesville (p less than 0.02). There was a striking similarity in mortality rates at both centers when comparing patients with the least severe head injuries and those with the most severe injuries according to the motor score of the Glasgow Coma Scale (GCS M). However, in the group with an abnormal but purposeful motor response (GCS M = 5), the mortality rate was 12.5% in New Delhi versus 4.8% in Charlottesville (p less than 0.01). The relative absence of prehospital emergency care and the delay in admission after head injury in New Delhi are cited as two possible causes for the differences in mortality rates in this subgroup of patients with "moderate" head injuries.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Effect of carrier selection on immunogenicity of protein conjugate vaccines against Plasmodium falciparum circumsporozoites.

Conjugate vaccines against the sporozoite stage of Plasmodium falciparum were synthesized by covalently coupling the recombinant protein R32 [with the one-letter amino acid code of MDP-[(NANP)15NVDP]2LR] to tetanus toxoid, cholera toxin, choleragenoid, and Pseudomonas aeruginosa toxin A. Conjugates were produced by using adipic acid dihydrazide as a spacer molecule and carbodiimide as a coupling agent. The molar ratio of R32 to carrier protein ranged from 2.5:1 to 8.4:1. These conjugates were found to be stable, nontoxic, and nonpyrogenic. When adsorbed onto Al(OH)3, all conjugates were capable of inducing anti-R32 antibody. Conjugates made with either cholera toxin or Pseudomonas aeruginosa toxin A were significantly more immunogenic than those constructed with tetanus toxoid or choleragenoid. However, the magnitude of the immune response to the R32 moiety was not governed by the antibody response to the carrier protein.     

Das Verhalten von Blutdruck und Nierendurchblutung während des Carotissinus-Reflexes am wachen Hund

Zusammenfassung An 15 Bastardhunden wurde der Einfluß einer Na-Pentobarbital-Narkose sowei einer zusätzlichen chirurgischen Präparation auf die Ruhewerte von Blutdruck und Nierendurchblutung und deren Änderung nach doppelseitigem Carotisverschluß im Vergleich zum wachen Tier untersucht.Barbiturat-Injektion (30 mg/kg i.v.) allein erhöhte die Herzfrequenz, den systolischen und diastolischen Blutdruck, änderte jedoch nicht die mittlere Nierendurchblutung. Zusätzliche chirurgische Präparation verstärkte diese Veränderungen mit Ausnahme vom systolischen Blutdruck und der Nierendurchblutung.Bei Carotisverschuluß kam es im steady state zu einer vermehrten reflektorischen Herzfrequenzsteigerung nach Barbiturat-Injektion sowie nach Barbiturat mit chirurgischer Präparation. In Barbiturat-Narkose stieg der mittlere Blutdruck stärker an als am wachen Tier; diese Veränderung war nach chirurgischer Präparation noch deutlicher ausgeprägt. Die mittlere Nierendurchblutung wurde im steady state in keiner der 3 Gruppen signifikant verändert. Der reflektorische Herzfrequenz- und Blutdruckanstieg erfolgte im Wachzustand rascher als nach Barbiturat und Barbiturat mit chirurgischem Trauma. Unter letzteren Bedingungen fehlte auch das im Wachzustand beobachtete Unterschießen der Herzfrequenz nach Öffnen der Carotismanschetten. Der druckpassive overshoot der Nierendurchblutung am wachen Tier fehlte sowohl nach Barbiturat als auch nach zusätzlicher chirurgischer Präparation.Die Ergebnisse zeigen, daß der mit Na-Pentobarbitural narkotisierte und der narkotisierte, akut operierte Hund gegenüber dem Wachzustand betreffend der Ruhewerte und der reflektorischen Veränderungen der Herzfrequenz und des Blutdrucks im steady state des Carotissinus-Reflexes zwei quantitativ unterschiedlich reagierende Kreilaufpräparate liefert. Gemessen an der Beseitigung sowohl der raschen Herzfrequenz- und Blutdruckveränderungen als auch des phasischen Einschwingvorganges der Nierendurchblutung durch Narkose und Narkose mit Trauma unterscheiden sich solche Präparate auch qualitativ vom Wachzustand.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

New provisional serovar (E10163) of Shigella boydii

A long-term outbreak of urinary tract-associated multiply resistant Providencia stuartii occurred in a large medical facility that included a 513-bed chronic care unit. The unique characteristics of this outbreak were that from within a single medical facility, P. stuartii with multiple serotypes, biotypes, and antibiograms could be identified. The organisms isolated had five different biotypes, seven different antibiograms, and two major serotypes. All of the organisms were susceptible to amikacin, cefamandole, and cefoxitin. Application of standard infection control measures impeded the spread of this outbreak, and it slowly terminated 16 months later.