p53 gene mutations are rare in human papillomavirus-associated colon cancer

Recent studies suggest that infection with high risk human papillomavirus (HPV) is a common event in colon tumors. Infection by oncogenic HPV may result in functional inactivation of the p53 protein in absence of mutations. Thus far no studies have been made to examine the frequency of p53 mutations in HPV-associated colon cancer. The purpose of this study was to investigate the interrelationship between p53 mutations and HPV infection. The 'hot-spot' region of the p53 gene for mutations was analyzed by PCR-SSCP and direct sequencing in HPV-positive tumor samples. Only 2 mutations were identified in 56 samples. This rate was much lower than reported for sporadic colon tumors. Our results indicate an inverse relationship between p53 mutations and HPV infection and suggest that p53 inactivation caused by HPV infection may play a role in the pathogenesis of colon cancer.     

Angiotensin converting enzyme gene polymorphism and development of post-transplant erythrocytosis

BACKGROUND: An increased activation of the renin-angiotensin system probably plays a major role in the development of post-transplant erythrocytosis (PTE). It is known that deletion type polymorphism (DD) in the angiotensin converting enzyme (ACE) gene is associated with higher circulating angiotensin II (AII) levels. The aim of this study was to investigate the effect of ACE gene polymorphism on development of PTE. METHODS: 86 PTE patients (male/female: 68/18, mean age: 32 +/- 10 years) and 68 consecutively transplanted non- PTE patients (male/female: 38/30, mean age: 31 +/- 10 years) were included; 140 patients (91%) had been transplanted from living donors; 92 patients (60%) had hypertension. ACE gene polymorphism was determined by polymerase chain reaction (PCR). RESULTS: The mean time to appearance of PTE was 8.8 +/- 7.9 (range of 1-53) months. DD genotype was detected in 65 patients. PTE patients had a higher prevalence of hypertension (70% vs. 46%, p=0.003) and a lower frequency of DD genotype (34% vs. 54%, p=0.014) as compared to non-PTE patients [OR: 2.2 (1.14-4.25, 95% CI)]. PTE developed more frequently in male patients (68/106: 64%) than females (18/48: 38%) (p=0.002). Patients with DD genotype had a significantly longer leading time to PTE in Kaplan-Meier survival analysis with log-rank (136 +/- 15 vs. 92 +/- 13 months, p=0.015). In Cox regression analysis, hypertension (p=0.002) and recipient ACE genotype (p=0.013) were retained as independent variables for predicting PTE development. CONCLUSIONS: PTE develops more frequently in male, hypertensive renal transplant recipients with good allograft function. DD-type ACE gene polymorphism seems to protect against PTE development.     

Behçet's disease: diagnostic and prognostic aspects of neurological involvement

This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n=18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet's syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet's syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7±2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.     

Large Ascending Aortic Aneurysm and Severe Aortic Regurgitation in a 7-year-Old Child with Marfan Syndrome and a Review of the Literature: Marfan Syndrome in Childhood

A 7-year-old girl was admitted because of dyspnea on exertion and palpitations. Her symptoms had gradually worsened for the last 6 months. She had physical features of the Marfan syndrome. Transthoracic echocardiography showed an ascending aortic aneurysm, severe aortic regurgitation, and mildly dilated left ventricle. Because of marked aortic aneurysm and severe aortic regurgitation, the patient was treated with a beta-blocker and an angiotensin converting enzyme inhibitor. Surgery was refused by her parents. We describe here a child with Marfan syndrome in whom significant dilatation of the ascending aorta and severe aortic regurgitation is encountered and major cardiovascular complications of Marfan syndrome were reviewed.     

The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: Results from two reference hospitals and review of literature

Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes. The subgroup analysis between the patients who developed nephrotoxicity during colistin treatment and those that did not, showed no significant difference in terms of age, underlying disease, cause for PICU admission and type of infection required colistin treatment, P values were 0.615, 0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant nephrotoxic agent (P = 0,355). The majority of the patients (52%) were having primary or secondary immune deficiency in treatment failure group and the most common cause of PICU admission was sepsis in treatment failure group, P values were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children. However, the patients have to be followed for side effects throughout colistin treatment, not for only early stage. And the clinicians should be aware of increase in the rate of nephrotoxicity in patients those have been receiving a concomitant nephrotoxic agent.     

Induction of apoptosis in tumor-associated endothelial cells and therapy of orthotopic human pancreatic carcinoma in nude mice

Although gemcitabine has been accepted as the first-line chemotherapeutic reagent for advanced pancreatic cancer, improvement of response rate and survival is not sufficient and patients often develop resistance. We hypothesized that the inhibition of phosphorylation of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) on tumor cells and tumor-associated endothelial cells, combined with gemcitabine, would overcome the resistance to gemcitabine in orthotopic pancreatic tumor animal model. L3.6pl, human pancreatic cancer cells growing in the pancreas, and tumor-associated endothelial cells in microorgan environment highly expressed phosphorylated EGFR, VEGFR, and Akt, which regulates antiapoptotic mechanism. Oral administration of AEE788 (dual tyrosine kinase inhibitor against EGFR and VEGFR) inhibited the phosphorylation of EGFR, VEGFR, and Akt on tumor-associated endothelial cells as well as tumor cells. Although intraperitoneal (i.p.) injection of gemcitabine showed limited inhibitory effect on tumor growth, combination with AEE788 and gemcitabine produced nearly 95% inhibition of tumor growth in parallel with a high level of apoptosis on tumor cells and tumor-associated endothelial cells, and decreased microvascular density and proliferation rate. Collectively, these data indicate that dual inhibition of phosphorylation of EGFR and VEGFR, in combination with gemcitabine, produces apoptosis of tumor-associated endothelial cells and significantly suppresses human pancreatic cancer in nude mice.     

The effect of desensitizing treatments on the bond strength of resin composite to dentin mediated by a self-etching primer

This study evaluated the bond strength of resin composite to dentin, mediated by a self-etching adhesive, following the application of various dentin desensitizing treatments and artificial saliva storage. The buccal cervical areas of 24 extracted human third molars were ground flat to expose cervical dentin. The dentin surfaces were polished with 1200-grit SiC paper, then the teeth were randomly assigned to six groups, five desensitizing treatments and one control: Group I-VivaSens; Group II-Fluor Protector; Group III-Isodan; Group IV-Futura Bond NR; Group V-Nd:YAG laser and Group VI-Control (without application of a desensitizing agent). After applying the desensitizing treatments and storing the molars in artificial saliva for 14 days at 37 degrees C, Futura Bond NR was used to bond resin composite to dentin. TPH composite build-ups were constructed incrementally to a height of 5 mm. The teeth were sectioned to obtain bonded slices of 0.7 mm thick specimens containing the resin-composite joint. The specimens were then trimmed into an hourglass shape and subsequently subjected to microtensile testing at a crosshead speed of 1 mm/minute. The data were analyzed using the Kruskal-Wallis analysis and multiple comparisons test. The control (Group VI) and Futura Bond NR self-etching treatment (Group IV) group yielded statistically significant higher bond strength values than the other desensitizing treatment groups tested (p < 0.005). While pretreatment of dentin surfaces with desensitizing agents (Fluor Protector, VivaSens and Isodan) and laser (Nd:YAG) reduced the bond strength values of the resin composite, higher bond strengths were achieved using a self-etching adhesive (Futura Bond NR) as a desensitizing agent.     

Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method

Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 ± 2.7 and 31.6 ± 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 ± 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.     

Takayasu disease with prominent pulmonary artery involvement: confusion with pulmonary disease leading to delayed diagnosis

Pulmonary artery involvement as the initial predominant clinical manifestation in Takayasu arteritis (TA) is rare. We describe a young adult female who presented with life-threatening complications of proximal pulmonary arterial involvement of Takayasu arteritis. In our case, atypical presentation of TA with pulmonary symptoms due to pulmonary artery involvement resulted in an erroneous initial diagnosis of sarcoidosis and then tuberculosis. The frequency of such a clinical form could be underestimated given the difficulties involved in its diagnosis and because its features are similar to those of pulmonary disease.     

Paradoxical embolism in Ebstein’s anomaly

A 26-year-old man with Ebstein’s anomaly had cerebellar infarction due to paradoxical embolism. Ebstein’s anomaly is characterized by a downward displacement of the tricuspid valve into the right ventricle due to anomalous attachment of the tricuspid leaflets. Echocardiography is the method of choice to diagnose Ebstein’s anomaly on its own or in association with other heart defects. Paradoxical embolism is a potential complication whenever a right to left shunt exists (for example, atrial septal defect). Ebstein’s anomaly diagnosed in adult life is a benign and stable disease, particularly if the patient is asymptomatic; surgical correction must be performed if the patient becomes symptomatic because of either paradoxical embolism or worsening of the tricuspid regurgitation.