A new model for the induction of tumours in the forestomach of rats by N-methyl-N-nitrosourea

BACKGROUND AND AIM: Experimental carcinogenesis models provide a useful tool in the study of the aetiopathogenesis and treatment of gastric cancer. We developed a model based on the administration of N-methyl-N-nitrosourea (NMU) in Wistar rats for the induction of maximal yield of gastric carcinomas with a short latency period, and being exclusively localized at the gastric level. METHODS: A gastric antiperistaltic fistula was performed in 90 Wistar rats classified into eight different groups. Fifteen days after surgery 5, 10, 15 or 20 mg of NMU/100 g were administered through the fistula once a week for a 3- to 5-week period. Before the administration of NMU, a pyloric blockade was made in order to obtain a temporary isolation of the stomach. At 20 weeks, animals were sacrificed and organs were removed for histological study. RESULTS: All rats treated with 15 mg NMU/100 g once a week for 5 weeks, after pyloric blockade maintained for 1 h, developed well-differentiated carcinomas in the forestomach. Carcinomas were multiple in 11% of cases and appeared with papillomatous lesions in 33% of rats. No tumours were observed in any other organs. In the other groups, no gastric carcinomas were diagnosed. CONCLUSION: The high incidence of carcinomas in the forestomach, the absence of tumours in other organs and the short latency period represent valuable criteria for the use of our model in chemotherapeutic investigations, as well as in the study of cancer evolution without interferences caused by tumour development in other organs.     

Monoamine oxidase inhibitory activities of the scorpion Mesobuthus gibbosus (Buthidae) venom peptides.

In the present study, crude venom of Mesobuthus gibbosus (Buthidae), a scorpion distributed all over Anatolia was isolated and purified by the Sephadex G-50 gel filtration and high pressure liquid chromatographic (HPLC) separation. Two of the five fractions (fractions 4 and 5) obtained from the Sephadex G-50 filtration and detected as lethal on mice and Musca domestica larvae in in vivo toxicity tests, were independently subjected to the HPLC separation. Only one of seven fractions (fraction 5.5*) obtained from the HPLC separation of the fraction 5 was found to be extremely lethal. Sodium dodecylsulfate polyacrylamide gel electrophoretic (SDS-PAGE) analysis of the crude venom and its chromatographic fractions demonstrated that crude venom consisted of peptides with molecular weights of 6500-210,000 Da. The neurotoxic fraction 5.5* appeared as a single band of 28,000 Da and two bands of 6200 and 22,000 Da in SDS-PAGE under non-reducing and reducing conditions, respectively, suggesting that it might consist of two chains attached by a disulfide bridge. Fractions 5 and 5.5* inhibited monoamine oxidase A (MAO-A) of rat liver reversibly and non-competitively, in a concentration-dependent manner. Fraction 5.5* appeared as a potent and specific MAO-A inhibitor with a Ki value of 0.12 mg venom proteinml(-1). The inhibitory effect of venom peptide 5.5* on MAO-A was found to be dependent on the preincubation time suggesting that the peptide binds to some site other than the substrate-binding site. Results of the present study demonstrated that M. gibbosus venom contains a peptide with specific MAO-A inhibitory activity which may be responsible for the anxiogenic effects of the scorpion venoms on animals and humans.     

Factors Predicting Iliac Metastasis and Overall Survival in Malignant Melanoma of the Lower Extremities

Background : To analyse the patient-related, disease-related and treatment-related factors in a group of melanoma patients to assess their impact on iliac metastasis and on overall survival.

Methods : Medical records of thirty nine patients with lower extremity malignant melanoma were retrospectively reviewed to confirm all of the clinical data. Age and gender were recorded as patient-related factors. Tumor location, size, histology, ulceration status, and TNM stage, Breslow thickness, Clark level, presence of inguinal LN metastases, and locoregional metastases (local recurrences, in transit metastases and regional LN metastases) were evaluated as disease-related factors. Type of surgery (en block excision of primary tumor, en block excision of primary tumor and inguinal lymph node dissection, en block excision of primary tumor and ilioinguinal lymph node dissection) and postoperative chemotherapy were taken into account as treatment-related factors.

Results : The presence of inguinal lymph node metastases was significantly associated with iliac metastasis (p = 0.015). Tumor size (p = 0.046), tumor TNM stage (p = 0.009), Breslow thickness (p = 0.033), Clark level (p = 0.029), presence of in transit metastases (p = 0.010) and postoperative chemotherapy (p = 0.002) has been related to impaired overall survival rate.

Conclusions : Therapeutic lymph node dissection appears to carry a small but definite therapeutic benefit. Selection of appropriate patients for the more extensive procedure would be ideal, but at present there are no well proven selection criteria. The authors advocate therapeutic dissection when the inguinal lymph nodes are involved.     

What might cervical vestibular–evoked myogenic potential abnormalities mean in essential tremor?

Aim/background

Essential tremor (ET) is one of the most common movement disorders. However, its pathogenesis is unclear. Human vestibular reflexes are essential not only for gait and posture but also for goal-directed voluntary movements. In this study, cervical vestibular–evoked myogenic potentials (cVEMPs), the electrophysiological equivalent of the vestibulo-collic reflex was studied in ET patients to understand the interaction between the tremor network and the vestibular neural pathways.

Methods

cVEMPs were recorded in 40 ET patients and 40 age and sex-matched healthy controls (HCs). The latencies of peaks p13 and n23 and peak-to-peak amplitude of p13-n23 were measured.

Results

There was no statistically significant difference between the p13 latencies of the HC and ET groups (p 0.79 and p 0.23 for the right and left sides respectively). n23 latency was shortened bilaterally in the ET group (p 0.009 and p 0.02 for the right and left sides respectively). p13-n23 amplitudes of the ET patients were bilaterally reduced when compared with the HC (p <0.001 and p 0.001 for the right and left sides respectively).

Conclusion

Information provided by vestibular afferents is crucial in the control of voluntary movements in humans. Despite this silent but significant effect, the role of the vestibular system in movement disorders is often overlooked. In this study, it was found that cVEMP responses reflecting the activity of the vestibulo-collic pathway were affected in ET which can be either caused by dysfunctional structures or pathways responsible from ET or an additional disorder of vestibular information processing in these patients.

     

Poststreptococcal reactive arthritis in children: is it really a different entity from rheumatic fever?

Poststreptococcal reactive arthritis (PSRA) is an acute, nonsuppurative arthritis following documented streptococcal infections. Although most authors accepted it as a different entity, the differences from acute rheumatic fever (ARF) are not clear. To document and compare the clinical and laboratory characteristics of PSRA and ARF, 24 patients with PSRA and 20 with ARF were enrolled in the study. The latency period from upper respiratory tract infection was shorter in patients with PSRA ( P<0.01). However, 25% of the patients with ARF had also short (<10 days) latency periods. Although symmetric and nonmigratory arthritis were more frequent in patients with PSRA, there was no significant difference for the distribution of mono-, oligo-, and polyarticular disease between PSRA and ARF patients. The frequency of small joint and hip involvement was also similar between the patient groups. Unresponsiveness of articular symptoms to salicylate therapy within 72 h was more frequent in patients with PSRA (P<0.001). However, in a substantial part of the patients with ARF (nine patients, 45%), joint symptoms also had no response during the first 72 h. Since there is a considerable overlap of symptoms, signs, and laboratory features of PSRA and ARF, a line between these two entities could not be easily drawn. We conclude that these two conditions are actually different presentations of the same disease.     

Clinical outcomes and mortality in elderly peritoneal dialysis patients

OBJECTIVES:

To evaluate the clinical outcomes and identify the predictors of mortality in elderly patients undergoing peritoneal dialysis.

METHODS:

We conducted a retrospective study including all incident peritoneal dialysis cases in patients ≥65 years of age treated from 2001 to 2014. Demographic and clinical data on the initiation of peritoneal dialysis and the clinical events during the study period were collected. Infectious complications were recorded. Overall and technique survival rates were analyzed.

RESULTS:

Fifty-eight patients who began peritoneal dialysis during the study period were considered for analysis, and 50 of these patients were included in the final analysis. Peritoneal dialysis exchanges were performed by another person for 65% of the patients, whereas 79.9% of patients preferred to perform the peritoneal dialysis themselves. Peritonitis and catheter exit site/tunnel infection incidences were 20.4±16.3 and 24.6±17.4 patient-months, respectively. During the follow-up period, 40 patients were withdrawn from peritoneal dialysis. Causes of death included peritonitis and/or sepsis (50%) and cardiovascular events (30%). The mean patient survival time was 38.9±4.3 months, and the survival rates were 78.8%, 66.8%, 50.9% and 19.5% at 1, 2, 3 and 4 years after peritoneal dialysis initiation, respectively. Advanced age, the presence of additional diseases, increased episodes of peritonitis, the use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis were predictors of mortality. The mean technique survival duration was 61.7±5.2 months. The technique survival rates were 97.9%, 90.6%, 81.5% and 71% at 1, 2, 3 and 4 years, respectively. None of the factors analyzed were predictors of technique survival.

CONCLUSIONS:

Mortality was higher in elderly patients. Factors affecting mortality in elderly patients included advanced age, the presence of comorbid diseases, increased episodes of peritonitis, use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis.     

DCE‐MRI findings of invasive aspergillosis in patient with acute myeloid leukemia

Thoracic radiography and high resolution computerized tomography is used to diagnose pulmonary infections in immunosuppressed patients, although in some cases these do not provide enough information about the lesion. Dynamic contrast‐enhanced magnetic resonance imaging may be useful in these cases, especially for the characterization of cavitary lesions and assessment of their contrast diffusion.     

Improvement of Endothelial Dysfunction with Simvastatin in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 ± 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 ± 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 ± 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 ± 21.7 pg/mL to 9.1 ± 3.5 pg/mL (P= 0.002).

Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin.