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Biomedical subjects

J A Morris

Publications and source records attributed to J A Morris.

At least 73 records · Page 4Linked to original sources

Hypothermia in critically ill trauma patients.

OBJECTIVE: To determine the incidence and mortality of hypothermia in trauma patients. METHODS: Retrospective review of patients admitted to the Surgical Intensive Care Unit (SICU) over 4 1/2 years. Hypothermia was defined as a temperature < 35 degrees C. RESULTS: There were 7045 admissions to the SICU, of which 661 (9.4%) had a recorded temperature of < 35 degrees C. Over half (395) were trauma patients, with a mortality of 52.7%. The temperature ranged from 27.1 to 34.9 degrees C, with a mean for survivors of 34.0 degrees C and 33.1 degrees C for those that died. There was a significant difference in Apache II scores (16.6 vs 25.4) and Injury Severity Scores (26.1 vs 33.4) between survivors and non-survivors. CONCLUSIONS: The incidence of hypothermia in trauma patients is significant and is independent of the month of admission. Mortality is high but there is no threshold below which mortality is assured. Unlike historical data, 13 patients survived temperatures < 32 degrees C.

APACHE↗

Fetal origin of maturity-onset diabetes mellitus: genetic or environmental cause?

Low birthweight is a risk factor for a number of diseases of adult life including non-insulin-dependent diabetes mellitus (NIDDM). This implies that either genetic constitution or factors operating during intrauterine development have a causal role in NIDDM. One reason for rejecting a genetic cause, however, is that there is a rapidly changing prevalence of NIDDM with the onset and establishment of affluence, which does not fit with conventional models of multifactorial genetic disease. But in this article a new model of genetic disease based on the concept of redundancy is explored. The idea is that mutant genes interact synergistically in highly redundant systems to degrade performance and increase the risk of disease. The mutational load is in turn determined by the pre-conceptual environment. This model can explain a rapidly changing prevalence of NIDDM.

Age of Onset↗

Niemann-Pick C disease: cholesterol handling gone awry.

Niemann-Pick C disease (NPC) is a debilitating, recessive disorder in humans that causes unrelenting neurological deterioration and is complicated by the presence of lipid-laden foamy cells in the major organs of the body. NPC fibroblasts cultured with an excess of low density lipoprotein (LDL) abnormally sequester cholesterol in their lysosomes. Biochemical analyses of NPC cells suggest an impairment in the intracellular transport of cholesterol to post-lysosomal destinations occurs in NPC. The recent identification of the NPC gene, NPC1, provides a definitive diagnosis of the disease and a means of studying this key component of intracellular cholesterol transport and homeostasis.

Animals↗

Elective bedside surgery in critically injured patients is safe and cost-effective.

OBJECTIVE: The success of elective minimally invasive surgery suggested that this concept could be adapted to the intensive care unit. We hypothesized that minimally invasive surgery could be done safely and cost-effectively at the bedside in critically injured patients. SUMMARY BACKGROUND DATA: This case series, conducted between October 1991 and June 1997 at a Level I trauma center, examined bedside dilatational tracheostomy (BDT), percutaneous endoscopic gastrostomy (PEG), and inferior vena cava (IVC) filter placement. All procedures had been performed in the operating room (OR) before initiation of this study. METHODS: All BDTs and PEGs were performed with intravenous general anesthesia (fentanyl, diazepam, and pancuronium) administered by the surgical team. IVC filters were placed using local anesthesia and conscious sedation. BDTs were done using a Ciaglia set, PEGs were done using a 20 Fr Flexiflow Inverta-PEG kit, and IVC filters were placed percutaneously under ultrasound guidance. Cost difference (delta cost) was defined as the difference in hospital cost and physician charges incurred in the OR as compared to the bedside. RESULTS: Of 16,417 trauma admissions, 379 patients (2%) underwent 472 minimally invasive procedures (272 BDTs, 129 PEGs, 71 IVC filters). There were four major complications (0.8%). Two patients had loss of airway requiring reintubation. Two patients had an intraperitoneal leak from the gastrostomy requiring operative repair. No patient had a major complication after IVC filter placement. Total delta cost was $611,994. When examined independently, the cost was $324,224 for BDT, $164,088 for PEG, and $123,682 for IVC filter. OR use was reduced by 506 hours. CONCLUSIONS: These bedside procedures have minimal complications, eliminate the risk associated with patient transport, reduce cost, improve OR utilization, and should be considered for routine use in the general surgery population.

Adult↗

The evolving role of a scientific society.

In summary, EAST is a very different organization today than it was 12 years ago when it was conceived in the lounge of the Washington airport. It started as a traditional scientific organization, but an organization with a very different mission. Its mission was to identify and nurture the young traumatologist and to provide that individual with the opportunity for academic advancement. The EAST of the next millennium will be different still. The new EAST will reside on the Internet. It will provide a creative forum for scientific content, educational content, and practice content. It will adjudicate that content rapidly, equitably, and educationally. It will disseminate that content to the membership, to the trauma community, and to the community at large. It will encourage discourse, the exchange of ideas, the exchange of data, and the exchange of content. Finally, EAST will continue to meet the challenge of creating new and innovative products to foster the career of young trauma surgeons worldwide. Will the new world be complex? Yes. Will it be possible to drown in information? Yes. Will EAST meet those challenges head on? Yes. Will we succeed? Yes. We will succeed because we will remember the mission.

Career Mobility↗

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome.

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments. METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments. RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks. CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Adult↗

Return to work following injury: the role of economic, social, and job-related factors.

OBJECTIVES: This study examined factors influencing return to work (RTW) following severe fracture to a lower extremity. METHODS: This prospective cohort study followed 312 individuals treated for a lower extremity fracture at 3 level-1 trauma centers. Kaplan-Meier estimates of the proportion of RTW were computed, and a Cox proportional hazards model was used to examine the contribution of multiple risk factors on RTW. RESULTS: Cumulative proportions of RTW at 3, 6, 9, and 12 months post-injury were 0.26, 0.49, 0.60, and 0.72. After accounting for the extent of impairment, characteristics of the patient that correlated with higher rates of RTW included younger age, higher education, higher income, the presence of strong social support, and employment in a white-collar job that was not physically demanding. Receipt of disability compensation had a strong negative effect on RTW. CONCLUSIONS: Despite relatively high rates of recovery, one quarter of persons with lower extremity fractures did not return to work by the end of 1 year. The analysis points to subgroups of individuals who are at high risk of delayed RTW, with implications for interventions at the patient, employer, and policy levels.

Absenteeism↗

Correlation between the measures of impairment, according to the modified system of the American Medical Association, and function.

We performed a prospective study of 302 patients who had a fracture of the lower extremity. Our purpose was to determine whether there was any association between impairment ratings of the lower extremity, derived with use of the Guides to the Evaluation of Permanent Impairment by the American Medical Association, and measurements of task performance based on direct observation as well as the patient's own assessment of activity limitation and disability as recorded on the Sickness Impact Profile. The mean residual impairment of the lower extremity according to the Guides was 27 per cent one year after the injury. Only 130 subjects (43 per cent) could perform all five functional tasks without difficulty. Eighty-four subjects (28 per cent) reported functional limitations that resulted in a score on the Sickness Impact Profile that was more than one standard deviation from the preinjury norm for the sample. Impairment ratings according to a modification of the system of the American Medical Association correlated strongly with the performance of functional tasks (r = 0.57) as well as the patients' reported activity limitations as recorded on the Sickness Impact Profile (r = 0.55). Correlations were highest when measures of impairment were based on strength rather than on range of motion. The relationship between the impairment rating and function (as observed by an examiner and as reported by the patient) was not influenced by the location of the fracture or the receipt of disability compensation. Our results suggest that the American Medical Association developed a valid approach for the measurement of physical impairment after a fracture of the lower extremity. In our study, the anatomical approach of evaluation based on muscle strength that was described in the Guides to the Evaluation of Permanent Impairment was the most sensitive measure of impairment compared with the anatomical measure based on range of motion and compared with the functional and diagnostic methods for the rating of impairment. Until the diagnostic and functional approaches for the measurement of musculoskeletal impairment are refined, we recommend use of the anatomical approach when evaluating impairment after a fracture of the lower extremity.

Activities of Daily Living↗

The long-term complications of percutaneous dilatational tracheostomy.

Percutaneous dilatational tracheostomy was adopted at our institution, because it was demonstrated to be more cost effective than standard open tracheostomy in critically ill patients. The objective of this study was to evaluate the long-term outcome and complication rate of percutaneous dilatational tracheostomy in critically ill patients. We performed a consecutive case study of all Level I trauma patients from August 1991 to May 1994 who underwent percutaneous dilatational tracheostomy. All patients were prospectively evaluated by a standard questionnaire a minimum of 1 year after the procedure. All symptomatic patients were offered fiberoptic laryngoscopy. Descriptive statistical methods and the Student's T test were used to analyze the data. Of 7054 consecutive trauma admissions, 237 tracheostomies were performed. A total of 143 tracheostomies (60%) were open, and 95 (40%) were percutaneous. Of the 95 patients, 20 were lost to follow-up, 12 died from causes unrelated to the procedure, 6 had severe traumatic brain injuries and were unable to participate, and 2 patients required conversion to an open procedure. This left a study group of 55 patients. At a minimum of 1 year follow-up, 40 patients (73%) were asymptomatic. Of the 15 (27%) symptomatic patients, two patients had acute airway compromise after decannulation secondary to subglottic stenosis. Both were recannulated and subsequently decannulated uneventfully. Six patients declined fiberoptic laryngoscopy, because their symptoms were minimal (minor voice changes in three and intermittent hoarseness in three). Nine patients underwent fiberoptic laryngoscopy, and all examinations were normal. The mean cost of standard open tracheostomy at our institution is $1134 (58%) more than the mean cost of percutaneous dilatational tracheostomy. Of the study group patients undergoing percutaneous dilatational tracheostomy, 27 per cent complained of symptoms a minimum of 1 year posttracheostomy. Of these patients, 60 per cent underwent fiberoptic laryngoscopy, and no subglottic lesions were identified. Our findings suggest that percutaneous dilatational tracheostomy is a safe, cost-effective alternative to standard tracheostomy in critically ill patients.

Adolescent↗

Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.

Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.

Amino Acid Sequence↗

Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.

An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.

Amino Acid Sequence↗

Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation.

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.

Animals↗

Immunoglobulin binding protein (BiP) function is required to protect cells from endoplasmic reticulum stress but is not required for the secretion of selective proteins.

BiP/GRP78 is a lumenal stress protein of the endoplasmic reticulum (ER) that interacts with polypeptide folding intermediates transiting the secretory compartment. We have studied the secretion and the stress response in Chinese hamster ovary (CHO) cells that overexpress either wild-type immunoglobulin binding protein (BiP) or a BiP deletion molecule (residues 175-201) that can bind peptides and ATP but is defective in ATP hydrolysis and concomitant peptide release. Overexpressed wild-type BiP was localized to the ER and unique vesicles within the nucleus, whereas overexpressed ATPase-defective BiP was localized to the ER and cytoplasmic vesicles but was absent from the nucleus. Compared with wild-type CHO cells, overexpression of ATPase-defective BiP prevented secretion of factor VIII, a coagulation factor that extensively binds BiP in the lumen of the ER. Under these conditions factor VIII was stably associated with the ATPase-defective BiP. In contrast, the secretion of monocyte/macrophage colony stimulating factor, a protein that is not detected in association with BiP, was not affected by overexpression of ATPase-defective BiP. These results show that BiP function is not required for secretion of some proteins and suggest that some proteins do not interact with BiP upon transport through the ER. The presence of unfolded protein in the ER induces transcription of BiP and also elicits a general inhibition of protein synthesis. Overexpression of wild-type BiP prevented the stress-mediated transcriptional induction of BiP in response to either calcium ionophore A23187 treatment or tunicamycin treatment. In contrast, overexpression of ATPase-defective BiP did not prevent the stress induction of BiP, showing that the ATPase activity is required to inhibit transcriptional induction. Overexpression of wild-type BiP, but not ATPase-defective BiP, increased survival of cells treated with A23187. The increased survival mediated by overexpressed wild-type BiP correlated with reduced translation inhibition in response to the stress condition. These results indicate that overexpressed BiP alleviated the stress in the ER to prevent BiP transcriptional induction and permit continued translation of cellular mRNAs.

Adenosine Triphosphatases↗

Abdominal compartment syndrome. The Nashville experience.

Intra-abdominal hypertension is an unusual and often lethal syndrome. It is most often seen in critically ill surgical patients. The most important component of therapy is reduction of intra-abdominal pressure. Unfortunately, even with appropriate treatment, mortality is still high.

Abdomen↗

Genetic control of redundant systems.

Concepts from information theory are used to develop a model in which genes control highly redundant systems. One consequence is that mutations interact synergistically and there will be selection against zygotes which have several mutations in any one system. This could explain why total mutational load in the human genome remains constant even though there are several new mutations per generation. This model has implications for fertility, polygenic disease and cancer. It also explains a fundamental biological problem concerning the advantage of sexual over asexual reproduction.

Animals↗

Using structured text and templates to capture health status outcomes in the electronic health record.

BACKGROUND: Because of the difficulty of implementing clinical outcomes-focused quality improvement (QI) projects, most organizations' efforts and comparative quality report cards have centered on structure and process indicators or on outcomes captured in administrative data systems. Ultimately, however, health care is intended to improve health. Health status is now frequently included in the set of quality of care information requested by purchasers of health care, accrediting and governmental agencies, and consumer groups. Subsequently, users of electronic health record (EHR) systems are demanding that the EHR support the collection and comparative analysis of health status information over time and by clinical population and provider. APPROACH: As opposed to the current practice in most organizations of collecting health status data via an annual mail survey, the approach discussed in this article utilizes standardized coding and classification (SCC) systems and standardized surveys to capture health status information in the EHR during the routine course of care delivery through the use of templates built on structured text. This method is illustrated with examples from the WAVE EHR. The EHR-based structured text and template approach facilitates the incorporation of health status measurement into the documentation of the patient-provider encounter, builds on recognized SCC systems and standardized surveys, and enables information retrieval for a variety of analyses, including those focused on QI. CONCLUSIONS: Health status outcomes are an essential component of an information set focused on health care quality. To routinely capture and analyze health status variables, SCC systems and standardized health status surveys are necessary.

Forms and Records Control↗

Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma.

BACKGROUND: Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. METHODS: This study was a prospectively conducted multi-center trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. RESULTS: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of > or = 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. CONCLUSIONS: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.

Adolescent↗