Correlation of the chemical structure of 4-nitroquinolines inactivating human cytomegalovirus and established in vivo carcinogenicity tests

Inactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) has been observed following exposure to 4-nitroquinoline 1-oxide (NQO) or its metabolite, 4-hydroxyaminoquinoline 1-oxide (HAQO). The present study of the specificity of the chemical structure of 4-nitroquinolines demonstrated that both the 4-nitro and 1-oxide groups were required for inactivation of virus infectivity. Reduction of the 4-nitro group to a 4-hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the same group of chemicals.     

Frequent transmission of enterococcal strains between mechanically ventilated patients treated at an intensive care unit

The objectives of this investigation were to study the respiratory tract colonization and transmission of enterococci between 20 patients treated with mechanical ventilation at an intensive care unit (ICU), to compare genotyping with phenotyping, and to determine the antibiotic susceptibilities of the isolated enterococci. Samples were collected from the oropharynx, stomach, subglottic space, and trachea within 24 h of intubation, every third day until day 18, and thereafter every fifth day until day 33. Enterococcal isolates (n = 170) were analyzed by pulsed-field gel electrophoresis and with the PhenePlate (PhP) system. The antimicrobial susceptibilities to five agents were determined. Seventeen of the 20 subjects were colonized with enterococci in the respiratory tract; 12 were colonized in the lower respiratory tract. Genotype analyses suggested that 13 patients were involved in a transmission event, including all patients intubated more than 12 days. In conclusion, colonization of resistant enterococci in the respiratory tract of intubated patients treated at an ICU was common. Transmission of enterococci between patients occurred frequently. Prolonged intubation period seems to be a risk factor for enterococcal cross-transmission.     

Ex vivo testing of the intravenous membrane oxygenator

Intravenous oxygenation represents a potential respiratory support modality for patients with acute respiratory failure or with acute exacerbations of chronic respiratory conditions. Our group has been developing an intravenous oxygenator, the IMO, which uses a constrained fiber bundle and a rapidly pulsating balloon within the fiber bundle. Balloon pulsation drives blood flow past the fibers at greater relative velocities than would otherwise exist within the host vessel, and gas exchange rates are enhanced. The purpose of this study was twofold: (1) to characterize the gas exchange performance of the current IMO in an extracorporeal mock vena cava vessel under conditions of known fixed vessel geometry and controlled blood flow rates; and (2) to compare the IMO gas exchange performance to that reported for the clinically tested IVOX device within a comparable ex vivo set-up. The ex vivo flow loop consisted of a 1 inch ID tube as a mock vena cava that was perfused directly from an anesthetized calf at blood flow rates ranging from 1 to 4 1/2 L/min. O2 and CO2 exchange rates were measured for balloon pulsation rates, which ranged from 0 to 180 bpm. Balloon pulsation significantly increased gas exchange, by 200-300% at the lowest blood flow rate and 50-100% at the highest blood flow rate. Balloon pulsation eliminated much if not all of the dependence of the gas exchange rate on blood flow rate as seen in passive oxygenators. This suggests that in clinical application the IMO may exhibit less gas transfer variability due to differences in cardiac output Over the entire flow rate range studied, the CO2 and O2 gas exchange rates of the IMO at maximal balloon pulsation varied from approximately 250 to 350 ml/min/m2. At maximum balloon pulsation the IMO exchanged CO2 and O2 at rates from 50-500% greater, depending upon the blood flow rate, than the exchange rates reported for the IVOX device in ex vivo tests.     

Determinants of long-term survival after isolated aortic valve replacement: a 10- to 17-year follow-up

During a 9-year period from January 1965 through December 1973, we performed isolated aortic valve replacement (AVR) for aortic stenosis (AS) or aortic regurgitation (AR) in 165 patients. All operations were done during total cardiac arrest using chemical cardioplegia according to the method of Bretschneider. The prostheses used were predominantly Starr-Edwards caged ball valves. One hundred thirty-nine patients were alive 30 days after operation. The 5-, 10-, and 15-year cumulative survival rates (+/- SE) were 78 +/- 4%, 62 +/- 4%, and 29 +/- 9%, respectively. In comparison to a sex- and age-matched control population, our patients had an excess mortality in the first postoperative year and again after the twelfth year. Patients who underwent AVR in 1972 and 1973 had better results than those who had operations in 1965 through 1971 (p < 0.05); the 1972-1973 patients had 5- and 10-year survival rates of 81 +/- 5% and 72 +/- 5%, respectively. The 1-year survival rate was 91% for patients with AS and 71% for those with AR (p < 0.05). In AS patients, long-term survival was adversely affected by a history of left ventricular failure, inclusion in NYHA functional class IV, cardiothoracic index of >/= 0.56, cardiac index of < 3.0 L/min/m(2), age > 55 years, previous myocardial infarction, systemic pulse pressure of /= 15 mm Hg, and mean pulmonary artery pressure of >/= 24 mm Hg. In AR patients, an adverse prognosis was associated with left ventricular failure, syncope, age >/= 60 years, and NYHA class IV status. These results indicate that, in both AS and AR patients, operation should be performed early, before severely limiting symptoms and signs arise.     

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.     

Creating patient-centered radiology reports to empower patients undergoing prostate magnetic resonance imaging

IntroductionAs we progress to an era when patient autonomy and shared decision-making are highly valued, there is a need to also have effective patient-centered communication tools. Radiology reports are designed for clinicians and can be very technical and difficult for patients to understand. It is important for patients to understand their magnetic resonance imaging (MRI) report in order to make an informed treatment decision with their physician. Therefore, we aimed to create a patient-centered prostate MRI report to give our patients a better understanding of their clinical condition.MethodsA prototype patient-centered radiology report (PACERR) was created by identifying items to include based on opinions sought from a group of patients undergoing prostate MRI and medical experts. Data was collected in semi-structured interviews using a salient belief question. A prototype PACERR was created in collaboration with human factors engineering and design, medical imaging, biomedical informatics, and cancer patient education groups.ResultsFifteen patients and eight experts from urology, radiation oncology, radiology, and nursing participated in this study. Patients were particularly interested to have a report with laymen terms, concise language, contextualization of values, definitions of medical terms, and next course of action. Everyone believed the report should include the risk of MRI findings actually being cancer in the subsequent biopsy.ConclusionsA prostate MRI PACERR has been developed to communicate the most important findings relevant to decision-making in prostate cancer using patient-oriented design principles. The ability of this tool to improve patient knowledge and communication will be explored.     

Devices for the diagnosis and treatment of temporomandibular disorders. Part I: Introduction, scientific evidence, and jaw tracking

This three-part series of articles summarizes the uses of several devices or groups of devices intended for the diagnosis or treatment of temporomandibular disorders (TMD) and compares their claimed clinical usefulness with the present scientific evidence. Part I of this review defines TMD; discusses the principal criteria for evaluating published scientific clinical evidence such as reliability, validity, sensitivity, and specificity; gives a rationale for the clinical "gold standard" against which diagnostic and therapeutic devices must be compared; and evaluates the status of jaw tracking for the diagnosis of TMD. This review and evaluation led to the conclusion that, at the present time, the claim that jaw-tracking devices have a diagnostic value for TMD is not well supported by the scientific evidence.     

Comparison of Intrinsic Connectivity in Different Areas of Macaque Monkey Cerebral Cortex

We have used small injections of biocytin to label and comparepatterns of intreareal, laterally spreading projections of pyramidalneurons in a number of areas of macaque monkey cerebral cortex.In visual areas (V1, V2, and V4), somatosensory areas (3b, 1,and 2), and motor area 4, a punctate discontinuous pattern ofconnections is made from 200-µm-diameter biocytin injectionsin the superficial layers. In prefrontal cortex (areas 9 and46), stripe-like connectivity patterns are observed. In allareas of cortex examined, the width of the terminal-free gapsis closely scaled to the average diameter of terminal patches,or width of terminal stripes. In addition, both patch and gapdimensions match the average lateral spread of the dendriticfield of single pyramidal neurons in the superficial layersof the same cortical region. These architectural features ofthe connectional mosaics are constant despite a twofold differencein scale across cortical areas and different species. They thereforeappear to be fundamental features of cortical organization.A model is offered in which local circuit inhibitory "basket"interneurons, activated at the same time as excitatory pyramidalneurons, could veto pyramidal neuron connections within eithercircular or stripe-like domains; this could lead to the formationof the pattern of lateral connections observed in this study,and provides a framework for further theoretical studies ofcerebral cortex function.