Effect of constant administration of a gonadotropin-releasing hormone agonist on reproductive activity in mares: induction of ovulation during seasonal anestrus

The potential of a gonadotropin-releasing hormone (GnRH) agonist (goserelin acetate), delivered constantly for 28 days via a subcutaneous depot, to induce ovulation in seasonally anestrous mares, was investigated. Two experiments were conducted, in which a range of doses (30 to 240 micrograms/mare/d) was examined. Mares were selected on the basis of lack of substantial follicular development (follicle diameter < 20 mm determined ultrasonically) and low serum concentrations of luteinizing hormone (LH) and progesterone. Constant administration of the GnRH agonist-induced ovulation in anestrous mares, but a dose-response relation was not observed. Furthermore, with identical doses tested in consecutive or alternate years, considerable variation was observed in the ovulatory response. In general, ovulation in all treated mares was accompanied by increased circulating concentrations of LH and a decrease in follicle-stimulating hormone values. Ovulation was preceded by an increase in estradiol and LH concentrations. In mares in which ovulation did not occur, concentration of LH increased during agonist treatment, whereas that of follicle-stimulating hormone either increased or did not change. It was concluded that constant administration of GnRH agonists may induce ovulation in mares during seasonal anestrus; however, percentage of mares ovulating and the lack of reproducibility of effect indicate that this approach is inappropriate for use as a reliable method to manipulate breeding activity in commercial broodmares.     

Non-deterministic exponential time has two-prover interactive protocols

We determine the exact power of two-prover interactive proof systems introduced by Ben-Or, Goldwasser, Kilian, and Wigderson (1988). In this system, two all-powerful noncommunicating provers convince a randomizing polynomial time verifier in polynomial time that the inputx belongs to the languageL. We show that the class of languages having tow-prover interactive proof systems is nondeterministic exponential time.We also show that to prove membership in languages inEXP, the honest provers need the power ofEXP only.The first part of the proof of the main result extends recent techniques of polynomial extrapolation used in the single prover case by Lund, Fortnow, Karloff, Nisan, and Shamir.The second part is averification scheme for multilinearity of a function in several variables held by an oracle and can be viewed as an independent result onprogram verification. Its proof rests on combinatorial techniques employing a simple isoperimetric inequality for certain graphs:     

Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635

Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encounters with unfamiliar conspecifics. We have now examined the effect of the 5-hydroxytryptamine1A receptor antagonist, WAY-100635, on fluoxetine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-100635 (0.1 mg/kg), which did not modify behaviour when given alone, potentiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the fluoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0.33 mg/kg/day), although the increase in aggression was smaller. Venlafaxine (5.54 mg/kg/day, alone or co-administered with WAY-100635) increased aggression by day 2. During chronic treatment, therefore, venlafaxine, at the dose used, had a more rapid onset of action than either fluoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated by WAY-100635. These studies further support the hypothesis that selective blockade of the 5-hydroxytryptamine1A receptor augments the effects of antidepressant drugs in an animal model predictive of antidepressant activity, presumably by concomitant blockade of the somatodendritic 5-hydroxytryptamine1A autoreceptor-mediated negative feedback system of serotonergic neurones.     

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

Bladder pseudotumor in childhood

The application of frozen and radiation sterilized allogenic bone grafts for reconstructions in orthopaedic operations is described. Analysis of results of treatment of 1125 patients was performed. It was found that use of preserved bone allows to reduce the extend and duration of surgery. Nearly total substitution of grafts may be seen in 3 to 8 months after surgery.