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Biomedical subjects

L Sullivan

Publications and source records attributed to L Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Diaphragm function in patients with cervical cord injury or prior poliomyelitis infection.

Diaphragm function was evaluated in cervical cord injury patients (CCI), 1-3 years after injury (CCI(1-3)) and 10 years or more after injury (CCI(> or = 10)), as well as in a group of prior poliomyelitis infection patients (PPI), requiring intermittent positive pressure ventilation (IPPV) for about 6 h per night. Measurements included transdiaphragmatic pressure swings (delta Pdi) at rest, during maximal inspiratory efforts against closed airways (delta Pdi(max)) and during sniff manoeuvres (ie maximal inhalation through the nose, delta Pdi(sniff)), vital capacity normalized to age and height (VC(%pred)), tidal volume (Vt), relative inspiratory time (Ti/Ttot), breathing frequency (f(b)), and the tension-time index of the diaphragm (TTdi = delta Pdi/delta Pdi(max) x Ti/Ttot). The median VC(%pred) was 50% in the CCI(1-3) group and 57% in the CCI (> or = 10) group, but only 28% in the PPI group. Delta Pdi(max) values were similar for the CCI(1-3) (11.8 kPa) and CCI(> or = 10) (11.9 kPa) groups but were lower (71. kPa) in the PPI group. Due to the reduction in delta Pdi(max), the PPI group had higher delta Pdi/delta Pdi(max) values than the CCI groups, however, the TTdi was similar amongst the different groups studied. A submaximal exercise test in five cervical cord injury patients and in five polio patients with similar delta Pdi(max), delta Pdi(sniff) and TTdi values at rest revealed clear group differences with respect to force development, in that CCI patients showed significant increases in TTdi, while PPI demonstrated only minor changes. In CCI patients, an increase in ventilation was accompanied by an increase in delta Pdi/delta Pdi(max) while in contrast, the PPI patients showed no increase in delta Pdi/delta Pdi(max). We conclude that CCI patients, both recently and previously injured, have a similar maximal inspiratory force and are less impaired than the PPI patients. The TTdi at rest is similar in all groups, but the PPI patients react to inspiratory loads with little increases in TTdi, while the CCI patients increase their TTdi above fatiguing (0.15) levels. The different behaviours may be linked to loss of sensory pathways in the CCI patients.

Adult↗
PubMed1996

Mechanical methods in refractive corneal surgery.

The past year has seen considerable advances and debate with regard to several new and some established mechanical means of refractive surgery. Lamellar in situ keratomileusis is gaining increased interest, especially for the treatment of moderate and high myopia, although considerable questions still exist with regard to its safety, predictability, and the possibility of loss of lines of best corrected visual acuity. Mini-radial keratotomy may be of benefit in reducing the risk of traumatic rupture of radial keratotomy incisions, and a refinement of the nomograms for astigmatic keratotomy in the treatment of congenital astigmatism has been proposed. Another report on the use of hexagonal keratotomy for the treatment of hyperopia again raised concerns of its predictability. A blind eye study of intrastromal corneal rings has provided some reassurance with regard to its safety but has also raised doubts over its predictability. Meanwhile, several more reports of the use of both anterior and posterior chamber phakic intraocular lenses for the treatment of myopia have been presented.

Cornea↗
PubMed1995

Effect of a prior-authorization requirement on the use of nonsteroidal antiinflammatory drugs by Medicaid patients.

BACKGROUND: Prior authorization--mandatory advance approval for the use of expensive medications--is now the primary method by which Medicaid programs control expenditures for drugs. However, whether this policy reduces expenditures for specific drugs without causing the unwanted substitution of other drugs or medical services has been largely unstudied. We evaluated the effects of a prior-authorization policy involving nongeneric nonsteroidal antiinflammatory drugs (NSAIDs) in the Medicaid program in Tennessee. METHODS: We compared monthly Medicaid expenditures that were potentially affected by the policy change during the year before and the two years after its implementation. We studied prescriptions for NSAIDs, other analgesic or antiinflammatory drugs, and psychotropic drugs, as well as outpatient services and inpatient admissions for the management of pain or inflammation. RESULTS: At the midpoint of the base-line year, 495,821 people were enrolled in Medicaid. During that year, mean annualized Medicaid expenditures for NSAID prescriptions amounted to $22.41. Expenditures decreased by 53 percent (95 percent confidence interval, 48 to 57 percent) during the next two years, for an estimated savings of $12.8 million. The reduction in expenditures resulted from the increased use of generic NSAIDs, as well as from a 19 percent decrease in overall NSAID use (95 percent confidence interval, 13 to 25 percent). There was no concomitant increase in Medicaid expenditures for other medical care. Regular users of nongeneric NSAIDs, those most affected by the policy change, had similar reductions in NSAID expenditures and use, with no increase in expenditures for other medical care. CONCLUSIONS: Prior-authorization requirements may be highly cost effective with regard to expenditures for NSAIDs, drugs that have very similar efficacy and safety but substantial variation in cost.

Adolescent↗
PubMed1995

Foot infections in diabetic patients. Decision and cost-effectiveness analyses.

OBJECTIVE: To examine the cost-effectiveness of approaches to the diagnosis and treatment of patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM) who have foot infections and suspected osteomyelitis. DESIGN: Decision and cost-effectiveness analyses were performed using a Markov model. We examined the prevalence of osteomyelitis, the major complications and efficacies of long-term antibiotic therapy and surgery, and the performance characteristics of four diagnostic tests (roentgenography, technetium Tc 99m bone scanning, indium in 111-labeled white blood cell scanning, and magnetic resonance imaging). Data were drawn from the English-language literature using MEDLINE searches and bibliographies from selected articles. SETTING: Primary care. PATIENTS: Patients with NIDDM who had foot infections and suspected osteomyelitis but no signs of systemic toxicity. INTERVENTIONS: Following hospitalization for surgical débridement and intravenous antibiotic therapy: (1) treatment for presumed soft-tissue infection, (2) culture-guided empiric treatment for presumed osteomyelitis, (3) 71 combinations of diagnostic tests preceding antibiotic therapy for osteomyelitis, (4) 71 combinations of tests preceding amputation, and (5) immediate amputation. MAIN OUTCOME MEASURES: Quality-adjusted life expectancy, average costs. RESULTS: Culture-guided empiric treatment for osteomyelitis with 10 weeks of oral antibiotic therapy has similar effectiveness to testing followed by a long course of antibiotic therapy if any test result is positive. However, empiric treatment is the least expensive strategy. CONCLUSIONS: Noninvasive testing adds significant expense to the treatment of patients with NIDDM in whom pedal osteomyelitis is suspected, and such testing may result in little improvement in health outcomes. In patients without systemic toxicity, a 10-week course of culture-guided oral antibiotic therapy following surgical débridement may be as effective as and less costly than other approaches.

Amputation, Surgical↗
PubMed1995

Lymphomagenesis in the SCID-hu mouse involves abundant production of human interleukin-10.

Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be important cofactors in the survival and growth of lymphoblastoid cell lines infected with Epstein-Barr virus (EBV). When mice with severe combined immune deficiency (SCID) are injected with human peripheral blood lymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymphoproliferative disease (EBV-LPD) of human B-cell origin, not unlike some cases of EBV-LPD that are seen in immunocompromised individuals. The role of huIL-10 or vIL-10 in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that develop EBV-LPD have significant elevation of serum huIL-10 levels compared with mice that do not develop EBV-LPD (P = .005). vIL-10 was undetectable in all animals. The EBV+ tumor samples express transcript for huIL-10 and huIL-10 receptor, express huIL-10 protein by immunohistochemical staining, and show specific binding of recombinant (r) huIL-10. In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV+ tumor cells shows that rhuIL-10 can prevent programmed cell death as well as promote proliferation and can do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 production by EBV+ tumor cells may contribute directly to their malignant outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: prevention of programmed cell death and proliferation. The implications of such findings with regard to EBV-LPD in humans is discussed.

Animals↗
PubMed1995

Influence of the sympathetic nervous system on insulin sensitivity and adipose tissue metabolism: a study in spinal cord-injured subjects.

To evaluate insulin sensitivity and adipose tissue metabolism, seven spinal cord-injured (SCI) subjects (age, 43 +/- 6 years; body mass index, 22.8 +/- 1.4; mean +/- SE) and their seven siblings (age, 45 +/- 6 years; body mass index, 24.8 +/- 0.8) were studied using oral glucose (100-g) tolerance tests (OGTTs), euglycemic insulin clamps (insulin infusion, 1 mU/kg.min), and microdialysis of the subcutaneous tissue. Blood glucose and insulin after oral glucose were significantly increased in SCI subjects as compared with their siblings. During insulin clamping, plasma adrenaline increased significantly in controls, but not in SCI subjects. However, the rates of glucose production (2.02 +/- 0.36 v 1.59 +/- 0.09 mg/kg.min) and utilization (5.13 +/- 0.71 v 5.78 +/- 0.34) were similar in the two groups. Furthermore, interstitial subcutaneous glycerol and lactate concentrations before and after oral glucose were similar in the two groups, even in neurally decentralized tissue with broken connection between the central nervous system and peripheral sympathetic nerves. The data suggest that (1) well-mobilized SCI subjects show minor insulin resistance, and (2) sympathetic nervous activity has a minor influence on adipose tissue metabolism in the postabsorptive state, but may affect insulin sensitivity during euglycemic clamping.

Adipose Tissue↗
PubMed1995

Clean intermittent catheterization in spinal cord injury patients: long-term followup of a hydrophilic low friction technique.

Clean intermittent self-catheterization is an established option in bladder management of spinal cord injury patients. Several early and a small number of long-term studies have reported good preventive or therapeutic effects on hydronephrosis, vesicourethral reflux, urinary tract infection and incontinence. Most reports describe the use of small catheters and liberal use of jelly but urethral complications, such as strictures and false passages, seem to increase with the length of followup. All 30 spinal cord injury patients in this retrospective study had used disposable hydrophilic, low friction catheters from the early shock phase to a median of 7 years (range 5 to 9). There were 26 upper motor neuron and 4 lower motor neuron lesions. After tap water soaking, the surface layer of the catheter coating has a friction constant more than 10 times lower than that for a regular plastic catheter (Nélaton) with chlorhexidine jelly. There was no hydronephrosis, pyelonephritis or renal scarring. In 3 patients who had decreased the clean intermittent self-catheterization regimen, signs of upper tract dilatation developed but the excretory urogram returned to normal after correction of the regimen. Of 30 patients 12 (40%) maintained sterile urine, while 4 of the remaining 18 with bacteriuria had episodes of urinary sepsis and chronic infections. Two patients had epididymitis. Of 6 men with occasional insertion difficulties when the clean intermittent self-catheterization regimen started after the indwelling catheter had been removed 4 showed yielding signs of strictures during the subsequent clean intermittent self-catheterization regimen. In 1 patient 2 dilation attempts had failed but the patient can perform the clean intermittent self-catheterization regimen. One patient with Crohn's disease had advanced urethral changes in the acute phase but could perform clean intermittent self-catheterization with a small catheter. One patient has had recurrent modifications of the urethral wall but no development of a false passage. The study indicates that patients who use hydrophilic low friction low friction catheters do as well as or better than patients using conventional catheters. Above all, there is no increase in severe urethral complications with time after injury. Progression towards strictures after early urethral trauma seems to be preventable by the use of this catheter.

Adult↗
PubMed1995

Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia.

PURPOSE: We administered capsaicin, a neurotoxic substance causing a reversible suppression of C fiber afferent neuronal activity, in an attempt to decrease bladder hyperreflexia. MATERIALS AND METHODS: Capsaicin solution (2 mM.) dissolved in 30% alcohol was instilled into the bladders of 10 men with traumatic chronic spinal lesions and left in place for 30 minutes. Effects on bladder function, including response to cold stimulation, were recorded during treatment, immediately after instillation and at followup. RESULTS: Bladder function improved in all but 1 patient, which was expressed as an increase in cystometric capacity and/or a decrease in maximal detrusor pressure. The effects lasted for 2 to 7 months. Immediately after capsaicin administration the ice water test was negative in half of the patients. CONCLUSIONS: The positive effects on bladder function of capsaicin treatment can be explained by the blocking of C fiber afferents. The optimum dose and treatment interval are presently not established. The ice water test might possibly be used as an instrument to monitor the ideal dosage.

Adolescent↗
PubMed1995

Development and testing of a new measure of case mix for use in office practice.

Case mix has been shown to be of critical importance in studies of effectiveness and quality of care using health outcomes. How these variables are defined, combined, and used to adjust or increase precision in tests for differences in health outcomes has been a source of controversy. Because existing measures were developed to adjust mortality and have marginal relevance for the adjustment of functional status outcomes, especially in ambulatory settings, the authors developed a measure of case (or patient) mix that is specifically designed to adjust functional status outcomes measured in office practice or out-of-hospital settings. This measure, developed as part of Type II Diabetes Patient Outcomes Research Team project, uses patients' reports of symptoms and conditions, as well as patients' ratings of symptom intensity to characterize total disease burden. It differs from other measures of case mix in lack of dependence on diagnoses. Separate measures were developed for each of 15 different disease categories (e.g., chronic lung disease) grouped by body system affected. Within each measure, questionnaire items were combined to rate the severity of that disease on a 1 to 4 scale, according to definitions provided by clinicians. A single, global measure was developed by aggregating the 15 measures, weighted according to the expected impact of each disease category on functional outcomes and disability. In a sample of 1,738 patients, significant relationships were observed between the global case mix measure and functional status, disability days, and service utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Embryo experimentation and the murder prohibition: a casuistic examination of the utilitarian and pro-life positions on the moral status of the embryo.

Argument concerning the permissibility of embryo experimentation has tended to proceed from the opposed ethical principles of utilitarianism and the sanctity of human life, neither of which entirely reflects Western society's present position on murder and moral obligations. Singer's utilitarian arguments propose a test of subject attributes for admission to the protection of morality, and it is argued that this approach is entirely at odds with our current axiomatic application of the murder prohibition of post-birth humans. Similarly, those arguing from a pro-life position do not take account of the ambivalence of our application of this principle to the pre-birth human, as seen in abortion. In the attempt to deal with the quandary of the moral position of the embryo, we should, following the philosophical precedent of casuistry, start from the position of our current moral certainties, rather than expose ourselves to the social dangers of an untried rationality divorced from practice.

Australia↗
PubMed1994

Principles and practice of case mix adjustment: applications to end-stage renal disease.

For optimal case mix adjustment, it is necessary to build risk or severity models to fit the disease and its outcome. For cardiac disease, for example, several risk models predict the outcome of mortality. These risk models include variables that, by themselves in multivariable models, predict death. If a variable is associated with death independent of treatment or quality of care, it has to be adjusted for and, therefore, included in the model. Similar models have to be developed and tested for end-stage renal disease. A complete risk model would consist of age, sex, the severity of the primary disease of interest (here, end-stage renal disease), not just the presence but also the severity of all co-morbid disease, and, finally, a measurement of functional status or quality of life. This last measurements is associated with outcome beyond and independent of the above noted severity components. These factors (or "severity" or "patient mix" dimensions) then have to be developed in relation to a specific outcome or response variable. Cholesterol and hypertension are risk factors for long-term events and mortality, but not for 2-year symptoms and quality of life. Thus, the model has to be defined by the type of outcome and by the time interval over which the variable acts. For end-stage renal disease, at least one of the major types of outcome will be quality of life. Our case mix measures for hospital co-morbidity and for office practice chronic disease are defined by and intended to predict functional status in the short run, because that is the outcome of interest for dollars spent and for most of the care rendered to patients with chronic disease before the very end stages. Creating a valid case mix or severity measurement aimed at or defined by quality of life thus involves the creation of new models, the testing of those models, the revision based on the empirical testing, and, finally, generalizing to other sites beyond which the data were collected. Useful case mix measurements will be parsimonious, feasible, reliable, validated against the outcome of interest, shown to work in diverse settings, and acceptable to users, especially clinicians.

Activities of Daily Living↗
PubMed1994

Selective accumulation of T cells according to T-cell receptor V beta gene usage in skin cancer.

To investigate whether specific T-cell populations are overrepresented in tumor-infiltrating lymphocytes (TIL) in skin cancer, we determined the T-cell receptor (TCR) diversity in biopsy specimens of basal cell carcinoma and squamous cell carcinoma. Immunostaining of tissue sections indicated that the majority of T cells expressed alpha beta TCRs. To assess diversity of the TCR beta chain, RNA was isolated directly from the tumor specimens and peripheral blood mononuclear cells (PBMC) from the same patient, cDNA was synthesized, and variable (V) beta chain gene usage was determined by the polymerase chain reaction (PCR). In each basal cell (n = 11) and squamous cell (n = 7) carcinoma studied, several V beta families were overrepresented in TIL versus PBMC, in that they accounted for greater than 5% of the repertoire in TIL and were at least 2% higher in TIL than in PBMC. The predominant V beta gene segments overrepresented in TIL generally differed from individual to individual. Simultaneous comparison of the V beta repertoire of TIL to that of uninvolved skin and PBMC from the same individual revealed preferential expression of V beta families within the TIL in three of five basal cell and four of four squamous cell carcinomas. Again, the predominant V beta s differed from individual to individual. Comparison of the TCR repertoire in uninvolved skin versus PBMC did indicate that some V beta families were overexpressed in the resident T-cell compartment in skin, although the overrepresented families were not constant from individual to individual. These data indicate the selective concentration of T cells bearing specific alpha beta TCRs in the local immune response to basal cell and squamous cell carcinomas.

Basal Cell Carcinoma↗
PubMed1994

The uses of outcomes research for medical effectiveness, quality of care, and reimbursement in type II diabetes.

Randomized controlled trials (RCTs), such as the Diabetes Control and Complications Trial (DCCT), usually evaluate the efficacy of a single treatment strategy. The DCCT, for example, evaluates intensive diabetes management aimed at achieving glucose levels as close to normal as possible to modify specific pathophysiological outcomes--specifically, the development or worsening of microvascular disease. In contrast, longitudinal observational studies, such as the type II diabetes Patient Outcome Research Team (PORT) study, address medical effectiveness; that is, how well prevailing treatments work in clinical practice settings. The PORT relies heavily on patient-reported measures of general and diabetes-specific health status, in addition to using complications as major study outcomes. In the type II diabetes PORT, 4,000 patients with type II diabetes and a wide range of socioeconomic, demographic, and disease characteristics, from three widely dispersed geographic settings and varying systems of care, are being followed for a 2.5-year period. Data are collected from periodic self-administered patient questionnaires and from administrative data bases. In the PORT study, nonmutable confounders, such as case-mix, and potentially mutable features, such as patients' preferences for treatment, health habits, regimen adherence, family support, and physician's interpersonal style, are carefully measured. The PORT study will examine the effectiveness of preventive care and established disease treatment in relation to eye, cardiovascular, and extremity disease, measuring and relating use of health-care services to patient outcomes. The results have the potential for maximizing quality of care and minimizing use of services in type II diabetes by matching physician-level profiles of patient outcomes with medical-care-process data and making this information accessible to practicing physicians.

Clinical Trials as Topic↗
PubMed1993

Choroidal melanoma in a dog.

B-scan ultrasonography of the right eye of a 6-year-old sexually intact female mixed-breed dog revealed complete retinal detachment and a semiconical solid mass of tissue that projected from the area of the optic disc into the vitreal space subretinally. Microscopic examination of an ultrasound guided fine-needle aspirate of the mass revealed a moderate number of mildly pleomorphic melanocytes. Histologic examination of the excised globe revealed a large, heavily pigmented intraocular neoplastic mass in the choroid around the optic nerve, bulging into the subretinal space. The histologic diagnosis was benign choroidal melanoma, with invasion into the intraocular portion of the optic nerve. In dogs, tumors of melanocytic origin are the most common primary ocular neoplasm, but primary choroidal melanocytic neoplasms are the rarest of this type.

Animals↗
PubMed1993

Immunochemical mapping of domains in human interleukin 4 recognized by neutralizing monoclonal antibodies.

Human interleukin 4 is a highly pleiotropic cytokine secreted by activated T cells that exerts multiple biological effects on B and T lymphocytes and other cell types. Elucidation of structure-function relations was accomplished by epitope mapping of a panel of monoclonal antibodies and by mutagenesis of selected amino acid residues. Epitope mapping of these monoclonal antibodies was achieved through binding studies with recombinant human interleukin 4 (rhuIL-4), proteolytic fragments produced by digestion with Staphylococcus aureus V8 protease and synthetic peptides derived from the sequence of the parent molecule. Monoclonal antibodies 25D2, 35F2, and 11B4 neutralized the in vitro T-cell proliferation activity of rhuIL-4 and also prevented binding of rhuIL4 to its cell surface receptor. These antibodies recognized sequences 104-129, 70-92, and 61-82, respectively. These regions comprise the BC loop/helix C (residues 61-92) and helix D (residues 104-129). A nonneutralizing monoclonal antibody (1A2) recognized a nonoverlapping region (residues 43-59) comprising almost entirely helix B. Mutagenesis of a cluster of residues within helix C showed that at least three residues (K84, R88, and N89) were potentially involved in receptor recognition. The existence of two distinct nonneighboring binding domains in the three-dimensional structure of rhuIL-4 provided preliminary evidence for a model of receptor interaction involving the formation of a ternary complex consisting of two molecules of the extracellular portion of the receptor and one molecule of rhuIL-4.

Antibodies, Monoclonal↗