Emergence of Salmonella enteritidis outbreaks in broiler chickens in the Lebanon: epidemiological markers and competitive exclusion control

This study investigates the first emergence of Salmonella Enteritidis outbreaks among chickens in the Lebanon and identifies the epidemiological markers of selected recovered Enteritidis strains. In addition, the authors evaluate a competitive exclusion approach to control infection in broiler chickens by Enteritidis organisms which possess the prevalent identified markers. The basic procedure in this investigation involved recording signs and lesions in eleven broiler chicken flocks on eleven farms, and culturing livers, spleens, and caeca of ten randomly selected birds per flock for Salmonella isolation and serotyping. Furthermore, culturing for Salmonella and serotyping was attempted from the livers, spleens, caeca and oviduct swabs of ten hens in four broiler breeder flocks which provided hatching eggs for the broilers under study. The identification of epidemiological markers in recovered S. Enteritidis included the determination of drug-resistance patterns and plasmid profiling. The competitive exclusion was evaluated by spraying the microflora on day-old broilers in the hatchery, followed by a controlled oral challenge at three days of age, with 2.85 x 10(5) colony-forming units of S. Enteritidis organisms per bird. Exclusion was evaluated by culturing for S. Enteritidis in anal swabs, spleens, livers, and caeca of individual challenged birds treated with the microflora and in untreated challenged birds. A total of 112 invasive S. Enteritidis strains were recovered on eleven farms from individual organs of broiler chickens with typical signs and lesions of salmonellosis. The prevalent resistance to drugs in such strains was to furaltadone and gentamycin, a marker identified in 93 strains (83%), recovered from nine out of eleven farms. The same resistance pattern was present in S. Enteritidis strains recovered from breeders on one out of four farms. The prevalent plasmid profile in nine S. Enteritidis organisms selected randomly from a pool of 93 strains (one per each of the nine broiler farms) was 14.1 kilobases (kb) and approximately 50.0 kb, a typical pattern to that identified in S. Enteritidis organisms recovered from oviducts of breeders on one out of four breeder farms. The exclusion significantly reduced cumulative mortality in birds of up to 45 days of age by 3.93%, in comparison to that observed in untreated challenged birds (P < 0.05). At 45 days of age, exclusion resulted in a 15.6% reduction in the percentage infection rate by S. Enteritidis in spleens or livers and a 34.4% reduction in the percentage infection rate of the caeca (P < 0.05).     

Dielectric Analysis of Phosphorylcholine Head Group Mobility in Egg Lecithin Liposomes

Purpose. A knowledge of the interfacial properties of lecithin underpins our understanding of many of the physicochemical characteristics of drug delivery systems such as liposomes and lecithin stabilized microemulsions. In order to further this understanding, a high frequency dielectric study of the interfacial properties of egg lecithin liposomes was undertaken. Methods. The effect of temperature, lecithin concentration and probe sonication on the interfacial dielectric properties of liposomal suspensions was investigated by high frequency dielectric relaxation spectroscopy between 0.2–6 GHz. Results. The frequency dependent permittivity of each suspension exhibited a dielectric dispersion centred around 100 MHz, corresponding to the relaxation of zwitterionic head groups. The activation energy for head group reorientation was estimated as H = 6.3 kJ mol^–1. There was an increase in extent of inter-head group interactions on increasing the liposome volume fraction, whereas the effect of probe sonication showed that: (i) head groups in both the outer and inner lamellae contribute to the dielectric response; (ii) the head groups may be less restricted in liposomes of high surface curvature with few lamellae; (iii) the high frequency permittivity of the suspension increased on sonication, as a result of a reduction in the amount of (depolarized) interlamellar water following a reduction in the number of lamellae per liposome. Conclusions. Dielectric analysis of the zwitterionic head groups of lecithin therefore provides a means for investigating the surface of lecithin liposomes, and may be used to investigate the effect of drugs and other solutes on membranes.     

Pharmacokinetic Analysis and Antiepileptic Activity of Tetra-Methylcyclopropane Analogues of Valpromide

Purpose. The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetra-methylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. Methods. The study was carried out by investigating the pharmacokinetics in dogs and pharmacodynamics (anticonvulsant activity and neurotoxicity) of the following three cyclopropane analogues of VPD: 2,2,3,3-tetramethylcyclopropane carboxamide (TMCD), N-methyl TMCD (M-TMCD) and N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycinamide (TMC-GLD). Results. The three investigated compounds showed a good anticonvulsant profile in mice and rats due to the fact that they were metabolically stable VPD analogues which were not biotransformed to their non-active acid, 2,2,3,3-tetramethylcyclopropane carboxylic acid (TMCA). M-TMCD was metabolized to TMCD and TMC-GLD underwent partial biotransformation to its glycine analogue N-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-glycine (TMC-GLN). Unlike TMC-GLN, the above mentioned amides had low clearance and a relatively long half life. Conclusions. In contrast to VPD which is biotransformed to VPA, the aforementioned cyclopropane derivatives were found to be stable to amide-acid biotransformation. TMCD and M-TMCD show that cyclic analogues of VPD, like its aliphatic isomers, must have either two substitutions at the position to the carbonyl, such as in the case of TMCD, or a substitution in the and in the positions like in the VPD isomer, valnoctamide (VCD). This paper discusses the antiepileptic potential of tetramethylcyclopropane analogues of VPD which are in animal models more potent than VPA and may be non-teratogenic and non-hepatotoxic.     

Tissue-conserving surgery for prognosis,treatment, and function preservation

Objectives: To describe an approach based on initial tissue-conserving surgery used to obtain histologically determined prognostic information that has therapeutic implications and the potential to enhance preservation of function. Study Design: Analysis of a group of patients with head and neck cancer treated initially with tissue-conserving surgery based on Mohs' histographic sectioning and selected neck dissection to derive histologically determined prognostic information with therapeutic implications and preservation in function. Methods: This study is primarily based on an analysis of patients from January 1, 1989, through June 4, 1996 assigned to a protocol evaluating resection of oral cavity squamous cell cancer with margin control using Mohs' histographic technique and/or a group of patients with neck assessment of N0 on clinical examination who are undergoing supraomohyoid neck dissections. Results: Thirty-three primary tumor resections were performed using the Mohs' technique, and 54% required two or more Mohs' sections before clear histologic margins were obtained following resection based on clinically determined negative margins. There were 44 patients who underwent unilateral or bilateral supraomohyoid neck dissections, and 33% had occult, histologically positive nodes. When compared with the disease of the neck specimens, a preoperative computed tomography scan had a sensitivity of 25%, a specificity of 77%, and an accuracy of 63%. Conclusions: This report describes the effectiveness of Mohs' histographic sectioning and selective neck dissection as a means of determining prognostic information that can be used to develop a focused and cost-effective treatment program that, along with contemporary reconstructive techniques, provides a potential enhancement of function preservation. Laryngoscope, 108:1599–1604, 1998     

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.     

Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.

Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.     

The role of lymphadenectomy in the management of renal cell carcinoma

The role of lymphadenectomy in the management of renal cell carcinoma has been established in staging but is less well defined as a therapeutic maneuver. Level one evidence suggests no survival benefit or increased complication rate with lymphadenectomy when performed concurrently with radical nephrectomy. However, several retrospective studies have identified a survival benefit when patients with increased risk of micrometastatic lymph node disease undergo lymphadenectomy. We perform a selective review of the literature and present the historical basis, risk assessment, use and development of nodal templates, and therapeutic benefits associated with the use of lymphadenectomy in the management of renal cell carcinoma.