Surgery for Hepatolithiasis: Single Center Experience of 12 Patients

Hellenic Journal of Surgery - Hepatolithiasis is the presence of stones within the intrahepatic bile ducts, regardless of common bile duct and gallbladder stones. It is rarely seen in our country...     

Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses

OBJECTIVE—To evaluate the efficacy, safety, and tolerability of pregabalin across the effective dosing range, to determine differences in the efficacy of three times daily (TID) versus twice daily (BID) dosage schedules, and to use time-to-event analysis to determine the time to onset of a sustained therapeutic effect using data from seven trials of pregabalin in painful diabetic peripheral neuropathy (DPN).RESEARCH DESIGN AND METHODS—Data were pooled across seven double-blind, randomized, placebo-controlled trials using pregabalin to treat painful DPN with dosages of 150, 300, and 600 mg/day administered TID or BID. Only one trial included all three of these dosages, and TID dosing was used in four. All studies shared fundamental selection criteria, and treatment durations ranged from 5 to 13 weeks.RESULTS—Pooled analysis showed that pregabalin significantly reduced pain and pain-related sleep interference associated with DPN (150, 300, and 600 mg/day administered TID vs. placebo, all P ≤ 0.007). Only the 600 mg/day dosage showed efficacy when administered BID (P ≤ 0.001). Pain and sleep interference reductions associated with pregabalin appear to be positively correlated with dosage; the greatest effect was observed in patients treated with 600 mg/day. Kaplan-Meier analysis revealed that the median time to onset of a sustained (≥30% at end point) 1-point improvement was 4 days in patients treated with pregabalin at 600 mg/day, 5 days in patients treated with pregabalin at 300 mg/day, 13 days in patients treated with pregabalin at 150 mg/day, and 60 days in patients receiving placebo. The most common treatment-emergent adverse events were dizziness, somnolence, and peripheral edema.CONCLUSIONS—Treatment with pregabalin across its effective dosing range is associated with significant, dose-related improvement in pain in patients with DPN.The prevalence of diabetic neuropathy is as high as 50% in patients who have had diabetes for 25 years (1), and painful diabetic peripheral neuropathy (DPN) occurs in up to 26% of all people with diabetes (2). Symptoms range from mild dysesthesias to severe unremitting pain that can profoundly impact patients’ lives (3,4).Medications of several different classes are used to treat painful DPN with varying degrees of efficacy, safety, and tolerability. The antiepileptic agents gabapentin and pregabalin have attained widespread use in the treatment of painful DPN. These agents bind to the auxiliary α2-δ subunit of the voltage-sensitive calcium channel, thereby decreasing Ca²⁺ influx at nerve terminals and modulating neurotransmitter release (5).There are seven double-blind, randomized, placebo-controlled trials in painful DPN with pregabalin (6–12), five of which are published in full (7–11). The effective dosing range for treatment of neuropathic pain syndromes is 150 to 600 mg/day, administered either three times daily (TID) or twice daily (BID). Among the seven trials, dosages of 150, 300, and 600 mg/day were used, but only one trial included all three of these dosages. Thus, individually, the seven trials present an incomplete picture of the effective dosing range. In addition, TID dosing was used in the first four trials, whereas the three most recent trials of pregabalin in painful DPN used BID dosing.The objective of the current report is to use the pooled data from these seven trials to evaluate the efficacy, safety, and tolerability of pregabalin across the effective dosing range. We also use these data to determine differences in the efficacy of TID and BID dosing schedules. Finally, we use a time-to-event analysis of the pooled data to determine the time to onset of a sustained therapeutic effect across the range of doses.     

Biomechanical investigation of maxillary implant-supported full-arch prostheses produced with different framework materials: a finite elements study

PURPOSEFour and six implant-supported fixed full-arch prostheses with various framework materials were assessed under different loading conditions.MATERIALS AND METHODSIn the edentulous maxilla, the implants were positioned in a configuration of four to six implant modalities. CoCr, Ti, ZrO₂, and PEEK materials were used to produce the prosthetic structure. Using finite element stress analysis, the first molar was subjected to a 200 N axial and 45° oblique force. Stresses were measured on the bone, implants, abutment screw, abutment, and prosthetic screw. The Von Mises, maximum, and minimum principal stress values were calculated and compared.RESULTSThe maximum and minimum principal stresses in bone were determined as CoCr < ZrO₂ < Ti < PEEK. The Von Mises stresses on the implant, implant screw, abutment, and prosthetic screws were determined as CoCr < ZrO₂ < Ti < PEEK. The highest Von Mises stress was 9584.4 Mpa in PEEK material on the prosthetic screw under 4 implant-oblique loading. The highest maximum principal stress value in bone was found to be 120.89 Mpa, for PEEK in 4 implant-oblique loading.CONCLUSIONFor four and six implant-supported structures, and depending on the loading condition, the system accumulated different stresses. The distribution of stress was reduced in materials with a high elastic modulus. When choosing materials for implant-supported fixed prostheses, it is essential to consider both the number of implants and the mechanical and physical attributes of the framework material.     

Relationship of the total atrial conduction time to subclinical atherosclerosis,inflammation and echocardiographic parameters in patients with type 2 diabetes mellitus

OBJECTIVES:

The aim of our study was to evaluate the total atrial conduction time and its relationship to subclinical atherosclerosis, inflammation and echocardiographic parameters in patients with type 2 diabetes mellitus.

METHODS:

A total of 132 patients with type 2 diabetes mellitus (mean age 54.5±9.6 years; 57.6% male) and 80 age- and gender-matched controls were evaluated. The total atrial conduction time was measured by tissue-Doppler imaging and the carotid intima-media thickness was measured by B-mode ultrasonography.

RESULTS:

The total atrial conduction time was significantly longer in the patients with type 2 diabetes mellitus than in the control group (131.7±23.6 vs. 113.1±21.3, p<0.001). The patients with type 2 diabetes mellitus had significantly increased carotid intima-media thicknesses, neutrophil to lymphocyte ratios and high-sensitivity C-reactive protein levels than those of the controls. The total atrial conduction time was positively correlated with the high-sensitivity C-reactive protein level, neutrophil to lymphocyte ratio, carotid intima-media thickness and left atrial volume index and negatively correlated with the early diastolic velocity (Em), Em/late diastolic velocity (Am) ratio and global peak left atrial longitudinal strain. A multiple logistic regression analysis demonstrated that the neutrophil to lymphocyte ratio, carotid intima-media thickness and global peak left atrial longitudinal strain were independent predictors of the total atrial conduction time.

CONCLUSIONS:

We suggest that subclinical atherosclerosis and inflammation may represent a mechanism related to prolonged total atrial conduction time and that prolonged total atrial conduction time and impaired left atrial myocardial deformation may be represent early subclinical cardiac involvement in patients with type 2 diabetes mellitus.     

Giant ethmoid osteoma with orbital extension presenting with epiphora

Paranasal sinus osteoma is a slow-growing, benign, encapsulated bony tumour that may be commonly asymptomatic, being detected incidentally in 1% of plain sinus radiographs or in 3% sinus computerized tomographic scans. In a patient presenting with epiphora and nasal obstruction, computed tomography disclosed a giant osteoma of the ethmoid. In this article, one patient having giant ethmoidal osteoma with orbital extension is described, and epidemiology, diagnosis, treatment, and pathological findings in paranasal sinus osteoma are reviewed.     

Evaluation and therapeutic regulation of erectile dysfunction with visual stimulation test. An objective approach by using sildenafil citrate test

AIM: An objective evaluation of the psychogenic cause of erectile dysfunction by performing the visual stimulation tumescence and rigidity (VSTR) test and sildenafil citrate test, together with the effectiveness of sildenafil citrate medication on impotence caused by different etiologies. MATERIAL AND METHODS: Between 1998 and 2000, a total of 36 men (12 patients with diabetic etiology, 5 patients with vasculogenic risk factor) were enrolled in this study. The mean age of patients was 53 (27-67) years. Following standard questionnaires, including a detailed anamnesis from an andrologic viewpoint, VST was performed in an ambulatory setting and beginning with a test dose of 50 mg. At the end of 2 h, the data was evaluated with computer assistance (Rigiscan device) and if a satisfactory erection had not occurred, an additional second dose of sildenafil citrate (50 mg) was given until there was a satisfactory erection. Results obtained from VST: results were classified as group I (fully rigidity, >10 min erection, >70% of rigidity, possible vaginal penetration), group II (unstable erection, 5 min erection, >70% of rigidity, possible vaginal penetration) and group III (tumescence without rigidity, <5 min erection, <70% of rigidity, impossible vaginal penetration). The results obtained during the first 1 h of the VSTR test were regarded as the patient's own erectile condition and later data was accepted as the real effect of sildenafil citrate. The Fisher exact test was used for statistical evaluation including pre- and post-sildenafil effect on erectile rigidity and duration of erection. RESULTS: The erection status of patients was sufficient in 17 (47.2%) in group I, it was insufficient but sufficient enough with an increased dose of sildenafil citrate in 10 (27.7%) in group II, and insufficient without/with full dose of sildenafil citrate in 9 (25%) in group III. Considering rigidity and total erectile period, there was a statistical significant difference between the first two groups with respect to the early and late sildenafil citrate effects on the VSTR test (p < 0.05). Again, 10 patients with known risk factors (diabetes mellitus 5 and vasculogenic 5) in the second group seemed to give a good response to repeated dosage of sildenafil citrate which has been found to be very interesting. However, the rest of the diabetic patients (n = 7) in the third group showed no erection despite the increasing and repeated doses of sildenafil citrate. CONCLUSION: Sildenafil citrate with the VSTR test has effective and reliable results which was regarded as very important to diagnose and determine objectively the amount of therapeutic doses in impotence. In accordance with the literature data, our results also confirm the reliability and the practical nature of the VSTR test, which is less time-consuming and cheaper than the nocturnal penile tumescence and rigidity (NPTR) test. In the VSTR test, necessary doses of medication needed for satisfactory erection were easily regulated in patients with certain kinds of impotence. Additionally, self-criticism advantage of the patients on erection and an unnecessary need for regular sexual partners may make this test preferable in the near future. However, we believe that a large group of patients with other definite parameters are certainly needed in order to obtain more reliable data.     

Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease

OBJECTIVE: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. METHODS: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). RESULTS: Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). CONCLUSIONS: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.     

Combined primary repair of tetralogy of Fallot and aortic root replacement

Tetralogy of Fallot associated with ascending aortic aneurysm and aortic valve regurgitation is unusual. This combination necessitates a change in operative strategy during complete tetralogy repair. We present a 43-year-old woman who successfully underwent composite graft replacement of the ascending aorta and aortic valve during primary complete tetralogy repair. Histologic examination of the aorta revealed medial degeneration.     

The Yeast Two-hybrid System and Its Pharmaceutical Significance

The detected phenotypes in many diseases are caused from dysfunction in protein-protein, protein-DNA and receptor-ligand interactions. Therefore, determination of these molecular interactions followed by designing or screening the compounds to target these interactions provides a significant challenge in drug development. This review aims to highlight the yeast two-hybrid system in determination of protein-protein interactions and its possible outcomes in pharmaceutical research. The variations of the basic methodology as one- and three-hybrid systems are also disussed in relation to their potential pharmaceutical applications.