105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

异基因造血干细胞移植受者代谢综合征的发生情况

异基因造血干细胞移植（hematopoieticcelltransplantation,HCT）后代谢综合征的发生主要由预处理导致的神经激素系统紊乱、血管内皮损伤、移植物的免疫和炎症作用以及继发的移植物抗宿主病及其治疗等引起。对代谢综合征及其组分（糖尿病、高血压、血脂紊乱等）的筛查可以尽早地调整治疗策略,控制危险因素的发生,进而降低远期的心血管疾病的发生率和致死率。为此,美国的研究人员回顾性分析了86例异基因HCT受者代谢综合征的发生情况,并与代谢综合征在普通人群中的流行情况进行比较。     

Glibenclamide effects on renal function and histology after acute hemorrhage in rats under sevoflurane anesthesia

INTRODUCTION: Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K(+)(ATP) channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. MATERIAL AND METHODS: Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 microg.g(-1)), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function - sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance - and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. RESULTS: Significant differences were found in para-aminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. CONCLUSION: Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.     

Organ Donation: Cross-Sectional Survey of Knowledge and Personal Views of Brazilian Medical Students and Physicians

Objective

To assess the knowledge, attitudes, and behavior associated with cadaver organ donation and transplantation among medical students and physicians.

Patients and Methods

We randomly selected 350 medical students, 150 physicians, and 150 intensive care unit physicians. Each completed a questionnaire consisting of 9 self-administered items, from which we gathered data about their knowledge about brain death and criteria for the diagnosis of brain death; their hypothetical behaviors, assuming willingness to donate their own or their family's organs; their trust in physicians; and their confidence in a diagnosis of brain death made by physicians.

Results

We observed that knowledge about brain death increased with medical education level; the best results were noted in intensive care unit physicians. Agreement to transplant organs from brain-dead donors (odds ratio [OR], 4.58), confidence in brain-death diagnosis by physicians (OR, 2.17), and knowledge about criteria for the diagnosis of brain death (OR, 2.26) were predictors of willingness to donate one's own organs.

Conclusion

Enhanced medical knowledge of and involvement in donation are needed to achieve cadaver organ donation.     

Evaluation of frozen thawed cauda epididymal sperms and in vitro fertilizing potential of bovine sperm collected from the cauda epididymal

In the present study, the fertilizing potential of semen recovered from slaughtered bulls epididymis was evaluated after cryopreservation, by conventional techniques and flow cytometry methods. The cauda epididymal was dissected and sperm were recovered and evaluated for volume, sperm concentration, and membrane and acrosome integrity using a flow cytometer. Sperm fertility potential was tested by in vitro fertilization (IVF). For each bull, three trials of IVF were performed. Before freezing, on average, the sperm concentration was 216 ± 27.5 × 10⁶ sperm/ml. Sperm viability averaged 86.5 ± 4%. The mean percentage of sperm with intact plasma membrane and acrosome before and after cryopreservation was 90.7 ± 2.9% and 90.8 ± 1.9% (P≥0.05), respectively. The fertilization rate using frozen/thawed epididymal semen averaged 64.1 ± 3.9% fertilization with no significant differences between bulls (P>0.05). For the bull considered as control, the fertilization rate was 72.2 ± 4.5%, differing significantly (P>0.05) from the frozen/thawed epididymal semen’s fertilization rate. In conclusion, it is possible to use in vitro techniques with cryopreserved spermatozoa obtained from bull’s epididymis using a controlled rate freezing method with a predetermined freezing curve, and with assessment of sperm’s viability by conventional techniques and flow cytometry methods, together with the fertilizing ability of cryopreserved epididymal spermatozoa.Key Words: Bovine, Cryopreservation, Epididymis, IVF, Semen     

Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

BACKGROUND/AIMS: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. METHODOLOGY: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. RESULTS: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long-term survival after complete resection can be achieved. CONCLUSIONS: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.     

Myocardial Infarction Triage and Intervention Project--phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy

Prehospital initiation of thrombolytic therapy by paramedics, if both feasible and safe, could considerably reduce the time to treatment and possibly decrease the extent of myocardial necrosis in patients with acute coronary thrombosis. Preliminary to a trial of such a treatment strategy, paramedics evaluated the characteristics of 2,472 patients with chest pain of presumed cardiac origin; 677 (27%) had suitable clinical findings consistent with possible acute myocardial infarction and no apparent risk of complication for potential thrombolytic drug treatment. Electrocardiograms (ECGs) of 522 of the 677 patients were transmitted by cellular telephone to a base station physician; 107 (21%) of the tracings showed evidence of ST segment elevation. Of the total 2,472 patients, 453 developed evidence of acute myocardial infarction in the hospital; 163 (36%) of the 453 had met the strict prehospital screening history and examination criteria and 105 (23.9%) showed ST elevation on the ECG and, thus, would have been suitable candidates for prehospital thrombolytic treatment if it had been available. The average time from the onset of chest pain to prehospital diagnosis was 72 +/- 52 min (median 52); this was 73 +/- 44 min (median 62) earlier than the time when thrombolytic treatment was later started in the hospital. Paramedic selection of appropriate patients for potential prehospital initiation of thrombolytic treatment is feasible with use of a directed checklist and cellular-transmitted ECG and saves time. This strategy may reduce the extent and complications of infarction compared with results that can be achieved in a hospital setting.     

Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.

BACKGROUND: Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging. METHODS AND RESULTS: This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (<10 seconds) of 400 mug. The primary endpoint was to demonstrate noninferiority by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63 +/- 0.03 for regadenoson-adenosine and 0.64 +/- 0.04 for adenosine-adenosine-a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P = .013). CONCLUSIONS: This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.     

Validation of a Fluorescence In Situ Hybridization Method Using Peptide Nucleic Acid Probes for Detection of Helicobacter pylori Clarithromycin Resistance in Gastric Biopsy Specimens

Here, we evaluated a previously established peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) method as a new diagnostic test for Helicobacter pylori clarithromycin resistance detection in paraffin-embedded gastric biopsy specimens. Both a retrospective study and a prospective cohort study were conducted to evaluate the specificity and sensitivity of a PNA-FISH method to determine H. pylori clarithromycin resistance. In the retrospective study (n = 30 patients), full agreement between PNA-FISH and PCR-sequencing was observed. Compared to the reference method (culture followed by Etest), the specificity and sensitivity of PNA-FISH were 90.9% (95% confidence interval [CI], 57.1% to 99.5%) and 84.2% (95% CI, 59.5% to 95.8%), respectively. In the prospective cohort (n = 93 patients), 21 cases were positive by culture. For the patients harboring clarithromycin-resistant H. pylori, the method showed sensitivity of 80.0% (95% CI, 29.9% to 98.9%) and specificity of 93.8% (95% CI, 67.7% to 99.7%). These values likely represent underestimations, as some of the discrepant results corresponded to patients infected by more than one strain. PNA-FISH appears to be a simple, quick, and accurate method for detecting H. pylori clarithromycin resistance in paraffin-embedded biopsy specimens. It is also the only one of the methods assessed here that allows direct and specific visualization of this microorganism within the biopsy specimens, a characteristic that allowed the observation that cells of different H. pylori strains can subsist in very close proximity in the stomach.