PROGNOSTIC VALUE OF ANGIOGENESIS IN OPERABLE NON-SMALL CELL LUNG CANCER

Tumour angiogenesis is an important factor for tumour growth and metastasis. Although some recent reports suggest that microvessel counts in non-small cell lung cancer are related to a poor disease outcome, the results were not conclusive and were not compared with other molecular prognostic markers. In the present study, the vascular grade was assessed in 107 (T1,2–N0,1) operable non-small cell lung carcinomas, using the JC70 monoclonal antibody to CD31. Three vascular grades were defined with appraisal by eye and by Chalkley counting: high (Chalkley score 7–12), medium (5–6), and low (2–4). There was a significant correlation between eye appraisal and Chalkley counting ( P <0·0001). Vascular grade was not related to histology, grade, proliferation index (Ki67), or EGFR or p53 expression. Tumours from younger patients had a higher grade of angiogenesis ( P =0·05). Apart from the vascular grade, none of the other factors examined was statistically related to lymph node metastasis ( P <0·0001). A univariate analysis of survival showed that vascular grade was the most significant prognostic factor ( P =0·0004), followed by N-stage ( P =0·001). In a multivariate analysis, N-stage and vascular grade were not found to be independent prognostic factors, since they were strongly related to each other. Excluding N-stage, vascular grade was the only independent prognostic factor ( P =0·007). Kaplan–Meier survival curves showed a statistically significant worse prognosis for patients with high vascular grade, but no difference was observed between low and medium vascular grade. These data suggest that angiogenesis in operable non-small cell lung cancer is a major prognostic factor for survival and, among the parameters tested, is the only factor related to cancer cell migration to lymph nodes. The integration of vascular grading in clinical trials on adjuvant chemotherapy and/or radiotherapy could substantially contribute in defining groups of operable patients who might benefit from cytotoxic treatment.     

Percutaneous Myocardial Laser Revascularization

Transmyocardial laser revascularization (TMR) is an experimental procedure for intractable angina that has demonstrated clinical benefit. The majority of patients who had TMR have significant reduction of angina. TMR has been performed exclusively by thoracic and cardiac surgeons using a handhold CO₂ laser device. The development of a prototype percutaneous device that delivers mid-infrared laser energy (Ho:YAG) through a 9Fr coaxial catheter system recently has been reported. The long-term benefits of this percutaneous approach is being defined in the context of the randomized PACIFIC Trial. The initial follow-up suggested significant relief of angina in the majority of treated patients, and the results are likely to be equal or similar to those of surgical TMR. The safety data of percutaneous myocardial revascularization (PMR) with the CardioGenesis system showed exceedingly low morbidity and mortality.     

The characteristics of acute non‐fatal medication‐related events attended by ambulance services in the Melbourne Metropolitan Area 1998–2002

Introduction and Aims. To describe the characteristics of non‐fatal medication‐related ambulance attendances in Melbourne. Design and Methods. A retrospective analysis of 16 705 patient care records completed by ambulance paramedics in Melbourne where medications had a causal role in the attendance. Results. A single medication only was implicated in 11 765 cases (70% of the total). Of these, 85% involved one of six types of medication: benzodiazepines (52%), paracetamol (15%), selective serotonin re‐uptake inhibitors (6.5%), combination paracetamol and opioids (4%), phenothiazines (3.4%) and tricyclic antidepressants (TCA) (3.7%). Cases involving benzodiazepines were significantly (P < 0.001) older (Average = 37 years) than those involving paracetamol (Average = 30 years). Thirty‐four per cent of cases involved concurrent alcohol use, and this varied according to drug type (paracetamol 26%, benzodiazepines 40%, selective serotonin re‐uptake inhibitors 35%, paracetamol and opioids 35%). An abnormal Glasgow Coma Scale score was found in 19% of cases, again varying according to drug type (paracetamol 10%, TCA 39%, benzodiazepines 21%, paracetamol and opioids 17%, phenothiazines 15%). Ten per cent of cases were not transported to hospital ranging from 3% for TCA to 13% for benzodiazepines. Discussion and Conclusions. The majority of non‐fatal medication events attended by ambulance paramedics involve one of six substances. Benzodiazepines were most commonly implicated and, as management may require only simple supportive treatment, significant numbers are not transported to hospital. The unique clinical population is identified in this study and the ongoing medical and psychiatric treatment of these patients not transported to hospital in the study period needs to be considered. [Hutton J, Dent A, Buykx P, Burgess S, Flander L, Dietze P. The characteristics of acute non‐fatal medication‐related events attended by ambulance services in the Melbourne Metropolitan Area 1998–2002. Drug Alcohol Rev 2009]     

THE CHEMISTRY AND CONFORMATIONAL AND BIOLOGICAL ANALYSIS OF VITAMIN D3, ITS METABOLITES AND ANALOGUES

The chemical properties, sterochemical relationships and solution confromation, as assessed in part by proton NMR spectroscopy, for vitamin D₃, its major metabolites [including 1α, 25-(OH)₂ D₃, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation ot their biological activity. In particular the relative ability of many of these seco-steroids to compet both with 25-OHD₃ for its chick serum binding protein and 1α, 25-(OH)₂-D₃ for its chick intenstinal cytosol-chromation receptor systme was quantitated, in vitro , Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectiveily these chemical and bilogical studies constitute a 'systems analysis'of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the bilogical actions of vitamin D.     

Cardiac Activation During External Cardiac Pacing

To determine which cardiac chambers are stimulated during external cardiac pacing we performed external pacing in eight normal volunteers while recording the esophageol electrogram. All subjects demonstrated evidence of pacing, which was ventricular in each case. The atrium was frequently activated retrogradely during pacing. We conclude that external cardiac pacing selectively stimulates the ventricle and is thus not of value for noninvasive atrial pacing studies.     

Interpretation of in-vitro thyroid function tests during pregnancy

Summary. In-vitro thyroid function tests are difficult to interpret in pregnancy because of, among other things, the effect of oestrogens on thyroid binding globulin (TBG) concentrations. In an attempt to clarify the position, serum concentrations of total thyroxine (T₄), free T₄, TBG, T₄/TBG ratio, tri-iodothyronine (T₃) and thyroid stimulating hormone (TSH) were measured. Total T₄ and TBG concentrations rose to above the non-pregnant reference range by 20 weeks. The T₄/TBG ratio fell to hypo-thyroid values by 20 weeks but although the free T₄ level was lower in the third trimester compared with values in the first and second trimesters, only a few subjects had hypothyroid values. The TSH values remained unchanged throughout pregnancy. The significance of these changes is discussed and reference ranges for these hormones at each trimester are provided.     

Case report: A patient with primary biliary cirrhosis and autoimmune haemolytic anaemia

Diseases of an autoimmune nature are well recognized in association with primary biliary cirrhosis. Although autoimmune thyroiditis and many rheumatological conditions are well described in primary biliary cirrhosis, autoimmune haematological diseases have been less well reported. We report on a 66 year old North American Indian man with coincident primary biliary cirrhosis and warm antibody haemolytic anaemia. This case report supports the suggestion of an association between autoimmune haemolytic anaemia and primary biliary cirrhosis.     

Anaesthetic management of a neonate with nesidioblastosis

Nesidioblastosis is a disorder which is characterized by autonomous insulin secretion that is not affected by decreases in blood glucose. Patients usually present during the neonatal or infantile period with hypoglycaemia associated with hyperinsulinaemia. Most cases of nesidioblastosis are sporadic; however, familial forms appear to be inherited in an autosomal recessive manner. We discuss the anaesthetic management of a patient with nesidioblastosis who presented for near total pancreatectomy and review the literature pertinent to the anaesthesiologist.