Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly

Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.     

Gastrointestinal autonomic nerve tumour presenting as small bowel volvulus: a rare disease with a rare presentation

A 78-year-old Chinese woman presented with recurrent postprandial abdominal pain. Computerised tomography revealed a small bowel tumour causing volvulus of a segment of the small bowel. Laparotomy confirmed an extraluminal ileal tumour with partial volvulus of the involved small bowel segment. Small bowel resection was done. Histological and ultrastructural studies confirmed a gastrointestinal autonomic nerve tumour. We review the medical literature on this rare tumour.     

Health trajectories: long-term dynamics among black and white adults

Flow cytometry is a unique technology useful in the examination of effects of immunotoxic agents on target cells of the immune system. The purpose of this workshop was to provide an overview of the use of flow cytometry in new and established models of immunotoxicity, with emphasis on the potential applications, assay validation, and potential pitfalls. This overview begins with a discussion of methods useful in the assessment of Ca2+-dependent mechanisms of lymphoid cell activation in surface marker-defined human B cells, T cells, and monocytes. A discussion of the use of flow cytometry in analysis of apoptosis is also presented in this paper. The second paper presents data on the development and use of flow cytometry as an alternative to a Cr51 release assay for an assessment of cytotoxic T cell activation. The use of surface markers for characterizing and distinguishing the effects of chemical irritants from sensitizers is next presented, followed by an overview of the use of fluorescent probes to assess cell thiol status and overall oxidant-induced injury to lymphoid cells. Finally, an interlaboratory study designed to compare and evaluate the use of flow cytometry procedures in rat splenic cell subtyping is presented. Overall, these studies demonstrate the utility of flow cytometry assays in immunotoxicologic research, but further efforts are needed in the validation of many of these assays for routine use in immunotoxicologic testing.     

Patient preference for self-collected cultures for group B streptococcus in pregnancy

The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.     

Cast titanium as implant material

The tissue response in rats to implants made of machined and cast titanium was evaluated after 1 and 12 weeks. The implants consisted of a circular plate portion, located in the abdominal wall, and a cylindrical rod portion protruding into the peritoneal cavity. The chemical and topographical surface properties of the two types of implants differed considerably. The implants with surrounding tissue were processed en bloc for light and electron microscopy. The bulk metal was removed by an electrochemical procedure which permitted the sectioning and evaluation of the intact implant-tissue interface. The general distribution of macrophages and fibroblasts was the same around the plate portion of both types of implants. Macrophages constituted the predominating cell type with the highest concentration in the innermost cell zone closest to the implant. The number of macrophages per section area was significantly higher around machined implants. Multinuclear giant cells, always located at the implant surface, were more frequent around cast implants. The majority of the intraperitoneal rod portions were partially (1 week) or completely (12 weeks) covered by tissue; partial or complete overgrowth of tissue was rare for machined rod portions. Imaging electron energy loss spectroscopy demonstrated the presence of titanium in macrophages in the peripheral part of the tissue capsule around cast, but not machined implants. We conclude that the tissue responses to the two types of titanium implants differed considerably in the two biological environments (soft tissue in abdominal wall; peritoneal cavity) examined and that the response in one environment does not predict the response in the other. We also believe that improvements have to be made in the casting procedure in order to reduce surface roughness and contamination before cast implants can be used in clinical applications.     

Glomerular tip lesions--a newly described glomerular change

Glomerular tip lesion is a newly described histopathological lesion characterized by a focal and segmental widening of the mesangial matrix without hypercellularity together with capillary dilatation, hyaline exudation on the inside of capillary walls and occurrence of vacuolized cells, localized to the peripheral segments of the glomerular tuft. Clinically, these patients have a pronounced nephrotic syndrome with slightly reduced renal function, but terminal renal failure is seldom seen, even after many years of disorder. Two characteristic case histories are presented. The classification of this lesion among the glomerular disorders is at present uncertain. It may represent a transitional form between minor lesion nephritis and focal segmental sclerosis, a separate disorder, or a functional lesion associated with high proteinuria.     

Implant exudate leucocyte response to anti-inflammatory drug treatment

Implantation of artificial materials elicits a local inflammatory response. In this study a chamber model technique, allowing sampling of the inflammatory exudate for further analysis in vitro, was used. Male Sprague-Dawley rats were injected daily with two different anti-inflammatory drugs, betamethasone and indomethacin, and the local cellular response was compared with a control group. The retrieved exudate was evaluated with respect to the number of leucocytes, cell viability, differential counts and serum-opsonized zymosan stimulated chemiluminescence (CL). In all groups the majority of cells were polymorphonuclear granulocytes (PMNGs). Betamethasone and high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment caused a marked reduction in the number of accumulated leucocytes 6 days after implantation. A substantial inhibition of the CL response was observed 6 days after treatment with betamethasone (4.23 mg kg^-1 body weight day^-1). An increased CL responsiveness was observed after 24 h with low-dose indomethacin (0.03 mg kg^-1 body weight day^-1) and after 6 days with high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment. In summary, depending on the anti-inflammatory drug treatment, dose and time after implant surgery, either an inhibition or stimulation of leucocyte accumulation and activation was observed. This study shows the possibilities of sampling the inflammatory exudate adjacent to a biomaterial implanted in vivo. This chamber model may be useful for the analysis of the inflammatory reaction around an implanted biomaterial during pharmacological treatment.     

Prolonged release Matrix Pellets Prepared by Melt Pelletization I. Process Variables

A melt pelletization process was investigated in an 8 litre laboratory scale high shear mixer using a formulation with paracetamol, glyceryl monostearate 40-50, and microcrystalline wax. The effects of jacket temperature, product temperature during massing, product load, massing time and impeller speed were investigated by means of factorially designed experiments. The maximum yield of pellets in the range of 500-1400μm was found to approx. 90%. For process conditions preventing deposition of moist mass, the process was found to be reproducible. Impeller speed and massing time were found to be important process variables. Remarkably low in vitro drug release rates were observed in USP-dissolution tests.