[Oriental cholangitis in Europe].
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Acute Disease↗
Biomedical subjects
I Paterson
Publications and source records attributed to I Paterson.
Interleukin-2 induces early multisystem organ edema mediated by neutrophils.
Interleukin-2 (IL-2), an agent known to activate neutrophils (PMN) with thromboxane (Tx)B2 release, produces pulmonary edema within 6 hours of intravenous infusion. This study tests the role of PMN in mediating the edema. Anesthetized rats received 10(6)U recombinant human IL-2 (n = 15) or vehicle (n = 14) as a constant intravenous infusion during a period of 1 hour. At this time there was leukopenia 3.63 +/- 0.43 (x10(3)/mm3) relative to vehicle-infused control rats 6.12 +/- 0.86 and a decline in PMN, 2.19 +/- 0.14 relative to control value of 3.33 +/- 0.05 (both p less than 0.05). After 6 hours edema, as measured by increase in the wet to dry weight (W/d) ratio, was present in the lungs (4.93 +/- 0.20 relative to control 4.06 +/- 0.10), heart (4.09 +/- 0.11 versus 3.76 +/- 0.08), liver (3.50 +/- 0.10 versus 3.18 +/- 0.10), and kidney (4.25 +/- 0.07 versus 4.00 +/- 0.07) (all p less than 0.05). There was increased lung permeability demonstrated by bronchoalveolar lavage fluid protein concentration of 1970 +/- 210 micrograms/mL relative to control 460 +/- 90 micrograms/mL (p less than 0.05). Interleukin-2 resulted in lung PMN sequestration of 53 +/- 7 PMN/10 high-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05) and increased plasma TxB2 levels to 1290 +/- 245 pg/mL relative to control 481 +/- 93 pg/mL (p less than 0.05). Pretreatment of other rats (n = 8) with selective anti-rat neutrophil antiserum 18 hours before the experiment led to a peripheral PMN count 10% of baseline and prevented edema in the lungs (W/d ratio 4.20 +/- 0.16) and heart (3.67 +/- 0.07) (both p less than 0.05) but not liver or kidney. Protein in lung lavage was reduced to 760 +/- 220 micrograms/mL (p less than 0.05). The protection afforded by leukopenia was associated with lack of PMN sequestration and prevention of the increase in plasma Tx levels (484 +/- 120 pg/mL, p less than 0.05). These data indicate that the rapid induction of lung and heart edema with a 1-hour infusion of IL-2 in the rat is mediated, in large part, by activated PMNs.
Animals↗
The epidemiology of malpractice.
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Malpractice↗
Neutrophil adherence receptors (CD 18) in ischemia. Dissociation between quantitative cell surface expression and diapedesis mediated by leukotriene B4.
Neutrophils and eicosanoid chemoattractants are centrally involved with ischemia-reperfusion (I/R) injury. The CD 18 complex of adhesive glycoproteins, readily up-regulated by chemoattractants in vitro, is required for polymorphonuclear leukocyte (PMN) adherence to endothelium. This study tests whether CD 18 is up-regulated by ischemia in vivo and its role in mediating PMN diapedesis. Anesthetized rabbits underwent 3 h of bilateral hindlimb tourniquet ischemia (n = 16). Ten min after tourniquet release, levels of plasma leukotriene (LT)B4 increased to 390 +/- 62 pg/ml (mean +/- SE), higher than 134 +/- 26 pg/ml in control rabbits (n = 13, p less than 0.01). Aliquots of plasma were added to whole blood from normal rabbits (n = 6) for flow cytometric analysis of neutrophils with the CD 18 mAb R 15.7. Addition of I/R plasma failed to demonstrate an increase in surface expression of CD 18. Similarly, no CD 18 up-regulation was observed in vivo upon reperfusion in ischemic animals pretreated with mAb R 15.7 (n = 3). However, I/R plasma when introduced into plastic chambers taped atop dermabrasion sites in normal rabbits (n = 12) resulted in diapedesis, measured by the accumulation after 3 h of 1130 +/- 125 PMN/mm3 in the chambers relative to 120 +/- 31 PMN/mm3 with control plasma (p less than 0.01). Diapedesis in response to I/R plasma was abolished by pretreatment with mAb R 15.7 (less than 5 PMN/mm3, n = 6), was reduced by U 75,302, an LTB4 receptor antagonist (253 +/- 101 PMN/mm3, n = 6) (both p less than 0.01) and was not protein synthesis dependent. These results demonstrate that PMN diapedesis in response to I/R plasma is exclusively dependent upon the CD 18 glycoprotein complex by an LTB4-dependent mechanism, despite the fact that CD 18 is not up-regulated on circulating PMN in ischemia. These data indirectly indicate the functional importance of conformational changes of CD 18 in determining PMN adhesion.
Animals↗
Expression of the pS2 gene in normal, benign and neoplastic human stomach.
The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.
Blotting, Northern↗
Intestinal obstruction in patients with gynaecological malignancies.
Bowel obstruction developing in patients with gynaecological malignancies may present as a therapeutic dilemma. The causes, and results of surgical and conservative management of 92 patients are analysed. The causes of obstruction in the 64 patients who were treated surgically were: tumour recurrence in 42, adhesions in 12, radiation stricture in 9 and pelvic abscess in 1. Surgical palliation was effective in 45 patients in this group, with another 12 patients being palliated initially but subsequently developing further obstructive symptoms. Surgical palliation was ineffective in 7. Conservative management was effective only in 12 of the 41 patients, and even in this group 8 developed further obstructive episodes within the first month of discharge. The median survival in the surgically treated group for benign and malignant causes is 57 and 10 weeks respectively; while it is 4 weeks for those treated conservatively.
Female↗
Medicolegal audit in the West Midlands region: analysis of 100 cases.
One hundred medicolegal cases were analysed to obtain quantitative data about diagnoses and the causes of litigation that affect hospital doctors in the National Health Service. Sixteen actions concerned minor problems that are an unavoidable risk of treatment, and 39 were due to natural causes. In other cases it was debatable whether a medical accident or negligence was responsible. At the end of three years 73 actions had been withdrawn, 12 settled out of court, and one lost in court by the plaintiff, and 14 were pending. Of these 14, nine were likely to reach court on charges of negligence. Contributory causes were failure of communication in 27 and matters connected with the patient's attitude or personality in 20. Because much time and money are spent on cases that should never have started a doctor should sit on the legal aid panel to give advice for medical cases. Also, solicitors should obtain an independent medical opinion when a complaint is first received from a patient. Consent forms should be more informative and give details of what can reasonably be expected from treatment and its possible risks.
England↗
Non-invasive biological dosimetry of the skin.
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Carboxylesterase↗
Detection of the effects of low dose ionising irradiation on epidermal function.
A non-invasive technique for the detection of small doses of X irradiation to the skin would be important for improvements in radiation protection. In this investigation we have studied the effects of doses of X rays of less than 2.0 Gy (suberythemal) on human skin in order to select such a technique. Our results indicate that a dose of X rays between 0.5 and 1.0 Gy was sufficient to depress significantly epidermal cell production in the basal layer. Accompanying this change in epidermal cell production after 1.0 Gy exposure, there was a reduction in the rate of desquamation of corneocytes. In the stratum granulosum, changes in "non-specific esterase" activity (a marker of lysosomal enzyme release) were also observed. Thus at three stages of the keratinisation process, functional alterations had occurred within three days of exposure to an X ray dose of 1.0 Gy. For this reason it seems likely that the various changes were at least partially independent of each other and that the stratum corneum may serve as a biological dosimeter for the detection of exposure to low doses of ionising radiation.
Aged↗