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Biomedical subjects

R B Lee

Publications and source records attributed to R B Lee.

At least 19 recordsLinked to original sources

The effect of mechanical stress on cartilage energy metabolism.

Cartilage is routinely subjected to varying mechanical stresses which are known to affect matrix turnover by a variety of pathways. Here we show that mechanical loads which suppress sulphate incorporation or protein synthesis by articular chondrocytes, also inhibit rates of oxygen uptake and of lactate production. Although the mechanisms have not been definitively identified, it has been shown that high hydrostatic pressures reduce the activity of the glucose transporter GLUT. Furthermore, fluid expression consequent on static loading changes intracellular pH and ionic strength; intracellular changes which would reduce the activity of glycolytic enzymes. Both pathways would thus lead to a fall in rates of glycolysis and a reduction in intracellular ATP, and - since ATP concentrations directly affect sulphation of proteoglycans - a rapid fall in sulphate incorporation. Our results suggest that load-induced changes in matrix synthesis in cartilage can occur by means other than changes in gene expression.

Adenosine Triphosphate↗

The pathophysiology of the intervertebral disc.

After a review of disk structure, the pivotal role of disk cells in producing and renewing the extracellular disk matrix is emphasized. Disk cells rely on nutrients that diffuse through the vertebral endplates. Microelectrode methods have been developed to study nutrient diffusion and endplate permeability. Mechanical stimuli modify disk cell activity. Scoliosis is associated with decreased endplate permeability, a factor that may play a role in disk degeneration and scoliosis progression.

Back Pain↗

Cytolethal distending toxin demonstrates genotoxic activity in a yeast model.

Cytolethal distending toxins (CDTs) are multisubunit proteins produced by a variety of bacterial pathogens that cause enlargement, cell cycle arrest, and apoptosis in mammalian cells. While their function remains uncertain, recent studies suggest that they can act as intracellular DNases in mammalian cells. Here we establish a novel yeast model for understanding CDT-associated disease. Expression of the CdtB subunit in yeast causes a G2/M arrest, as seen in mammalian cells. CdtB toxicity is not circumvented in yeast genetically altered to lack DNA damage checkpoint control or that constitutively promote cell cycle progression via mutant Cdk1, because CdtB causes a permanent type of damage that results in loss of viability. Finally, we establish that CDTs are likely to be potent genotoxins, as indicated by in vivo degradation of chromosomal DNA associated with expression of CdtB-suggesting that the varied distribution of CDT in bacteria implicates many human pathogens as possessors of genotoxic activity.

Bacterial Toxins↗

The surgical spectrum of pulmonary neuroendocrine neoplasms.

OBJECTIVES: The purpose of this study is to review our experience with the spectrum of neuroendocrine neoplasms of the lung with emphasis on the histopathologic classification and surgical therapy of each class of neoplasm. DESIGN: This retrospective review covers the entire spectrum of neuroendocrine neoplasms of the lung over an 11-year period (January 1985 to December 1995) in a university hospital setting. Only patients who underwent surgical resection were included in this review. PATIENTS: During this period, a total of 77 patients underwent lung resection for the following neuroendocrine neoplasms: typical carcinoid (TC), 50 patients; atypical carcinoid (AC), 5 patients; large cell neuroendocrine carcinoma (LCNEC), 9 patients; mixed large-small cell neuroendocrine carcinoma (LSNEC), 4 patients; or small cell neuroendocrine carcinoma (SCC), 9 patients. There were 37 men (48.1%) and 40 women (51.9%) among the patients, with a mean age of 57.9 years (range, 14 to 87 years). INTERVENTIONS: Primary surgical resection consisted of the following procedures: 52 lobectomies (67.5%); 10 pneumonectomies (13%); 13 limited resections (16.9%); 1 left main bronchus sleeve resection; and 1 carinal resection. Six patients had the following concomitant procedures: pericardiectomy, 2 patients; mediastinoscopy, 1 patient; chest wall resection, 1 patient; stapling blebs, 1 patient; and transdiaphragmatic liver biopsy, 1 patient. Four patients underwent bilobectomies, and two patients underwent multiple wedge resections. RESULTS: The hospital mortality rate was 2.6% (2 of 77 patients), and both patients died of pulmonary failure. Follow-up was obtained in 62 of 77 patients (80.9%) for an average of 38.1 months (range, 2 to 132 months). There were a total of 13 deaths, and 8 were disease-related (LCNEC, 4 deaths; SCC, 2 deaths; LSNEC, 1 death; and AC tumor, 1 death. The mean disease-free intervals for patients with these neoplasms were the following: TC tumor, 41.3 months; AC tumor, 20 months; LCNEC, 20.4 months; LSNEC, 25 months; and SCC, 48 months. The overall 3-year survival rate was 45.2% (28 of 62 patients). CONCLUSION: This report will emphasize the classification, surgical management, and treatment considerations of pulmonary neuroendocrine neoplasms. Despite the poor overall prognosis in high-grade neuroendocrine tumors of the lung, surgery remains a viable adjunct in the early stages of this disease.

Adolescent↗

Department of defense eye injuries from fiscal year 1988-1998.

BACKGROUND: The U.S. Army Safety Center, U.S. Navy Safety Center, and U.S. Air Force Safety Center collect data on occupational injuries that occur in each respective military service. METHODS: An 11-year retrospective study of ground eye injuries collected by the Army Safety Center, Navy Safety Center, and Air Force Safety Center, from Fiscal Year (FY) 1988 through FY 1998 was performed. Demographic data analyzed included rank, gender, age, and military/civilian status. Injury data analyzed included severity of injury, eye protection use, injury cost, work days lost due to injury, and days hospitalized due to injury. RESULTS: Statistics for Department of Defense (DoD) eye injuries indicate the average military individual who sustains an eye injury is a 20- to 24-year-old male, E3-E5. This individual is not wearing eye protection and will lose an average of 5.9 days from work at a cost averaging $6,295. The average civil service employee who sustains an eye injury is a WG6-10 who is a 30- to 39-year-old male. This individual is not wearing eye protection and will lose an average of 3.5 days from work at a cost averaging $1,598. Statistically significant differences in the numbers of eye injuries were observed between military occupational groups. In addition, incidence rates between military occupational groups were statistically significant. Category 1, Infantry, Gun Crews, and Seamanship Specialists, has the highest count of injuries and Category 7, Craftsworkers, has the highest incidence. CONCLUSIONS: Proactive vision conservation education at local levels needs to focus on these military occupational groups.

Adult↗

Surgical palliation of airway obstruction resulting from lung cancer.

Bronchogenic carcinoma remains a relentless plague of modern society causing far more deaths than the well-popularized "AIDS epidemic" and secondary only to cardiovascular disease as a cause of death in America. Despite medical advances and treatment breakthroughs, only 40% of newly identified lung cancer patients are "potentially curable". Therefore, a large portion of this patient population will require palliative care and treatment. Surgical palliation is somewhat a misnomer in that most endobrachial lesions causing significant obstruction that result in dyspnea are not amenable to surgical intervention, i.e., operative resectional therapy. The palliative management options of airway obstruction resulting from advanced stage lung cancer will be reviewed, including the historical aspects, development and current use of laser resection, airway stenting, and endobrachial brachytherapy for management of unresectable airway tumors. These modalities frequently are used simultaneously in the same patient and may be used in conjunction with current chemotherapeutic and conventional external-beam radiation protocols.

Airway Obstruction↗

A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study.

BACKGROUND: Some endometrial cancers are hormonally dependent. A principal source of circulating estrogen is conversion of adrenal androstenedione by aromatase. Anastrozole (Arimidex) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer. This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma. METHODS: Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease, a GOG (Zubrod) performance status of < or = 2, no more than one prior hormonal therapy regimen, and no prior chemotherapy were eligible. Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days. RESULTS: Twenty-three patients were entered on this trial. On central pathology review, 9 of them had grade 2 and 14 had grade 3 tumors. One to 24 courses (median: 1) of therapy were administered. Two partial responses were noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short-term stable disease. With the exception of 1 case of venous thrombosis, the toxicity profile was mild. Median durations of progression-free survival and overall survival are 1 and 6 months, respectively. CONCLUSIONS: Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer.

Administration, Oral↗

Intratracheal instillation of zinc-cadmium sulfide (ZnCdS) in Fischer 344 rats.

The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.

Acid Phosphatase↗

A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions.

BACKGROUND: The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). METHODS: In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. RESULTS: The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. CONCLUSIONS: A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis.

Catheters, Indwelling↗

Cutaneous uptake of 14C-HD vapor by the hairless guinea pig.

The hairless guinea pig (HGP) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD), bis(2-chloroethylsulfide), exposure. We determined the HD content in the skin of HGP after a 7-min exposure to vapors saturated with a mixture of HD and 14C-HD. Concentration/time (CT) values in the range of 2 micrograms/cm2/min were determined by counting skin 14C disintegrations per min (dpm) in animals euthanized immediately after exposure. These values are similar to human penetration rates obtained by other investigators. A rate curve monitoring the reduction in skin 14C dpm was developed for animals euthanized between 0 and 24 hr post- exposure. This curve showed the greatest change after 1 hr. The epidermal (62%) to dermal (38%) ratio of 14C at 24 hr was measured for two animals. We saw no site preference for HD penetration among the 8 sites used. The 14C content of template adhesive tape was determined to follow HD distribution. These results contribute to a better understanding of the cutaneous response to HD in the HGP model.

Animals↗

Evaluation of treatment modalities for thoracic empyema: a cost-effectiveness analysis.

BACKGROUND: Empyema thoracis is treated with a multitude of therapeutic options. Optimal therapy and cost-containment requires selection of the most appropriate initial intervention. METHODS: A retrospective review of treatment modalities was performed on 77 patients diagnosed with empyema thoracis from 1990 to 1997 at one institution. Mean age was 59 years (range, 21 to 90 years); 52 were men and 25 were women. RESULTS: Sixty-five percent (50/77) were parapneumonic and 68% (52/77) were multiloculated. Treatment modalities were as follows: group 1, antibiotics only (n = 4); group 2, primary intervention: image-directed catheter (n = 20) or tube thoracostomy (n = 24); and group 3, secondary intervention: decortication (n = 17), rib resection or muscle interposition (n = 12). Thirty-four percent (9/20 image-directed catheter and 8/24 tube thoracostomy) had failure of initial intervention. Patients undergoing decortication more often had multiloculated empyema thoracis (16 of 17) compared with those undergoing image-directed catheters (8 of 20) or tube thoracotomy (16 of 24). Length of stay was reduced for decortication patients (17 days) compared with those having image-directed catheters (21.8 days), failed image-directed catheters (29.7 days), or tube thoracostomies (19.6 days). Hospital charges per patient between decortication and image-directed catheter ($34,770.79 versus $37,869.41) were comparable, but charges were significantly decreased in decortication patients as compared with failed image-directed catheters ($55,609.32; p < 0.05). CONCLUSIONS: Our series revealed that early decortication has charges similar to those of primary intervention (image-directed catheter or tube thoracostomy) but is more cost-effective than failed image-directed catheter. We advocate the use of early surgical intervention as the most optimal and cost-effective initial modality for the treatment of empyema thoracis.

Anti-Bacterial Agents↗

Cognitive screening examinations for silent cerebral infarcts in sickle cell disease.

OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts are the most frequent cause of neurologic injury. We determined the sensitivity and specificity of selective neurocognitive measures when separating children with silent cerebral infarcts and SCD from sibling controls. Additionally, we tested the validity of the same cognitive measures to identify patients with overt strokes. METHODS: We examined performance on a neuropsychologic battery containing measures of attention/executive, spatial, language, memory, and motor functioning for seven children with SCD and silent cerebral infarct, 21 children with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct was based on results of MRI. RESULTS: Measures from the attention and executive domains were the most useful for identifying children with silent cerebral infarct. The Test of Variables of Attention was the most robust measure and yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS: Brief cognitive screening measures, if properly constructed, may be an effective means of identifying children with silent cerebral infarct. Future prospective studies should be pursued to assess the utility of cognitive screening for silent cerebral infarcts in SCD.

Adolescent↗

Pathologic findings in lung volume reduction surgery.

PURPOSE: Lung volume reduction surgery (LVRS) has re-emerged as an alternative in the management of patients with chronic, debilitating, emphysematous lung disease. This has permitted the formal evaluation of pathologic pulmonary changes present in these patients. This study seeks to describe systematically the pathologic findings present in patients undergoing LVRS. METHODS: Tissue sections stained with hematoxylin-eosin, as well as special stains, were retrospectively reviewed from the specimens of 65 nonconsecutive LVRS patients (male patients, 66%; female patients, 31%; mean age, 63.2+/-6.76 yr). All operations were conducted via an open technique (bilateral, 83%; unilateral, 17%). RESULTS: Histologic emphysema grade was mild in 9%, moderate in 72%, and severe in 19% of patients. Microscopic bullae were noted in 75% of specimens. Three patients, each with radiographic evidence of a lesion preoperatively, had small (1.1 to 2.8 cm) adenocarcinomas. Granulomatous bronchiolitis and pneumonitis were noted in one patient who postoperatively developed progressive respiratory compromise. An old, inactive aspergilloma was found in the specimen of another patient. Additional findings of potential clinical significance included bronchiolitis (54), bronchiolectasis (6), and bronchoalveolar metaplasia (1). Incidental findings included interstitial fibrosis and scar (55), interstitial inflammation (20), calcification (20), and ossification (11), bone marrow emboli (4), chemodectoma (2), and carcinoid tumorlets (1). CONCLUSION: This systematic analysis of the resected specimens from patients undergoing LVRS describes a wide range of pathologic findings, including those clinically relevant, as well as incidental. As the application of LVRS continues to expand, the likelihood of discovering clinically significant pathologic lesions (eg, carcinoma) will undoubtedly increase.

Aged↗

Evidence for a negative Pasteur effect in articular cartilage.

Uptake of external glucose and production of lactate were measured in freshly-excised bovine articular cartilage under O2 concentrations ranging from 21% (air) to zero (N2-bubbled). Anoxia (O2 concentration < 1% in the gas phase) severely inhibited both glucose uptake and lactate production. The decrease in lactate formation correlated closely with the decrease in glucose uptake, in a mole ratio of 2:1. This reduction in the rate of glycolysis in anoxic conditions is seen as evidence of a negative Pasteur effect in bovine articular cartilage. Anoxia also suppressed glycolysis in articular cartilage from horse, pig and sheep. Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or fluoride) strongly decreased aerobic lactate production and ATP concentration, consistent with the belief that articular cartilage obtains its principal supply of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide lowered the ATP concentration in aerobic cartilage to approximately the same extent as did anoxia but, because glycolysis (lactate production) was also inhibited by these treatments, the importance of any mitochondrial ATP production could not be assessed. A negative Pasteur effect would make chondrocytes particularly liable to suffer a shortage of energy under anoxic conditions. Incorporation of [35S]sulphate into proteoglycan was severely curtailed by treatments, such as anoxia, which decreased the intracellular concentration of ATP.

Adenosine Triphosphate↗

Belsey Mark IV antireflux procedure for complicated gastroesophageal reflux disease.

BACKGROUND: Over the past 20 years, medical management of gastroesophageal reflux disease has met with increasing success, but a proportion of patients continue to have symptoms or complications requiring surgical treatment. The variety of operations available attests to the general lack of satisfaction with any single procedure. METHODS: A retrospective study was conducted of 276 patients who underwent the Belsey Mark IV antireflux procedure at our institution between 1979 and 1995. The indication for operation was gastroesophageal reflux disease refractory to medical therapy in 137 patients, gastroesophageal reflux disease with symptomatic stricture or Schatzki's ring in 36, achalasia or epiphrenic diverticulum in 74, paraesophageal hernia in 27, and esophageal mass in 2. Fifteen patients (5.4%) had undergone prior antireflux operations. RESULTS: There was one perioperative death (0.4%) resulting from an apparent myocardial infarction in an 87-year-old woman who underwent operation for paraesophageal hernia with volvulus. Two patients had contained leaks diagnosed by routine postoperative contrast studies; both were managed successfully without operation. Two patients required early reoperation for recurrent symptoms: 1 underwent a repeated Belsey Mark IV procedure and the other underwent an esophagogastrectomy. An additional 7 patients experienced late recurrence of symptoms requiring surgical management. The overall complication rate was 10.1%, with minor pulmonary complications (2.1%) and atrial arrhythmias (1.8%) occurring most commonly. CONCLUSIONS: The Belsey Mark IV procedure is a safe and effective operation for the management of gastroesophageal reflux disease with complications, and it compares favorably with other antireflux procedures.

Adolescent↗