DFNB74, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 12q14.2-q15

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species.     

龙岩市1995～2000年涂阳肺结核病人随访研究

目的：分析福建省龙岩市结核病控制五年效果。为结核病控制可持续发展提供技术政策依据。方法：收集并分析1995年-2000年福建省龙岩市肺结核月报表和年报表及有关资料，采用队列分析方法对登记治疗管理的初，复治涂阳肺结核病人进行分析。结果：1995年-2000年涂阳肺结核病人发现率从4.9/10万上升到22.7/10万；初治涂阳治愈率从63.4%上升到95.8%；复治涂阳病人治愈率从50%上升到85.6%。结论：涂阳肺结核病人的高发现率和高治愈率是因为1999年开始实施结核病归口管理和DOTS策略，应以持续发燕尾服。     

实施现代结核病控制策略对传染性肺结核患者发现与治疗效果的影响

目的：分析实施DOTS策略对传染性肺结核病例发现与治疗效果的影响。方法：通过对1995—2000年分批实施的卫生部加强与促进结核病控制项目、WHO西太区结核病控制项目及福建省结核病控制项目资料进行分析。结果涂阳病例新登记率由1995年的6．3／10万提高到2000年的19．0／10万，涂片阳性占活动性病例比例由21．5％提高到37．4％，新发涂阳病例治愈率由80．7％提高到89．2％，病例丢失率由7．3％下降到2．7％，治疗失败率由6．9％下降到1．4％。流动人口传染性肺结核病例治愈率仅59．7％。结论：实施DOTS策略，重视流动人口结核病治疗管理，提高涂阳病例发现率、治愈率，减少病例丢失和治疗失败，有效控制结核病。     

Unresolved questions regarding human hereditary deafness

Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non‐syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by d eafness, o nychodystrophy (alteration of toenail or fingernail morphology), o steodystrophy (defective development of bone), mental r etardation, and s eizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.     

Protective effects of dietary potassium chloride on hemodynamics of Dahl salt-sensitive rats in response to chronic administration of sodium chloride

BACKGROUND: Dietary potassium supplementation decreases blood pressure and prevents strokes in humans, and prevents strokes and renal damage in Dahl salt-sensitive (DSS) rats. OBJECTIVE: To study the effects of various concentrations of dietary potassium chloride (KCl) on the hemodynamics of Dahl salt-resistant (DSR) and DSS rats receiving a 1% sodium chloride (NaCl) diet for 8 months, to determine whether there is an optimal dietary concentration of KCl that minimizes increases in blood pressure and causes least impairment of blood flow in the brain and kidneys. METHODS AND RESULTS: We found a biphasic effect on hemodynamic parameters as a function of dietary KCl in DSS rats of the Rapp strain fed 1% NaCl with increasing dietary KCl (0.7, 2.6, 4 and 8%). After 8 months receiving a diet containing 1% NaCl and 0.7% KCl, DSS rats had mean arterial pressures (MAP), plasma volumes, cardiac outputs and renal and cerebral vascular resistances that were significantly increased compared with those of DSR rats receiving the same diet. With a 2.6% KCl diet, all these parameters were significantly reduced compared with those in DSS rats fed the 0.7% KCl diet and were similar to those in DSR rats fed 2.6% KCl. Total peripheral resistance in DSR and DSS rats was similar on all diets. When KCl was increased to 4 and 8%, MAP, plasma volume, cardiac output and renal vascular resistance progressively increased in DSR and DSS rats, without changing total peripheral resistance. These changes paralleled increases in plasma aldosterone, which resulted from adrenocortical stimulation by the increasing dietary KCl; however, cerebral vascular resistance of DSR and DSS rats decreased significantly with a 4% KCl diet, despite increased aldosterone and sodium retention. Only DSS rats fed a 2.6% KCl diet had hemodynamics similar to those of DSR control rats fed the same diet, and hyperaldosteronism, sodium retention and increased plasma volume did not occur. CONCLUSION: 'Optimal' dietary KCl (2.6%) prevents hypertension and preserves cerebral and renal hemodynamics in DSS rats fed a diet containing 1% NaCl for 8 months, which causes hypertension when dietary KCl is limited or excessive.     

A proposal for applying molecular markers as an aid to identifying potential cases of imported tuberculosis in immigrants

In recent years, the percentage of tuberculosis (TB) cases in immigrants in Spain has increased markedly. In this context, discrimination between cases with potentially imported TB and cases likely to have acquired it by recent transmission after arrival is a basic issue. In this study, we evaluated molecular markers to obtain information on the geographic origin of Mycobacterium tuberculosis (MTB) strains and to determine whether they could help to identify imported TB cases. We analyzed the pks15/1 gene, spoligotype, and MIRU locus 24 in 168 MTB isolates from immigrants of 32 nationalities and from a selection of autochthonous cases. In non-Asian immigrants we could not detect major differences with the autochthonous cases. For the Asian cases, we found some specific features for these markers. pks15/1 was intact in 69% of the Asian patients, but this gene had a 7-bp deletion in all non-Asian and Spanish (non-Beijing) cases. The spoligotype-defined lineages EAI and CAS, and the allele with two repetitions in MIRU locus 24 was found exclusively among Asian immigrants. The analysis of certain bacterial molecular markers could help to discriminate between potentially imported TB cases and those more probably acquired in the host country.     

Humoral Na+-K+ pump inhibitory activity in essential hypertension and in normotensive subjects after acute volume expansion

Plasma from black male patients with essential hypertension was bioassayed for vascular Na+-K+ pump inhibitory activity. Halves of the same rat tail artery were incubated for two hours in boiled plasma supernates from a hypertensive patient and a paired age-, sex-, and race-matched normotensive subject and then ouabain-sensitive 86Rb uptake was measured. Ouabain-sensitive 86Rb uptake by their leukocytes was also measured. Eighteen pairs of subjects were studied. The uptakes were not significantly different in the hypertensive patients and control subjects. However, when we selected from the eighteen hypertensive patients, nine with low plasma renin activity on the day of the study, uptakes were reduced in the hypertensive patients relative to the paired control subjects. We also assayed plasma supernates from normotensive black and white male subjects before and after acute volume expansion (2.5 L saline IV + 1.5 L distilled water orally over a three-hour period) and from paired normotensive subjects before and after sham volume expansion and obtained a positive bioassay in the expanded subjects both on intraindividual and interindividual comparisons. These studies demonstrate increased vascular Na+-K+ pump inhibitory activity in the plasma of black male patients with low renin essential hypertension and in the plasma of normotensive subjects after acute volume expansion. The findings suggest that the inhibitory activity in the hypertensive subjects' plasma is related to volume expansion, relative or absolute.     

Interpretation of chest roentgenograms by primary care physicians

In a prospective study, radiologists judged chest x-ray interpretations of family practice physicians. Though discrepancies were frequent, they led to no demonstrable clinical consequences. Potentially significant misreadings did occur, and clinically insignificant errors may still be worth noting for academic as well as patient advocacy reasons.