Accuracy of CGM Systems During Continuous and Interval Exercise in Adults with Type 1 Diabetes.

BACKGROUND: continuous glucose monitoring systems (CGMs) play an important role in the management of T1D, but their accuracy may reduce during rapid glucose excursions. The aim of study was to assess the accuracy of recent rt-CGMs available in Italy, in subjects with T1D during 2 sessions of physical activity: moderate continuous (CON) and interval exercise (IE). METHOD: we recruited 22 patients with T1D, on CSII associated or integrated with a CGM, to which a second different sensor was applied. Data recorded by CGMs were compared with the corresponding plasma glucose (PG) values, measured every 5 minutes with the glucose analyzer. To assess the accuracy of the CGMs, we evaluated the Sensor Bias (SB), the Mean Absolute Relative Difference (MARD) and the Clarke error grid (CEG). RESULTS: a total of 2355 plasma-sensor glucose paired points were collected. Both average plasma and interstitial glucose concentrations did not significantly differ during CON and IE. During CON: 1. PG change at the end of exercise was greater than during IE (P = .034); 2. all sensors overestimated PG more than during IE, as shown by SB (P < .001) and MARD (P < .001) comparisons. Classifying the performance according to the CEG, significant differences were found between the 2 sessions in distribution of points in A and B zones. CONCLUSIONS: the exercise affects the accuracy of currently available CGMs, especially during CON, suggesting, in this circumstance, the need to maintain blood glucose in a "prudent" range, above that generally recommended. Further studies are needed to investigate additional types of activities.

Method-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in Candida and Aspergillus Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion Methods.

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.

Lessons from the Past: Some Histories of Alpha-1 Antitrypsin Deficiency Before Its Discovery.

A1AT deficiency- a genetically inherited autosomal codominant disease with more than 120 identified alleles- was first identified by Laurell and Eriksson in 1963. The most common hereditary disorder in adults, A1AT causes an increased risk of developing pulmonary emphysema and liver disease. In A1AT patients, lung disease generally presents at a younger age than "usual" chronic obstructive pulmonary disease (COPD) and it may be misdiagnosed as asthma. Because A1AT deficiency patients can show the same clinical features as non-deficient COPD (including increased evidence of bronchiectasis, frequent exacerbations, impaired health status and a degree of reversibility of airflow obstruction), the World Health Organization recommend to test every patient with a diagnosis of COPD or adult-onset asthma for A1AT deficiency. Despite these recommendations, the epidemiology of A1AT deficiency remains uncertain. Although recently discovered A1AT deficiency has affected human populations since antiquity. By using scientific data and recently studied skeletons and historical cases, we show that it is now possible to reconstruct the natural history of pathological processes, whether due to genetic, infectious or environmental factors. We believe that the evolution of disease in patients and research to elucidate the relationship between social science and environmental are pertinent contemporaneous subjects.

Association of free-living physical activity measures with metabolic phenotypes in type 2 diabetes at the time of diagnosis. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS).

BACKGROUND AND AIM: Lifestyle is considered a major determinant of risk of type 2 diabetes (T2D). We investigated whether daily physical activity (DPA) is associated with beta-cell function (BF) and/or insulin sensitivity (IS) in patients with T2D at the time of diagnosis. METHODS AND RESULTS: In 41 subjects enrolled in the Verona Newly-Diagnosed Type 2 Diabetes Study we assessed: (1) IS, by euglycaemic insulin clamp; (2) BF, estimated by prolonged-OGTT minimal modeling and expressed as derivative and proportional control; (3) DPA and energy expenditure (EE), assessed over 48-h monitoring by a validated wearable armband system. Study participants (median [IQR]; age: 62 [53-67] years, BMI: 30.8 [26.5-34.3] Kg m-2, HbA1c: 6.7 [6.3-7.3]%; 49.7 [45.4-56.3] mmol/mol) were moderately active (footsteps/day: 7773 [5748-10,927]; DPA≥3MET: 70 [38-125] min/day), but none of them exercised above 6 metabolic equivalents (MET). EE, expressed as EETOT (total daily-EE) and EE≥3MET (EE due to DPA≥3MET) were 2398 [2226-2801] and 364 [238-617] Kcal/day, respectively. IS (M-clamp 630 [371-878] µmol/min/m2) was positively associated with DPA and EE, independent of age, sex and BMI (p < 0.05). Among the DPA and EE parameters assessed, DPA≥3MET and EETOT were independent predictors of IS in multivariable regression analyses, adjusted for age, sex, BMI (R2 = 16%, R2 = 19%, respectively; p < 0.01). None of model-derived components of BF was significantly associated with DPA or accompanying EE. CONCLUSIONS: Our study highlighted moderate levels of DPA and total EE as potential determinants of IS, but not BF, in T2D at the time of diagnosis. Intervention studies are needed to conclusively elucidate the effect of DPA on these features. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01526720.

Posaconazole MIC Distributions for Aspergillus fumigatus Species Complex by Four Methods: Impact of cyp51A Mutations on Estimation of Epidemiological Cutoff Values.

Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 µg/ml for the CLSI method and 0.25 µg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 µg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 µg/ml. The tentative ECOFFinder ECV with SYO was 0.06 µg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 µg/ml (CLSI, EUCAST, Etest) or 0.06 µg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.

Effects of aerobic or resistance exercise training on cardiovascular autonomic function of subjects with type 2 diabetes: A pilot study.

BACKGROUND AND AIMS: Both aerobic (AER) and resistance (RES) training improve metabolic control in patients with type 2 diabetes (T2DM). However, information on the effects of these training modalities on cardiovascular autonomic control is limited. Our aim was to compare the effects of AER and RES training on cardiovascular autonomic function in these subjects. METHODS AND RESULTS: Cardiovascular autonomic control was assessed by Power Spectral Analysis (PSA) of Heart Rate Variability (HRV) and baroreceptors function indexes in 30 subjects with T2DM, randomly assigned to aerobic or resistance training for 4 months. In particular, PSA of HRV measured the Low Frequency (LF) and High Frequency (HF) bands of RR variations, expression of prevalent sympathetic and parasympathetic drive, respectively. Furthermore, we measured the correlation occurring between systolic blood pressure and heart rate during a standardized Valsalva maneuver using two indexes, b2 and b4, considered an expression of baroreceptor sensitivity and peripheral vasoactive adaptations during predominant sympathetic and parasympathetic drive, respectively. After training, the LF/HF ratio, which summarizes the sympatho-vagal balance in HRV control, was similarly decreased in the AER and RES groups. After AER, b2 and b4 significantly improved. After RES, changes of b2 were of borderline significance, whereas changes of b4 did not reach statistical significance. However, comparison of changes in baroreceptor sensitivity indexes between groups did not show statistically significant differences. CONCLUSION: Both aerobic and resistance training improve several indices of the autonomic control of the cardiovascular system in patients with T2DM. Although these improvements seem to occur to a similar extent in both training modalities, some differences cannot be ruled out. CLINICAL TRIAL REGISTRATION NUMBER: NCT01182948, clinicaltrials.gov.

Was Ugo Foscolo (1778-1827) affected by alpha-1 antitrypsin deficiency?

Niccolò Ugo Foscolo (1778-1827), known as Ugo, is one of the masters of the Italian poetry. A writer and a revolutionary, he embraced the ideals of the French Revolution and took part in the stormy political discussions, which the fall of the Republic of Venice had provoked. Despite his poor health, Foscolo lived an adventurous life serving as a volunteer in the Guardia Nazionale and in the Napoleonic army. Following Napoleon's fall (1814), he went into voluntary exile in early 1815. He reached London in Sept. 1816 and lived in poverty at Turnham Green (Chiswick) until his premature death. Foscolo's medical history has been poorly investigated and the cause of his death remains unclear. In an attempt to shed light on his clinical history, we analyzed his Correspondence (Epistolario), a series of more than 3000 letters written between 1794 and 1827. From the age of 26 (1808), Foscolo had frequent episodes of cough and dyspnea that progressively worsened. Four acute respiratory exacerbations occurred in 1812. Between September 1812 and April 1813, he had breathlessness as that of asthma. Frail and ailing, he developed a chronic liver disease in 1826. In August 1827, weakness, dyspepsia and drowsiness further increased and dropsy became manifest. He went into coma on September 7, 1827 and died aged 49 three days later. Based on a brief history of urethritis and urinary obstructions (1811-1812), previous scholars have suggested that Foscolo had urethral stenosis that caused a chronic bladder outlet obstruction and led to consequent renal failure. This hypothesis, however, does not mention the respiratory symptomatology present since 1804, which is a pivotal feature of Foscolo's illness. We surmise that Foscolo suffered from alpha-1 anti trypsin (AAT) deficiency, a rare genetic disease, which caused his premature death and support our interpretation with documental evidence.

Composition-driven Cu-speciation and reducibility in Cu-CHA zeolite catalysts: a multivariate XAS/FTIR approach to complexity.

The small pore Cu-CHA zeolite is attracting increasing attention as a versatile platform to design novel single-site catalysts for deNO x applications and for the direct conversion of methane to methanol. Understanding at the atomic scale how the catalyst composition influences the Cu-species formed during thermal activation is a key step to unveil the relevant composition-activity relationships. Herein, we explore by in situ XAS the impact of Cu-CHA catalyst composition on temperature-dependent Cu-speciation and reducibility. Advanced multivariate analysis of in situ XANES in combination with DFT-assisted simulation of XANES spectra and multi-component EXAFS fits as well as in situ FTIR spectroscopy of adsorbed N2 allow us to obtain unprecedented quantitative structural information on the complex dynamics during the speciation of Cu-sites inside the framework of the CHA zeolite.

Psychological distress, self-efficacy and glycemic control in type 2 diabetes.

AIM: To investigate the association of glycemic control with depression, anxiety, self-efficacy and other diabetes-specific psychological measures in a cohort of adult patients with type 2 diabetes (T2D) free of severe chronic diabetes-related complications. METHODS AND RESULTS: In 172 T2D outpatients consecutively recruited at the Diabetes Center of Verona City Hospital, we performed a standard medical assessment and completed the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI) and the Multidimensional Diabetes Questionnaire (MDQ) Age, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were (median [IQR]): 64.0 [58.0-69.0] years, 31.0 [28.0-34.4] kg/m2, and 7.3 [6.7-8.0] %, respectively. The overall prevalence of anxiety and depression was 14.5% and 18.6%, respectively. Higher levels of HbA1c were significantly (p < 0.001) associated with a number of MDQ dimensions, such as higher perceived interference with daily activities (Spearman's rho coefficient = 0.33), higher perceived diabetes severity (rho = 0.28) and lower self-efficacy (rho = -0.27), but not with depression or anxiety. These three variables were also independent predictors of higher HbA1c levels, when entered in a multivariable stepwise-forward regression model that also included age, BMI, diabetes duration and diabetes-specific social support as covariates. CONCLUSION: Lower self-efficacy and higher diabetes distress were closely associated with poorer glycemic control. No direct association between HbA1c and clinical psychological symptoms was detected. These results highlight that a number of diabetes-specific psychological variables may play a role amidst psychological distress and glycemic control. Further studies are needed to elucidate the relevance of diabetes distress and self-efficacy to the achievement of individual glycemic targets.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

AIM: To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. METHODS: People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. RESULTS: We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). CONCLUSIONS: In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control.

Cryptic and rare Aspergillus species in Brazil: prevalence in clinical samples and in vitro susceptibility to triazoles.

Aspergillus spp. are among the most common causes of opportunistic invasive fungal infections in tertiary care hospitals. Little is known about the prevalence and in vitro susceptibility of Aspergillus species in Latin America, because there are few medical centers able to perform accurate identification at the species level. The purpose of this study was to analyze the distribution of cryptic and rare Aspergillus species among clinical samples from 133 patients with suspected aspergillosis admitted in 12 medical centers in Brazil and to analyze the in vitro activity of different antifungal drugs. The identification of Aspergillus species was performed based on a polyphasic approach, as well as sequencing analysis of the internal transcribed spacer (ITS) region, calmodulin, and ß-tubulin genes and phylogenetic analysis when necessary. The in vitro susceptibility tests with voriconazole, posaconazole, and itraconazole were performed according to the CLSI M38-A2 document (2008). We demonstrated a high prevalence of cryptic species causing human infection. Only three isolates, representing the species Aspergillus thermomutatus, A. ochraceus, and A. calidoustus, showed less in vitro susceptibility to at least one of the triazoles tested. Accurate identifications of Aspergillus at the species level and with in vitro susceptibility tests are important because some species may present unique resistance patterns against specific antifungal drugs.

Crossover from adiabatic to antiadiabatic quantum pumping with dissipation.

Quantum pumping, in its different forms, is attracting attention from different fields, from fundamental quantum mechanics, to nanotechnology, to superconductivity. We investigate the crossover of quantum pumping from the adiabatic to the antiadiabatic regime in the presence of dissipation, and find general and explicit analytical expressions for the pumped current in a minimal model describing a system with the topology of a ring forced by a periodic modulation of frequency ω. The solution allows following in a transparent way the evolution of pumped dc current from much smaller to much larger ω values than the other relevant energy scale, the energy splitting introduced by the modulation. We find and characterize a temperature-dependent optimal value of the frequency for which the pumped current is maximal.

Variants and haplotypes of TCF7L2 are associated with ß-cell function in patients with newly diagnosed type 2 diabetes: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1.

CONTEXT: Intronic variants of TCF7L2 are confirmed genetic risk factors for type 2 diabetes and are associated to alterations in beta cell function in nondiabetic individuals. OBJECTIVE: The objective of the study was to test whether TCF7L2 variability may affect ß-cell function also in patients with type 2 diabetes. DESIGN: This was a cross-sectional association study. SETTING: The study was conducted at a university hospital referral center for diabetes. PATIENTS: Patients included 464 (315 males and 149 females) glutamic acid decarboxylase-negative patients [age: median 59 yr (interquartile range: 52-65); body mass index: 29.3 kg/m(2) (26.5-32.9); fasting plasma glucose: 7.0 mmol/liter (6.1-8.0)] with newly diagnosed type 2 diabetes. INTERVENTION(S): Interventions included frequently sampled oral glucose tolerance test and euglycemic insulin clamp. MAIN OUTCOME MEASURE(S): ß-Cell function (derivative control and proportional control); insulin sensitivity; genotypes of the following TCF7L2 single-nucleotide polymorphisms: rs7901695, rs7903146, rs11196205, and rs12255372. RESULTS: Both rs7901695 and rs7903146 diabetes risk alleles were associated with reduced proportional control of ß-cell function (P = 0.019 and P = 0.022, respectively). Two low-frequency haplotypes were associated with extreme (best and worst) phenotypes of ß-cell function (P < 0.01). No associations between TCF7L2 genotypes and insulin sensitivity were detected. CONCLUSIONS: TCF7L2 diabetes risk variants, either as single-nucleotide polymorphisms or as haplotypes, detrimentally influence ß-cell function and might play a role in determining the metabolic phenotype of patients with newly diagnosed type 2 diabetes.

Glomerular filtration rate, albuminuria and risk of cardiovascular and all-cause mortality in type 2 diabetic individuals.

BACKGROUND AND AIMS: To assess all-cause and cardiovascular mortality in type 2 diabetic individuals according to estimated glomerular filtration rate (eGFR) and albuminuria. METHODS AND RESULTS: We followed 2823 type 2 diabetic outpatients for a median period of 6 years for the occurrence of all-cause and cardiovascular mortality. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease study equation. At baseline, an eGFR < 60 ml/min/1.73 m² and abnormal albuminuria were present in 22.5% and 26.0% of participants, respectively. During follow-up, a total of 309 patients died, 53% of deaths were secondary to cardiovascular causes. Risks of all-cause and cardiovascular mortality increased progressively with decreasing eGFR and increasing albuminuria. After adjustment for age, sex, body mass index, smoking, hypertension, diabetes duration, hemoglobin A1c, plasma lipids, medications use (hypoglycemic, anti-hypertensive, anti-platelet or lipid-lowering drugs) and albuminuria, the hazard ratios of all-cause and cardiovascular mortality per 1-SD decrease in eGFR were 1.53 (95%CI 1.2-2.0; p < 0.0001) and 1.51 (95%CI 1.05-2.2; p=0.023), respectively. A similar pattern in the risk of all-cause and cardiovascular mortality was seen for albuminuria (1.14, 1.01-1.3, p=0.028 and 1.19, 1.01-1.4, p=0.043 per 1-SD increase in albuminuria, respectively) after adjustment for eGFR and other potential confounders. CONCLUSIONS: These findings suggest that both decreasing eGFR and rising albuminuria are associated with all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of traditional risk factors and diabetes-related variables.

Embutidos cocidos funcionales / Functional cooked sausage-type product

Se ha optimizado, desde el punto de vista funcional, un embutido cocido, útil para prevenir la aterosclerosis, usando aceites vegetales con alto contenido en ácidos grasos poliinsaturados.El producto obtenido a nivel artesanal y posteriormente a nivel industrial con el apoyo de importante frigorífico, no posee grasas animales adicionadas, no contiene ácidos grasos trans, tiene bajo contenido en sodio, es bajo en calorías, no presenta cambios organolépticos considerables con relación a productos similares de primeras marcas, y esta enriquecido con AGPIw3 obteniéndose una relación w6:w3 ideal.

Embutidos cocidos funcionales / Functional cooked sausage-type product

Se ha optimizado, desde el punto de vista funcional, un embutido cocido, útil para prevenir la aterosclerosis, usando aceites vegetales con alto contenido en ácidos grasos poliinsaturados.El producto obtenido a nivel artesanal y posteriormente a nivel industrial con el apoyo de importante frigorífico, no posee grasas animales adicionadas, no contiene ácidos grasos trans, tiene bajo contenido en sodio, es bajo en calorías, no presenta cambios organolépticos considerables con relación a productos similares de primeras marcas, y esta enriquecido con AGPIw3 obteniéndose una relación w6:w3 ideal.(AU)

Familial adenomatous polyposis. Surgical treatment: when and how.

Familial adenomatous polyposis is an autosomal dominated inherited disease, caused by the mutation of the tumour suppressor gene adenomatous polyposis coli on chromosome 5. Despite being a rare disorder, accounting for some 1% of colorectal cancers, it represents an interesting model of hereditary disease, because of its intrinsic characteristics, conventionally defined by the presence of more than 100 colorectal polyps, as well as extra-colon manifestations, the attenuated form of the disease, genetic aspects, the inevitable progression to colorectal cancer and hence the correct therapy to treat or prevent the fatal evolution of the disease. Surgical treatment is based above all on two techniques: ileorectal anastomosis, which requires careful surveillance of rectal remnant, and ileal pouch-anal anastomosis, which totally eradicates the disease. The suitability of using these two techniques is discussed in view of new genetic and clinical findings, acquired from personal experience and from the literature.

Effects of topoisomerase II inhibitors on gastric cancer cells characterized by different genetic lesions.

Gastric cancer is poorly-responsive to widely used antitumour drugs, the efficacy of which is thought to be related to the capacity of triggering apoptosis. This process requires a series of gene products including a functional p53 protein. We tested the effects of two DNA topoisomerase II poisons, etoposide and doxorubicin, on gastric cancer cell lines with different genetic lesions. We characterised MKN74 and MKN28 cells for p53 gene status and for the expression of p53 and p21 proteins, as well as of topoisomerase II alpha and beta isoforms. After drug treatments, the cells were analysed for drug cytotoxicity, colony forming ability, cell cycle distribution and presence of apoptotic features. Our findings demonstrated that both etoposide and doxorubicin have a potent anti-proliferative effect on gastric cancer cells. Cell death kinetics was different in the two cell lines, MKN74 cells being more sensitive than MKN28 to the drugs. MKN74 cells, although harboring a wt p53 gene, were unable to undergo a massive apoptosis following etoposide treatment. The response of this cell line might be related to the topoisomerase II beta isozyme, the expression of which proved to be undetectable.