Impact of Induction Chemotherapy and Preoperative Chemoradiotherapy on Operative Morbidity and Mortality in Patients with Locoregional Adenocarcinoma of the Stomach or Gastroesophageal Junction

Background Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX–CTXRT). However, the influence of CTX–CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX–CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma. Methods A prospectively collected database on 71 consecutive patients who underwent CTX–CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis. Results Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50–50.6)] and body mass index (BMI) of 26 kg/m² or above [relative risk 4.08 (95% confidence interval 1.08–15.4)] were significant risk factors for overall complications. Conclusions CTX–CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.     

Comparative analysis of mRNA and protein expression of Popdc1 (Bves) during early development in the chick embryo.

The isolation of the Popeye gene family was based on its preferential expression in striated muscle tissue. Recently, a monoclonal antibody against chick Popdc1 (also known as Bves) became available and was used in this study to comparatively analyze the expression pattern of Popdc1 at both the protein and mRNA level during early chick embryogenesis. Using whole-mount immunohistochemistry, expression in the heart was first observed at Hamburger and Hamilton (HH) stage 10 in the presumptive left ventricular segment. Cardiac expression was confined to differentiated cardiac myocytes, and undifferentiated myocytes at the anterior and posterior pole showed little expression. After looping, the outer curvature myocardium showed prominent Popdc1 staining, whereas the inner curvature was unlabeled. Despite previous reports, Popdc1 protein was not detectable at any time point in the proepicardium, epicardium, or the smooth muscle layer of the coronary vessels. Whole-mount in situ hybridization using a full-length Popdc1 probe detected novel expression domains, which have not been described previously. Popdc1 mRNA was found in Hensen's node at HH stage 4, and by HH stage 5+, expression became asymmetric. In addition, Popdc1 mRNA was found in pharyngeal endoderm and in the notochordal plate. Subsequently, beginning at HH stage 9, Popdc1 mRNA expression was found in the cardiac mesoderm and expression was maintained in the heart in a pattern very similar to the one observed by antibody staining.     

Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial.

BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis. METHODS: We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate. RESULTS: We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90). CONCLUSIONS: We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.     

Resolution of peripheral artery catheter-induced ischemic injury following prolonged treatment with topical nitroglycerin ointment in a newborn: a case report.

Tissue ischemia, necrosis, and gangrene are uncommon but well-described complications of arterial catheterization in the neonate. Treatment options for progressive tissue necrosis following arterial embolization and/or vasospasm are limited in these patients secondary to unpredictable pharmacokinetics and risks associated with systemic anticoagulation or vasodilatation in newborns. We report a case of a multidose regimen of topical 2% nitroglycerin ointment for reversing severe tissue ischemia following peripheral arterial line placement. The favorable response in this infant suggests that topical nitroglycerin therapy should be considered as potential therapy to ameliorate the effects of vascular compromise following arterial line placement in neonates.     

Superior Transseptal Approach for Surgical Removal of Left Atrial Myxoma

A bstract Eight patients (4 men, 4 women), mean age 51 years, referred to our Institution for left atrial myxoma underwent removal of the tumor through a superior transseptal approach. All patients in sinus rhythm with normal conduction time. The myxomas were localized in the fossa ovalis (3 cases), interatrial septum (2 cases), left appendage (2 cases), and mitral annulus (1 case). One patient died in hospital after emergency operation for low-output syndrome complicated by septic shock. All other patients had an uneventful postoperative course. Atrial arrhythmias did not represent a major postoperative complication. Transient PR interval elongation was occasionally seen. Electrophysiological studies showed normal sinus node function. At 6 months following operation, patients were evaluated with transeso-phageal echocardiography. There was no tumor recurrence. There were no episodes of arrhythmia in 24-hour electrocardiographic monitoring, and all patients were in NYHA Class I. We believe that the superior transseptal approach gives optimal exposure of the left atrial cavity, overcoming all difficulties related to a small left atrium which is an usual pattern in left atrial myxomas.     

Effects of pyridostigmine on spontaneous and growth hormone-releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation

OBJECTIVES: We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)-releasing hormone (GHRH)-induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients. DESIGN: We performed a randomized, single-blind, cross-over study. PATIENTS: We studied three male and three female juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose +/- SEM, 5.92 +/- 0.63 mg/day) and five normal children (four males, one female). MEASUREMENTS: Both nocturnal spontaneous and morning GHRH-induced GH secretion were evaluated after administration of placebo, 1 tablet p.o., or pyridostigmine, 2 mg/kg p.o. RESULTS: Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10.8 +/- 2.0 mU/l) was not significantly different with respect to normal children (mean GH level 12.8 +/- 1.2 mU/l); pyridostigmine: nocturnal GH secretion was significantly increased as compared to placebo in subjects with liver transplantation but not in normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P less than 0.05) increased as compared to placebo and did not differ significantly in the two groups. CONCLUSIONS: Our data suggest a steroid-mediated increase in hypothalamic somatostatin tone in liver transplanted children.     

-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats

L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria.     

Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction.

Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals.     

Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.