Positive end-expiratory pressure and the damaged right ventricle. An experimental open versus closed chest study

Hemodynamic changes after isolated impairment of right ventricular function (produced by increasing afterload by temporary banding of the pulmonary artery) were studied in 22 ventilated pigs during increased levels of positive end-expiratory pressure (4, 8, 12, and 16 cm H2O). In the open chest group, application of positive end-expiratory pressure produced only a slight decrease of cardiac index. After right ventricular damage a decrease of cardiac index of more than 25% occurred only when higher levels of positive end-expiratory pressure were applied. In contrast to the open chest group, the closed chest group showed more distinct cardiovascular responses after positive end-expiratory pressure. In the damaged right ventricle with a positive end-expiratory pressure of 16 cm H2O, right ventricular end-diastolic pressure increased more than 100%. With positive end-expiratory pressure, cardiac index decreased 34% before and 47% after right ventricular damage. We conclude that positive end-expiratory pressure induces a more pronounced decrease in cardiac index if right ventricular function is impaired. During open chest conditions with lower levels of positive end-expiratory pressure, these changes are only small, however, and probably irrelevant. During closed chest conditions, the hemodynamic changes are much more pronounced. High right ventricular end-diastolic pressures resulting from impaired right ventricular contractility as well as from high levels of positive end-expiratory pressure may have an impact on biventricular function and right ventricular coronary driving pressure.     

The development of a research human milk bank.

Although there are well-established clinical human milk banks in the United States, there are no milk banks specifically intended to foster research on human milk. The authors' goal was to establish a milk bank with a core data set to support exploratory and hypothesis-driven studies on human milk. Donations to the Cincinnati Children's Research Human Milk Bank are accepted within the context of ongoing, hypothesis-driven research or on an ad hoc basis. Donors must give informed consent, and scientists wishing to use the samples must have Institutional review board approval for their use. Development of more research human milk banks can potentially provide resources for multidisciplinary collaboration and advance the study of human milk and lactation.     

Ethik in der Intensivmedizin

In more than 30 years of development of intensive care medicine (ICM), our speciality has acquired moral and ethical standpoints, although not without public pressure and discussions. Special commissions dealing, e.g., with brain death, terminal care, ethics of foregoing life-sustaining treatment in the critically ill, withholding or withdrawing mechanical ventilation, and other issues have meen formed in a number of medical societies. International consensus conferences have helped to clarify some of the issues. With increasing experience, a multitude of ethical problems have arisen in ICM that have to be dealt with, such as the issue of quality of life. What is an unworthy life? Are we allowed to make judgments for our patients? What is cost-effectiveness in ICM? Other restrictions include bed and equipment shortages in the intensive care unit (ICU), the necessity for triage – undisputed in catastrophe medicine – and how one should proceed in managing elective patients? In situations of limited ICU bed availability, sicker patients will be admitted, sparing out patients who are less ill for observation and those with poor quality of life and poor prognosis. For the future, it will likely be necessary to define the patients who should be admitted to an ICU more than those who should not be admitted. An ICU treatment entitlement index would be directly proportional to the probability of successful outcome and the quality of the remaining life, and would be inversely related to costs for achieving success. The ICU outcome with survival, hospital mortality, and follow-up of ICU patients is considered. DNR (do not resuscitate), the dying patient, terminal care, terminal weaning – DNT (do not treat) – active and passive euthanasia, living wills, quality of life, and cost-effectiveness for ICU patients are defined. Their application in the ICU will be discussed and problems pointed out. Outcome predictions using scores (APACHE III, SAPS II, MPM) have been developed based on previous experience, but should only be applied to patient groups and for quality assurance in ICUs. The most frequent and difficult problem in the ICU is the vegetative state, which requires an exact diagnosis. The differential diagnosis from other comatose states such as coma, brain death, and locked-in-syndrome is depicted. The ethics of interrupting life-sustaining treatment in critically ill patients have been worked out by a Task Force on Ethics of the Society of Critical Care Medicine (1990). A consensus was found that the patient may judge to forego therapy; ethically it is then appropriate to withhold or withdraw therapy. According to the consensus, withdrawing an already initiated treatment should not necessarily be regarded as more problematic than a decision not to initiate treatment. In my mind, however, there is a great difference between withdrawing or withholding, e.g., ventilation. A dissentive opinion by some members of the Task Force stated that hydration and nutrition other than high-technology or parenteral nutrition are key components of patient care, and should not be equated with medical intervention. The ethical problems associated with active euthanasia (physician-assisted suicide or death) as practised in the Netherlands are also discussed. In most countries this practice seems unacceptable. From 30 years experience in ICM, there are many more ethical questions and case reports without clear solutions. Care decisions for single patients in unacceptable situations should be made after medical evaluation by the intensivist with the medical team and, if possible, by the patient and/or his or her surrogate. Legislation and solutions cannot be expected for single patients, but ethics committees could be helpful in decision-making.     

Association between platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31) polymorphisms and acute myocardial infarction: a study in patients from Sicily.

Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leucocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. A few studies have investigated an association between coronary heart disease and single nucleotide polymorphisms (SNPs) located in functionally important domains of the PECAM-1/CD31 gene. In particular, Ser563Asn and Gly670Arg SNPs have been described as susceptibility factors involved in acute myocardial infarction (AMI) in the Japanese male population. To confirm these observations, we studied 96 male patients (mean age 40 years; age range 20-46) affected by AMI and 118 healthy male controls (mean age 38 years, age range: 20-55), and analysed for the following PECAM-1/CD31 SNPs: Val125Leu, Asn563Ser and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with AMI (58.9% vs. 48.3%; P = 0.019), whereas the frequencies of the other two SNPs (Leu125Val and Ser563Asn) were not significantly different between patients and controls. By comparing the observed number of 670Arg/Arg genotypes in the patients with the expected number, calculated from the allele frequency in a healthy population, a significance of P = 0.02 (odds ratio, 2.04; 95% CI: 1.1-3.7) was obtained, supporting a recessive model of inheritance. Hence, the differences between patients and controls are significant, but relatively small. However, as AMI is a multifactorial disease, any single mutation will only provide a small or modest contribution to the risk, which also depends on environmental interaction. All in all, we believe that the results of the present study would add support to the role of pro/anti-inflammatory genotypes in determining susceptibility or resistance to immune-inflammatory diseases, including atherosclerosis.     

Report of an unusual lymphoma arising from parafollicular B-lymphocytes (PBLs) or so-called "monocytoid" lymphocytes

A distinctive B-cell has been recognized recently in reactive lymph nodes, especially those of toxoplasmic lymphadenitis. Previously designated as "immature sinus histiocytes" or "monocytoid" cells, these B-lymphocytes proliferate in subcapsular and parenchymal sinuses and the parafollicular area of nodes. The authors now report a 55-year-old male who developed a malignant lymphoma composed of cells with light microscopic, immunologic, and ultrastructural characteristics identical with these newly described B-cells. The term parafollicular B-lymphocytes (PBLs) is recommended herein to emphasize their morphologic and immunologic features. An unusual feature of this PBL lymphoma is the numerous benign-appearing hyperplastic follicles surrounded by the neoplastic infiltrate, mimicking the cytologic appearance and distribution of PBLs seen in toxoplasmic lymphadenitis. The function of these recently recognized B-cells is unknown; their anatomic relationship with hyperplastic follicular centers in reactive states and the lymphoma herein described suggests a role in follicular function.     

Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer.

PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. CONCLUSION: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.