Effects of simulated altitude and exercise upon ECGs of young black men.

Twenty-five healthy black men between 17 and 21 years of age were evaluated. Their resting and exercise electrocardiograms were recorded at simulated sea level and at a simulated altitude of 4,000 m. Sea level exercise caused a reduction in the amplitudes of R waves and a lowering of J points. Exercise at a simulated altitude of 4,000 m caused a lowering of the J point in several leads and a reduction of the R wave amplitude in lead aVF. Hypoxia caused a reduction in the amplitudes of the T waves and a lowering of the J points in several leads. These effects of exercise and altitude, to a great extent, eliminated the appearance of "early repolarization," which is very common among young black men.     

Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE--The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT--We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS--Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS--Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.     

Extracellular potassium concentrations in red blood cell suspensions after irradiation and washing

BACKGROUND: Extracellular potassium concentration [K(+)e] increases with duration of red blood cell storage. Sometimes red blood cells (RBC) are washed before transfusion to infants to reduce [K(+)e] of these components. AABB standards permit storage of washed RBCs at 4 degrees C for 24 hours. The [K(+)e] of washed RBCs during storage is not known. Experiments were performed to provide those data. STUDY DESIGN AND METHODS: One day after outdating, 26 RBC units were washed without irradiation or before or after irradiation (25 Gy), and [K(+)e] was measured for 24 hours. [K(+)e] was measured also immediately before transfusion of 29 nonoutdated irradiated and washed RBC units. RESULTS: After washing, [K(+)e] increased in a time-dependent fashion. [K(+)e] increased more rapidly in preparations of irradiated than nonirradiated RBCs. [K(+)e] was less after washing after irradiation (1.6 +/- 0.3, 2.4 +/- 0.3, 3.0 +/- 0.3, 3.6 +/- 0.3. 4.2 +/- 0.4, 5.3 +/- 0.5, 8.6 +/- 1.0, and 14.3 +/- 1.3 mEq/L at 0, 1, 2, 3, 4, 6, 12, and 24 hr; mean +/- SD) than washing before irradiation (p < 0.001). The increase in [K(+)e] during the first 6 hours after washing after irradiation was linear (0.61 +/- 0.08 mEq K(+)/L/hr). The probability of a unit of RBCs having a [K(+)e] greater than 5 mEq per L is 0.0 to 0.2 percent 3 hours after washing irradiated RBCs and 0.0 to 1.1 percent 6 hours after washing nonirradiated RBCs. CONCLUSIONS: [K(+)e] increases after washing irradiated and nonirradiated packed RBCs. After irradiation and washing, the [K(+)e] for the initial 6 hours can be predicted from the [K(+)e] immediately after washing. There is a low probability that a unit of RBCs would have a [K(+)e] greater than 5 mEq per L during 6 hours of storage at 4 degrees C after washing if the cells are not irradiated and for 3 hours if the cells are irradiated.     

Pediatric sleep disorders

Pediatric sleep disorders represent a heterogeneous collection of disturbances that require varied intervention strategies. The diagnosis of some sleep disorders (eg, OSAS, narcolepsy, PLMD) require PSG, whereas others can be diagnosed during an office visit with a thorough medical,psychiatric, and sleep history. Sleep disorders place children at risk for school failure, accidents, and social problems, and can place a significant burden on families and the parent-child relationship.     

Increased levels of basic fibroblast growth factor are found in the cross-clamped heart during cardiopulmonary bypass

BACKGROUND: High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized. PATIENTS AND METHODS: Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass. RESULTS: In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements. CONCLUSIONS: Plasma bFGF levels increase during cardiopulmonary bypass. The source of this elevation is the lungs and heart.     

Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury

There is emerging evidence that platelets are major contributors to inflammatory processes through intimate associations with innate immune cells. Here, we report that activated platelets induce the formation of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRALI), which is the leading cause of death after transfusion therapy. NETs are composed of decondensed chromatin decorated with granular proteins that function to trap extracellular pathogens; their formation requires the activation of neutrophils and release of their DNA in a process that may or may not result in neutrophil death. In a mouse model of TRALI that is neutrophil and platelet dependent, NETs appeared in the lung microvasculature and NET components increased in the plasma. We detected NETs in the lungs and plasma of human TRALI and in the plasma of patients with acute lung injury. In the experimental TRALI model, targeting platelet activation with either aspirin or a glycoprotein IIb/IIIa inhibitor decreased NET formation and lung injury. We then directly targeted NET components with a histone blocking antibody and DNase1, both of which protected mice from TRALI. These data suggest that NETs contribute to lung endothelial injury and that targeting NET formation may be a promising new direction for the treatment of acute lung injury.     

Prognostic role of echocardiography and brain natriuretic peptide in symptomatic breathless patients in the community

Aims: Brain natriuretic peptide (BNP), left ventricular (LV) systolicfunction, and mitral filling pattern (MFP) are prognostic indicatorsin patients with heart failure (HF). This study evaluated thepotential role of E/Ea for predicting cardiovascular (CV) eventsin patients with suspected HF. This non-invasive measure ofLV filling pressure has been shown to predict outcome in moreadvanced HF, but not in mild HF in the community. Methods and results: Two hundred and twenty-eight elderly symptomatic general practicepatients (dyspnoea/oedema) were recruited and underwent clinicalevaluation, NT-proBNP assay, and comprehensive echocardiography.The Kaplan–Meier analysis of time to first CV hospitalizationor CV death was performed for 1 year after presentation accordingto nominated thresholds of LV systolic function, NT-proBNP,MFP, and E/Ea ratio. Mean age was 70.3 ± 7.3 years, meanNT-proBNP was 111.4 ± 185.8, and 148 (65%) were female.Twenty-six patients (11%) experienced a CV event within 18 monthsof baseline (6 deaths and 20 admissions). Time to first CV eventpredicted by NT-proBNP (P < 0.0001), MFP (P = 0.009), andE:Ea (P = 0.0076), but not EF (P = 0.098). When NT-proBNP waselevated, E:Ea >15 identified a group of patients with lowersurvival (P < 0.0001). Conclusion: Both E/Ea and NT-proBNP predicted hospitalization and when usedin a two-step approach (NT-proBNP first, followed by E/Ea),the combination of both (elevated NT-proBNP and elevated E/Ea)identified those patients at highest risk, thus supporting acomplementary approach for echocardiography and NT-proBNP inpatients with HF symptoms.     

肠毒素大肠杆菌攻毒小鼠模型的建立以及疫苗候选株保护效果的评价

目的:建立肠毒素大肠杆菌攻毒小鼠模型以及应用模型对疫苗候选株免疫效果进行评价．方法:通过鼻饲半数致死量(LD50)肠毒素大肠杆菌E44813,E44815和E11881A观察小鼠肺病理学变化、肺部细菌清除情况变化,建立肠毒素大肠杆菌鼻饲小鼠模型;应用鼻饲小鼠模型观察疫苗候选株FE1,FE3,FE6保护效果．结果:鼻饲LD50剂量肠毒素大肠杆菌小鼠的病理特征是肺组织存在大量的淋巴细胞、巨噬细胞、中性粒细胞和浆细胞,为多病灶支气管肺炎,肺部细菌清除缓慢,至第7天仍能检测到105数量级的细菌．应用疫苗候选株免疫后进行攻毒,小鼠没有发病和死亡,病理特征主要是淋巴细胞少量增多,肺部细菌清除迅速,至第7天已检测不到细菌,与对照有显著性差异(0 CFU／g vs 6．2×105,5．4×105,2．3×105 CFU／g,P<0．05)．结论:肠毒素大肠杆菌鼻饲小鼠模型能够为疫苗筛选和评价提供了有效途径,同时也证实了疫苗候选株FE1,FE3,FE6具有良好的免疫保护效果．     

Using genetic information to make surgical decisions

PURPOSE: We report the case of a boy aged 13 years who was diagnosed with a Dukes B obstructing cancer of the sigmoid colon. At the time of diagnosis, he underwent a Hartmann's procedure with end colostomy. Because of his unusually young age, he was referred to the Familial GI Cancer Registry at Mount Sinai Hospital for genetic assessment. A detailed pedigree revealed no significant history other than lung cancer in his maternal grandfather. METHODS: We obtained his tumor specimen and performed molecular analysis of both normal colonic and tumor DNA. Specifically, we identified replication errors (RER) in the patient's tumor DNA when compared with normal colonic DNA. RER has been found in more than 90 percent of tumors from patients with Hereditary Nonpolyposis Colon Cancer (HNPCC) and is, thus, considered to be one of the hallmarks of this disease. Because HNPCC patients have a 40 percent risk of synchronous or metachronous tumors, the recommended surgery for HNPCC should be at least a subtotal colectomy with ileorectal anastomosis. RESULTS: Based on molecular results, we were able to recommend that the patient have a subtotal colectomy performed instead of merely colostomy closure, to reduce his lifetime risk of developing further colon tumors and to make surveillance of the remaining rectum relatively easy. In this patient, we subsequently identified a germline mutation of the mismatch repair gene hMSH2 that is implicated in HNPCC. The possibility of HNPCC should be considered in adolescents who are diagnosed with colorectal cancer, so appropriate surgical decisions can be made.