Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy.
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Autoimmune Diseases of the Nervous System↗
Biomedical subjects
G Lanza
Publications and source records attributed to G Lanza.
Resistive load of laryngeal mask airway and ProSeal laryngeal mask airway in mechanically ventilated patients.
BACKGROUND: The ProSeal Laryngeal Mask Airway (PLMA) ventilation tube is narrower and shorter than the standard Laryngeal Mask Airway (LMA) and is without the vertical bars at the end of the tube. In this randomized, crossover study, PLMA and LMA resistances were compared. METHODS: Respiratory mechanics was calculated in 26 anesthetized, mechanically ventilated patients with both LMA and PLMA. The laryngeal mask positioning was fiberoptically evaluated. Differences in the respiratory mechanics of the LMA and the PLMA were attributed to the differences between the laryngeal masks. RESULTS: In the total study population the airway resistance was 1.5 +/- 2.6 hPa.l-1.s-1 (P = 0.005) higher with the PLMA than with the LMA. During the PLMA use, the peak expiratory flow reduced by 0.02 +/- 0.05 l min-1 (P = 0.046), the expiratory resistance increased by 0.6 +/- 1.3 hPa.l-1.s-1 (P = 0.022), and the time constant of respiratory system lengthened by 0.09 +/- 0.18 s (P = 0.023). These differences doubled when the LMA was better positioned than the PLMA, whereas they disappeared when the PLMA was positioned better than the LMA. CONCLUSIONS: The standard LMA offers a lower resistive load than the PLMA. Moreover, the fitting between the laryngeal masks and the larynx, as fiberoptically evaluated, plays a major role in determining the resistive properties of these devices.
Adult↗
Comparison of the standard laryngeal mask airway and the ProSeal laryngeal mask airway in obese patients.
BACKGROUND: The ProSeal laryngeal mask airway (PLMA) may have advantages over the laryngeal mask airway (LMA) in obese patients. We tested this hypothesis in a clinical setting. METHODS: Sixty obese patients (BMI >30) were randomized to receive mechanical ventilation (tidal volume 7 ml kg(-1), PEEP 10 cm H(2)O), through either the PLMA or the LMA. A gastric tube was used in all patients. Cuff pressure was set at 60 cm H(2)O and increased progressively until excessive leak occurred. The incidence of sore throat was assessed at recovery and after 1 week. RESULTS: The mean leak fraction was 6.1 (SD 2.9)% with the LMA and 6.4 (3.5)% with the PLMA (P=0.721). With the PLMA, with no sign of ventilation problems, the drainage tube was not patent in three patients. The cuff pressure was >100 cm H(2)O in 38% of the LMA group and 7% of the PLMA group (P=0.05). The incidence of sore throat was similar in both groups and it was similarly scored in the recovery room and 1 week after surgery. CONCLUSIONS: Both the PLMA and the LMA can be used for mechanical ventilation of obese patients. The patency of the PLMA drainage tube needs to be checked constantly even when an optimal airtight seal is present. In obese patients the LMA requires a greater cuff pressure than the PLMA, but sore throat is not related to the cuff pressure. Sore throat assessment in the recovery room appears as reliable as assessment later.
Adult↗
Impact of laryngeal mask airway and tracheal tube on pulmonary function during the early postoperative period.
BACKGROUND: The tracheal tube (TT) produces reversible bronchoconstriction and increases pulmonary airway resistance compared to the laryngeal mask airway (LMA). The possible persistence of this effect in the postoperative period has not been studied. The aim of this study was to compare the early postoperative pulmonary function in healthy patients undergoing minor surgical procedures with the LMA or with the TT. METHODS: Sixty patients scheduled for saphenous vein stripping under general anaesthesia were randomised to receive the LMA or the TT. Before anaesthesia and 20 min after LMA or TT removal, pulse oxymetry values (SpO(2)) were recorded and patients performed forced spirometry in the supine position. RESULTS: Preoperative pulmonary function was normal in both groups. There were no differences between groups in the preoperative respiratory function test and SpO(2). Following surgery SpO(2), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) decreased in both groups. The FEV1/FVC did not change in either of the groups. In the TT group, compared to patients using the LMA, there was a greater relative decrease of SpO(2) (2.7 +/- 2.7% vs. 1.3 +/- 2.2%, P=0.017), FEV1 (17.6 +/- 12.2% vs. 8 +/- 17.4%, P=0.008), FVC (15.8 +/- 12.4% vs. 9 +/- 13.4%, P=0.023) and PEF (20.6% +/- 15.3% vs. 8.1 +/- 33.3%, P=0.033). CONCLUSIONS: This study demonstrates greater early postoperative respiratory restrictive syndrome and lower arterial oxygen saturation following tracheal intubation compared to LMA use in patients without respiratory disease.
Blood Gas Analysis↗
[Indications for treatment of carotid stenosis. Choice of loco-regional anesthesia and general anesthesia].
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Anesthesia, Conduction↗
Fluorouracil-induced coronary artery spasm.
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Angina Pectoris↗
Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis.
Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.
Aged↗
Pressure controlled versus volume controlled ventilation with laryngeal mask airway.
STUDY OBJECTIVE: To quantify the impact on peak airway pressure of pressure-controlled and volume-controlled ventilation during Laryngeal Mask Airway (LMA) use. DESIGN: Prospective, crossover clinical study. SETTING: University-affiliated hospital. PATIENTS: 32 ASA physical status I and II patients undergoing general anesthesia with the LMA. INTERVENTIONS: Patients were ventilated for three minutes both with pressure-controlled and volume-controlled ventilation, provided that tidal volume (V(T) ) and inspiratory time (It) were constant. MEASUREMENTS AND MAIN RESULTS: The monitored parameters were electrocardiography, arterial blood pressure, pulse oximetry, capnography, neuromuscular transmission, airway pressure and flow, and concentration of ventilated vapors and gases. The actually delivered V(T) was similar with both types of ventilation (volume-controlled = 0.67 +/- 0.13 lt, pressure-controlled = 0.67 +/- 0.14 lt; p = 0.688). Peak airway pressure was lower during pressure-controlled ventilation (14.6 +/- 3.5 cmH(2)O) than during volume-controlled ventilation (16 +/- 4 cmH(2)O) (p < 0.001). Furthermore, we noted that the higher the airway pressure with volume-controlled ventilation, the greater was the reduction in airway pressure during pressure-controlled ventilation. CONCLUSIONS: Pressure-controlled rather than volume-controlled ventilation can improve the effectiveness of mechanical ventilation in patients with high airway pressure.
Adult↗
Reverse engineering of metabolic pathways from observed data using genetic programming.
Recent work has demonstrated that genetic programming is capable of automatically creating complex networks (such as analog electrical circuits and controllers) whose behavior is modeled by linear and non-linear continuous-time differential equations and whose behavior matches prespecified output values. The concentrations of substances participating in networks of chemical reactions are also modeled by non-linear continuous-time differential equations. This paper demonstrates that it is possible to automatically create (reverse engineer) a network of chemical reactions from observed time-domain data. Genetic programming starts with observed time-domain concentrations of input substances and automatically creates both the topology of the network of chemical reactions and the rates of each reaction within the network such that the concentration of the final product of the automatically created network matches the observed time-domain data. Specifically, genetic programming automatically created metabolic pathways involved in the phospholipid cycle and the synthesis and degradation of ketone bodies.
Biomedical Engineering↗
[Pathological factors involved in lymph node status determination in colorectal carcinoma: analysis of 166 cases with long-term follow-up].
Lymph node status has great clinical importance in the management of patients with colorectal cancer. Several pathologic factors may affect the accuracy of nodal status assessment in this tumor type. The aim of the present study was to evaluate, in a series of 166 stage II and stage III colorectal adenocarcinomas, the following pathologic parameters: number of lymph nodes recovered and examined, number of lymph nodes with metastases, and number of tumor nodules (TNs) in the perirectal or pericolic adipose tissue greater or smaller than 3 mm in diameter (TNs > 3 mm and TNs < 3 mm, respectively). The prognostic significance of these parameters, as well as of other histopathologic variables, was determined using univariate and multivariate survival analyses. Our results indicate that the examination of a small number of regional lymph nodes may result in understaging of tumors classified as pN0 (stage II). In addition, our data suggest that TNs > 3 mm and TNs < 3 mm represent distinct pathologic entities. TNs > 3 mm should be considered the prognostic equivalent of lymph node metastases as recommended by the 1997 TNM classification. In contrast, TNs < 3 mm probably originate by intravascular or perivascular tumor extension. Their presence is associated with adverse clinical outcome in stage III patients, regardless of the number of lymph node metastases.
Adenocarcinoma↗
Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability.
BACKGROUND: Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at > or = 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at < 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. METHODS: MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. RESULTS: The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P < 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86. 0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. CONCLUSIONS: Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.
Adaptor Proteins, Signal Transducing↗
Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes.
Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGFbetaRII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGFbetaRII and BAX first, followed by frameshifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits.
Adenosine Triphosphatases↗
Carotid endarterectomy in an awake patient with contralateral carotid occlusion: influence of selective shunting.
The objectives of this study were to determine whether the presence of a contralateral carotid occlusion increases risk and whether the perioperative results are influenced by a systematic or selective policy of shunting during carotid endarterectomy (CEA) in an awake patient. In a retrospective study we compared patients with and without contralateral carotid occlusion (group I, n = 198 - group II, n = 1068) who required CEA. In 77 patients of group I, a shunt was systematically adopted (subgroup A); in the other 121 patients (subgroup B) and in all patients of group II a selective shunting policy was adopted. The risk for the patients with contralateral carotid occlusion was not significantly higher than that for patients without occlusion. Results were not influenced by systematic/selective shunting policy, and the incidence of signs of cerebral ischemia was higher in patients with contralateral carotid occlusion.
Aged↗
Microsatellite instability in multiple colorectal tumors.
Tumor multiplicity is a hallmark of hereditary cancers: in the colon-rectum multiple tumors represent 5-10% of all colorectal cancer cases. A portion of these cases belongs to hereditary non-polyposis colorectal cancer (HNPCC), a genetic cancer syndrome due to mismatch repair (MMR) gene mutations, phenotypically expressed as microsatellite instability (MSI); the majority of multiple tumors, however, is apparently without any family history. We analyzed 78 (38 synchronous and 40 metachronous) neoplasms from 37 patients with multiple tumors of the large bowel, both HNPCC and sporadic, with the aim of identifying a common genetic basis in multiple tumors. DNA was extracted from normal and cancerous formalin-fixed tissue and was analyzed for MSI using 6 markers. Tumors showing MSI in at least 2 of 6 microsatellite loci were defined as MSI(+). The overall number of MSI(+) tumors was 22 (28.2% of the total). A significant difference in the rate of MSI(+) between HNPCC and sporadic tumors was observed (85% vs. 17%). In the same patients, the MSI phenotype of synchronous tumors (both HNPCC and sporadic) tended to be more concordant than that of the metachronous ones. The higher frequency of MSI in HNPCC than in sporadic tumors, even when multiple, suggests that the involvement of MMR genes in the pathogenesis of the sporadic cases may be uncommon, thus confirming that screening for MSI in multiple colorectal tumors could be a useful tool in the identification of HNPCC in the general population.
Colorectal Neoplasms↗
Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival.
PURPOSE: Recent studies suggest the existence of a distinct class of poorly differentiated large bowel adenocarcinomas, usually termed medullary-type adenocarcinomas (MTAs). The aim of the present study was to accurately define the clinical, histopathologic, biologic, and genetic features of this tumor type. MATERIALS AND METHODS: Among 1,265 surgically resected sporadic colorectal carcinomas, 45 MTAs were identified on the basis of the following criteria: predominantly solid growth pattern (at least 70% of the tumor area) and lack of marked nuclear pleomorphism. The clinicopathologic, biologic, and genetic characteristics of MTAs were compared with those of a series of 457 common glandular colorectal adenocarcinomas. RESULTS: The significantly different clinicopathologic features of MTAs were proximal location, large size, invasion into adjacent organs, expanding pattern of growth, low incidence of distant metastases, more frequent conspicuous peritumoral lymphocytic infiltration, and Crohn's-like lymphoid reaction. Furthermore, young patients with MTAs often demonstrated a family history highly suggestive of a hereditary background. Unlike glandular adenocarcinomas, the large majority of MTAs were DNA diploid by flow cytometric analysis (21 of 25, 84%) and p53 negative by immunohistochemistry (36 of 41, 87.8%). In addition, 18 of the 20 MTAs examined by DNA microsatellite analysis demonstrated widespread microsatellite instability (90% of cases). Patients with MTAs showed a better clinical outcome with respect to patients with common poorly differentiated adenocarcinomas (PDAs) (P <.0001) and well- or moderately differentiated adenocarcinomas (WMDAs) (P =.133). In particular, none of the 33 patients with completely resectable stage II and III MTAs developed tumor recurrence during the observation period. Conversely, 24.7% of patients with stage II and III WMDAs and 48.9% of patients with stage II and III PDAs, who had undergone curative surgical resection, died of recurrent disease (P =.01 and P <.0001, respectively). CONCLUSION: All these data strongly indicate that MTAs represent a distinct pathologic entity, with specific histologic appearance and peculiar clinical and genetic features. These tumors need to be classified separately from other poorly differentiated colorectal carcinomas.
Adenocarcinoma↗
[Colorectal adenoma-carcinoma. Guidelines and minimal diagnostic criteria. Italian Group for Pathology of the Digestive System].
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Adenocarcinoma↗
Chromosome 18q allelic loss and prognosis in stage II and III colon cancer.
The prognostic significance of chromosome 18q allelic loss was evaluated in a series of 118 patients with curatively resected TNM stage II or stage III colon cancer. Chromosome 18q status was determined on frozen tumour samples, using microsatellite markers and the polymerase chain reaction (PCR). Mean follow-up in surviving patients was 75.9 months. Chromosome 18q allelic loss was significantly related to tumour site, extramural venous invasion, flow cytometric nuclear DNA content and p53 protein expression. Patients whose tumour had no evidence of chromosome 18q allelic loss showed a better disease-free and overall survival than patients whose tumour demonstrated 18q allelic loss. When patients were stratified by tumour stage, a significant survival advantage for patients whose tumour had no allelic loss on chromosome 18q was observed in stage II as well as in stage III disease. In particular, patients with stage II disease whose tumour had no chromosome 18q allelic loss demonstrated an excellent clinical outcome, with a 5-year disease-free survival rate of 96%. In contrast, the 5-year disease-free survival rate of patients with stage II disease and chromosome 18q allelic loss was only 54%. In multivariate analysis, status of chromosome 18q was the only significant independent prognostic factor for both disease-free and overall survival. These results indicate that assessment of chromosome 18q status provides relevant prognostic information in colon cancer and might be employed in the selection of patients for adjuvant therapy.
Adult↗
Prognostic significance of DNA ploidy in patients with stage II and stage III colon carcinoma: a prospective flow cytometric study.
BACKGROUND: The prognostic value of flow cytometric DNA ploidy in colorectal carcinoma has not been defined clearly. Most previous studies were conducted retrospectively using archival formalin fixed, paraffin embedded tumor samples. Conversely, few data on prospective studies employing fresh or frozen tissue specimens are available. There is general agreement that fresh/frozen material is more reliable than paraffin embedded tissue for DNA ploidy analysis by flow cytometry. METHODS: In the current investigation we evaluated the prognostic significance of nuclear DNA content in a prospective series of 191 patients with curatively resected TNM Stage II (n = 107) or Stage III (n = 84) sporadic colon carcinomas. DNA ploidy status was assessed by flow cytometry utilizing multiple frozen tumor samples. Mean follow-up in surviving patients was 48.5 months (median, 46.9 months; range, 29-77 months). The Cox proportional hazards model was used to adjust for several clinical and pathologic covariates. RESULTS: Of the 191 carcinomas examined, 47 (24.6%) were classified as DNA diploid and 144 (75.4%) as DNA aneuploid. DNA ploidy pattern was significantly related to tumor site (P < 0.0001), histologic type (P = 0.0002), and grade of differentiation (P = 0.009), but not to other clinical and pathologic variables. Patients with DNA diploid tumors showed a better disease free (P = 0.013) and overall survival (P = 0.021) than patients with DNA aneuploid adenocarcinomas. In particular, patients with Stage II DNA diploid tumors (n = 30) had an excellent clinical outcome, with an overall 5-year survival rate of 97%. When patients were analyzed according to the anatomic site of the tumor, a significant relationship between DNA ploidy status and disease free and overall survival was observed in the group of patients with carcinomas of the proximal colon (n = 84) (P = 0.004 and P = 0.002, respectively), but not among patients whose tumors were sited distally to the splenic flexure (n = 107). In multivariate analysis, nuclear DNA content was demonstrated to be an independent prognostic variable for both disease free and overall survival. Furthermore, in the group of patients with tumors of the proximal colon, DNA ploidy pattern was the single most important prognostic factor. CONCLUSIONS: Our results confirm that flow cytometric DNA ploidy status is a significant and independent prognostic factor in patients with colon carcinoma. These findings may have clinical implications for the management of affected patients, especially those with Stage II disease.
Adenocarcinoma↗