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Biomedical subjects

M Peterson

Publications and source records attributed to M Peterson.

At least 19 recordsLinked to original sources

Spinous process osteotomies to facilitate lumbar decompressive surgery.

STUDY DESIGN: A technique for lumbar decompression using spinous process osteotomies is described, and the outcomes are studied prospectively. OBJECTIVE: To describe a technique that affords a wide exposure for decompression while minimizing damage to surrounding tissues, and to analyze the outcomes formally using the technique. SUMMARY OF BACKGROUND DATA: Commonly used techniques of lumbar decompression, which include bilateral takedown of paraspinal musculature and aggressive bony resection, can result in significant iatrogenic sequelae, whereas minimally invasive techniques often provide inadequate visualization and/or decompression. METHOD: Unilateral limited takedown of the multifidus is undertaken, followed by spinous process osteotomies at the involved levels. The spinous processes with the attached interspinous/supraspinous ligaments are then retracted. A complete "trumpeted" decompression is then undertaken. Fifty consecutive patients undergoing the procedure were analyzed prospectively and at follow-up by an independent observer using a validated functional outcome measure, a visual analog pain scale, and a patient satisfaction score. RESULTS: Functional outcome scores improved on average by 47%, pain levels were reduced by 66%, and high satisfaction rates were reported by 83% of patients. CONCLUSIONS: The technique affords excellent visualization and a wide area available for Kerrison use and angulation while minimizing destruction to tissues not directly involved in the pathologic process, including the paraspinal musculature as well as the interspinous/supraspinous ligament complex and facets. Additionally, it minimizes dead space and improves the cosmetic result.

Aged

The inability of the nonobese diabetic class II molecule to form stable peptide complexes does not reflect a failure to interact productively with DM.

Sequence variability in MHC class II molecules plays a major role in genetically determined susceptibility to insulin-dependent diabetes mellitus (IDDM). It is not yet clear whether MHC class II polymorphism allows selective binding of diabetogenic peptides or regulates some key intracellular events associated with class II-restricted Ag presentation. In this study, we have employed gene transfer techniques to analyze the intracellular events that control peptide acquisition by the unique class II molecule expressed by nonobese diabetic mice (I-Ag7). This structurally unique class II molecule fails to demonstrate stable binding to antigenic peptides and fails to undergo the conformational change associated with stable peptide binding to class II molecules. The experiments reported here demonstrate that I-Ag7 can productively associate with two protein cofactors important in class II-restricted Ag presentation, invariant chain (Ii) and DM. DM participates in the removal of the Ii-derived class II-associated Ii chain peptide and the p12 degradation product from the I-Ag7 molecule. In addition, I-Ag7 undergoes a conformational change when DM is expressed within the APC. Finally, DM can mediate accumulation of peptide/class II complexes on the surface of APCs. Collectively, our experiments indicate that the failure of the I-Ag7 molecule to stably bind peptide cannot be attributed to a failure to interact with the DM or Ii glycoproteins.

Animals

N-terminal proANF in acute atrial fibrillation: a biochemical marker of atrial pressures but not a predictor for conversion to sinus rhythm. Digitalis in Acute Atrial Fibrillation (DAAF) Trial group.

BACKGROUND: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF. METHODS: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate. RESULTS: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters. CONCLUSION: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.

Acute Disease

Placental pathology in systemic lupus erythematosus: a prospective study.

OBJECTIVES: Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus. STUDY DESIGN: Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively. RESULTS: Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings. CONCLUSIONS: Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.

Adult

Marimastat inhibits neointimal thickening in a model of human vein graft stenosis.

BACKGROUND: There is now accumulating evidence that matrix metalloproteinases (MMPs), the physiological mediators of matrix deposition and degradation, play an important role in the development of intimal hyperplasia following arterial bypass. This study investigated the effect of marimastat, an orally active specific MMP inhibitor, on neointima formation in cultured human saphenous vein. METHODS: Segments of human saphenous vein obtained from ten patients undergoing arterial bypass surgery were cultured for 14 days in serum-supplemented RPMI medium (controls) or in control medium supplemented with marimastat at three different concentrations (treatment groups). Following culture, half of each segment was prepared for histological examination and MMPs were extracted from the other half for gelatin zymography. RESULTS: Marimastat inhibited neointimal thickening in a concentration-dependent manner; inhibition was significant at 10(-5) and 10(-6) mol/l (P=0.006). This observation was paralleled by a significant reduction in the levels of MMP-2 and MMP-9 in the tissues. CONCLUSION: Marimastat significantly reduced neointimal thickening in this laboratory model. MMP inhibitors may offer a potential therapeutic strategy in the prevention of intimal hyperplasia.

Cells, Cultured

Analysis of a worksite health promotion program's impact on job satisfaction.

This study assessed the impact of participation in a health promotion program and engagement in healthy behaviors on job satisfaction. A survey response rate of 70% (n = 1,283) was obtained at a northern state university with an established worksite health promotion program. Significant differences in job satisfaction were obtained by education level, job classification, marital status, dependents, and regular exercise behaviors. No differences in job satisfaction were obtained by health promotion program involvement or any other health behavior other than regular exercise. Results suggest that health promotion programs do not significantly impact job satisfaction. Rather, job design and the psychosocial aspects of the work environment may be more influential in improving job satisfaction. Based on the results of this study, organizations attempting to improve employee health should provide health promotion programs and address the job itself. To improve job satisfaction, attention to the job itself is required.

Educational Status

Venous haemodynamics after total knee arthroplasty: evaluation of active dorsal to plantar flexion and several mechanical compression devices.

We performed a crossover study to evaluate the haemodynamic effect of active dorsal to plantar flexion and seven pneumatic compression devices in ten patients who had a total knee arthroplasty. Using the Acuson 128XP/10 duplex ultrasound unit with a 5MHz linear array probe, we assessed the augmentation of peak venous velocity and venous volume above and below the junction of the greater saphenous and common femoral veins in order to study both the deep and superficial venous systems. The pneumatic compression devices evaluated included two foot pumps (A-V Impulse System and PlexiPulse Foot), a foot-calf pump (PlexiPulse Foot-Calf), a calf pump (VenaFlow System) and three calf-thigh pumps (SCD System, Flowtron DVT and Jobst Athrombic Pump). The devices differed in a number of ways, including the length and location of the sleeve and bladder, the frequency and duration of activation, the rate of pressure rise, and the maximum pressure achieved. A randomisation table was used to determine the order of the test conditions for each patient. The enhancement of peak venous velocity occurred primarily in the deep venous system below the level of the saphenofemoral junction. The increases in peak venous velocity were as follows: active dorsal to plantar flexion 175%; foot pumps, A-V Impulse System 29% and PlexiPulse 65%; foot-calf pump, PlexiPulse, 221%; calf pump, VenaFlow, 302% and calf-thigh pumps, Flowtron DVT 87%, SCD System 116% and Jobst Athrombic Pump 263%. All the devices augmented venous volume, the greatest effect being seen with those incorporating calf compression. The increases in ml/min were found in the deep venous system as follows: foot pumps, A-V Impulse System 9.6 and PlexiPulse Foot 16.7; foot-calf pump, PlexiPulse, 38.1; calf pump, VenaFlow, 26.2; calf-thigh pumps, Flowtron DVT 61.5, SCD System 34.7 and Jobst Athrombic Pump 82.3. Active dorsal to plantar flexion generated 8.5 ml for a single calf contraction.

Aged

Dosage titration of a characterized competitive exclusion culture to inhibit Salmonella colonization in broiler chickens during growout.

Broiler chicks were spray treated on the day of hatch with titrated dosages (10(6), 10(7), or 10(8) anaerobic CFU) of a characterized competitive exclusion culture (CF3) and challenged orally on day 3 with 10(4) CFU of Salmonella typhimurium. On day 10, cecal contents from control and CF3-treated chicks were cultured for S. typhimurium to determine the minimal efficacious dosage of the CF3 culture. The experiment was repeated in three replicated trials. Resistance to Salmonella cecal colonization was dosage related and progressively enhanced at the 10(7)- and 10(8)-CFU dosages compared with the 10(6)-CFU dosage. The 10(7)-CFU dosage was selected as the minimal effective dosage and evaluated for efficacy during a 43-day broiler growout study. Six hundred broilers were spray treated on the day of hatch and compared with 600 controls. One-half of the control and CF3-treated birds were challenged orally on day 3 with 10(4) CFU of S. typhimurium and designated "seeders." The remaining unchallenged birds were designated "contacts." Compared with the controls, the recovery of Salmonella cells from the ceca of the CF3-treated broilers was significantly decreased (P < 0.01) in the challenged seeders on days 21 and 43 of growout. Salmonella contamination of floor pen litter was significantly reduced (P < 0.05) in pens of CF3-treated birds compared with controls. The transmission of Salmonella cells from seeder to contact birds in the same pens was decreased significantly (P < 0.01). The results indicated that treatment of broiler chicks on the day of hatch with the 10(7)-CFU dosage of CF3 culture effectively increased resistance to S. typhimurium challenge during growout to market age.

Animals

Surgical correction of primary hyperparathyroidism improves quality of life.

BACKGROUND: The SF-36 health status assessment tool is well suited for measuring the morbidity associated with primary hyperparathyroidism (HPT). The purpose of this study was to test the hypothesis that surgical correction of primary HPT leads to measurable improvement in patient reported functional health status and well-being. METHODS: For the past 4 years patients with primary HPT have been asked to complete the SF-36 and to provide additional demographic and condition-specific information for study before operation. They then completed the SF-36 again by mail 2 months and 6 months after operation. RESULTS: One hundred forty patients entered the study through March 1998; 110 patients completed follow-up at 2 months and 82 at 6 months. Marked impairment compared to population norms occurred before operation in 7 of 8 domains of health status. Substantial improvement occurred in 5 of 8 domains of health status at 2 months and in 6 of 8 domains at 6 months. Statistically significant improvement was demonstrated in limitations caused by physical and emotional role function, social function, bodily pain, and vitality. CONCLUSIONS: Successful operation to correct primary HPT significantly improves patient reported functional health status and quality of life. Most improvement is seen within 2 months, but additional improvement in both physical and mental function is seen at 6 months.

Adult

Measuring health-status improvement after surgery: experience with the SF-36.

The outcomes of care delivery are increasingly being measured and managed by health care providers and clinicians. The authors describe an outcomes monitoring program implemented in one tertiary care center that uses both generic and condition-specific instruments to monitor patient recovery after routine surgery. The SF-36 Health Survey was shown to be a useful tool for measuring changes in functional status and well-being after inguinal hernia repair, cholecystectomy, and parathyroidectomy. Recommendations for its successful adoption in a clinical setting are presented.

Activities of Daily Living

In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM.

The independent influences of invariant chain (Ii) and HLA-DM molecules on the array of naturally processed peptides displayed by HLA-DR molecules were studied using transfected cell lines. The absence of Ii led to an altered set of HLA-DR-bound peptides as judged by the discriminating responses of alloreactive T cell clones. While most T cell clones raised against DR+Ii+DM+ peripheral blood mononuclear cells (PBMC) failed to respond to DR+Ii-DM- cells, T cell clones raised against DR+Ii-DM- transfectants were not stimulated by DR+Ii+DM+ cells. Furthermore, coexpression of HLA-DM with HLA-DR1 in the absence of Ii augmented responses of anti-PBMC T cell clones but inhibited allorecognition by T cell clones raised against DR+Ii-DM- transfectants. The conformational integrity of the class II molecules, as judged by serology, suggests that the patterns of reactivity of the T cell clones reflect specificity for different alloantigen-bound peptides. Hence, discordant regulation of expression of major histocompatibility complex class II, Ii, and HLA-DM molecules in vivo may lead to the display of novel self-peptides and possible interruption of self-tolerance.

Antigen-Presenting Cells

Is esophagectomy following upfront chemoradiotherapy safe and necessary?

OBJECTIVE: To examine the safety and necessity of esophagectomy following upfront chemoradiotherapy (CRT) in patients with potentially resectable esophageal cancer. DESIGN: Cohort analytic study during a 4-year period. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients who completed CRT and underwent esophagectomy as compared with 30 patients who underwent esophagectomy alone without pretreatment during the same period. MAIN OUTCOME MEASURES: Resection-related events, perioperative morbidity and mortality, response to CRT, site of residual disease following CRT, and survival of partial responders. RESULTS: Patients receiving CRT followed by esophagectomy were similar to patients who underwent esophagectomy alone for operative characteristics, postoperative course, and perioperative morbidity and mortality. Of the 33 patients who achieved an objective response to CRT, 23 had residual tumor in the resection specimen. Of the 18 patients alive with no evidence of disease at a median follow-up of 30 months, 50% had residual tumor following CRT. CONCLUSIONS: Upfront CRT did not adversely affect resection-related outcome and may facilitate resection by downstaging disease. A considerable number of patients had prolonged survival after esophageal resection despite having residual tumor present following treatment with upfront CRT. Therefore, esophagectomy following upfront CRT can improve locoregional control of disease and should remain a critical component of any multimodality regimen.

Aged

Core outcomes measures for inguinal hernia repair.

BACKGROUND: Demands on the medical profession to develop performance measures and demonstrate cost-effectiveness make it imperative that a uniform approach to the measurement of outcomes for common conditions be adopted. We report here on patient acceptance, response rates, and utility of a new set of core outcomes measures for patients with inguinal hernia (IH), which incorporates patient reporting of outcomes. METHODS: Beginning in March 1994, a convenience sample of patients scheduled for IH repair completed a series of questionnaires addressing a range of patient case mix and outcomes dimensions, including demographics, comorbid conditions, SF-36 health status (Medical Outcomes Study 36-item short-form health survey), and condition-specific questions, expectations, and responses to the surgical experience before and after operation. Surgical data were abstracted from the medical records. RESULTS: One hundred three patients were entered in the study; 63 completed 2-month reports and 44 completed 6-month reports. Acceptance of the study and response rates were excellent. Differences in health status associated with IH have been identified in two SF-36 domains, and changes in function after repair noted in several others, supporting the applicability of this measure. Outcomes may also differ by type of hernia and type of repair performed. CONCLUSIONS: A core outcomes measurement set for IH that encompasses demographics, comorbidities, health status, expectations, utilization, and condition-specific data provides a portrait of patient outcomes that is useful to providers and patients, and combined with cost and satisfaction data, it can be used for benchmarking and improving surgical care.

Adult

A novel Sec18p/NSF-dependent complex required for Golgi-to-endosome transport in yeast.

The vacuolar protein-sorting (VPS) pathway of Saccharomyces cerevisiae mediates localization of proteins from the trans-Golgi to the vacuole via a prevacuolar endosome compartment. Mutations in class D vacuolar protein-sorting (vps) genes affect vesicle-mediated Golgi-to-endosome transport and result in secretion of vacuolar proteins. Temperature-sensitive-for-function (tsf) and dominant negative mutations in PEP12, encoding a putative SNARE vesicle receptor on the endosome, and tsf mutations in VAC1, a gene implicated in vacuole inheritance and vacuolar protein sorting, were constructed and used to demonstrate that Pep12p and Vac1p are components of the VPS pathway. The sequence of Vac1p contains two putative zinc-binding RING motifs, a zinc finger motif, and a coiled-coil motif. Site-directed mutations in the carboxyl-terminal RING motif strongly affected vacuolar protein sorting. Vac1p was found to be tightly associated with membranes as a monomer and in a large SDS-resistant complex. By using Pep12p affinity chromatography, we found that Vac1p, Vps45p (SEC1 family member), and Sec18p (yeast N-ethyl maleimide-sensitive factor, NSF) bind Pep12p. Consistent with a functional role for this complex in vacuolar protein sorting, double pep12tsfvac1tsf and pep12tsf vps45tsf mutants exhibited synthetic Vps- phenotypes, the tsf phenotype of the vac1tsf mutant was rescued by overexpression of VPS45 or PEP12, overexpression of a dominant pep12 allele in a sec18-1 strain resulted in a severe synthetic growth defect that was rescued by deletion of PEP12 or VAC1, and subcellular fractionation of vac1 delta cells revealed a striking change in the fractionation of Pep12p and Vps21p, a rab family GTPase required for vacuolar protein sorting. The functions of Pep12p, Vps45p, and Vps21p indicate that key aspects of Golgi-to-endosome trafficking are similar to other vesicle-mediated transport steps, although the role of Vac1p suggests that there are also novel components of the VPS pathway.

Adaptor Proteins, Signal Transducing

Use of relational database management system by clinicians to create automated MICU progress note from existent data sources.

We designed and built an application called MD Assist that compiles data from several hospital databases to create reports used for daily house officer rounding in the medical intensive care unit (MICU). After rounding, the report becomes the objective portion of the daily "SOAP" MICU progress note. All data used in the automated note was available in digital format residing in an institution wide Sybase data repository which had been built to fulfill data needs of the parent enterprise. From initial design of target output through actual creation and implementation in the MICU, MD Assist was created by physicians with only consultative help from information systems (IS). This project demonstrated a method for rapidly developing time saving, clinically useful applications using a comprehensive clinical data repository.

Database Management Systems

Alternative processing of the sarco/endoplasmic reticulum Ca(2+)-ATPase transcripts during muscle differentiation is a specifically regulated process.

Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) requires activation of an otherwise inefficient splice process at the 3'-end of the primary gene transcript. We provide evidence that SERCA2 splicing is a specifically regulated process, rather than the result of an increase in general splice efficiency or a decrease in polyadenylation efficiency at the 5'-most polyadenylation site. This is indicated by the fact that changes in general splice and polyadenylation efficiency, as observed during B-cell maturation, did not affect SERCA2 splicing. Furthermore, expression and overexpression studies did not support the hypothesis that changes in the level of the alternative splice factor ASF/SF2 or other arginine and serine rich proteins are sufficient to obtain the regulation of muscle- and neuronal-specific splicing.

Alternative Splicing