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Biomedical subjects

J Gaynor

Publications and source records attributed to J Gaynor.

At least 19 recordsLinked to original sources
PubMed2000

Sedative and cardiopulmonary effects of medetomidine and reversal with atipamezole in desert tortoises (Gopherus agassizii).

Ten desert tortoises (Gopherus agassizii) were given i.m. injections of 150 microg/kg of medetomidine. Sedation was achieved in all tortoises by 20 min postinjection and was accompanied by a significant decrease in mean heart and respiratory rates, systolic, diastolic, and mean ventricular pressures, and mean ventricular partial pressure of oxygen (PO2). There was no change in mean blood pH, HCO3, Na+, K+, ionized calcium values, and mean ventricular partial pressure of carbon dioxide (PCO2). There were statistically significant but clinically insignificant changes in mean base excess and pH-corrected ionized calcium values. Atipamezole given to five of the tortoises at 0.75 mg/kg i.m. significantly reversed the sedative effects of the medetomidine, with all tortoises returning to a normal state by 30 min after administration of the reversal agent. In comparison, the other five tortoises given an equal volume of physiologic saline in place of atipamezole (control group) remained significantly sedated for the duration of the study. In addition, the heart rate and ventricular PO2 returned to baseline, but the respiratory rate and ventricular blood pressures were not significantly altered by the atipamezole as compared with those of the control group. These cardiopulmonary and physiologic effects are similar to those seen in some domestic mammals. Medetomidine can be used to safely induce sedation in desert tortoises. For procedures lasting greater than 120 min, supplemental oxygen should be provided. Atipamezole will reverse the sedation but not all of the cardiopulmonary effects, thus necessitating continued monitoring after reversal. Future studies should address the anesthetic and cardiopulmonary effects of medetomidine in combination with other agents such as ketamine and/or butorphanol.

Acid-Base Equilibrium↗
PubMed1999

Sevoflurane anesthesia in desert tortoises (Gopherus agassizii).

The effects of sevoflurane on anesthesia induction, recovery, ventricular pressures, heart rate, ventricular pH, blood gas values, and electrolytes were evaluated in desert tortoises (Gopherus agassizii). Tortoises were orotracheally intubated while awake and ventilated manually with 3-7% sevoflurane in oxygen (1 L/min) to achieve desired expired sevoflurane concentrations. Data, consisting of induction time, recovery time, systolic, diastolic, and mean ventricular pressures, heart rate, ventricular pH, blood gas values, and electrolytes, were collected prior to anesthesia and sequentially at 2.50% and 3.75% expired sevoflurane as measured at the junction of the endotracheal tube and the breathing circuit. Blood pressure was measured and blood samples were collected through a 25-ga needle passed through a cardiac access port that was placed while the tortoises were in dorsal recumbency. Mean (+/-SE) induction time was 2.55+/-0.55 min, recovery time was 27.58+/-7.55 min, and duration of anesthesia was 105+/-12 min. Mean (+/-SD) values for systolic, diastolic, and mean ventricular pressures in awake tortoises were 28+/-3 mm Hg, 22+/-2 mm Hg, and 24+/-2 mm Hg, respectively. Sevoflurane (2.5% expired) significantly decreased systolic (14+/-3 mm Hg), diastolic (12+/-1 mm Hg), and mean (13+/-1 mm Hg) ventricular pressures compared with those of awake tortoises. Ventricular pressures did not decrease further with increasing depth of anesthesia. Heart rate (32+/-4 beats/min) did not change significantly under sevoflurane anesthesia. Sevoflurane administration increased ventricular PO2 but did not change Na+, K+, or iCa++ concentrations. Sevoflurane appears to provide safe and effective anesthesia with rapid induction and recovery.

Anesthetics, Inhalation↗
PubMed1997

Diagnosis and surgical repair of partial atrioventricular septal defects in two dogs.

Partial atrioventricular (AV) septal defects consist of an ostium primum defect and malformation of the septal cusp of the mitral valve. A partial AV septal defect was diagnosed by means of echo-cardiography in 2 dogs. Transatrial septal blood flow was high enough in both dogs to warrant surgical correction. Defects were repaired through right fifth intercostal thoracotomies, with the aid of cardiopulmonary bypass. An incision was made in the right atrium to expose the AV septal defect, and the mitral valve was inspected through the septal defect. The cleft in the septal cusp of the mitral valve was repaired with mattress sutures of 6-0 polypropylene. The septal defect was closed with autogenous pericardium harvested from the right aspect of the pericardial sac. Both dogs survived surgery and were alive 15 and 42 months, respectively, after surgery, however, 1 dog developed progressive mitral regurgitation after surgery. Partial AV septal defects can be successfully repaired in dogs. Long-term prognosis probably depends on the adequacy of the mitral valve repair.

Animals↗
PubMed1996

Long-term subjective functional outcome of surgery plus postoperative radiotheraphy for advanced stage oral cavity and oropharyngeal carcinoma.

BACKGROUND: Although long-term cures have been achieved for locally advanced squamous cell carcinomas of the head and neck, there is a paucity of information available regarding patients' perspectives of their functional outcome. PATIENTS AND METHODS: Thirty-five long-term survivors free of disease following surgery and postoperative radiotherapy for advanced cancers of the oral cavity and oropharynx were sent questionnaires to evaluate their long-term functional outcome after therapy. The questionnaires included a subjective performance status scale that assessed the patient perceived (1) ability to eat in public, (2) understandability of speech, and (3) normalcy of diet. Twenty-nine of 35 patients participated in this function assessment and are the subjects of this report. RESULTS: The mean function scores for all patients were as follows: 72 for eating in public, 69 for understandability of speech, and 58 for normalcy of diet. Functional results were further analyzed by T stage and anatomic subsite. Inferior results were noted with increasing T stage. A two-way analysis of variance showed that this difference was significant even after adjusting for the effect of anatomic subsite (P = 0.0002, P = 0.018, and P = 0.0018 for the three outcome variables). In addition, patients with base of tongue lesions had a worse functional outcome for both early T state (T1/T2) and advanced T stage (T3/T4) when compared to other subsites. This difference averaged across T stage was statistically significant for understandability of speech (P = 0.0019) and normalcy of diet (P = 0.013), but was not significant for eating in public (P = 0.16). CONCLUSIONS: This performance status scale was found to be a useful tool for functional assessment following definitive therapy for advanced stage head and neck carcinomas. These subjective functional scores deteriorated with increasing T stage. In addition, functional scores for oral tongue, floor of mouth, and tonsillar primaries were superior to those for base of tongue lesions. These functional outcome scores are consistent with the extent of surgery required for the base of tongue subsite and are in direct relation to the patients' T stage in this study population.

Adult↗
PubMed1996

Brief hypoxic stress downregulates E. coli-induced IL-1 alpha and IL-1 beta gene expression in perfused liver.

Hepatic cytokine gene expression is independently stimulated by circulating microbial products and reductions in the cellular O2 supply. Although these stimuli occur sequentially after gram-negative bacteremia, it is unknown whether their interplay augments production of interleukin (IL)-1 by the liver. We studied the effects of intraportal Escherichia coli (EC) bacteremia and secondary constant-flow hypoxia (Po2, approximately 46 Torr for 30 min) on IL-1 alpha and IL-1 beta gene expression in ex situ buffer-perfused rat livers over 180 min (n = 67). At t = 0, normoxic EC and normal saline (NS) controls received 10(9) live EC serotype 055:B5 and 0.9% NaCl, respectively; in livers subjected to EC+hypoxia-reoxygenation (H/R) and NS+H/R, hypoxia began 0.5 h after EC or NS and was followed by 120 min of reoxygenation. Portal and hepatic venous perfusates were serially analyzed for bacterial colony-forming units, O2 uptake, and aspartate aminotransferase. At 60 min (peak hypoxia) and 180 min, cDNAs for IL-1 alpha and IL-1 beta were hybridized to whole liver RNA, and IL-1 beta protein levels in venous perfusates were assessed. Intrahepatic levels of reduced glutathione (GSH) were measured as an index of oxidative stress. Compared with normoxic EC, IL-1 alpha transcripts decreased at 180 min in EC+H/R livers (P < 0.0001) as did IL-1 beta mRNA (P < 0.05), despite similar EC clearance, GSH levels, posthypoxic O2 uptake, and aspartate aminotransferase release. Hepatic secretion of IL-1 beta likewise fell in EC+H/R vs. EC controls (P < 0.005). Prostaglandin H synthase-2 (COX-2) message accumulation was not enhanced by H/R, and indomethacin did not reverse H/R-mediated suppression of IL-1 production. In contrast, H/R-related falls in EC-induced IL-1S expression were reversed by allopurinol or catalase. Thus brief hypoxic stress of the liver causing neither GSH depletion nor functional impairment downregulates postbacteremic IL-1 expression by a mechanism involving O2 radicals but not cyclooxygenase metabolites.

Animals↗
PubMed1995

The effect of diagnosis and treatment delay on prognostic factors and survival in endometrial carcinoma.

OBJECTIVE: The aim of this study was to assess the association of diagnosis and treatment delay with established prognostic factors and survival. STUDY DESIGN: The study group comprised 181 consecutive patients with endometrial carcinoma diagnosed between 1970 and 1986, whose records contained details with regard to diagnosis delay; 174 of them also contained details with regard to treatment delay. RESULTS: The significant prognostic factors that we found, namely, age, clinical stage, grade, depth of myometrial invasion, and histologic type, are in line with those of other studies. However, no significant correlation was found between the duration of delay and these prognostic factors or with survival. CONCLUSION: We conclude that delay of diagnosis (< 1 year) and of treatment of < 4 months do not compromise survival of patients with endometrial cancer.

Adenocarcinoma↗
PubMed1993

Carcinoma of the ampulla of Vater.

We reviewed our experience with 69 patients with carcinoma of the ampulla of Vater admitted to the Memorial Sloan-Kettering Cancer Center, New York, from October 1983 to October 1990. Of the 69 patients, 66 were explored and 55 underwent resection (83 percent resectability). The median length of survival for the 55 patients who underwent resection was 51 months, compared with eight months for the 14 patients who did not undergo resection (p = 0.000004). Of the variables evaluated, only resectability was a statistically significant predictor of survival. Positive lymph nodes in 17 of 55 patients who underwent resection were not predictive of long term survival.

Actuarial Analysis↗
PubMed1993

Severe toxicity limits intensification of induction therapy for acute lymphoblastic leukemia.

Fourteen adult patients with newly-diagnosed acute lymphoblastic, leukemia (ALL), and lymphoblastic lymphoma, were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission, in an attempt to increase the fraction of patients who are long-term disease-free survivors. The induction regimen included vincristine, prednisone, intermediate-dose cytarabine (Ara-C), and idarubicin, all given during the first week of therapy. This combination led to significant hepatic, gastro-intestinal, infectious, and neurologic toxicity. There was unacceptable treatment-related mortality (29%). After the first eight patients, the study was modified, omitting the Ara-C from the induction phase. Gastrointestinal morbidity was less in the cohort treated without Ara-C; however, infectious morbidity persisted at unacceptable levels and this program was terminated as too toxic to administer. There were nine complete remissions, three early deaths, and two patients with resistant disease. There have been six relapses, three of which occurred in patients who, because of protracted grade III/IV toxicity, were no longer receiving chemotherapy. With a minimum follow-up of 20 months, only three patients are still alive. We conclude that this combination of vincristine, prednisone, Ara-C, and idarubicin, is too toxic to be used as induction therapy for adult patients with ALL and lymphoblastic lymphoma.

Adult↗
PubMed1992

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.

Adolescent↗
PubMed1991

The role of multimodality therapy in soft-tissue sarcoma.

Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation.

Adolescent↗
PubMed1991

Limited small-cell lung cancer: do favorable short-term results predict ultimate outcome?

Advances in the treatment of limited small-cell lung cancer (L-SCLC) have led to improved short-term outcome. However, it is not clear how well this predicts the ultimate fate of the patients. This may be affected by late relapse of SCLC, the development of second malignancies, and the long-term toxicity of therapy. To address this issue we report follow-up in excess of 5 years on a cohort of 36 patients who had high short-term survival resulting from treatment with chemotherapy combined with cranial and thoracic irradiation. All patients were followed until death or the time of analysis. The initially promising result of 31% survival at 3 years, was reflected in survival from SCLC of 27% at 5 years, and 23% at 9 years. However, when death from all causes was analyzed, survival was only 19% at 5 years and 7% at 9 years. There were 2 survivors disease-free at 7 and 8 years; 7 patients died of other causes without any evidence of SCLC. Among those not dying of SCLC, 4 patients developed second malignancies with a risk of 22% at 3.2 years and 50% at 8 years. Clinical neurotoxicity developed in 3 patients. These data suggest that cure of SCLC is possible in a modest proportion of patients with limited disease, but that the survivors are at significant risk of developing second malignancies which emerge as the most common cause of death during prolonged follow-up. Successful outcome of treatment is further hampered by the occurrence of neurotoxicity. Clinical strategies to prevent these sequelae of therapy are discussed.

Adult↗
PubMed1990

Importance of long-term follow-up in evaluating treatment regimens for adults with acute lymphoblastic leukemia.

During the past 20 years, we have treated 250 previously untreated adults (greater than age 15 years) with acute lymphoblastic leukemia (ALL) with five successive multidrug protocols: L2, L10, L10M, L17/17M, and L20. The L10 and L10M protocols had the highest percentage of long-term (greater than 5 years) remissions (52% and 40% respectively) compared with the L2 and more recent protocols (24%-32%); this is partly attributable to a greater prevalence of adverse risk factors among the latter protocols. The overall long-term survival of the first 199 patients with minimum 3 years follow-up is now 31%, with 35% of the 163 patients achieving complete remission (CR) remaining free of relapse for greater than 5 years. The disease-free survival of the 163 patients reaches a plateau of 33% after 6 years. The percentages of patients subsequently relapsing after remaining in continuous CR for 1.5, 3, and 5 years are 42%, 28%, and 6%, respectively; no relapses have yet occurred after 6 years in this series. Postrelapse survival improved progressively with longer duration of first remission. The results of treatment in second or later remission with either chemotherapy or bone marrow transplantation (BMT) were unsatisfactory and there were only a few long-term survivors. Recently we have attempted to select patients at highest risk of early relapse for BMT in first remission, but the number of eligible patients actually having BMTs has been low for a variety of reasons, including early death, failure to reach CR, early relapse, patient refusal, or medical contraindications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol.

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.

Age Factors↗
PubMed1988

A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969.

Results of a multivariable analysis of prognostic factors are reported for 199 previously untreated adults with acute lymphoblastic leukemia (ALL). These patients have long-term follow-up, and the probability of cure is estimated at approximately 35%. The cause-specific hazard rate analysis found lower rates of achieving complete remission (CR) in patients with WBC greater than 10,000/microL, AUL (undifferentiated) morphology, and older age. Since these patients required additional time to respond, fewer of them actually achieved CR. Characteristics directly associated with a higher rate of death during induction therapy due to severe bone marrow suppression were low serum albumin concentration (less than or equal to 3.5 g/dL), age greater than 50 years, acute undifferentiated leukemia (AUL) morphology, low Karnofsky performance status, and weight loss greater than 5%. Factors associated with a higher rate of relapse were WBC greater than 20,000/microL, non-T cell ALL, age greater than 60 years, Ph' + ALL, and time to achieve CR greater than 5 weeks. These criteria were used to identify patients at high risk of relapse. In addition, the predictive value of high WBC was found to disappear by 18 months of continuous CR. Finally, the rate of death following first relapse was higher in patients with a short first remission duration, high percentage weight loss at initial diagnosis, and older age. In summary, factors associated with a higher rate of death during attempted induction (ie, low albumin, high percent weight loss, and poor performance status) had no association with the patient's ability to remain relapse-free. Conversely, factors correlating with more extensive or resistant disease (ie, high WBC, null or B cell ALL, or Ph' + ALL) showed no association with the ability to tolerate therapy. Thus, a less toxic but more effective induction regimen is needed for patients with a poor clinical status, whereas a more intensive form of therapy appears warranted for patients presenting with more extensive or resistant disease.

Adult↗