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Biomedical subjects

J R Roberts

Publications and source records attributed to J R Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2000

Preemptive gastrointestinal tract management reduces aspiration and respiratory failure after thoracic operations.

OBJECTIVES: Respiratory failure is the major mode of death after general thoracic operations. However, respiratory failure may develop from two very different mechanisms: aspiration, often caused by ileus, and pneumonia, which often results from poor pain control. Epidural catheters help control pain and prevent pneumonia but contribute to ileus and may increase aspiration. We report a decrease in the incidence of aspiration after changing postoperative care to include gastrointestinal tract management. METHODS: All patients undergoing elective thoracotomy by a single surgeon were evaluated for hospital mortality and morbidity. For the first 21 months, patients did not receive an intraoperative nasogastric tube and were prescribed an "advance as tolerated" diet after the operation (n = 125). For the second period, nasogastric tubes were placed intraoperatively and patients received nothing by mouth the day of operation, clear liquids the first day, and a regular diet the second day (n = 153). Pneumonia was considered to have developed if infiltrates developed in a single lobe or two adjoining lobes and culture of the sputa grew a dominant organism. Patients were considered to have aspirated if diffuse infiltrates developed or cultures grew multiple organisms. Significance of results was determined by chi(2) testing. RESULTS: A total of 278 patients underwent elective lung resection over a 3(1/2)-year period, 125 with ad libitum dietary management and 153 with intensive management of the gastrointestinal tract. Six patients (4.84%) aspirated before the institution of gastrointestinal tract management, whereas none (0.0%) aspirated after the change. This difference was significant (P =.01). Respiratory mortality was eliminated in the group with gastrointestinal tract management (P =.04). CONCLUSIONS: Aspiration and its subsequent respiratory failure and mortality can be decreased with preemptive gastrointestinal tract management.

Diet↗
PubMed2000

Active CMV infection before lung transplantation: risk factors and clinical implications.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity following lung transplantation, but active CMV infection has not been described before transplantation. Since 1990, we have screened all lung-transplant recipients for CMV infection with viral urine cultures on the day of transplantation. We retrospectively reviewed the medical records of all 102 lung-allograft recipients transplanted between March 1990 and September 1998. Patients with positive urine cultures for CMV were compared to culture negative patients for age, gender, pretransplant diagnosis, time from diagnosis to transplantation, CMV serostatus, use of pretransplant immunosuppression, T-lymphocyte subsets, and presence of fever. Posttransplant outcomes assessed were duration of intubation and hospitalization, acute rejection, frequency of CMV disease, duration of Nashville rabbit antithymocyte serum or globulin (N-RATS/G) and ganciclovir, and survival. Five (5%) of 102 patients had positive urine cultures for CMV; none had symptoms of CMV infection. All 5 had idiopathic pulmonary fibrosis (IPF) (5/5 vs 27/97; p = 0.002). The age, gender, and CMV serostatus of these patients did not differ from the 97 patients in the culture negative group. Four (80%) of the 5 patients with positive cultures were receiving treatment with azathioprine or cyclophosphamide vs only 18 (19%) of the 97 patients with negative cultures (p = 0.007), and all 5 (100%) were receiving steroids compared to 50 (52%) of 97 patients with negative cultures (p = 0.06). Culture-positive IPF patients, when compared with the 27 culture-negative IPF patients, did not differ in any demographic variable or in the use of immunosuppression, but culture-positive patients were more likely to have a CD4/CD8 T-cell subset ratio <1.0 (p = 0.02). Following transplantation, 3 (60%) of 5 IPF patients with positive CMV cultures developed CMV disease compared to 3 (11%) of 27 IPF patients with negative cultures (p = 0.03). Patients with positive cultures also received more days of parenteral antiviral therapy (mean 44 +/- 11 days vs 16 +/- 10 days; p < 0.001). Utilizing pretransplant screening, we have discovered that 16% of patients with IPF had active CMV infection, which was associated with both alterations in their T-cell subsets and a greater risk for CMV disease after transplantation. This occurrence of occult CMV infection in patients with IPF has not been previously recognized, and has important implications.

Animals↗
PubMed2000

Subchronic silica exposure enhances respiratory defense mechanisms and the pulmonary clearance of Listeria monocytogenes in rats.

Both Listeria monocytogenes infection and silica exposure have been shown to significantly alter immune responses. In this study, we evaluated the effect of preexposure to silica on lung defense mechanisms using a rat pulmonary L. monocytogenes infection model. Male Sprague-Dawley rats were instilled intratracheally with saline (vehicle control) or silica using either an acute treatment regimen (5 mg/kg; 3 days) or a subchronic treatment protocol (80 mg/kg; 35 days). At 3 or 35 days after silica instillation, the rats were inoculated intratracheally with either approximately 5000 or 500,000 L. monocytogenes. At 3, 5, and 7 days postinfection, the left lung was removed, homogenized, and cultured on brain heart infusion agar at 37 degrees C. The numbers of viable L. monocytogenes were counted after an overnight incubation. Bronchoalveolar lavage (BAL) was performed on the right lungs, and BAL cell differentials, acellular lactate dehydrogenase (LDH) activity and albumin content were determined. Alveolar macrophage (AM) chemiluminescence (CL) and phagocytosis were assessed as a measure of macrophage function. Lung-associated lymph nodes were removed, and lymphocytes were recovered and differentiated. Preexposure to silica significantly increased the pulmonary clearance of L. monocytogenes as compared to saline controls. Exposure to silica caused significant increases in BAL neutrophils, LDH and albumin, and lymph-nodal T cells and natural killer (NK) cells in infected and noninfected rats. CL and phagocytosis were also elevated in silica-treated rats. In summary, the results demonstrated that exposure of rats to silica enhanced pulmonary immune responses, as evidenced by increases in neutrophils, NK cells, T lymphocytes, and macrophage activation. These elevations in pulmonary immune response are likely responsible for the increase in pulmonary clearance of L. monocytogenes observed with preexposure to silica.

Animals↗
PubMed2000

Changes in F-actin organization induced by hard metal particle exposure in rat pulmonary epithelial cells using laser scanning confocal microscopy.

Chronic inhalation of hard metal (WC-Co) particles causes alveolitis and the eventual development of pulmonary fibrosis. The initial inflammatory response includes a change in the alveolar epithelial cell-capillary barrier, which has been shown to be regulated by the state of assembly and organization of the actin cytoskeletal network. The objective of this study was to evaluate the effect WC-Co particles have on F-actin organization of lung epithelial cells in an in vitro culture system. Rat lung epithelial (L2) cells were exposed to 5, 25, and 100 microg/mL of WC-Co particles, as well as the individual components (Co and WC) of the hard metal mixture particles for 24 h. The effect on F-actin organization was visualized by laser scanning confocal microscopy (LSCM) following Bodipy-Phallacidin staining. Minimal changes in the F-actin microfilaments of L2 cells were observed by LSCM after exposure to WC and WC-Co at 5 and 25 microg/mL, while at 100 microg/mL, there was a noticeable disruption in the uniform distribution of L2 cell F-actin microfilaments. After exposure to Co, a dose-dependent change in the F-actin organization of the L2 cells was observed. Little change in F-actin assembly was observed after treatment with 5 microg/mL of Co (the concentration equivalent to the 5% amount of Co commonly present in 100 microg/mL of the WC-Co sample mixture). However, at 100 microg/mL of Co, the microfilaments aggregated into homogeneous masses within the cells, and a significant loss in the organization of L2 F-actin was observed. These dramatic alterations in F-actin organization seen after exposure to the higher doses of Co were attributed to an increase in L2 cell injury as measured by lactate dehydrogenase and trypan blue exclusion. We conclude the pulmonary response evoked in the lung by inhalation of high levels of WC-Co particles is unlikely due to alterations in the F-actin microfilaments of lung-epithelial cells.

Actin Cytoskeleton↗
PubMed2000

Weekly irinotecan and concurrent radiation therapy for stage III unresectable NSCLC.

In preclinical studies, the topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) has demonstrated activity as a radiosensitizer, probably due to its ability to inhibit potentially lethal radiation damage repair. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly irinotecan with concurrent thoracic radiation therapy for patients with unresectable stage III non-small-cell lung cancer. For this study, 13 patients received three dose escalations (from 30 to 40 to 50 mg/m2/wk). At the first dose level, one patient developed grade 5 esophagitis. Accrual was expanded to seven patients. None of the remaining six patients developed esophagitis. At the second dose level (40 mg/m2/wk), the worst toxicity, which developed in one patient, was grade 2 esophagitis. At the third dose level (50 mg/m2/wk), two of three patients developed grade 4 nausea and vomiting; grade 3 or 4 esophagitis also occurred in two patients. Of the 12 evaluable patients, seven achieved a partial response, for an overall response rate of 58%. In conclusion, nausea, vomiting, and esophagitis appear to be the principal DLTs of concurrent weekly irinotecan and thoracic radiation in the outpatient setting. The MTD of concurrent weekly irinotecan with thoracic radiation therapy appears to be 40 mg/m2 weekly for 6 weeks. To confirm the MTD of this combination, this study is still open to accrual at the second dose level (40 mg/m2) in combination with carboplatin.

Antineoplastic Agents, Phytogenic↗
PubMed2000

The complex challenge of HIV/AIDS care: a global perspective: an update from XIIIth International AIDS Conference.

This article provides an overview of important findings and discussion from the XIIIth International AIDS Conference held in Durban, South Africa, July 2000. It addresses global epidemiology, the sociopolitical impact of HIV disease, newer strategies to combat disease including medications and microbicides, advances laying the groundwork for vaccine development, and concerns about the economics of care. It highlights the need to recognize the complexity of the threat to the well-being of the entire global village posed by this epidemic.

AIDS Vaccines↗
PubMed1999

Prospective comparison of radiologic, thoracoscopic, and pathologic staging in patients with early non-small cell lung cancer.

BACKGROUND: More accurate staging at the time of initial presentation could improve design of clinical trials and avoid inappropriate surgical decisions in individual patients. Preresection staging of patients with non-small cell lung cancer (NSCLC) is not straightforward, especially in patients with negative mediastinal nodes. The purpose of this study was to compare the results of radiologic, thoracoscopic, and pathologic staging in patients with NSCLC and negative mediastinoscopy. METHODS: All patients with NSCLC underwent computed tomographic (CT) scanning before surgical staging with mediastinoscopy. Patients with negative mediastinoscopy then underwent thoracoscopic staging with examination of pleural surfaces, and identification of T (visceral and parietal pleural invasion, sampling of pleural fluid, and pleural lavage) and N (intraparenchymal and inferior mediastinal nodal sampling, if possible) stage descriptors before resection. RESULTS: Thoracoscopy was more accurate than CT scanning in the staging of 50 patients with early lung cancer (stages IA, IB, IIA, and IIB), especially as regards T stage. Further, thoracoscopic examination ruled out malignant pleural effusions in 7 (14%) patients with radiologically obvious effusions, and identified radiologically silent malignant pleural effusions in 3 (6%) patients. Chest wall invasion was accurately identified at thoracoscopy in most patients. Finally, 3 patients with T1 lower lobe lesions and negative mediastinoscopy were found to have involvement of inferior mediastinal nodes (level 8 or 9) at thoracoscopy. However, thoracoscopy did not allow sampling of aortopulmonary window nodes in some patients with bulky left upper lobe lesions. CONCLUSIONS: Errors in thoracoscopic staging resulted in no inappropriate operations. However, errors in CT staging would have resulted in operations unlikely to help the patients, or would have inappropriately excluded patients from surgery. Thoracoscopic staging was more accurate than CT staging in this cohort of patients with NSCLC and negative mediastinoscopy.

Adult↗
PubMed1999

The clinical pharmacology of brompheniramine in children.

BACKGROUND: Brompheniramine has been widely used in the treatment of allergic rhinitis and other disorders during the past 4 decades. There are no published studies of its clinical pharmacology in children. OBJECTIVES: This study was performed to test the hypothesis that brompheniramine would have a prompt onset of action and a 24-hour duration of action in children. METHODS: Before brompheniramine 4 mg was ingested, and at intervals from 0.5 to 30 hours thereafter, blood samples were obtained for quantitation of plasma brompheniramine concentrations by means of HPLC. Concurrently, epicutaneous tests with histamine phosphate were performed; wheals and flares were traced at 10 minutes, and the areas were measured by using a computerized digitizing system. RESULTS: In 14 children, mean age 9.5 +/- 0.4 years (SEM), the peak brompheniramine concentration was 7.7 +/- 0.7 ng/mL, and the time at which peak concentrations occurred was 3.2 +/- 0.3 hours. The terminal elimination half-life was 12.4 +/- 1.1 hours, and the oral clearance was 20.2 +/- 2.1 mL/min/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate 1 mg/mL were significantly decreased from 0.5 to 30 hours and from 1 to 30 hours, respectively (P <.05), with mean maximum inhibition at 12 (52% +/- 9%) and 6 hours (72% +/- 10%), respectively. CONCLUSIONS: In children a single dose of brompheniramine produces prompt, long-lasting peripheral H1 -blockade. Revised dosage regimens may be needed in this population.

Adolescent↗
PubMed1999

Medical informatics education in paediatric residency training.

OBJECTIVES: The objective of this study was to determine whether Medical Informatics education among house staff is included in the current residency curriculum, and to present ways in which this type of education may be improved. DESIGN: During autumn 1996 a mailed survey was distributed to chief residents of American paediatric residency programmes. Questions included the resident's use of computers, the influence of Informatics-trained faculty members on programme education and plans for curriculum expansion. SETTING: Division of General Paediatrics, University of Alabama, United States. SUBJECTS: Paediatric chief residents. RESULTS: Eighty programmes (63%) returned a survey. An average of 97% of residents use the computer for looking up patient laboratory results, while 70% use it for Medline searches. Less than half of all residents use the Internet or computer-based learning programmes. Thirty-seven per cent of programmes provided formal lectures on computer topics, and 22% of programmes provided hands-on Internet training. There was no association between the presence if Informatics faculty and current programmes; however, programmes with Informatics faculty were more likely to have future curriculum plans (P=0.04). Some of the programmes' future plans are described. CONCLUSIONS: We felt that an overall description of what is currently being done with computers would be helpful as a baseline for other programmes considering new curricula changes. Residents use the computer often to check patient laboratory results but not as much for self-education. Many programmes are expanding their Informatics curriculum. Faculty without formal Informatics training can take part in basic computer education for residents. A self-study approach by the residents has been received positively.

Computer-Assisted Instruction↗
PubMed1999

Application of laser scanning confocal microscopy in the analysis of particle-induced pulmonary fibrosis.

Laser scanning confocal microscopy (LSCM) allows us to simultaneously quantitate the degree of lung fibrosis and distinguish various pathological lesions of intact lung tissue. Lucifer Yellow has been shown an ideal fluorescent stain to examine the connective tissue matrix components of embedded lung tissue with LSCM. We evaluated the use of LSCM in quantitating lung fibrosis and compared this procedure with the more traditional method of assessing fibrosis by measuring hydroxyproline, a biochemical assay of collagen. CD/VAF rats were intratracheally dosed with silica (highly fibrogenic), Fe2O3 (non-fibrogenic), and saline (vehicle control) at a high dose of 10-mg/100 g body weight. At 60 days post-instillation, the left lung was dissolved in 6 M HCl and assayed for hydroxyproline. Silica induced increases of 58% and 94% in hydroxyproline content over the Fe2O3 and control groups, respectively. The right lung lobes were fixed, sectioned into blocks, dehydrated, stained with Lucifer Yellow (0.1 mg/ml), and embedded in Spurr plastic. Using LSCM and ImageSpace software, the tissue areas of ten random scans from ten blocks of tissue for each of the three groups were measured, and three-dimensional reconstructions of random areas of lung were generated. The silica group showed increases of 57% and 60% in the lung areas stained by Lucifer Yellow over the Fe2O3 and control groups, respectively. Regression analysis of hydroxyproline vs. lung tissue area demonstrated a significant positive correlation (p < 0.05) with a correlation coefficient of 0.91. Histological analysis of right lung tissue revealed a marked degree of granulomatous interstitial pneumonitis for the silica group, which was absent in the Fe2O3 and control groups. No significant differences (p < 0.05) in hydroxyproline content and measured tissue area were observed between the Fe2O3 and control groups. LSCM, and its associated advanced image analysis and three-dimensional capabilities, is an alternative method to both quickly quantitate and examine fibrotic lung disease without physical disruption of the tissue specimen.

Animals↗
PubMed1999

Multimodality treatment of malignant superior vena caval syndrome.

Malignant superior vena caval (SVC) syndrome due to non-small cell lung cancer is invariably fatal, with most therapy directed toward palliating the manifestations of the disease. A cure, by means of any modality, is unusual. We report a patient with SVC syndrome secondary to documented ipsilateral peritracheal nodal involvement (stage IIIB disease) who underwent neoadjuvant chemoradiotherapy and resection. At surgery, his superior vena cava was not involved and his tumor had been downstaged to stage I (T1 nanoseconds). He remains alive and free of disease 60 months after surgery. Neoadjuvant chemoradiotherapy may be used to downstage malignant SVC syndrome to resectable lesions in good functional candidates.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Surgical treatment of mesothelioma: pleurectomy.

Malignant diffuse mesothelioma is the most common type of mesothelioma, with a median survival ranging from 8.5 to 18 months after diagnosis. Good performance status, absence of chest pain, age < 50 years, and epithelial histology are all associated with improved survival. Several investigators have described staging systems for this tumor and have emphasized the importance of thoracoscopy in the diagnosis and staging of the disease. Pleurectomy is the most common surgery employed to manage patients with diffuse mesothelioma, and this procedure is associated with minimal postoperative morbidity and mortality. Because mesothelioma usually recurs locally after surgery, efforts at optimizing local control have included both intraoperative phototherapy and chemotherapy. However, neither of these techniques has demonstrated any significant benefit to date and thus should not be considered as standards of care. No studies have compared pleurectomy to extrapleural pneumonectomy (EPP) in randomized trials. However, nonrandomized series suggest a significant improvement in disease-free survival for those undergoing EPP versus pleurectomy. Other data suggest that EPP may improve local control but may predispose the patient to distant metastases. A randomized comparison of these techniques may be beneficial in identifying the most effective procedure for patients with malignant diffuse mesothelioma.

Age Factors↗
PubMed1999

Trimodality therapy for non-small-cell lung cancer.

Prospects for the multimodality treatment of non-small-cell lung cancer have improved substantially with the demonstration of fairly dramatic results, in terms of 5-year survival, in several phase III trials that employed neoadjuvant chemoradiotherapy prior to surgical resection in patients with locally advanced, resectable disease. Moreover, the combination of chemotherapy and radiation therapy has an established role in the treatment of unresectable stage III non-small-cell lung cancer. The history of the development of multimodality therapies will be reviewed and compared with postoperative adjuvant therapy. The role of trimodality therapy in patients with stage IIIB disease is discussed, along with future directions for improving the cure rates of advanced non-small-cell lung cancer.

Antineoplastic Agents↗
PubMed1998

Inhibition of erythrocyte selenium-glutathione peroxidase by auranofin analogues and metabolites.

The effect of gold ligation on the inhibition of bovine erythrocyte selenium-glutathione peroxidase (GSH-Px) was examined. The anti-arthritic drug auranofin [2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S)(triethylp hosphine) gold(I)] (Et3PAuSATg) and its analogue, Et3PAuCl, exhibited experimentally equivalent Ki values (11.6+/-0.8 and 10.8+/-0.5 microM, respectively), despite the greatly disparate affinities of their ligands for gold(I): 2,3,4,6-tetra-O-acetyl-1-thiolato-beta-D-glucopyranose (ATgS-) >> Cl-. This similarity reflects ligand exchange reactions that generate the glutathione complex Et3PAuSG from the excess glutathione (GSH, 1 mM) used in the assay. The Ki values for bis(glutathionato)gold(l) (Au(SG)2-) and gold(I) thioglucose (AuSTg) were also found to be equal (2.8+/-0.4 and 2.4+/-0.5 microM, respectively). This confirms the previous postulate of Chaudiere and Tappel (J Inorg Biochem 20: 313-325, 1984) that Au(SG)2- is generated from AuSTg in the presence of excess glutathione. Since auranofin metabolites accumulate in red blood cells, the inhibition of intracellular GSH-Px was examined by using intact erythrocytes. There was greater inhibition of the reaction when the cells were resuspended in isotonic buffer than in whole blood, because serum albumin in the latter competes for the auranofin and decreases the uptake by erythrocytes. After correction for the extent of gold uptake, the Ki values were determined to be the same as those observed for Au(SG)2- in the extracellular assay, indicating loss of both the Et3P and ATgS- ligands from auranofin. Thus, the inhibition of GSH-Px by gold complexes is dependent on their ligation, and the ultimate gold(I) compound that interacts with erythrocyte GSH-Px in intact red cells, Au(SG)2-, is radically different from the original auranofin molecule.

Animals↗
PubMed1998

The effect of acute or chronic administration of prolactin on renal function in feral chickens.

The role of the hormone prolactin in avian osmoregulation has not been clearly defined. The increases in plasma prolactin concentrations which have been demonstrated in previous studies in response to osmotic stress are strongly suggestive of a role for prolactin in avian osmoregulation. The present study investigated the effects of either acute or chronic administration of ovine prolactin on plasma electrolytes and renal function in the feral chicken. The effect of acute administration of prolactin depended on the dose of prolactin used. All plasma concentrations of prolactin achieved by the infusions were greater than reported values for endogenous prolactin. Acute infusion of prolactin at the lower dose increased the fractional excretion of sodium and chloride significantly, whereas the higher dose of prolactin had no effect. However, chronic administration of ovine prolactin had no significant effects on plasma electrolytes and renal function. It is possible that the role of prolactin in avian osmoregulation is a combination of its effects on the kidneys and also on extrarenal tissues such as the intestine and nasal salt glands (where present).

Animals↗
PubMed1998

Seasonal changes in glomerular filtration rate in Antechinus stuartii (Marsupialia: Dasyuridae).

The small marsupial Antechinus stuartii experiences a synchronised life cycle that culminates in complete male mortality (within 3 weeks) following the 1 week mating period in mid-August (late winter). There are pronounced physiological changes in male A. stuartii over the life cycle and renal function was assessed for correlation with these changes. Glomerular filtration rate and urine and plasma electrolytes were determined in male and female A. stuartii in February, May, July and August. Females showed little change in glomerular filtration rate, except for pre-mating values in August which decreased. In contrast, glomerular filtration rate of males decreased significantly in July and August. Plasma sodium and chloride levels were higher in males than females and were higher in animals in July and August than in February and May. Plasma potassium levels dropped in both males and females in July and August. Plasma osmolality was higher in animals in February compared to animals from May and August. However, there were no significant sex or seasonal differences in urine electrolytes, although urea concentration was higher in females than males. Urine osmolality was higher in both sexes in July and August. There were no significant differences in total excretory rates of sodium, potassium or chloride between sexes or between seasons. Many of the alterations in renal function are correlated with known physiological and hormonal profiles in A. stuartii. This is the first observation of seasonal changes in glomerular filtration rate that are unrelated to dietary and water stresses.

Animals↗