Exposure to sheep dip and the incidence of acute symptoms in a group of Welsh sheep farmers.

OBJECTIVES: To measure the exposure of a group of farmers to organophosphate pesticide in sheep dip, and to record the incidence of symptoms after exposure. DESIGN: A prospective study of the autumn 1992 dipping period. Working methods were assessed by questionnaire. Absorption of organophosphate pesticide was estimated before, immediately after, and six weeks after dipping by measuring plasma cholinesterase, erythrocyte cholinesterase, and dialkylphosphate urinary metabolites of organophosphates. Symptoms were recorded by questionnaire at the same time as biological monitoring. Possible confounding factors were identified by medical examination of the subjects. SETTING: Three community council electoral wards in Powys, typical of hill sheep farming areas in Wales. SUBJECTS: All (38) men engaged in sheep dipping living in the three community council electoral wards. RESULTS: 23 sheep farmers and one dipping contractor completed the study--a response rate of 63%. A sample of seven men who refused to enter the full study had similar working practices to the 24 subjects. Subjects reported inadequate handling precautions, and significant skin contamination with dip. Two men reported under diluting dip concentrate for use. Both had significant depression of erythrocyte cholinesterase after dipping. This indicated some absorption of organophosphate pesticide--but this did not reach levels usually associated with toxicity. It was not clear whether the symptoms of these two mens were caused by organophosphate exposure. Measurement of dialkylphosphate urinary metabolites in a single specimen of urine voided shortly after the end of dipping could not be correlated with individual exposure. CONCLUSIONS: Sheep dipping is strenuous and dirty work and sheep farmers find it difficult to wear personal protective equipment and avoid skin contamination with dip. In this limited study, farmers did not seem to have significant organophosphate toxicity, despite using inadequate handling precautions.     

Advancing Nursing Practice with a Unit-based Clinical Expert

Objective: To explore patterns in the practice of nursing and patient outcomes.
Design: Qualitative field research.
Population, Sample, Setting: Populations were critical care nurses and critically ill adult patients in the 10-bed medical critical care unit of a 900-bed teaching hospital. A convenience-purposive sample of 27 nurses and 31 patients was studied in 1985.
Methods: Six months of participant observation, unstructured interviews, and the constant comparison method of grounded theory.
Findings: Markedly different patterns were found in expert and nonexpert practice. The substantive theory of conversion helped explain how the majority of nonexpert nurses advanced their practice. The metaphor of catalyzed conversion captures how a unit-based expert nurse serves as a catalyst to advance the practice of nonexperts. Presence, defined as the way of being within a given clinical context, differentiated nurses.
Conclusions: (a) Expert and nonexpert practices are substantively different, (b) Expert and nonexpert practice results in different patient outcomes, (c) Conversion helps explain changes in nonexpert practice.
Clinical Implications: A unit-based expert nurse can increase patient-focused care.     

The mechanism of yohimbine-induced renin release in the conscious rat

Summary These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3–10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the -intercept was positive in every case and the 1 mg/ kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C₈ caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional ₂-adrenoceptors and 3) vasodepressor effects of the larger doses yohimbine cause a baroreflexly-mediated increase in sympathetic activity which interacts in a positive fashion with the central and peripheral sympathoexcitatory effects of yohimbine. Send offprint requests to T. K. Keeton     

Changes in lymphocyte subset distribution aid in the differential diagnosis of renal allograft dysfunction

The distribution of selected lymphocyte subset populations in renal transplant patients was used to assist in the differential diagnosis of graft dysfunction. Patients experiencing dysfunction due to rejection showed consistent and significant decreases in relative numbers of CD 8 (cytotoxic/suppressor) lymphocytes. The ratio of CD 4 cells to CD 8 cells in this group of patients was generally greater than 2.00 due to decreases in CD 8 cells. Patients showing graft dysfunction due to viral infections showed consistent and significant increases in CD 8 cells which also bear the HNK-1 or the HLA-Dr determinants. Serial monitoring for these dual-marked lymphocytes on a weekly basis can be of considerable use in determining the etiology of graft dysfunction. Increases in other "activation" markers, including transferrin receptors, CD 38, and a T cell lineage specific activation antigen (TLiSA) were not specific for rejection; in fact, increases in CD38 were more often associated with viral infections. These studies indicated that lymphocyte subset determinations done on a regular basis can help distinguish graft dysfunction due to viral infections from other causes. The ability to distinguish rejection episodes from stable grafts is less obvious. Although the alterations in lymphocyte subset distribution are not entirely specific, they can distinguish viral infections from rejection.     

Evaluation of stromal metalloproteinases and vascular endothelial growth factors in a spontaneous metastasis model

This study aims to investigate MMP2 and MT1-MMP protein as well as VEGF-C and VEGF-D mRNA expression in tumor cells and distant organs considered to be targets for metastasis in a tumor spontaneous metastasis model previously described. Cultured tumor cells, able to express pro-MMP2, MMP2, pro-MMP9, and MT1-MMP, develop tumor growth and metastasis, mainly in the liver and spleen, when they are injected in the mammary pad gland of Wistar rats. Immunohistochemical studies of tumor masses showed small groups of tumor cells staining for MT1-MMP but not for MMP2. In the liver, tumor metastatic foci and a stromal positive staining for both MMP2 and MT1-MMP were shown. The spleen and lymph nodes, with only scattered metastatic cells, did not show MMPs immunostaining. Using RT-PCR, a significantly higher VEGF-C and VEGF-D gene expression was shown in the liver of tumor-bearing rats respect to normal rats, whereas spleen and lymph nodes did not show significant differences in mRNA VEGF-C/D levels. Taken together, our results suggest that the stroma microenvironment of target organs for metastasis has the ability to produce MMPs and VEGFs that facilitate the anchorage of tumor cells and promote tumor cell growth and angiogenesis.     

2Mouse PAI-1 promotes placentation by increasing foetal and maternal angiogenesis

Introduction: Murine placentation is associated with trophoblast cells invasion of the maternal endometrium and extensive maternal and foetal angiogenesis. Both processes involve proteases‐dependent extracellular matrix remodelling. Among the protease inhibitors, plasminogen activator inhibitor‐1 (PAI‐1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at days 10.5‐11.5 day post‐coitum (dpc). Although accumulating evidence demonstrates the key role of PA‐1 in pathological angiogenesis, its function during placental vascularisation remains to be elucidated. PAI‐1 knockout mice are fertile and the litter sizes are normal. We have therefore analysed the consequence of PAI‐1 deficiency on murine placentation. Material and Methods: We have studied the possible role of PAI‐1 by quantitating the placental vessel density, the relative thickness of the labyrinth, decidua and spongiotrophoblast at day 10.5, 12.5 and 14.5 dpc in mice deficient for PAI‐1 or in control mice. An original method of computer‐assisted image analysis allowed us to quantify alterations of several placental compartments identified with specific monoclonal antibodies (keratin, desmin, fibrinogen and MECA‐32). To investigate the differentially expressed genes, we performed laser capture microdissection (LCM), followed by genome‐wide expression profiling using high‐density oligonucleotides microarray analysis (GeneChip Mouse Genome 430 2.0 Array, Affymetrix). Data were analysed using Ingenuity Pathways Analysis (Ingenuity Systems^®, http://www.ingenuity.com ). Results: At 10.5 and 12.5 dpc, an abnormal placental morphology was observed in both labyrinth and spongiotrophoblast layers in PAI‐1‐/‐ mice. Lack of PAI‐1 resulted in a transient decreased maternal and fetal vascularisation of the placenta that caused (1) an enhancement in the decidua/labyrinth and labyrinth/spongiotrophoblast thickness ratios, (2) a significant increase of trophoblast density. Normalization of placental morphology occurred by day 14.5 dpc in PAI‐1 deficient mice. Statistical analysis of microarrays revealed 706 genes differentially expressed between PAI‐1 deficient and normal mice in the labyrinth zone at 10.5 dpc. At 14.5 dpc, only 205 genes are differentially expressed. Using Ingenuity Pathways Analysis, most of those genes were found to be associated to lipid metabolism, cellular growth and proliferation. Conclusion: Despite a transient PAI‐1 requirement for optimal placental angiogenesis, this gene does not appear to be essential for trophoblast invasion and placentation.