A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.     

Quantitative in situ hybridization of three gonadotropin-releasing hormone-encoding mRNAs in castrated and progesterone-treated male tilapia

We investigated the effects of castration and progesterone administration on the three gonadotropin-releasing hormone (GnRH)-encoding mRNAs in sexually mature male tilapia Oreochromis niloticus. In situ hybridization histochemistry was performed using 35S-labeled antisense oligonucleotide probes complementary to salmon-, seabream-, and chicken II-GnRH cDNAs to quantify cellular GnRH mRNA expression in the terminal nerve ganglia (nucleus olfactoretinalis), preoptic area, and midbrain tegmentum of animals castrated for 2 weeks and injected intraperitoneally with sesame oil or progesterone. Castration significantly elevated salmon-GnRH mRNA but not seabream- or chicken II-GnRH mRNA levels. Progesterone treatment had no effect on salmon-, seabream-, or chicken II-GnRH mRNA levels. Comparisons between intact, castrated, and progesterone-treated animals showed no change in the total volume of nucleus olfactoretinalis, cell sizes, and total numbers of cells expressing GnRH mRNA within the midbrain and preoptic area. These results demonstrate that salmon-GnRH but not seabream- or chicken II-GnRH-synthesizing neurons are under a gonadal steroid negative feedback control and that progesterone might not be the main hormone regulating the three GnRH-encoding mRNAs in the male tilapia.     

Ecto-nucleotidases terminate purinergic signalling in the cochlear endolymphatic compartment

There is strong evidence for a purinergic signalling system in the inner ear which regulates auditory sensitivity. This study describes the terminating mechanism for purinergic signalling in the cochlear endolymphatic compartment via ecto-nucleotidases. Exogenous ATP was introduced into the scala media (SM) of the isolated, perfused guinea-pig cochlea, and the effluent was assayed for the adenine nucleotide metabolites by reverse-phase HPLC. Tissue viability was confirmed by fluorescence imaging of cochlear tissues. Extracellular ATP degradation to adenosine was Ca2+/Mg2+ dependent, and was not affected by inhibitors of intracellular ATPases and non-specific alkaline phosphatase. High azide concentration (5 mM) and suramin produced an inhibitory effect on ATP hydrolysis, consistent with inhibition of E-type ATPase activity. The Vmax of ATP hydrolysis (2564 mumol min-1 SM-1) was indicative of high ecto-ATPase activity. Our results support the role of ecto-nucleotidases as a principal mechanism for termination of purinergic signalling within SM, a compartment of the cochlea showing considerable P2X receptor expression.     

Expression of vimentin and cytokeratin in eutopic and ectopic endometrium of women with adenomyosis and ovarian endometrioma

Tuberculosis is a continuous threat for health in all parts of the world. In industrialized centers an emerging increase of tuberculosis is observed due to low health standards, poor health education and control, increasing migration and the HIV epidemic. This should alert the pediatrician, since most tuberculosis infections in childhood start with contacts of infected adults with children. There is still a good response to most drugs against tuberculosis, but in some parts of the world the resistance to conventional treatment is an emerging problem. In general incidence, morbidity and mortality of tbc in children of the western world is low and has good prognosis. However, the diagnostic principles and the education of pediatricians for recognizing tbc is still of utmost importance.     

Effect of nisin on heat injury and inactivation of Salmonella enteritidis PT4

To gain more insight into decision making around the termination of resuscitation (CPR), we studied factors which influenced the time before discontinuing resuscitation, and the criteria on which those decisions were based. These criteria were compared with those of the European Resuscitation Council (ERC) and the American Heart Association (AHA). For this study, we reviewed the audiotapes of resuscitation attempts in a hospital. A total of 36 attempts were studied, involving 27 men and nine women, mean (S.D.) age 64 (18) years. A total of 19 patients received resuscitation on general wards, and 17 in the emergency room after an out-of-hospital circulatory arrest. The median interval time (range) from start to termination was 33 min (8-81 min). Results from multiple linear regression showed that a delay greater than 5 min in first advanced life support measures, drawing a sample for biochemical analysis, and the patient's response shown by return of spontaneous circulation were independently associated with the time of terminating resuscitation. The team used a number of criteria which can be found in the guidelines of the ERC and the AHA, but also used additional criteria. The ERC and the AHA criteria were not sufficient to cover all termination decisions. We conclude that the point in time to terminate resuscitation is not always rationally chosen. Updating of the current guidelines for terminating resuscitation and training resuscitation teams to use these guidelines is recommended.     

Paracetamol poisoning in the north east of England: presentation, early management and outcome

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.     

Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential

BACKGROUND: The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone-related protein (PTHrP) both increase heart rate. METHODS AND RESULTS: We used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated rabbit sinus node myocytes. Sinus node maximum diastolic potential, activation voltage, and amplitude were unchanged by PTH or PTHrP (P>.05). However, the slope of phase 4 and the automatic rate were increased at PTH and PTHrP > or = 10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study the I(f) pacemaker current in sinus node. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increased I(f) at -65 mV by 68+/-41% (n=5) and 69+/-50% (n=5), respectively. Actions of both agents were reversible. The increase in I(f) appeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation. CONCLUSIONS: These observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.     

Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors

1. Ketamine has a number of effects that suggest that it may interact with alpha- and beta-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to alpha- and beta-adrenoceptors. 2. Membrane preparations of alpha 1- and beta 2-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]-prazosin for alpha 1-adrenoceptor binding sites and [125I]-cyanopindolol (CYP) for the beta 2-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displace [3H]-prazosin revealed a Kd of 3.40 +/- 1.23 x 10(-3) mol/L for ketamine binding to alpha 1-adrenoceptors. Displacement studies of [125I]-CYP by ketamine showed a Kd of 0.35 +/- 0.03 x 10(-3) mol/L for ketamine binding to beta 2-adrenoceptors. 4. We conclude that ketamine interacts directly with both alpha 1- and beta 2-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.