One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes two clinically distinct phenotypes.

BACKGROUND: Papillon-Lefévre syndrome (PLS; OMIM 245000) and Haim-Munk syndromes (HMS; OMIM 245010) are phenotypic variants of the same rare disease caused by mutations of the cathepsin C (CTSC) gene, and they exhibit autosomal recessive inheritance. AIMS: To identify diseases caused by mutations of the CTSC gene in two Hungarian patients and to perform haplotype analysis to elucidate any familial relationship between them. METHODS: Mutation screening and polymorphism analysis were performed by direct sequencing of the CTSC gene. RESULTS: Mutation screening of the CTSC gene from the two patients revealed the presence of the same homozygous nonsense mutation (c.748C/T; p.Arg250X). However, one patient exhibited the PLS phenotype and the other the HMS phenotype. Although these patients were not aware that they were related, haplotype analysis, especially the genotypes of the rs217116 and the rs217115 polymorphisms, clearly indicated that the patients carry the same haplotype, whereas the unrelated healthy controls carried several different haplotypes. CONCLUSIONS: Our results demonstrate that PLS and HMS are phenotypic variants of the same disease and, additionally, exclude the presence of a putative genetic modifier factor within the CTSC gene that is responsible for the development of the two phenotypes. We suggest that this putative genetic modifier factor is located outside the CTSC gene, or alternatively, that the development of the different phenotypes is the consequence of different environmental or lifestyle factors.

[Effectiveness of Lisinopril in the treatment of heart failure]. / Lisinopril-kezelés hatékonyságának vizsgálata kardiális dekompenzációban szenvedó betegeken.

A prospective study was performed in patients (30 M, 16 F, mean age of 56.0 +/- 9.2 [42-73] years) with congestive heart failure to assess the efficacy of lisinopril during a 16 weeks treatment period. Changes in clinical signs, functional capacity, blood pressure, heart rate, echocardiographic parameters, exercise duration, laboratory data and quality of life were measured. After a 2-week run-in period starting daily dose of study drug was 5 mg, and an increase of medication was considered at 4 weeks. At the end of the study mean daily dose of lisinopril was 15.1 +/- 6.2 mg. Improvement of NYHA status by 2 grades was observed in 4 cases (9%), by 1 grade in 24 cases (51%), there was no change in 17 cases (38%), and worsening was observed in 1 case (2%). During the study both systolic (p = 0.001) and diastolic blood pressure (p = 0.0006) decreased significantly, the changes in pulse rate were not significant. Left ventricular end systolic (p = 0.001) and end diastolic (p = 0.003) dimensions decreased, ejection fraction rose by 4.4% (p = 0.0002). One patient was removed from the study because of drug-induced cough. Comparison of all the laboratory data for pre and post-study periods did not reveal any significant difference. Patients treated with lisinopril improved significantly for clinical, haemodynamic, echocardiographic and quality of life parameters, with few adverse experiences, good tolerability and once-daily dose.

[Infection control in dentistry. II.: Disinfection od dental handpieces]. / Higiénia a fogászatban. II.: Kézidarabok dezinficiálasa.

The effectiveness of three different kind of sterilization or disinfection procedures was investigated in case of contaminated turbine handpieces. The results demonstrated that formaldehyde, isopropyl-alcohol and ethylenoxid are equally effective to disinfect or sterilize handpieces. The isopropyl-alcohol solving in pure ethyl-alcohol is one of the material which complies most of the requirements, as described by the authors.

[Hygiene in dentistry. I. Contamination of handpieces and dental units]. / Higiénia a fogászatban. I. Kézidarabok és az egységkészülékek fertözöttsége.

The microbial contamination was examined after clinical use in three groups: 1. autoclaved, 2. disinfected, 3. non treated dental turbine handpieces. The results did not show any difference in contamination between groups of handpieces. The authors described their recommendations how to use dental handpieces in cases of different cooling water supply of units.

[Calcium antagonists and ischemic heart disease]. / Kalcium-antagonisták és ischaemiás szívbetegség.

The authors give a short account about the significance, basic rules in regulation of intracellular (cytosolic) calcium homeostasis, distribution of calcium channels in different organs and characteristics of L channels in cardiovascular system. The different types of calcium channel blockers (dihydropyridines, phenylalkilamines, benzothiazepines), their similarities, dissimilarities (cardio, -vascular selectivity) are discussed. Differences in calcium homeostasis, in sympathetic innervation between vascular smooth- and heart muscle in briefly disputed. The basic role of endothel cell dysfunction in development of ischemic heart disease, the possible mechanisms (potential anti-remodeling, antifissuring, antiischemic, cardioprotective, sympaticolytic effects) of different calcium antagonists in the treatment of patients with ischemic heart disease are reviewed. Potential adverse effects of calcium channel blockers (proischemic, proarrhythmic, procongestive, prohaemorrhagic effects) are also mentioned. Finally the up-date preventive and therapeutic indications of different calcium channel blockers in the clinical management of patients with stable, unstable angina pectoris, silent myocardial ischemia, vasospastic angina, acute myocardial infarction is shortly reported.