Microvesicular steatosis: a missed item in the management of nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease and cirrhosis. In NAFLD, histological course of steatosis is usually macrovesicular (MacroS), but it may be accompanied by varying degrees of microvesicular steatosis (MicroS). Thus, in this study, we aimed to evaluate the prevalence and significance of MicroS in subjects with NAFLD. METHODS: A retrospective analysis of clinical and laboratory data of patients with histologically proven NAFLD was performed. The liver biopsy specimens which stained with hematoxylin eosin, reticulin, and Masson's Trichrome stains were evaluated by single expert liver pathologist. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). Grading for steatosis, steatosis type, zonal distribution of steatosis and other histological findings were also determined. RESULTS: The prevalence of MicroS among the study population (n= 191) was 30.4%. There was no difference regarding the demographic and biochemical parameters between patients with or without MicroS. On the other hand, the prevalence of ballooning injury and megamitochondria were higher in patients with MicroS (p= 0.019 and p= 0.036, respectively). There was a significant association of MicroS with ballooning injury (OR 2.65, 95% CI= 1.26-5.55 ; p= 0.005) and the presence of megamitochondria (OR 3.72, 95% CI= 1.00-13.72 ; p= 0.037). CONCLUSION: MicroS is common in patients with NAFLD and is associated with early histological findings in this clinically relevant condition. Further longitudinal studies are needed to characterize the role of MicroS in the natural history of NAFLD.

Bilateral massive pneumonia as an unusual manifestation of Puumala hantavirus infection.

Renal involvement due to European Puumala virus (PUUV) is frequent but pulmonary involvement is quite rare. We present here, a 24-year-old male with atypical clinical presentation of acute PUUV infection with gross pulmonary and minimal renal involvement. Severe pulmonary manifestations of PUUV infection, in this case, highlights that hantavirus infection should be considered in the differential diagnosis of atypical pneumonia.

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

Tetanus in adults: results of the multicenter ID-IRI study.

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

Plasma pentraxin-3 is associated with endothelial dysfunction in non-alcoholic fatty liver disease.

OBJECTIVE: Pentraxin-3 (PTX-3) is an acute-phase protein belonging to the PTX family. It has been reported that PTX-3 is significantly associated with obesity, metabolic syndrome, and cardiovascular diseases (CVD). Non-alcoholic fatty liver disease (NAFLD) is strongly associated with atherosclerosis and CVD. In this study, we aimed to investigate the relationship of PTX-3 with circulating markers of endothelial dysfunction and atherosclerosis in patients with NAFLD. PATIENTS AND METHODS: Seventy patients with biopsy-proven NAFLD and seventy healthy controls were enrolled in the study. Plasma asymmetric dimethylarginine (ADMA), adiponectin, and PTX-3 levels were determined using enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive protein (hsCRP) serum levels were measured with the immunoturbidimetric assay. Insulin resistance was estimated using the HOMA-IR index. RESULTS: PTX-3 and hsCRP levels were higher and adiponectin levels were lower in the NAFLD group compared to the healthy controls (p < 0.001 for all). In correlation analysis, a significant association was observed between PTX-3 and ADMA levels (r = 0.423, p < 0.001). CONCLUSIONS: Our study demonstrated for the first time that increased circulating PTX-3 is strongly associated with endothelial dysfunction in subjects with NAFLD. However, large prospective studies are needed to establish the independent predictive value of PTX-3 for CVD endpoints in this clinically relevant condition.

Evaluation of tularaemia courses: a multicentre study from Turkey.

In this multicentre study, which is the largest case series ever reported, we aimed to describe the features of tularaemia to provide detailed information. We retrospectively included 1034 patients from 41 medical centres. Before the definite diagnosis of tularaemia, tonsillitis (n = 653, 63%) and/or pharyngitis (n = 146, 14%) were the most frequent preliminary diagnoses. The most frequent clinical presentations were oropharyngeal (n = 832, 85.3%), glandular (n = 136, 13.1%) and oculoglandular (n = 105, 10.1%) forms. In 987 patients (95.5%), the lymph nodes were reported to be enlarged, most frequently at the cervical chain jugular (n = 599, 58%), submandibular (n = 401, 39%), and periauricular (n = 55, 5%). Ultrasound imaging showed hyperechoic and hypoechoic patterns (59% and 25%, respectively). Granulomatous inflammation was the most frequent histological finding (56%). The patients were previously given antibiotics for 1176 episodes, mostly with ß-lactam/ß-lactamase inhibitors (n = 793, 76%). Antituberculosis medications were provided in seven (2%) cases. The patients were given rational antibiotics for tularaemia after the start of symptoms, with a mean of 26.8 ± 37.5 days. Treatment failure was considered to have occurred in 495 patients (48%). The most frequent reasons for failure were the production of suppuration in the lymph nodes after the start of treatment (n = 426, 86.1%), the formation of new lymphadenomegalies under treatment (n = 146, 29.5%), and persisting complaints despite 2 weeks of treatment (n = 77, 15.6%). Fine-needle aspiration was performed in 521 patients (50%) as the most frequent drainage method. In conclusion, tularaemia is a long-lasting but curable disease in this part of the world. However, the treatment strategy still needs optimization.

Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia.

The aim of this study was to compare the responses of colistin treatment alone vs. a combination of colistin and rifampicin in the treatment of ventilator-associated pneumonia (VAP) caused by a carbapenem-resistant A. baumannii strain. Forty-three patients were randomly assigned to one of two treatment groups. Although clinical (P = 0·654), laboratory (P = 0·645), radiological (P = 0·290) and microbiological (P = 0·597) response rates were better in the combination group, these differences were not significant. However, time to microbiological clearance (3·1 ± 0·5 days, P = 0·029) was significantly shorter in the combination group. The VAP-related mortality rates were 63·6% (14/22) and 38·1% (8/21) for the colistin and the combination groups (P = 0·171), respectively. Our results suggest that the combination of colistin with rifampicin may improve clinical and microbiological outcomes of VAP patients infected with A. baumannii.

Characterization of imipenem resistance mechanisms in Pseudomonas aeruginosa isolates from Turkey.

The emergence of carbapenem resistance in Pseudomonas aeruginosa threatens the efficacy of this important anti-pseudomonal antibiotic class. Between 2003 and 2006, an increase in the number of carbapenem-resistant P. aeruginosa isolates at the Zonguldak Karaelmas University Hospital was observed (Zonguldak, Turkey). To assess the imipenem resistance mechanisms emerging in these P. aeruginosa isolates, they were characterized by amplified fragment length polymorphism typing, which revealed diversity among imipenem-resistant isolates as well as two clonally related outbreak groups. The molecular mechanism of carbapenem resistance was characterized in a representative isolate from each clonal group. Mutational disruption of oprD was the most frequently encountered resistance mechanism (23/27 isolates).

Thermogenic response and leptin levels rise after recovery of the euthyroid state.

OBJECTIVE: The aims of the study were to compare: a) the thermogenic responses in subclinical hypothyroidism (SH) and euthyroid state; b) the relationship between thermogenic response and leptin level. METHODS: Thirty women diagnosed with SH (mean age 39.9+/-4.1 yr; body mass index 23.2+/-2.5 kg/m(2)) were enrolled in the study. Thyroid function tests, leptin, and lipid profiles were measured during SH and after stable euthyroidism was recovered. Thermogenic response was measured by Water Immersion Calorimetry during SH and after the euthyroid state was attained. RESULTS: The mean level of thermogenic response was found to be 1.45+/-0.43 kcal/kg*h in women with SH. It changed to 1.54+/-0.77 kcal/kg*h (p=0.01) in the euthyroid state; the change was statistically significant. Mean level of leptin was found to be 7.22+/-2.6 ng/ml in SH; and 15.8+/-8.0 ng/ml in the euthyroid state. There was a positive correlation between leptin and free T(3) (r=0.460, p=0.009) levels in SH. There were positive correlations between leptin level and fat mass in SH (r=0.820, p=0.01) and in the euthyroid state (r=0.700, p=0.03). CONCLUSIONS: No correlations were found between thermogenic response and leptin levels in SH and in the euthyroid state. Thermogenic response and leptin levels rose after the euthyroid state was recovered.

Unexpected tigecycline resistance among Acinetobacter baumannii Isolates: high minor error rate by Etest.

Tigecycline seems to be a promising agent for treatment of resistant Acinetobacter baumannii infections, however approved criteria for susceptibility testing are still lacking. The aim of this study was to evaluate tigecycline activity against multidrug resistant A. baumannii clinical isolates, as well as susceptibility testing methods and disk diffusion (DD) breakpoints. Reference broth microdilution (BMD), Etest and DD methods were used. MIC(50 )and MIC(90 )by the reference method were 1 and 8 microg/ml, respectively. Applying the breakpoints for enterobactericeae, 85.7% of the isolates were sensitive to tigecycline. The Etest resulted in lower susceptibility rates (63.7%). Essential agreement between Etest and BMD was 75.8%. 21.9% of the strains were susceptible by BMD and intermediate by Etest. Provisional DD breakpoints >or=19/or=17/or=17/

First isolation of vancomycin-resistant enteroccoci and spread of a single clone in a university hospital in northwestern Turkey.

Reported here is the first isolation of vancomycin-resistant Enterococcus (VRE) at a hospital in northwestern Turkey and a description of the ensuing outbreak investigation. The first isolate was obtained from a wound culture of a patient in an intensive care unit. Thereafter, a total of 205 rectal swabs, 67 skin swabs and 123 environmental samples were screened, revealing five more VRE isolates. All isolates showed similar antibiotic resistance patterns, except for two that differed regarding gentamicin resistance. The vanA gene was present in all isolates. Pulsed-field gel electrophoresis demonstrated that all isolates belonged to a single clone, with the gentamicin-resistant isolates demonstrating two-band differences. This is the first outbreak to be caused by spread of a single VRE clone in Turkey; it was successfully controlled by strict adherence to appropriate infection control practices.

Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry.

Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5+/-2.05 kg/m2 in the placebo group, decreased to 30.4+/-2.94 kg/m(2) after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5+/-4.1 kg/m(2) to 30.9+/-4.8 kg/m(2) (P<.05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27+/-0.29 kcal/kg/h to 1.44+/-0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56+/-0.27 kcal/kg/h; it changed to 1.33+/-0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.

The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.

In this clinical trial, we examined the efficacy of intra-articular hyaluronic acid (HA) treatment in 38 patients with reducing displaced disc of the temporomandibular joint (TMJ). Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart. Efficacy was based on the following measurements: pain and sound intensity of the joint measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers. These measurements were performed before the first injection and 1 and 6 months after the last injection. In the treatment group (n=19), all measurements improved significantly at month 1 and at month 6 compared with the baseline (P < 0.01). The same measurements, in the placebo group (n=19), did not show any change, except for the pain intensity which improved at month 1 and month 6 (P < 0.05). The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals. This study demonstrates that intra-articular sodium hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a reducing displaced disc.

Testing of nonlinear electrofrictiophoresis in agarose gel.

It was theoretically predicted earlier that if a periodic force without constant component is applied to a particle, then the particle can produce a directed drift in some direction. The effect is named nonlinear electrofrictiophoresis, because it is crucial for its appearance that the friction force depends on the particle's velocity in a nonlinear manner. We test a possibility to observe this effect when a mixture of fragments of DNA (the DNA ladder) moves in the agarose gel. For this purpose, we study the nonlinear characteristics of a DNA ladder movement in the gel. The gels with the ladder were run under various electric field strengths. It was found that the friction coefficient for each DNA fragment in the ladder depends on the migration velocity, suggesting that energy dissipation during migration is a nonlinear function of velocity. This nonlinearity makes the system under consideration suitable for observing nonlinear electrofrictiophoresis. A possible velocity of directed drift under periodic electric drive without constant component was estimated numerically for experimentally observed dependencies. The velocity appeared to be comparable with that of migration under a constant field of moderate strength. A possible mechanism of energy dissipation during movement of DNA through the gel is discussed.

Electrodiagnostic methods for neurogenic dysphagia.

OBJECTIVE: Swallowing mechanisms and neurogenic dysphagia have not been systematically studied by the EMG technique. It is desirable to evaluate neurogenic dysphagia for diagnostic and possibly for therapeutic purposes using electrophysiological methods. METHODS: The following methods were described: mechanical upward/downward movements of the larynx were detected using a piezoelectric sensor, while submental integrated EMG activity was recorded during dry and wet swallowing. The EMG activity of cricopharyngeal muscle of the upper oesophageal sphincter was also recorded in some normal subjects and patients. Piecemeal deglutition and the dysphagia limit were determined in all patients to detect dysphagia objectively. In this study 75 normal subjects and 177 neurological patients with various degrees of dysphagia were investigated. RESULTS: Voluntarily triggered oropharyngeal swallowing was commonly pathological in the majority of patients, with or without overt dysphagia. The dysphagia limit appeared to be an objective measure of the degree of dysphagia in more than 90% of patients. Pathophysiological mechanisms were different in at least three groups of patients with neurogenic dysphagia. In the group of patients with muscular disorders, laryngeal elevators were involved while the CP-sphincter was intact. The second group included patients with the clinical signs of corticobulbar fibre involvement such as amyotrophic lateral sclerosis and pseudobulbar palsy. In these patients, there was incoordination between paretic laryngeal elevators and hyperreflexic CP-sphincter. In the third group (patients with Parkinson's disease), the swallowing reflex was delayed and prolonged. CONCLUSIONS: EMG methods described in the present study are very useful for the diagnosis of neurogenic dysphagia, objectively and quickly. They are important to understand the physiological mechanisms for deglutition and its disorders.

Effects of bolus volume on oropharyngeal swallowing: an electrophysiologic study in man.

OBJECTIVE: Different variables of oropharyngeal swallowing change in response to bolus volume and consistency as determined by manometric/videofluoroscopic studies. But the subject is debatable especially from the physiologic point of view. No electrophysiologic studies are available on human subjects. METHODS: The effects of bolus volume and viscosity on different variables of oropharyngeal swallowing were investigated using electrophysiologic methods. Mechanical upward and downward laryngeal movements and submental electromyographic (SM-EMG) activity of the laryngeal elevator muscles were recorded during dry and 3-, 10-, and 20-ml water swallowing in 14 normal subjects. Cricopharyngeus (CP) muscle was investigated during 3- and 10-ml water swallowing in 10 normal subjects. Semisolid and liquid swallowing were compared in eight normal subjects. RESULTS: The total duration of SM-EMG, time necessary for larynx elevation, CP-EMG pause related with upper esophageal sphincter opening and swallowing variability (jitter) all increased significantly with increasing bolus volume. Laryngeal superior relocation time and CP-EMG pause were shorter for semisolid swallowing compared with swallowing the same amount of liquid. CONCLUSION: The duration of SM-EMG activity, laryngeal upward-downward movements, and CP-EMG pause are affected by sensory inputs such as volume and viscosity of the bolus swallowed. The results indicate that sensory input modifies the central swallowing pattern although basic events remain the same in normal human subjects.

Electrodermal activity in patients with Parkinson's disease.

Peripheral sympathetic activity was investigated in 25 Parkinson's disease (PD) patients and 27 healthy subjects by measuring the skin resistance level (SRL) and skin resistance response (SRR) at the palm of the hand during rest, auditory stimulation and patellar tendon tapping. Blood flow to the hand was also monitored. Normal responses were obtained from all the 27 healthy subjects with both stimuli. All but one of the 25 PD patients responded to sound, six patients failed to respond to patellar tendon tapping and one patient failed to respond to both stimuli. The SRRs (when detectable) of PD patients were always smaller in amplitude than those of normal subjects. It was also observed that while an electrodermal response was present, no vasomotor response could be elicited by either stimulus in some patients. The opposite was true in some other patients. When response latencies were evaluated, it was found that although the mean latency of SRRs evoked by tendon taping was shorter than the mean latency of responses to auditory stimuli in normal subjects, this was not the case in PD patients. SRR mean latency to patellar tendon tapping was significantly longer in PD patients compared with that in normal subjects. Mean latencies of responses to auditory stimuli were the same for both normal subjects and patients. The ratio of the SRR amplitude to SRL (i.e. relative change in SRL) during both types of stimulation was significantly smaller in PD patients than in normal subjects. All the above findings were also true when blood flow to the tissue was interrupted briefly. These findings support the conjecture that the abnormal peripheral sympathetic neural responses associated with PD may arise from a functional disorder in the basal ganglia that influence the efferent autonomic pathway, from impairment of the intermediolateral column of the spinal cord, and possibly from cognitive deficits.

Effect of tibial tubercle elevation on patellofemoral compressive force in patellofemoral arthrosis.

In this study, the effect of tibial tubercle elevation on the patellofemoral compressive force (PFCF) was investigated in patients with patellofemoral arthrosis. Fifteen (11 women and 4 men) patients who had undergone tibial tubercle elevation were included in the study. The average follow-up was 4.5 years. The mean age of the patients was 59 years (range 34-71 years). They were able to maintain a normal pain-free daily life. Maximal isometric quadriceps force (Q) was calculated by equating the moment generated by this force to the moment of the force measured at the ankle by a modified hand dynamometer. PFCF was calculated from the quadriceps and patellar tendon forces. Statistical analyses were then applied to the measured and calculated quantities. The mean quadriceps force in the operated knee decreased by 20%. Likewise, the mean PFCF was found to be reduced by 30% in the operated knees as compared with the asymptomatic contralateral knees. The above differences in Q and PFCF between the operated knee and the asymptomatic knee were statistically significant (P < 0.05). Therefore, the results of this study do not agree with the previously held view that Q and PFCF increase due to the removal of pain after the elevation operation. It is our contention that comparison of the forces measured preoperatively in a painful joint with the forces that can be attained postoperatively in the pain-free joint can lead to errors in biomechanical evaluations.