T2 prolongation in the cerebellar vermis on prenatal MRI of fetuses with Chiari 2 malformations.

AIM: To describe a new finding in fetuses with Chiari 2 malformations recognised at in utero (iu) magnetic resonance imaging (MRI), specifically T2 prolongation (high signal) in the cerebellar vermis. MATERIALS AND METHODS: This was a prospective observational study of iuMRI studies performed at two time points on 20 fetuses with Chiari 2 malformations and 10 control fetuses at the same time points. High T2 signal in the cerebellar vermis was noted and correlated with posterior fossa dimensions was assessed. RESULTS: High T2 signal in the cerebellar vermis was found in over half of the fetuses with a Chiari 2 malformation, but was not correlated with the degree of reduction in size of the bony posterior fossa. CONCLUSION: The present findings suggest that abnormal high T2 signal in the cerebellum is common in fetuses with Chiari 2 malformations and although the cause of the signal change is not known at present it may represent vasogenic oedema as a result of restricted venous drainage.

The effect of detergents on the basement membrane complex of a biologic scaffold material.

The basement membrane complex (BMC) is a critical component of the extracellular matrix (ECM) that supports and facilitates the growth of cells. This study investigates four detergents commonly used in the process of tissue decellularization and their effect upon the BMC. The BMC of porcine urinary bladder was subjected to 3% Triton-X 100, 8mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 4% sodium deoxycholate or 1% sodium dodecyl sulfate (SDS) for 24h. The BMC structure for each treatment group was assessed by immunolabeling, scanning electron microscopy (SEM) and second harmonic generation (SHG) imaging of the fiber network. The composition was assessed by quantification of dsDNA, glycosaminoglycans (GAG) and collagen content. The results showed that collagen fibers within samples treated with 1% SDS and 8mM CHAPS were denatured, and the ECM contained fewer GAG compared with samples treated with 3% Triton X-100 or 4% sodium deoxycholate. Human microvascular endothelial cells (HMEC) were seeded onto each BMC and cultured for 7 days. Cell-ECM interactions were investigated by immunolabeling for integrin ß-1, SEM imaging and semi-quantitative assessment of cellular infiltration, phenotype and confluence. HMEC cultured on a BMC treated with 3% Triton X-100 were more confluent and had a normal phenotype compared with HMEC cultured on a BMC treated with 4% sodium deoxycholate, 8mM CHAPS and 1% SDS. Both 8mM CHAPS and 1% SDS damaged the BMC to the extent that seeded HMEC were able to infiltrate the damaged sub-basement membrane tissue, showed decreased confluence and an atypical phenotype. The choice of detergents used for tissue decellularization can have a marked effect upon the integrity of the BMC of the resultant bioscaffold.

Safe initiation of oral diets in hospitalized patients based on passing a 3-ounce (90 cc) water swallow challenge protocol.

BACKGROUND: Safe and timely oral alimentation is crucial for optimum patient care. OBJECTIVE: To determine the short-term success of recommending specific oral diets, including drinking thin liquids, to acute care hospitalized patients at risk for dysphagia based on passing a 3-ounce water swallow challenge protocol. DESIGN: Prospective single group consecutively referred case series. SETTING: Large, urban, tertiary care, teaching hospital. PARTICIPANTS: 1000 hospitalized patients. INTERVENTION: 3-ounce (90 cc) water swallow challenge protocol. MEASUREMENTS: Specific diet recommendations and volume (in cc) of liquid ingested at the next day's meal 12-24 h after passing a 3-ounce challenge protocol were accessed electronically from oral intake information entered on each participant's daily care logs. Eating and drinking success, clinically evident aspiration events and compliance with ordering the recommended diet were recorded. Care providers were blinded to the study's purpose. RESULTS: Of 1000 patients, 907 met the inclusion criteria of stable medical, surgical or neurological conditions 12-24 h after passing a 3-ounce water swallow challenge protocol. All 907 were both eating and drinking thin liquids successfully and without overt signs of dysphagia. Median volume of liquid ingested was 340 cc [interquartile range (IQR), 240-460]. Specific diet recommendations were followed with 100% accuracy. CONCLUSION: A 3-ounce water swallow challenge protocol successfully identified patients who can be safely advanced to an oral diet without subsequent identification of overt signs of aspiration within 12-24 h of testing. Importantly, when a clinical 3-ounce challenge protocol administered by a trained provider is passed, specific diet recommendations, including drinking thin liquids, can be made safely and without the need for additional instrumental dysphagia testing.

Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall-cell lung cancer.

BACKGROUND: Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naïve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standard, front-line, platinum-based doublets have not been extensively explored. We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naïve patients with advanced, nonsquamous NSCLC. METHODS: Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m(2)), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Secondary endpoints included safety, response rates, and overall survival. RESULTS: The median number of chemotherapy and maintenance bevacizumab cycles/patient was 6 and 2, respectively. Grades 3-5 adverse events included febrile granulocytopenia (10%), infections (13%), bleeding (13%), thrombotic events (13%), hypertension (5%), bowel perforation (5%), and proteinuria (3%). Median progression-free survival was 7.9 months and median overall survival was 16.5 months. Partial responses were observed in 21 patients (53%), and stable disease >or=6 weeks occurred in another 17 patients (43%), for a disease control rate of 95%. CONCLUSIONS: Carboplatin, docetaxel, and bevacizumab were feasible and effective for front-line treatment of advanced, nonsquamous NSCLC. These data provide further evidence that bevacizumab may be used in combination with multiple standard, platinum-based doublets in this setting.

A frame-based representation for a bedside ventilator weaning protocol.

We describe the use of a frame-based knowledge representation to construct an adequately-explicit bedside clinical decision support application for ventilator weaning. The application consists of a data entry form, a knowledge base, an inference engine, and a patient database. The knowledge base contains database queries, a data dictionary, and decision frames. A frame consists of a title, a list of findings necessary to make a decision or carry out an action, and a logic or mathematical statement to determine its output. Frames for knowledge representation are advantageous because they can be created, visualized, and conceptualized as self-contained entities that correspond to accepted medical constructs. They facilitate knowledge engineering and provide understandable explanations of protocol outputs for clinicians. Our frames are elements of a hierarchical decision process. In addition to running diagnostic and therapeutic logic, frames can run database queries, make changes to the user interface, and modify computer variables.

The Rotational Spectra, Structure, Internal Dynamics, and Electric Dipole Moment of the Argon-Ketene van der Waals Complex.

Pulsed-beam Fourier transform microwave spectroscopy was used to observe and assign the rotational spectra of the argon-ketene van der Waals complex. Tunneling of the hydrogen or deuterium atoms splits the a- and b-type rotational transitions of H(2)CCO-Ar, H(2)(13)CCO-Ar, H(2)C(13)CO-Ar, and D(2)CCO-Ar into two states. This internal motion appears to be quenched for HDCCO-Ar where only one state is observed. The spectra of all isotopomers were satisfactorily fit to a Watson asymmetric top Hamiltonian which gave A=10 447.9248(10) MHz, B=1918.0138(16) MHz, C=1606.7642(15) MHz, Delta(J)=16.0856(70) kHz, Delta(JK)=274.779(64) kHz, Delta(K)=-152.24(23) kHz, delta(J)=2.5313(18) kHz, delta(K)=209.85(82) kHz, and h(K)=1.562(64) kHz for the A(1) state of H(2)CCO-Ar. Electric dipole moment measurements determined &mgr;(a)=0.417(10)x10(-30) C m [0.125(3) D] and &mgr;(b)=4.566(7)x10(-30) C m [1.369(2) D] along the a and b principal axes of the A(1) state of the normal isotopomer. A least squares fit of principal moments of inertia, I(a) and I(c), of H(2)CCO-Ar, H(2)(13)CCO-Ar, and H(2)C(13)CO-Ar for the A(1) states give the argon-ketene center of mass separation, R(cm)=3.5868(3) Å, and the angle between the line connecting argon with the center of mass of ketene and the C=C=O axis, θ(cm)=96.4 degrees (2). The spectral data are consistent with a planar geometry with the argon atom tilted toward the carbonyl carbon of ketene by 6.4 degrees from a T-shaped configuration. Copyright 2001 Academic Press.

Support for basic gerontological research in the USA.

Support for research in basic gerontology in the United States of America is briefly described. The support mechanisms, how to apply for a grant, and priority areas of research are outlined, and recent progress in a few of these priority areas is discussed. In general, government support for biogerontology research has been generous, and as a result considerable progress has been made in understanding the molecular mechanisms of aging in animal model systems. Translation of these findings to humans, and development of interventions to promote healthy aging in humans remain an unfulfilled priority, but new knowledge and development of better technologies and model systems suggest an optimistic future.

The case for supporting basic research in gerontology.

Basic research on aging has moved well beyond describing the aging of physiological systems and developing theories of aging, to the pursuit of mechanistic answers to questions such as: Why do we age? Why do individuals within a population age differently? Why do different species have such different life spans? How do aging changes increase the risk of developing age-related disease? and Can we develop safe and effective interventions to reduce age-related disability? Two general areas of research promise to provide answers to these questions. One is the attempt to understand the mechanisms by which caloric restriction extends longevity and delays the onset of age-related disease. The other is the identification of genes which strongly influence the rate of aging in various animal model systems. Recent results in the latter area of research are providing new insights into the answers to these central aging questions and may help us understand how caloric restriction retards aging.

Program for testing biological interventions to promote healthy aging.

The National Institute on Aging (NIA) sponsored a workshop on September, 1999 to discuss the feasibility of establishing a program to evaluate potential intervention strategies to decelerate the rate of aging in mammals. The ultimate goal is to identify promising interventions in animals that might lead to clinical trials in humans. The participants discussed various animal models, biological endpoints and possible structure of such a program. The ability to implement such a program will require a decision by NIA staff about whether the anticipated benefits to be derived from identification of effective interventions under well controlled conditions in an animal model, in this case the mouse, would justify the anticipated cost of the testing program.

Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database.

The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality is not based on research data. We assessed suicides, suicide attempts, and depressive symptom reduction in studies of 7 new antidepressants using the Food and Drug Administration database. Among 19,639 participating patients, 34 committed suicide (0.8% per year), and 130 attempted suicide (2.9% per year). Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups. Annual rates of suicide and attempted suicide were 0.4% and 2.7% with placebo, 0.7% and 3.4% with active comparators, and 0.8% and 2.8% with investigational antidepressants, respectively. Symptom reduction was 40.7% with investigational drugs (n = 4,510), 41.7% with active comparators (n = 1,416), and 30.9% with placebo (n = 2,805). These data may help inform discussions about the use of placebo in antidepressant clinical trials.

Making the invisible, visible.

Special needs children experience all the difficulties experienced by any child admitted to hospital although these are hugely magnified. Parents continue to carry the burden of care, even after hospital admission, when their child has complex needs. Nurses need to remember that these children have all the needs of any child in addition to needs specific to their disability. Nurses should focus what the child can do, rather than what they cannot do.

Modeling empiric antibiotic therapy evaluation of QID.

At AMIA 1997, we reported on the design and development of a new computer-based tool, called QID, for empiric antibiotic decision support. QID was designed to help physicians identify the antibiotic regimens with the highest probability of covering the pathogens that are most likely to be present in individual patients. QID creates a list of antibiotics, ordered by potential benefit in treatment, for a patient with a suspected infection before culture results are available. Since our initial publication, a "before and after" study has been done using 20 internal medicine residents and the same number of internal medicine attendings. In order to test the hypothesis that physician's would make more appropriate empiric antibiotic choices with the aid of QID, we chose University of Utah physicians and had each evaluate four infectious disease cases that were abstracted from medical record infectious disease cases. Immediately following their initial review and determination of antibiotic therapy for each case, the study participants were presented with QID's antibiotic recommendations on the same case to see if this information would change their initial drug regimen. The tool was shown to have a greater impact on the most difficult cases but statistically improved scores overall (p < .001). Details of our study design and results are presented.

The HELP hospital information system: update 1998.

The HELP hospital information system has been operational at LDS Hospital since 1967. The system initially supported a heart catheterization laboratory and a post open heart Intensive Care Unit. Since the initial installation the system has been expanded to become an integrated hospital information system providing services with sophisticated clinical decision-support capabilities to a wide variety of clinical areas such as laboratory, nurse charting, radiology, pharmacy, etc. The HELP system is currently operational in multiple hospitals of LDS Hospital's parent health care enterprise--Intermountain Health Care (IHC). The HELP system has also been integrated into the daily operations of several other hospitals in addition to those at IHC. Evaluations of the system have shown: (1) it to be widely accepted by clinical staff; (2) computerized clinical decision-support is feasible; (3) the system provides improvements in patient care; and (4) the system has aided in providing more cost-effective patient care. Plans for making the transition from the 'function rich' HELP system to more modern hardware and software platforms are also discussed.

Apoptosis: a two-edged sword in aging.

It is now recognized that apoptosis plays an important role in many physiological processes, including aging and age-related diseases. Apoptosis plays both positive and negative roles in aging, and some of these roles are reviewed here. Of particular importance are the roles of apoptosis in reducing cancer incidence, and in promoting neurodegenerative disease. Therefore, the regulation of apoptosis is an inviting target for therapeutic interventions in aging and age-related disease.