Response of Müller cells following experimental lensectomy-vitrectomy

We used morphological, biochemical and immunohistochemical methods to assess the response of Müller cells after experimental lensectomy-vitrectomy in rabbits. We observed widened intercellular spaces between the Müller cells and nerve fibers of ganglion cells, and increased electron opacity in the Müller cells of eyes injected with silicone oil. No apparent morphological changes were detected in the Müller cells of air-injected eyes. The specific and total activities of Müller cell-marker enzymes (glucose 6-phosphatase and glutamine synthetase) showed an initial increase, followed by a decrease. Glial fibrillary acidic protein immunoreactivity was not found in the Müller cells of the normal rabbit retina but was exhibited after surgery. Our results showed that markers of Müller cells associated with glycogenolysis and/or gluconeogenesis, glutamate-glutamine cycle and cytoskeletal protein metabolism were affected by the experimental lensectomy-vitrectomy.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Adrenomedullin in cultured human retinal pigment epithelial cells

PURPOSE: To determine whether adrenomedullin (ADM), a vasorelaxant peptide is produced and secreted by human retinal pigment epithelial (RPE) cells, whether ADM expression is regulated by inflammatory cytokines and a growth factor, and whether ADM has proliferative effects on these cells. METHODS: Production and secretion of ADM by cultured human RPE cells were examined by Northern blot analysis and radioimmunoassay. Regulation of the ADM expression by basic fibroblast growth factor, interferon (IFN)-gamma, tumor necrosis factor-alpha, interleukin (IL)1beta, or all-trans-retinoic acid was studied. In addition, proliferative effects of ADM on human RPE cells were examined by modified 3-(4,5-dimetylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: ADM mRNA was expressed constitutively in all three human RPE cell lines (F-0202, D407, and ARPE-19) examined. Immunoreactive ADM was detected in the cultured media by radioimmunoassay. Sephadex G-50 column chromatography of the cultured medium showed a single peak eluting in the position of ADM-(1-52). Treatment with IFN-gamma or IL-beta increased ADM mRNA levels and immunoreactive-ADM levels in the medium in dose- and time-dependent manners in ARPE-19 cells. Exogenously added ADM increased the number of F-0202 cells and ARPE-19 cells, and the treatment with ADM antibody or ADM-(22-52) (an ADM antagonist) decreased it. CONCLUSIONS: Human RPE cells produced and secreted ADM. IFN-gamma and IL-1beta induced ADM expression in ARPE-19 cells. Furthermore, ADM stimulated proliferation of RPE cells. These results raise the possibility that ADM is related to the pathophysiology of some inflammatory and proliferative ocular diseases.     

A rapid agglutination assay to detect anti-streptokinase antibodies

Background Streptokinase resistance may cause suboptimal thrombolytic therapy. Aim To develop a rapid latex-bead assay to detect streptokinase antibodies. Methods Sera were obtained from 16 patients presenting with acute myocardial infarction (MI) before treatment with streptokinase and 1 and 6 months post treatment, and from 100 controls. Sera were assayed for anti-streptokinase antibodies using a functional streptokinase-neutralising assay. Results Streptokinase-neutralising activity was low in controls (54±5U/ml) and patients prior to treatment (101±18), increasing to 2,110±823 and 1,017±169 at 1 and 6 months (mean±SEM). The latex assay had a sensitivity of 94% and a specificity of 93% for detecting individuals with >350U/ml of streptokinase resistance, which is sufficient to neutralise the drug clinically. Conclusions Estimation of streptokinase resistance using an enzyme immunoassay and a latex bead assay correlated well with serum neutralising activity. This assay can rapidly identify patients who have a high level of streptokinase-neutralising activity.     

Novel antiinflammatory analgesics: 3-(2-/4-pyridylethyl)-benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives

Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one. Their chemical structures have been proven by IR. 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster's Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2.     

Bronchopulmonary dysplasia: radiographic appearance in middle childhood

Chest radiographs were compared for three groups of children 8-9 years old: 23 survivors of bronchopulmonary dysplasia (BPD), 33 survivors of hyaline membrane disease without BPD, and 35 survivors of premature birth without neonatal respiratory problems. Only four children in the second group and three in the third had abnormal lungs. Linear shadows, apparently representing strands of fibrosis or deep pleural fissuring, were seen more frequently (15 of 23) in the BPD group than in the others (P less than .0001). Seventeen children in the BPD group had definite pulmonary abnormalities, none of them severe. The anteroposterior dimension of the chest in survivors of BPD tended to be decreased (P less than .001 vs that of reported control subjects).     

Inhibition of human lymphocyte reactivity by plasma fibronectin in vitro

The effect of purified human plasma fibronectin (FN) on the reactivity of human lymphocyte-rich mononuclear cells to mitogens and allogeneic cell interactions was studied. Concentrations of FN from 25 to 100 micrograms per 250 microL of culture consistently depressed phytohemagglutinin (PHA) responses. To exert an inhibitory effect, FN must be present within 20 hours after the addition of PHA to cells, and, therefore, it appears to interfere with early events in the transformation process. Increasing the concentration of PHA failed to reduce the inhibitory effect of FN, which suggests that the depressed response was not the result of FN-PHA complex formation, which would reduce the amount of mitogen available for stimulation. This possibility was supported by the finding that FN also inhibited the mixed lymphocyte response (MLR), in a reaction that was not dependent on the activity of soluble antigen or mitogen. In contrast, the stimulation of lymphocytes to undergo transformation that is induced by the nonlectin mitogen, sodium periodate, was unaffected by FN. Periodate-treated cells are, however, already stimulated to undergo transformation, prior to their exposure to FN. FN did not interfere with the activity of interleukin-2, nor did it indirectly regulate lymphocyte responses by modifying the production and/or effect of humoral regulatory factors released from the adherent accessory cells (macrophages). These studies show that FN is a potent immunosuppressive agent in vitro.