Insight into the mechanisms underlying tumor response to boron neutron capture therapy in the hamster cheek pouch oral cancer model

Objective: The therapeutic success of different boron neutron capture therapy (BNCT) protocols employing the hamster cheek pouch oral cancer model has been previously reported by our laboratory. The aim of this study was to explore potential mechanisms of BNCT‐induced damage to tumor in terms of potential inhibition in DNA synthesis and induction of apoptosis in the tumors that underwent partial remission following application of the different BNCT protocols in this model. Materials and methods: We evaluated DNA synthesis employing incorporation of 5‐bromo‐2′‐deoxyuridine as an end‐point. Apoptosis was evaluated by immunohistochemistry employing the deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end‐labeling technique and Bax and Bcl‐2 labeling. These studies were performed in tumors that underwent partial remission 1–30 days post‐BNCT mediated by boronophenylalanine (BPA), GB‐10 (Na₂¹⁰B₁₀H₁₀) or (BPA + GB‐10). Results: BNCT exerted a marked inhibitory effect on DNA synthesis in tumors for all the protocols under study. The inhibitory effect of BPA‐BNCT occurred as soon as 1 day post‐treatment (P < 0.001). Conversely, the effect of GB‐10‐BNCT became apparent 7–14 days after therapy (P < 0.001) and was sustained until killed at 30 days post‐treatment (P < 0.001). (GB‐10 + BPA)‐BNCT exerted a rapid and persistent effect, conceivably because of the combined effect of BNCT mediated by both boron compounds. The apoptosis studies did not show differences between the pre‐treatment group and any of the BNCT groups. Conclusions: One of the mechanisms involved in BNCT‐induced tumor control in our model would be an inhibitory effect on DNA synthesis. Apoptosis does not seem to have a significant role in BNCT‐induced tumor control in our model.     

Vasculogenesis in infantile hemangioma

Infantile hemangioma is a vascular tumor that occurs in 5–10% of infants of European descent. A defining feature of infantile hemangioma is the dramatic growth and development into a disorganized mass of blood vessels. Subsequently, a slow spontaneous involution begins around 1 year of age and continues for 4–6 years. The growth and involution of infantile hemangioma is very different from other vascular tumors and vascular malformations, which do not regress and can occur at any time during childhood or adult life. Much has been learned from careful study of the tissue morphology and gene expression patterns during the life-cycle of hemangioma. Tissue explants and tumor-derived cell populations have provided further insight to unravel the cellular and molecular basis of infantile hemangioma. A multipotent progenitor cell capable of de novo blood vessel formation has been isolated from infantile hemangioma, which suggests that this common tumor of infancy, long considered to be a model for pathologic angiogenesis, may also represent pathologic vasculogenesis. Whether viewed as angiogenesis or vasculogenesis, infantile hemangioma represents a vascular perturbation during a critical period of post-natal growth, and as such provides a unique opportunity to decipher mechanisms of human vascular development.     

Feasibility of the transseptal approach for fast and unstable left ventricular tachycardia mapping and ablation with a non-contact mapping system

Background Radiofrequency ablation of fast and unstable left ventricular tachycardia (VT) usually requires non-contact mapping. The procedure is usually performed by a retrograde-transaortic route, requiring a double femoral artery puncture, for the 9F multielectrode catheter and the 7F ablation catheter which are advanced through the aorta and aortic valve into the left ventricle (LV). Reported limitations of the procedure are due to the stiffness of the balloon catheter, particularly in patients with tortuous peripheral arteries, atherosclerotic aorta, or with aortic stenosis. The aim of our study was to test the feasibility and assess the safety of a transseptal approach for left VT non-contact mapping and ablation.Materials and methods Ten patients with multiple cardiac defibrillator shocks because of fast and unstable VT were selected for non-contact mapping and ablation. After a double transseptal puncture the multielectrode catheter (Ensite Array™, St. Jude Medical) was advanced through a standard 10F introducer to a stable position in the LV apex over a 260 cm length 0.035 J-tip guidewire. The ablation catheter (Celsius™ Thermo-cool, Biosense Webster) was then inserted through the second 8F introducer. Twenty-five monomorphic sustained ventricular tachycardia were induced and ablated at the level of the diastolic pathway or exit point revealed by unipolar isopotential mapping. The total procedural and fluoroscopy times were 209 ± 32 min and 28.5 ± 9.27 min, respectively, which were comparable to those described with the traditional retrograde-transaortic approach. No major complication related with the transseptal approach were reported.Conclusion A transseptal approach can be a feasible and effective alternative approach for mapping and ablation of fast and unstable left VT with a non-contact mapping system.     

Physiologic Changes of the Anorectum After Pelvic Radiotherapy for the Treatment of Prostate and Bladder Cancer

INTRODUCTION: The effect of pelvic radiotherapy on anorectal function is not clearly documented and is investigated in this prospective study. METHODS: Thirty-one males (median age, 70 years) with carcinoma of the prostate (n = 28) and bladder (n = 3) completed proctitis/incontinence symptom score questionnaires and anorectal physiology studies before and six weeks after pelvic radiotherapy. At six months after completion of radiotherapy, 25 of these patients were studied again. The results were expressed as medians and ranges and compared by the Mann-Whitney U test (2-tailed). RESULTS: Six weeks and six months after treatment, respectively, the proctitis symptom scores (0 (0-4) vs. 2 (0-7) (P < 0.001) vs. 2 (0-5) (P < 0.001)) and the incontinence symptom scores (0 (0-5) vs. 4 (0-11) (P < 0.001) vs. 3 (0-14) (P < 0.001)) increased. Urgency, frequency of defecation, anorectal pain, incontinence to liquid stool and to flatus, and alteration in lifestyle were significant symptoms after treatment. The following measurements decreased: anal canal resting pressure (83 (35-137) vs. 79 (26-152) (P = NS) vs. 71 (29-97) (P < 0.01) cm H2O), the squeeze increment (152 (51-135) vs. 162 (63-321) (P = NS) vs. 108 (45-296) (P < 0.042) cm H2O), and the maximum tolerated rectal volume (245 (115-450) vs. 194 (112-344) (P < 0.05) vs. 200 (109-350) (P < 0.138) ml). The rectal electrosensory threshold increased (20 (5.4-44) vs. 22 (9-50.5) (P < 0.134) vs. 31.5 (13.6-76) (P < 0.001) mA). CONCLUSIONS: Anorectal symptoms at six weeks after pelvic radiotherapy are related to reduced rectal capacity and compounded at six months by diminished internal and external sphincter function and rectal mucosal sensitivity.     

Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults

The rise in didanosine concentrations in plasma when given with tenofovir raises concern for a high risk of toxic effects. Recommendations to reduce didanosine dose have been issued, but only for adults weighing more than 60 kg. We reviewed cases of pancreatitis in patients receiving didanosine plus tenofovir, didanosine alone, and tenofovir alone to assess the incidence of and risk factors for pancreatitis. Between Aug 1, 2001, and Nov 30, 2003, five of 185 (2.7%) patients receiving didanosine plus tenofovir, one of 182 (0.5%) on didanosine without tenofovir, and none of 208 on tenofovir without didanosine developed pancreatitis (p=0.016). Co-administration of both drugs versus each of them individually was an independent risk factor for pancreatitis (crude hazard ratio 10.666, 95% CI 1.246-91.294, p=0.031). These results suggest that the risk of pancreatitis is heightened when didanosine and tenofovir are given together.     

Virologic and genetic evaluation of vemurafenib-induced skin cancers

We describe the occurrence of a giant squamous cell carcinoma in a patient receiving vemurafenib for the treatment of late melanoma mestastases. Although the development of keratoacanthomas and squamous cell carcinomas (SCC) has been described during vemurafenib therapy, most of the reported cases are treated with surgical excision. In the present case, SCC regressed after drug withdrawal.     

Understanding college student spring break drinking: Demographic considerations,perceived norms and travel characteristics

Research has documented normative perceptions of others' alcohol use and how these related to increased rates of drinking and related problems among college students. Recently, research has expanded this concept to specific events (21st birthday drinking and tailgating). No studies to date examine the construct of normative perceptions of alcohol use for spring break (SB). SB is a known time of risk for increased alcohol use, and understanding whether students overestimate SB drinking norms, variables that influence norms perceptions (gender, ethnicity and travel) and whether SB norms relate to one's own drinking can inform future prevention and intervention efforts. We extend the literature by examining SB normative perceptions: (1) whether or not these perceptions are accurate and (2) the relationship to students' own drinking and related consequences. A random sample (N?=?1583) of students were asked about their SB drinking, consequences and norm perceptions. Students' SB drinking in this study was lower than their perception of typical student SB drinking (p?<?0.001), and women's perceptions were higher than men's (p?<?0.001). After adjusting for demographics and typical drinking, SB norms were significantly associated with SB drinking among those taking a trip over SB (p?<?0.001). After controlling for SB drinking, SB drinking norms were unrelated to consequences. Similar misperceptions exist for SB drinking. Prevention and intervention efforts aimed at reducing SB drinking and consequences, particularly for those planning a trip, may incorporate SB specific social norms education.     

Renal Replacement Therapy for Acute Kidney Injury in Severe Alcohol-Associated Hepatitis as a Bridge to Transplant or Recovery

Digestive Diseases and Sciences - Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy...