Adenosquamous carcinoma of the colon

Two cases of primary adenosquamous carcinomas of the sigmoid colon and rectum are presented. Clinical features and pathologic findings of both primary and metastatic lesions are reported (including immunohistochemistry and electron microscopy). We emphasize that the presence of a metastatic squamous tumor in a patient with an unknown primary does not exclude the possibility of colonic carcinoma. Comparison with other reports in the American medical literature indicates that these are very aggressive tumors that may have a worse prognosis than the more common form of colonic adenocarcinoma. Furthermore, the squamous component, in particular, may have a greater potential for metastasizing and can do so as an undifferentiated-appearing carcinoma. In view of this, the authors suggest that very poorly differentiated areas within colonic adenocarcinomas should be very carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in an attempt to identify squamous features.     

Pancreatic adenocarcinoma: Outstanding problems

Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%.Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma.About 40% of patients have locally advanced nonresectable disease.In the past,determination of pancreatic cancer resectability was made at surgical exploration.The development of modern imaging techniques has allowed preoperative staging of patients.Institutions disagree about the criteria used to classify patients.Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis.There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition ofborderline resectable pancreatic cancer is also lacking.Thus,there is much room for improvement in all aspects of treatment for pancreatic cancer.Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer.With improved surgical techniques and advanced perioperative management,vascular resection and reconstruction are performed more frequently;patients thought once to be unresectable are undergoing radical surgery.However,when attempting heroic surgery,a realistic approach concerning the patient’s age and health status,probability of recovery after surgery,perioperative morbidity and mortality and life quality after tumor resection is necessary.     

Chimerism and tolerance in rat recipients of intestinal allografts from ALS-treated donors with and without adjunct naïve-donor-strain bone-marrow cells

BACKGROUND: BN --> LEW small-intestine transplantation (SITx) given a 28-day course of tacrolimus results in partial tolerance and prolonged alloengraftment despite the development of indolent chronic rejection (CR). We determined whether the CR was associated with the quantity or quality of passenger leukocytes contained in the unmodified or antilymphocyte serum (ALS)-depleted BN intestine at the time of transplantation, and with the subsequent migration and persistence of these donor leukocytes in the LEW recipients (chimerism). METHODS: Four experimental cohorts were defined by differences of the BN allografts and by the infusion (or not) of na?ve donor (bone marrow cells [BMC]) on the day of the BN --> LEW SITx. All LEW recipients were treated with the same 28-day course of tacrolimus. The LEW animals received: (1) unaltered intestine; (2) intestine from ALS-treated donor; (3) intestine from ALS-treated donor plus BMC from naive BN donor on day 0; and (4) unaltered intestine and BMC from unmodified (na?ve) BN donor. RESULTS: Blood chimerism during the first 2 weeks after transplantation was lowest in the recipients of intestine from ALS-treated donors (groups 2 and 3), apparently because of the nearly complete elimination from the bowel of alphabetaTCR+ passenger leukocytes. After 2 weeks posttransplant to 5 months, greater than 2% of circulating donor cells were seen in animals given adjunct BMC from na?ve BN donors (groups 3 and 4); this was associated with the absence of CR in the intestinal allografts. With lower levels of chimerism, moderate CR including arteritis and fibrosis in the Peyer's patches and mesenteric lymph nodes was found in the intestinal grafts of all group 1 and group 2 animals. Nevertheless, the CR-prone recipients in groups 1 and 2 had equivalent weight gain for greater than or equal to 150 days as in the CR-free groups 3 and 4. Detailed tissue chimerism studies in groups 1 to 3 showed that most of the donor cells in the gut-associated lymphoid tissues were rapidly replaced, but that the residual donor constituency of up to 6% in the allografts of group 3 was nearly 10-fold greater at 150 days than in groups 1 and 2 and closely reflected the findings in blood. CONCLUSION: The development of CR in intestinal allografts to which the recipients are partially tolerant is associated with a decline with time of donor-leukocyte chimerism. Multilineage chimerism in the recipient, and a similar profile of donor cells in the allografts, is better achieved with infused donor BMC than with the normal intestinal passenger leukocytes of the intestine. The difference may be because of a higher number of precursor and pluripotent stem cells in BMC.     

Bilateral plasmacytoma of the breast: a case report

Plasmacytoma of the breast is a rare condition that may occur as a solitary finding or in association with multiple myeloma. Of the cases of plasmacytoma of the breast that have been described, nearly half have been bilateral. We report a case of bilateral plasmacytoma of the breast detected on a routine screening mammogram in a patient with a recent diagnosis of multiple myeloma.     

Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Conceptualizing a resilience research framework at The National Institutes of Health

The National Institutes of Health (NIH) have recently gathered internal and external input towards a shared understanding of resilience in the wide context of human health and the biomedical sciences that would help accelerate advances in human health and its maintenance. This shared view is that resilience refers in general to a system's capacity to recover, grow, adapt, or resist perturbation from a challenge or stressor. Over time, a system's response to a challenge might show varied degrees of reactions that likely fluctuate in response to the type of challenge (internal and/or external), severity of the challenge, the length of time exposed to the challenge, other external factors and/or biological factors (innate and/or external). We have embarked on this special issue as an opportunity to explore commonalities amongst viewpoints on the science of resilience covered by the various NIH Institutes, Centers, and Offices (ICOs) with respect to the characterization of various systems, stressors, outcomes measures and metrics, and interventions and/or protective factors that are shared within each domain and across multiple domains. Here, resilience is characterized broadly by four areas of scientific study: molecular/cellular, physiologic, psychosocial and spiritual, and environmental/community resilience. Each area or domain provides general frameworks for designing studies that may help advance the science of resilience within the context of health maintenance. This special issue will also acknowledge the remaining gaps that impede advancement of the science of resilience and offer considerations for potential next steps towards addressing the research gaps.     

AT-1 receptor antagonism modifies the mediation of endothelin-1, thromboxane A2, and catecholamines in the renal constrictor response to angiotensin II

OBJECTIVE: The present study investigated the consequences of partial AT(1) receptor blockade on the participation of catecholamines, thromboxane A(2) (TXA(2)), and endothelin-1 (ET-1) in the renal vasoconstriction induced by angiotensin II (Ang II). METHODS: For this purpose, the increase in renal perfusion pressure (RPP) produced by Ang II was studied in isolated kidneys from untreated or irbesartan-treated Wistar Kyoto and spontaneously hypertensive rats (SHR), in absence or presence of the alfa-1 receptor antagonist, prazosin, the TXA(2) receptor antagonist, ifetroban, or the ET(A)/ET(B) receptor antagonist, PD145065. RESULTS: Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in WKY. Increases in RPP produced by Ang II were comparable in kidneys from both untreated groups. Treatment with irbesartan reduced SAP and RPP in both strains in a comparable extent. Presence of prazosin, ifetroban, or PD145065 in perfusion media reduced (P < 0.05) Ang II maximal response in all groups. Maximal inhibition of Ang II-induced vasoconstriction produced by the 3 antagonists was comparable in untreated WKY, but that of ifetroban and PD145065 was lower (P < 0.05) than that of prazosin in untreated SHR. Maximal inhibition of Ang II-induced vasoconstriction produced by the 3 antagonists was comparable in WKY treated with irbesartan, and not different to that observed in untreated WKY. Maximal inhibitory effect of the 3 antagonists was higher (P < 0.05) in treated than in untreated SHR. CONCLUSION: The study further supports the importance of catecholamines, TXA(2), and ET-1 as mediators of the renal vasoconstriction induced by Ang II in both normotensive and hypertensive rats. Hypertensive conditions appeared to reduce the participation of TXA(2) and ET-1 in Ang II-induced vasoconstriction when compared with normotensive conditions. Chronic partial blockade of AT(1) receptors did not affect the participation of catecholamines, TXA(2), and ET-1 in normotensive rats, but increased the participation of the 3 mediators in SHR. This suggests that when AT(1) receptors are partially blocked, other vasoconstrictor factors could exert part of the renal vasoconstrictor effects of Ang II.     

Genes of tumor necrosis factors and their receptors and the primary open angle glaucoma in the population of Central Russia

AIM: To examine the association of genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 with the development of primary open angle glaucoma (POAG) among people in Central Russia. METHODS: The study sample included 443 individuals, of which 252 patients with POAG and 191 individuals in the control group. Genotyping of (-308)G/A TNFα, (+250)A/G Ltα, (+36)A/G TNFR1, (+1663)A/G TNFR2 was performed using polymerase chain reaction. The distribution of alleles and genotypes of the studied DNA markers in the groups was examined by 2×2 contingency tables and χ2 with the Yates’s correction for continuity and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Allele (-308)G TNFα (Р=0.01, OR=1.78, 95%CI 1.12-2.85) was identified as a risk factor for POAG. Homozygotes (-308) AA TNFα are at a lowest risk for development of the disease (Р=0.01, OR=0.0005). The following combination of genetic variants of cytokines were associated with a reduced risk of POAG: (+1663)A TNFR2 and (+250)G Ltα (OR=0.34) CONCLUSION: Genetic polymorphisms (-308)G/A TNFα, (+250)A/G Ltα, (+1663)A/G TNFR2 associated with the development of POAG in the population of Central Russia.