Suppression of maintenance of alcohol-drinking behavior by the concurrent availability of saccharin in Sardinian alcohol-preferring (sP) rats.

In the current study, we investigated the effect of the concurrent presentation of saccharin on the maintenance of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Rats were initially given access to alcohol [10% (volume/volume) in water] and water under the home cage, two-bottle, free-choice regimen, with unlimited access for 24 h/day for eight consecutive weeks. Next, a third bottle, containing saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], was concomitantly offered for an additional 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, with the 0.1% saccharin solution being the highest accepted. Alcohol intake was a U function of saccharin concentration, being reduced by 65%-95% in the group of rats exposed to the 0.1% saccharin solution. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin markedly reduced alcohol intake in alcohol-experienced sP rats and (2) the reducing effect of saccharin solutions on the alcohol intake in sP rats was positively related to their degree of acceptability. We hypothesized that saccharin solutions may have functioned as a reinforcer, partially substituting for alcohol reinforcement and rendering alcohol drinking less urgent.     

Physician attitudes regarding cardiovascular risk reduction: the gaps between clinical importance, knowledge, and effectiveness.

Reducing risk factors for patients with vascular disease can reduce the subsequent incidence of cerebro-cardiovascular disease. While physicians have had extensive training in the importance of atherosclerotic vascular disease risk factor modification, evidence suggests that they systematically miss opportunities for clinical prevention during routine practice. The aim of this study was to identify whether physicians felt confident in their knowledge and effectiveness regarding counseling patients to reduce cardiovascular risk and to determine barriers to prevention interventions in the office setting. Surveys were mailed to 509 physicians affiliated with an academic community hospital. Nonrespondents were sent reminders and a second survey. Comparisons were made using chi-square analysis. Two hundred and five surveys were returned (40.3%). Thirty-six percent of physicians felt knowledgeable about weight management techniques, compared to 3% who were confident that they succeeded in their practice (p < 0.001). Similar patterns were found for Tobacco Cessation (62% versus 14%, p = 0.001), Alcohol Reduction (46% versus 7%, p < 0.001), Stress Management (35% versus 5%, p < 0.001), Exercise (53% versus 10%, p < 0.001), Nutrition (36% versus 8%, p < 0.001), Diabetes Management (48% versus 23%, p < 0.001), Blood Pressure Management (57% versus 43%, p < 0.001) and Lipid Management (59% versus 38%, p < 0.001). We identified a significant gap between physician confidence in their knowledge about risk factors and their effectiveness at providing counseling and obtaining results in their office. Most physicians felt that the routine office follow-up visit was an ineffective method for instituting vascular risk factor reduction. Alternate settings for risk factor reduction may be needed for improving atherosclerosis prevention.     

Presence of delayed myelination and macrocephaly in the sister of a patient with vacuolating leukoencephalopathy with subcortical cysts

Leukoencephalopathy with swelling and a discrepantly mild clinical course ("van der Knaap disease") is a recently identified syndrome. It is characterised by macrocephaly occurring during the first year of life, initially normal or nearly normal development, and slowly progressive ataxia and spasticity with initial preservation of intellectual functions. MRI shows diffuse abnormality in signal intensity, as well as swelling of the hemispheral white matter with subcortical cyst-like spaces in the fronto-parietal and anterior temporal areas. It is thought to have an autosomal recessive mode of inheritance, since many patients have consanguineous parents and more than one affected patient is often present within the same family. We report on two sibs: a 5-year old boy affected with "van der Knaap disease" and his macrocephalic sister whose first MRI (2 years 6 months) showed delayed myelination, which led us to suspect the same disease as her brother, however with subsequent normalisation at the second MRI (3 years 6 months).     

Distinct roles for GFRalpha1 and GFRalpha2 signalling in different cranial parasympathetic ganglia in vivo

Neurturin (NRTN), signalling via the GDNF family receptor alpha2 (GFRalpha2) and Ret tyrosine kinase, has recently been identified as an essential target-derived factor for many parasympathetic neurons. NRTN is expressed in salivary and lacrimal glands, while GFRalpha2 and Ret are expressed in the corresponding submandibular, otic and sphenopalatine ganglia. Here, we have characterized in more detail the role of GDNF and NRTN signalling in the development of cranial parasympathetic neurons and their target innervation. Gfra1 mRNA was expressed at E12 but not in newborn cranial parasympathetic ganglia, while Gfra2 mRNA and protein were strongly expressed in newborn and adult cranial parasympathetic neurons and their projections, respectively. In newborn GFRalpha1- or Ret-deficient mice, where many submandibular ganglion neurons were still present, the otic and sphenopalatine ganglia were completely missing. In contrast, in newborn GFRalpha2-deficient mice, most neurons in all these ganglia were present. In these mice, the loss and atrophy of the submandibular and otic neurons were amplified postnatally, accompanied by complete loss of innervation in some target regions and preservation in others. Surprisingly, GFRalpha2-deficient sphenopalatine neurons, whose targets were completely uninnervated, were not reduced in number and only slightly atrophied. Thus, GDNF signalling via GFRalpha1/Ret is essential in the early gangliogenesis of some, but not all, cranial parasympathetic neurons, whereas NRTN signalling through GFRalpha2/Ret is essential for the development and maintenance of parasympathetic target innervation. These results indicate that GDNF and NRTN have distinct functions in developing parasympathetic neurons, and suggest heterogeneity among and within different parasympathetic ganglia.     

Is cell-mediated immunity affected by laparoscopic cholecystectomy?

It is well known that surgery significantly decreases cell-mediated immunity. Laparoscopic cholecystectomy is a so-called minimally invasive surgical procedure, and on the basis of this consideration we investigated whether and how the immune system is modified in patients after laparoscopic cholecystectomy compared to those undergoing open cholecystectomy. Immune activity (neutrophils, total lymphocyte count, lymphocyte subpopulations, multiple skin tests) was evaluated in 82 patients on postoperative day 1 and on postoperative days 1, 3 and 6. Forty-two patients underwent open cholecystectomy and 40 laparoscopic cholecystectomy. On postoperative day 1 patients treated by open cholecystectomy showed a significant increase (P < 0.05) in plasma neutrophils, whereas this parameter was unchanged in patients undergoing laparoscopic cholecystectomy. Skin tests revealed a hypo- or anergic response in the majority of patients (81.8%) undergoing open surgery compared to those treated laparoscopically (10.5%). Total lymphocyte count and lymphocyte subpopulations were normal in the two groups. Four cases of respiratory tract infection (4.8%) were detected after open cholecystectomy. Laparoscopic cholecystectomy substantially reduces postoperative pain and hospitalisation, promotes an earlier recovery and return to normal activity and is not associated with postoperative immunosuppression, with a more positive postoperative morbidity profile compared to open surgery.     

Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.

PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.     

Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.     

Assessment of chitosan derivatives as buccal and vaginal penetration enhancers.

The aim of the present work was to evaluate the mucoadhesive and penetration enhancement properties via the buccal and vaginal mucosae of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan (MPC), two low molecular weight chitosans (DC1 and DC2) and a partially reacetylated chitosan (RC). Chitosan HCl was used as a reference. Polymer solutions (4% w/w) were prepared in media simulating the buccal (pH 6.4 buffer or water) and the vaginal (pH 5.0 buffer) environments and subjected to rheological characterization. Acyclovir was added to the polymer solutions at 5% (w/w) concentration. The mucoadhesive properties of the polymer solutions were measured using excised porcine cheek or vaginal mucosa and mucin dispersions to simulate the buccal or vaginal environments, respectively. Drug permeation and penetration tests were carried out using porcine cheek and vaginal mucosae as model membranes. Acyclovir aqueous suspensions prepared in pH 6.4 and 5.0 buffers were used as blanks. Drug release measurements were also carried out in the same conditions employed for the permeation and penetration tests. Methyl-pyrrolidinone chitosan shows the best mucoadhesive and penetration enhancement properties in both buccal and vaginal environments. The capability to enhance the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial reacetylation.     

Boerhaave syndrome. A case report and review of the literature

Spontaneous esophageal perforation (Boerhaave's syndrome) remains a difficult diagnostic and management problem with controversial recommendations regarding its treatment. The clinical manifestations of the disease are variable, and may be misleading, thus delaying accurate recognition. On the other hand, in view of the rapid onset of severe complications, particularly mediastinitis, a prompt diagnosis is essential to a better prognosis, successful operative outcome and potential survival. A case of spontaneous perforation of the thoracic esophagus penetrating the left pleural space treated within 4 hours from admission to the Emergency Room, with minimal surgical intervention is presented. Despite negative chest X-ray, a thoracic TC showed a small right sided effusion with left sided hydropneumothorax, and the definitive diagnosis was obtained by contrast study with a water soluble medium which showed the leak communicating freely with the left pleural space. The patient underwent repair by thoracic approach, the rupture was closed with a primary suture without flap reinforcement and the pleural space drained with the placement of single chest thoracostomy tube. The recovery was uneventful. The analysis of this case report and of the appropriate literature reveals that a poor prognosis is correlated with the time elapsed between the perforation and treatment. In conclusion the importance of an early aggressive surgical treatment for the Boerhaave's syndrome is emphasized, because any perforation treated more than 24 hours after the onset of symptoms, irrespective of the procedure used, is associated with a significantly higher morbility and mortality.     

Intraoperative sestamibi scanning in reoperative parathyroidectomy

BACKGROUND: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations. PATIENTS AND METHODS: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay. RESULTS: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels. CONCLUSIONS: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.