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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Survival after conservative (palliative) management of pleural malignant mesothelioma.

BACKGROUND AND OBJECTIVES: Malignant mesothelioma is a lethal disease. Aggressive multimodality treatment protocols are reportedly associated with improved survival, but the apparent survival benefits may simply reflect patient selection and the variable natural history of this malignancy. Before embarking on our own protocol of experimental treatment for mesothelioma, we sought to identify important prognostic factors and document the survival of patients treated conservatively (with palliative intent only) in our region. METHODS: We performed a retrospective review of all patients with a diagnosis of malignant mesothelioma seen at our center between 1987 and 1999. Since curative intent treatment had not been given, we assumed that measured survival would largely reflect the natural history of the malignancy. RESULTS: There were 101 patients (80 males and 21 females). Mean age was 65 +/- 9.2 years. Symptoms of disease were present for a median time of 5 months before the diagnosis was established. The most common presenting symptoms were dyspnea (46 patients), chest pain (30 patients), and weight loss (22 patients). Sixty-eight patients (68%) had a history of asbestos exposure. Mesothelioma subtypes included epithelial (43 patients), sarcomatous (26 patients), mixed (19 patients), desmoplastic (4 patients), and unspecified (9 patients). All 101 patients were treated with palliative intent. Talc pleurodesis was performed in 70 patients. At the time of analysis, 90 patients had died and 11 remained alive. Median survival was 213 (95% CI 137-289) days. Survival for the three major histological subtypes was significantly different (log rank, P = 0.0016). Histological subtype (epithelial favorable) was the only significant independent prognostic factor (Cox proportional hazard regression, P = 0.0009). CONCLUSIONS: Patients with epithelial mesothelioma survive longer than those with other histological subtypes. Conservatively managed patients with pleural malignant mesothelioma have a median survival of approximately 7 months. These data from conservatively treated patients can serve as baseline information for future studies of experimental treatments.

Adult↗
PubMed2001

A meta-analysis of randomized controlled trials of route of reconstruction after esophagectomy for cancer.

BACKGROUND: A gastric conduit is usually used to reconstruct the foregut after esophagectomy for cancer. It can be transposed through a posterior or anterior mediastinal route. The choice of route is often debated but there is little evidence to support the use of one route over the other. We performed a meta-analysis of randomized controlled trials (RCTs) to determine the effect of route of reconstruction on patient outcomes. METHODS: Medline and manual searches were done (completed independently and in duplicate) to identify all published RCTs that addressed the issue of route of gastric conduit reconstruction after esophagectomy for cancer. The selection process was inclusive; no trials were excluded. Trial validity assessment was done and a trial quality score was assigned. Major outcomes for quantitative data synthesis included operative mortality, anastomotic leaks, cardiac morbidity, and pulmonary morbidity. A random-effects model was used and relative risk was the principal measure of effect. Systematic qualitative review was used for other outcomes such as duration of ventilation, length of hospital stay, operative blood loss, duration of surgery, anastomotic strictures, dysphagia, gastric emptying, and quality of life. Data on cancer survival were not available in the RCTs. RESULTS: Six RCTs were selected with quality scores ranging from 1 to 4 (5-point Jadad scale). Selection and validity agreement was strong. Relative risk (95% confidence interval; P value), expressed as posterior versus anterior mediastinal route (treatment versus control), was 0.56 (0.17, 1.82; P = 0.34) for mortality, 1.01 (0.35, 2.94; P = 0.98) for leaks, 0.43 (0.17, 1.12; P = 0.08) for cardiac complications, and 0.67 (0.34, 1.33; P = 0.26) for pulmonary complications. Systematic qualitative review did not suggest any difference in other perioperative outcomes or conduit function for the two routes of reconstruction. CONCLUSIONS: Data synthesized from existing RCTs show that posterior and anterior mediastinal routes of reconstruction are associated with similar outcomes after esophagectomy for cancer. However, a difference in outcomes for the two reconstructive routes remains possible. Further trials with larger numbers of patients are needed.

Esophageal Neoplasms↗
PubMed2001

Self-inflicted pneumothoraces.

Self-inflicted pneumothoraces are rare manifestations of psychiatric illness. Two patients with self-inflicted pneumothoraces are reported, and the typical clinical features of factitious disorders are described. If thoracic surgeons are aware of these conditions, inappropriate surgery- and poor outcomes-can be avoided.

Adult↗
PubMed2001

Open lung biopsy as an outpatient procedure.

BACKGROUND: Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. Both limited thoracotomy (open lung biopsy) and thoracoscopy can be used for lung biopsies, but both procedures have traditionally required hospital admission. We report a series of patients that underwent outpatient open lung biopsy to show the safety and effectiveness of this practice. METHODS: We reviewed records of ambulatory, nonoxygen dependent patients with a clinical diagnosis of diffuse interstitial lung disease that underwent outpatient open lung biopsy between January 1997 and December 1999. All procedures were done by a senior surgeon using single lumen endotracheal anesthesia, a small anterolateral thoracotomy without rib spreading, stapled wedge resection, and no chest tube. Patients were discharged the same day. RESULTS: Thirty-two patients with a clinical diagnosis of diffuse interstitial lung disease underwent outpatient open lung biopsy. Mean age was 58 years (range, 21 to 74 years). Preoperative forced expiratory volume in 1 second was 74.3%+/-7.0% of predicted. A pathologic diagnosis was established in all patients: usual interstitial pneumonia, 26 patients; sarcoidosis, 2; metastatic carcinoma, 2; desquamative interstitial pneumonia, 1; and mixed dust pneumoconiosis, 1 patient. No patient required a chest tube, overnight observation, or hospital admission. No complications occurred. CONCLUSIONS: Selected patients with a clinical diagnosis of diffuse interstitial lung disease can safely and effectively undergo diagnostic outpatient open lung biopsy. However, careful patient selection and attention to operative detail are essential.

Adult↗
PubMed2001

CD8 binding to MHC class I molecules is influenced by T cell maturation and glycosylation.

CD8 serves both as an adhesion molecule for class I MHC molecules and as a coreceptor with the TCR for T cell activation. Here we study the developmental regulation of CD8-mediated binding to noncognate peptide/MHC ligands (i.e., those not bound by the TCR). We show that CD8's ability to bind soluble class I MHC tetramers and to mediate T cell adhesion under shear flow conditions diminishes as double-positive thymocytes mature into CD8(+) T cells. Furthermore, we provide evidence that this decreased CD8 binding results from increased T cell sialylation upon T cell maturation. These data suggest that CD8's ability to interact with class I MHC is not fixed and is developmentally regulated through the T cell's glycosylation state.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

High-affinity interactions of ligands at recombinant guinea pig 5HT7 receptors.

The serotonin 5HT7 receptor has been implicated in numerous physiological and pathological processes from circadian rhythms to depression and schizophrenia. Clonal cell lines heterologously expressing recombinant receptors offer good models for understanding drug-receptor interactions and development of quantitative structure-activity relationships (QSAR). Comparative Molecular Field Analysis (CoMFA) is an important modern QSAR procedure that relates the steric and electrostatic fields of a set of aligned compounds to affinity. Here, we utilized CoMFA to predict affinity for a number of high-affinity ligands at the recombinant guinea pig 5HT7 receptor. Using R-lisuride as the template, a final CoMFA model was derived using procedures similar to those of our recent papers. The final cross-validated model accounted for >85% of the variance in the compound affinity data, while the final non-cross validated model accounted for >99% of the variance. Model evaluation was done using cross-validation methods with groups of 5 ligands. Twenty cross-validation runs yielded an average predictive r2(q2) of 0.779 +/- 0.015 (range: 0.669-0.867). Furthermore, 3D-chemical database search queries derived from the model yielded hit lists of promising agents with high structural similarity to the template. Together, these results suggest a possible basis for high-affinity drug action at 5HT7 receptors.

Animals↗
PubMed2001

Handsewn or stapled esophagogastric anastomoses after esophagectomy for cancer: meta-analysis of randomized controlled trials.

Gastric transposition with esophagogastric anastomosis is a common method of reconstruction after esophagectomy for cancer. The anastomosis can be fashioned using a handsewn or stapled technique. The choice of anastomotic technique is often debated but there is little evidence to support the use of one method over the other. We performed a meta-analysis of randomized controlled trials (RCTs) to determine the effect of esophagogastric anastomotic method (handsewn or circular stapled) on patient outcomes. Medline and manual searches were done (completed independently and in duplicate) to identify all published RCTs that addressed the issue of handsewn or stapled esophagogastric anastomosis after esophagectomy for cancer. The selection process was inclusive; no trials were excluded. Trial validity assessment was done and a trial quality score was assigned. Major outcomes for quantitative data synthesis included operative mortality, anastomotic leaks, anastomotic strictures, cardiac morbidity, and pulmonary morbidity. A random-effects model was used and relative risk was the principal measure of effect. Systematic qualitative review was used for other outcomes such as duration of operation and time to complete the anastomosis. Data on cancer survival were not available in the RCTs. Five RCTs were selected with quality scores ranging from 2 to 3 (5-point Jadad scale). Selection and validity agreement was strong. Relative risk (95% confidence interval, CI; P-value), expressed as handsewn vs. stapled (treatment vs. control), was 0.45 (0.20, 1.00; P=0.05) for operative mortality, 0.79 (0.44, 1.42; P=0.43) for anastomotic leaks, 0.60 (0.27, 1.33; P=0.21) for anastomotic strictures, 0.99 (0.55, 1.77; P=0.97) for cardiac morbidity, and 0.93 (0.63, 1.37; P=0.72) for pulmonary morbidity. Data synthesized from existing RCTs show that handsewn and circular stapled esophagogastric anastomotic techniques give similar results for anastomotic outcomes, such as leaks and strictures. The stapled anastomotic method appears to increase operative mortality (P=0.05). Although it is difficult to explain this finding, it should not be dismissed. Several hypotheses are discussed.

Aged↗
PubMed2001

Dalteparin vs. enoxaparin as prophylaxis for deep-vein thrombosis after total hip or knee arthroplasty: a retrospective analysis.

OBJECTIVE: To assess the clinical and economic consequences of a formulary switch from enoxaparin to dalteparin as first-line prophylaxis for deep-vein thrombosis in patients undergoing inpatient rehabilitation after total hip arthroplasty or total knee arthroplasty. DESIGN: Retrospective cohort study. RESULTS: There were 461 patients eligible for the study. The age-adjusted risk of a deep-vein thrombosis event confirmed by duplex ultrasonography among patients treated with dalteparin was substantially lower than among patients treated with enoxaparin, whereas the age-adjusted risk of a bleeding event in the dalteparin group was also lower than that in the enoxaparin group. Adjusted per capita costs of deep-vein thrombosis prophylaxis during the rehabilitation stay were $129 lower among subjects treated with dalteparin. CONCLUSION: The switch to dalteparin as a first-line therapy for deep-vein thrombosis prophylaxis in the rehabilitation period after total hip arthroplasty or total knee arthroplasty has led to substantial cost savings for Kessler Institute without compromising patient care.

Aged↗
PubMed2001

Personality disorders as extreme variants of common personality dimensions: can the Five-Factor Model adequately represent psychopathy?

The present study examined Widiger and Lynam's (1998) hypothesis that psychopathy can be represented using the Five-Factor Model (FFM) of personality. Participants in the study consisted of 481 21-22-year-old men and women who are part of an ongoing longitudinal study. Psychopathy was assessed by the degree of similarity between an individual's NEO-PI-R and an expert-generated FFM psychopathy prototype. The expert-based prototype supported the account of Widiger and Lynam (1998), as did the correlations between the NEO-PI-R Psychopathy Resemblance Index (PRI) and the individual personality dimensions. The PRI was also related in predicted ways to measures of antisocial behavior, drug use, and psychopathology. The results support the contention that psychopathy can be understood as an extreme variant of common dimensions of personality, and underscore the utility of a dimensional model of personality disorders.

Adult↗
PubMed2001

Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23-31 yr) performed high-intensity aerobic training for 9-12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O(2) uptake (VO(2)), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased (P < 0.05) peak VO(2) (12-36%) but did not significantly change submaximal VO(2) or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training (P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg VO(2) was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.

Adult↗
PubMed2001

Factors that affect the occurrence of fumonisin.

The two important Fusarium ear rots of corn, Gibberella ear rot (Fusarium graminearum, formally F. moniliforme and allied species) and Fusarium ear rot (F. verticillioides and allied species) grow under different environmental conditions. F. graminearum grows well only between 26 and 28 degrees C and requires rain both at silking and during disease progression. F. verticillioides grows well at higher temperatures, and ear rot and fumonisin accumulation are associated with drought and insect stress and growing hybrids outside their areas of adaptation. In southern Transkei, where esophageal cancer has been associated with the consumption of F. verticillioides and fumonisin-contaminated corn, environmental conditions favor this fungus in most years. In the nearby areas where the soils, crops, food consumption, and populations are the same and where esophageal cancer is low, temperatures are cooler and F. graminearum is favored. Although F. verticillioides is associated with a disease of corn, it may be that this fungus is a mutualistic endophyte of the plant. Perhaps because of this, breeding for resistance to Fusarium ear rot has produced inconclusive results to date. The best available strategies for reducing the risk of fumonisin contents of maize are to ensure that hybrids are adapted to the environment and to limit drought stress and insect herbivory. It may also be necessary to make use of alternative strategies such as producing hybrids that contain enzymes to degrade fumonisin as it is produced.

Animals↗
PubMed2001

Cost effectiveness of HMG-CoA reductase inhibition in Canada.

OBJECTIVE: To assess the cost effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor therapy, particularly atorvastatin, in primary and secondary prevention of coronary artery disease (CAD) in Canada. METHODS: A Markov model was developed in which costs and effectiveness of atorvastatin were compared with those of other statins and with no drug therapy in primary and secondary prevention of CAD. PATIENTS: Cost effectiveness was assessed for cohorts of patients with risk profiles defined by CAD status, age, sex, pretreatment low density lipoprotein cholesterol level and presence of sentinel coronary risk factors. Coronary risk was estimated by using initial and subsequent event coronary risk equations from the Framingham Heart Study, and risk factors were estimated by using Canadian population survey data. Recent estimates of the costs of CAD-related medical care in Canada were used to assign costs to health states and acute coronary events. INTERVENTIONS: Interventions included atorvastatin 10 mg, simvastatin 10 mg, pravastatin 20 mg, fluvastatin 20 mg, lovastatin 20 mg and no pharmacological therapy. RESULTS: Incremental cost effectiveness ratios (CDN$/year of life gained) relative to no therapy were lowest for atorvastatin and highest for pravastatin across all risk profiles. Atorvastatin was less costly and more effective than lovastatin, pravastatin and simvastatin in primary and secondary prevention, and conferred additional health benefits at a reduced cost per year of life gained compared with fluvastatin. CONCLUSIONS: Atorvastatin was found to be the most cost effective statin in primary and secondary prevention of CAD.

Aged↗
PubMed2001

Prophylactic intracavitary (pneumonectomy space) antibiotic instillation: a comparative study.

BACKGROUND AND OBJECTIVES: Postpneumonectomy empyema is a dreaded complication of pneumonectomy. The effectiveness of prophylactic intracavitary antibiotic instillation is not known. We conducted a retrospective review to assess the effect of pneumonectomy space antibiotic instillation on septic complications (empyema and bronchial fistula) of pneumonectomy. METHODS: Ninety-three consecutive patients underwent pneumonectomy at our institution over a three-year period. Their charts were reviewed retrospectively and data was collected on age, gender, diagnosis, intravenous antibiotics, intracavitary (pneumonectomy space) antibiotics, empyemas, bronchial fistulas, length of hospital stay, and operative mortality. RESULTS: All 93 patients received 3 perioperative doses of prophylactic intravenous antibiotics. One group (n=47) of patients also received intraoperative intracavitary instillation of an antibiotic solution (penicillin G: 5 million units, bacitracin: 50,000 units, gentamicin: 60 mg, in 1 litre of saline) while the other group (n=46) did not. Age, gender, diagnosis, and length of stay were not significantly different in the two groups. There were no empyemas or bronchial fistulas in the intracavitary antibiotic group. Postpneumonectomy empyemas occurred in 6 (13%) patients (empyema with bronchial fistula: 5, empyema alone: 1) that had not received intracavitary antibiotics (p=0.012). There were 4 deaths (9%) in each group (p=0.63). CONCLUSIONS: Prophylactic intraoperative intracavitary antibiotic instillation may reduce the incidence of empyemas after pneumonectomy. However, a randomized trial would be needed to prove the effectiveness of this form of prophylactic antibiotic strategy.

Aged↗
PubMed2001

Local recurrence after total or subtotal esophagectomy for esophageal cancer.

Cancer recurrence is a common problem after esophagectomy for esophageal cancer. Local recurrence is especially problematic because it often negates the palliative benefit of esophagectomy. We conducted a retrospective review to assess the effect of extent of esophageal resection (subtotal or total esophagectomy) on local cancer recurrence. Seventy-four consecutive patients with esophageal cancer underwent esophagectomy at our institution over a four-year period. Their charts were reviewed retrospectively and data was collected on age, gender, histology, stage, tumor location, operation, resection margin status, anastomotic leaks, operative mortality, adjuvant therapy, cancer survival, and local recurrence. Total esophagectomy was done in 19 patients (transhiatal - 3; McKeown - 16) and subtotal esophagectomy was done in the other 55 patients (Lewis - 25; left thoracoabdominal - 30). The two groups were similar with respect to age, gender, histology, stage, anastomotic leaks, operative mortality, adjuvant therapy, and overall survival. Resection margins were positive for residual tumor in 2 out of 19 (11%) total esophagectomies and 9 out of 55 (16%) subtotal esophagectomies (p=0.42). Local recurrence occurred in 3 of 19 (16%) patients treated with total esophagectomy and 23 out of 55 (42%) patients treated with subtotal esophagectomy (p=0.04). We conclude that total esophagectomy is associated with fewer local cancer recurrences than subtotal esophagectomy. We, therefore, recommend total esophagectomy for the surgical treatment of esophageal cancer.

Adenocarcinoma↗
PubMed2001

Anastomotic leaks after esophagectomy for esophageal cancer: a comparison of thoracic and cervical anastomoses.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks remain a significant problem after esophagectomy for esophageal cancer. Many investigators have reported that leaks are more frequent after cervical, as opposed to thoracic, esophagogastric anastomoses. We conducted a retrospective review to assess the effect of anastomotic location (thoracic or cervical) on anastomotic leak incidence and severity. METHODS: Seventy-four consecutive patients with esophageal cancer underwent esophagectomy and esophagogastric anastomoses at our institution over a four-year period. Their charts were reviewed retrospectively and data was collected on age, gender, histology, stage, resection margin status, adjuvant therapy, cancer survival, anastomotic location, anastomotic leaks, and operative mortality. RESULTS: Cervical anastomoses were done in 19 patients and thoracic anastomoses were done in the other 55 patients. The two groups were similar with respect to age, gender, histology, stage, adjuvant therapy, and overall survival. Operative mortality for the entire group of 74 patients was 4% (3 patients). Resection margins were positive for residual tumor in 2 of 19 (11%) patients with cervical anastomoses and 9 of 55 (16%) patients with thoracic anastomoses (p=0.42). Leaks complicated 1 of 19 (5%) cervical and 9 of 55 (16%) thoracic esophagogastric anastomoses (p=0.21). Positive resection margins and anastomotic leaks were not significantly related (p=0.54). One of 9 (11%) leaks in the thoracic group proved fatal. CONCLUSIONS: In our experience cervical esophagogastric anastomoses do not have a higher incidence of leaks than thoracic anastomoses.

Aged↗
PubMed2000

Acute brachial plexus neuritis: an uncommon cause of shoulder pain.

Patients with acute brachial plexus neuritis are often misdiagnosed as having cervical radiculopathy. Acute brachial plexus neuritis is an uncommon disorder characterized by severe shoulder and upper arm pain followed by marked upper arm weakness. The temporal profile of pain preceding weakness is important in establishing a prompt diagnosis and differentiating acute brachial plexus neuritis from cervical radiculopathy. Magnetic resonance imaging of the shoulder and upper arm musculature may reveal denervation within days, allowing prompt diagnosis. Electromyography, conducted three to four weeks after the onset of symptoms, can localize the lesion and help confirm the diagnosis. Treatment includes analgesics and physical therapy, with resolution of symptoms usually occurring in three to four months. Patients with cervical radiculopathy present with simultaneous pain and neurologic deficits that fit a nerve root pattern. This differentiation is important to avoid unnecessary surgery for cervical spondylotic changes in a patient with a plexitis.

Acute Disease↗