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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1994

Ethical implications of standardization of ICU care with computerized protocols.

Ethical issues related to the use of computerized protocols to control mechanical ventilation of patients with Acute Respiratory Distress Syndrome (ARDS) are identical to the ethical issues surrounding the use of any therapy or intervention. Four ethical principles must be considered: nonmaleficence, beneficence, autonomy, and distributed justice. The major ethical challenges to computerized protocol use as a specific application of clinical decision support tools are found within the principles of nonmaleficence and of beneficence. The absence of credible outcome data on which ARDS patient survival probabilities with different therapeutic options could be based is a constraint common to most ICU clinical decision making. Clinicians are thus deprived of the knowledge necessary to define benefit and are limited to beneficent intention in clinical decisions. Computerized protocol controlled decision making for the clinical management of mechanical ventilation for ARDS patients is ethically defensible. It is as well supported as most ICU therapy options.

Clinical Protocols↗
PubMed1994

Magnetic resonance features in carbon monoxide poisoning.

The authors describe unusual magnetic resonance findings due to carbon monoxide poisoning in a 34-year-old woman. With T2-weighted imaging, increased signal intensity was observed bilaterally in the putamen and the caudate nucleus. Lesions of high signal intensity in the globus pallidus, which have been previously reported, were also observed.

Adult↗
PubMed1994

Pseudodelta sign on computed tomography: an indication of bilateral interhemispheric hemorrhage.

The "pseudodelta sign" is introduced as an indicator of interhemispheric hemorrhage. This sign, appearing in computed tomography (CT) scans, consists of hyperattenuated extra-axial blood surrounding blood flowing in the superior sagittal sinus, which shows lower attenuation. To determine the prevalence of interhemispheric hemorrhage and the pseudodelta sign in patients with post-traumatic extra-axial hemorrhage, the authors reviewed the charts and CT scans of 198 such patients. The patients had been admitted to a tertiary-care hospital between Jan. 1, 1986, and Dec. 1, 1990. Interhemispheric hemorrhage was visible in 18 cases; the pseudodelta sign was seen in 14 of these. In 8 of the 14 cases the interhemispheric hemorrhage consisted of bilateral subdural hematoma, and in 3 it consisted of unilateral subdural hematoma. In the remaining three cases the appearance of the interhemispheric blood was nonspecific, and the hemorrhage may have been subdural or subarachnoid. The pseudodelta sign may be a good indicator of interhemispheric hemorrhage in either the subdural or subarachnoid space.

Adolescent↗
PubMed1993

Understanding cytochrome c function: engineering protein structure by semisynthesis.

Semisynthesis is a method of protein engineering that relies primarily on chemical manipulations of peptide fragments derived from natural proteins to produce intermediates for reassembly into defined analogs. In this respect it differs fundamentally from total chemical synthesis, but like it, it has unique capabilities for introducing noncoded amino acids or site-specific labels into the protein product. A favorite subject for semisynthesis is the redox protein cytochrome c: a vital link in the respiratory chain. The tactics that have evolved in the half dozen laboratories so engaged are briefly described. More than 100 semisynthetic analogs of this protein have resulted from this effort and have contributed to our understanding of the way in which the function of cytochrome c is determined by its three-dimensional structure. Questions concerning the folding and stability of the protein, the setting of heme redox potential, control and specificity of interaction with potential redox partners, and the mechanism of electron transfer are considered. A growing synergy between this approach and genetic methods will ensure that protein engineering by semisynthesis continues to increase our knowledge of this and other proteins.

Animals↗
PubMed1993

The curious case of protein splicing: mechanistic insights suggested by protein semisynthesis.

The gradual accumulation of examples of protein splicing, in which a nested intervening sequence is spliced out of the interior of a polyprotein precursor, suggests that this curious phenomenon might prove to have universal phylogenetic distribution and biological significance. The known examples are reviewed, with the aim of establishing underlying patterns, and a generalized mechanism of autocatalytic protein splicing is proposed. The testable consequences of such a proposal and the possible evolutionary origins of the phenomenon are discussed.

Amino Acid Sequence↗
PubMed1993

ATP binding to cytochrome c diminishes electron flow in the mitochondrial respiratory pathway.

Eukaryotic cytochrome c possesses an ATP-binding site of substantial specificity and high affinity that is conserved between highly divergent species and which includes the invariant residue arginine91. Such evolutionary conservatism strongly suggests a physiological role for ATP binding that demands further investigation. We report the preparation of adducts of the protein and the affinity labels 8-azido adenosine 5'-triphosphate, adenosine 5'-triphosphate-2',3'-dialdehyde, and 5'-p-fluorosulfonylbenzoyladenosine. The two former reagents were seen to react at the arginine91-containing site, yet the reaction of the latter, although specific, occurred elsewhere, suggesting caution is necessary in its use. None of the adducts displayed significant modification of global structure, stability, or physicochemical properties, leading us to believe that the 8-N3-ATP and oATP adducts are good stabilized models of the noncovalent interaction; yet modification led to significant, and sometimes pronounced, effects on biological activity. We therefore propose that the role of ATP binding to this site, which we have shown to occur when the phosphorylation potential of the system is high under the equivalent of physiological conditions, is to cause a decrease in electron flow through the mitochondrial electron transport chain. Differences in the degree of inhibition produced by differences in adduct chemistry suggest that this putative regulatory role is mediated primarily by electrostatic effects.

Adenosine↗
PubMed1993

Psychiatric rehabilitation.

The financial, personal, and societal costs of severe mental illness are extraordinarily high. Individuals suffering from schizophrenia occupy 25 percent of all hospital beds and account for 40 percent of all long-term care days. The rate of Supplemental Security income (SSI) and Social Security disability insurance (SSDI) beneficiaries who are disabled because of a mental disorder has increased more than 50 percent since 1986, and a total of more than 1.1 million individuals received benefits in 1991 because of their mental disorders. All of these costs have continued to rise despite the nearly ubiquitous administration of antipsychotic medication with its well-documented benefits. The most promising treatment to complement medication and produce better outcomes is psychiatric rehabilitation. It is based on the same rationale as rehabilitation for physically challenged individuals--illness produces impairments that make individuals less able to perform basic life skills that handicap them when they try to be students, workers, spouses, parents, etc. Rehabilitation teaches individuals to perform the basic skills using methods that compensate for the impairments, and modifying the environment so the new methods are successful or the skills are not required. Rehabilitation with severely mentally ill individuals is particularly challenging because of the extent of their impairments and disabilities. The impairments--flagrant symptoms that unpredictably wax, wane, and persist even with medication; reduced motivation to participate in community life; residual deficits in the most elemental cognitive processes of attention, memory, and abstraction--clearly limit individuals' abilities to perform life skills and function in major societal roles. Moreover, the challenge of successful rehabilitation is magnified by the individual-to-individual, time-to-time, and disorder-to-disorder variations in these impairments and disabilities. Given this challenge, how well does psychiatric rehabilitation work in practice? Two types of studies provide answers to this question; those that have focused exclusively on teaching skills to severely mentally ill individuals, and those that have focused on larger units of care, case management, and vocational rehabilitation, that typically include skills training as one of their services. The first type of study provides "pure" information but sacrifices, to some extent, clinical utility and immediate generality. The second provides information that can be transferred to clinical practice but sacrifices clarity about what is the effective ingredient in a set of intermingled services. The results of the first type have generally indicated, with some qualifications, that severely mentally ill individuals learn skills, use them in their own environments, and may receive other clinically meaningful benefits.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1993

Clinical performance of a rule-based decision support system for mechanical ventilation of ARDS patients.

We developed a clinical decision support system--ventilation protocols--that managed tidal volume and ventilator rate settings during mechanical ventilation of patients with the Adult Respiratory Distress Syndrome (ARDS). We applied these protocols for a total of 10,903 hours in 40 ARDS patients. The clinical staff suspended the protocols for only 5% of the total application time due to medical procedures, surgeries, transient clinical problems not addressed by the protocols, or because of attending physician request. Of 3,148 instructions generated by the ventilation protocols, the clinical staff followed 2,932 (93%). The staff did not follow some instructions because of patient data errors, computer software and protocol logic errors, inability of the clinical staff to implement protocol instructions because of more pressing duties, and clinical staff objections to specific instructions. Sixty percent of the patients treated by the ventilation protocols survived. Our results demonstrate that the ventilation protocols provided a practical and safe decision support system for the mechanical ventilation of ARDS patients.

Clinical Protocols↗
PubMed1993

Cystic intracranial schwannoma.

The development of cystic components in intracranial schwannoma is not rare but has not been emphasized in any previous series or reviews. Cystic areas usually develop from coalescence of mucinous or microcystic areas in Antoni B tissue of the schwannoma. Hemorrhagic degeneration or necrosis due to the characteristic vascular abnormalities of these lesions may cause the formation of tiny cysts but not large ones. The formation of an associated arachnoid cyst and, rarely, the formation of cysts in glandular or pseudoglandular elements have also been reported. Awareness of the potential for partially or largely cystic schwannoma of the acoustic or trigeminal nerve is important for both the differential diagnosis and surgical planning. Surgically proven large cysts (occupying more than 50% of tumour volume) were detected preoperatively by computed tomography (CT) in 7 of the 35 cases of acoustic nerve schwannoma and both cases of trigeminal nerve schwannoma managed surgically at the authors' institution between 1980 and 1990. In a review of the literature the authors found descriptions of low-attenuation regions in CT scans for an average of 13% of acoustic and 29% of trigeminal nerve sheath tumours. Magnetic resonance imaging, ideally performed after intravenous administration of contrast material, also plays an important role in the detection and delineation of these tumour cysts.

Brain Neoplasms↗
PubMed1993

Adenoid cystic carcinoma: an unusual sellar mass.

Adenoid cystic carcinoma represents approximately 20% of tumours of the minor salivary glands. It can originate in the sphenoidal sinus and invade the sella turcica. The authors describe a patient in whom a tumour of this type was shown by computed tomography.

Adult↗
PubMed1992

Functional role of heme ligation in cytochrome c. Effects of replacement of methionine 80 with natural and non-natural residues by semisynthesis.

The nature of the axial ligation to heme iron has been suggested to be the major determinant of the oxidation-reduction potential of a particular cytochrome, but natural cytochromes that vary significantly in E'm invariably differ from one another in many ways. We proposed to clarify this issue by engineering many different ligation patterns within the same basic molecule, mitochondrial cytochrome c. Since many of the potentially informative substitutions require non-coded amino acids, semisynthesis was the approach we chose, and solid-phase peptide synthesis was used to make a set of nin 39-residue peptides that have been incorporated by autocatalytic fragment religation into the structure of horse cytochrome c. An additional two analogues modified at this position were made by chemical modification of the whole protein. As well as looking at the effect on reduction potential, we examined the effect of varying the ligand sphere on the efficiency of the autocatalytic fragment religation reaction, on the conformation of cytochrome c, on its spectroscopic properties, and in promoting electron transfer between heme c and other redox centers. Substitute residues were chosen to put sulfur, selenium, oxygen, and nitrogen, or even no ligating atom at all in the place of methionine sulfur. We found both subtle and dramatic alterations in spectral properties, which were informative about changes in internal structure and stability brought about by the modifications and which may be useful in identifying novel natural ligation patterns. An unexpected finding was that alanine 80 cytochrome c acquires a hemoglobin-like spectrum, and binds O2 most effectively. Reduction potential changes of greater than 300 mV with nitrogen, greater than 400 mV with oxygen, and greater than 300 mV with thiol sulfur ligation were observed, confirming that variation of the ligand sphere is indeed the most effective way in which the protein coat may modulate the potential of the redox center it encloses. Finally, we obtained more evidence that this axial ligand plays an active role in electron transfer and discovered that histidine could be even more effective in this role.

Amino Acids↗
PubMed1992

Deficits in social schemata in schizophrenia.

Several recent studies have examined the manner in which social information is processed in an attempt to better understand the interpersonal functioning deficits of schizophrenia. In this study, the manner in which schizophrenic subjects represent social information, and the relationships between these social representations and measures of information processing, are examined. Specifically, 30 DSM-IIIR patients with schizophrenia and 15 normal controls were assessed on measures of social schema processing, information processing, and symptomatology. Results showed that schizophrenic patients earned significantly lower schema processing scores than the normal comparison group. Schema deficits of the schizophrenic group were significantly associated with recall memory and vigilance. These findings suggest that deficits in the representation of social information provides a unique perspective for understanding the interpersonal dysfunctions of schizophrenia.

Adult↗
PubMed1992

Effectiveness and replicability of modules for teaching social and instrumental skills to the severely mentally ill.

OBJECTIVE: This study evaluated the effectiveness and replicability of psychoeducational modules designed to improve the social and instrumental competencies of severely mentally ill patients. METHOD: Staff in seven facilities used the modules to teach 108 severely mentally ill patients. Staff received 2 days of formal training followed by periodic consultation. Each module's effectiveness was measured by a test of the patients' knowledge and performance of the skills taught in that module. Staff's adherence to the instructional techniques specified in the modules was measured by directly observing them and assessing the fidelity of their behaviors to those specified in the modules. RESULTS: The patients' skills significantly improved and were maintained during a 1-year follow-up, and staff accurately followed the modules with minimal consultation. CONCLUSIONS: These training modules are effective and replicable techniques for teaching social and instrumental skills to severely mentally ill patients. The modules can be easily disseminated to a variety of facilities and used as components in a comprehensive rehabilitation program.

Activities of Daily Living↗
PubMed1992

A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients.

We have developed a computerized protocol that provides a systematic approach for management of pressure control-inverse ratio ventilation (PCIRV). The protocols were used for 1,466 h in ten around-the-clock PCIRV evaluations on seven patients with severe adult respiratory distress syndrome (ARDS). Patient therapy was controlled by protocol 95 percent of the time (1,396 of 1,466 h) and 90 percent of the protocol instructions (1,937 of 2,158) were followed by the clinical staff. Of the 221 protocol instructions, 88 (39 percent) not followed were due to invalid PEEPi measurements. Compared with preceding values during CPPV, the expired minute ventilation was reduced by 27 percent during PCIRV while maintaining a pH that was not clinically different (mean difference in pH = 0.02). There was no difference in the PaO2, PEEPi, or the FIO2 between PCIRV and CPPV. The PEEP setting was reduced by 33 percent from 9 +/- 0.05 to 6 +/- 0.6 and the I:E ratio increased from 0.64 +/- 0.04 to 2.3 +/- 0.10. Peak airway pressure was reduced by 24 percent (from 59 +/- 1.5 to 45 +/- 0.6) and mean airway pressure increased by 27 percent (from 22 +/- 0.8 to 28 +/- 0.6) in PCIRV. Right atrial and pulmonary artery pressures were higher and cardiac output lower in PCIRV but blood pressure was unchanged. The success of this protocol has demonstrated the feasibility of using PEEPi as a primary control variable for oxygenation. This computerized PCIRV protocol should make the future use of PCIRV less mystifying, simpler, and more systematic.

Adult↗
PubMed1992

Multiple sclerosis: the impact of MR imaging.

MR imaging has had a significant impact on the understanding of multiple sclerosis. The procedure now plays an important role in initial diagnostic workup, replacing some other radiologic and paraclinical tests and often confirming clinically suggested locations of lesions. It also has contributed greatly to the understanding of the natural history of this disease, allowing objective assessment of disease load, detection of asymptomatic lesions, and differentiation between acute and chronic lesions. MR imaging is highly sensitive to inflammation and demyelination caused by multiple sclerosis, and although there is a long differential diagnosis for some of the MR findings, increasing experience has defined a number of relatively specific criteria for multiple sclerosis. Recent advances may allow faster imaging and highly objective lesion quantification, which will aid in therapeutic trials.

Brain↗
PubMed1992

Calcified herniations of the thoracic disk: role of magnetic resonance imaging and computed tomography in surgical planning.

Herniations of thoracic disks are uncommon, and their surgical management can be challenging. Magnetic resonance imaging (MRI) is rapidly becoming the method of choice for assessing degenerative disease in thoracic disks. However, calcification may be difficult to detect with MRI and plain films alone. The authors report a case in which MRI and myelography underestimated the true extent of disk calcification, the detection of which would have altered the initial surgical approach.

Adult↗