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.     

Effect of oral medroxyprogesterone acetate on menopausal symptoms in patients with endometrial carcinoma

A double-blind cross-over study was performed on 21 patients treated for endometrial carcinomas who had severe menopausal symptoms. The patients were randomized into two groups and received medroxyprogesterone acetate (MPA) 100 mg twice daily per os for 12 weeks and a placebo for 12 weeks. A significantly better effect on hot flushes and sweating was obtained with MPA than with the placebo. On average the maximum effect was achieved by MPA after 4-6 weeks. Six patients had a weight gain of more than 3 kg during the MPA administration, compared with none during the placebo administration. No significant difference was found in the blood pressure increase above 160/90 mmHg between MPA and placebo groups. Patients with endometrial carcinoma may risk exacerbation of their disease by undergoing therapy with exogenous estrogen. In contrast, MPA has been found of value in the treatment of disseminated endometrial carcinomas. In this study oral MPA was effective in the treatment of vasomotor menopausal symptoms and may be an alternative in women for whom estrogens might be hazardous.     

The Process of Engineering and Its Management

ABSTRACT

The central theme of this article is that engineering should be viewed primarily as a process rather than as a body of knowledge and that only by understanding this process can it be effectively managed. As a consequence, engineering management cannot be synonymous with project management. The article then gives an overview of engineering as a process, emphasizing the important part played by the top-down systems engineering methodology.     

Threshold of the optical backward-wave parametric oscillator

We present a discussion of the threshold condition for the optical backward-wave parametric oscillator, taking into account diffraction due to the finite transverse extent of the fields, and using three transverse modes of both the forward- and backward-wave fields. The coupled differential equations are solved numerically, and the threshold is obtained by minimizing the pump field with respect to the parameters of the forward- and backward-wave fields. Denoting the confocal parameters byb_{1}, b_{2}, and b3for the backward, forward, and pump waves, respectively, and if the length of the crystal is 1, we find that for1/b_{3} geq 2, we may setb_{1} = b_{2} =b_{3}. For most purposes, the phase-matching condition may be taken ask_{2} = k_{1} + k_{3}. Also, when calculating the threshold, it is adequate to consider only the two lowest order transverse modes of the forward-and backward-wave fields.     

Radiology--an exciting specialty, unsatisfactory training situation?

Despite the medical and technological advances during the last decade, there have been problems in attracting new recruits for radiology specialization in Norway. The increasing number of vacancies is a cause for concern. To address this problem, we held interviews with six residents--three males and three females aged between 30 and 39 years. They had from four months to three years of experience in diagnostic radiology at the time of the study. The data were analyzed according to the principles of Giorgi. The participants found radiology both interesting and challenging, but considered the specialist training inadequate, mainly because there were too many routine tasks and not enough supervision.