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Biomedical subjects

T Kennedy

Publications and source records attributed to T Kennedy.

At least 19 recordsLinked to original sources
PubMed2004

Coccidiosis control by administering toltrazuril in the drinking water for a 2-day period.

A 56-day floor pen study was conducted to determine the appropriate time to administer toltrazuril (Baycox) (TOL) for control of coccidiosis in broiler chickens. Litter was seeded with field strains of Eimeria acervulina, Eimeria maxima and Eimeria tenella. On Days 0, 21, 35 and 56, all birds and feed were weighed. Starting on Day 14, weekly lesion scores and oocyst counts were performed. The treatments were 125 ppm nicarb (NIC) in the starter to 66 ppm salinomycin (SAL) in the grower with no TOL (NIC/SAL/no TOL), 66 ppm salinomycin in both the starter and the grower but no TOL (SAL/SAL/no TOL), or no in-feed medication with the following TOL treatment: TOL Days 2-3, TOL Days 6-7, TOL Days 10-11, TOL Days 14-15, TOL Days 18-19, and as control NM/NM/no TOL (NM). The withdrawal feed was nonmedicated. TOL was administered in the drinking water at the rate of 7 mg/kg body weight. Oocysts per gram litter and lesion scores showed a significant infection in the NM birds, which peaked about Day 21. The NIC/SAL gave excellent early protection but only moderate protection during the SAL phase. The final performance for the SAL/SAL was significantly less compared to all TOL and NIC/SAL birds. All TOL treatments but Days 2-3 provided good coccidiosis control with accompanying performance. The absence of clinical coccidiosis relapse during the last third of the growout along with moderate oocyst counts and low lesions was indicative of unimpaired coccidiosis immunity. It can be inferred from the overall results that the use of TOL as the sole anticoccidial for two consecutive days in the drinking water between Days 10 and 14 would be the best time for good coccidiosis control allowing full performance.

Animals↗
PubMed2001

Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV).

BACKGROUND: The role of surgery in aggressive chemoradiation protocols for advanced head and neck cancer has been questioned because of the quoted high clinical response rates in many series. METHODS: The role of surgical resection was examined in an aggressive neoadjuvant protocol of weekly paclitaxel, carboplatin, and radiation for stage III and IV with completion of radiation to 72 Gy if biopsy at the primary site was negative after administration of 45 Gy. Of 43 patients enrolled, 38 completed the protocol. The clinical response was 100% (including 18 complete and 20 partial responses). RESULTS: The complete pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%). Of patients who presented with N1 to N3 nodes, neck dissection revealed residual nodal metastases in 22%. Surgical resection of the primary site was required in 13 patients, including 5 with larynx cancer and 2 with base of tongue cancers. Four patients had resection with reconstruction for advanced mandible floor of mouth cancer, and one had resection of nasal-maxillary cancer. Functional resection was performed in 9 of 12 patients. The median progression free and overall survival was 64% and 68%, respectively, at median follow-up of 50 months. Nine patients developed recurrence (three local and six distant). There were no failures in the neck. Salvage surgery was performed in one patient with local and one with distant disease. CONCLUSIONS: Surgical resection is an essential component of aggressive chemoradiation protocols to ensure tumor control at the primary site and in the neck.

Adult↗
PubMed2001

Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy.

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate method of detecting malignant lymphadenopathy. The optimal methods for performing EUS-FNA to maximize sensitivity and to minimize the number of needle passes necessary are unknown. This is a report of the results of a prospective randomized controlled trial to determine the effect of suction, the site of FNA (edge or center of lymph node), and the method of preparation of cytologic specimens on accuracy, number of needle passes needed, and specimen quality. METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA. Each lymph node was sampled with or without suction and from the edge or center in a 2 x 2 factorial design. The samples were expressed onto slides for cytology, and the residual material in the needle was analyzed by the cytospin-cellblock technique. Each aspirate was individually characterized for a diagnosis of malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%). The use of suction was associated with an increase in the cellularity of the specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR 1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from the edge of the lymph node (compared with the center) did not increase the likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of malignant lymph nodes, the correct diagnosis was obtained on the first needle pass and for 100% by the third pass. Cytospin-cellblock methods did not add any additional diagnostic information compared with direct smear cytology. CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not improve diagnostic accuracy and worsens specimen bloodiness compared with FNA without suction. The site of FNA within the lymph node does not affect accuracy. When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction from the most convenient and safe location within abnormal-appearing lymph nodes.

Biopsy, Needle↗
PubMed2000

The prevalence of gastro-oesophageal reflux symptoms in a UK population and the consultation behaviour of patients with these symptoms.

BACKGROUND: Patients consulting with gastro-oesophageal reflux symptoms (GORS) may differ from nonconsulters. AIM: To describe these differences in a UK population. METHODS: A postal questionnaire was sent to 4432 adults. Definitions used were GORS (either heartburn or acid regurgitation on more than six occasions during the previous year), dyspepsia (upper abdominal pain or discomfort on more than six occasions during the previous year) and irritable bowel syndrome (abdominal pain with three or more Manning criteria). Socio-economic status was identified by the Standard Occupational Classification. RESULTS: With a 71.7% response, GORS were reported by 28.7% of the sample, it was unaffected by gender and age but was more common among the socially disadvantaged (P < 0. 005). Less than 25% of GORS patients consulted during the previous year. Increasing age (chi2 for trend; P < 0.001) and coexisting upper abdominal symptoms (chi2 P < 0.001) positively influenced consultation behaviour, but it was unaffected by socio-economic status, gender, or the coexistence of irritable bowel syndrome. Dyspepsia and nausea independently predicted consultation. CONCLUSIONS: GORS are especially common among the deprived. Socio-economic variables do not affect consultation behaviour, but the patient's age and the burden (number and type) of associated symptoms do.

Adult↗
PubMed2000

The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.

Adult↗
PubMed1998

Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution.

Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Provo, Utah, an area where an increase in respiratory symptoms in relation to levels of particulate pollution has been well documented. Provo particulates caused cytokine-induced neutrophil chemoattractant-dependent inflammation of rat lungs. Provo particulates stimulated interleukin-6 (IL-6) and IL-8 production, increased IL-8 messenger RNA (mRNA) and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured BEAS-2B cells, and stimulated IL-8 secretion in primary cultures of human bronchial epithelium. Cytokine secretion was preceded by activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and was reduced by treatment of cultures with superoxide dismutase, deferoxamine, or N-acetylcysteine. These biologic effects were replicated by culturing BEAS cells with quantities of Cu2+ found in Provo extract. IL-8 secretion by BEAS cells could be modified by addition of normal constituents of airway lining fluid to the culture medium. Mucin significantly reduced IL-8 secretion, and ceruloplasmin significantly increased IL-8 secretion and activation of NF-kappaB. These findings suggest that copper ions may cause some of the biologic effects of inhaled particulate air pollution in the Provo region of the United States, and may provide an explanation for the sensitivity of asthmatic individuals to Provo particulates that has been observed in epidemiologic studies.

Air Pollution↗
PubMed1998

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

PURPOSE: Combined modality therapy for non-small-cell lung cancer (NSCLC) has produced promising results. A multiinstitutional phase II clinical trial was conducted to evaluate the activity and toxicity of paclitaxel, carboplatin, and concurrent radiation therapy on patients with locally advanced NSCLC. PATIENTS AND METHODS: Forty previously untreated patients with inoperable locally advanced NSCLC entered onto a phase II study from March 1995 to December 1996. On an outpatient basis for 7 weeks, patients received paclitaxel 50 mg/m2 weekly over 1 hour; carboplatin at (area under the curve) AUC 2 weekly; and radiation therapy of 66 Gy in 33 fractions. After chemoradiation therapy, patients received an additional two cycles of paclitaxel 200 mg/m2 over 3 hours and carboplatin at AUC 6 every 3 weeks. RESULTS: Thirty-nine patients were eligible for the study. The survival rates at 12 months were 56.3%, and at 24 months, 38.3%, with a median overall survival of 20.5 months. The progression-free survival rates at 12 months were 43.6%, and at 24 months, 34.7%, with a median progression-free survival of 9.0 months. Two patients did not receive more than 2 weeks of concurrent chemoradiotherapy and were not assessable for toxicity and response. The overall response rate (partial plus complete response) of 37 assessable patients was 75.7%. The major toxicity was esophagitis. Seventeen patients (46%) developed grade 3 or 4 esophagitis. However, only two patients developed late esophageal toxicity with stricture at 3 and 6 months posttreatment. CONCLUSION: Combined modality therapy with paclitaxel, carboplatin, and radiation is a promising treatment for locally advanced NSCLC that has a high response rate and acceptable toxicity and survival rates. A randomized trial will be necessary to fully evaluate the usefulness of these findings.

Adult↗
PubMed1998

Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy.

BACKGROUND: In the treatment of lung cancer, the best outcome is achieved when the lesion is discovered in the intraepithelial (preinvasive) stage. However, intraepithelial neoplastic lesions are difficult to localize by conventional white-light bronchoscopy (WLB). OBJECTIVE: To determine if autofluorescence bronchoscopy, when used as an adjunct to WLB, could improve the bronchoscopist's ability to locate and remove biopsy specimens from areas suspicious of intraepithelial neoplasia as compared with WLB alone. METHOD: A multicenter clinical trial was conducted in seven institutions in the United States and Canada. WLB followed by fluorescence examination with the light-induced fluorescence endoscopy (LIFE) device was performed in 173 subjects known or suspected to have lung cancer. Biopsy specimens were taken from all areas suspicious of moderate dysplasia or worse on WLB and/or LIFE examination. In addition, random biopsy specimens were also taken from other parts of the bronchial tree. RESULTS: The relative sensitivity of WLB + LIFE vs WLB alone was 6.3 for intraepithelial neoplastic lesions and 2.71 when invasive carcinomas were also included. The positive predictive value was 0.33 and 0.39 and the negative predictive value was 0.89 and 0.83, respectively, for WLB+LIFE and WLB alone. CONCLUSION: Autofluorescence bronchoscopy, when used as an adjunct to standard WLB, enhances the bronchoscopist's ability to localize small neoplastic lesions, especially intraepithelial lesions that may have significant implication in the management of lung cancer in the future.

Adult↗
PubMed1997

Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis.

Individuals with one aerodigestive tract malignancy have a high incidence of second primary aerodigestive tumors. The mechanism for this field effect has not been determined. We studied an individual with widespread dysplastic changes in the respiratory epithelium but no overt carcinoma. The entire tracheobronchial tree obtained at autopsy was embedded in paraffin, and bronchial epithelial cells were isolated by microdissection. DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identical point mutation consisting of a G:C to T:A transversion in codon 245 was identified in bronchial epithelium from 7 of 10 sites in both lungs. Epithelium at sites containing the p53 mutation was morphologically abnormal, exhibiting squamous metaplasia and mild to moderate atypia. No invasive tumor was found in the tracheobronchial tree or any other location. Cells from peripheral blood, kidney, liver, and lymph node exhibited no abnormality in the p53 gene. The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.

Aged↗
PubMed1997

Homozygous deletions of human chromosome 3p in lung tumors.

Cytogenetic and loss of heterozygosity (LOH) studies have demonstrated that deletions of chromosome 3p occur at a high frequency in all forms of lung cancer. To clarify the role of 3p in lung tumorigenesis and to more precisely identify targets for positional cloning efforts, we have performed 3p deletion analyses (microsatellite and fluorescence in situ hybridization) in a series of lung cancer cell lines and uncultured tumor samples. Importantly, we identified homozygous deletions in four uncultured tumors and one cell line. Homozygous deletions were found in three squamous tumors within a region of 3p21 which had previously been described only in cell lines, a 1-2-megabase homozygous deletion in a small cell tumor at 3p12, and a 3p14.2 homozygous deletion in a non-small cell lung carcinoma cell line. The detection of homozygous deletions affecting these multiple regions in uncultured tumor cells substantiates the belief (previously based on deletions found only in tumor cell lines) that these sites contain important tumor suppressor genes. Along with previously reported homozygous deletions in a distal portion of 3p21.3, we now have evidence for four separate regions of 3p which undergo homozygous deletions in either uncultured lung tumors or cell lines.

Carcinoma, Small Cell↗
PubMed1997

Selective O-desulfation produces nonanticoagulant heparin that retains pharmacological activity in the lung.

Heparin has potential use as an antiinflammatory treatment in many lung diseases but its therapeutic use is limited by inherent anticoagulant activity. The anticoagulant nature of heparin can be eliminated by a number of chemical treatments, but often not without loss of other important pharmacological activities. Lyophilization of porcine mucosal heparin under extreme alkaline conditions (pH > or = 13) produces a nonanticoagulant heparin remarkable for the selective loss of only 2-O and 3-O sulfates, leaving 6-O and N-sulfates intact. In contrast to the commonly used nonanticoagulant analog N-desulfated, N-reacetylated heparin, selectively O-desulfated heparin retains potent activity as an inhibitor of the cationic neutrophil proteases human leukocyte elastase and cathepsin G, both in vitro and in vivo. Selectively O-desulfated heparin also inhibits complement lysis of erythrocytes, prevents ischemia-reperfusion injury of the lung, remains a potent antiproliferative treatment for cultured airway smooth muscle and normalizes altered neuronal M2 muscarinic receptor sensitivity and bronchial hyperreactivity after antigen challenge. These retained pharmacologic properties suggest possible use of this new nonanticoagulant heparin for the treatment of a variety of lung disorders.

Animals↗
PubMed1996

Phase II study of 5-fluoruracil leucovorin and azidothymidine in patients with metastatic colorectal cancer.

The primary objective of this study was to determine the response rate of patients with metastatic colorectal cancer to combined therapy with 5-fluorouracil (5-FU), leucovorin, and intravenous azidothymidine (AZT), a thymidine nucleoside analog. By itself, AZT has limited antineoplastic efficacy. However, experimental studies indicate that 5-FU enhances the antitumor activity of AZT by inhibiting synthesis of normal thymidine nucleotides with which AZT competes for incorporation into nucleic acids. A phase I study defined the maximum tolerated dose of AZT as 7 g/m2 with hypotension during the infusion being the dose-limiting toxicity. A phase II study was performed with oral leucovorin (100 mg p.o. hourly for 4 h prior to 5-FU and 4 h and 8 h after 5-FU), bolus 5-FU (400 mg/m2) followed 1 h later by a 2-h infusion of AZT (7 g/m2). Treatment was given weekly for 4 weeks followed by a 1-week break, which constituted a cycle of therapy. Responses were evaluated after every two cycles. Patients continued on therapy as long as they tolerated treatment and did not have progressive disease. Of 15 evaluable patients who had received no chemotherapy there was 1 complete response and 4 partial responses (a 33% response rate), whereas only 1 of 6 patients who had received prior adjuvant chemotherapy had a partial response (17%). An additional 10 patients had stable disease lasting 2-14 months. Therapy was well tolerated with the only one instance each of grade 3 nausea and vomiting, diarrhea, anemia, and hypotension. Approximately 50% of treatments were accompanied by mild hypotension, which was easily corrected by increasing the rate of normal saline infusion. There was no difficulty administering this regimen in the outpatient setting. While the overall response rate (29%) is comparable to that seen with combinations of 5-FU and leucovorin alone, in most reported series a considerably higher dose of 5-FU was utilized than in this study. Since patients in the present study experienced relatively little 5-FU toxicity, increasing the dose of 5-FU in this regimen would appear to be feasible and might result in a higher response rate.

Adenocarcinoma↗