Andermann syndrome in a Turkish patient

Agenesis of the corpus callosum with peripheral neuropathy or Andermann syndrome is an autosomal recessive disorder rarely found outside certain regions of the province of Quebec, Canada. We report a 5-year-old Turkish patient with Andermann syndrome born to consanguineous parents. She presented with diffuse hypotonic weakness, predominantly in the distal extremities, and mild mental retardation. Electromyography showed axonal-demyelinating sensorimotor neuropathy. Sural nerve biopsy was compatible with demyelinating neuropathy. Cranial magnetic resonance imaging revealed total agenesis of the corpus callosum, dilatation of the interhemispheric fissure, and enlargement of the cisterna magna. The molecular genetic analysis using microsatellite DNA markers covering the agenesis of the corpus callosum with peripheral neuropathy locus on chromosome 15q13-q15 showed that the patient is homozygous for the whole region. Our findings confirm that Andermann syndrome is a genetically homogeneous disorder.     

GJB2 gene mutations causing familial hereditary deafness in Turkey

Mutations in Connexin 26 (Cx26) play an important role in autosomal non-syndromic hereditary hearing loss. In this study, our objective was to find out the significance of Cx26 mutations in Turkish families who had hereditary deafness. Fourteen families who had at least two prelingually deaf children per family were included in the study. One affected child from each of the 14 families was selected for single-stranded conformational polymorphism SSCP analysis. Three PCR reactions were used for each subject to amplify the entire Cx26 coding region with overlap. PCR products were sequenced on an Applied Biosystems (ABI) model 3700 automated sequencer. Six of the 14 representative family members (42.9%) demonstrated shifts on SSCP and were subsequently sequenced for Exons 1 and 2 of GJB2 and were tested for the 432 kb upstream deletion. No mutations were found in Exon 1 and no 432 kb deletions were noted. Three different GJB2 mutations were found in Exon 2 of the probands, which were 35delG, 299-300delAT, and 487G > A (M163V). GJB2 mutations were detected in 21.4% of the families. Two patients were homozygous for 35delG and 299-300delAT mutations, and were given a diagnosis of DFNB1 deafness (14.3%). Two different polymorphisms, 457G > A (V153I) and 380G > AG (R127H) were also found. In conclusion, although GJB2 mutations were detected in 21.4% of the families tested, only 14.3% of subject representatives were homozygous and therefore deafness caused by Cx26 mutation segregated with DFNB1. Thus, contribution of GJB2 mutations appears less significant in familial deafness. This necessitates further assessment for the other known gene regions as well as a search for new genetic factors in familial type of genetic deafness.     

Risk factors for permanent laryngeal nerve paralysis in patients with thyroid carcinoma.

OBJECTIVES: This study investigated the incidence of and risk factors for permanent recurrent laryngeal nerve paralysis for patients with thyroid malignancy. DESIGN: Retrospective chart review. SETTING: Tertiary oncology referral centre. PARTICIPANTS: Records of 290 consecutive patients treated between 1997 and 2001 were reviewed. All patients who have had one or more operations. Patients with preoperative recurrent laryngeal nerve paralysis and patients who underwent thyroidectomy in conjunction with laryngectomy were excluded. The incidence of postoperative permanent cord palsy was calculated in relation to the number of patients. MAIN OUTCOME MEASURES: Age, gender, thyroid functions, tumour localisations and size, multicentricity, thyroid capsule invasion, extrathyroidal soft tissue invasion, differentiation, histological type, co-existence of lymphocytic thyroiditis, total number of dissected and metastatic nodes, type of surgery, the place of surgery and number of operations were the risk factors investigated for permanent recurrent laryngeal nerve paralysis. Univariate and multivariate analyses were performed. RESULTS: Permanent recurrent laryngeal nerve paralysis developed in 27 (9%) of 290 patients with thyroid carcinoma. Transient and permanent paralysis rates in total or subtotal thyroidectomy, completion thyroidectomy and neck dissection groups were 5/3%, 7/3% and 24/17% respectively. Cox regression analysis identified the type of surgery [adjusted relative risk (RR) = 2.1, 95% confidence interval (CI) = 1.1-4.0, P = 0.01], extrathyroidal soft tissue invasion (RR = 5.7, 95% CI = 2.0-15.7, P = 0.001) and number of metastatic nodes (RR = 1.6, 95% CI = 1.1-2.5 P = 0.01). CONCLUSIONS: The factors related with recurrent laryngeal nerve paralysis post-thyroid carcinoma surgery are linked to special features of the tumour and to the type of surgery.     

Circadian pattern of spontaneous ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators.

BACKGROUND: Previous studies have reported a circadian variation of ventricular tachyarrhythmias. However, there is no detailed information of the daily distribution of ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes. The purpose of this study was to evaluate the daily distribution of episodes of ventricular tachyarrhythmia in patients with implantable cardioverter defibrillators. MATERIAL/METHODS: We used data stored by last-generation implantable cardioverter-defibrillators (ICD) to retrospectively evaluate the circadian distribution of VT and VF in 70 patients with ICD. The distribution of tachyarrhythmias was categorized into four time zones: zone 1 (06:00-11:59), zone 2 (12:00-17:59), zone 3 (18:00-23:59), and zone 4 (00:00-05:59). RESULTS: During a follow-up of a mean of 3.1+/-1.3 years, a total of 791 ventricular arrhythmias were recorded from which 631 events were VT and 160 VF. A circadian variation of episodes of ventricular tachyarrhythmia was evident. The incidence of ventricular arrhythmia sharply increased in zone 1 (8.82+/-2.13, p<0.0001). Episodes of VT had peaks in zones 1 and 2 (7.44+/-2.03 and 2.70+/-0.65, p<0.001) and episodes of VF had peaks in zones 1 and 4 (1.38+/-0.39 and 1.30+/-0.51, p<0.011). No difference was observed between patients who used betablocker and those who did not. CONCLUSIONS: Malignant ventricular tachyarrhythmias have a circadian distribution. VT peaks occur in the morning and noon hours and VF peaks occurs at the night and morning hours. Betablocker and/or amiodarone usage do not alter this distribution.     

The value of resection of primary tumor in gastric cancer patients with liver metastasis

Purpose  

Surgery for gastric cancer with synchronous liver metastasis is applied for palliation. The aim was to determine whether surgical removal of the primary tumor provides a better survival and disease progression     

Postural balance in pregnancies complicated by hyperemesis gravidarum

Objective: To assess postural balance in females with pregnancies complicated by hyperemesis gravidarum (HG).

Methods: In this observational study, postural balance during the first trimester was measured using the Biodex Balance System (BBS) in 41 pregnant females (20 females with pregnancies complicated by HG and 21 healthy controls). The overall stability index (OA), anterior-posterior stability index (APSI), medial-lateral stability index (MLSI) and fall risk test (FRT) scores were obtained from the mean scores of three trials on the BSS. The four measurements obtained from the BBS (OA, APSI, MLSI and FRT) were compared between healthy pregnant females and those with pregnancies complicated by HG (HG group).

Results: The mean OA and APSI scores were significantly higher in the HG group compared to healthy pregnant controls (p?p?>?0.05). The FRT scores of HG patients were higher than healthy pregnant females (p?=?0.001).

Conclusions: Pregnant females with HG have poor postural stability/balance and high fall risk test scores. HG causes decreased postural equilibrium in the first trimester of pregnancy.     

Effects of sunitinib and bevacizumab on VEGF and miRNA levels on corneal neovascularization

Aim: To evaluate the effects of sunitinib (0.5?mg/ml) and bevacizumab (5?mg/ml) on VEGF-A, VEGFR-2 and microRNA (miRNA) levels on corneal neovascularization (CNV).

Methods: In this study, CNV was induced by silver nitrate application to the cornea, and 40 Albino male rats were equally divided into four subgroups:

Group 1 (sunitinib): After silver nitrate application to the cornea, 0.5?mg/ml sunitinib eyedrop was administered twice daily for two weeks (n?=?10).

Group 2 (bevacizumab): After silver nitrate application to the cornea, 5?mg/ml bevacizumab eyedrop was administered twice daily for two weeks (n?=?10).

Group 3 (control): After silver nitrate application to the cornea, normal saline eyedrop was administered twice daily for two weeks (n?=?10).

Group 4 (vehicle): After silver nitrate application to the cornea, 1% DMSO eyedrop was administered twice daily for two weeks (n?=?10).

After two weeks from the silver nitrate application, corneas were evaluated by hand-held biomicroscope for their vascularization status. Then, corneas were excised and the expression levels of VEGFR-2, VEGF-A and the common miRNA markers for neovascularization (miR-15?b, miR-16, miR-23a, miR-126, miR-188, miR-210, miR-221, miR-222, miR-410 and miR-423) were evaluated by real-time PCR.

Results: It was seen that the CNV was decreased in sunitinib- and bevacizumab-administered groups compared to the control and DMSO groups. Also, in comparison with the control group; VEGF-A expression was downregulated by nearly 0.75 times in sunitinib group and nearly 0.52 times in bevacizumab group. VEGFR-2 expression was downregulated by 0.89 times in sunitinib group and 0.68 times in bevacizumab group, compared to the control group. miR-15?b, miR-16 and miR-126 levels were statistically lower in sunitinib and bevacizumab groups, but miR-188 and miR-410 levels were two-fold higher compared to the control group. The miR-210 level was found higher only in sunitinib group compared to the control group. There were no statistically significant changes in miR-23a, miR-221, miR-222 and miR-423 levels among the groups.

Conclusion: Topical application of bevacizumab (5?mg/ml) and sunitinib (0.5?mg/ml) decreases the levels of VEGFR-2 and VEGF-A in CNV. Further studies are needed for detailed analysis of genes which are targeted by up- or downregulated miRNAs in this study.