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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial.

200 adult respiratory distress syndrome patients were included in a prospective multicenter randomized trial to determine the efficacy of computerized decision support. The study was done in 10 medical centers across the United States. There was no significant difference in survival between the two treatment groups (mean 2 = 0.49 p = 0.49) or in ICU length of stay between the two treatment groups when controlling for survival (F(1df) = 0.88, p = 0.37.) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group (F(1df) = 4.1, p = 0.04) as well as significantly lower incidence and severity of overdistension lung injury (F(1df) = 45.2, p < 0.001). We rejected the null hypothesis. Efficacy was best for the protocol group. Protocols were used for 32,055 hours (15 staff person years, 3.7 patient years or 1335 patient days). Protocols were active 96% of the time. 38,546 instructions were generated. 94% were followed. This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical settings and significantly improve patient morbidity.

Adult↗
PubMed1998

Movements modulate the reflex responses of human flexor pollicis longus to stretch.

The reflex responses to brisk, ramp stretch perturbations of the human flexor pollicis longus muscle (FPL) were recorded during isometric and slow concentric or eccentric contractions at similar levels of muscle excitation. The subjects flexed their thumb to push down against a thumb-rest, whose position was controlled by a servo-controlled motor. In different runs, the stretch perturbations were imposed when the thumb-rest was stationary (isometric) or was flexing or extending the interphalangeal joint of the thumb at a constant velocity, i.e. during concentric or eccentric contractions of FPL. The latency of the most prominent component of the electromyographic reflex in the isometrically contracting muscle was about 60 ms, measured from the command signal. The amplitude of this response was sharply reduced during the non-isometric contractions. While not dependent on the direction, this modulation of the reflex response increased with the speed of active movement of the interphalangeal joint (flexion or extension). The response was greatly reduced during concentric or eccentric movements as slow as 1.6 mm x s[-1] (approximately 5 degrees x s (-1) at the joint). When the force rather than the position of the thumb-rest was servo-controlled, the stretch response to perturbation again diminished with speed in a self-paced flexion task, compared with an isometric "hold" condition.

Adult↗
PubMed1998

Evaluation of compliance with a computerized protocol: weaning from mechanical ventilator support using pressure support.

STUDY OBJECTIVES: To use a computerized consultation system to evaluate the feasibility of a mechanical ventilator weaning protocol which used the rapid shallow breathing index to guide adjustments in pressure support. A program to monitor user compliance and reasons for noncompliance was built into the computerized consultation system. METHODS: A total of nine critically ill patients (ten weaning episodes) were enrolled in the protocol. The respiratory therapists performed routine computer charting in the electronic database. They accepted or declined the explicit instructions generated by the computerized protocol and displayed on the bedside terminal. The consultation program monitored whether accepted instructions were implemented by the user. RESULTS: Patient's therapy was controlled by protocol for a total of 1075 h (mean 108 h, range 4 to 339 h) and 94.8% (1321/1394) of instructions were followed by the clinical staff. Of the 42 instructions clinical staff refused to follow, 23 (55%) were extubation instructions. There were 52 (3.7%) incorrect instructions generated with 24 software errors, 21 errors in underlying logic, and seven user misunderstanding errors. CONCLUSIONS: A high level of user compliance with this protocol was achieved. The methods described herein to monitor compliance and reasons for noncompliance within a protocol are reusable in the domain of mechanical ventilation and possibly in other domains.

Evaluation Studies as Topic↗
PubMed1998

Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia.

OBJECTIVE: The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with the latter conducted by paraprofessionals. METHOD: Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through "doctor's choice" by psychiatrists who were blind to the psychosocial treatment assignments. RESULTS: Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning. CONCLUSIONS: Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy.

Activities of Daily Living↗
PubMed1998

Teaching psychiatric inpatients to re-enter the community: a brief method of improving the continuity of care.

OBJECTIVE: The study evaluated the effects of a brief manualized treatment program that taught patients skills to re-enter the community and actively follow through with their own care. METHODS: A total of 59 recently admitted inpatients with schizophrenia or schizoaffective disorder were randomly assigned to either the community re-entry program or an equally intensive regimen of occupational therapy. The community re-entry program consisted of eight 45-minute sessions conducted with groups of six to eight patients on a continuous, twice-a-day, four-day-a-week schedule. The effects were measured by a review of the records of aftercare services that patients received in the month after discharge from the inpatient facility. Patients' knowledge and performance of the specific material taught in the community reentry program was ascertained through assessments conducted before and after training. RESULTS: Results indicated that patients in the community re-entry program significantly improved their knowledge and performance of the skills taught in the sessions, compared with patients in the occupational therapy group. Community re-entry participants were also significantly more likely to attend their first aftercare appointment than were occupational therapy participants (85 percent versus 37 percent). CONCLUSIONS: Not only can patients learn relatively complex material during a brief typical inpatient stay despite the acuteness of their illnesses, but they can also meaningfully improve the continuity of their own care by participating in a brief and highly structured training program. The program fits well within the time and staffing constraints of typical inpatient facilities.

Activities of Daily Living↗
PubMed1998

Applying Senge's concepts of organizational learning to clinical outcomes research and practice.

The purpose of this article is to use Senge's concepts of organizational learning as a framework for discussing issues and challenges in clinical outcomes research. Clinical outcomes research is about learning how to improve clinical practice. A learning organization balances attention to the structure and the culture in order to produce effective results. Future health care leaders will need to understand and attend to the importance of the organization's structure, but their greatest contribution will be in attending to the organizational culture to produce enduring organizational change.

Humans↗
PubMed1997

A rationale for the absolute conservation of Asn70 and Pro71 in mitochondrial cytochromes c suggested by protein engineering.

The absolutely conserved residues Asn70 and Pro71 of mitochondrial cytochrome c have been targeted for protein engineering by semisynthesis. Neither residue has even been implicated in mechanistic schemes, and we reasoned that the conservation of this dipeptide was to fulfill a crucial structural role. Semisynthesis was through condensation by autocatalytic fragment religation of natural fragment 1-65 (H) of the horse protein and synthetic 39-residue peptides containing noncoded amino acids prepared by solid-phase methods. High yields of the purified analogs, homoserine70 and norvaline71 cytochromes c, were obtained. Functional tests revealed minor destabilization of the Hse70-containing structure, with little adverse effect in in vitro assays, but [Nva71] cytochrome c was essentially devoid of activity in these systems. This appeared to be a consequence of a shift, more pronounced than any yet reported, in the conformational equilibrium between the active state III conformer and the inactive, 'alkaline' state IV. The results support our view that this dipeptide is optimal for, and rigidifies, the right-angle bend between two alpha-helices, thus determining the conformation of the 70s loop that terminates in the sixth ligand Met80, and 'forcing' the coordination of iron by thioether sulfur in the presence of the adjacent more avid amine ligands of state IV. Not only is [Nva71] cytochrome c inactive at pH 7, but it also proves to be an extremely potent inhibitor of electron transfer by native state III, thus providing the rationale for the evolutionary conservation of a high pK for the ligand exchange reaction.

Amino Acid Sequence↗
PubMed1997

The invariant ARG91 is required for the rupture of liposomes by cytochrome C.

Lipid binding properties of cytochrome c (cyt c) were investigated by using semisynthetic mutant protein having amino acid substitution on the evolutionary invariant residue Arg91. We demonstrate here that the membrane binding properties of cyt c are dramatically altered by substituting norleucine for the invariant Arg91. More specifically, while the binding of this mutant to liposomes per se is indistinguishable from the wild type protein, it completely lacks the ability of the native cyt c to rupture liposome bilayers.

Animals↗
PubMed1997

Relationship between motor unit short-term synchronization and common drive in human first dorsal interosseous muscle.

We assessed the strength of motor unit (MU) short-term synchronization and common fluctuations in mean firing rate (common drive) in the same pairs of MUs in order to evaluate whether these features of voluntary MU discharge arise from a common mechanism. Shared, branched-axon inputs, with the most important being widely divergent monosynaptic projections to motoneurons from motor cortical cells, are regarded as the principal determinants of MU short-term synchronization. It is not known to what extent these synaptic inputs are responsible for common drive behaviour of MUs. MU spike trains from 77 pairs of concurrently active MUs in first dorsal interosseous muscle of 17 subjects were discriminated with the high reliability needed for common drive analysis. For each MU pair, the data used for comparison of the two analyses of correlated MU discharge came from a single trial (1-5 min duration) of isometric abduction of the index finger. Linear regression revealed a weak, significant positive correlation between the strength of MU short-term synchronization and the strength of common drive in the MU pairs (r2 = 0.06, P < 0.05, n = 77), which was slightly stronger when MU pairs with broad synchronous peaks (> 20 ms) were excluded (r2 = 0.09, P < 0.05, n = 63). These data suggest that less than 10% of the variation in the strength of common drive exhibited by pairs of MUs could be accounted for by differences in the strength of MU short-term synchronization. These two phenomena are therefore likely to arise predominantly from separate mechanisms. At least under these task conditions, the widely divergent, branched-axon inputs from single corticospinal neurons which are important in the generation of MU short-term synchronization play only a minor role in the production of common drive of MU discharge rates.

Adolescent↗
PubMed1997

Social processing correlates of nonverbal social perception in schizophrenia.

This study examines the relationship of nonverbal social perception to other areas of social functioning in schizophrenia. One model of interpersonal problem-solving skills presents a sequence of receiving, processing, and sending skills. Social perception skills best fit the first stage in this model: receiving skills. As expected, schizophrenic subjects (N = 29) were less skillful than normal subjects (N = 15) on measures of social problem solving, understanding of social sequences, and social judgment. In addition, performance on these tasks was significantly related to nonverbal social perception, but only for the schizophrenic group. Thus, deficits in nonverbal social perception are related to other measures of social functioning in schizophrenia. Implications of these findings for understanding and treating social deficits in schizophrenia are discussed.

Adult↗
PubMed1996

Synergy in protein engineering. Mutagenic manipulation of protein structure to simplify semisynthesis.

Semisynthesis is a chemical technique of protein engineering that provides a valuable complement to directed mutagenesis. It is the method of choice when the structural modification requires, for example, a noncoded amino acid. The process involves specific and limited protein fragmentation, structural manipulation of the target sequence, and subsequent religation of fragments to give the mutant holoprotein. We suggested and demonstrated that mutagenesis and semisynthesis could be used synergistically to achieve protein engineering goals otherwise unobtainable, if mutagenesis was used to shuffle methionine residues in the yeast cytochrome c sequence (Wallace, C. J. A., Guillemette, J. G., Hibiya, Y., and Smith, M. (1991) J. Biol. Chem. 266, 21355-21357). These residues can not only be sites of specific cleavage by CNBr but also of spontaneous peptide bond synthesis between fragments in noncovalent complexes, which greatly facilitates the semisynthetic process. We have now used an informed "methionine scan" of the protein sequence to discover other useful sites and to characterize the factors that promote this extraordinary and convenient autocatalytic religation. Of eight sites canvassed, in a wide range of settings, five efficiently provoked peptide bond synthesis. The principal factor determining efficiency seems to be the hydropathy of the religation site. The mutants created have also provided some new insights on structure-function relationships in the cytochrome.

Chemical Phenomena↗
PubMed1996

Definition of a nucleotide binding site on cytochrome c by photoaffinity labeling.

We have used TNP-8N3-AMP (2'(3')-O-(2,4,6-trinitrophenyl)-8-azidoadenosine monophosphate) and TNP-8N3-ATP to probe the ATP binding site(s) of cytochrome c. Irradiation of cytochrome c with close to stoichiometric amounts of TNP-8N3-AMP at low ionic strength derivatized approximately half of the protein, with the mono-derivatized species being associated with four peaks (B, 6%; C, 17%; D, 24%; E, 4%) eluted from a cation exchange column. Irradiation in the presence of ATP suggested that the main peaks C and D resulted from more specific nucleotide binding. Thermolysin digestion and TNP-peptide purification and sequencing revealed that peak C was associated with derivatization of mainly Lys-86 and to a lesser extent Lys-72 and peak D with mainly Lys-87 and less so with Lys-72. Minor peaks B and E could not be identified. TNP-8N3-ATP photolabeling produced similar results, showing favored interaction of the adenyl ring with Lys-86 and Lys-87 and to a lesser extent with Lys-72. The results are compatible with previous findings that suggest that the principal locus of ATP binding is at nearby Arg-91 (Corthesy, B. E., and Wallace, C. J. A.(1986) Biochem. J. 236, 359-364). Molecular modeling with energy-minimized docking of ATP between the 60s helix and the 80s stretch with the gamma-phosphate constrained to interact with Arg-91, places the 8 position close to Lys-86 and Lys-87 in the anti conformation about the glycosidic bond and to Lys-72 in the syn conformation, and the ribose hydroxyls within H-bonding distance of Glu-69.

Adenosine Monophosphate↗
PubMed1996

Multifocal white matter lesions.

There is a long differential diagnosis for multifocal white matter lesions on MR. The most common causes are prominent Virchow-Robin spaces, white matter ischemic change, and multiple sclerosis, but many other causes have been reported. Most of these are related to vascular or other demyelinating etiologies, but infectious/inflammatory disease, trauma, and neoplastic and other unusual causes may also be responsible. Typical imaging features of the more common multifocal white matter disorders are outlined, and the rarer causes are discussed briefly. An approach to imaging differential diagnosis is given, with emphasis on the differences between white matter ischemic lesions and multiple sclerosis.

Brain Diseases↗
PubMed1996

Training hospitalized patients with schizophrenia in community reintegration skills.

OBJECTIVE: The study examined the effectiveness of the Community Re-Entry Program, a brief, time-limited skills training module designed to help acutely ill inpatients become engaged in community-based treatment programs. METHODS: Of 84 consecutive admissions to a chronic psychotic disorders unit, 44 completed assessments and attended the Community Re-Entry Program. The program consists of 16 daily small-group therapy sessions that engage the patient in efforts to define discharge readiness, identify symptoms and medication effects, and assist with discharge planning. Skill levels and positive and negative symptoms were assessed on admission and on completion of training, and a subsample of patients received two-week postdischarge follow-up assessments. RESULTS: From admission to discharge, positive symptoms diminished substantially, negative symptoms diminished to a lesser but statistically significant degree, and skill levels increased significantly. Posttraining skill level was predicted by pretraining skill level and level of participation in the skills training module. Patients' symptom levels did not predict participation in the program or skill acquisition. Skill level at discharge was also more predictive of two-week postdischarge community adjustment than were symptom levels. CONCLUSIONS: Although further controlled studies are required to fully establish the efficacy of the Community Re-Entry Program, these data suggest that brief, focused skills training may play an important role in augmenting optimal pharmacotherapy for hospitalized patients with chronic psychotic disorders.

Activities of Daily Living↗
PubMed1996

Quality improvement and substance abuse: rethinking impaired provider policies.

Substance abuse is known to be our nation's number one public health problem. Physicians and other health providers can develop chemical dependency problems that create significant quality assurance and risk management dilemmas. Not all of society understands drug dependence to be a treatable medical disease and behavioral problem. Sometimes impaired providers are ignored or punished rather than treated and rehabilitated. This results in an enormous waste of human and monetary resources. In the last 10 years, impaired physician programs have developed focus and credibility. But certain difficulties exist in these programs: namely, that such programs are affected by tensions between medical societies and state licensing boards; that substance-dependent providers escape detection by moving to other states; that existing impaired provider programs have limited practical application within the federal health care system; and that liability risks are incurred if institutions rely on impaired provider policies that do not include all members of the medical staff. Hence, we argue that existing impaired provider policies might be worth rethinking. To promote that dialogue, we offer a sample policy for consideration and review. It includes specific actions and procedures for the identification, referral, and reentry of impaired providers and allows for National Practitioner Data Bank reporting in that process. The Data Bank has been in place for only a few years and offers society and the health community a new opportunity to better control chemically dependent, licensed medical staff without dismantling existing impaired provider programs. The policies for managing chemically dependent health professionals are changing from a focus on stigma and prosecution to one of early identification, rehabilitation, and reentry. We hope to advance that process.

Humans↗
PubMed1996

Radiation-associated gliosarcoma.

The authors report a case of radiation-associated intracerebral gliosarcoma with fibrosarcomatous predominance, arising at the site of a low-grade glioma treated 10 years previously. The features of this case conform to the accepted criteria for radiation-induced tumour, in that the tumour developed within the radiation field, differed dramatically in histologic features from the original tumour and did not develop until 10 years after treatment. Although such tumours are most uncommon, this case suggests that radiation-induced gliosarcoma should be considered in the differential diagnosis of recurrent mass at the site of a treated intracranial neoplasm.

Adolescent↗
PubMed1996

Reverse enhancement of hemorrhagic brain lesions on postcontrast MR: detection with digital image subtraction.

PURPOSE: To investigate the decrease in signal intensity on T1 - weighted MR images of some hemorrhagic intracranial lesions after administration of contrast material. METHODS: Postprocessing digital image subtraction was performed in 16 MR studies (13 patients) of lesions that showed hyperintensity on noncontrast T1-weighted images. Repetition time and echo time were identical for all precontrast and postcontrast studies. Regions of interest were measured in each lesion, contralateral white matter, and background (before and after contrast enhancement). RESULTS: In six of 16 MR studies, a significant net decrease in signal intensity was seen within the hemorrhagic lesion after contrast enhancement (reverse enhancement). All the lesions were hematomas within residual or recurrent malignant tumors. CONCLUSIONS: Digital image subtraction confirms the existence of reverse enhancement. This phenomenon is due to the combined T2-shortening effects of two paramagnetic substances, methemoglobin and gadolinium, which cause the signal reduction produced by the T2 effects to occur at lower concentrations of gadolinium.

Adolescent↗