Risk stratification using the Society of Thoracic Surgeons Program

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.     

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

Enhancement of adenovirus-mediated gene transfer to human bone marrow cells

Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on the multiplicity of infection (MOI), time of incubation, the volume in which the co-incubation occurs and the presence or absence of growth factors. Studies revealed that a brief co-incubation (1-8 hours), resulted in low levels of transgene expression, suggesting that adenovirus infection of CD34+ cells occurs slowly, and optimal transduction requires a 24 hour exposure to adenovirus. Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction efficiency but inhibited hematopoietic function. However, treatment at a MOI of 50-100 resulted in efficient transduction (10.7-15.7% positive) without detectable toxicity. Secondary proof of adenovirus transgene expression was demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta-gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has no significant effect on hematopoietic function. Adenovirus-mediated transduction of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with improved gene delivery and maintenance of hematopoietic function. In summary, adenovirus vectors can be used to transiently transduce stem cells, and conditions have been defined to maximize expression and limit inhibitory effects on CD34+ cells. These data support continued investigation of this vector for local cytokine delivery and purging of stem cell products.     

Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus retinitis and elevated CD4+ counts

OBJECTIVE: To determine whether maintenance therapy can be discontinued safety in patients with quiescent cytomegalovirus retinitis (CMVR) and increased CD4+ counts after treatment with highly active antiretroviral therapy (HAART). DESIGN: A prospective observational case series. PARTICIPANTS: Eight human immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were taking HAART and had CD4+ counts above 100 cells/microliter elected to discontinue anti-CMV maintenance treatment. INTERVENTION: Biweekly-to-monthly indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts, and quarterly HIV viral loads were ordered. MAIN OUTCOME MEASURES: Twelve previously affected eyes were examined for evidence of recurrent retinitis, which was defined as any retinal whitening, border opacification, or expansion of areas of retinal pigment epithelial (RPE) atrophy greater than 750 microns. Four previously unaffected fellow eyes were observed for new CMVR. RESULTS: There was no reactivation or progression of retinitis in any patient during the mean follow-up interval of 11.4 months (range, 3-16 months). No previously unaffected eye developed CMVR. CD4+ remained elevated in all patients (range, 70-725; mean, 255). The HIV viral load ranged from undetectable to 139,000 copies. CONCLUSION: Discontinuation of maintenance therapy may be considered in patients with HAART-induced elevated CD4+ counts above 100 cells/microliter, prolonged relapse-free intervals during the reconstitution period before CD4+ counts rise above 100 cells/microliter, and completely quiescent retinitis characterized by RPE scarring only. Reduced risks of drug toxicity and drug-resistant organisms are potential benefits. Close observation for evidence of recurrent retinitis is indicated.     

English teaching in the Italian medical faculties: results of a survey

BACKGROUND: Although a compulsory examination in medical English has been present in the medical degree curriculum in Italy since 1990, guidelines indicating what should be learnt and suggesting some means of overcoming the various problems this entails are still lacking. OBJECTIVE: To investigate the main features of teaching English in the Medical Faculties and enquire into how the various problems are solved in the individual English teaching units. METHOD: A questionnaire addressing the above issues was sent out to all the Italian Universities with a Medical Faculty. RESULTS: The first finding of our survey was that response was very poor: less than 30% of the survey volunteered any reply. Within the very reduced sample which responded, there was a high degree of variation among the solutions adopted, although the underlying problems were perceived to be much the same throughout Italy. CONCLUSIONS: The general objective of the English course for medicine should be more precisely defined, together with a series of specific minimum skills the student should possess to pass the final examination. A closer collaboration among the English teaching units might help to standardize these requirements, improve the quality of the teaching and hence the level of proficiency in English for the specific purpose of medical practice.     

Expansion and length-dependent fragility of CTG repeats in yeast

Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.     

Predictors of GBV-C infection among patients referred for renal transplantation

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.     

Protein phosphatases and the regulation of MAP kinase activity

A family with hereditary factor X deficiency is presented. One member, a 25-year-old man, showed a mild bleeding tendency. His factor X activity (extrinsic: 56%; intrinsic: 55%; Russell's viper venom: 57%) and his level of circulating factor X antigen (55% of normal) were markedly reduced. Analysis of his factor X gene revealed a single point mutation within exon II resulting in the substitution of +25 Gla (GAA) by Lys (AAA). The mutation was determined by gene analysis to be heterozygous in this patient, his mother and one of his brothers. Clotting assays of factor X purified from the plasma of the index patient revealed an activity of 89% of normal upon activation with Russell's viper venom, 77% of normal in the intrinsic and 81% of normal in the extrinsic coagulation pathway. The mutation responsible for the substitution of Lys for Gla+25 was introduced into an expression plasmid containing a wild type factor X cDNA and expressed in a mammalian cell line. Factor X antigen levels in the cell lysates and in the supernatant were identical in the mutant and wild type constructs. The specific activity of the factor X expressed from the mutant construct was 3% compared with the wild type construct. These data demonstrate that the substitution of Lys for Gla+25 results not only in a reduced level of factor X in the affected family members, but also in a substantial loss of specific factor X activity.     

Learning curve for oesophageal cancer surgery

BACKGROUND: Surgical training and experience are frequently claimed to influence early and late outcome measures. The aim of this study was to examine any improvement in an individual surgeon's performance in one operation over a period of 7 years from initial appointment to date. METHODS: Patients undergoing Ivor Lewis subtotal oesophagectomy performed by a single surgeon between April 1990 and December 1996 were identified from a prospectively compiled oesophageal cancer database. Operating time (abdominal, thoracic and 'one-lung time'), blood loss, transfusion requirements (intraoperative and total), extent of lymphadenectomy (number of lymph nodes sampled), intensive treatment unit (ITU) stay, hospital stay, postoperative morbidity and mortality, pathological stage, grade and survival were recorded. RESULTS: The records of 150 patients were identified for analysis. The cohort was split into five groups, each of 30 patients operated on consecutively. Each of the groups was comparable for age, sex, smoking history, preoperative haemoglobin and creatinine levels, weight loss, American Society of Anesthesiologists' grade, and histological stage and grade of disease. Analysis of the variables pertaining to operation revealed a significant improvement with time including reduced single-lung operating time (P=0.01), reduced blood loss (P=0.03), reduced transfusion requirement (P < 0.0001), reduced ITU stay (P< 0.0001), reduced inpatient stay (P< 0.0001) and an increased yield of lymph nodes (P < 0.0001). CONCLUSION: This study showed a continuing improvement in a surgeon's performance over a 7-year period. With the current trend to shorter training periods there is a case for continuing supervision of the 'fully trained' surgeon within highly specialist units.