Investigating the genetic role of aquaporin4 gene in migraine

Aquaporin4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. The purpose of our work was to evaluate the association of polymorphisms in the AQP4 gene with the risk and the clinical features of migraine. A total of 293 migraineurs and 249 controls were involved in the study. They were genotyped for four single nucleotide polymorphisms (SNPs) of AQP4 gene. No significant difference in the distribution of AQP4 genotypic and allelic frequencies between cases and controls was found. In addition, haplotype analysis did not show any significant difference. Comparison of the clinical features of the disease according to different AQP4 genotypes showed no significant difference. Our data do not support the hypothesis that the AQP4 gene could represent a genetic susceptibility factor for migraine.     

Intraportal hepatocyte transplantation in the pig: hemodynamic and histopathological study

BACKGROUND: Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs. METHODS: Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min. RESULTS: The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal. CONCLUSION:. These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.     

The role of 99mTc-tetrofosmin scintigraphy for staging patients with laryngeal cancer

Diagnosis and staging of laryngeal cancer is currently based on physical examination, endoscopy, and imaging techniques such as computed tomography (CT) and/or magnetic resonance (MR) and histology. While imaging techniques have a pivotal role for defining the size of the primary tumor, they are less accurate for defining metastatic involvement of regional lymph nodes, especially if lymph nodes are smaller than 10-15 mm. The aim of this study was to comparatively assess the relevance of (99m)Tc-tetrofosmin scintigraphy for the staging of laryngeal tumors versus the CT scan. We evaluated the sensitivity of imaging with (99m)Tc-tetrofosmin in 28 consecutively enrolled patients with squamous cell laryngeal carcinoma. Total-body scintigraphy with 99mTc-tetrofosmin was performed preoperatively, and the results were compared to CT images of the neck and mediastinum. CT and (99m)Tc-tetrofosmin scintigraphy were equally sensitive (96%) in identifying the primary tumor. While CT was more sensitive for detecting metastatic lymph nodes (100% versus 50%), (99m)Tc-tetrofosmin scintigraphy was more specific (100% versus 56%; p < 0.04). The overall diagnostic capabilities of the two techniques for detecting lymph node metastases were comparable (Youden Index: J = 0.56 for CT and J = 0.50 for (99m)Tc-tetrofosmin scintigraphy). (99m)Tc-tetrofosmin scintigraphy is a useful complement to CT for staging laryngeal tumors, especially for detecting metastatic lymph nodes and distant metastases.     

Familiar history and predictive risk factors to type 2 diabetes: a cross sectional study in young Sicilian subjects of both sexes

AIM: For many industrialised populations, family history to type 2 diabetes mellitus (DM) is a risk factor to the development of illness, inducing early anthropometric and metabolic modifications. Aim of this study was to confirm in Sicilian population the influence of family history to type 2 DM on anthropometric data and basal blood pressure, considering the different degrees of familiar history to illness. METHODS: In a cohort of 680 young healthy Sicilian subjects (278 men and 402 women) we analysed the relations of family history degree of DM on anthropometric data, such as body mass index (BMI), waist/hip ratio (WHR) and triceps skinfold. Degree of family history of DM was defined as presence in the family of at least one sibling of first degree or a parent with documented DM (FHDM++), of at least one family member of second degree with documented DM (FHDM+). RESULTS: In both sexes the FHDM++ groups showed the highest values of body weight (P<0.001 for men, P<0.0001 for women), BMI (P<0.0005 for both sexes), WHR (P<0.0001 for men, P<0.01 for women), triceps skinfold (P<0.0001 for men, P<0.001 for women), with consequently higher proportion of obesity and overweight in the group with FHDM++. Subjects with FHDM+ were closer to control subject without family history of DM. FHDM++ was also associated with tendency to higher diastolic and systolic blood pressure values in both sexes. CONCLUSIONS: The study shows that young subjects with familiar history of type 2 diabetes have a higher prevalence of overweight and central obesity compared to other groups, suggesting that obesity in adolescents and young adults may be a strong pathophysiologic mechanism predictive of higher degree of future development of type 2 diabetes and hypertension.     

Structure-based phylogeny of the metallo-beta-lactamases

The metallo-beta-lactamases fall into two groups: Ambler class B subgroups B1 and B2 and Ambler class B subgroup B3. The two groups are so distantly related that there is no detectable sequence homology between members of the two different groups, but homology is clearly detectable at the protein structure level. The multiple structure alignment program MAPS has been used to align the structures of eight metallo-beta-lactamases and five structurally homologous proteins from the metallo-beta-lactamase superfamily, and that alignment has been used to construct a phylogenetic tree of the metallo-beta-lactamases. The presence of genes from Eubacteria, Archaebacteria, and Eukaryota on that tree is consistent with a very ancient origin of the metallo-beta-lactamase family.     

Differences between measured and resultant joint moments during voluntary and artificially elicited isometric knee extension contractions

OBJECTIVE: Examine two hypotheses: (a) during isometric knee extension contractions the moment measured at the dynamometer is different from the resultant moment in the same plane around the knee joint and (b) during isometric contractions, at the same given resultant moment the knee angle while loading is different from the knee angle while unloading. DESIGN: Comparative study in which the geometrical and the kinetic differences between joint and dynamometer were determined. BACKGROUND: It is usually assumed that the moment measured by the dynamometer is equivalent to the resultant joint moment. The non-rigidity of the dynamometer-leg system can influence the equivalence of these two moments. METHOD: Twenty seven subjects performed isometric maximal knee extension contractions and contractions induced by electrostimulation on a dynamometer. The kinematics of the leg were recorded using 8 cameras (120 Hz). RESULTS: The resultant moment at the knee joint and the moment measured by the dynamometer are different. During a knee extension effort the knee angle changes significantly. At identical resultant knee joint moments the knee angles are different when comparing the loading and the unloading phases. CONCLUSIONS: The differences between the measured and the resultant joint moments might influence the estimation of parameters as: muscle forces, moment-angle relationship and strain and hysteresis of tendons and aponeuroses. RELEVANCE: Torque dynamometers have been often used to estimate muscle forces, to examine neuromuscular processes and to determine the mechanical properties of tendons and aponeuroses.     

Radioguided sentinel lymph node biopsy in patients with malignant cutaneous melanoma: the nuclear medicine contribution

As for other solid tumors, malignant cutaneous melanoma drains in a logical way through the lymphatic system, from the first to subsequent levels. Therefore, the first lymph node encountered (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Sentinel lymph node biopsy distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, and those with metastatic involvement who might benefit from additional therapy. This procedure represents a significant advantage as a minimally invasive procedure, considering that only an average 20% of melanoma patients with Breslow thickness between 1.5 and 4 mm harbour metastasis in their sentinel node(s) and are therefore candidates to elective lymph node dissection procedures. The cells that originate cutaneous melanomas are located between dermis and epidermis, a zone that drains to the inner lymphatic network in the reticular dermis, in turn to larger collecting lymphatics in subcutis. Therefore, the optimal modality of interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is through intradermal/subdermal injection. (99m)Tc-labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas located in the midline area of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the node(s). The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is about 98% in institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. The procedure is becoming the standard of care for patients with cutaneous melanoma because of its high prognostic value that has led to include the procedure in the most recent version of the TNM staging system.     

Mutation, fitness, viral diversity, and predictive markers of disease progression in a computational model of HIV type 1 infection

The aim of this study was to develop a computational model of HIV infection able to simulate the natural history of the disease and to test predictive parameters of disease progression. We describe the results of a numerical simulation of the cellular and humoral immune response to HIV-1 infection as an adaptive pathway in a "bit-string" space. A total of 650 simulations of the HIV-1 dynamics were performed with a modified version of the Celada-Seiden immune system model. Statistics are in agreement with epidemiological studies showing a log normal distribution for the time span between infection and the development of AIDS. As predictive parameters of disease progression we found that HIV-1 accumulates "bit" mutations mainly in the peptide sequences recognized by cytotoxic CD8 T cells, indicating that cell-mediated immunity plays a major role in viral control. The viral load set point was closely correlated with the time from infection to development of AIDS. Viral divergence from the viral quasispecies that was present at the beginning of infection in long-term nonprogressors (LTNP) was found to be similar to that found in rapid progressors at the time CD4 T cells drop below the critical value of 200 cells/microl. In contrast, the diversity indicated by the number of HIV strains present at the same time was higher for rapid and normal progressors compared to LTNP, suggesting that the early immune response can make the difference. This computational model may help to define the predictive parameters of HIV dynamics and disease progression, with potential applications in therapeutic and vaccine simulations.