Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene

BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.     

Role of taurine accumulation in keratinocyte hydration

Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum-stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed human skin for the presence of the taurine transporter (TAUT) and studied the accumulation of taurine as one potential mechanism protecting epidermal keratinocytes from dehydration. According to our results, TAUT is expressed as a 69 kDa protein in human epidermis but not in the dermis. For the epidermis a gradient was evident with maximal levels of TAUT in the outermost granular keratinocyte layer and lower levels in the stratum spinosum. No TAUT was found in the basal layer or in the stratum corneum. Keratinocyte accumulation of taurine was induced by experimental induction of skin dryness via application of silica gel to human skin. Cultured human keratinocytes accumulated taurine in a concentration- and osmolarity-dependent manner. TAUT mRNA levels were increased after exposure of human keratinocytes to hyperosmotic culture medium, indicating osmosensitive TAUT mRNA expression as part of the adaptation of keratinocytes to hyperosmotic stress. Keratinocyte uptake of taurine was inhibited by beta-alanine but not by other osmolytes such as betaine, inositol, or sorbitol. Accumulation of taurine protected cultured human keratinocytes from both osmotically induced and ultraviolet-induced apoptosis. Our data indicate that taurine is an important epidermal osmolyte required to maintain keratinocyte hydration in a dry environment.     

Surgical treatment for pulmonary hydatidosis (a review of 422 cases)

OBJECTIVE: Hydatidosis in man is frequently encountered in sheep and cattle raising regions of the world. We reviewed 422 patients, treated surgically for pulmonary hydatid disease in our clinic between January 1980 and January 1998, assessing the clinical features and results of results of operative treatment management in our centre. PATIENTS AND METHODS: 52 of the patients were female and 370 were male. The median age of the patients was 33 years (range, 11 to 66 years). The cysts were located in the right lung in 214 (50.7%) patients, the left lung in 156 (37%) and bilaterally in 17 (4%) cases. We found an intrathoracic extrapulmonary cyst in 35 (8.3%) patients. We performed enucleation and capitonnage in 202 cases, wedge resection in 40, cystotomy and capitonnage in 171, and lobectomy in 9 patients. The high-risk patients were treated with Albendazol (10 mg/kg/day), for a period of 3 months postoperatively. RESULTS: Preoperative diagnosis was based primarily on chest roentgenograms and led to correct diagnosis in 347 cases (82.2%). An additional computerised tomography (CT) scan in 56 cases and magnetic resonavive imaging (MRI) were required in 15 cases. The diagnosis is established intraoperatively in 4 cases. Most (296) patients presented with a solitary lung cyst. The rest were found to have multiple cysts in one or more lobes. 87 of 422 also had cysts in the liver, 19 in the spleen, and 1 in the pancreas. The follow-up data was completed in 392 of 422 (92.8%) patients. The mean follow-up period was 4.3 years (2 to 19 years). We detected recurrence in 3 patients (0.71%). CONCLUSION: The effective treatment of hydatid cyst(s) in the lung is complete excision of the cyst(s) with maximum preservation of the lung parenchyma. Additional medical treatment with Albendazole should be carried out for high-risk group patients.     

Phases of A beta-deposition in the human brain and its relevance for the development of AD

BACKGROUND: The deposition of the amyloid beta protein (Abeta) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Abeta-deposition. OBJECTIVE: To clarify whether there is a hierarchical involvement of the regions of the entire brain as well and whether there are differences in the expansion of Abeta-pathology between clinically proven AD cases and nondemented cases with AD-related pathology, the authors investigated 47 brains from demented and nondemented patients with AD-related pathology covering all phases of beta-amyloidosis in the MTL (AbetaMTL phases) and four control brains without any AD-related pathology. METHODS: Abeta deposits were detected by the use of the Campbell-Switzer silver technique and by immunohistochemistry in sections covering all brain regions and brainstem nuclei. It was analyzed how often distinct regions exhibited Abeta deposits. RESULTS: In the first of five phases in the evolution of beta-amyloidosis Abeta deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Abeta deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Abeta-deposition. The 17 clinically proven AD cases exhibit Abeta-phases 3, 4, or 5. The nine nondemented cases with AD-related Abeta pathology show Abeta-phases 1, 2, or 3. CONCLUSIONS: Abeta-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Abeta-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Abeta. There are also indications that clinically proven AD cases with full-blown beta-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Abeta pathology.     

超滤法分析黄芪水煎液中胶体态铜的分布

目的建立黄芪水煎液中胶体态铜的分析方法。方法采用0.45μm微孔滤膜、截留相对分子质量为14万、5万、1万、0.4万超滤膜组成的超滤系统,对黄芪水煎液进行分级处理,用石墨炉原子吸收法测定超滤液中元素铜。结果截留相对分子质量1万的超滤膜对相对分子质量4万的聚乙烯吡咯烷酮(PVP)具有良好的截留效率(0.99)和较小的吸附损失(4.3%);元素铜在超滤过程中的回收率介于93.8%~105.1%之间,RSD<12.2%;黄芪水煎液可溶态中,元素铜主要与相对分子质量大于5万和小于0.4万的胶体颗粒结合,这与黄芪多糖分子质量分布相吻合。结论本法操作简便、快速,适用于黄芪水煎液中胶体态铜的分析,结果令人满意。     

Adjustable laparoscopic gastric banding in patients with morbid obesity: radiographic management, results, and postoperative complications

PURPOSE: To determine the role of radiographic assessment in patients who underwent an adjustable laparoscopic gastric banding (ALGB) for the treatment of morbid obesity, and to evaluate the frequency and type of postoperative complications. MATERIALS AND METHODS: From September 1995 to March 1998, 98 consecutive patients (18 men, 80 women; mean age, 39 years; age range, 22-62 years) with morbid obesity (mean body weight, 132 kg; mean body mass index, 47.1 kg/m(2)) underwent ALGB. In all patients, fluoroscopy was performed postoperatively to confirm band position and to exclude perforation and at 6-8 weeks later to measure and adjust the stoma between the pouch and stomach for optimal weight loss. All patients underwent another examination 12 months postoperatively, whereas patients with unsatisfactory weight loss or patients suspected of having complications were examined earlier and on several occasions. RESULTS: Port puncture was feasible in all cases, and stomal adjustments could easily be repeated. Absolute (ie, total) weight loss after 1 year ranged from 8.8% to 39.2% (mean, 18.3%). Twenty patients showed unsatisfactory weight loss. No early complications occurred. Late complications occurred in 34 patients and included pouch dilatation (concentric or eccentric with posterior slippage), eccentric band herniation, band penetration, disconnection, axial pouch herniation, and port-site infection. CONCLUSION: ALGB is an effective method in the treatment of morbid obesity. Radiographic assessments are crucial in the management of weight loss and detection of postoperative complications.     

Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

Background&nbsp;&nbsp;

The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation.     

Changes in prevalence and severity of asthma among schoolchildren in a Swedish district between 1985 and 1995

The same questionnaire and study design was used in two surveys of asthma among all the children attending the 9-y compulsory school in Sundsvall in 1985 (n = 10 527) and 1995 (n = 9 165). A detailed questionnaire was distributed by post to the parents of all children who had answered in the affirmative to a simple screening question on asthmatic symptoms at the beginning of the autumn term. The questionnaire contained detailed questions on symptoms and asthma management. Our findings indicated a moderate increase in reported asthma-like symptoms and physician-diagnosed asthma between 1985 and 1995. The severity of symptoms was unchanged, despite a large community-based asthma campaign and a tenfold increase in the number of children receiving inhaled steroids. A validation analysis included an interview by a physician, a skin prick test, determination of specific IgE antibodies and spirometry. The oral interviews suggested that undertreatment was common. Many children had adequate medication at home, but this medication was not used properly. Finally, all 13-14-y-old children also replied to written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). It is likely that differences in study design explained the much higher prevalence of wheezing in this part of the study.