A validated simple model to predict coexistent coronary disease in patients undergoing mitral valve surgery

OBJECTIVE: The primary limitation of the American Heart Association/American College of Cardiology guidelines is specificity. To improve the selection process, we proposed a simple additive model including age (1 point for every 5 years above 50), male sex (2 points), hypercholesterolemia (2 points), angina (3 points), and electrocardiographic evidence of ischemia (3 points). We recommend screening angiography at 3 or more points. This model was previously derived from 359 patients at Papworth Hospital. METHODS: The validation cohort was a consecutive series of patients who underwent mitral valve surgery at the Royal Brompton Hospital. Preoperative coronary angiography reports were obtained, and coronary disease was defined as luminal narrowing of 50% in 2 or more views. Sensitivities and specificities were calculated for the American Heart Association/American College of Cardiology criteria, the simple additive model, and a logistic regression model. Receiver operating characteristic curves were used to validate accuracy and compare discrimination with logistic regression. RESULTS: From 1998 through 2003, angiographic details were available for 342 (86%) of 396 patients who underwent mitral valve surgery. The sensitivity and specificity of the American Heart Association/American College of Cardiology guidelines were 100% and 5%, respectively; those of the simple additive model were 91% and 44%, respectively; and those of logistic regression were 93% and 41%, respectively. The receiver operating characteristic areas for the simple additive and logistic regression model were 0.78 (95% confidence interval, 0.73-0.84) and 0.80 (95% confidence interval, 0.74-0.85), respectively. CONCLUSIONS: This is the third independent cohort to highlight the poor specificity of the American Heart Association/American College of Cardiology guidelines. Although high sensitivity is achieved, the cost is the majority of patients requiring screening angiography. Our validated simple model improved the specificity and selection; however, this was achieved at the expense of decreased sensitivity.     

Fetal and neonatal gene therapy: benefits and pitfalls

The current approaches to gene therapy of monogenetic diseases into mature organisms are confronted with several problems including the following: (1) the underlying genetic defect may have already caused irreversible pathological changes; (2) the level of sufficient protein expression to ameliorate or prevent the disease requires prohibitively large amounts of gene delivery vector; (3) adult tissues may be poorly infected by conventional vector systems dependent upon cellular proliferation for optimal infection, for example, oncoretrovirus vectors; (4) immune responses, either pre-existing or developing following vector delivery, may rapidly eliminate transgenic protein expression and prevent future effective intervention. Early gene transfer, in the neonatal or even fetal period, may overcome some or all of these obstacles. The mammalian fetus enjoys a uniquely protected environment in the womb, bathed in a biochemically and physically supportive fluid devoid of myriad extra-uterine pathogens. Strong physical and chemical barriers to infection might, perhaps, impede the frenetic cell division. The physical support and the biochemical support provided by the fetal-maternal placental interface may, therefore, minimize the onset of genetic diseases manifest early in life. The fetal organism must prepare itself for birth, but lacking a mature adaptive immune system may depend upon more primordial immune defences. It is the nature of these defences, and the vulnerabilities they protect, that are poorly understood in the context of gene therapy and might provide useful information for approaches to gene therapy in the young, as well as perhaps the mature organism.     

Incidence and risk factors of fall injuries among infants: a study in Greece

OBJECTIVE: To assess the incidence of fall injuries among infants in Greece, overall and by type of nursery equipment. DESIGN: Review of data from a large injury database. SETTING: The Emergency Department Injury Surveillance System in Greece. PATIENTS: A total of 2672 injured infants. INTERVENTIONS: Specially trained health visitors performed in-person interviews with the children's guardians, using a precoded questionnaire. The results of an independent survey of 777 mothers of noninjured children younger than 2 years attending the same emergency departments were used to allow quantification of the role of specific nursery equipment in the causation of infant fall injuries. MAIN OUTCOME MEASURES: Annual rate of injury by falling in infants, overall and by cause. RESULTS: About 4400 infant fall injuries occur annually in Greece, corresponding to an annual incidence rate of 44 injuries per 1000 infants. The incidence of falls increases with increasing infant age. A high percentage of severe injuries was detected, most of them concussions (14.3%) and fractures (9.4%). Approximately 10% of infants with fall-related injuries required hospitalization. More than 36% of fall injuries involved nursery equipment. Infant walker use was associated with a higher incidence of falls (about 9 per 1000 infant-years), and these falls occasionally involved stairs and caused serious injuries. Infant bouncers, strollers, and changing tables were all associated with a similar incidence of falls (about 4 per 1000 infant-years). CONCLUSIONS: Falls are a common cause of serious infant injuries, and nursery equipment is frequently involved in the injury-causing event.     

Tri-iodothyronine and a deleted form of hepatocyte growth factor act synergistically to enhance liver proliferation and enable in vivo retroviral gene transfer via the peripheral venous system

Retroviral vectors integrate into the target cell genome in a stable manner and therefore offer the potential for permanent correction of the genetic diseases that affect the liver. These vectors, however, usually require cell division to occur in order to allow provirus entry into the nucleus. We have explored clinically acceptable methods to improve the efficiency of retroviral gene transfer to the liver, which avoid the need for liver damage. Tri-iodothyronine (T3) and recombinant hepatocyte growth factor have previously been used to induce hepatocyte proliferation in rat livers and allow in vivo retroviral gene transfer. We investigated the combined effects of these growth factors, with their differing mechanisms of action, on hepatocyte proliferation in vivo and assessed their effectiveness in priming cells for retroviral gene transfer. During the phase of hepatocyte proliferation retrovirus was administered via either the portal or tail vein. Acting synergistically, T3 and a truncated form of recombinant hepatocyte growth factor (dHGF) induced 30% of hepatocytes in normal rat liver to enter DNA synthesis at 24 h. This increased proliferation enabled the liver to be transduced in vivo by retroviral vectors via either the portal or peripheral venous system, achieving transduction efficiencies of 6.9 +/- 1.6% and 4.3 +/- 0.4% respectively. Thus, the liver can be simply and conveniently transduced in vivo with integrating vectors, introduced via the peripheral venous system during a wave of growth factor-induced proliferation, pointing the way to clinically applicable gene transfer techniques.     

Withdrawal of red meat from the usual diet reduces albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria

BACKGROUND: Replacement of red meat in the diet with chicken has reduced the urinary albumin excretion rate (UAER) and serum cholesterol in microalbuminuric type 2 diabetes patients. The effects of withdrawing red meat are unknown in the more advanced stages of diabetic nephropathy. OBJECTIVE: Our objective was to assess the effects of replacing red meat in the usual diet (UD) with chicken (CD) and of consuming a lactovegetarian low-protein diet (LPD) on renal function, fatty acid, and lipid profile in macroalbuminuric type 2 diabetes patients. DESIGN: A crossover controlled trial was conducted in 17 type 2 diabetes patients with macroalbuminuria (24-h UAER > or = 200 microg/min). Each patient followed the UD, CD, and LPD in a random order for 4 wk. After each diet, glomerular filtration rate, UAER, serum fatty acid, lipid profile, glycemic control, anthropometric indexes, and blood pressure were measured. RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD. Compared with the UD, an increase in serum total polyunsaturated fatty acids was also observed (CD: 39.8 +/- 2.6%; LPD: 39.7 +/- 4.4%; UD: 37.3 +/- 3.1%; P = 0.029). CONCLUSION: In macroalbuminuric patients with type 2 diabetes, withdrawing red meat from the diet reduces the UAER.