Impact of Travel Distance and Urban-Rural Status on the Multidisciplinary Management of Rectal Cancer.

OBJECTIVES: Optimal treatment of rectal cancer (RC) requires multidisciplinary care. We examined whether distance to treatment center or community size impacts access to multimodality care and population-based outcomes in RC. METHODS: Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6 regional cancer centers in British Columbia were reviewed. Distance to treatment center was determined for each patient. Communities were classified as rural, small, medium, and large population centers. Logistic and Cox regression models assessed associations of distance and community size with treatment received as well as cancer-specific (CSS) and overall survival (OS). RESULTS: Of 3,158 patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic consultation was longer for those >100 km from a treatment center or residing in medium/rural communities. Logistic regression demonstrated no correlation between distance or community size and receipt of treatment modality. Univariate analysis showed similar CSS (P = .18, .88) and OS (P = .36, .47) based on community size and distance, respectively. In multivariate analysis, distance >100 km had inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no consistent trend between decreasing community size and outcomes; however, living in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). CONCLUSIONS: In this population-based study, there were no urban-rural differences in access to multidisciplinary care, but increased distance may be associated with worse cancer-specific outcomes.

Diabetes and radiocontrast media increase endothelin converting enzyme-1 in the kidney.

Plasma endothelin-1 levels rise in diabetes and after exposure to contrast media suggesting a role in progressive diabetic and acute radiocontrast nephropathies. Here we studied individual and combined effects of streptozotocin-induced diabetes and contrast media on renal endothelin converting enzyme-1 levels in the rat. In vivo, medullary (but not cortical) endothelin converting enzyme protein gradually increased 4 to 5-fold following the induction of diabetes or after the administration of contrast media but rose 15-fold when diabetic rats were given contrast media. Changes in mRNA expression paralleled those of the protein. Immunohistochemistry confirmed that increased tubular and endothelial cell endothelin converting enzyme-1 were most pronounced in the medulla. In vitro, endothelin-1 levels increased 3-fold following incubation of endothelial cells with media high in glucose or with contrast and 4-fold with their combination. Endothelin converting enzyme-1 protein and mRNA expression changed in a similar pattern while prepro endothelin-1 mRNA increased with each insult but not in an additive way. Our study shows that diabetes and contrast media up-regulate renal medullary endothelin converting enzyme-1 expression and synthesis.

Adaptation to hypoxia in the diabetic rat kidney.

Hypoxia of the kidney in diabetes could predispose it to develop acute and chronic renal failure. To examine the relationship between renal hypoxia and renal failure, we measured hypoxia (as a pimonidazole adducts), hypoxia-inducible factors (HIFs), and a hypoxia target gene heme oxygenase-1. The studies were performed in rats with streptozotocin (STZ)-induced diabetes, Cohen diabetes sensitive rats, and during short-term artificial hyperglycemia in rats induced by intravenous glucose and octreotide. STZ-treated rats received insulin, the superoxide dismutase mimetic tempol, or contrast medium. Radiocontrast media causes hypoxia and HIF induction. Hypoxia, HIFs, and heme oxygenase were undetectable in controls, but transiently activated in STZ-treated and the Cohen diabetes sensitive rats. Different patterns of HIFs and pimonidazole were observed between the three models. Insulin abolished pimonidazole and HIF induction, whereas tempol lead to increased HIFs and heme oxygenase induction at similar levels of pimonidazole. When compared with control rats, STZ-treated rats exhibited more intense and protracted renal pimonidazole, with augmented hypoxia inducible factor production and reduced GFR following contrast media. Our data suggest that both regional hypoxia and hypoxia adaptation transiently occur in early stages of experimental diabetes, largely dependent on hyperglycemia or after contrast media. Tempol may augment the HIF response in diabetes.

Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome.

Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (V(H)), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the V(H) mutation status has not been found to significantly correlate with patient survival. In this study, we assessed V(H) mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J(H), in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were 'mutated', with <98% homology. V(H)1-69, V(H)4-59 and V(H)3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive V(H) rearrangements were more frequent in the mutated group. Patients with the 'mutated' genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the V(H) mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the V(H) mutation status may be a useful prognostic marker for these patients.

[Use of fragmin in program hemodialysis of patients with terminal chronic renal failure].

The subjects of the study were 60 patients at the end stage of chronic renal failure of various origins, who were on program hemodialysis (PHD) in Dialysis Center of City hospital #20. The main group consisted of 25 patients, who were administered fragmin (Pfizer, USA), a low-molecular heparin, for hypocoagulation during the procedure of hemodialysis. The drug was administered in a bolus dose of 5000 aXa ICU into the arterial line after connecting it to a fistula needle. The control group (35 patients) received unfranctionated heparin (UFH) in a conventional way (a bolus of 2000 to 2500 IU before the beginning of the procedure, followed by 1200 to 1500 IU/h in a continuous infusion, stopped 1 hour prior to the end of the dialysis). The following parameters were measured at the beginning and the end of the procedure: the number of thrombocytes, hemoglobin and hematocrit levels, activated partial thromboplastin time, activated coagulation time, antithrombin III level, and anti-Xa factor activity. Standard regimen of UFH administration allowed satisfactory hypocoagulation, but the necessary dose was hard to select. A bolus dose of fragmin led to adequate hypocoagulation in all the patients: there were no fibrin or blood clots in the lines or the dialyzer, or hemorrhage from the sites of puncture after the procedure. Anti-Xa-factor activity grew after a bolus injection of fragmin. By the end of the procedure the inhibitory activity of fragmin towards Xa-factor remained at the level of 0.44 +/- 0.7 IU/ml. The results show that a single dose of fragmin is effective and safe during a standard procedure of hemodialysis lasting up to 5 hours.

[Association of the complex of polymorphic markers of ACE genes, aldosteron synthetase and endothelial synthetase of nitric oxide with progression of chronic glomerulonephritis]. / Assotsiatsiia kompleksa polimorfnykh markerov genov angiotenzinprevrashchaiushchego fermanta, sintazy al'dosterona i éndotelial'noi sintetazy okisi azota s progressirovaniem khronicheskogo glomerulonfrita.

AIM: To study association of the complex of polymorphic markers of ACE genes (ACE complex), aldosteron synthetase gene (CYP11B2) and endothelial synthetase of nitric oxide (NOS3) with onset, course and progression of chronic glomerulonephritis (CGN). MATERIAL AND METHODS: 117 CGN patients were examined. Genetic predisposition to CGN development was studied by comparison of distributions of alleles and genotypes of polymorphic markers of genes ACE, CYP11B2 and NOS3 in CGN patients and controls (n = 80) free of renal diseases and arterial hypertension (AH). The course of CGN was analysed with consideration of the following factors: AH severity, proteinuria persistence, nephritic level for 6 months and longer, immunosuppressive therapy and response to it, therapy with ACE inhibitors and/or blockers of antiotensin II receptors (ARB). CGN progression rate end point was doubling of initial blood creatinine level. RESULTS: Significant differences in the incidence of the above alleles and genotypes in the patients and controls were not found. The patients were divided into two groups: group 1 consisted of 25 patients carrying the combination of alleles D+C+4a, group 2 consisted of the rest 92 patients. The groups did not differ by CGN course parameters, but renal survival was significantly lower in carriers of the allele combination D+C+4a. Cox's mono- and multifactorial regression analysis has shown that carriage of the allele combination D+C+4a is an independent riskfactor of renal survival deterioration. CONCLUSION: No association was detected between polymorphic markers of genes ACE, CYP11B2 and NOS3 and onset of CGN. Carriage of D+C+4a allele combination is an independent factor of risk for fast progression of chronic renal failure.

[Chronic viral infection in patients with alcoholic liver involvement]. / Khronicheskaia virusnaia infektsiia u bol'nykh s alkogol'nym porazheniem pecheni.

AIM: Detection of viral hepatitides markers in patients with alcoholic damage to the liver. MATERIALS AND METHODS: Virological, immunological and histochemical tests were performed in 36 chronic alcoholics who had enlarged liver and/or abnormal hepatic characteristics. RESULTS: 60% of the examinees carried chronic HBV, HCV, HDV infection. The activity of chronic inflammation of hepatic parenchyma was associated with biological phase of the viral infection development. The degree of hepatic parenchyma morphological changes was unrelated to the virus type. (HBV, HCV, HDV). CONCLUSION: Alcoholic hepatic damages often combine with viral hepatitis.

[Effects of intravasal laser irradiation of blood on lipid peroxidation in patients with abdominal surgery]. / Vliianie éndovazal'nogo lazernogo oblucheniia krovi na protsessy perekisnogo okisleniia lipidov u bol'nykh s abdominal'nymi operatsiiami.

Lipid peroxidation and the antioxidant system were studied in 36 patients with surgical diseases of the gastrointestinal tract. Time course of these parameters was studied in the postoperative period. Differences in lipid peroxidation during standard endovascular laser therapy were revealed, caused by the initial status of the antioxidant system. Combined use of endovascular laser irradiation of the blood and antioxidant therapy helped rule out the undesirable induction of free-radical processes in these patients.

[A new method of studying blood aggregation in geriatric surgical patients]. / Novyi metod izucheniia agregatsii trombotsitov u gerontokhirurgicheskikh bol'nykh.

A new technique of nephelometry based on the determination of optic radius of platelets and their aggregates has been tested in surgical patients of very advanced age with abdominal pathology. The technique in question makes it possible to use subthreshold inducer doses compatible with their real concentration in vivo. The nature of changes in platelet aggregation at preoperative stage has been described, postoperative course of hyperaggregation syndrome has been followed and qualitative disorders in aggregate forming processes have been specified. It has been shown that intravascular blood irradiation with low-intensive laser is effective for the correction of high platelet sensitivity.

[The effect of nitroglycerin on the Ca2+ ion level in the cytoplasm of human lymphocytes]. / Vliianie nitroglitserina na soderzhanie ionov Ca2+ v tsitoplazme limfotsitov cheloveka.

Fluorescence was used to examine the effects of nitroglycerin (60 microM) on basal and mitogen-induced (ConA, 25 micrograms/ml) Ca2+ levels in the human lymphocytic cytoplasm. Calcium-blocking effect of nitroglycerin was markedly shown in the medium containing 1 mM CaCl2 and virtually absent in calcium-free buffer. It is concluded that nitroglycerin affects cellular Ca2+ entry. A 120-minute preincubation led to a complete loss of the inhibitory effects of the drug on mitogen-induced Ca2+ responses of lymphocytes. Human lymphocytes are proposed as an experimental model for investigating the effects of nitrates and the mechanisms of their tolerance development.

[Evaluation of lipid peroxidation in surgical patients using chemiluminescence]. / Otsenka sostoianiia perekisnogo okisleniia lipidov u khirurgicheskikh bol'nykh metodom khemiliuminestsentsii.

Blood plasma Fe(2+)-induced chemiluminescence was employed to assess lipid peroxidation in 30 patients after surgical interventions. Blood plasma fluorescence intensity was different in the patients before surgery, which fact is explained by specific features of lipid peroxidation processes. After surgical intervention more intensive lipid peroxidation is observed in the patients with peptic ulcers and malignant tumors.

[The effect of nitroglycerin, nitrosorbide and nitroprusside on the intracellular content of Ca2+ ions in human lymphocytes]. / Vliianie nitroglitserina, nitrosorbida i nitroprussida na vnutrikletochnoe soderzhanie ionov Ca2+ v limfotsitakh cheloveka.

We used Fura-2 fluorometry to observe the effects of nitroglycerin (NG), isosorbide--2,5--dinitrate (ISDN) and sodium nitroprusside (NP) on basal and mitogen-induced (Con A, 25 micrograms/ml) cytoplasmic Ca++level ([Ca++]) in human blood lymphocytes. It is shown that nitrates dose-dependently decrease Con-A-induced increase in [Ca++]i. When compared for the effect on calcium metabolism, NP appeared most potent (IC50 = 4.1 x 10(-7) M). The drug action was not reported when the cells were exposed to Ca(++)-free solution. 120-min preincubation with 10(-4) M NG led to complete abolishment of the ISDN and NG effects. The results suggest that human lymphocytes may be used as an experimental model of nitrates action and mechanisms underlying tolerance to them.

[Effects of nitroglycerin on intracellular concentration of calcium in human blood platelets]. / Vliianie nitroglitserina na kontsentratsiiu vnutrikletochnogo kal'tsiia v trombotsitakh cheloveka.

It is shown that nitroglycerin has a calcium-blocking property in human platelets both at basal and ADP-induced calcium level, determined by fluorescence techniques (Fura-2). The study demonstrated a dose-dependent inhibitory effect of nitroglycerin on calcium rise, induced by ADP. 30-min preincubation with 60 microM nitroglycerin increased IC50 from 44 (without preincubation) to 320 microM, indicating the development of nitrate tolerance. It was suggested, that human platelet may be used as an experimental model of nitrate tolerance.