Differences in response of chickens from two genetic lines to diisopropyl phosphorofluoridate

Neurotoxicity of diisopropyl phosphorofluoridate (DFP) was examined at 85 weeks of age in hens of two lines selected for high (HA) and low (LA) antibody response to sheep erythrocytes. DFP was administered by subcutaneous injection in doses of 0.25, 0.50 and 1.00 mg/kg and hens were observed for cholinergic signs at 30 min and for delayed neuropathy 8 to 14 days post-administration. Toxicity to DFP increased in severity with the dose and genetic differences were present because hens of line HA were more sensitive to DFP than were those of line LA. HA hens also had lower A-esterase activities and higher heterophil-to-lymphocyte ratios. No line x treatment interaction was evident, however, for activities of neurotoxic esterase or brain cholinesterase measured 24 hr after DFP administration.     

Allomorphic relationships from hatching to 56 days in parental lines and F1 crosses of chickens selected 27 generations for high or low body weight

Allomorphic relationships in chickens selected for high or low juvenile body weight and their reciprocal crosses were examined from hatch to 56 days of age (doa). Those organs whose relationships to whole body weight were most divergent in the parental populations were weights of the gizzard, small intestine, breast, legs, feathers, abdominal fat and lengths of the shank, esophagus and small intestine. Relative weights of feathers, abdominal fat and small intestine were influenced mainly by additive genetic variation, whereas relative weights of breast, legs, and gizzard were influenced by additive genetic variation at younger ages (0 to 24 doa) and by both additive and non-additive genetic variation thereafter. In utilization of resources for high growth velocity and growth rate factor, crosses were 20 to 30% more efficient than their parental populations, demonstrating hybrid vigor. Relationships of rate of development of specific organs to total body weight varied with age and were noted as correlated responses to artificial selection for body weight. Selection for high and for low body weight at 56 days of age resulted in compromises in resource allocations. Specifically, selection for high juvenile body weight favored relatively heavier breasts, legs, abdominal fat depots and small intestines while selection for low juvenile body weight favored relatively heavier feathers and gizzard.     

Growth factors as novel therapeutic targets in neoplastic disease

The emerging concept of autocrine/paracrine control of tumour cell proliferation coupled with the identification of several polypeptide mitogens has created new opportunities for the discovery of novel classes of antineoplastic drugs. Growth factors (for example, transforming growth factor alpha, fibroblast growth factor and platelet-derived growth factor) and, in certain cases, their receptors have been identified in a number of human tumours and their expression may contribute to unregulated cell proliferation. Selective antagonists that block the activity of these mediators may have important therapeutic utility in the management of cancer patients, particularly in metastatic disease where patterns of tumour cell dissemination may be strongly influenced by paracrine mediators. However, since many, if not all, of these growth factors are polypeptides with molecular weights over 5 kDa, the discovery of potent antagonists represents an important pharmacological challenge. Advances in understanding protein structure-function relationships will be essential in guiding rational attempts at generating growth factor antagonists through site-directed mutagenesis and peptide synthesis, while better insights into the mechanisms by which growth factors are synthesized, processed, released and exert their mitogenic effects may also reveal new sites for pharmacological assault. The availability of (low molecular weight) potent growth factor antagonists will allow the autocrine/paracrine hypothesis to be clinically tested and in the process will throw considerable light on the function of these growth regulatory molecules in vivo.     

The Impact of Posture on Cardiac Repolarization: More Than Heart Rate?

INTRODUCTION: The effect of standing on heart rate and QT is well known but its impact on QTc is less clear. METHODS: Serial supine and standing 12-lead ECGs (seven pairs each day) were recorded from 54 healthy volunteers each day of a three-day period. ECGs were captured digitally and over-read by a cardiologist. RESULTS: A statistically significant shortening of RR (216 ms), QT (40 ms), and decreases in QTc-F (Fridericia) and QTc-LR (Framingham) were demonstrated on standing (8.3 and 6.9 ms, respectively). In contrast, QTc-B (Bazett's) significantly increased by 9.6 ms. Two subject-individualized correction methods were derived using each subject's supine measurements. Both showed significant decreases in QTc of approximately 13-14 ms upon standing. Using the bin analysis method, comparisons between positions using 25 ms interval RR bins revealed significant QT shortening of up to 15 ms upon standing. CONCLUSION: We have demonstrated a postural effect on cardiac repolarization independent of heart rate using two individualized correction methods, as well as QTc-F and QTc-LR, and the bin method. Characterization of postural differences in QT/QTc (other than QTc-B) may provide a safe and inexpensive physiological control to validate the ECG methodology used in clinical trials to assess potential drug-induced QT interval changes.     

Optimizing the integration of advanced practitioners in a department of surgery: An operational improvement model

Physician assistants (PAs) and nurse practitioners (NPs) have established themselves as key members of the healthcare team to supplement practicing physicians in patient care. PAs and NPs are collectively referred to as “advanced providers” (APs) and work not only in primary care but in general surgery and surgical subspecialties. Studies have addressed AP integration into the profession of medicine and have examined cost and efficacy of APs, attitudes about APs among residents, and educational impact of APs, but very little literature exists that describes a formalized approach to AP integration into a department of surgery, specifically with AP/resident integration. The purpose of this paper is to describe an initiative for developing an operational improvement model for APs working with residents on surgical inpatient services in a large academic health center. The model consists of four components and each component is described in detail from discovery state towards continuous improvement. Formal professional development opportunities for APs as well as appointing a Clinical Director for Surgical APs have positively impacted AP integration into the department of surgery.     

Isolation and properties of cell lines from the metastasising rat mammary tumour SMT-2A

A new cell line Rat mammary (Rama) 900 was isolated from the ascitic version of the SMT-2A metastasising rat mammary tumour by stepwise adaptation of the tumour cells to tissue culture. The cells grew mainly as loosely-adherent aggregates, and were dependent during the first 18 passages in vitro on a feeder layer of mesothelial-like cells (Rama 950) obtained from the same tumour. Subcutaneous injection of Rama 900 cells in fat pads of syngeneic Wistar Furth rats yielded anaplastic primary tumours and extensive, gross metastases including those in lungs, lymph nodes, liver and bones, similar to the parental transplantable tumour. The extent of metastatic spread from subcutaneous fat pads was increased by passage 17 in vitro for the Rama 900 cells. A similar extent of metastatic spread was achieved at earlier times by injecting the original cells with the non-tumorigenic Rama 950 cells in vivo. Subcutaneous injection of Rama 900 into thymectomised rats or MF1 nu/nu mice yielded fewer tumours, most of which regressed. No metastases occurred in the thymectomised rats and fewer metastases, mainly in lungs but not in lymph nodes, livers or bones, were seen in the nude mice. The ascitic tumours formed by intraperitoneal injection of nude mice contained both anaplastic rat cells similar to Rama 900 and mouse mesothelial-like cells similar to Rama 950. Although these anaplastic ascites cells failed to yield any tumours in syngeneic or thymectomised rats, they still produced tumours and metastases, including those in lymph nodes, in nude mice.     

Graft appendiceal fistulas

We report the fifth case of a graft appendiceal fistula. The four previously reported cases are reviewed. This is the first report of the utility of the tagged red blood cell study in the evaluation of a patient with a graft appendiceal fistula.