Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism

Objective Nonsyndromic autosomal recessively inherited nongoitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2‐5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG. Design Because consanguinity in individuals with a presumptive genetic condition is often an indicator of an autosomal recessive inheritance and allows firmer correlations to be established between genotype and phenotype, we planned to execute our study in consanguineous families. Patients Hundred and thirty‐nine children with CHNG phenotype born to consanguineous families. Measurements First, we investigated cases for evidence of linkage to the four known CHNG genes by microsatellite marker analysis. Mutation analysis by direct sequencing was then performed in those cases in whom linkage to the relevant candidate gene could not be excluded. In addition, in silico analysis of the predicted structural effects of TSHR mutations was performed and related to the mutation‐specific disease phenotype. Results Homozygous germline TSHR mutations were detected in six families (5%), but no mutations were detected in PAX8, TSHB and NKX2‐5. Four of TSHR mutations had not previously been described. Genotype–phenotype correlations were established and found to be related to the predicted structural effects of the mutations. Conclusions Known causative genes account for the development of CHNG only in a minority of cases, and our cohort should provide a powerful resource to identify novel causative genes and to delineate the extent of locus heterogeneity in autosomal recessively inherited CHNG.     

Effect of Intraoperative Paracetamol on Catheter-Related Bladder Discomfort: A Prospective,Randomized, Double-Blind Study

Background

The insertion of urinary catheters during urinary surgical interventions may lead to catheter-related bladder discomfort (CRBD) in the postoperative period.

Objective

We aimed to evaluate the effect of single-dose intravenous paracetamol on CRBD.

Methods

In this randomized, controlled, double-blind study, 64 patients (age >18 years, American Society of Anesthesiologists Physical Status I–II) requiring urinary bladder catheterization for percutaneous nephrolithotomy were assigned to groups that received either intravenous paracetamol (15 mg/kg) (group P) or NaCl 0.9% solution (control group [group C]) 30 minutes before the end of surgery. Patients received patient-controlled analgesia (10-mg bolus of meperidine, without infusion, 20-minute lock out) postoperatively. CRBD and pain status were assessed at 30 minutes and 1, 2, 4, 6, and 12 hours postoperatively. Postoperative meperidine requirement and patient and surgeon satisfaction were assessed.

Results

Group P had significantly lower CRBD scores at all time points except at 12 hours postoperatively compared with group C (P < 0.05). Total meperidine consumption was significantly higher in group C (P < 0.05). Patient and surgeon satisfaction scores were significantly higher in group P (P < 0.05).

Conclusions

Intraoperative single-dose paracetamol was found to be effective in reducing the severity of CRBD and pain in urologic surgery. We suggest that it may be an efficient, reliable, easy-to-apply drug for CRBD. ClinicalTrials.gov identifier: NCT01652183.     

The acute cardioprotective effect of glucocorticoid in myocardial ischemia–reperfusion injury occurring during cardiopulmonary bypass

The purpose of this study was to evaluate the acute cardioprotective effect of high-dose methylprednisolone (25 mg/kg) in the controlled in vivo model of myocardial ischemia–reperfusion injury occurring during cardiopulmonary bypass. Forty nondiabetic male patients with three-vessel disease undergoing first-time bypass surgery were enrolled for this double-blind prospective study. Patients were randomized to be given 25 mg/kg methylprednisolone (Group I) and saline (Group II) 1 h before cardiopulmonary bypass. The levels of cardiac troponin-I (cTnI) were used as a marker of myocardial tissue damage in myocardial ischemia–reperfusion injury. The cTnI levels were measured before surgery, at the second hour after cardiopulmonary bypass, at the 6th and 24th hours, and 5th day postoperatively. There was no significant difference between the two groups in respect to the duration of ischemia and reperfusion. The preoperative cTnI levels were 0.22 ± 0.29 ng/ml in Group I and 0.23 ± 0.28 ng/ml in Group II. cTnI levels increased to 2.40 ± 1.0 ng/ml in Group I and 3.19 ± 0.88 ng/ml in Group II at the 2nd hour after cardiopulmonary bypass. When the differences between T1 and T0 level that showed the amount of troponin release occurring due to ischemia–repefusion injury was calculated and then compared, there was a significant difference between Groups I and II (P = 0.024). The cTnI levels measured at 6 h after CPB were 1.98 ± 0.63 ng/ml in Group I and 2.75 ± 1.15 ng/ml in Group II (P = 0.049). cTnI levels decreased to 0.22 ± 0.10 ng/ml in Group I and 0.49 ± 0.25 ng/ml in Group II on the postoperative day 5 (P = 0.0001). Univalent regression analysis showed that preoperative high-dose corticosteroid usage decreased the troponin release in about 12% and this effect was statistically significant (R² = 0.12, P < 0.05). A single dose of intravenous methylpredisolone (25 mg/kg) given 1 h before ischemia reduced myocardial ischemia–reperfusion injury. These results demonstrated that the acute cardioprotective effect of corticosteroids has much potential in the future for reducing ischemia–reperfusion injury occurring during cardiopulmonary bypass when it is inevitable.     

High-resolution structure of hair-cell tip links

Transduction-channel gating by hair cells apparently requires a gating spring, an elastic element that transmits force to the channels. To determine whether the gating spring is the tip link, a filament interconnecting two stereocilia along the axis of mechanical sensitivity, we examined the tip link's structure at high resolution by using rapid-freeze, deep-etch electron microscopy. We found that the tip link is a right-handed, coiled double filament that usually forks into two branches before contacting a taller stereocilium; at the other end, several short filaments extend to the tip link from the shorter stereocilium. The structure of the tip link suggests that it is either a helical polymer or a braided pair of filamentous macromolecules and is thus likely to be relatively stiff and inextensible. Such behavior is incompatible with the measured elasticity of the gating spring, suggesting that the gating spring instead lies in series with the helical segment of the tip link.     

Low fetuin-A level in migraine: a case–control study

Migraine is a type of primary headache which is caused by the alterations in trigeminovascular system. Migraine attacks are associated with neurovascular inflammation of the cerebral and extracerebral vessels, but its pathophysiological mechanisms have not still been fully delineated. Also, migraine has been found to be associated with higher risks for various metabolic disorders. Thus, we aimed to investigate the matrix metalloproteinases (MMP), fetuin-A, ghrelin, and omentin levels which have important roles in metabolic disorders and inflammation, and to examine their relationship with migraine subtypes and attack frequency. Forty-nine migraine patients and 30 age- and sex-matched healthy control subjects were enrolled. Migraine diagnosis was confirmed according to the International Classification of Headache Disorders-II diagnostic criteria. Analyses of MMP9,MMP3, ghrelin, omentin, and fetuin-A were performed by the ELISA method. Fetuin-A, MMP-9, and MMP-3 levels were significantly lower in migraine than controls (p < 0.05). There were no significant differences between groups with respect to omentin and ghrelin (p > 0.05). In migraine patients, serum fetuin-A levels were positively correlated with MMP-9 and negatively correlated with MMP-3. MMP-3, MMP-9, fetuin-A, omentin and ghrelin levels did not correlate with age, disease duration, or frequency of migraine headache (p > 0.05). Migraine patients have lower fetuin-A, MMP-3 and MMP-9 levels than healthy individuals. Migraine patients have low fetuin-A levels, which may be related to the pathogenesis of migraine. The importance and impact of our findings on the pathogenesis, characteristics, and treatment of migraine needs to be investigated in further detailed studies.     

Increased fibrinogen,d-dimer and galectin-3 levels in patients with migraine

There are limited studies evaluating the fibrinogen levels in patients with migraine. It remains unknown whether the levels of the haematological marker of thromboembolism, d-dimer, and the levels of galectin-3, which plays an important role in inflammation as a proinflammatory mediator, change during the attacks in patients with migraine. The present study aims to compare galectin-3, fibrinogen and d-dimer levels in patients with migraine during the attacks and interictal periods, and to compare galectin-3, fibrinogen and d-dimer levels between patients with migraine and healthy controls to investigate the role of these parameters in the pathogenesis of migraine. Fifty-nine patients with migraine and 30 age-gender matched healthy control subjects were enrolled in the study. Blood galectin-3, fibrinogen and d-dimer levels were measured in patients with migraine. Patients with migraine had higher levels of galectin-3, fibrinogen and d-dimer compared to the healthy controls (p < 0.05). No statistically significant difference was found between galectin-3 and fibrinogen levels during the attacks and interictal period in the migraine group (p > 0.05). Migraine patients had higher d-dimer levels during the attacks compared to the patients in the interictal period in the migraine group (p = 0.05). In conclusion, we found increased levels of fibrinogen, d-dimer and galectin-3 in patients with migraine compared to the healthy control group. Furthermore, we showed increased galectin-3 levels in patients with migraine, and higher d-dimer levels during migraine attacks compared to the interictal periods for the first time. These findings may be associated with the hypercoagulability and neurogenic inflammation during migraine headaches.     

Delay by Staged Elevation of Flaps and Importance of Inclusion of the Perforator Artery

“Surgical delay” is aimed at increasing blood flow to adjacent angiosomes by opening choke vessels, to obtain larger and more reliable flaps. We hypothesized that staged elevation (delay) from distal to proximal, in addition to preservation perforator artery near the base will improve survival. Thirty-two Sprague–Dawley rats were divided into 4 groups and 3x8cm caudal McFarlane flaps were elevated. In “delay” groups the 3 × 4 cm distal part was elevated and sutured back, with complete elevation (3 × 8 cm) after 4 days. The deep circumflex iliac artery (DCIA) at the base was either preserved or transected. The groups were: group A (Delay/DCIA preserved), group B (Delay/DCIA transected), group C (No Delay/DCIA preserved), group D (No Delay/DCIA transected). The percentage of surviving flap area was measured after 7 days with digital planimetrics. Statistics were done with ANOVA and unpaired T-test. The survivals were: 98.44 ± 3.13 %(group A), 69.33 ± 5.51 %(group B), 76.50 ± 8.91 %(group C) and 52.89 ± 3.15 %(group D). Delay lead to a greater degree of survival whether the arteries were preserved (p = 0.002) or transected (p = 0.01). In groups where the DCIA was preserved, the delay lead to a greater area of survival (p = 0.002). Inclusion of arteries lead to a greater degree of survival whether delay was performed (p = 0.003) or not (p = 0.005). Necropsy showed that the DCIAs were dilated bilaterally when preserved with vascular arcades reaching all viable areas. When the DCIA was transected, the gluteal perforators were dilated bilaterally with the vascular arcades reaching all viable areas. Staged elevation is an effective method of delay in both random and rando-axial flaps. When this is combined with preserving the perforator artery, survival rates are further enhanced.