X-linked Charcot-Marie-Tooth disease: phenotypic expression of a novel mutation Ile127Ser in the GJB1 (connexin 32) gene

We report a family with X-linked dominant Charcot-Marie-Tooth disease (CMTX1). Three affected family members are described, who underwent detailed clinical, electrophysiological, molecular genetic, and histopathological studies. A novel isoleucine at position 127 with serine (Ile127Ser) mutation in the gap junction protein beta 1 (GJB1) gene was detected. The electrophysiological findings were consistent with a primary demyelinating neuropathy with secondary axonal loss and support this model of disease progression. All patients having the CMT phenotype and intermediate conduction velocities who are negative for CMT1A duplication/hereditary neuropathy with liability to pressure palsies (HNPP) deletion, and whose family shows a dominant trait without male-to-male transmission, should be screened for CMTX1.     

Report of a case of immunosuppression with prednisone in an 8-year-old boy with an acute onset of hypocretin-deficiency narcolepsy

OBJECTIVE: To explore whether acute destruction of hypocretin cells in a patient with narcolepsy could be detected and if the course of the disease could be reversed or altered by the use of prednisone for immunosuppression. DESIGN: Case report. SETTING: A sleep-clinic population in a tertiary-care hospital. PATIENT: An 8-year-old boy with a very acute recent (< 2 month) onset of sleepiness. METHODS: Sleep studies; fluid-attenuated inversion recovery and gadolinium magnetic resonance imaging studies with a focus on the hypothalamus; examinations of cerebrospinal fluid for cytology, protein, and hypocretin-1 levels; and HLA typing were performed. INTERVENTION: A 3-week regimen of 1 mg x kg(-1) x day(-1) of prednisone was administered in an attempt to modify the course of the disease. RESULTS AND CONCLUSION: Sleep evaluations were consistent with a diagnosis of narcolepsy. Hypocretin-1 was absent in the cerebrospinal fluid, and HLA-DQB1*0602 was present. All other results were within normal limits, and prednisone did not have any noticeable effects. Clinical manifestation of narcolepsy might occur when the hypocretin cell damage is too advanced to be reversible.     

A quantitative evaluation of blood-lymphocyte subpopulation in herpetic ocular disease

Data on changing contents of blood-lymphocytes' subpopulations in patients with ophthalmoherpes are reported. A higher number of blood cells expressing the surface activation antigens of HLA-DR+, CD71+ and CD95+, a lower number of T-helpers and a reduced value of the immune-regulating index were found to be typical of such changes. A more significant increase in the quantity of CD95+ lymphocytes, as observed in cases of severe ophthalmoherpes versus its moderate clinical course, could be a prognostication criterion. The essential shifts occurring in the T-cells' population denote the status of tension in the immune response provoked by an intensified reproduction of herpes simplex virus (HSV); at the same time, they are indicative of a certain deficit in the immune-protection mechanisms.     

Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo

Glyco-coat changes on cancer cells due to aberrant glycosylation are potential targets for immune recognition through lectin-like receptors on immune cells. These cells include natural killer (NK), CD8+ and CD4+ lymphocytes, all reported to have, together with cytokines, important functions in antitumor immunity. The aim of this study was to evaluate a possible role of synthetic monodisperse multivalent neo-glycoconjugates, namely glycodendrimers, as a new approach to anticancer immune modulation through carbohydrate-mediated immune recognition. Octavalent polyamidoamine dendrimers functionalized with N-acetyl-glucosamine residues (PAMAM-GlcNAc8), with in vitro high affinity for the recombinant lymphocyte receptor NKR-P1A, were employed. To follow the fate of the compound, a fluorescent marker was conjugated to the tetra-branched semi-component of the dendrimer. Tumor development and immunity were evaluated in C57BL/6 mice. Animals were inoculated with B16F10 melanoma cells and underwent different protocols of PAMAM-GlcNAc8 administration. Advantages on survival and reduction of tumor growth were obtained in dose-dependent manner, by IP route. Increase of CD69+ cells in the spleen and their appearance inside the tumors, early progressive release of IL-1beta, a later production of INFgamma and IL-2 concomitant to an increment of CD4+ cells were observed. Cytotoxicity assays, performed ex vivo, showed an enhanced NK cell activity proportioned to the percentage of activated NK cells. Our data suggest that well-defined multivalent neo-glycoconjugates can stimulate an antitumor immune response engaging both innate and acquired immunity.     

Genetic and Preventive Services for Hereditary Breast and Ovarian Cancer in the Czech Republic

The majority of hereditary breast and ovarian cancers can be accounted for by germline mutations in the BRCA1 and BRCA2 genes. Genetic counselling and testing in high-risk patients in the Czech Republic began in 1997 in two centres (Masaryk Memorial Cancer Institute in Brno, MMCI, and the General University Hospital plus the First Faculty of Medicine, Charles University in Prague, 1FMUK). Health insurance covers testing in MMCI, whereas testing at 1FMUK is covered by research grants. The spectrum of mutations in the BRCA1 gene is similar in the Bohemian (western) and Moravian (eastern) regions of the country but the mutation spectrum observed in the BRCA2 gene is completely different. There are three BRCA1 gene mutations that are responsible for 69% and 70.4% of all BRCA1 mutations identified in women reporting to the Brno and Prague centres, respectively. The two most frequent mutations in the BRCA2 gene, which comprises 41.5% of all detected BRCA2 mutations in Brno, were not found in women tested in the Prague centre. The testing of BRCA1/BRCA2 or other possible predisposition genes for hereditary breast/ovarian cancer is determined by medical geneticists after genetic counselling. Predictive testing is offered to persons older than 18 years of age. Genetic counselling centres are easily accessible to all inhabitants in the country. Specialized preventive care is mostly organized by MMCI and the General University Hospital in Prague; however, some patients and their family members are under the care of other oncology departments and clinics. The quality of preventive care in different hospitals is currently being investigated.     

A meta-analysis of four European genome screens (GIFT Consortium) shows evidence for a novel region on chromosome 17p11.2-q22 linked to type 2 diabetes

Positional cloning is expected to identify novel susceptibility genes underlying complex traits, but replication of genome-wide linkage scan findings has proven erratic. To improve our ability to detect and prioritize chromosomal regions containing type 2 diabetes susceptibility genes, the GIFT consortium has implemented a meta-analysis of four scans conducted in European samples. These included the Botnia I and Botnia II scans, with respectively 58 and 353 pedigrees from Finland and Sweden, the Warren 2 scan performed in 573 multiplex sibships from the UK, and a scan of 143 families from France. The meta-analysis was implemented using the genome-search analysis method (GSMA), an exploratory data analysis technique which is robust across study designs. The analysis provided evidence for linkage of type 2 diabetes to six regions, with the strongest evidence on chromosome 17p11.2-q22 (P=0.0016), followed by 2p22.1-p13.2 (P=0.027), 1p13.1-q22 (P=0.028), 12q21.1-q24.12 (P=0.029), 6q21-q24.1 (P=0.033) and 16p12.3-q11.2 (P=0.033). Linkage analysis of the pooled raw genotype data generated maximum LOD scores in the same regions as identified by GSMA. Altogether, our results have indicated that GSMA is a valuable tool to identify chromosomal regions of interest and that accumulating evidence for linkage from small peaks detected across several samples may be more important than getting a high peak in a single sample. This meta-analysis has led to identification of a novel region on chromosome 17 linked to type 2 diabetes; this region has not been highlighted in any published scan to date but on the basis of these data justifies further exploration.     

Laparoscopic donor nephrectomy vs. open live donor nephrectomy: a quality of life and functional study

BACKGROUND: Few studies have compared the quality of life (QoL) and functional recuperation of laproscopic donor nephrectomy (LDN) vs. open donor nephrectomy (ODN) donors. This study utilized the SF-36 health survey, single-item health-related quality of life (HRQOL) score, and a functional assessment questionnaire ('Donor Survey'). METHODS: Questionnaires were sent to 100 LDN and 50 ODN donors. These donors were patients whose procedures were performed at The University Hospital and The Christ Hospital in Cincinnati, Ohio. RESULTS: A total of 46 (46%) LDN and 21 (42%) ODN donors returned the completed surveys. The demographics of the two groups were similar. LDN patients reported a more rapid return to 100% normal health (69 vs. 116 d; p = 0.24), part-time work (21.9 vs. 23.2 d; p = 0.09), and necessitated fewer physician office visits post-operative (2.8 vs. 4.4; p = 0.01). ODN patients reported shorter duration of oral pain medication use (13.4 vs. 7.2 d; p = 0.02). However, a greater number of ODN patients reported post-surgical chronic pain (3 vs. 6; p < 0.05) and hernia (0 vs. 2; p = 0.19). The overall QoL for both groups was comparable with the general USA population. CONCLUSIONS: The results of this study support the decisions of many kidney transplant centers to adopt LDN programs as standard of care.     

Rhinophyma treated with kilovoltage photons

A 72-year-old retired truck driver presented with a 10-year history of rhinophyma and was successfully treated with 90-kV photons to a total dose of 40 Gy in 20 daily fractions. A brief discussion of radiotherapy in the treatment of rhinophyma follows.     

Augmentation by autologous adipose tissue in cleft lip and nose. Final esthetic touches in clefts: part I

Although patients with a cleft lip and palate undergo many surgeries and other therapeutic procedures in the course of their treatment, many are still deeply concerned with their handicap and continue searching for perfection in their appearance. Augmentation using the subject's own fat cells involves minor invasion, is readily available, is an unpretentious method regarding time and cost, and has no contraindications. This method can serve to supplement a hypotrophic scarred upper lip and nasal columella, and by improving the volume, it induces a more natural contour, which reduces the stigmatizing deformity as well as the visibility of externally apparent scars. Using this approach, five patients with a complete cleft have been treated. The median follow-up interval is 22 months (through January 2003). The procedure and postoperative course had a pleasing outcome and were without any complications. The disadvantage was the temporary effect of the outcome, which necessitated repeated application every 7 months on average.