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2.
Transl Psychiatry ; 12(1): 145, 2022 04 07.
Article in English | MEDLINE | ID: mdl-35393395

ABSTRACT

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.


Subject(s)
Antipsychotic Agents , Clozapine , Cytochrome P-450 CYP2C19 , Schizophrenia , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2D6/genetics , Genome-Wide Association Study , Humans , Schizophrenia/drug therapy , Schizophrenia/genetics
3.
Niger J Clin Pract ; 20(3): 361-368, 2017 03.
Article in English | MEDLINE | ID: mdl-28256493

ABSTRACT

BACKGROUND AND AIMS: The aim of this study is to compare patients with atherosclerosis and chronic periodontitis and patients who are systemically healthy and chronic periodontitis using alteration of adrenomedullin (ADM), chemokine (C-C motif) ligand 28 (CCL-28), white blood cell levels, platelet levels, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein, creatinine, and fibrinogen. MATERIALS AND METHODS: Totally, 40 patients were involved in study; a test group of 20 patients with atherosclerosis-chronic periodontitis and a control group of 20 patients who were nonatherosclerosis-chronic periodontitis. Nonsurgical periodontal treatment was offered to all patients, in whom systemic markers of atherosclerosis were measured in serum; ADM and CCL-28 biomarkers were measured in gingival crevicular fluid. RESULTS: Systemic markers of atherosclerosis, ADM, and CCL-28 levels have changed significantly in the test group compared to the control group after nonsurgical periodontal treatment. CONCLUSIONS: Treatment of local inflammation and reduction of systemic inflammatory markers are believed to lower the diagnostic criteria for atherosclerosis as well. It is possible to conclude that nonsurgical periodontal treatment of chronic periodontitis, which is a risk factor for atherosclerosis, has a positive effect on the atherosclerosis prognosis.


Subject(s)
Adrenomedullin/metabolism , Atherosclerosis/blood , Chemokines, CC/metabolism , Chronic Periodontitis/metabolism , Chronic Periodontitis/therapy , Gingival Crevicular Fluid/metabolism , Adult , Aged , Atherosclerosis/complications , Biomarkers/metabolism , C-Reactive Protein/metabolism , Chronic Periodontitis/complications , Creatinine/blood , Fibrinogen/metabolism , Humans , Leukocyte Count , Lipoproteins, HDL/blood , Middle Aged , Periodontal Index
4.
J Periodontal Res ; 49(3): 282-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23721053

ABSTRACT

BACKGROUND AND OBJECTIVE: Cathelicidin (LL-37) and human ß-defensin-2 (hBD-2) are antimicrobial peptides that have additional functions in innate immunity. The purpose of this study was to evaluate LL-37 and hBD-2 levels in the following patient groups: non-smoker patients with gingivitis (G), smoker patients with gingivitis (SG), non-smoker patients with generalized aggressive periodontitis (AgP) and smoker patients with generalized aggressive periodontitis (SAgP). MATERIAL AND METHODS: A total of 80 patients, including 20 G, 20 SG, 20 AgP and 20 SAgP were enrolled in the study. Clinical periodontal parameters, including periodontal status were assessed by measuring bleeding on probing, plaque index, gingival index, probing depth and clinical attachment loss. Enzyme-linked immunosorbent assays were done to quantify LL-37 and hBD-2 levels in gingival crevicular fluid. RESULTS: Clinical periodontal parameters were found to have no statistically significant differences between the SAgP and AgP groups or between the SG and G groups. LL-37 and hBD-2 levels were significantly lower in G patients than in other groups. LL-37 and hBD-2 levels in the gingival crevicular fluid of SAgP patients were significantly higher than in other groups. LL-37 and hBD-2 levels in SG patients were also significantly higher than in G patients. CONCLUSIONS: Epithelial cells in contact with microorganisms release LL-37 and hBD-2 to eliminate them. The release response of LL-37 and hBD-2 formed against microorganisms can change depending on factors such as smoking, which activates the nicotinic receptors present on epithelial surfaces. This interaction can increase the release of LL-37 and hBD-2. Smoking may also affect the capillary tissues and reduce leukocytic chemotaxis. The increased number of colonized microorganisms may lead to higher levels of LL-37 and hBD-2 release in the tissues of smokers than in non-smokers.


Subject(s)
Aggressive Periodontitis/metabolism , Antimicrobial Cationic Peptides/analysis , Gingival Crevicular Fluid/chemistry , Gingivitis/metabolism , Smoking/metabolism , beta-Defensins/analysis , Adult , Cross-Sectional Studies , Dental Plaque Index , Female , Humans , Male , Nicotine/pharmacology , Periodontal Attachment Loss/classification , Periodontal Attachment Loss/metabolism , Periodontal Index , Periodontal Pocket/classification , Periodontal Pocket/metabolism , Young Adult , Cathelicidins
5.
J Periodontal Res ; 49(4): 480-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23898869

ABSTRACT

BACKGROUND AND OBJECTIVE: To achieve satisfactory osseointegration, primary stability and healthy peri-implant tissue must be available. In this study, our objective was to compare the adrenomedullin, human beta-defensin (hBD)-1 and hBD-2 levels in implants with different implant stability quotient (ISQ) values and with different peri-implant tissue health values in the peri-implant crevicular fluid. MATERIAL AND METHODS: Thirty patients with 60 endosseous osseointegrated implants were included in this study. Following the completion of the osseointegration process, these implants were divided into two main groups: a group of 15 implants with peri-implantitis (peri-implantitis: 40 ≤ ISQ ≤ 80 peri-implantitis, n = 15) and a group of 45 implants with healthy peri-implant tissue. The healthy peri-implant tissue group was further divided into three subgroups according to their ISQ values (Healthy-60: 60 ≤ ISQ ≤ 70, healthy peri-implant, n = 15; Healthy-80: 71 ≤ ISQ ≤ 80, healthy peri-implant, n = 15; and Healthy-100: 81 ≤ ISQ ≤ 100, healthy peri-implant, n = 15). The levels of adrenomedullin, hBD-1 and hBD-2 in the peri-implant crevicular fluid were assessed using ELISAs. RESULTS: When the peri-implant clinical measurements were compared within groups, they were found to be highest in the peri-implantitis group and lowest in the Healthy-100 group. The adrenomedullin, hBD-1 and hBD-2 levels in the peri-implant crevicular fluid of the peri-implantitis group were found to be significantly higher than those in the Healthy-60, Healthy-80 and Healthy-100 groups. When only the healthy peri-implant tissue groups were evaluated, the adrenomedullin, hBD-1 and hBD-2 levels in the peri-implant crevicular fluid of the Healthy-60 group were found to be significantly higher than those in the Healthy-80 and Healthy-100 groups. The lowest adrenomedullin, hBD-1 and hBD-2 levels were observed in the Healthy-100 group. CONCLUSION: In cases of peri-implantitis, higher adrenomedullin, hBD-1 and hBD-2 levels were observed. These results indicate the presence of a tissue response to prevent the creation of a pathological environment in the peri-implant tissue. In groups with healthy peri-implant tissues, the ISQ value decreases as the adrenomedullin, hBD-1 and hBD-2 levels increase. This condition is thought to be caused by increased dental plaque accumulation and bone resorption in addition to increased lateral implant movements and colonization of microorganisms in the microcavities between the implant elements.


Subject(s)
Adrenomedullin/analysis , Dental Implants , Gingival Crevicular Fluid/chemistry , Osseointegration/physiology , beta-Defensins/analysis , Adult , Alveolar Bone Loss/metabolism , Antimicrobial Cationic Peptides/analysis , Dental Plaque Index , Double-Blind Method , Female , Gingivitis/metabolism , Humans , Male , Mandible/physiology , Peri-Implantitis/metabolism , Periodontal Index , Periodontal Pocket/metabolism
6.
Aust Dent J ; 58(2): 170-5, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23713636

ABSTRACT

BACKGROUND: Beta-2 microglobulin (B2M) and alpha-2 macroglobulin (A2M) play key roles in the immune system. The aim of this study was to compare B2M and A2M levels in patients with different periodontal diseases. METHODS: Eighty patients (20 periodontally healthy, 20 with gingivitis, 20 with chronic periodontitis and 20 with generalized aggressive periodontitis) were enrolled in the study. The analysis of B2M and A2M was performed on gingival crevicular fluid (GCF) using an enzyme-linked immunosorbent assay in GCF. RESULTS: The total levels of B2M and A2M were statistically lower in the periodontally healthy group than in the other groups (p < 0.05) and significantly higher in the generalized aggressive periodontitis group compared to the other groups (p < 0.05). CONCLUSIONS: B2M and A2M play key roles in the balance between periodontal health and disease. It is proposed that tissues release B2M and A2M to stop inflammation and inhibit the proliferation of microorganisms and this may be the reason for the high levels of B2M and A2M in the generalized aggressive periodontitis and chronic periodontitis groups. B2M and A2M are assumed to be user-friendly and cost-effective markers for periodontal disease to identify asymptomatic diseases.


Subject(s)
Aggressive Periodontitis/metabolism , Chronic Periodontitis/metabolism , Gingivitis/metabolism , alpha-Macroglobulins/analysis , beta 2-Microglobulin/analysis , Adult , Aggressive Periodontitis/immunology , Chronic Periodontitis/immunology , Enzyme-Linked Immunosorbent Assay , Female , Gingival Crevicular Fluid/immunology , Gingivitis/immunology , Humans , Male
7.
Pharmazie ; 68(2): 110-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23469682

ABSTRACT

In this study, clozapine orally disintegrating tablets (ODTs) were prepared by direct compression method. Disintegration time, resistance to crushing of tablets, porosity, friability, dissolution tests were performed and dissolution profiles of ODTs were investigated. Morphological and interaction studies were also performed. Friability values were found to be less than 1%. All tablet formulations disintegrated within 1 min and fulfilled the 3 min disintegration time required for ODTs given in the European Pharmacopoeia. More than 85% of the labeled amount of clozapine was dissolved in 15 min from the ODTs. No interaction or changes were found between active substance and excipients. As a result of the studies, ODT formulations developed in this study can be suggested as promising formulations, which assist development and manufacturing a generic product of clozapine.


Subject(s)
Antipsychotic Agents/administration & dosage , Antipsychotic Agents/chemistry , Clozapine/administration & dosage , Clozapine/chemistry , Calorimetry, Differential Scanning , Carboxymethylcellulose Sodium , Chemistry, Pharmaceutical , Drug Compounding , Excipients , Hardness Tests , Kinetics , Microscopy, Electron, Scanning , Porosity , Povidone , Solubility , Spectroscopy, Fourier Transform Infrared , Starch , Tablets , X-Ray Diffraction
8.
J Periodontal Res ; 48(4): 475-82, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23278469

ABSTRACT

BACKGROUND AND OBJECTIVE: Human ß-defensins (hBDs) have a strong antibacterial action against various microorganisms, especially periodontal pathogens. The aim of this study was to compare the total levels of hBD-1 and hBD-3 in the gingival crevicular fluid of healthy patients with gingivitis (HG), healthy patients with chronic periodontitis (HP), patients with type 2 diabetes mellitus (DM) and gingivitis (DM2G) and patients with type 2 DM and chronic periodontitis (DM2P). MATERIAL AND METHODS: A total of 80 patients were included: 20 HG, 20 HP, 20 DM2G and 20 DM2P. The levels of hBD-1 and hBD-3 in gingival crevicular fluid were measured using ELISA. RESULTS: The DM2P group had significantly higher periodontal clinical parameters at sites from which gingival crevicular fluid was collected compared with the other groups. The HG group had significantly lower periodontal clinical parameters within the gingival crevicular fluid-collected sites than did the HP, DM2G and DM2P groups. The gingival crevicular fluid of the DM2P group had significantly higher levels of total hBD-1 and hBD-3 than did that of the other groups; the hBD-1 and hBD-3 levels were significantly higher in the gingival crevicular fluid of the DM2G group than in that of the the non-DM type 2 groups (HG and HP). The gingival crevicular fluid of the HP group had significantly higher levels of total hBD-1 and hBD-3 in comparison with that of the HG group. CONCLUSION: As a result of the observed vascular and cell activity changes that occur within patients diagnosed with DM, periodontal diseases become more severe. These changes hinder the migration and the ability of chemotactic factors and leukocytes to protect periodontal tissues from the effects of microorganisms. In order to eliminate microorganisms, the epithelial cells in patients with DM may release more hBD-1 and hBD-3 into the gingival crevicular fluid. Determining the amount of hBD-1 and hBD-3 in the gingival crevicular fluid of patients with and without DM will help to elucidate the relationship among hBD-1, hBD-3, DM and periodontal disease.


Subject(s)
Anti-Infective Agents/analysis , Chronic Periodontitis/metabolism , Diabetes Mellitus, Type 2/metabolism , Gingival Crevicular Fluid/chemistry , beta-Defensins/analysis , Adult , Cross-Sectional Studies , Dental Plaque Index , Female , Gingivitis/metabolism , Humans , Male , Periodontal Attachment Loss/classification , Periodontal Attachment Loss/metabolism , Periodontal Index , Periodontal Pocket/classification , Periodontal Pocket/metabolism
9.
J Periodontal Res ; 48(3): 342-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23039712

ABSTRACT

BACKGROUND AND OBJECTIVE: Adrenomedullin, an antimicrobial peptide, has biological applications in many tissues, but its main attribute is its ability to lower arterial pressure. The plasma adrenomedullin level is elevated in pathophysiological conditions such as arterial hypertension, acute coronary syndrome, renal diseases, diabetes mellitus and periodontal diseases. The aim of this study was to compare the amounts of adrenomedullin in the gingival crevicular fluid of periodontally healthy individuals, individuals with chronic periodontitis, periodontally healthy individuals with diabetes mellitus type 2 and individuals with chronic periodontitis and diabetes mellitus type 2. MATERIAL AND METHODS: Eighty-four individuals were included in this study: 21 periodontally healthy individuals; 21 individuals with chronic periodontitis; 21 periodontally healthy individuals with diabetes mellitus type 2; and 21 individuals with chronic periodontitis and diabetes mellitus type 2. An ELISA was performed to measure the adrenomedullin levels in gingival crevicular fluid. RESULTS: Groups with diabetes mellitus type 2 (periodontally healthy individuals and individuals with chronic periodontitis) had significantly higher periodontal clinical indices than did nondiabetes mellitus groups (periodontally healthy individuals and individuals with chronic periodontitis). The group of individuals with chronic periodontitis and diabetes mellitus type 2 had a significantly higher total adrenomedullin level compared with the other groups. Also, a significantly higher total adrenomedullin level was found in diabetes mellitus type 2 groups (periodontally healthy individuals and individuals with chronic periodontitis) compared with nondiabetes mellitus groups (periodontally healthy individuals and individuals with chronic periodontitis). CONCLUSIONS: An increased adrenomedullin level was found in individuals with chronic periodontitis and also in individuals with diabetes mellitus. It is thought that the effect of diabetes mellitus on the pathogenesis of chronic periodontitis could have been achieved through antimicrobial peptides such as adrenomedullin, or that increased adrenomedullin was released in individuals with diabetes mellitus in order to ensure no further periodontal tissue loss.


Subject(s)
Adrenomedullin/metabolism , Antimicrobial Cationic Peptides/metabolism , Chronic Periodontitis/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Gingival Crevicular Fluid/chemistry , Adrenomedullin/analysis , Adult , Antimicrobial Cationic Peptides/analysis , Case-Control Studies , Chronic Periodontitis/complications , Female , Humans , Male , Middle Aged , Statistics, Nonparametric
10.
J Periodontal Res ; 48(1): 44-51, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22812409

ABSTRACT

BACKGROUND AND OBJECTIVE: Cytokines produced by various cells are strong local mediators of inflammation. Mucosa-associated epithelial chemokine (CCL28), interleukin-8 (IL-8), interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL-8, IL-1ß and TNF-α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. MATERIAL AND METHODS: A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL-8, IL-1ß and TNF-α were analyzed using enzyme-linked immune sorbent assay (ELISA). RESULTS: The total levels of CCL28 and IL-8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL-1ß and TNF-α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). CONCLUSION: CCL28, IL-8, IL-1ß and TNF-α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among many factors that trigger periodontal tissue destruction. Identification of the mediators that influence the development and progression of inflammation in periodontal diseases may be very important in understanding the prognoses of periodontal diseases.


Subject(s)
Aggressive Periodontitis/immunology , Chemokines, CC/analysis , Chronic Periodontitis/immunology , Gingivitis/immunology , Immunity, Mucosal/immunology , Interleukin-1beta/analysis , Interleukin-8/analysis , Tumor Necrosis Factor-alpha/analysis , Adolescent , Adult , Alveolar Bone Loss/immunology , Female , Gingival Crevicular Fluid/immunology , Gingival Hemorrhage/immunology , Humans , Male , Periodontal Attachment Loss/immunology , Periodontal Pocket/immunology , Periodontium/immunology , Young Adult
11.
Article in English | MEDLINE | ID: mdl-22640753

ABSTRACT

We compared the effects of subchronic clozapine and haloperidol administration on the expression of SNAP-25 and synaptophysin in an animal model of schizophrenia based on the glutamatergic hypothesis. Mice were first treated with a non-competitive NMDA antagonist MK-801 (0.3 mg/kg/day) or saline for 5 days, and then clozapine (5 mg/kg/day), haloperidol (1 mg/kg/day) or saline was administered for two weeks. The locomotion test, as a behavioral model of the positive symptoms of schizophrenia, was applied after MK-801/saline administration on day 6 for acute effects and after antipsychotic/saline administration on day 19 for enduring effects on mice activity. Memory function was assessed by the Novel Object Recognition (NOR) test, one day after the last day of antipsychotic/saline administration (day 20). Western Blotting technique was used to determine SNAP-25 and synaptophysin expressions in the hippocampus and frontal cortex. Both antipsychotics reversed the enhanced locomotion effects of MK-801. MK-801 and haloperidol decreased recognition memory performance. On the other hand, clozapine did not compromise memory. It also did not reverse the negative effects of MK-801 on memory performance. MK-801 did not change SNAP-25 and synaptophysin expressions in the hippocampus and frontal cortex. Clozapine increased hippocampal SNAP-25, decreased hippocampal synaptophysin expression, whereas frontal SNAP-25 and synaptophysin expressions remained unchanged. Haloperidol had no effects on levels of SNAP-25 and synaptophysin in the frontal cortex and hippocampus. These findings support the idea that the differential effects of clozapine might be related to its plastic effects and synaptic reorganization of the hippocampus.


Subject(s)
Antipsychotic Agents/pharmacology , Hippocampus/drug effects , Presynaptic Terminals/metabolism , Recognition, Psychology/drug effects , Schizophrenia/metabolism , Synaptophysin/biosynthesis , Synaptosomal-Associated Protein 25/biosynthesis , Animals , Clozapine/pharmacology , Disease Models, Animal , Dizocilpine Maleate/antagonists & inhibitors , Frontal Lobe/drug effects , Frontal Lobe/metabolism , Haloperidol/pharmacology , Hippocampus/metabolism , Male , Mice , Motor Activity/drug effects
12.
Eur Arch Psychiatry Clin Neurosci ; 261(1): 69-78, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20517698

ABSTRACT

Most studies point to an increased prevalence of metabolic syndrome (MS) and an increased risk of coronary heart disease (CHD) in schizophrenia patients with MS. The aims of this study were to compare the prevalence of MS in schizophrenia patients with the general population, to explore the clinical correlates and predictors of MS and to evaluate the risk for CHD within 10 years. Consecutive 319 patients, aged 18-75 years, with a diagnosis of schizophrenia according to the DSM-IV were enrolled. The ATP-III, the ATP-IIIA and the IDF criteria were used to define MS. 10-year risk of CHD events was calculated with the Framingham score. One hundred nine (34.2%) patients met the ATP-III criteria, 118 (37%) the ATP-IIIA and 133 (41.7%) the IDF criteria for MS. Patients with MS were older, had a later onset of illness and an older age at first hospitalization. The prevalence of MS in schizophrenia patients was higher from the general population only within the 20-29 age group. Patients with MS had a higher age and sex-corrected 10-year risk of CHD events. The only predictor of MS was the age of illness onset. In conclusion, countries where the general population prevalence of MS is already too high, schizophrenia patients younger than 30 years of age might be under higher risk of morbidity and mortality related with MS. This study points to the necessity for aggressive interventions to correct MS in schizophrenia as early as possible, within the first 10 years of post detection.


Subject(s)
Metabolic Syndrome/epidemiology , Schizophrenia/epidemiology , Adolescent , Adult , Aged , Blood Glucose , Comorbidity , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Middle Aged , Prevalence , Risk Factors , Schizophrenia/complications , Schizophrenia/diagnosis , Turkey/epidemiology
13.
J Pediatr Endocrinol Metab ; 23(7): 719-23, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20857844

ABSTRACT

BACKGROUND: The etiology of hyperinsulinemic hypoglycemia in adolescents is similar to that of adults. Patients resistant to medical treatment may undergo pancreatectomy. Diazoxide is the mainstay of medical treatment. Rarely bone marrow suppression is reported due to diazoxide. PATIENT: An adolescent with severe hyperinsulinemic hypoglycemia was referred for pancreatectomy after she was treated with high doses of diazoxide, octreotide and glucose. She developed anemia and febrile neutropenia in the course of diazoxide treatment that resolved with cessation of medication. The cause of the hyperinsulinemia proved to be classical Munchausen by proxy. CONCLUSION: This is the first report of bone marrow suppression involving erythroid series by diazoxide. Follow-up of blood count may be considered in patients on high dosages since anemia may be dose dependent. Munchausen by proxy poses a serious threat to children with significant morbidity and mortality. Awareness and a high index of suspicion in clinical settings with unusual causes are the mainstay for the diagnosis.


Subject(s)
Anemia/chemically induced , Diazoxide/adverse effects , Fever/etiology , Hyperinsulinism/drug therapy , Munchausen Syndrome by Proxy/complications , Neutropenia/chemically induced , Bone Marrow/drug effects , Child , Female , Humans , Hyperinsulinism/etiology
14.
Acta Psychiatr Scand ; 105(3): 196-201, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11939973

ABSTRACT

OBJECTIVE: The purpose of the present study was to examine the relationship of disability with neurocognitive deficits and symptoms in schizophrenia. METHOD: Sixty patients with schizophrenia and 30 healthy controls matched for age, sex and level of education were included in the study. Neurocognitive tests measuring attention, visual memory and executive functions were given. Severity of symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS). Disability level of the subjects was assessed by World Health Organisation-Disability Assessment Schedule 2 (WHO-DAS-2). RESULTS: PANSS total score and the subscores were all correlated with DAS scores at a significant level. Neurocognitive test scores were not significantly associated with disability level. Regression analysis furthermore showed that symptom severity was predictive of the disability level. CONCLUSION: These results suggest that, rather than neurocognitive deficits, symptoms appear to have direct impact on the functioning of patients with schizophrenia in many domains of life.


Subject(s)
Cognition Disorders/complications , Schizophrenia/complications , Schizophrenic Psychology , Adolescent , Adult , Cognition , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Disability Evaluation , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Schizophrenia/physiopathology , Severity of Illness Index
15.
Arch Esp Urol ; 53(5): 491-3, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10961018

ABSTRACT

OBJECTIVES: Although there are numerous case reports of spontaneous rupture of the collecting system, especially including the calyceal fornix or the renal pelvis, spontaneous rupture of the ureter is a rare condition. METHODS: Herein, we present a case of a patient who suffered symptoms of acute abdomen due to rupture of the proximal ureter. Extensive assessment revealed no etiological factor as to the extravasation. RESULTS/CONCLUSIONS: The condition was managed conservatively by insertion of a double-J catheter. The double-J ureteral stent was removed on the first postoperative month under local anesthesia uneventfully. One year after the spontaneous ureteral extravasation, the patient remained without clinical problems. The diagnosis, pathogenesis and complications of this unusual condition are reviewed.


Subject(s)
Stents , Ureteral Diseases/surgery , Equipment Design , Humans , Urine
16.
Int Urol Nephrol ; 31(5): 611-7, 1999.
Article in English | MEDLINE | ID: mdl-10755351

ABSTRACT

This study was aimed to investigate Epidermal Growth Factor Receptor (EGF-R) expression after ischaemic injury in renal tissue and the effects of calcium channel blockers in the prevention of damage due to ischaemic insult. Simple nephrectomy was performed in a group of Sprague-Dawley rats, and kidneys were grouped according to cold ischaemia time (1, 6, 12, 24 and 48 hours, respectively) and to the type of calcium channel blockers (diltiazem and verapamil) used. EGF-R expression status was investigated in each group by immunohistochemistry on paraffin sections. Overall expression of EGF-receptor was detected in 8 (22.8%) kidneys. In terms of localization of EGF-receptor expression cortical tubular staining was detected in 8 (100%) kidneys, medullar tubular staining in (62.5%) kidneys and glomerular mesangial staining in 5 (62.5%) kidneys. There was no difference between various ischaemia times and different calcium channel blockers used. It has been concluded that hypoxia and cold ischaemia causes widespread down-regulation of EGF-receptor expression in renal tissue regardless of treatment with calcium channel blockers.


Subject(s)
ErbB Receptors/metabolism , Ischemia/metabolism , Kidney/blood supply , Kidney/metabolism , Animals , Down-Regulation , Evaluation Studies as Topic , Immunoenzyme Techniques , Kidney Tubules/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley
17.
Acta Paediatr Jpn ; 40(2): 131-4, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9581302

ABSTRACT

Shigellosis is still an important health problem in developing and underdeveloped countries as it is resistance to commonly used antibiotics including ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline. Between May 1996 and October 1996, in a prospective randomized double-blind trial, cefixime was compared with ampicillin-sulbactam, both given orally for a period of 5 days, for the treatment of 80 children with acute bloody diarrhea. Forty patients were treated with a single-dose (8 mg/kg per day) of cefixime and the other 40 patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam. After identification of Shigella organisms in stool specimens, nine patients in the cefixime receiving group and six patients in the ampicillin-sulbactam receiving group were excluded from the study. Differences in average age, sex and weight between the cefixime and ampicillin-sulbactam group were statistically meaningless (P > 0.05). Fever and bloody diarrhea were universal features. The efficacy of cefixime was found to be better than ampicillin-sulbactam. Patients given cefixime had a shorter duration of fever (P < 0.01), shorter duration to disappearance of blood in the stool (P < 0.01), reduced time with diarrhea (P < 0.01) and reduced hospitalization time during the 5 study days (P < 0.01) than patients given ampicillin-sulbactam. No adverse effects were observed in the two study groups. This controlled trial showed good efficacy with cefixime compared to ampicillin-sulbactam in the treatment of shigellosis. Single-dose daily oral therapy with cefixime also showed good tolerability. Cefixime should be considered as an alternative drug of choice for shigellosis in children.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cefotaxime/analogs & derivatives , Dysentery, Bacillary/drug therapy , Adolescent , Ampicillin/therapeutic use , Cefixime , Cefotaxime/therapeutic use , Child , Child, Preschool , Double-Blind Method , Female , Humans , Infant , Male , Prospective Studies , Sulbactam/therapeutic use
20.
J Cardiovasc Surg (Torino) ; 18(5): 465-8, 1977.
Article in English | MEDLINE | ID: mdl-591554

ABSTRACT

A rare variant of cor triatriatum is presented with a large true atrial septal defect and partial anomalous pulmonary venous return into the right atrium. The correct diagnosis was made at the operation and abnormal left atrial septum was excised completely and a new interatrial septum was created with pericardial patch in such a position that the abnormally drained right upper pulmonary vein was left in the left atrium. It was thought to use the abnormal left atrial septum to close the atrial septal defect by excising only the right lateral border of this abnormal septum and resuturing it to the right atrial wall to close the true atrial septal defect. This thought could not be realized because of the small size of this abnormal septum and large size of the atrial septal defect. This technique can be realized in small or medium sized atrial septal defects associated with cor triatriatum.


Subject(s)
Heart Atria/abnormalities , Heart Septal Defects, Atrial/complications , Pulmonary Veins/abnormalities , Child , Heart Atria/surgery , Heart Septal Defects, Atrial/surgery , Humans , Male
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