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Biomedical subjects

W Mitchell

Publications and source records attributed to W Mitchell.

At least 19 recordsLinked to original sources

Comparative genomes of Chlamydia pneumoniae and C. trachomatis.

Chlamydia are obligate intracellular eubacteria that are phylogenetically separated from other bacterial divisions. C. trachomatis and C. pneumoniae are both pathogens of humans but differ in their tissue tropism and spectrum of diseases. C. pneumoniae is a newly recognized species of Chlamydia that is a natural pathogen of humans, and causes pneumonia and bronchitis. In the United States, approximately 10% of pneumonia cases and 5% of bronchitis cases are attributed to C. pneumoniae infection. Chronic disease may result following respiratory-acquired infection, such as reactive airway disease, adult-onset asthma and potentially lung cancer. In addition, C. pneumoniae infection has been associated with atherosclerosis. C. trachomatis infection causes trachoma, an ocular infection that leads to blindness, and sexually transmitted diseases such as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and epididymitis. Although relatively little is known about C. trachomatis biology, even less is known concerning C. pneumoniae. Comparison of the C. pneumoniae genome with the C. trachomatis genome will provide an understanding of the common biological processes required for infection and survival in mammalian cells. Genomic differences are implicated in the unique properties that differentiate the two species in disease spectrum. Analysis of the 1,230,230-nt C. pneumoniae genome revealed 214 protein-coding sequences not found in C. trachomatis, most without homologues to other known sequences. Prominent comparative findings include expansion of a novel family of 21 sequence-variant outer-membrane proteins, conservation of a type-III secretion virulence system, three serine/threonine protein kinases and a pair of parologous phospholipase-D-like proteins, additional purine and biotin biosynthetic capability, a homologue for aromatic amino acid (tryptophan) hydroxylase and the loss of tryptophan biosynthesis genes.

Amino Acid Sequence

Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis.

Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism.

Aerobiosis

Resection and graft repair for localized hypertrophic neuropathy.

OBJECTIVES: Formulation of surgical management recommendations for localized hypertrophic mononeuropathy has been difficult because of the infrequency of the lesion, lack of precise pathological diagnosis, and uncertainties regarding its cause. The purpose of this retrospective review of the Louisiana State University (LSU) experience with this unusual neuropathy was to evaluate the efficacy of lesion resection and interposition grafting in its management. METHODS: The charts of 15 patients operated on at LSU during a 15-year period with a pathological diagnosis of localized hypertrophic neuropathy were reviewed. RESULTS: Hypertrophic lesions were located on major named peripheral nerves of the extremities, distributed equally to the upper and lower extremities. Family history was negative for all patients, and entrapment or trauma, other than previous surgery, were unlikely by symptom location or history. Weakness was the most common presentation. The mean length of symptoms was 76 months. Atrophy, sensory loss, Tinel's sign, focal tenderness, and a mass were found in the majority of patients. Preoperative electrophysiological studies showed chronic denervational changes in all patients. At surgery, if no action potential or one of low amplitude was recorded across the lesion, the lesion was resected and an autologous nerve graft measuring from 3.5 to 8.5 cm in length was interposed. During follow-up periods of 1 or more years, seven of nine patients with localized hypertrophic mononeuropathy treated with graft repairs were either unchanged or improved. CONCLUSION: Localized hypertrophic mononeuropathy is a progressive process associated with pathological nerve changes that correlate with eventual severe functional loss. If intraoperative histological examination shows onion bulb neuropathy and intraoperative nerve action potentials confirm a nonfunctioning or poorly functioning segment, lesion resection with interposition graft repair provides the possibility of some degree of recovery.

Action Potentials

Collagen shortening. An experimental approach with heat.

Decreasing joint laxity is a clinical goal of ligament reconstructions. This in vitro study examined the structural and histologic effects of heat shrinkage of human collagen. Two preliminary studies were performed to assess the effect of heat on fresh frozen human tendons obtained from a local tissue bank. As heat was applied to tissue in a saline solution, the percent shrinkage was plotted against temperature. A second study used a freebeam Nd:YAG laser to maximally shrink patellar tendons measuring percent shrinkage versus energy applied. Finally, the effects of 10% shrinkage of fresh frozen human patellar tendons were analyzed mechanically and histologically. Consistent tendon shrinkage curves were found with increasing temperatures in a saline solution. A sharp increase in shrinkage to approximately 70% of resting length was noted around 70 degrees C. Tendon shrinkage by laser induced heat was precise and dose related. Tensile testing of the tendons shortened 10% of their resting length showed a decrease in load to failure to approximately 1/3 compared with that of historical control specimens. Histologic sections showed a well demarcated site of diffuse denaturation and degeneration of collagenous elements. Normal collagen was present adjacent to these thermal changes. These experiments showed that collagen tissue can be shortened precisely by the application of heat. Future studies need to examine the in vivo biologic response of shortened collagen tissue with time, especially recollagenization, restoration of length, and the long term biomechanical effects.

Biomechanical Phenomena

The effects of deinstitutionalization on adults with learning disabilities.

We compared a group of people with learning disabilities who have been deinstitutionalized with a control group remaining in an institution on measures of adaptive and maladaptive behaviour, community living skills, social skills, and quality of life. In general, there was no change over 30 months for the control group. Changes for the experimental group were either not seen or were generally modest in scale, and tended to occur within 6 months of moving, the measures staying relatively stable thereafter. Implications for detailed examination of the effects of deinstitutionalization were discussed.

Activities of Daily Living

Pharmaceutical prices, quantities and innovation. Comparing Japan with the US.

Per capita expenditure on pharmaceuticals is higher in Japan than in the US, despite a series of drug price reductions instigated by the Japanese Ministry of Health and Welfare that began in 1981. For some individual products, these price reductions cumulatively totalled more than 50%. This article argues that although the price of individual drugs is lower in Japan than in the US, aggregate expenditure is higher because of the greater use of newly-introduced original drugs and lower use of generics. Providers and consumers also tend to use drugs in larger quantities in Japan, because of polypharmacy and greater use of vitamins and nutrients, antihypertensives, cerebral metabolic activators (e.g. idebenone) and milder-acting drugs (i.e. drugs with low toxicity but unproven clinical efficacy). The level of expenditure is unlikely to decline, despite changes to pricing policy and ongoing efforts to improve the pharmaceutical distribution system and to discourage physician dispensing activities.

Cross-Cultural Comparison

Analysis of the bone surface area in resected tibia. Implications in tibial component subsidence and fixation.

Anterior subsidence of the tibial component is still a clinical complication requiring revision in total knee replacement. Using the scanning electron microscope, a quantitative 3-dimensional stereoscopic and digitizing study was conducted on the cortical and cancellous bone surface area from 10 resected human cadaveric tibia. The data demonstrated that the cortical bone surface area covered an average of 6% of the total tibial surface area, cancellous bone 18%, and bone marrow space 76%. By conducting anatomic regional analysis, the data showed significantly higher (p < or = 0.05) bone quantities in the posteromedial and medial regions as compared with the anterior and anterolateral regions. These data help to explain why tibial component subsidence occurs anteriorly in total knee replacement. The data also suggest that if long-term component subsidence and loosening is to be limited, either biologic cement or bone cement would be required to increase the surface attachment between the tibial component and resected cancellous bone.

Adult

Differentiating between marketing-driven and technology-driven vendors of medical information systems.

Buyers of medical information systems such as laboratory information systems need to recognize that the vendors of such systems may pursue corporate strategies emphasizing expenditures on marketing and client services, expenditures on technology and research and development (R&D), or a more balanced approach. The strategic goals and objectives of a vendor of an information system should align closely with those of a potential hospital client. A restless hospital client seeking cutting-edge technology will probably be dissatisfied with a system vendor who emphasizes slow ongoing incremental system development. Objective criteria for distinguishing between a marketing-driven vendor and a technology-driven vendor of medical information systems, and their variants, are presented based on the ratio of marketing expenditures to sales revenue compared with the ratio of research and development expenditures to sales revenue of the company. More subjective narrative criteria are also offered for making such distinctions.

Hospitals

Pseudoexstrophy.

Pseudoexstrophy is a rare, mild exstrophy variant which involves the major musculoskeletal defects of the exstrophy complex without any associated defect in the urinary system. A case is reported presenting at birth as an umbilical positional anomaly. Differential diagnosis and management are reviewed.

Bladder Exstrophy

Differential effects of a misattribution manipulation on sexually functional and dysfunctional men.

Ten sexually functional and 10 dysfunctional men viewed sexually explicit films following ingestion of each of three placebo pills described as an erection enhancement pill, an erection detraction pill, and a placebo pill. Functionals evidenced a reverse placebo effect with significantly higher erectile response under the detraction relative to the enhancement and placebo conditions. Dysfunctionals evidenced a direct placebo effect with significantly lower erectile response under the detraction relative to the enhancement and placebo conditions. Fifteen Ss (75%) responded according to group patterns. Results suggest yet another arena in which functional and dysfunctional men respond in a fundamentally different manner. This pattern of differential responding may be due to relative differences in level of interoceptive awareness and/or interoceptive avoidance between functional and dysfunctional Ss and reflect on the nature of anxiety.

Adult

Integrating information from decentralized laboratory testing sites. The creation of a value-added network.

The decentralization of laboratory testing provides distinct advantages for clinicians and patients, such as the reduction of test turnaround time, but also promotes the development of scattered caches of results. This problem could be ameliorated by the creation of an integrated laboratory data base. Such an approach would provide clinicians with a patient view of laboratory information in addition to the functional view of it that is offered currently. Impressive technologic advances are being made in the development of a distributed computer architecture in which processing tasks and information are shared across multiple hardware platforms attached to a network. Such architecture could be used to create a regional value-added laboratory network to integrate test information generated in decentralized testing sites. Independent reference laboratories and tertiary-care referral hospitals are the most likely candidates to create distributed value-added networks. Pathologists should view themselves as health-care professionals responsible for the processing, storage, and transmission of information, as well as for its generation. In time, the partition of information along hospital geopolitical boundaries will appear archaic and will be replaced by an emphasis on local and regional integration of medical information similar to that advocated here.

Clinical Laboratory Information Systems

Teaching tomorrow's health care leaders.

Business school curricula have traditionally emphasized functional skills for people who will work in functional departments and general management skills for people who will organize interdepartmental work. Recently, some business schools have begun to develop programs that teach cross-functional work and team skills to functional specialists. Students educated in such programs will be well prepared to meet the new challenges that health care organizations will face.

Commerce

Health care costs of veterans with multiple sclerosis: implications for the rehabilitation of MS. VA Multiple Sclerosis Rehabilitation Study Group.

We retrospectively determined health care costs among veterans with multiple sclerosis (MS) and correlated the costs with neurologic dysfunction. Total health care costs for the 165 patients averaged $35,000/year. VA benefits and homecare together accounted for 85% of the total costs. Total health care costs correlated with two measures of neurologic dysfunction, the Expanded Disability Status Scale (EDSS) (r = 0.61, p < 0.001) and the Incapacity Status Scale (ISS) (r = 0.64, p < 0.001). The costs of VA benefits, homecare, and hospitalizations also correlated with the EDSS, ISS, and other measures of neurologic dysfunction whereas the cost of outpatient clinic visits did not. In a period of three years, there were 40 hospitalizations, at a total cost of $412,800, that were potentially preventable with appropriate outpatient management. Improving selfcare and avoiding preventable hospitalizations might lower the considerable health care costs of MS.

Activities of Daily Living

An analysis of the relationship between a pathology department and its laboratory information system vendor.

The ongoing collaborative relationship between a pathology department and the vendor of its laboratory information system is vitally important because of the strategic importance of the laboratory information system in managing the information product of the department. Laboratory information system vendors are value-added resellers in that they produce software and package it with hardware manufactured by another manufacturer. The success of laboratory information system value-added resellers in creating information systems that are highly functional depends on their forward vertical quasi-integration into pathology departments. Because of this relationship, laboratory information system value-added resellers exert a significant degree of control over departments, largely through the creation of switching costs. There are a number of strategies by which departments can exercise greater control over vendors, one of which is to serve as either an alpha- or beta-development site for the vendor's software. Such a strategy is not without risk, but it achieves the dual purpose of enhancing both the expertise of departmental personnel and the quality of the software product.

Clinical Laboratory Information Systems

Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.

Adipose Tissue

Using the laboratory information system to achieve strategic advantage over the competitors of hospital-based clinical laboratories.

The competitors of hospital pathologists are commercial reference laboratories, hospital special function laboratories, pathology groups in neighboring hospitals, hospital mainframe computer personnel, and users of patient proximity testing systems. The laboratory information system can provide a strategic advantage over these competitors by matching, exceeding, or substituting for their capabilities and by creating switching costs for clinics, administrations, and patients. For example, the installation of microcomputers in clinicians' private offices provides them with ready access to the pathology data base, bonds them to the hospital, and capitalizes on the willingness of the hospital to invest in information technology.

Clinical Laboratory Information Systems

Malignant fibrous histiocytoma arising from descending thoracic aorta.

Cases of malignant fibrous histiocytoma arising from the aorta are rare and have a dismal outlook despite treatment. The longest reported survival period following resection is only 28 months. A patient with malignant fibrous histiocytoma of the descending thoracic aorta was successfully treated with resection and reconstruction with a prosthetic graft. The patient developed metastatic disease eight months postoperatively. With aggressive triple regimen chemotherapy, complete remission has been obtained. The patient is alive and free of disease six years postoperatively.

Aged