The frequency of osteoporosis in patients with predialysis chronic renal failure and the factors affecting the development of osteoporosis.

BACKGROUND: Osteoporosis is a common public health problem in chronic kidney patients. The risk factors for osteoporosis in patients with nondialysis CKD have not been fully investigated. It is not known exactly whether the risk factors of osteoporosis in the general population are also valid for the nondialysis CKD patients. Aims: This study aims to determine the frequency of osteoporosis and the risk factors for osteoporosis in nondialysis CKD patients. PATIENTS AND METHODS: Our study was performed with 283 nondialysis stage 3-5 CKD patients. According to the BMD results, the patients were classified into groups as normal, osteopenia and osteoporosis according to World Health Organization criteria. Monocyte/high-density lipoprotein-cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) were calculated individually for all cases. RESULTS: According to our BMD results, 67 (24%) patients were found to have osteoporosis. In the osteoporosis patient group, compared to the normal BMD group, females were higher and the mean age was higher (P = 0.025, P = 0.028). Body mass index (BMI) and eGFR were lower in the osteoporosis group (P = 0.013). Parathyroid Hormone and Platelet-to-lymphocyte ratio in the patients in the osteoporosis group was higher than of those in the normal group (P = 0.026, P = 0.035). In the multivariate logistic regression analysis, advanced age, female gender, and low BMI were determined as independent risk factors for the development of osteoporosis in nondialysis CKD patients. CONCLUSION: Advanced age, female gender and low BMI are the risk factors for osteoporosis in nondialysis CKD patients. It may be a rational approach to measure BMD for the diagnosis of osteoporosis in nondialysis CKD patients who are elderly, female and have low BMI.

ESR investigations of gamma irradiated medical devices.

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) biomaterials have been employed in recent years for periodontal procedures. In the present study, widely used dental GTR/GBR biomaterials (grafts: G1, G2, G3 and membranes: M1, M2, M3, M4) were exposed to gamma irradiation at an absorbed dose range of 0-50kGy and the radiolytic intermediates that have been created in the samples upon irradiation were characterized in detail by Electron Spin Resonance (ESR) spectroscopy. We aimed to standardize the measurement conditions for practical applications of gamma radiation sterilization of GTR/GBR biomaterials. We investigated the characteristic features of free radicals in gamma irradiated GTR/GBR biomaterials and examined the stability of the induced radicals at room temperature and accelerated stability conditions with ESR spectroscopy including dose-response curves, microwave power studies, dosimetric features of the biomaterials, variations of the peak heights with temperature, and long term stabilities of the radical species. Long-term stability studies have shown that G1 is quite stable even in accelerated storage conditions. The signal intensities of graft-type GTR/GBR biomaterials stored in normal and stability conditions have decreased very rapidly even only a few days after gamma irradiation sterilization. Thus, those samples indicating relatively low stability features can be very good candidates for the radiosterilization process. The beta-tricalcium phosphate and PLGA containing G1 and M1 respectively have found to be the most gamma stable bone substitute biomaterials and be safely sterilized by gamma radiation. ESR spectroscopy is an appropriate technique in giving important detailed spectroscopic findings in the gamma radiation sterilization studies of GTR/GBR biomaterials.

Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance.

UNLABELLED: Inhibitors of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway hold promise for the treatment of breast cancer, but resistance to these treatments can arise via feedback loops that increase surface expression of the receptor tyrosine kinases (RTK) epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 3 (HER3), leading to persistent growth pathway signaling. We developed PET probes that provide a method of imaging this response in vivo, determining which tumors may use this escape pathway while avoiding the need for repeated biopsies. METHODS: Anti-EGFR-F(ab')2 and anti-HER3-F(ab')2 were generated from monoclonal antibodies by enzymatic digestion, conjugated to DOTA, and labeled with (64)Cu. A panel of breast cancer cell lines was treated with increasing concentrations of the AKT inhibitor GDC-0068 or the PI3K inhibitor GDC-0941. Pre- and posttreatment expression of EGFR and HER3 was compared using Western blot and correlated to probe accumulation with binding studies. Nude mice xenografts of HCC-70 or MDA-MB-468 were treated with either AKT inhibitor or PI3K inhibitor and imaged with either EGFR or HER3 PET probe. RESULTS: Changes in HER3 and EGFR PET probe accumulation correlate to RTK expression change as assessed by Western blot (R(2) of 0.85-0.98). EGFR PET probe PET/CT imaging of HCC70 tumors shows an SUV of 0.32 ± 0.03 for vehicle-, 0.50 ± 0.01 for GDC-0941-, and 0.62 ± 0.01 for GDC-0068-treated tumors, respectively (P < 0.01 for both comparisons to vehicle). HER3 PET probe PET/CT imaging of MDAMB468 tumors shows an SUV of 0.35 ± 0.02 for vehicle- and 0.73 ± 0.05 for GDC-0068-treated tumors (P < 0.01). CONCLUSION: Our imaging studies, using PET probes specific to EGFR and HER3, show that changes in RTK expression indicative of resistance to PI3K and AKT inhibitors can be seen within days of therapy initiation and are of sufficient magnitude as to allow reliable clinical interpretation. Noninvasive PET monitoring of these RTK feedback loops should help to rapidly assess resistance to PI3K and AKT inhibitors and guide selection of an appropriate combinatorial therapeutic regimen on an individual patient basis.

PET imaging of glioblastoma multiforme EGFR expression for therapeutic decision guidance.

After initial therapy and total resection of glioblastoma multiforme (GBM), 80-90% of recurrences occur at the surgical margins. Insufficient sensitivity and specificity of current imaging techniques based on non-specific vascular imaging agents lead to delay in diagnosis of residual and/or recurrent disease. A tumor-specific imaging agent for GBM may improve detection of small residual disease in the post-operative period, and improve ability to distinguish tumor recurrence from its imaging mimics that can delay diagnosis. To this end, we developed an EGFR-targeted PET probe and assessed its ability to image EGFR WT (U87) and EGFRvIII (Gli36vIII) expressing GBMs in both murine intra-cranial xenografts and in a surgical-resection model. The developed imaging probe, (64)Cu-DOTAcetuximab-F(ab´)2, binds with a Kd of 11.2 nM to EGFR expressing GBM. (64)Cu-DOTA-cetuximab-F(ab´)2 specifically localized to intra-cranial tumor with a significant difference in SUVmean between tumor and contralateral brain for both Gli36vIII and U87 tumors (P<0.01 for both comparisons), with mean TBR of 22.5±0.7 for Gli36vIII tumors and 28.9±2.1 for U87 tumors (TBR±SEM). Tracer uptake by tumor was significantly inhibited by pre-injection with cetuximab (P<0.01 for both), with SUVmean reduced by 68% and 58% for Gli36vIII and U87 tumors, respectively. Surgical resection model PET-CT imaging demonstrates residual tumor and low nonspecific uptake in the resection site. We conclude that (64)Cu-DOTA-cetuximab-F(ab´)2 binds specifically to intracranial EGFR WT and EGFRvIII expressing GBM, demonstrates excellent TBR, and specifically images small residual tumor in a surgical model, suggesting future clinical utility in identifying true tumor recurrence.

The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study.

The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.

An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas in the setting of colitis.

Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes. We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models. Cetuximab F(ab')2 fragments were enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was performed with (67)Ga for cell based studies and (64)Cu for in vivo imaging. Competitive binding studies were performed on CT26 cells to assess affinity (KD) and receptors per cell (Bmax). In vivo imaging using the EGFR targeted PET probe and (18)F FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged. The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 ± 5% and ≥99% radiochemical purity. The KD was 6.6 ± 0.7 nM and the Bmax for CT26 cells was 3.3 ± 0.1 × 10(6) receptors/cell. Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both (18)F-FDG (3.95 ± 0.13) and the developed (64)Cu-DOTA-cetuximab-F(ab')2 probe (4.42 ± 0.11) in control mice. The TBR for the EGFR targeted probe remained high (3.78 ± 0.06) in the setting of colitis, while for (18)F FDG, this was markedly reduced (1.54 ± 0.08). Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo. A clinically translatable PET imaging probe was successfully developed to assess EGFR. The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high-risk patients.

Genitourinary brucellosis: results of a multicentric study.

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections.

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Perceptions of preoperative expectations and postoperative outcomes from orthognathic surgery: part I: Turkish female patients.

This study was conducted in Turkish female patients to investigate their preoperative concerns, motivation, expectations, preoperative preparation for surgery and perception of outcomes concerning orthognathic surgery. Thirty women, with an age range of 18 to 31 years (mean age 21.8+/-3.8 years), participated in the study. The expectations and the results of orthognathic treatment were assessed based on the patients' subjective appraisal. Patients completed questionnaires before and after the operations, designed to investigate the preoperative and postoperative psychological impact of the surgery, the perception of problems with physical and psychological functioning, self-image, body image and satisfaction with surgical outcome. The questionnaires were evaluated statistically with SPSS 11.5 for Windows. The patients' perception of their psychological improvement, faith in the surgical team, physical functioning, self-esteem, social confidence, body image and satisfaction after dentofacial correction were higher than the preoperative levels. The conclusions of the study support the theory that enhancement of facial appearance by orthognathic surgery improves the psychological status of females with growth disturbances of the jaw.

Clinical and laboratory aspects of a trichinellosis outbreak in Izmir, Turkey.

Epidemiological, clinical and laboratory data were collected during an outbreak of trichinellosis, which occurred in Izmir, Turkey, between January and March 2004. The source of the infection was raw meatballs made with a mixture of uncooked beef and pork. Of 474 persons who were admitted at the Ataturk Training and Research Hospital during this period with a history of raw meatball consumption, the diagnosis of trichinellosis was confirmed for 154 (32.5%, 87 males and 67 females; mean age 31 years, range 6-67 years). Among persons with a confirmed diagnosis, 79% had myalgia, 77% weakness and malaise, 63% arthralgia, 40% jaw pain, 68% fever, 63% periorbital and/or facial oedema, 49% oedema at the trunk and limb, 42% abdominal pain, 40% nausea and vomiting, 28% diarrhoea, 23% subconjunctival haemorrhage, 25% macular or petechial rash, 4% subungual haemorrhage, 15% cardiac complaints and 0.2% neurological complaints. Nine patients (5.8%) were hospitalised due to severe myalgia (n = 2), high fever (n = 3), neurological manifestations (n = 1), thrombophlebitis (n = 2) and palmar erythema (n = 1). Eosinophilia was present in 88% of the confirmed cases at the admission. Elevated levels of serum creatine phosphokinase, lactic dehydrogenase and aspartate aminotransferase were detected in 72%, 70% and 16% of the confirmed cases, respectively. The seroconversion occurred in most of the infected people between the 4th and 6th weeks after the infection. All of the confirmed cases were treated with mebendazole. People with severe symptoms were treated also with prednisolone (60 mg/day for three days) and those with a moderately severe clinical pattern received a non-steroid anti-inflammatory drug (naproxen sodium, 550 mg/day). All confirmed cases recovered without any clinical sequela.

Clinical and radiological evaluation of cherubism: a sporadic case report and review of the literature.

Many cases have been published on cherubism since Jones described it first time in three children of the same family [Am. J. Cancer 17 (1933) 946]. Cherubism is an autosomal-dominant disorder in which the normal bone is replaced by cellular fibrous tissue and immature bone. Extracranial skeletal involvement is rarely seen in hereditary and non-hereditary forms of the disorder. The mandible is the most severely affected craniofacial component, in which uncontrolled growth of the malady deteriorates the aesthetic balance of the face. Bilateral swelling of the cheeks, mandibular enlargement and maxillary spongious hypertrophy cause orbital manifestations and tendency of eyes looking up to the sky. Thus, the pathognomic clinical feature resembles the appearance of "raised to heaven" Renaissance cherubs. The sporadic case concerns a child affected by cherubism. Radiographic and clinical data of the patient are presented and brief review of the literature is included.

Effect of pH and temperature on the thermostability of prickly pear (Opuntia ficus-indica) yellow-orange pigments.

The colour stability of the yellow-orange pigment (lambda max = 476 nm) of prickly pear (Opuntia ficus-indica) fruit was determined as a function of temperature and pH. The experiments were carried out at three different temperatures (50, 70 and 90 degrees C) with pigment solutions at pH values ranging from 2-7. The degree of pigment retention decreased with increasing temperature as a function of increasing thermal exposure time with least pigment degradation at pH 5. The reaction rate constants were determined as 0.0062, 0.0383 and 0.1102 min-1 for a thermal degradation reaction rate of pseudo-first order. The activation energy was calculated as 65.1 kJ.mol-1.