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Biomedical subjects

P A Johnson

Publications and source records attributed to P A Johnson.

At least 19 recordsLinked to original sources
PubMed1998

The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma: results of a North Central Cancer Treatment Group Phase III Study.

BACKGROUND: A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy. METHODS: This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30). RESULTS: A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy. CONCLUSIONS: These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted.

Adult↗
PubMed1998

Clinical correlates and prognostic significance of early negative exercise tolerance test in patients with acute chest pain seen in the hospital emergency department.

An exercise tolerance test (ETT) is often performed to identify patients for early discharge after observation for acute chest pain, but the safety of this strategy is unproven. We prospectively studied 276 low-risk patients who underwent an ETT within 48 hours after presentation to the emergency department with acute chest pain. The ETT was considered negative if subjects achieved at least stage I of the Bruce protocol and the electrocardiogram showed no evidence of ischemia. There were no complications associated with ETT performance. The ETT was negative in 195 patients (71%); there was no identifiable subsets of patients at very low probability of an abnormal test. During the 6-month follow-up, patients with a negative ETT had fewer additional visits to the emergency department (17% vs 21%, respectively; p < 0.05) and fewer readmissions to the hospital (12% vs 17%; p < 0.01) than those with positive or inconclusive ETTs. No patient with a negative ETT died and only 4 patients with a negative ETT experienced a major cardiac event (myocardial infarction, coronary angioplasty, or bypass) within 6 months. Among these 4 patients, only 1 had an event within 4 months. In conclusion, our results suggest that ETT can be safely used to identify patients at low risk of subsequent events. Patients without a clearly negative test are at increased risk for readmission and cardiac events, and should be reevaluated either during the same admission or shortly after discharge.

Aged↗
PubMed1998

Cardiac troponin I as a predictor of major cardiac events in emergency department patients with acute chest pain.

OBJECTIVES: We sought to evaluate the diagnostic and prognostic value of cardiac troponin I (cTnI) in emergency department (ED) patients with chest pain. BACKGROUND: Although cTnI has been shown to correlate with an increased risk for complications in patients with unstable angina, the prognostic significance of this assay in the heterogeneous population of patients who present to the ED with chest pain is unclear. METHODS: cTnI and creatine kinase-MB fraction (CK-MB) mass concentration were collected serially during the first 48 h from onset of symptoms in 1,047 patients > or =30 years old admitted for acute chest pain. Sensitivity, specificity and receiver operating characteristic curves were calculated for cTnI and CK-MB collected in the first 24 h. RESULTS: The sensitivity, specificity and positive predictive value of cTnI for major cardiac events were 47%, 80% and 19%, respectively. Among patients were who ruled out for myocardial infarction, cTnI was elevated in 26% who had major cardiac complications compared with 5% for CK-MB; the positive predictive value for an abnormal cTnI result was 8%. Elevated cTnI in the presence of ischemia on the electrocardiogram was associated with an adjusted odds ratio of 1.8 (95% confidence interval 1.1 to 2.9) for major cardiac events within 72 h. Among patients without a myocardial infarction or unstable angina, cTnI was not an independent correlate of complications. CONCLUSIONS: In patients presenting to the ED with acute chest pain, cTnI was an independent predictor of major cardiac events, However, the positive predictive value of an abnormal assay result was not high in this heterogeneous cohort.

Adult↗
PubMed1998

Glove perforation during surgical extraction of wisdom teeth.

OBJECTIVE: This study investigated the incidence of sterile surgical glove perforation during hospital-based surgical extractions of wisdom teeth performed with patients under general anesthesia. STUDY DESIGN: A total of 104 consecutive patients (420 gloves) were studied prospectively. A standardized water inflation technique was used. RESULTS: The operative perforation rate was 8.6%, or 4.3% per surgeon per operative side. The individual glove perforation rate was 2.1% per operation. Over 55% of perforations were not noticed at the time of surgery. There were no skin-penetrating injuries or visible contamination with body fluids. The perforation rate was the same with drill and chisel. CONCLUSIONS: The incidence of glove perforation is lower than previously reported. The surgical extraction of wisdom teeth carries a relatively low yet still significant risk with regard to exposure to bloodborne cross-infection. We recommend that high-quality surgical gloves be used and that universal precautions be adhered to.

Anesthesia, Dental↗
PubMed1998

Expression pattern of messenger ribonucleic acid for follistatin and the inhibin/activin subunits during follicular and testicular development in gallus domesticus.

The expression of mRNA for follistatin and the inhibin/activin subunits was investigated in the follicles of laying hens and the testes of immature and mature roosters. Total RNA was isolated from immature and mature testes and from individual granulosa layers of the F1 through F5 follicles, from a pool of the F6-F8 follicles, from the small yellow follicles, and from the combined granulosa and theca layers of the large white follicles. Northern blot analysis was performed, and a follistatin mRNA transcript of approximately 2. 4 kilobases (kb) was detected in immature testes and in the following follicles: F5, the pool of F6-F8, and small yellow and large white follicles. The greatest expression of follistatin occurred in the small yellow follicles, and in this tissue two minor transcripts of approximately 1.7 and 3.7 kb were also detected. The inhibin alpha subunit was expressed in both testes samples and in all of the follicles except the large white follicles. Expression of the alpha subunit was greatest in the F5 follicle, and expression decreased with follicle maturity. As previously reported, the inhibin/activin ssA subunit was found in the greatest abundance in the F1 follicle, with lesser amounts detected in the other hierarchical follicles and immature testes. In contrast to the ssA subunit, the inhibin/activin ssB subunit was not detected in the four largest hierarchical follicles but was expressed in greatest abundance in the pool of F6-F8 and small yellow follicles. This represents the first report, to our knowledge, of the detection of follistatin mRNA in the hen ovary and rooster testes. The restriction of follistatin mRNA expression to the small follicles suggests that follistatin, by regulating activin and/or inhibin availability, may play a critical role in early follicular development.

Activins↗
PubMed1997

A critical pathway for management of patients with acute chest pain who are at low risk for myocardial ischemia: recommendations and potential impact.

BACKGROUND: Use of resources for patients with acute chest pain may be improved with clinical strategies that integrate research, Bayesian analysis, and expert opinion. OBJECTIVES: To 1) develop a critical pathway for management of patients with acute chest pain who are at low risk for complications of ischemic heart disease and 2) assess the potential effects of implementation of the pathway on patient safety and resource use. DESIGN: Evidence-based consensus and prospective cohort study. SETTING: Urban teaching hospital. PATIENTS: Patients at least 30 years of age who were seen in the emergency department for chest pain and who did not have a history of trauma or abnormalities on radiologic study. INTERVENTION: Physician-opinion leaders defined criteria for patient inclusion in the pathway and for remaining on the pathway after 6 or 12 hours of observation. Criteria were defined for appropriateness of direct admission, direct discharge, or 6 hours of observation followed by exercise treadmill testing. MEASUREMENTS: Number of patients admitted to the hospital, number of days that patients were hospitalized, and clinical outcome. RESULTS: 2898 of 4585 patients (63%) were admitted to the hospital; of the 2898, 1152 (40%) were classified as potentially eligible for the pathway and 1068 (93%) had a benign clinical course during the initial observation period. The 1068 patients had a mean length of stay of 2.8 +/- 4.8 days. If 47% of these patients had been discharged after observation and exercise testing, implementation of the pathway would have reduced the number of admissions by 505 (17%) and days of hospitalization by 1407 (11%). CONCLUSIONS: Retrospective analysis suggests that a critical pathway for patients with acute chest pain may substantially reduce resource use. Prospective study is needed to ensure increased efficiency without increased adverse outcomes.

Acute Disease↗
PubMed1997

Impact of valvular regurgitation and ventricular dysfunction on long-term survival in patients with chest pain.

Doppler echocardiography is often used in evaluating patients with chest pain, but information on prognostic value of this testing and data to help guide selective use are limited. We prospectively studied 448 patients admitted from the emergency department for acute chest pain to assess the utility of qualitative echocardiographic data in predicting long-term survival and the incremental value of this information over routine clinical and electrocardiographic data. Doppler echocardiograms, recorded an average of 21 hours after presentation, were analyzed independently by 2 echocardiographers for global left and right ventricular function and valvular disease. Regional function was assessed by wall motion index. Data on long-term survival were collected with an average follow-up of 35.0 +/- 12.1 months. In univariate Cox regression analysis, left ventricular function and size, wall motion index, right ventricular function, and aortic, mitral, and tricuspid insufficiency were significant predictors of total and cardiovascular mortality. In multivariate analysis, moderate or severe left ventricular dysfunction (mortality rate ratio 3.2, 95% confidence intervals 1.8 to 5.8] and more than mild valvular regurgitation (mortality rate ratio 2.0, 95% confidence interval 1.1 to 3.6) were independent predictors of mortality in a model adjusted for clinical and electrocardiographic data. These factors were more common in patients aged >60 years, in those with prior acute myocardial infarction or angina, and in those with rales on physical examination. In the absence of these clinical characteristics, only 8 of 124 patients (7%) had moderate or severe left ventricular dysfunction or valvular regurgitation. In patients with moderate or severe regurgitation, a murmur was noted on the admission physical examination in 41 of 69 cases (59%). We conclude that echocardiographic evidence of moderate or severe left ventricular dysfunction or valvular regurgitation identifies a high-risk group for overall and cardiovascular mortality in patients with chest pain, and this evidence may not be detected clinically.

Adult↗
PubMed1997

A randomized phase II trial of two dosage levels of letrozole as third-line hormonal therapy for women with metastatic breast carcinoma.

BACKGROUND: It is common practice to utilize a series of different hormonal agents in the treatment of postmenopausal women who, despite disease progression, continue to be candidates for hormonal therapy on a clinical basis. Letrozole is a new highly selective and potent aromatase inhibitor. There are limited data on third-line hormonal therapy in general, and this study was undertaken to evaluate letrozole in this context. METHODS: A randomized trial involving two independent Phase II trials of two letrozole dosage levels, 0.5 mg and 2.5 mg per day, was performed. Eligibility requirements included failure on two prior hormonal therapies and measurable or evaluable disease. RESULTS: Ninety-one patients, 46 receiving 0.5 mg and 45 receiving 2.5 mg of letrozole per day, were assessable for response. At the lower dose, 9 patients (20%) achieved an objective response; 6 patients (13%) had this documented on 2 occasions separated by 3 months. At the higher dose, 10 patients (22%) achieved a response; 8 patients (18%) had this documented on 2 occasions separated by 3 months. The median times to progression were 97 days for the lower dose and 154 days for the higher dose. Toxicity was considered acceptable. CONCLUSIONS: Letrozole has definite antitumor activity as third-line hormonal therapy for women with metastatic breast carcinoma at doses of 0.5 and 2.5 mg per day. It is an effective and generally well-tolerated hormonal agent.

Antineoplastic Agents, Hormonal↗
PubMed1997

Echocardiographic prediction of complications in patients with chest pain.

The optimal role of Doppler echocardiography in the evaluation of patients with acute chest pain syndromes is unclear. We prospectively studied a cohort of 466 patients admitted with acute chest pain syndromes to clarify the relation between echocardiographic data and the risk of serious predischarge complications, and to determine if echocardiographic data can provide incremental prognostic information beyond clinical and electrocardiographic variables. Doppler echocardiograms, performed an average of 21 hours after presentation, were independently analyzed by 2 echocardiographers for information on global left and right ventricular function and valvular disease. Regional function was assessed by a wall motion index (WMI). A composite complications end point was positive if significant recurrent myocardial ischemia, heart failure, or arrhythmia developed after the echocardiogram. In univariate analysis, left (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.6, 5.1) and right (OR 2.7, 95% CI 1.2, 6.2) ventricular function, left ventricular end-diastolic (OR 1.6/cm, 95% CI 1.1, 2.3) and end-systolic (OR 1.4/cm, 95% CI 1.1, 1.9) dimensions, and WMI (OR 3.0, 95% CI 1.8, 4.8) predicted complications that developed after the echocardiogram. In multivariate analysis, WMI remained an incremental predictor of risk with an OR of 2.2/unit (95% CI 1.2, 3.9) scaled from 1 to 4. Even in the subset of 403 patients without acute myocardial infarction, WMI was associated with an OR of 1.9 (95% CI 1.0, 3.7). We conclude that early echocardiography provides incremental prognostic information concerning risk of subsequent complications in patients hospitalized with chest pain.

Adult↗
PubMed1997

Expression and regulation of mRNA for inhibin/activin alpha- and betaA-subunits in the granulosa layer of the two largest preovulatory follicles during the hen ovulatory cycle.

In order to understand the role of inhibin and activin in regulating follicular development in the hen, the steady-state mRNA levels of inhibin/activin alpha- and betaA-subunits in the granulosa layer of the largest (F1) and second largest (F2) follicles of the hen were investigated at 4-hr intervals throughout the ovulatory cycle. In addition, because it was hypothesized that luteinizing hormone (LH) regulated betaA-subunit expression, the effect of in vivo administration of ovine LH (oLH) on the expression of these subunits during the early- and mid-ovulatory cycle was examined. Northern blot analysis, using 32P-labeled cDNA probes of chicken inhibin/activin alpha- and betaA-subunits and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal control), revealed that in the F1 follicle, the relative level of betaA-mRNA (n = 3) was low at 23.5 hr and increased (P < 0.05) at 19.5, 15.5, and 11.5 hr before the next predicted ovulation. It then decreased (P < 0.05) at 7.5 hr and was further reduced at 3.5 and 0.5 hr prior to ovulation. In the F2 follicle, betaA-mRNA was maintained at a basal level throughout the sampling period except for a brief increase (P < 0.05) at 0.5 hr before ovulation. In contrast to the betaA-subunit, inhibin alpha-mRNA was abundantly expressed with no significant variations throughout the ovulatory cycle in either the F1 or the F2 follicle. When oLH was injected at 18 hr before ovulation, 200 but not 100 or 50 microg/kg (n = 3 hens per dose) significantly (P < 0.05) reduced the betaA-mRNA level in the F1 follicle by 2 hr after injection compared to the control (saline). The experiment was repeated at 12 hr before ovulation and both 100 and 200 but not 50 microg/kg oLH significantly (P < 0.05) reduced the expression of betaA-subunit mRNA with no significant difference between 100 and 200 microg/kg oLH. In contrast to the betaA-subunit, inhibin alpha-subunit mRNA was abundantly expressed and not affected by oLH treatment. Our data indicate that the expression of inhibin/activin betaA- but not alpha-subunit mRNA is developmentally regulated in the granulosa layer of the two largest follicles during the hen ovulatory cycle. In addition, LH may participate, directly or indirectly, in negative regulation of the betaA-subunit.

Activins↗
PubMed1997

Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data.

OBJECTIVES: We sought to evaluate the prognostic significance of cardiac troponin T (TnT) serum levels after noncardiac surgery. BACKGROUND: Cardiac TnT has been found to be marker for myocardial injury, but elevations of TnT are common in patients undergoing noncardiac surgery without clinical evidence of severe ischemia. METHODS: We studied 772 patients who underwent major noncardiac procedures and did not have major cardiovascular complications during their inpatient course. Total serum creatine kinase (CK) and cardiac TnT were measured according to a protocol that included sampling in the recovery room and during the next 2 days. A 6-month follow-up interview was performed for 722 (94%) of the patients. RESULTS: Elevated cardiac TnT and CK-MB results were detected for 92 (12%) and 211 (27%) patients, respectively. During the follow-up period, there were 19 (2.5%) major cardiac complications, including 14 cardiac deaths, 3 nonfatal myocardial infarctions and 2 admissions for unstable angina. Compared with patients with cardiac TnT values < 0.1 ng/ml, patients with elevated TnT had a relative risk for cardiac events of 5.4 (95% confidence interval: 2.2 to 13, p = 0.001), whereas CK-MB was not correlated with postdischarge cardiac events. In multivariate logistic regression analysis adjusting for preoperative clinical and CK-MB data, a cardiac TnT value > 0.1 ng/ml was in independent correlate of cardiac events (adjusted odds ratio 4.6, p < 0.05). This correlation was a function of the relation of elevated TnT levels with postoperative in-hospital congestive heart failure and new sustained arrhythmias, suggesting that elevated postoperative TnT levels detected myocardial ischemia during these clinical events. CONCLUSIONS: We conclude that an abnormal TnT level in patients undergoing noncardiac surgery may be a useful marker of ischemic disease and a predictor of 6-month prognosis.

Arrhythmias, Cardiac↗
PubMed1997

Up-regulation of the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) by autoantibodies in autoimmune vasculitis.

Autoimmune vasculitis is characterized by the presence of autoantibodies, particularly anti-neutrophil cytoplasmic antibodies (ANCA) and anti-nuclear antibodies (ANA), in patient sera. These autoantibodies have an incompletely understood role in development of vascular injury. The expression or up-regulation of cell adhesion molecules is an early phase in the development of an inflammatory vascular lesion. Autoantibody-positive sera from patients with vasculitis were assessed for their ability to modulate adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). Autoantibody-positive serum samples from 11 out of 21 patients with primary vasculitis produced substantial up-regulation of ICAM-1 on HUVEC. Autoantibody-negative samples did not produce adhesion molecule up-regulation. Up-regulation of adhesion molecules on HUVEC was observed with samples positive for ANA, a phenomenon not previously reported. Preincubation of the sera with purified antigens recognized by ANCA failed to block this activation. In addition, MoAbs to ANCA antigens were ineffective at inducing ICAM-1 up-regulation, suggesting that activation is independent of the molecular specificity of the antibody. This capacity of ANCA- and ANA-positive sera to up-regulate adhesion molecules on endothelial cells may be a factor in the vessel wall inflammation seen in ANCA-associated vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Up-regulation of the granulocyte adhesion molecule Mac-1 by autoantibodies in autoimmune vasculitis.

The characteristic finding of autoantibodies in patients with vasculitis has raised the possibility that these antibodies play a role in the pathogenesis of the disease. The expression of adhesion molecules (AM) on leucocytes and endothelial cells is believed to be integral to the development of vasculitis. We therefore investigated the effect of sera, positive for anti-neutrophil cytoplasmic antibodies (ANCA) or anti-nuclear antibodies (ANA) from patients with vasculitis, on granulocyte expression of the adhesion molecule Mac-1 (CD11b). Autoantibody-positive sera from 15 out of 35 patients with vasculitis stimulated an up-regulation of Mac-1 on granulocytes. In most cases this effect was reproduced by the autoantibody-positive purified IgG fraction. Autoantibody-negative samples did not stimulate AM up-regulation. Of interest, preincubation of sera with purified antigens did not inhibit AM up-regulation by the autoantibody samples. Blocking the Fc receptors on granulocytes did result in a decrease of Mac-1 up-regulation, but this trend was not statistically significant. These results suggest that both ANCA and ANA have the capacity to up-regulate granulocyte AM expression, and that while Fc interaction with granulocyte Fc receptors is important, it is not the only mechanism whereby such autoantibodies activate cells.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Clinical and echocardiographic correlates of health status in patients with acute chest pain.

OBJECTIVE: To assess the ability of echocardiographic data to predict important functional status outcomes in patients with chest pain. DESIGN: Prospective cohort study. SETTING: A large, urban teaching hospital. PATIENTS: Three hundred thirty-three patients admitted from the Emergency Department for evaluation of chest pain. MEASUREMENTS AND MAIN RESULTS: Patients underwent two-dimensional and Doppler echocardiography as well as a face-to-face interview during their initial hospitalization and a telephone interview 1 year thereafter. The interview included the Medical Outcomes Study 36-Item Short Form (SF-36) health inventory, a generic health status instrument with a physical function subscale. The relation between clinical and echocardiographic factors and functional status was explored by univariable and multivariable linear regression and logistic regression analyses. Multiple clinical and echocardiographic factors correlated significantly with functional status measures at 1 year. For the SF-36 score at 1 year, age, male gender, white race, the presence of rales, and a comorbidity score were independently predictors in multivariate analysis; echocardiographic findings of severe left ventricular dysfunction (parameter estimate [PE] -27.6; 95% confidence interval [CI] -43.1, -12.2) and aortic insufficiency (PE -16.7; 95% CI -26.4, -7.0) added independent predictive information. Explanatory power (r2) for models using clinical and demographic variables was .27 and increased after inclusion of echocardiographic data to an r2 of .35. Results in the subset of patients (n = 148) with acute coronary syndromes such as unstable angina or myocardial infarction were qualitatively similar. Selected factors (rales on examination, electrocardiographic changes suggestive of ischemia, and moderate to severe mitral regurgitation) also predicted which patients would die or have a decline in their functional status. In multivariate analysis, only rales remained an independent predictor of poor outcome (odds ratio 2.4; 95% CI 1.2, 4.5). CONCLUSIONS: Echocardiographic data are correlated with measures of functional status in patients with chest pain, but the ability to predict future functional status from clinical or echocardiographic information is limited. Because functional status cannot be predicted adequately from either patients' characteristics or echocardiographic testing, it must be assessed directly.

Aged↗
PubMed1997

Reconstruction techniques in oral carcinoma.

Resection of oral carcinoma can cause serious problems with speech, mastication and swallowing. Several methods of reconstruction of the defects caused by tumour resection are available to the modern oral and maxillofacial/head and neck surgeon, some of which are more effective and aesthetically pleasing than others. This article discusses the methods available, their advantages and disadvantages, and gives guidelines on the circumstances in which each is ideally used.

Female↗