Biomedical subjects

T Delaney

Publications and source records attributed to T Delaney.

29 records · Page 2Linked to original sources

PubMed1990

Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model.

Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2. This implies that the enhancement of survival time after irradiation results from selective protection of normal brain in this model.

Animals↗

PubMed1990

Cerebral radioprotection by pentobarbital: dose-response characteristics and association with GABA agonist activity.

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose (60 mg/kg intraperitoneally). Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time. Ketamine and hypothermia were without protective effect. Protection from acute radiation-induced mortality by pentobarbital in the rat model is a reproducible phenomenon and is associated with the GABA agonistic activity of the compound. This property of GABA agonists offers the potential for a novel approach to enhancement of the efficacy of radiation therapy in the treatment of brain tumors.

Anesthesia, General↗

PubMed1989

Bronchoscopic phototherapy at comparable dose rates: early results.

Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in the 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant.

Adult↗

PubMed1986

Morphine: sites of action in guanosine nucleoside pathway.

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Animals↗

PubMed1984

Selective denervation of the S-A node in the treatment of progressive central vagal bradycardia.

The condition of central hypervagism and central vagal bradycardia, up to now, have been largely overlooked. Selective surgical vagal denervation of the SA node for progressive central and local episodic reflex arc bradycardia, via right thoracotomy, is a well-tolerated procedure even in the debilitated child. The bradycardia must, of course, be atropine-responsive. It appears to be a valuable alternative to pacemakers, especially because of the necessity of using the sequential type in this form of heart block. Our follow-ups are from 8 months to 13 years in seven children (five central and two peripheral). Up to now, in an admittedly small series, there has been only one recurrence of bradycardia. This was from crossover left vagal innervation of the SA node. The incidence of this is 10% to 15%. It responded to right cervical vagotomy, following a preliminary diagnostic novocain block. We hope that these findings may lead to more awareness and investigations of conditions due to autonomic dysfunction--both central and peripheral--which may help among other conditions in the elucidation and prevention of sudden infant death syndrome (SIDS) and other related problems, and that this surgical approach will be a definitive means for the control of refractory, persistent, or recurrent vagal bradycardia.

Atropine↗

PubMed1983

Unsuspected vascular disease: a potential limitation to the use of the intra-aortic balloon.

Since vascular tortuosity of stenosis may preclude placement of the intra-aortic balloon, 63 consecutive patients (37 men) having routine Judkins' cardiac catheterization had an aortogram prior to withdrawal of the last catheter. No patient had a history of claudication, palpable aneurysms, pulse deficit, or bruit. No complications occurred. Significant peripheral vascular disease was found in ten patients: three had aortic, one had iliac, and six had femoral stenosis or tortuosity. All were men. The age of patients with peripheral vascular disease was 61.4 +/- 7.7 years, while those without were 56.9 +/- 9.3 years (P = NS). No difficulty was encountered entering the femoral artery in any patient; there was difficulty advancing the catheter in five of ten (50%) patients with peripheral vascular disease and in three of 54 (6%) patients without (P less than 0.002). Fifteen patients without peripheral vascular disease had normal coronary arteries, while none with peripheral vascular disease was normal. In patients with coronary disease, the number of vessels involved was the same in both groups. Peripheral vascular disease that might preclude placement of the intra-aortic balloon occurs in 14% of patients undergoing cardiac catheterization and 18% of patients with coronary artery disease. Aortography may be safely performed and should be considered during routine cardiac catheterization in patients who may require intra-aortic balloon placement.

Adult↗

PubMed1981