Antihypertensive Combination Therapy: Optimizing Blood Pressure Control and Cardiovascular Risk Reduction

Treating hypertension reduces the rates of myocardial infarction, stroke, and renal disease; however, clinical trial experience suggests that monotherapy is not likely to be successful for achieving goal blood pressure (BP) levels in many hypertensive patients. In multiple recent clinical trials including various subsets of hypertensive patients, the achievement of BP goal has typically required the combination of 2 or more medications, particularly in patients with BP levels >160/100 mm Hg. When initiating combination therapy for hypertension, careful consideration must be given to the choice of medication. Clinical trial evidence has shown the efficacy of various combinations of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics in reducing BP and cardiovascular risk. Ongoing trials should provide additional guidance on the optimal choice of combination regimens in specific clinical settings.     

Surgical Management of Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus

Background. The optimal management of patients with renal cell carcinoma with inferior vena cava tumor thrombus remains unresolved. Traditional approaches have included resection with or without the use of cardiopulmonary bypass. Chemotherapy has played a minor role except for biotherapeutic agents used for metastatic disease.

Methods. From January 1989 to January 1996, 37 patients with renal cell carcinoma and inferior vena cava tumor thrombus underwent surgical resection. The 27 men and 10 women had a median age of 57 years (range, 29 to 78 years). Thirty-six patients presented with symptoms; 21 had hematuria. Distant metastases were present in 12 patients. Tumor thrombi extended to the infrahepatic inferior vena cava (n = 16), the intrahepatic inferior vena cava (n = 16), the suprahepatic inferior vena cava (n = 3), and into the right atrium (n = 2). All tumors were resected by inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of the vena cavotomy. Cardiopulmonary bypass was necessary in only 2 patients with intraatrial thrombus.

Results. Complications occurred in 11 patients, and 1 patient died 2 days postoperatively of a myocardial infarction (mortality, 2.7%). Twenty patients are alive; overall 2- and 5-year survival rates were 61.7% and 33.6%, respectively. For patients without lymph node or distant metastases (stage IIIa), 2- and 5-year survival rates were 74% and 45%, respectively. The presence of distant metastatic disease (stage IV) at the time of operation did not have a significant adverse effect on survival, as reflected by 2- and 5-year survival rates of 62.5% and 31.3%, respectively. Lymph node metastases (stage IIIc) adversely affected survival as there were no long-term survivors.

Conclusions. Resection of an intracaval tumor thrombus arising from renal cell carcinoma can be performed safely and can result in prolonged survival even in the presence of metastatic disease. In our experience, extracorporeal circulatory support was required only when the tumor thrombus extended into the heart.     

Early noncardiogenic pulmonary edema and the use of PEEP and prone ventilation after emergency liver transplantation.

Noncardiogenic pulmonary edema in liver transplant recipients is usually secondary to TRALI (transfusion related acute lung injury) or liver ischemic-reperfusion injury. If persistent, the resultant hypoxemia is associated with increased ventilator days, prolonged length of stay (intensive care and hospital) and increased 28-day mortality. Ventilation strategies for the management of hypoxemia in acute lung injury include moderate to high levels of PEEP (positive and expiratory pressure) and prone ventilation (PV). Such strategies have theoretical adverse effects on graft perfusion. Evidence does however exist to demonstrate that maintenance of cardiac output and correct positioning of the prone patient to allow abdominal excursion can negate the deleterious effects of PEEP and PV. A liver transplant recipient became profoundly hypoxemic on our intensive care unit following the onset of noncardiogenic pulmonary edema. A risk-benefit assessment performed at the time deemed that the potential adverse effects of PEEP and PV were outweighed by the life-threatening nature of hypoxemia. The patient's condition improved following prone positioning and application of PEEP (10-15 cm H(2)O). We conclude that such ventilation strategies are appropriate in hypoxemic liver transplant recipients if an appropriate risk-benefit assessment is performed.     

Clinical and educational telepsychiatry applications: a review.

OBJECTIVE: Telepsychiatry in the form of videoconferencing brings enormous opportunities for clinical care, education, research, and administration. Focusing on videoconferencing, we reviewed the telepsychiatry literature and compared telepsychiatry with services delivered in person or through other technologies. METHODS: We conducted a comprehensive review of telepsychiatry literature from January 1, 1965, to July 31, 2003, using the terms telepsychiatry, telemedicine, videoconferencing, effectiveness, efficacy, access, outcomes, satisfaction, quality of care, education, empowerment, and costs. We selected studies for review if they discussed videoconferencing for clinical and educational applications. RESULTS: Telepsychiatry is successfully used for various clinical services and educational initiatives. Telepsychiatry is feasible, increases access to care, enables specialty consultation, yields positive outcomes, allows reliable evaluation, has few negative aspects in terms of communication, generally satisfies patients and providers, facilitates education, and empowers parties using it. Data are limited with regard to clinical outcomes and cost-effectiveness. CONCLUSIONS: Telepsychiatry is effective. More short- and long-term quantitative and qualitative research is warranted on clinical outcomes, predictors of satisfaction, costs, and educational outcomes.     

What Are the Etiology and Epidemiology of Out‐of‐hospital Pediatric Cardiopulmonary Arrest in Ontario,Canada?

Background: Pediatric cardiopulmonary arrest (CPA) outside of the hospital has a very high mortality rate. Objectives: To evaluate the etiology and initial compromise of pediatric CPA cases in hopes of developing strategies to improve out‐of‐hospital resuscitation. Methods: The Ontario Prehospital Advanced Life Support (OPALS) study was a large multicenter initiative to evaluate the impact of emergency medical services (EMS) programs on 17 communities with 40,000 critically ill and injured patients who were older than 11 years. As part of this study, the authors conducted a retrospective observational cohort study that included all children younger than 18 years of age with out‐of‐hospital CPA, during an 11‐year period from 1991–2002. CPA was defined as patient being pulseless, apneic, and requiring chest compressions. Data were collected from ambulance call reports and centralized dispatch data and were reviewed by two independent investigators. Results: There were 503 children with CPA in the sample. Mean age was 5.6 years (range, 0–17 yr); 58.4% of patients were male, and 37.8% were younger than 1 year of age. Cardiopulmonary resuscitation (CPR) first was started by a bystander in 32.4% of cases, whereas 66.0% were unwitnessed arrests. Initial rhythms were asystole 77.2% of the time, pulseless electrical activity 16.4% of the time, and ventricular fibrillation or ventricular tachycardia 4% of the time. Annual incidence was 9.1/100,000 children. CPA was witnessed in 34.0% of cases; 80.7% of these were bystander‐witnessed, and 18.1% were EMS‐witnessed. Primary pathogenic cause of arrest was medical in 61.2% of cases, trauma in 37.2% of cases, and indeterminate in 1.6% of cases. Initial underlying physiologic compromise of witnessed arrests was judged to be respiratory in 39.8% of cases, sudden collapse (presumed electrical) in 16.4% of cases, progressive shock in 1.2% of cases, and indeterminate in 42.6% of cases. Presumed etiology was trauma, 37.6%; sudden infant death syndrome (SIDS), 20.3%; and respiratory disease, 11.6%, most commonly. Survival to hospital discharge was 2.0%. Conclusions: This is one of the largest population‐based, prospective cohorts of pediatric CPA reported to date, and it reveals that most pediatric arrests are unwitnessed and receive no bystander CPR. Those that are witnessed most often are caused by respiratory arrests or trauma. Trauma, SIDS, and respiratory disease are the most common etiologies overall. These data are vital to planning large resuscitation trials looking at specific interventions (i.e., increasing bystander CPR) and highlight the need for better strategies for prevention and early recognition.     

The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding.

We have found that amino acid residues necessary for C1q and Fc gamma R binding of human IgG1 are located in the N-terminal region of the CH2 domain, residues 231-238, using a matched set of engineered antibodies based on the anti-HLA-DR antibody L243. Changing the leucine 235 in the CH2 region of IgG3 and IgG4 to glutamic acid was already known to abolish Fc gamma RI binding. We have confirmed this for IgG1 and also found a concomitant abolition of human complement lysis with retention of Fc gamma RIII-mediated function. Changing the glycine at 237 to alanine of IgG1 also abolished Fc gamma RI binding and reduced human complement lysis and Fc gamma RIII-mediated function. Exchanging the whole region 233-236 with the sequence found in human IgG2, abolished Fc gamma RI binding and human complement lysis and reduced Fc gamma RIII-mediated function of IgG1. In contrast, a change in the previously described C1q-binding motif, from lysine at 320 to alanine, had no effect on IgG1-mediated complement lysis.     

Identification and isolation of OKT4+ suppressor cells with the monoclonal antibody WR16.

The monoclonal antibody WR16 was secreted by a hybridoma produced by fusing splenocytes from a BALB/c mouse immunized with human T-cell chronic lymphocytic leukaemia cells and the murine myeloma cell line NS-O. WR16 reacts specifically with human lymphocytes and binds to 48% of OKT4+ T lymphocytes and the majority of B lymphocytes. Human OKT4+ tonsil lymphocytes were subfractionated into WR16-/OKT4+ and WR16+/OKT4+ subpopulations by the panning technique. The capacity of these cells to help or suppress pokeweed mitogen-induced immunoglobulin (Ig) secretion by autologous B lymphocytes was monitored after 9 days of coculture. Cells of phenotype WR16-/OKT4+ enhanced Ig secretion in excess of that found with non-fractionated OKT4+ lymphocytes, whilst WR16+/OKT4+ lymphocytes suppressed Ig secretion when added to a mixture of B lymphocytes and non-fractionated OKT4+ cells. The WR16-/OKT4+ subpopulation was further fractionated by use of the MoAb Leu 8. Forty-two percent of WR16-/OKT4+ lymphocytes bound Leu 8, and cells of the phenotype WR16-/OKT4+/Leu 8+ were found to induce B-lymphocyte Ig secretion, whilst WR16-/OKT4+/Leu 8- lymphocytes were less active in this system. These data confirm the heterogeneity of the human T helper/inducer subset and indicate the existence of a population of OKT4+ lymphocytes that can suppress Ig secretion in the absence of OKT8+ lymphocytes.     

Behavior in chimeric mice combining differently behaving strains

A/J and C57BL/6J mice behave differently in tests for alcohol preference, open-field activity, defecation in the open field, cricket attacking, and rope climbing. Chimeric mice, i.e., mice containing both A/J cells and C57BL/6J cells, were constructed and tested for these behaviors. Patterns of behavior among A/JC57BL/6J chimeras are such as to suggest that none of these behavior differences is controlled by a single cell or clone and that the same cell population that gives rise to the strain difference in alcohol preference also gives rise to the differences in open-field activity and defecation, while separate cell populations control cricket killing and rope climbing.This research was supported by Research Grants AA 00388 and HD 03015 to M. N. N. and MH 18996 to K. B. Computing assistance was obtained from the Health Sciences Computing Facility, UCLA, supported by NIH Special Research Resources Grant RR-3.