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Biomedical subjects

T Hurst

Publications and source records attributed to T Hurst.

At least 37 records · Page 2Linked to original sources
PubMed1996

Augmentation of hypoxic pulmonary vasoconstriction by N(G)-L-methyl-arginine in a rabbit model of thermal injury.

We tested deeply anesthetized rabbits to determine if a burn acutely diminished the strength of hypoxic pulmonary vasoconstriction (HPV) and if this could be augmented by L-NMMA, a nitric oxide synthase inhibitor. We induced a burn using water heated to 75 degrees C and assessed the strength of HPV as the difference in pulmonary vascular resistance during 100% and 13% O2 ventilation. The rabbits then were randomized to receive 10 mg/kg L-NMMA (n = 8) or a placebo (n = 8). The strength of HPV decreased from 0.42 +/- 0.11 mm Hg/mL/min preburn to 0.22 +/- 0.11 mm Hg/mL/min postburn (P <.05). L-NMMA administration augmented HPV to a postburn value of 0.48 +/- 0.014 mm Hg/mL/min (P <.05). We speculate that the loss of HPV following a burn could worsen ventilation to perfusion mismatch and thereby aggravate the hypoxia associated with burns. Augmentation of HPV might be a short-term goal during the acute stabilization of hypoxic burn patients.

Animals↗
PubMed1996

Anti-CD18 antibodies improve cardiac function following cardiopulmonary bypass in dogs.

PURPOSE: Cardiopulmonary bypass is associated with activation of neutrophils, which may adhere to vascular endothelium causing lung, heart, and brain injury. We tested whether blocking neutrophil adherence would improve organ function following cardiopulmonary bypass in dogs. MATERIALS AND METHODS: All dogs received a standard anesthetic, and then one group (n = 6) received 2 hours of cardiopulmonary bypass followed by 4 hours of observation. A second group (n = 6) received a monoclonal antibody (6 mg/kg) to CD18, a neutrophil adherence factor, immediately before cardiopulmonary bypass. A third group (n = 6) did not receive cardiopulmonary bypass or antibody. RESULTS: Using flow cytometry we found that the antibody bound essentially all neutrophil CD18 sites. All three groups had similar gas exchange and hemodynamics. Lung and heart histology results were similar between groups. By echocardiography, five animals receiving cardiopulmonary bypass alone showed regional wall abnormalities, whereas only one receiving antibody showed wall motion abnormality (P < .05). Following cardiopulmonary bypass, intracellular myocardial pH was higher (P < .05) in the antibody-treated group compared with the group that had cardiopulmonary bypass alone (7.23 +/- 0.05 v 7.07 +/- 0.07 respectively). CONCLUSION: Monoclonal antibodies to CD18 can prevent the deterioration in cardiac function routinely observed following cardiopulmonary bypass.

Analysis of Variance↗
PubMed1996

Respiratory function after cardiac surgery.

STUDY OBJECTIVE: Cardiac surgery is complicated by decreased postoperative respiratory muscle strength and spirometry with accompanying increased atelectasis. The specific respiratory symptoms attributable to these physiologic changes are unknown, and this study looked at the symptoms and underlying physiology. DESIGN: Convenience sampling of observational cohort. SETTING: Tertiary care university hospital. PATIENTS: One hundred thirty-eight patients undergoing elective surgery were enrolled. INTERVENTIONS: Changes from admission to 8-week postoperative values in atelectasis, pleural effusions, spirometry (forced vital capacity and forced expiratory volume in one second), and respiratory muscle strength (negative inspiratory pressure) were measured. These physiologic changes were compared with changes in respiratory symptoms of cough, wheeze, phlegm, and dyspnea on walking up a slight hill noted from admission to 8-week follow-up by stepward logistic regression. MEASUREMENTS AND RESULTS: Spirometry and negative inspiratory pressure decreased and atelectasis increased from admission to discharge. These disturbances had only incompletely resolved at 8-week follow-up. Some patients reported fewer symptoms of cough (11%), phlegm (9%), wheeze (35%), and dyspnea (46%) at 8 weeks follow-up. Other patients reported increased symptoms of cough (15%), phlegm (10%), wheeze (6%), and dyspnea (4%) at 8 weeks follow-up. Residual atelectasis at 8 weeks was predictive of fewer symptoms of dyspnea (odds ratio [OR] 0.335, p = 0.199; 95% confidence interval [CI] 0.188, 0.597), increased symptoms of dyspnea (OR 855, p = 0.006; 95% CI 6.6, 11052), and increased symptoms of cough (OR 260, p = 0.023; 95% CI 2.13, 31829). Negative inspiratory pressure at 8 weeks was predictive of fewer symptoms of dyspnea (OR 1.05, p = 0.032; 95% CI 1.02, 1.09) and increased symptoms of wheeze (OR 0.7, p = 0.45; 95% CI 0.533, 0999). Forced vital capacity at 8 weeks was predictive of increased symptoms of wheeze (OR 0.005; p = 0.015; 95% CI 0.0060, 0.775). CONCLUSIONS: Postoperative changes in respiratory muscle strength and spirometry can persist up to at least 8 weeks postoperatively. Many patients report a change in respiratory symptoms of cough, phlegm, dyspnea, or wheeze. The change in respiratory symptoms at 8 weeks is correlated with residual respiratory muscle weakness, decrease in spirometry, and residual atelectasis.

Adult↗
PubMed1995

Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer.

The genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-H1), and an inverse relationship between NME1 expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from 33 patients were available for Northern blot analysis. We observed variable levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NME1 in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over-expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study.

Base Sequence↗
PubMed1995

Postoperative physical therapy after coronary artery bypass surgery.

Coronary artery bypass surgery is frequently complicated by postoperative atelectasis. Although routinely prescribed, the efficacy of any specific chest physical therapy is not well established. We studied patients at a university center undergoing elective coronary artery bypass surgery. Based upon chest X-ray criteria at extubation, patients (n = 228) were classified as demonstrating greater or lesser degrees of atelectasis. Those with a lesser degree of atelectasis were randomized to receive either early mobilization or sustained maximal inflations (SMI). Those with greater a degree of atelectasis were separately randomized to receive either SMI or single-handed percussions (SSP). We found the extent of atelectasis at extubation did not predict the risk of developing pneumonia. Hospital stays and intensive care unit stays were similar regardless of treatment. Physical therapy costs were highest in the most labor-intensive therapy group (SSP). We conclude that postoperative respiratory dysfunction is common but does not commonly cause significant morbidity or prolong hospital stay. Adding SMI to patients with minimal atelectasis at extubation does not improve clinical outcomes. Similarly, adding SSP to patients with marked atelectasis does not improve outcomes over those obtained with SMI and early ambulation.

Aged↗
PubMed1994

Effect of interferon gamma and tumour necrosis factor alpha on sensitivity to cisplatin in ovarian carcinoma cell lines.

This study aimed to investigate whether the biological response modifiers (BRM) interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN gamma was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs.

PURPOSE: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis. METHODS: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. RESULTS: In endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs. CONCLUSIONS: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.

Analysis of Variance↗
PubMed1994

Effect of interferon-gamma and TNF-alpha on MUC1 mucin expression in ovarian carcinoma cell lines.

In view of the potential uses of cell surface tumour associated antigens in novel anticancer treatment, a study was designed to investigate whether the biological response modifiers interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) could effect the expression of an epitope on the tumour associated MUC1 epithelial mucin. Four ovarian carcinoma cell lines showing high (OAW42 and GG) and low (JAM and PE01) basal expression of MUC1 were treated with 10-1000 U/mL of IFN-gamma or TNF-alpha for one or five days. Changes in MUC1 expression in cells exposed to IFN-gamma or TNF-alpha were monitored using an ELISA technique with the monoclonal antibody BC2 which reacts with a core protein epitope on the MUC1 mucin, and then corrected for the number of viable cells present. TNF-alpha had little effect on MUC1 expression, but one or five days exposure to IFN-gamma significantly increased MUC1 expression (p < 0.01) in all cell lines including the two cell lines that initially showed little or no expression.

Antigens, Neoplasm↗
PubMed1994

Homozygous deletions on the short arm of chromosome 9 in ovarian adenocarcinoma cell lines and loss of heterozygosity in sporadic tumors.

Rat ovarian surface epithelial cells transformed spontaneously in vitro have been found to have homozygous deletions of the interferon alpha (IFNA) gene. This suggests that inactivation of a tumor-suppressor gene in this region may be crucial for the development of ovarian cancer. We therefore used microsatellite markers and Southern analysis to examine the homologous region in humans--the short arm of chromosome 9--for deletions in sporadic ovarian adenocarcinomas and ovarian tumor cell lines. Loss of heterozygosity occurred in 34 (37%) of 91 informative sporadic tumors, including some benign, low-malignant-potential and early-stage tumors, suggesting that it is an early event in the development of ovarian adenocarcinoma. Furthermore, homozygous deletions on 9p were found in 2 of 10 independent cell lines. Deletion mapping of the tumors and lines indicates that the candidate suppressor gene inactivated as a consequence lies between D9S171 and the IFNA locus, a region that is also deleted in several other tumors and that contains the melanoma predisposition gene, MLM.

Adenocarcinoma↗
PubMed1994

Respiratory health status in swine producers relates to endotoxin exposure in the presence of low dust levels.

We conducted an assessment of respiratory health status including questionnaire and spirographic measurements in 54 male swine producers age 36.3 +/- 11.1 years (mean +/- SD) who worked an average of 10.7 +/- 6.3 years in the industry and spent 4.7 +/- 2.1 hours per day in the swine barns, and we also measured atmospheric contaminants including carbon dioxide, ammonia, total dust, respirable dust, and airborne endotoxin. Mean atmospheric dust contaminant levels were as follows: carbon dioxide, 2632 +/- 807 ppm; ammonia, 11.3 +/- 4.2 ppm; total dust, 2.93 +/- 0.92 mg/m3; respirable dust, 0.13 +/- 0.05 mg/m3; and endotoxin, 11,332 +/- 13,492 endotoxin units/m3. Of these, endotoxin related to forced vital capacity (P < .05) and endotoxin x hours per day was related to forced vital capacity (P < .05) and to forced expiratory volume in 1 second (P = .06). Respiratory symptoms and lung function studies did not relate to categories of low, medium, and high exposure to respirable dust. However, categories of endotoxin (available on 46 workers) related to respiratory symptoms (cough, P = .02; chronic bronchitis, P = .06; and to forced vital capacity, P < .01). These data suggest that respiratory health status relates to endotoxin levels but not to dust level exposures in the presence of low dust levels and indicates that control measures should include endotoxin as well as dust control.

Adult↗
PubMed1994

Neutrophil-mediated acute lung injury after extracorporeal perfusion.

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Animals↗
PubMed1993

The prognostic value of clinical, pathologic, and biologic parameters in ovarian cancer.

BACKGROUND: The prognosis in ovarian cancer remains poor, and there is a need to identify patients who are less likely to respond to treatment. METHODS: In a study of 133 unselected patients with ovarian adenocarcinoma treated by a standard protocol, variables such as age, tumor type, International Federation of Gynecology and Obstetrics stage, cellular differentiation, amount of residual disease after surgery, and results from flow cytometry were correlated with survival and relapse at 24 months. RESULTS: Although stage and cellular differentiation were found to be significant associations with survival and relapse, multivariate analyses identified only residual disease and ploidy status (and the related DNA index and percentage of aneuploid cells) as independent prognostic variables. The magnitude of the effect of ploidy depended on the amount of residual disease; among patients with less disease (< 2 cm), the mortality rate was nearly fourfold higher for those with aneuploid tumors than for those with diploid tumors. CONCLUSIONS: Routine use of ploidy determination in ovarian cancer is an important prognostic indicator, especially for a subgroup of patients with minimal residual disease.

Adenocarcinoma↗
PubMed1993

In-hospital experience with multiprogrammable implantable antitachycardia/antifibrillation devices.

Multiprogrammable, automatic internal defibrillators with (n = 45) and without (n = 15) antitachycardia pacing features were implanted in 60 consecutive patients with refractory, malignant ventricular tachycardia (VT) (n = 42) or fibrillation (VF) (n = 18). Left ventricular (LV) ejection fraction was reduced to 39% +/- 12% as a result of structural heart disease in 56 patients. The complexity of the systems caused no additional risks to the surgical procedure or postoperative management. VT/VF detection parameters were individually adjusted to the arrhythmia type (detection cycle length 323 +/- 40 ms in patients with VF vs 405 +/- 40 ms for VT patients, P < 0.05) and incidence (longer detection periods if frequent nonsustained VT was also present). Shock energy was reduced in patients with VT as compared to VF (11J vs 24J, P < 0.05). Antitachycardia pacing was activated in 19/28 (68%) patients with well tolerated VT. Signal, telemetry, as detected by the device, combined with programmability allowed the device to be checked for correct decisions (these were inappropriate in four patients in three of whom corrections were non-invasive) prior to discharge. In conclusion, in the automatic tachyarrhythmia control devices we studied, programmability and flexibility appeared to be clinically safe and useful. Prolonged observation periods are required, however, to evaluate the true clinical safety and persistent efficacy of device programmability and flexibility.

Algorithms↗
PubMed1993

Chemosensitivity testing of primary cultures of Merkel cell cancer.

Twenty-seven tumor specimens from patients with Merkel cell carcinoma (MCC) were tested for chemosensitivity against a battery of nine cytotoxic drugs in a short-term antimetabolic assay measuring inhibition of thymidine incorporation. Dose-response curves were constructed by plotting drug concentration in micrograms/ml versus % control [3H]thymidine incorporation. Specimens were considered 'sensitive' to a drug if, at the approximate peak plasma concentration (PPC), the inhibition of [3H]thymidine was greater than 50% when compared with untreated control primary cultures. The assay revealed a 'sensitive' tumor in 19 of 20 specimens and 16 of 17 patients had a tumor that was 'sensitive' to at least one drug tested in the assay system. The highest sensitivity in order of frequency was found with doxorubicin, epirubicin, cyclophosphamide, etoposide and cisplatin. At least 40% of the tumors were 'sensitive' to these five drugs. Cyclophosphamide was chosen as the most active drug (at PPC) in 10 of 19 assays (53%), etoposide in seven of 17 (41%), doxorubicin in four of 19 (21%), chlorambucil in one of 12 (8%) and cisplatin in one of 18 (5%) of assays. Though our results are preliminary, we have identified for the first time a range of cytotoxic drugs which appear effective against MCC in vitro. Our main task now is to determine whether our in vitro predictive assay will correlate with clinical benefit to the patient.

Antineoplastic Agents↗
PubMed1993

NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.

Animals↗
PubMed1993

Characterization of 86 bruxing patients with long-term study of their management with occlusal devices and other forms of therapy.

Of 353 patients screened, 86 answered positively to questions designed to identify bruxers. The bruxing patient profile revealed that 100% had working excursive interferences, 78% had balancing excursive interferences, and 95.4% had a premature contact into maximum intercuspation. Most of the bruxing patients had a chief complaint that related to pain, and 89.6% of the patients had a craniomandibular disorder. The patients were initially managed with an anterior deprogrammer and were later managed with other occlusal devices as signs and symptoms dictated. Definitive treatment was determined by the patient's maxillomandibular relationship.

Adult↗
PubMed1992

Combination chemotherapy tested in a short-term thymidine incorporation assay in primary cultures of ovarian adenocarcinomas.

Fifty-six tumor specimens from patients with ovarian adenocarcinoma were tested for sensitivity to single and combination drug regimens in a short-term antimetabolic assay measuring inhibition of thymidine incorporation. Response in primary cultures to drug combinations was compared with response to each component drug: cisplatinum, chlorambucil, adriamycin, etoposide and activated cyclophosphamide. Using cut-off criteria previously shown to correlate with "sensitive" and "resistant" tumors for single drugs, 11% of tumors showed increased sensitivity to a combination compared with the single drugs, but 10% showed decreased sensitivity to a combination. The majority of tumors remained in the same "sensitive" or "resistant" categories obtained with the single drugs. Analysis by isobolograms demonstrated synergy, addition or antagonism with the same combination on different tumors. No significant difference between combinations and the best single drug used alone was found in 70% of assays. Overall thymidine incorporation inhibition by the combination and by the best single drug was highly correlated. It is suggested that the best single drug predicts the effectiveness of its combination regimens.

Adenocarcinoma↗