Triple A syndrome: genotype-phenotype assessment

The triple A or Allgrove syndrome is an autosomal-recessive disease (MIM*231550) characterized by the triad of achalasia, alacrima and adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency. Associated features of the syndrome are neurological and dermatological abnormalities. Until the discovery of the AAAS gene as the responsible gene in triple A syndrome, the diagnosis was based on characteristic clinical features. Here we present the clinical and molecular genetic data which demonstrated the marked phenotypic variability in three unrelated patients with triple A syndrome. The final diagnosis of triple A syndrome was confirmed by molecular analysis. In one patient with isolated achalasia, the diagnosis of triple A syndrome could only be made on the basis of the molecular genetic analysis of the AAAS gene. We therefore suggest that the diagnosis of triple A syndrome should be considered in patients who exhibit only one or two of the main symptoms (i.e. alacrima, achalasia or adrenal insufficiency). These patients require careful neurological investigation, and mutation analysis of the AAAS gene should be performed.     

瞬目反射、脑干听觉诱发电位、经颅多普勒超声对椎基底动脉供血不足的诊断价值

目的：观察瞬目反射（ＢＲ）、脑干听觉诱发电位（ＢＡＥＰ）、经颅多普勒超声（ＴＣＤ）对椎基底动脉供血不足（ＶＢＩ）的诊断意义。方法：对４１例已经临床确诊的ＶＢＩ病人在间歇期进行ＢＲ、ＢＡＥＰ及ＴＣＤ检查。结果：ＴＣＤ、ＢＲ、ＢＡＥＰ异常率分别为８３％、８０％、６８％。ＢＲ提示脑桥损害１例、延髓损害１５例、广泛性脑干损害１７例；ＢＡＥＰ发现内耳听力减退２０例、脑干病变１３例；ＴＣＤ发现多血管流速异常１４例、一支流速改变１６例，有或伴有血管张力异常１３例。结论：由于ＢＲ、ＢＡＥＰ反射路径不同，检测结果不尽一致。联合检查有助于对病损部位进行定位。ＴＣＤ则有助于定性诊断     

Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats

The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.     

Androgen insufficiency in women: diagnostic and therapeutic implications

The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. The diagnosis of FAIS is made on the basis of these symptoms in the setting of a low serum free testosterone level. However, there is currently no readily available inexpensive assay which reliably measures free testosterone levels in the female range. The diagnosis of FAIS is further complicated by the lack of data demonstrating a minimum serum free testosterone level which, if below this, correlates with the symptoms of FAIS. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. There is a need for formulations of testosterone therapy specifically designed for use in women, along with clear guidelines regarding optimal therapeutic doses and long-term safety data.     

Electrophysiology of rat distal colon after partial nephrectomy

Previous in vivo studies in rat and man indicate that chronic renal insufficiency leads to an increase in the capacity of the large intestine for K secretion. The present studies were performed in isolated rat distal colon with conventional and K-sensitive microelectrodes to determine the cellular basis for enhanced colonic K secretion after 70% nephrectomy. The data revealed that in animals fed a regular diet, nephrectomy had no effect on the Na or K conductance of the apical membrane, or the kinetics of the basolateral membrane Na-K pump, but intracellular K activity decreased from 70±4 mmol/l to 58±4 mmol/l (P<0.005). In control (non-nephrectomised) animals, feeding a diet modestly (4-fold) enriched with K resulted in small but significant increases in the Na and K conductance of the apical membrane, no change in the kinetics of the basolateral membrane Na-K pump, and a rise in intracellular K activity from 70±4 mmol/l to 94±7 mmol/l (P<0.005). In contrast, in animals fed the K enriched diet, nephrectomy resulted in (i) large, amiloride-sensitive increases in transepithelial voltage and total tissue conductance (consistent with an appreciable degree of secondary hyperaldosteronism), (ii) marked increases in the Na and K conductance of the apical membrane, (iii) significant hyperpolarisation of the basolateral membrane, (iv) a 100% increase (P<0.02) in the maximum activity of the basolateral membrane Na-K pump, and (v) a rise in intracellular K activity from 94±7 mmol/l to 129±7 mmol/l (P<0.0025). These data suggest that the combination of modest dietary K enrichment and 70% nephrectomy stimulated an active K secretory process which reflected an increase in the K excretory load applied to the colonic mucosa, and the effects of aldosterone. In this model of renal insufficiency, enhanced K secretion by the transcellular and paracellular (potential-dependent) pathways results in a marked rise in the K excretory capacity of the colon.     

Vitamin D Status in Adolescents during COVID-19 Pandemic: A Cross-Sectional Comparative Study

Vitamin D has been claimed to be effective in the response to infections, including the respiratory syndrome coronavirus 2 (SARS-CoV-2). It is supposed that lockdown measures and fear of SARS-CoV-2 infection might reduce vitamin D levels through the modification of lifestyle. However, very few data exist on the association between lockdown measures and vitamin D status in humans. For this cross-sectional comparative study, adolescents (n = 298) aged 18 to 19 years were enrolled during the compulsory military fitness-for-duty evaluation between July and December 2020 in Southern Switzerland. Beyond anthropometric measurements, participants filled in a structured questionnaire about their lifestyle and a blood specimen was sampled for the determination of total 25-hydroxy-vitamin D. The obtained data were compared with those of 437 adolescents enrolled at the military fitness-for-duty evaluation during the same period of the year in the context of the CENERI study (2014–2016). The anthropometric measures were similar between the two study groups. The levels of vitamin D were also comparable (77 (64–91) vs. 74 (60–92) nmol/L, p = 0.50; median and interquartile range). A total of 38 (13%) and 43 (9.8%) subjects presented insufficient (<50 nmol/L) levels of vitamin D (p = 0.42) during the current pandemic and in the CENERI study, respectively. These data do not support the hypothesis that during the SARS-CoV-2 pandemic, late adolescents are at higher risk of vitamin insufficiency.     

慢性肺心病急性失代偿性呼吸衰竭营养支持治疗的效果

①目的观察营养支持疗法辅助治疗慢性肺心病急性失代偿性呼吸衰竭的效果.②方法慢性肺心病急性失代偿性呼吸衰竭病人56例,随机分成两组,对照组(n=27)采用常规吸氧、抗生素、支气管解痉剂、祛痰剂、呼吸兴奋剂治疗;治疗组(n=29)在此基础上加用营养支持疗法复方氨基酸注射液250mL静滴,每日1次;100g/L脂肪乳注射液500mL静滴,每日1次,连用7～10d.比较两组病人的治疗效果及住院时间.③结果治疗组显效9例,有效16例;对照组显效4例,有效12例,两组疗效比较差异有显著意义(uc=2.09,P＜0.05).治疗组住院时间为(20.3±4.2)d,对照组为(28.6±3.7)d,两组比较差异有显著意义(t=7.82,P＜0.05).④结论营养疗法在慢性肺心病急性失代偿性呼吸衰竭治疗中有重要意义.     

The Functional Status of the ACL in Varus OA of the Knee: The Association With Varus Deformity and Coronal Tibiofemoral Subluxation

BackgroundThe present article analyzes the association of the functional anterior cruciate ligament (ACL) status and the overall varus deformity and coronal tibiofemoral subluxation (CTFS) in varus OA of the knee.MethodsOne hundred consecutive knees with varus OA in 84 patients were prospectively included. Knees were divided into two groups, in accordance with the ACL status (functionally sufficient or insufficient). All included patients were potential candidates for unicompartmental knee arthroplasty with predominantly medial compartment OA. Knees with Kellgren/Lawrence ≥ grade 3 in the lateral compartment were excluded leaving 79 knees to be included in this study. Mechanical varus deformity and CTFS were evaluated on AP radiographs and valgus stress radiographs, and compared between the two groups.ResultsKnees with a functionally insufficient ACL had significantly more varus deformity on hip-to-ankle AP standing radiographs (P = .001) and on valgus stress radiographs (P = .017). CTFS on AP standing radiographs was significantly higher (P = .045) in knees with a functionally insufficient ACL. Seventy-three percent (8/11) of the ACL-insufficient knees had a varus deformity of ≥10° and 64% (7/11) of ACL-insufficient knees had CTFS ≥ 6mm. By contrast, only one patient (2%, 1/41) with an insufficient ACL had< 10° varus deformity and a CTFS of < 6mm.ConclusionFunctional ACL insufficiency in osteoarthritic varus knees is associated with greater varus deformity and more advanced CTFS. Seventy-three percent of ACL-insufficient knees had a varus deformity of ≥10° and 64% of ACL-insufficient knees a CTFS of ≥ 6mm. In the work-up for medial unicompartmental knee arthroplasty, functional ACL insufficiency is likely in knees with varus deformity of ≥10° and CTFS of ≥ 6mm.     

No justification of routine screening for 22q11 deletions in patients with overt cleft palate

The velo-cardio-facial syndrome (VCFS), caused by a submicroscopic deletion of chromosome 22q11, is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is routine screening for 22q11 deletions in all infants with cleft palate (CP). The purpose of this study was to evaluate whether this strategy is preferable to testing on clinical suspicion. At the Nijmegen Cleft Palate Craniofacial Center, 58 new patients with overt CP were routinely tested, using fluorescence in situ hybridization (FISH), for a 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study (n = 45) and the literature (n = 54), the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, is estimated to be one in 99. We take the view that this figure is rather low and that early discovery will rarely have significant clinical or genetic consequences. Because CP patients remain under medical attention, almost all of the infants with isolated CP and VCFS will be recognized as having the syndrome at a later age when additional features have developed. Therefore, we conclude that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed.     

Ultrastructural morphometric analysis of human myocardial left ventricles with mitral insufficiency

Summary 15 biopsies of dilated and hypertrophied human left ventricles in mitral insufficient hearts were morphometrically investigated. On light and electron microscopical level the results were compared with those received from normally loaded human left ventricles and from hypertrophied human left ventricles found in hearts with aortic valve disease. The results demonstrate alterations when compared with the results from normally loaded left ventricles. The differences between normally loaded and volume loaded left ventricles are smaller than those in pressure loaded left ventricles from aortic valve diseased hearts.This work was supported gratefully by the Deutsche Forschungsgemeinschaft, SFB 104