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Biomedical subjects

M J Young

Publications and source records attributed to M J Young.

At least 55 records · Page 3Linked to original sources

Office evaluation and management of bladder neoplasms.

Transitional cell carcinoma is the predominant bladder neoplasm. These tumors are heterogeneous, and the risk of recurrence and progression should guide further management. When this approach is used, patients at lower risk avoid the morbidity and expense of unnecessary interventions and tests, whereas higher-risk patients are treated more aggressively. Cystoscopy and IVP remain the standard initial evaluation for patients suspected of having a bladder neoplasm. Intravesical chemotherapy and immunotherapy can be administered safely in the office to reduce disease recurrence when appropriate. The advent of lasers has permitted fulgaration of low-grade neoplasms in the office with local anesthesia. Surveillance of patients with superficial disease is still largely dependent on office-based cystoscopy. Tumor markers for the identification of recurrent disease are being investigated and may prove useful to reduce the number of negative cystoscopic evaluations performed for surveillance. Patients postcystectomy are followed up with attention to detection of recurrent disease in remnant urothelium, metastatic disease, and metabolic and nutritional disturbances, which may result from urinary diversion.

Disease Progression↗

How a community teaching hospital is changing to better serve its community.

In recent years increased attention has been focused on the importance of teaching hospitals' serving the health of their communities. A community teaching hospital may have a special impetus and some advantages because of its linkage to a defined geographic community and a traditional mission of providing clinical and other services to that community. The authors describe how their community teaching hospital, the health and education services network it belongs to, and the integrated delivery system of which it is a member work together to respond to the current challenge to provide care and education to local communities. In particular, they describe how since 1995 the hospital has used an approach (called Measurably Enhancing the Status of Health) to create and operate its new Department of Community Health and Health Studies and associated new programs to benefit the community. The new department combines innovative community outreach programs with an emphasis on the qualitative and quantitative evaluation of the these programs. There are also programs of medical education in the hospital and at the Pennsylvania State University College of Medicine, and other programs that have community educational components (e.g., a coalition to reduce the number of smokers; a center to reduce health risks and prevent disease). The authors and their hospital colleagues have found three concepts to be helpful as they reflect on what they have learned since 1995 and continue to refine their community outreach work: community, complexity, and collaboration/competition. They explain these concepts and suggest that other institutions in academic medicine may find them and the ideas and programs of their hospital useful as the seek ways to care for, educate, and measure the health status of their own communities.

Community Medicine↗

Measuring and evaluating hospital restructuring efforts. Eighteen-month follow-up and extension to critical care, Part 1.

Increasingly, hospital restructuring is viewed with skepticism because of a lack of systematic and rigorous evaluation of its impact on quality of care. This first article in a two-part series describes comprehensive evaluation of the effects of hospital restructuring on patient satisfaction, nurse satisfaction, costs of care, and clinical quality on four medical-surgical units at a large tertiary hospital. In addition, early application of the model to critical care is described. A quasiexperimental pre- and post-design combined with concurrent control units for selected measures was the overall strategy. The authors conclude that comprehensive restructuring of hospital-based care can take place in a manner that preserves multiple dimensions of quality while decreasing costs. This only can be ascertained, however, through rigorous and systematic measurement and evaluation. Part 2 will detail application and evaluation of the restructuring model in the critical care environment.

Critical Care↗

Measuring and evaluating hospital restructuring efforts: 18-month follow-up and extension to critical care, Part 2.

Critical care has enjoyed unobstructed growth during the past two decades; however, to remain viable, process and role changes are pivotal to ensuring continued quality, cost-effective, and efficient care. In this article, the second in a two-part series, the authors describe restructuring efforts, inclusive of their measurement and evaluation strategies, within four critical care units at an acute care, tertiary institution. Special emphasis is placed on the process, the authors' observations, and lessons learned to date. Part 1 (September 1998) presented evaluation data of the effects of hospital restructuring on patient and nurse satisfaction, costs of care, and clinical quality in four medical-surgical units.

Critical Care↗

Measuring critical care redesign: impact on satisfaction and quality.

This report describes restructuring on four critical care units at an acute, tertiary care hospital in South-east Pennsylvania. Utilizing a Patient Centered Care conceptual framework that had been successfully applied in the medical-surgical areas, restructuring involved three main areas: revamping of work processes, inclusive of redesigned staff roles; environmental and facility changes; and enhancement of telecommunication and information systems. Preliminary analyses six months post redesign revealed improvements and maintenance in four outcomes areas--satisfaction, quality and efficiency, and costs of care.

Critical Care↗

The evaluation of hospital restructuring efforts: satisfaction, quality, and costs.

This article reports on study evaluating the effects of hospital restructuring on patient satisfaction, nurse satisfaction, cost of care, and clinical quality. The restructuring involved facility redesign, telecommunications enhancement, and implementation of patient care processes incorporating multiskilled personnel and case facilitation systems. The results indicate improved patient and nurse satisfaction, decreased length of stay and variable cost per patient day, and good clinical outcomes.

Hospital Bed Capacity, 500 and over↗

Parameters of transplant-mediated pupilloconstriction in rats with unilateral olivary pretectal lesions.

Embryonic retina, transplanted to the midbrain of neonatal rats, innervates the host brain and mediates a pupilloconstrictor response in the host eye. We hypothesise that there is a dynamic interaction between normal host and transplant photic input to the pupilloconstrictor centres. This study aims to characterise the nature of these interactions and determine the impact of experimental lesions on this reflex system. Pupillary diameter in normal rats is regulated by integration of intensity levels of the light delivered to the two eyes. The integration occurs at the primary input nucleus, the olivary pretectal nucleus, and at the output nucleus, the Edinger-Westphal nucleus. We have examined the pattern of integration of inputs delivered through the host eye and a retinal transplant placed over the midbrain at birth. Restriction of the site of integration to one olivary pretectal nucleus by ablating the contralateral nucleus causes a substantial enhancement of the transplant-mediated response and a major reduction in the host eye-mediated response. Although the pattern of change is quite similar to that seen between the two eyes of a normal animal after a similar lesion, the magnitude of improvement of the transplant response is much greater. The integration that occurs between transplant and host inputs is dynamic, and the efficacy of the transplant can be modulated by the competing host input. These results have implications for the use of neural transplants in degenerative diseases and might also offer insight into the limited functional recovery that occurs after neurological injury.

Animals↗

Characterization of a disassembly deficient mutant of cowpea chlorotic mottle virus.

An understanding of virus disassembly requires a detailed understanding of the protein-protein and protein-nucleic acid interactions which stabilize the virion. We have characterized a mutant of cowpea chlorotic mottle virus [cpR26C (coat protein R26C)] that displays increased virion stability and is abnormal in virion disassembly when purified under nonreducing conditions. Reduced virions are infectious, whereas nonreduced virions are noninfectious. The cpR26C mutant virions purified under nonreducing conditions resist disassembly in 0.5 M CaCl2, pH 7.5. The nonreduced cpR26C mutant virions swell in neutral pH conditions (pH 7.5) but do not disassociate when the ionic strength is increased. In contrast, wild-type virions or cpR26C mutant virions isolated under reducing conditions completely disassociate into the RNA and capsid protein components at pH 7.5 and high ionic strength (i > 1.0). Sequence analysis of the cpR26C mutant identified a single C to U nucleotide change at position 1435 of RNA 3 (position 86 of RNA 4), which results in a arginine to cysteine change at position 26 of the coat protein. The cpR26C mutant provides an ideal chemical switch for examining virion assembly and disassembly.

Bromovirus↗

The relationship of static foot structure to dynamic foot function.

Many theories have been advanced concerning the relationship between structure and function in the human foot, yet few of these theories have been subjected to quantitative examination. In this study, foot structure was characterized by 27 measurements taken from standardized lateral and dorsi-plantar weight-bearing plain radiographs of 50 healthy adult subjects. Regional plantar pressure distribution data collected from the same feet were chosen as the functional measures. A stepwise regression analysis was performed to (1) explore what portion of the variance in peak plantar pressure during walking can be explained by the radiographic measurements, and (2) identify structural characteristics of the foot which are significant predictors of peak plantar pressure under the heel and the first metatarsal head (MTH1). Most of the radiographic measurements were highly reliable. However, only 31 and 38% of the variance in peak plantar pressure at the heel and MTH1, respectively, could be explained using multiple regression analyses with the radiographic measurements as independent variables. Among the structural predictors that were identified, soft tissue thickness (e.g. calcaneus or sesamoid heights), and arch-related measurements were the strongest predictors of plantar pressure under both the heel and the first metatarsal head. We conclude that, in normal subjects, only about 35% of the variance in dynamic plantar pressure can be explained by the measurements of foot structure derived from radiographs. This implies that the dynamics of gait are likely to exert the major influences on plantar pressure during walking.

Adult↗

Redesigning primary care processes to improve the offering of mammography. The use of clinic protocols by nonphysicians.

OBJECTIVE: To develop, within the framework of continuous quality improvement, new processes for offering mammography and determine whether protocols executed completely by nonphysicians would increase mammography utilization. DESIGN: A prospective follow-up study with patients from an intervention clinic and two control clinics. SETTING: Three general internal medicine clinics in a large, urban teaching hospital in Detroit, Michigan. PATIENTS/PARTICIPANTS: A total of 5,934 women, aged 40 through 75 years, making 16,546 visits to one of the clinics during the study period (September 1, 1992, through November 31, 1993). INTERVENTION: Medical assistants and licensed practical nurses in the intervention clinic were trained to identify women due for screening mammography, and to directly offer and order a mammogram if patients agreed. MEASUREMENTS AND MAIN RESULTS: Patients were considered up-to-date with screening if they had a mammogram within 1 year (if age 50-75) or 2 years (if age 40-49) prior to the visit or a mammogram within 60 days after the visit. The proportion of visits each month in which a woman was up-to-date with mammography was calculated using computerized billing records. Prior to the intervention, the proportion of visits in which women were up-to-date was 68% (95% confidence interval [CI] 63%, 73%) in the intervention clinic and 66% (95% CI 61%, 71%) in each of the control clinics. At the end of the evaluation, there was an absolute increase of 9% (95% CI 2%, 16%) in the intervention clinic, and a difference of 1% (95% CI -5%, 7%) in one of the control clinics and -2% (95% CI -3%, 5%) in the other. In the intervention clinic, the proportion of visits in which women were up-to-date with mammography increased over time and was consistent with a linear trend (p = .004). CONCLUSIONS: Redesigning clinic processes to make offering of mammography by medical assistants and licensed practical nurses a routine part of the clinic encounter can lead to mammography rates that are superior to those seen in physicians' usual practice, even when screening levels are already fairly high. Physicians need not be considered the sole, or even the primary, member of the health care team who can effectively deliver some preventive health measures.

Adult↗

In vitro interactions of the aphid endosymbiotic SymL chaperonin with barley yellow dwarf virus.

Barley yellow dwarf virus (BYDV)-vector relationships suggest that there are specific interactions between BYDV virions and the aphid's cellular components. However, little is known about vector factors that mediate virion recognition, cellular trafficking, and accumulation within the aphid. Symbionins are molecular chaperonins produced by intracellular endosymbiotic bacteria and are the most abundant proteins found in aphids. To elucidate the potential role of symbionins in BYDV transmission, we have isolated and characterized two new symbionin symL genes encoded by the endosymbionts which are harbored by the BYDV aphid vectors Rhopalosiphum padi and Sitobion avenae. Endosymbiont symL-encoded proteins have extensive homology with the pea aphid SymL and Escherichia coli GroEL chaperonin. Recombinant and native SymL proteins can be assembled into oligomeric complexes which are similar to the GroEL oligomer. R. padi SymL protein demonstrates an in vitro binding affinity for BYDV and its recombinant readthrough polypeptide. In contrast to the R. padi SymL, the closely related GroEL does not exhibit a significant binding affinity either for BYDV or for its recombinant readthrough polypeptide. Comparative sequence analysis between SymL and GroEL was used to identify potential SymL-BYDV binding sites. Affinity binding of SymL to BYDV in vitro suggests a potential involvement of endosymbiotic chaperonins in interactions with virions during their trafficking through the aphid.

Amino Acid Sequence↗

Virion swelling is not required for cotranslational disassembly of cowpea chlorotic mottle virus in vitro.

The mechanism by which virions of cowpea chlorotic mottle virus (CCMV) disassemble and allow for translation of the virion RNA is not well understood. Previous models have suggested that virion swelling is required to expose the virion RNA for translation in a process referred to as cotranslational disassembly (M. Brisco, R. Hull, and T. M. A. Wilson, Virology 148:210-217, 1986; J. W. Roenhorst, J. W. M. van Lent, and B. J. M. Verduin, Virology 164:91-98, 1988; J. W. Roenhorst, J. M. Verduin, and R. W. Goldbach, Virology 168:138-146, 1989). Previous work in our laboratory has identified point mutations in the CCMV coat protein which result in virions with altered swelling characteristics (J. Fox, F. G. Albert, J. Speir, and M. J. Young, Virology 227:229-233, 1997; J. M. Fox, X. Zhao, J. A. Speir, and M. J. Young, Virology 222:115-122, 1996). The wild-type and mutant CCMV virions were used to correlate virion swelling with the ability of virion RNA to be translated in a cell-free wheat germ extract. Mutant virions unable to swell (cpK42R) are as infectious as wild-type virions in vivo, and the levels of translated encapsidated virion RNA are similar to those of wild-type virions in vitro. Mutant virions capable of swelling but not of disassembling in vitro (cpR26C) are noninfectious and have severely reduced levels of translation of the encapsidated virion RNA in vitro. These studies suggest that virion swelling is not required for the cotranslational disassembly of CCMV. Additionally, the results indicate that there is a pH-dependent structural transition in the virion, other than swelling, that results in the RNA's being exposed for translation in vitro. An alternative model suggesting that cotranslational disassembly of CCMV involves presentation of the virion RNA through the virion fivefold axis is proposed.

Cell-Free System↗

Light induced EEG desynchronization and behavioral arousal in rats with restored retinocollicular projection by peripheral nerve graft.

Peripheral nerve (PN) was grafted to sectioned optic nerve and was bridged to the superior colliculus in adult rats. To test functional recovery of restored retinocollicular pathway, we examined cortical electroencephalogram (EEG) and behavioral arousal responses to light stimuli. In eight of 10 recording trials in PN grafted rats (n = 6) and in all of eight trials in normal rats (n = 5), cortical EEGs showed desynchronization to light stimuli. On the other hand, after bilateral sections of the optic nerve (n = 3) EEG desynchronization to light disappeared while it was induced by a white noise. Mean threshold duration of light for EEG desynchronization was significantly longer in the PN grafted rats (440 ms) than in normal rats (173 ms). In three of six trials in PN grafted rats (n = 4), and in four of eight trials in normal rats (n = 4), EEG desynchronization elicited by light stimulus was accompanied by behavioral arousal responses, whereas no behavioral arousal could be induced by light in blind rats (n = 3). These results strongly suggest that visual information processed through the restored retinocollicular pathway was further transmitted to the cerebral cortices and ultimately resulted in behavioral arousal of the PN grafted rats.

Animals↗

Analysis of a salt stable mutant of cowpea chlorotic mottle virus.

An understanding of virion assembly and disassembly requires a detailed understanding of the protein-protein and protein-nucleic acid interactions which stabilize the virion. We have characterized a mutant of cowpea chlorotic mottle virus (CCMV) that is altered in virion stability. The mutant virions resist disassembly in 1.0 M NaCl, pH 7.5, whereas the wild-type virions completely disassociate into RNA and capsid protein components. Sequence analysis of the mutant coat protein gene identified a single A to G nucleotide change at position 1484 of RNA 3 (position 134 of RNA 4), which results in a lysine to arginine change at position 42 of the coat protein. Introduction of the K42R mutation into wild-type CCMV coat protein results in a salt stable virion phenotype. Likewise, expression of the K42R mutant coat protein in Escherichia coli followed by in vitro assembly produces virions that exhibit the salt stable phenotype. Analysis of this mutation demonstrates how a single amino acid change in the primary structure of the coat protein leads to tertiary interactions which stabilize the virion.

Bromovirus↗

The association between callus formation, high pressures and neuropathy in diabetic foot ulceration.

The presence of an ulcer beneath callus on the diabetic foot has been a well-documented and common clinical finding. We have conducted a prospective study to examine whether callus can be used to predict plantar intrinsic neuropathic diabetic foot ulcer formation. Sixty-three diabetic patients (43 male, 25 Type 1), median age 62 years (IQ range 52, 67), median diabetes duration 17 years (IQ range 8,25) participated in the study. All had neuropathy and peak plantar foot pressures (measured using a dynamic optical pedobarograph) > or = 10 kg cm-2. Calluses and previous ulcers were documented and classified. All ulcers occurring prior to and during the study were recorded, re-examination was 15.4 (range 10-22) months from baseline. Seven ulcers (6 patients) occurred during the study. Pressures were higher in the ulcer than non-ulcer sub-group (p = 0.04) with a relative risk of developing an ulcer of 4.7 for an area of elevated plantar pressure. This compares with a relative risk of 11.0 for an ulcer developing under an area of callus, and a relative risk of 56.8 for an ulcer developing on a site of previous ulceration. This study confirms that a history of previous ulceration is the highest risk factor for ulceration and demonstrates, for the first time, that the presence of plantar callus is highly predictive of subsequent ulceration. Careful history taking and examination of the foot to detect the presence of callus require no special training or equipment and callus should be recognized as a 'high risk' factor for foot ulceration.

Callosities↗

Mineralocorticoids, salt, hypertension: effects on the heart.

In uninephrectomized rats on 1% NaCl solution to drink, aldosterone (0.75 micrograms/h subcutaneously for 8 weeks) raises blood pressure and causes marked interstitial and perivascular cardiac fibrosis, effects not seen in animals on a low salt intake. In extending these initial findings, we have shown that cardiac fibrosis (i) is not reversed by correction of mineralocorticoid-induced hypokalemia; (ii) appears not to involve the plasma or tissue renin-angiotensin systems, as fibrosis is largely unaffected by concurrent administration of Losartan or Perindopril; (iii) is independent of cardiac hypertrophy, in that it is equally seen in right and left ventricles, and in rats rendered hypertensive without cardiac hypertrophy by the administration of 9 alpha-fluorocortisol; (iv) is independent of elevated blood pressure, in that it is found in normotensive animals infused peripherally with aldosterone and intracerebroventricularly with the mineralocorticoid receptor (MR) antagonist RU28318; (v) is via classical MR, in that it is blocked by concurrent administration of the MR antagonist potassium canrenoate; and (vi) may or may not be a direct cardiac effect, inasmuch as data for in vivo effects on collagen formation by cardiac fibroblasts are conflicting. Although there is a high probability that the action of aldosterone to cause cardiac fibrosis in this experimental model is an effect via non-epithelial MR, the locus of aldosterone action remains to be established, as do the molecular mechanisms linking MR occupancy by aldosterone and collagen deposition. In addition, and in particular, the mechanisms underlying the crucial contribution of high salt intake in this model of mineralocorticoid excess await exploration.

Aldosterone↗

Balancing service and education: improving internal medicine residencies in the managed care era.

BACKGROUND: Internal medicine training programs must adapt to health care systems faced with balancing the competitive priorities of patient-care responsibilities and educational needs. OBJECTIVE: To evaluated the effects of a major organizational change on the inpatient service of an internal medicine residency program in a vertically integrated health system. METHODS: We changed the structure of our program from a system in which the hospitalized patients' primary physicians were responsible for daily inpatient management, while teaching was assigned to a defined teaching rounder, to a method in which the rounding attending was responsible for both teaching and patient care. Measurements before and after the change in the rounding system included: the McGill University clinical tutor evaluations, time-motion observations of house staff, patient satisfaction surveys, average length of stay data, and physician focus groups to assess physician satisfaction. RESULTS: The rounding attendings consistently received excellent to superior ratings by the house staff both before and after the implemented change. Compared to time-motion observations performed before the change, observations recorded after the change suggested that a greater percent of house staff time was spent on educational activities. The responses of patient satisfaction surveys indicated that the perception of quality of care remained high after the system change. Lastly, the average length of stay for patients on the general internal medicine and subspecialty services was reduced from 7.6 days before the change to 6.6 days after the change, a difference of 0.92 day (95% confidence interval 1.3 to 0.6, P < 0.001). CONCLUSIONS: Through organizational restructuring, it is possible to improve the quality of patient care and improving the efficiency of patient-care management.

Hospital Bed Capacity, 500 and over↗

Rheological and microvascular parameters in diabetic peripheral neuropathy.

1. In order to determine whether rheological changes occur in neuropathic diabetic patients in the absence of smoking, proteinuria, retinopathy or other factors thought to influence haemorheology, three groups of subjects were studied; 24 non-diabetic control subjects (C), 24 non-neuropathic (D) and 24 neuropathic (N) diabetic patients. The groups were matched for age, sex, type and duration of diabetes. No patient or control was a current smoker. No patient had clinically detectable retinopathy or microalbuminuria. Neuropathy was defined as a peroneal conduction velocity < 40 ms-1. All subjects were tested resting semi-recumbent after a light breakfast. 2. There were no significant differences in rheological or microvascular parameters between uncomplicated diabetic patients and non-diabetic control subjects, although peroneal nerve motor conduction velocity was significantly reduced in otherwise uncomplicated diabetic patients [C 51.7 +/- 6.0 ms-1 (mean +/- SD) versus D 45.1 +/- 5.2 ms-1 (P < 0.05 C versus D)]. 3. Transcutaneous oxygen and laser Doppler flux measured at 44 degrees C were higher in control subjects than in neuropathic diabetic patients [C 76 +/- 16 mmHg versus D 71 +/- 10 mmHg versus N 63 +/- 9 mmHg, and C 72 +/- 40 flow units versus D 64 +/- 41 flow units versus N 50 +/- 26 flow units respectively (both P not significant C versus D, P < 0.05 N versus C). 4. Erythrocyte aggregation, plasma viscosity and plasma fibrinogen were all significantly higher in the neuropathic diabetic patients compared with non-diabetic control subjects (all P < 0.05 N versus C). Erythrocyte filtration was not significantly different between groups but was lower in diabetic patients. Whole-blood viscosity (corrected to 45% haematocrit) was significantly higher at both high (100 s-1) and low (1 s-1) shear rates in neuropathic diabetic patients than in non-diabetic control subjects (both P not significant C versus D, P < 0.05 N versus C). There were no significant differences in whole-blood viscosity at a shear rate of 0.01 s-1. 5. In summary, there were no significant differences in rheological or microvascular parameters between matched groups of uncomplicated diabetic patients and control subjects, but erythrocyte aggregation, fibrinogen and plasma and corrected whole-blood viscosity were all significantly different in neuropathic diabetic patients compared with control subjects, as were assessments of microvascular flow. These results suggest that haemorheological changes are associated with disturbances of microvascular flow and diabetic peripheral neuropathy in the absence of other diabetic complications.

Adult↗