Comorbidity of psychiatric disorders and symmetric distal polyneuropathy among type II diabetic outpatients

The objective of the present study was to establish the frequency of psychiatric comorbidity in a sample of diabetic patients with symmetric distal polyneuropathy (SDPN). Sixty-five patients with type 2 diabetes mellitus were selected consecutively to participate in the study at Instituto Estadual de Diabetes e Endocrinologia. All patients were submitted to a complete clinical and psychiatric evaluation, including the Portuguese version of the structured clinical interview for DSM-IV, the Beck Depression Inventory, the Neuropathy Symptom Score, and Neuropathy Disability Score. SDPN was identified in 22 subjects (33.8%). Patients with and without SDPN did not differ significantly regarding sociodemographic characteristics. However, a trend toward a worse glycemic control was found in patients with SDPN in comparison to patients without SDPN (HbA1c = 8.43 ± 1.97 vs 7.48 ± 1.95; P = 0.08). Patients with SDPN exhibited axis I psychiatric disorders significantly more often than those without SDPN (especially anxiety disorders, in general (81.8 vs 60.0%; P = 0.01), and major depression - current episode, in particular (18.2 vs 7.7%; P = 0.04)). The severity of the depressive symptoms correlated positively with the severity of SDPN symptoms (r = 0.38; P = 0.006), but not with the severity of SDPN signs (r = 0.07; P = 0.56). In conclusion, the presence of SDPN seems to be associated with a trend toward glycemic control. The diagnosis of SDPN in diabetic subjects seems also to be associated with relevant psychiatric comorbidity, including anxiety and current mood disorders.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Modelling Cutting States in Rough Turning of 34CrNiMo6 Steel

Rough turning is an important form of manufacturing cylinder-symmetric parts. Thus far, increasing the level of automation in rough turning has included process monitoring methods or adaptive turning control methods that aim to keep the process conditions constant. However, in order to improve process safety, quality and efficiency, an adaptive turning control should be transformed into an intelligent machining system optimizing cutting values to match process conditions or to actively seek to improve process conditions. In this study, primary and secondary chatter and chip formation are studied to understand how to measure the effect of these phenomena to the process conditions and how to avoid undesired cutting conditions. The concept of cutting state is used to address the combination of these phenomena and the current use of the power capacity of the lathe. The measures to the phenomena are not developed based on physical measures, but instead, the severity of the measures is modelled against expert opinion. Based on the concept of cutting state, an expert system style fuzzy control system capable of optimizing the cutting process was created. Important aspects of the system include the capability to adapt to several cutting phenomena appearing at once, even if the said phenomena would potentially require conflicting control action.

13CO2 recovery fraction in expired air of septic patients under mechanical ventilation

The continuous intravenous administration of isotopic bicarbonate (NaH13CO2) has been used for the determination of the retention of the 13CO2 fraction or the 13CO2 recovered in expired air. This determination is important for the calculation of substrate oxidation. The aim of the present study was to evaluate, in critically ill patients with sepsis under mechanical ventilation, the 13CO2 recovery fraction in expired air after continuous intravenous infusion of NaH13CO2 (3.8 µmol/kg diluted in 0.9% saline in ddH2O). A prospective study was conducted on 10 patients with septic shock between the second and fifth day of sepsis evolution (APACHE II, 25.9 ± 7.4). Initially, baseline CO2 was collected and indirect calorimetry was also performed. A primer of 5 mL NaH13CO2 was administered followed by continuous infusion of 5 mL/h for 6 h. Six CO2 production (VCO2) measurements (30 min each) were made with a portable metabolic cart connected to a respirator and hourly samples of expired air were obtained using a 750-mL gas collecting bag attached to the outlet of the respirator. 13CO2 enrichment in expired air was determined with a mass spectrometer. The patients presented a mean value of VCO2 of 182 ± 52 mL/min during the steady-state phase. The mean recovery fraction was 0.68 ± 0.06%, which is less than that reported in the literature (0.82 ± 0.03%). This suggests that the 13CO2 recovery fraction in septic patients following enteral feeding is incomplete, indicating retention of 13CO2 in the organism. The severity of septic shock in terms of the prognostic index APACHE II and the sepsis score was not associated with the 13CO2 recovery fraction in expired air.

Systematic head and neck physical examination as a predictor of obstructive sleep apnea in class III obese patients

Our aim was to determine if anatomical abnormalities of the upper airway (UA) and facial skeleton of class III severely obese patients are related to the presence and severity of obstructive sleep apnea syndrome (OSAS). Forty-five patients (69% females, mean age 46.5 ± 10.8 years) with a body mass index (BMI) over 40 kg/m² underwent UA and facial skeletal examinations as well as polysomnography. Mean BMI was 49 ± 7 kg/m² and mean neck circumference was 43.4 ± 5.1 cm. Polysomnographic findings showed that 22% had a normal apnea-hypopnea index (AHI) and 78% had an AHI over 5. The presence of OSAS was associated with younger age (P = 0.02), larger neck circumference (P = 0.004), presence of a voluminous lateral wall (P = 0.0002), posteriorized soft palate (P = 0.0053), thick soft palate (P = 0.0014), long uvula (P = 0.04), thick uvula (P = 0.0052), and inferior turbinate hypertrophy (P = 0.04). A larger neck circumference (P = 0.02), presence of a voluminous lateral wall (P = 0.04), posteriorized soft palate (P = 0.03), and thick soft palate (P = 0.04) were all associated with OSAS severity. The prevalence of OSAS in this group was high. A larger neck circumference and soft tissue abnormalities of the UA were markers for both the presence and severity of OSAS. Conversely, no abnormalities in the facial skeleton were associated with OSAS in patients with morbid obesity.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

Noninvasive assessment of endothelial function and ST segment changes during exercise testing in coronary artery disease

Endothelial function (EF) plays an important role in the onset and clinical course of atherosclerosis, although its relationship with the presence and extent of coronary artery disease (CAD) has not been well defined. We evaluated EF and the ST segment response to an exercise test in patients with a broad spectrum of CAD defined by coronary angiography. Sixty-two patients submitted to diagnostic catheterization for the evaluation of chest pain or ischemia in a provocative test were divided into three groups according to the presence and severity of atherosclerotic lesions (AL): group 1: normal coronaries (N = 19); group 2: CAD with AL <70% (N = 17); group 3: CAD with AL ≥70% (N = 26). EF was evaluated by the percentage of flow-mediated dilatation (%FMD) in the brachial artery during reactive hyperemia induced by occlusion of the forearm with a pneumatic cuff for 5 min. Fifty-four patients were subjected to an exercise test. Gender and age were not significantly correlated with %FMD. EF was markedly reduced in both groups with CAD (76.5 and 73.1% vs 31.6% in group 1) and a higher frequency of ischemic alterations in the ST segment (70.8%) was observed in the group with obstructive CAD with AL ≥70% during the exercise test. Endothelial dysfunction was observed in patients with CAD, irrespective of the severity of injury. A significantly higher frequency of ischemic alterations in the ST segment was observed in the group with obstructive CAD. EF and exercise ECG differed among the three groups and may provide complementary information for the assessment of CAD.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Evaluation of piroxicam-β-cyclodextrin as a preemptive analgesic in functional endoscopic sinus surgery

The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-β-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-β-cyclodextrin, group 2 received 40 mg piroxicam-β-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU), at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P < 0.05). During the postoperative period, morphine consumption was 3.03 ± 2.54, 2.7 ± 2.8, and 5.56 ± 3.12 mg for each group, respectively (P < 0.05). As a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. However, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. Similar hematological test results were obtained for all groups. Preemptive administration of piroxicam-β-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-β-cyclodextrin without side effects during the postoperative period.

Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine

The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4% in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95%; P = 0.001). The most common adverse events were drowsiness/fatigue (57%), memory/concentration difficulties (24%), and sexual dysfunction (11%) in the clonazepam group and drowsiness/fatigue (81%), sexual dysfunction (70%), and nausea/vomiting (61%) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Anticonvulsant and antiarrhythmic effects of nifedipine in rats prone to audiogenic seizures

Calcium ion participates in the regulation of neural transmission and the presynaptic release of neurotransmitters. It is also involved in epileptic events, cardiac arrhythmias and abnormal conduction of stimuli. The purpose of the present study was to evaluate the effects of nifedipine, a calcium channel blocker, on epileptic seizures and on reperfusion arrhythmias in rats prone to audiogenic epileptic seizures (Wistar audiogenic rats, WAR) and in normal Wistar rats (N = 6/group). The seizure severity index was applied after an intraperitoneal injection of 20 or 40 mg/kg nifedipine (N20 and N40 groups, respectively). The Langendorff technique was used to analyze cardiac function, as well as the incidence and severity of the reperfusion arrhythmias after ligature and release of the left coronary artery in rats treated or not with nifedipine. We found that nifedipine treatment decreased seizure severity (0.94 ± 0.02 for WAR; 0.70 ± 0.10 for WAR + N20; 0.47 ± 0.08 for WAR + N40) and increased the latent period (13 ± 2 s for WAR; 35 ± 10 s for WAR + N20; 48 ± 7 s for WAR + N40) for the development of seizures in WAR. Furthermore, the incidence and severity of the reperfusion arrhythmias were lower in WAR and normal Wistar rats injected with nifedipine. In WAR, these effects were mediated, at least in part, by a decrease in heart rate. Thus, our results indicate that nifedipine may be considered to be a potential adjuvant drug for epilepsy treatment, especially in those cases associated with cardiac rhythm abnormalities.