Glucagon-like peptide-1 receptor-agonists treatment for cardio-metabolic parameters in schizophrenia patients: a systematic review and meta-analysis.

Aims: We performed this meta-analysis to evaluate the efficacy and safety of glucagon-like peptide-1 receptor-agonists (GLP-1RA) treatment on cardio-metabolic parameters among antipsychotic-treated patients with schizophrenia. Methods: We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, and Scopus for relevant Randomized Clinical trials (RCTs) from inception until 1 August 2022. Documents were screened for qualified articles, and all concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) in the meta-analysis models using Review Manager (RevMan version 5.4). Results: Pooling data from 7 RCTs (398 patients) showed that GLP-1 RA was superior to placebo with regard to body weight [MD = - 4.68, 95% CI (-4.90,-4.46), P < 0.00001], waist circumference [MD = - 3.66, 95% CI (-3.89,-3.44), P < 0.00001], body mass index (BMI) [MD = - 1.09, 95% CI (-1.25,-0.93), P < 0.00001], systolic blood pressure (SBP) [MD = - 3.07, 95% CI (-3.61,-2.53), P < 0.00001], and diastolic blood pressure (DBP) [MD = - 2.02, 95% CI (-2.42,-1.62), P < 0.00001]. The total effect did not favor either of the two groups with respect to insulin and respiratory adverse events {[MD = - 0.06, 95% CI (-0.36, 0.24), p = 0.70], [RR = 0.66, 95% CI (0.31, 1.40), p = 0.28]; respectively}. Conclusion: Our analysis revealed that GLP-1 RA treatment is safe and effective on cardio-metabolic parameters over control in antipsychotic-treated patients with schizophrenia. Nevertheless, the present evidence is not sufficient to confirm the safety and efficacy of GLP-1RA treatment on insulin and respiratory adverse events. Therefore, further studies are recommended. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333040.

Analysis of SLC7A9 gene mutations among Jordanian patients with cystinuria.

BACKGROUND: Cystinuria is known as a heritable disorder affecting the cysteine reabsorption by renal system as well as the reabsorption of dibasic amino acids. The main objectives of the present study were to identify genetic mutations in SLC7A9 gene associated with cystinuria. METHODS: A cross sectional study design was conducted. A total of 28 patients diagnosed with cystinuria were included. Molecular techniques were applied to identify genetic mutations in SLC7A9 gene. RESULTS: The mean age of study participants was 31.57 ± 2.88 years, and slightly more than two thirds of participants were males. Mutations of SLC 7A9 gene showed that the majority of cases (57.1%) were homogeneous, (7.1%) heterogeneous, and slightly more than one third of patients had no mutations. There was no statistically significant relationship between mutations for the SLC7A9 gene and gender (p = 0.249). CONCLUSION: Mutations in the SLC7A9 gene are prevalent and can be used as molecular tools to diagnose cystinuria.

The association between gastroesophageal flap valve function and gastroesophageal reflux symptoms.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal endoscopic examination is usually the first step in the evaluation of patients with suspected gastroesopageal reflux disease. The primary aim of this study was to investigate the association between gastroesophageal flap valve function (GEFV) and gastroesophapgeal reflux symptoms in patients undergoing routine upper endoscopy. Patients and methods: 1507 patients were included into the study and the GEFV graded I to IV as follows: Hill I-II: normal GEFV, and Hill III-IV: abnormal GEFV. RESULTS: Patients in abnormal GEFV group had a higher incidence of reflux symptoms compared to normal GEFV group (53.4% vs 47.4% for heartburn p=0.03 and 53.2% vs 42.4% for regurgitation, p<0.01). In abnormal GEFV patients, esophagitis was more common compared to those with normal GEFV (32.6% vs 11.1%, p<0.01). Presence of heartburn and regurgitation (n =556) correlated with Hill III-IV grades (n = 184/556), (sensitivity: 33%, p = 0.003). In contrast, 24.6% (157/638) of patients without reflux symptoms were in abnormal GEFV group. In patients undergoing endoscopy because of reflux symptoms, Grade III-IV valve was detected more commonly in patients with reflux symptoms compared to patients without reflux symptoms (p = 0.01). CONCLUSIONS: Patients with abnormal valves (Hill grades III and IV) but without reflux symptoms, esophagitis and hiatal hernia should be evaluated individually by means of the presence of gastroesophageal reflux disease which means that GEFV is not a good indicator of reflux disease.

INFLAMMATORY BOWEL DISEASE-LIKE PHENOTYPE IN A YOUNG GIRL WITH PROLIDASE DEFICIENCY: A NEW SPECTRUM OF CLINICAL MANIFESTATION.

Prolidase deficiency (PD) is an inherited disorder associated with cutaneous ulcers, intellectual disability, unusual facial appearance, skeletal deformities, hematological anomalies, splenomegaly, and chronic infections. We report a girl with PD who presented with early inflammatory bowel disease (IBD). A 2-month-old girl with a dysmorphic face presented with recurrent respiratory tract infections, vomiting, diarrhea and hepatosplenomegaly. She had steatorrhea, abnormal liver enzymes, hypergammaglobulinemia, autoantibody positivity and steatohepatitis in liver biopsy. On follow-up, skin lesions, pruritus and developmental delay were added. At the age of 21 months, IBD was diagnosed with persistent diarrhea, fever, hypoalbuminemia, elevated inflammatory markers, fecal leukocytes and aphthous ulcers in colon. Remission was achieved with prednisone and continued with mesalasine. Thrombocytopenia developed after 3 years. Her findings prompted us to further investigations. PD as the underlying molecular cause of the disease was detected by exome sequencing. In conclusion, PD should be considered in the differential diagnosis of some IBD patients.

Crigler-Najjar syndrome type I in a Turkish newborn caused by a novel mutation and Gilbert type genetic defect.

Crigler-Najjar syndrome (CNS), caused by deficiency of bilirubin uridine diphosphate glucuronosyltransferase (UGT) 1A1, is a rare and autosomal recessive inherited disorder characterized by severe unconjugated nonhemolytic hyperbilirubinemia since birth. We present a girl with CNS type I caused by a novel mutation and Gilbert type genetic defect. Gilbert's Syndrome (GS) and CNS type I both involve abnormalities in bilirubin conjugation secondary to deficiency of bilirubin UGT. The combined defects even in benign genetic forms were shown to cause more serious clinical disease. The patient has been treated with daily home-based phototherapy for more than nine months and considered as a candidate for liver transplantation.

Antimicrobial resistance in gram-negative hospital isolates: results of the Turkish HITIT-2 Surveillance Study of 2007.

Resistance rates to amikacin, ciprofloxacin, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam in Escherichia coli (n= 438), Klebsiella pneumoniae (n= 444), Pseudomonas aeruginosa (n= 210) and Acinetobacter baumanni (n=200) were determined with e-test in a multicenter surveillance study (Hitit-2) in 2007. ESBL production in Escherichia coli and K. pneumoniae was investigated following the CLSI guidelines. Overall 42.0% of E.coli and 41.4% of K. pneumoniae were ESBL producers. In E. coli , resistance to imipenem was not observed, resistance to ciprofloxacin and amikacin was 58.0% and 5.5% respectively. In K. pneumoniae resistance to imipenem, ciprofloxacin and amikacin was 3.1%, 17.8% 12.4% respectively. In P. aeruginosa the lowest rate of resistance was observed with piperacillin/tazobactam (18.1%). A. baumanni isolates were highly resistant to all the antimicrobial agents, the lowest level of resistance was observed against cefoperazone/sulbactam (52.0%) followed by imipenem (55.5%). this study showed that resistance rates to antimicrobials are high in nosocomial isolates and show variations among the centers.

Effect of high temperature on neuromuscular jitter in myasthenia gravis.

To examine if the effect of temperature on neuromuscular jitter differs in myasthenics and normals, we performed single fiber electromyography (SFEMG) in 10 myasthenics and 10 healthy controls after heating the upper extremity to 37 and 42 degrees C. In each case, 10-24 mean consecutive difference (jitter) values were obtained at both temperatures. All jitters were pooled appropriately and the groups were compared with each other. The mean jitter was 33.4 +/- 10.4 micros at 37 degrees C and 28.2 +/- 11.4 micros at 42 degrees C in controls, and 48.3 +/- 18.3 micros at 37 degrees C and 54.8 +/- 24.9 micros at 42 degrees C in patients. Seven out of 10 patients showed SFEMG abnormalities at 37 degrees C. The number of patients with SFEMG abnormalities rose to 9 after heating to 42 degrees C. Heating decreases neuromuscular jitter in controls and increases it in myasthenics. SFEMG performed at higher temperatures may increase the diagnostic sensitivity of the method in myasthenia gravis. The change of jitter with temperature in opposite directions in myasthenics and normals could be helpful to detect neuromuscular dysfunction.

Choroidal neovascularization following photodynamic therapy in a patient with chronic central serous chorioretinopathy.

PURPOSE: To present the clinical features and treatment of subfoveal choroidal neovascularization complicating photodynamic treatment (PDT) performed for chronic central serous chorioretinopathy (CSC). METHOD: A 48-year-old healthy woman who had chronic visual deterioration in her right eye due to chronic CSC was treated with standard PDT protocol. RESULTS: Three weeks after the initial PDT, she experienced recovery in her vision and neurosensory detachment subsided clinically. However, six weeks after the PDT she returned with decreased visual acuity and metamorphopsia in the right eye. Fluorescein angiogram and optic coherence tomography delineated a classic subfoveal subretinal neovascular membrane. PDT was reperformed two more times, three months apart and closure of neovascular membrane was obtained. CONCLUSION: Choroidal neovascularization might have occurred during the natural course of disease process or as a consequence of PDT. PDT seems to be effective for treating the choroidal neovascularization complicating PDT performed for CSC.

Is there any relationship between toxoplasma infection and reactive arthritis?

BACKGROUND: The diagnosis of reactive arthritis is a challenging clinical problem in daily practice. Although there are many triggering infectious agents for reactive arthritis, Toxoplasmosis, a worldwide parasitic infection has not been reported. AIM: We investigated the serologic evidence of Toxoplasma gondii ( T. gondii ) infection in patients with newly diagnosed reactive arthritis after six weeks of the onset of the first symptom but no demonstrable triggering agent for reactive arthritis. SETTING AND DESIGN: Clinical controlled study. MATERIALS AND METHODS: We screened serologically the serum toxoplasma IgM and IgG antibody (Ab) titers which revealed toxoplasma infection in 50 patients with reactive arthritis (40 female, 10 men) and no demonstrable triggering agent and control subjects (32 female, 8 male). STATISTICAL ANALYSIS: SPSS 10.0 software package program was used. RESULTS: The mean age of the patients and controls was similar (41.3+/- 12.0 vs. 39.6+/-11.8 years) respectively. The prevalence of IgG Ab titers of T. gondii in patients and controls were found to be 52% and 47.5%, respectively. Mean serum Toxoplasma IgG Ab levels were found to be 16.5+/-14.5 IU/ml, and 16.9+/-13.8 IU/ml in patients and control subjects respectively ( P> 0.05). We did not find any Toxoplasma IgM Ab titer demonstrating the acute or sub-acute infection in the serum of patients or controls. CONCLUSION: Although past Toxoplasma infection was prevalent in both groups, we did not find any subject with acute Toxoplasma infection in patients with newly diagnosed reactive arthritis and healthy controls. Despite the fact that our study group was small, we suggest that T. gondii does not seem to be a triggering agent for reactive arthritis and past infection may be a coincidental finding.

Susceptibility of bacterial isolates from Turkey--a report from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program.

The study monitored the susceptibility of nosocomial pathogens to meropenem and comparator antimicrobial agents isolated as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program from Turkish university hospitals. In terms of minimum inhibitory concentration 90% (MIC(90)) values, meropenem was two- and eight-fold more active than imipenem against Escherichia coli and Klebsiella pneumoniae, respectively. 40.5% of K. pneumoniae, 23.1% of Klebsiella oxytoca and 15.3% of E. coli isolates were extended-spectrum beta-lactamase (ESBL) producers. Piperacillin/tazobactam was the most active agent against isolates of Pseudomonas aeruginosa, followed by meropenem and imipenem. Against Acinetobacter baumannii isolates, meropenem and imipenem were the most active agents. Continued surveillance by the MYSTIC Program appears to be prudent to help focus on effective empiric treatment regimens.

Inhibition of vascular endothelial growth factor-induced retinal neovascularization by retinoic acid in experimental retinopathy of prematurity.

Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of retinopathy of prematurity (ROP) and inhibition of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP. It is suggested that retinoids exert a highly potent antiangiogenic activity by inhibiting VEGF expression. The aim of this study was to demonstrate the preventive effect of retinoic acid (RA) on the VEGF-induced retinal neovascularization in a rat model of ROP. Wistar albino rats were placed into incubators at birth and exposed to an atmosphere alternating between 50 % and 10 % O(2) every 24 hours. After 14 days, the animals were removed to room air and received either an intraperitoneal injection of RA (5 mg/kg/day) (n=9) or saline (n=4) daily for six days, and sacrificed at 21 days. Other rats (n=4) were raised in room air and served as age-matched controls. The globe of each eye was cut through the cornea and embedded in paraffin. Serial sections were stained with hematoxylin-eosin for quantification of neovascular nuclei. The avidin-biotin peroxidase method was performed for evaluation of VEGF expression. The average number of neovascular nuclei was significantly lower in the control group compared to that in the ROP groups. In addition, it significantly decreased in the RA-treated ROP group compared to that of the saline-administrated ROP group. VEGF immunostaining was overall negative in room air-exposed rats. The VEGF immunostaining score significantly decreased in the RA-treated ROP group compared to that in the saline-administered ROP group. RA treatment might be beneficial in preventing neovascularization resulting from oxygen-induced retinopathy by downregulation of VEGF expression.

Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group.

A total of 155 patients with acute myeloid leukemia (AML) received hematopoietic stem cell transplants from unrelated donors after standard conditioning. Clinical outcome after the use of two different antithymocyte globulins for the prevention of graft-versus-host disease (GvHD) was analyzed in a retrospective study as follows: rabbit ATG (Thymoglobulin Sangstat/Genzyme, n=49, median age 42 years, 53% in CR, further ATG-S); rabbit ATG (ATG-Fresenius, n=38, median age 42 years, 58% in CR, further ATG-F) or no ATG (n=68, median age 36 years, 55% in CR). The groups were comparable regarding disease status at transplant, age, CMV status and cytogenetics. Grade III-IV acute GvHD was found in 15% in the ATG and 27% in the no ATG group (P=0.44). The most important independent risk factors for chronic GvHD (cGvHD) were the use of ATG, disease status at transplant and conditioning. cGvHD developed significantly more frequently in no ATG group. With the median follow-up of 34 months, the 5-year survival is 42% for those transplanted in CR. To conclude, these data demonstrate that the transplants performed in CR, with ATG, are associated with a good outcome, low incidence of cGvHD and no increase of relapse.

Etiology of childhood blindness in Izmir, Turkey.

PURPOSE: To identify the anatomic sites and the etiology of childhood blindness and to discern treatable and preventable causes. METHODS: The records of 998 patients seen in the authors' pediatric ophthalmology unit between June 1998 and May 2002 were examined retrospectively. A total of 148 patients who had visual impairment and blindness according to World Health Organization criteria were included in the study. They are classified according to the etiology based on time of insult and the anatomic site of visual loss. RESULTS: The most common anatomic site of visual loss was retina, with a rate of 25.0%. The etiology according to the time of insult was unknown in 45.2% of the patients, of whom 20.2% had cataract. Genetic disorders were responsible in 25.0% of the patients. In 69.6% of the patients, the causes of visual impairment were considered either preventable or treatable, including cataract, retinopathy of prematurity, genetic disorders, and refractive errors. CONCLUSIONS: A high percentage of our patients had avoidable causes of childhood blindness. Genetic counseling services, as well as national screening programs for amblyopia, red fundus reflex, and retinopathy of prematurity, should be established.

Ocular myasthenia gravis coincident with thyroid ophthalmopathy.

Graves' disease and myasthenia gravis are both auto-immune diseases and the coexistence of these two diseases is well recognized. Myasthenia gravis is more frequent in patients with thyroid disease. Here we present a case of thyroid ophthalmopathy and ocular myasthenia.

Surveillance of antimicrobial resistance in gram-negative isolates from intensive care units in Turkey: analysis of data from the last 5 years.

A multicenter antimicrobial surveillance program was established in Turkey in 1995 to monitor the predominant Gram-negative pathogens from intensive care units (ICUs) and antimicrobial resistance patterns of these isolates. Sixteen hospitals participated in the study and a total of 1479 isolates from 1,100 patients were collected. The isolates were tested for their susceptibility against 13 antibiotics by E-test method. Minimum inhibitory concentrations (MICs) for each isolate were determined for imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam, ceftriaxone, cefepime, cefuroxime, piperacillin-tazobactam, ticarcillin-clavulanate, gentamicin, amikacin and ciprofloxacin. The most common isolates were Pseudomonas spp. (28.2%), Escherichia coli (19.2%) and Klebsiella spp. (19.1%). We found very high resistance rates to all major antibiotics that are used to treat serious infections. Although imipenem is the most active agent, it had an overall susceptibility rate of 68%. Half of the tested Klebsiella spp. strains were found to produce ESBL. This is a very high rate when compared with the literature. Cross-resistance among species was also investigated. 52% of ciprofloxacin-resistant strains were also resistant to imipenem, 80% to ceftazidime, 97% to ceftriaxone, 86% to amikacin and 19% of imipenem-resistant strains were susceptible to ceftazidime and 18% to amikacin. When susceptibilities of the years 1995 and 1999 were compared, the most interesting finding was the decrease in resistance to 3rd generation cephalosporins. In conclusion, this national clinical isolate database shows that resistance rates are high, the change over years is not predictable and continuous surveillance is necessary to monitor antimicrobial resistance and to guide antibacterial therapy.

Alternative methods of terminal sterilization for biologically active macromolecules.

The traditional perception within the pharmaceutical industry of the manufacture of injectable drug products is that active pharmaceutical ingredients (API) that are peptides, proteins or biopolymers, such as poly(DL-lactide) (PLA) and poly(DL-lactideco-glycolide) (PLGA), cannot be terminally sterilized. This perception exists largely because terminal sterilization is assumed by many to be only carried out by steam sterilization in a standard autoclave. Thus, it is understood that these API candidates must be manufactured by aseptic techniques. With the current technological advances in the area of protein and peptide sterilization, which has largely come from the food industry and has in recent years been developed for pharmaceutical use, techniques have been developed for the terminal sterilization of thermally sensitive APIs and biopolymers. In this review, the focus will be on the four major types of sterilization that are presented in the literature: (i) gamma-irradiation; (ii) e-Beam; (iii) natural light; and (iv) microwave. Each of these sterilization techniques present advantages and disadvantages for use in large-scale terminal sterilization of bioactive macromolecules.