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Introduction: To define approach of pulmonologists in Turkey to noninvasive mechanical ventilation (NIV) use for chronic respiratory failure (CRF), the most currently applied technique for home mechanical ventilation., Patients and Methods: A 38-question survey, developed and tested by the authors, was distributed throughout Turkey to 2205 pulmonologists by e-mail., Result: Twenty-seven percent of the pulmonologists responded (n=596). Domiciliary NIV was reported to be prescribed by 340 physicians [57.1% of all responders and 81% of pulmonologists practicing NIV at clinical practice (n= 420)]. NIV prescription was associated with physician's title, type of hospital, duration of medical license, total number of patients treated with NIV during residency and current number of patients treated with NIV per week (p< 0.05). Main estimated indications were listed as chronic obstructive pulmonary disease (median, 25-75 percentile of the prescriptions: 75%, 60-85), obesity hypoventilation syndrome (10%, 2-15), overlap syndrome (10%, 0-20) and restrictive lung disease (5%, 2-10). For utilization of NIV at home, Bilevel positive airway pressure-spontaneous mode (40%, 0-80) and oronasal mask (90%, 60-100) were stated as the most frequently recommended mode and interface, respectively. Pressure settings were most often titrated based on arterial blood gas findings (79.2%). Humidifier was stated not to be prescribed by approximately half of the physicians recommending domicilliary NIV, and the main reason for this (59.2%) was being un-refundable by social security foundation., Conclusion: There is a wide variation in Turkey for prescription of NIV, which is supposed to improve clinical course of patients with CRF. Further studies are required to determine the possible causes of these differences, frequency of use and patient outcomes in this setting.

Malaria caused by P. falciparum, is endemic in tropical and subtropical areas but is seen as sporadic cases in our country. A patient, early diagnosed and succesfully treated with antimalarial drug administration and a patient, with severe clinical manifestations and succesfully treated with antimalarial medication as well as Erythrocyte Exchange Transfusion (EET), who were not applied chemoprophylaxis are presented. The cases are presented in order to emphasize on the necessity of giving education to the people going to endemic areas from our country for work or travel and on the necessity of taking chemoprophylaxis and to take attention that EET may be preffered in the therapy of severe malaria cases.

Brucellosis is mainly transmitted to humans by direct contact with infected animals, consumption of non-pasteurized dairy products or through inhalation of aerosols. However, the disease may also be transmitted by exposure to Brucella vaccination that is used in veterinary medicine. In the literature, there were a few case reports of persons who developed brucellosis after unintentional inoculation or conjunctival exposure to the live Brucella vaccine. Here, we describe a sheep farmer with acute brucellosis that occurred as a result of unintentional percutaneous exposure to Brucella melitensis Rev 1 animal vaccine while vaccinating lambs.

Introduction: Noninvasive mechanical ventilation (NIV) has been increasingly used worldwide for acute respiratory failure (ARF), especially in patients with chronic lung disorders. We aimed to define the approach of pulmonologists in Turkey to NIV use for ARF management., Materials and Methods: A 38-question survey, developed and tested by authors, was distributed by e-mail to a total of 2.205 pulmonologists in Turkey., Result: Response rate was 27% (n= 596). Seventy-one percent of responders were practicing NIV in clinic. NIV use was found to be associated with responder's academic title, age, duration of medical license, type of physician's hospital and its region, patient load, NIV experience during residency, and duration of NIV and intensive care unit (ICU) experience (p< 0.001). Based on sub-group analysis of responders using NIV, median number of NIV patients followed-up per week was 4 [interquartile range (IQR): 2-6]. Most of the NIV users reported employment of wards (90%) and/or ICUs (86%) to follow-up patients, while 8.4% of the responders were applying NIV only in ICU's. Chronic obstructive lung disease (COPD) (99.5%), obesity hypoventilation syndrome (93.7%) and restrictive lung disease (89.4%) were the most common indications. Majority of NIV users (87%) were applying NIV to > 60% of patients with COPD, and success rate in COPD was reported as over 60% by 93% of users. Oronasal mask (median and IQR 90, 80-100%, respectively) and home care NIV ventilators (median and IQR 50, 10-85%, respectively) were the most commonly utilized equipment., Conclusions: NIV use in ARF varies based on hospital type, region and, especially, experience of the physician. Although consistent with guidelines and general practice, NIV use can still be improved and increased.

Background: Pyogenic vertebral osteomyelitis (PVO) is a severe infection that requires prolonged antimicrobial therapy and/or surgical interventions. Limited data are available on the safety and clinical efficacy of tigecycline in PVO. The objective of this study was to describe the clinical outcomes of patients treated with tigecycline for culture-negative PVO that was unresponsive to empirical antibiotic therapy including intravenous ampicillin-sulbactam plus ciprofloxacin or ampicillin-sulbactam alone., Methods: We retrospectively reviewed 15 patients with culture-negative PVO from 2009 through 2014. The patients received tigecycline as secondary empirical therapy, after not responding to the first empirical therapy. Clinical success was defined as recovery from symptoms and normalization of laboratory parameters at the end of therapy. Continued clinical success at 24 weeks after the end of the therapy was defined as sustained clinical success., Results: Tigecycline treatment was completed in 14 patients and discontinued in 1 due to severe nausea and vomiting. The mean age of the patients was 67.7 years (range 58-77 years), and 57.1% (8/14) were women. In all, 78.6% (11/14) of patients had risk factors for probable resistant staphylococcal and gram-negative infections such as diabetes mellitus, presence of hemodialysis catheters, and prior antibiotic usage. The average duration of tigecycline treatment was 8.3 weeks (range 6-11 weeks). Sustained clinical success was obtained in all patients., Conclusions: Tigecycline should be considered as an alternative agent for the treatment of PVO in selected patients due to microbiological activity against resistant gram-positive and gram-negative bacteria.

The molecular mechanisms and pathogenesis of chronic hepatitis C (CHC) infection are unclear. Innate immune cells such as natural killer (NK) cells and dendritic cells are responsible from molecular mechanism of CHC. NK cell cytotoxicity such as TRAIL expression is important pathway for viral clearance. The aim of this study was to evaluate the relationship between HCV RNA and sTRAIL levels during the first 12 weeks of Peg-IFNα and ribavirin treatment. Twelve treatment naive patients with CHC treated with Peg-INFα and ribavirin were included in this study. Circulating sTRAIL and HCV RNA levels were measured at baseline, 4th and 12th week of treatment and their correlation was investigated. sTRAIL and HCV RNA levels decreased gradually with Peg-INFα plus ribavirin treatment. The differences were significant between day 0, 4th week and 12th week of treatment. The expression of sTRAIL was correlated with HCV RNA level at baseline, at 4th and 12th week of treatment (P = 0.021 P = 0.012, P = 0.001 respectively). IFN binds to its receptor on the infected hepatocyte surface during Peg-IFNα and ribavirin treatment. So the polarized phenotype of NK cell is not displayed and NK cell cytotoxicity such as TRAIL expression is blocked. We suggest that the decreased level of circulating sTRAIL may reflect increased binding to its ligand expressed on hepatocyte and decreased TRAIL production under the influence of Peg-IFNα plus ribavirin treatment. Therefore TRAIL may be probably a immunologically predictive factor such as HCV RNA during treatment.

Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria have become a growing problem limiting therapeutic options. The aim of this study was to investigate the clinical and microbiological efficacy of amikacin treatment in adult patients with lower UTIs due to ESBL-producing Escherichia coli (Ec) or Klebsiella pneumonia (Kp). We conducted a retrospective study of 36 outpatients aged >18 years with dysuria or problems with frequency or urgency in passing urine; pyuria and a positive urine culture (10(5) cfu/ml) for ESBL producing Ec or Kp which is also resistant to nitrofurantoin, fosfomycin, quinolones and trimethoprim/sulfamethoxazole, between January 2013 and February 2014. Patients received intramuscular amikacin 15 mg/kg/day for 10 days. Clinical success was defined as disappearance of symptoms. Bacteriological success was defined as sterile control urine cultures. 58.3% of patients were female. Age range was 18-89 years. All of the patients had at least one complicating factor. 77.8% of the isolates were E. coli. Clinical success rate was 97.2%. Overall bacteriological success rates were 91.7% on the 3 day of treatment, 97.1% at the end of the treatment and 94.1% on the 7-10 days after treatment. After 28-32 days following the treatment, reinfection was found in 12% whereas relapse was not determined. Nephrotoxicity was developed in one patient. The clinicians should keep in mind that amikacin treatment is an efficient and safe alternative treatment option before the carbapenem treatment especially in patients with lower UTIs caused by ESBL-producing Ec or Kp that are resistant to all oral antibiotics., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Daily chlorhexidine (CHG) bathing has been used as a precaution to reduce the rate of healthcare-associated bloodstream infections (HA-BSI). The application frequency of CHG bathing remains unclear, this procedure has been implemented daily by this time. The aim of this study was to determine the efficacy of weekly whole-body douche with CHG shower gel on rates of HA-BSI., Methods: We conducted a prospective intervention trial in medical, surgical, and anesthesiology intensive care units (ICUs) in a tertiary teaching hospital from June 2011 to November 2012. This study included three periods. During the first period, patients received a daily bed bath by wiping with water and soap. In the second period patients were given a weekly douche with water and soap; in the third period patients were given a weekly douche with CHG shower gel. The rates of HA-BSI were compared between the three periods using Poisson regression analysis., Results: The central line-associated bloodstream infection rates did not decline significantly between periods (p = 0.76). The laboratory-confirmed bloodstream infection (LCBSI) rates in the first, second, and third periods were 7.1, 4, and 1.7, respectively. The LCBSI rates were reduced 43.7% from the first period to the second period (p = 0.03). In addition, there was a 57.5% reduction in LCBSI rates between the second and third periods (p < 0.001). Interestingly, the major decline (76.1%) was determined from the first to the third period (p < 0.002)., Conclusions: Weekly douche with CHG shower gel significantly reduced LCBSI rates. Further studies are needed to validate the clinical impact of different intervals of CHG bathing.

Objective: The aim our study was to establish a core curriculum (CC) for spine surgery incorporating knowledge, skills and attitudes to help define spine surgery as a medical specialty and serve as a guide for specific spine surgery training., Methods: A committee was established to prepare the CC. Five modules were established; Basic Sciences, Spinal Trauma, Degenerative Spine Diseases, Destructive Spine Pathologies and Spinal Deformity. Prepared CC modules were evaluated in a consensus meeting, translated and reevaluated in a second consensus meeting before being accepted as final., Results: In the five modules, 54 subject headings (19 for Basic Sciences, 10 for Spinal Trauma, 4 for Degenerative Spine Diseases, 4 for Destructive Spine Pathologies and 17 for Spinal Deformity) and 165 specific subjects (59 for Basic Sciences, 32 for Spinal Trauma, 10 for Degenerative Spine Diseases, 23 for Destructive Spine Pathologies and 41 for Spinal Deformity) were defined. Learning outcomes and entry and exit criteria were defined for all subjects., Conclusion: This CC may form the basis of spinal surgery training, defining spinal surgery as a medical specialty and help us spine surgeons to develop better defined identities.

Purpose: Cerebral palsy (CP) is the most common disability in childhood. The gross motor function classification system (GMFCS) has become an important tool to assess motor function in CP patient. In 2007, the expanded and revised (E&R) version of GMFCS which includes age band for youth 12-18 years of age was developed. The aim of this study was to evaluate reliability of Turkish version of expanded and revised GMCS., Methods: We assessed interobserver reliability between two physical medicine and rehabilitation specialists in 136 children with CP and test-retest reliability within a subgroup of 48 patients. Percent agreement, intraclass correlation coefficient (ICC) and μ statistics were used to evaluate reliability., Result: The ICC between two physicians was 0.97 and the total agreement was 89%. This result indicates excellent agreement. The overall weighted μ was 0.86. High test-retest reliability was found (ICC: 0.94 95% confidence interval) and the total agreement was 75% for test-retest reliability., Conclusion: The Turkish version of the E&R GMFCS is shown to be reliable and valid for assessment of Turkish CP children.

Aims: To investigate patterns of delays among patients with non-small-cell lung cancer and to identify reasons for the delays., Methods: This prospective study included 101 patients with non-small-cell lung carcinoma. Clinical files of the patients were analyzed and a questionnaire was created to obtain data. Several time intervals and delays were determined for each patient. The reasons for the delays were also evaluated., Results: The mean time was 59.9 days for the application interval, 40.3 days for the referral interval, 16.4 days for the diagnostic interval, and 24.7 days for the treatment interval. The application interval was longer than 30 days (patient's delay) in 48 patients (48.5%). There was a doctor delay in 54 (53.5%) patients, a referral delay in 47 (46.5%) patients, a diagnostic delay in 37 (36.6%) patients, and a treatment delay in 57 (56.4%) patients. The mean total time was 119.6 days. Sixty-two patients (62.6%) had a total delay. The most common reason for patient's delay was neglect of symptoms by patients. A low index of suspicion for lung cancer was the most common cause for referral delay. The low performance of diagnostic tests was the frequent reason for diagnostic delay., Conclusions: Patient's and doctor's delays were a common problem among patients with non-small-cell lung cancer. The rate of doctor's delay was higher than that of patient's delay. Several efforts such as education of the physicians and people about lung cancer should be made to reduce these delays.

A 50-year-old-male was admitted to our hospital in March 2007, complaining of cough and hemoptysis for 3 months. Postero-anterior chest X-ray showed an opacity on right upper zone. Computed tomography of the thorax showed a mass lesion occupying the right upper lobe and superior segment of the lower lobe and invading the mediastinum. Fiberoptic bronchoscopy showed total occlusion of the right upper lobe bronchus by the mass and infiltration of the bronchus intermedius. Bronchoscopic biopsies were nondiagnostic. PET-CT revealed SUVmax of 18.8. Right thoracotomy was performed. Vena cava superior and right pulmonary artery was invaded by the mass. Biopsies were performed. Histopathologic examination demonstrated an inflammatory pseudotumor. Corticosteroid treatment was started. The tumor was clinically and radiologically unresponsive to corticosteroids. He was referred to oncology department for radiotherapy. The patient died on November 2007.

To compare volume- and pressure- controlled ventilation (VCV-PCV) as an initial ventilatory mode in chronic obstructive pulmonary disease (COPD) patients. Case-control study conducted in respiratory intensive care unit (RICU) at a large teaching hospital, between January 2002 and January 2004. PCV was applied in 20 COPD patients with ARF more than 24 hours. Their outcomes were compared with those of a control group of 20 COPD patients matched on age, sex, Acute Physiology Assessment and Chronic Health Evaluation (APACHE) II score, pH and PaCO(2) at the time of intubation previously treated with VCV. The effectiveness of matching was 99%. Groups were compared according to complication and mortality rates, total duration of invasive mechanical ventilation (IMV) and length of RICU stay. Mortality and complication rates, and length of RICU stay were similar in groups but, the mean duration of MV was longer in PCV (198 +/- 177 h vs. 79 +/- 56 h, p< 0.003). PCV group spended significantly longer IMV hours for weaning period (138.6 +/- 164 vs. 34 +/- 33 h, p< 0.01), pre-weaning periods of IMV were found similar. These data suggest that both ventilatory approach have similar outcomes in COPD patients with ARF. Randomize-controlled trials are needed to confirm our results.

Although there are many reports regarding the spinal surgical applications before the 19th century, the definition of spinal disorders and application of the most novel surgical techniques have been performed in last 2 centuries. Lumbar spinal stenosis was reported in the first half of the 20th century. The definition of the lumbar spinal stenosis was commonly attributed to Dr. Verbiest. However, there were some reports regarding the symptoms attributable to lumbar spinal stenosis before him. On the other hand, Dr. Sarpyener, a Turkish surgeon, reported for the first time congenital spinal stenosis, a special variety of spinal stenosis. The aim of this study is to review the biography, scientific studies, and spine applications of Dr. Sarpyener, a pioneer in the field of spina bifida and congenital spinal stenosis.

Botulinum toxin type A can be both safe and effective in relieving spasticity in pediatric patients with cerebral palsy. In our prospective study, we evaluated the functional effect of botulinum toxin A in spastic diplegic-type cerebral palsy. Patients were examined on enrollment and at 1, 3, and 6 months after injection. Passive dorsiflexion of the ankle joint was measured using a goniometer as an angle of possible maximal dorsiflexion with the knee extended and flexed. Spasticity was graded using the Modified Ashworth Scale. Selective motor control at the ankle was assessed, and observational gait analysis was done. The functional status of the patients was determined by using the gross motor classification system. Botulinum toxin A was injected into the gastrocnemius muscle in all patients, and in four patients with concomitant jump knee gait, a hamstring muscle injection was added. Fourteen patients were included in the study. The mean age was 58.81 +/- 15.34 months. Following injection, spasticity was clinically decreased and statistically significant improvement was noticed in all clinical parameters after 1, 3, and 6 months of injection. The improvement in the clinical parameters decreased after 6 months but not to the baseline. One patient was Level II, four patients were Level III, and six patients were Level IV according to the Gross Motor Function Classification System at baseline. Improvement in the gross motor classification system is continued after 6 months in 12 children. The main goal of spasticity treatment in cerebral palsy is functional improvement. In our study, most of our patients had functional improvement according to the gross motor function classification system and did not change at 6 months.

The unfolded states of three homologous proteins with a very similar fold have been investigated by heteronuclear NMR spectroscopy. Secondary structure propensities as derived from interpretation of chemical shifts and motional restrictions as evidenced by heteronuclear (15)N relaxation rates have been analyzed in the reduced unfolded states of hen lysozyme and the calcium-binding proteins bovine alpha-lactalbumin and human alpha-lactalbumin. For all three proteins, significant deviations from random-coil predictions can be identified; in addition, the unfolded states also differ from each other, despite the fact that they possess very similar structures in their native states. Deviations from random-coil motional properties are observed in the alpha- and the beta-domain in bovine alpha-lactalbumin and lysozyme, while only regions within the alpha-domain deviate in human alpha-lactalbumin. The motional restrictions and residual secondary structure are determined both by the amino acid sequence of the protein and by residual long-range interactions. Even a conservative single point mutation from I to L in a highly conserved region between the two alpha-lactalbumins results in considerable differences in the motional properties. Given the differences in oxidative folding between hen lysozyme and alpha-lactalbumin, the results obtained on the unfolded states suggest that residual long-range interactions, i.e., those between the alpha- and the beta-domain of lysozyme, may act as nucleation sites for protein folding, while this property of residual structure is replaced by the calcium-binding site between the domains in alpha-lactalbumin.

Objectives: We evaluated the relationship between functional objective and patient-based subjective assessments and quality of life in patients with lumbar spinal stenosis (LSS)., Methods: Thirty patients (25 females, 5 males; mean age 62+/-9 years; range 41-78 years) were prospectively studied. All were diagnosed as having LSS by clinical and radiological evaluations. Pain was assessed by a visual analog scale. The patients were evaluated by the two-staged treadmill exercise tolerance (TET) test, SF-36 health status survey, and Oswestry Disability Index (ODI). The relationships between the TET test, which is an objective functional assessment, and patient-based assessments (SF-36 and ODI), pain and age were investigated., Results: There were significant differences between the functional grades of the patients at the speed of 1.9 km/hour with respect to ODI scores, the physical component scale of SF-36, age, and the preferred speed of the patients (p<0.05). These differences emerged from the fourth functional stage (p<0.01). Oswestry disability scores and the physical component scores of SF-36 worsened in parallel with the stages of the TET test. The preferred speed of the patients at the TET test was positively correlated with the physical component scores of SF-36 and negatively correlated with Oswestry disability scores (p<0.05). There was a negative correlation between the physical component scores of SF-36 and Oswestry disability scores (p<0.05)., Conclusion: The TET test used to determine the functional capacity seems to be correlated well with subjective patient-based assessments. This objective tool, when combined with subjective assessments, may be helpful in the evaluation and treatment of patients with LSS.

Study Design: Outcome study to determine the internal consistency, and validity of adapted Turkish version of Scoliosis Research Society-22 (SRS-22) Instrument., Objectives: To evaluate the validity and reliability of adapted Turkish Version of SRS-22 questionnaire., Summary of Background Data: The SRS-22 questionnaire is a widely accepted questionnaire to assess the health-related quality of life for scoliotic patients in the United States. However, its adaptation in languages other than the source language is necessary for its multinational use., Methods: Translation/retranslation of the English version of the SRS-22 was done, and all steps for cross-cultural adaptation process were performed properly by an expert committee. Later, SRS-22 questionnaires and previously validated Short Form-36 (SF-36) outcome instruments were mailed to 82 patients who had been surgically treated for idiopathic scoliosis. All patients had a minimum of 2 years follow-up. Fifty-four patients (66%) responded to the first set of questionnaires. Forty-seven of the first time respondents returned their second survey. The average age of the 47 patients (12 male, 35 female) was 19.8 years (range, 14-31 years). The two measures of reliability as internal consistency and reproducibility were determined by Cronbach alpha statistics and intraclass correlation coefficient, respectively. Concurrent validity was measured by comparing with an already validated questionnaire (SF-36). Measurement was made using the Pearson correlation coefficient (r)., Results: The study demonstrated satisfactory internal consistency with high Cronbach alpha values for the four of the corresponding domains (pain, 0.72; self-image, 0.80; mental health, 0.72; and satisfaction, 0.83). However, the Cronbach alpha value for function/activity domain (0.48) was considerably lower than the original questionnaire. The intraclass correlation coefficient for the same domains was 0.80, 0.82, 0.78, 0.81, and 0.76, respectively, demonstrating a satisfactory test/retest reproducibility. Considering concurrent validity, two domains had excellent correlation (r = 0.75-1), while 9 had good correlation (r = 0.50 to 0.75), and 6 had moderate correlation (r =0.25-0.50). Based on these results, question 18 in the function/activity domain with lower Cronbach alpha value was revised while question 15 was excluded. The revised SRS-22 was given to 30 adolescent idiopathic scoliosis patients not included in the index study. The revision could improve the Cronbach alpha value for function/activity domain from 0.48 to 0.81., Conclusion: This study demonstrated that, if measures are to be used across cultures, the items must not only be translated well linguistically but also must be culturally adapted to maintain the content validity of the instrument at a conceptual level across different cultures. This may necessitate several validation studies to ensure and improve consistency in the content and face validity between source and target versions of a questionnaire due to difficulty in detecting subtle differences in the living habits of different cultures.

Background: The annual incidence of tuberculous meningitis (TM) is unknown. TM is a disease that still often results in residual sequelae, and has a mortality rate ranging between 15 and 51%. Experience of countries such as Turkey where drug-resistant tuberculosis and TM are prevalent is important., Methods: Clinical and laboratory findings of 42 patients with TM, followed between 1991 and 2002, were evaluated retrospectively., Results: Twenty-eight female and 14 male patients were included in this study. The mean age of the patients was 33.9 +/- 13.2 years (range, 16-60 years). Fourteen had a history of pulmonary tuberculosis; 12 reported close contact with a person with active pulmonary tuberculosis; three were diagnosed with active pulmonary tuberculosis; two, with HIV infection; two, with Pott's disease; and one, with systemic lupus erythematosus. On admission, 17 patients were diagnosed with stage I; 15, with stage II; and 10, with stage III disease. Hemiparesis (35.7%), cranial nerve palsy (30.9%), and altered consciousness (26.9%) were the most common neurological deficits. Prolonged duration of pre-existing symptoms and female gender were found as significant risk factors in those who develop neurological sequelae (p < 0.01 and p < 0.05, respectively). Cranial computerised tomography revealed various pathological findings in all but five patients. Sulcus effacement was the most common radiological finding. Enlargement of ventricles, focal cerebral oedema/shunt, calcification of meninges, tubercle, and infarction were other common abnormal radiological findings., Conclusions: Prolonged duration of pre-existing symptoms and female gender are predictors of neurological sequelae of TM. Early identification of such patients and prompt initiation of anti-tuberculosis therapy may improve their outcome.

F(420)-dependent secondary alcohol dehydrogenase (Adf) from methanogenic archaea is a member of the growing bacterial luciferase family which are all TIM barrel enzymes, most of which with an unusual nonprolyl cis peptide bond. We report here on the crystal structure of Adf from Methanoculleus thermophilicus at 1.8 A resolution in complex with a F(420)-acetone adduct. The knowledge of the F(420) binding mode in Adf provides the molecular basis for modeling F(420) and FMN into the other enzymes of the family. A nonprolyl cis peptide bond was identified as an essential part of a bulge that serves as backstop at the Re-face of F(420) to keep it in a bent conformation. The acetone moiety of the F(420)-acetone adduct is positioned at the Si-face of F(420) deeply buried inside the protein. Isopropanol can be reliably modeled and a hydrogen transfer mechanism postulated. His39 and Glu108 can be identified as key players for binding of the acetone or isopropanol oxygens and for catalysis.

Tuberculosis continues to be a significant cause of morbidity and mortality. Although tuberculosis usually attacks the lungs, other organs can also be affected, leading to extrapulmonary tuberculosis (EPT) or disseminated tuberculosis. This study retrospectively analysed the incidence, clinical sites and risk factors for EPT in 252 patients with EPT between 1 January 1991 and 30 June 2003. EPT was defined as clinical, laboratory, imaging, and/or histopathological evidence of mycobacterial infection in a site other than hilar lymph nodes or lung parenchyma. In our study group, tuberculous lymphadenitis (36.5%) was found to be the most common clinical presentation of EPT. 119 (47.2%) patients developed the severe form of EPT, according to the WHO report, and 133 (52.8%) patients developed the less severe form. A case history of pulmonary tuberculosis was found to be a risk factor for the development of EPT (p <0.05). The study showed that EPT is still a public health problem. These findings suggested that pulmonary tuberculosis may play a critical role in the development of EPT. 12-month therapy may be chosen in patients with EPT considering acceptable adverse effects without relapses.

Background: In the ongoing discussion concerning the realization of an epiretinal prosthesis for electric stimulation of retinal ganglion cells, long-term fixation of such a device is a crucial question. We evaluated surgical techniques for implantation and fixation of electrically inactive microelectrode arrays (MA) into the retinas of rabbits and secondary tissue reactions to the implant., Methods: Vitrectomy and laser coagulation of the prospective fixation area were performed in rabbits. Implantation of MAs was performed 3 weeks later in 10 animals. The MA was fixated using retinal tacks. The follow-up included ophthalmoscopy and electrophysiology. At the end of the follow-up, the enucleated eyes were processed for light microscopy using standard procedures and grinding techniques., Results: Nine of 10 rabbits were implanted without serious complications. Clinical and electrophysiologic data through 6 months of follow-up did not indicate any adverse effect of the surgery, the implant, or the tack itself. No change in retinal architecture underneath the implant was found by light microscopy. In these cases, the implant was stable at its original fixation area. In three cases, mild cataract formation was observed, and in one case, a total retinal detachment was found., Conclusion: Tack fixation of electrode arrays for electric stimulation of the inner retinal surface seems to be a useful approach in long-term implantation of an epiretinal prosthesis.

F420H2:NADP oxidoreductase is found in methanogenic, sulfate-reducing and halophilic archaea and also in some bacteria. The putative gene encoding the enzyme was cloned from Methanobacterium thermoautotrophicum (strain Marburg) and heterologously expressed in Escherichia coli. The overproduced active enzyme was purified, characterized and crystallized.

Methanogenic archaea growing on ethanol or isopropanol as the electron donor for CO2 reduction to CH4 contain either an NADP-dependent or a coenzyme F420-dependent alcohol dehydrogenase. We report here that in both groups of methanogens, the N5, N10-methylenetetrahydromethanopterin dehydrogenase and the N5, N10-methylenetetrahydromethanopterin reductase, two enzymes involved in CO2 reduction to CH4, are specific for F420. This raised the question how F420H2 is regenerated in the methanogens with an NADP-dependent alcohol dehydrogenase. We found that these organisms contain catabolic activities of an enzyme catalyzing the reduction of F420 with NADPH. The F420-dependent NADP reductase from Methanogenium organophilum was purified and characterized. The N-terminal amino acid sequence showed 42% sequence identity to a putative gene product in Methanococcus jannaschii, the total genome of which has recently been sequenced.

The adenylate kinase genes (adkA) were cloned from four closely related methanogenic members of the Archaea: the mesophile Methanococcus voltae (Mv), the thermophile M. thermolithotrophicus (Mt) and the hyperthermophiles M. jannaschii (Mj) and M. igneus (Mi). All four genes encode a protein of 192 amino acids (aa), and the four enzymes were closely related, with 68-81% aa identity in pairwise comparisons. It is anticipated that the enzyme set will provide the basis for studies that can establish the structural basis for ADK thermal stability. Mj and Mi contained a gene homologous to M. vannielii sec Y upstream of adkA, while Mv and Mt contained an unidentified, yet conserved, upstream open reading frame (ORF). Mt, Mj and Mi, but not Mv, contained an unidentified, yet highly conserved, ORF directly downstream of adkA. Based on their size, predicted secondary structure and phylogenetic relation to bacterial and eukaryotic adenylate kinases (ADK), it was concluded that the archaeal adkA genes encoded a unique class of ADK, and suggested that Euryarchaeotal and Crenarchaeotal branches of the Archaea contain separate subclasses of the enzyme.

The two diastereotopic protons at C4 of NAD(P)H are seen separately in 1H-NMR spectra. This fact was used to determine the stereospecificity at C4 of NAD(P) for the NADP-dependent alcohol dehydrogenase from Methanogenium organophilum and for the NAD-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans. The reduction of NADP+ with [2H6]ethanol was found to yield (4R)-[4-2H1]NADPH and the oxidation of (4R)-[4-2H1]NADH with 2-oxoglutarate to yield unlabelled [4-1H]NAD+. These results indicate that both enzymes are Re-face stereospecific at C4 of the pyridine nucleotides.

Coenzyme F420 is a 5-deazaflavin. Upon reduction, 1,5-dihydro-coenzyme F420 is formed with a prochiral center at C5. In this study we report that the F420-dependent glucose-6-phosphate dehydrogenase from Mycobacterium smegmatis and the F420-dependent alcohol dehydrogenase from Methanoculleus thermophilicus are Si-face stereospecific with respect to C5 of the 5-deazaflavin. These results were obtained by following the stereochemical course of the reversible incorporation of 3H into F420 from tritium-labeled substrates. Our findings bring to eight the number of coenzyme-F420-dependent enzymes shown to be Si-face stereospecific. No F420-dependent enzyme with Re-face stereospecificity is known. This is noteworthy since coenzyme F420 is functionally similar to pyridine nucleotides for which both Si-face and Re-face specific enzymes have been found.

Calcium hydroxide, in its various forms, has become the preferred agent of most practitioners who perform pulp capping. The application of calcium hydroxide to the pulp stimulates the growth of new dentin and protects the pulp from subsequent irritation. However, the new dentin generated by the pulp may, in turn, infringe on the pulp. If the thickness of the pulp tissue is large, this infringement will not be significant. If the volume of pulp tissue is shallow, the same amount of infringement may cause sufficient impairment of circulation to the cornal area of the pulp, leading to an area of the necrosis may then contaminate the entire pulp, and root canal therapy will become necessary. Therefore, pulpal amputation is the preferred treatment in such situations.