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Biomedical subjects

R L Page

Publications and source records attributed to R L Page.

At least 127 records · Page 7Linked to original sources

Clinical indications and applications of radiotherapy and hyperthermia in veterinary oncology.

The response of dogs and cats with neoplasia to radiation therapy has improved significantly during the past 10 years. This has largely been due to more aggressive radiation therapy treatment schedules, more accurate planning, and refinement of clinical indications. Sufficient numbers of dogs and cats irradiated with curative intent have not been accumulated to yet define the full impact of more aggressive therapy. However, many tumors will likely remain resistant to irradiation because of concomitant normal tissue injury that must be minimized. Systematic investigation of combination therapy (surgery, radiation, chemotherapy, and hyperthermia) should succeed in reducing local tissue side effects and increased local tumor control. A comprehensive approach to tumor management begins with decisions thoughtful of optimal treatment for suspected malignant tumors even at the time of initial examination and client counseling. An incisional biopsy provides essential information to determine the therapeutic course and should be considered prior to initial excision. More aggressive treatment, of even small tumors, early in the clinical course will lead to prolonged tumor control. Radiation therapy should be considered fundamental in the comprehensive treatment plan of many solid tumors.

Animals↗

Immunohistochemical detection of a hypoxia marker in spontaneous canine tumours.

An immunoperoxidase technique has been used to detect the in vivo binding of a 2-nitroimidazole hypoxia marker in histochemical sections of a variety of excised canine tumours. The binding occurred 10-12 cell diameters away from tumour blood vessels, consistent with the expected location of hypoxic cells in tissues in which oxygen concentration gradients are established by diffusion. Hypoxic fractions ranging from 4 to 13% have been estimated on the basis of morphometric analysis of multiple tumour sections. The binding of the marker was restricted to the cytoplasm of the cells. The marker appeared in regions adjacent to necrosis but also in regions free of necrosis. As in earlier autoradiography studies, binding was occasionally observed in cells adjacent to tumour blood vessels. Generally, binding to normal tissues was not observed. However, binding to smooth muscle cells surrounding arterioles in some sections of normal tissue and tumour tissue was observed.

Animals↗

Unexpected toxicity associated with use of body surface area for dosing melphalan in the dog.

A multiinstitutional Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was administered at 7.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, less than 1500/mm3; and/or thrombocytopenia, less than 80,000/mm3), whereas only three of 13 dogs (23%) weighing greater than 14 kg developed severe myelosuppression (P = 0.016). We concluded that small dogs are at greater risk of developing bone marrow toxicity from i.v. melphalan than large dogs if body surface area is used to calculate the dose. Although both body surface area and weight were found to be significantly correlated with severity of toxicity, melphalan-induced toxicity in dogs can be more accurately estimated by body weight than by surface area, P = 0.008 versus P = 0.022, respectively. It may be necessary to prescribe antineoplastic agents that are eliminated by processes not primarily under metabolic influence or that produce side effects on tissue not correlated to basal metabolic rate on a parameter other than body surface area. In dogs, melphalan should be dosed on a weight basis, and treatment groups should be stratified by weight in randomized clinical studies, particularly when the weight range of treated subjects is great.

Animals↗

The use of high dose inhaled beclomethasone dipropionate as a means of assessing steroid responsiveness in obstructive airways disease.

The use of high dose inhaled beclomethasone dipropionate (BDP) as a means of assessing steroid responsiveness in chronic obstructive airways disease (COAD) was assessed in 22 patients in a study involving three consecutive 2-week periods of placebo, inhaled BDP (1500 micrograms daily), and oral prednisolone (30 mg daily). Five of the 22 patients were considered steroid responsive following the course of oral corticosteroids and in each case this responsiveness had been identified by inhaled BDP therapy. It is concluded that high dose inhaled BDP (1500 micrograms daily) may be used to assess corticosteroid responsiveness in COAD.

Administration, Inhalation↗

Profiles of non-compliance with antituberculous therapy.

Treatment compliance was assessed by testing multiple urine samples for rifampicin in 113 consecutive patients taking a rifampicin containing regimen for tuberculosis. Nineteen (16.8%) patients had at least one negative urine sample after chromatographic analysis and these patients were more likely to be from social classes IV and V, to be Asian, and to have defaulted from at least one clinic appointment without good reason. A questionnaire was completed by 70 of the patients and four (6%) admitted to having omitted at least one treatment weekly; two of these also had at least one negative urine test. Physicians were only partly successful in identifying non-compliers. The relevance of these findings is discussed.

Adolescent↗

Fibreoptic bronchoscopy in the elderly: 4 years' experience.

We reviewed the records of all patients over the age of 80 years undergoing fibreoptic bronchoscopy in St James's Hospital between May 1982 and May 1986, to assess the safety and clinical usefulness of the procedure in this group of patients. Sixty bronchoscopies were performed in this time, 21 patients had histologically proven bronchogenic carcinoma, oma, one had tuberculosis, and one a benign polyp. There was no mortality and no serious morbidity. We concluded that fibreoptic bronchoscopy is a safe, useful procedure which was helping in planning future management in this group of patients.

Aged↗

Use of insulation to reduce extremity temperature nonuniformity during whole body hyperthermia in dogs.

Previously we have shown in dogs that tibial bone marrow and s.c. tissue temperatures are lower than rectal temperature during the plateau phase of whole body hyperthermia with the use of a radiant heating device. In an attempt to increase thermal dose to these sites during whole body hyperthermia, we applied insulation to an extremity prior to the plateau phase of heating. We found that extremity insulation during whole body hyperthermia resulted in increased s.c. tissue and tibial bone marrow temperatures. With insulation, tibial bone marrow and rectal temperature were nearly equal but s.c. tissue temperature, although greater than without insulation, remained lower than rectal temperature. High efficiency extremity insulation or supplemental heating techniques may be necessary during whole body hyperthermia with the use of the radiant heat device in order to assure that extremities receive the prescribed thermal dose.

Animals↗

Circus movement in the canine atrium around the tricuspid ring during experimental atrial flutter and during reentry in vitro.

A Y-shaped lesion in the right atrium allows induction of atrial flutter in dogs. We recorded the activation sequence during this tachycardia from 96 endocardial bipolar electrodes using intracavitary electrode arrays during 12 separate episodes in three isolated perfused hearts. In each case a reentrant impulse circulated around the tricuspid valve orifice in either a clockwise or counter-clockwise direction. Cutting the pathway terminated the rhythm and prevented its reinduction. There was no discrete segment of markedly slow conduction in the reentrant circuit. The tachycardia cycle length was decreased by methacholine and increased by lidocaine. Reentry was also induced in atrial tissue around the tricuspid orifice when this structure was isolated and superfused in vitro. Tachycardia cycle lengths varied from 205 to 399 msec, depending on the circumference of the ring and temperature. Induction of tachycardia by premature stimulation depended on differences in the duration of the effective refractory period among parts of the ring. Conduction velocity was relatively uniform and was slower during tachycardias than during pacing at long cycle lengths. Analysis of the response to premature stimuli that reset the tachycardia provided evidence for incomplete recovery of excitability between depolarizations during the tachycardia. Fast-response action potentials were recorded throughout the pathway and up to six to eight cell layers deep. Histologic studies showed the supravalvular lamina, a circumferential band of fibers several cell layers below the endocardial surface, to be continuous around the tricuspid orifice. Propagation through this layer best explains the conduction velocities observed in the intact heart during flutter in this preparation.

Action Potentials↗

Pharmacokinetics and toxicity of intraperitoneal cisplatin combined with regional hyperthermia.

Hyperthermia (HT) potentiates in vitro cytotoxicity of cisplatin, providing a rationale for HT enhancement of cisplatin effect in vivo. In this study, regional abdominal HT was combined with intraperitoneal (IP) cisplatin in canines to characterize temperature distributions, as well as pharmacokinetics and toxicity of IP cisplatin with and without HT. Cisplatin (65 mg/m2) in normal saline was administered IP with a two-hour dwell time in ten Beagle dogs. Five of the ten dogs were randomly selected to receive concurrent regional microwave-producing HT at approximately 41.5 degrees C (IP) for a 60-minute period. Systemic temperatures in heated animals ranged from 37 degrees C to 40 degrees C; IP temperatures ranged from 39 degrees C to 44 degrees C. Initial IP temperatures ranged from 39 degrees C to 44 degrees C. Initial IP cisplatin concentrations were ten to 22 times greater than serum levels; the IP drug half-lives were 133 +/- 9 minutes and 68 +/- 15 minutes in heated and unheated dogs, respectively (P less than .001). Total concentrations of serum and urine cisplatin did not differ between the heated and unheated controls. The area under the concentration v time curve for free, ultrafilterable cisplatin in serum in units of percent minutes was 40 +/- 8 in heated and 60 +/- 7 in unheated controls (P = .006). Except for transient nausea and vomiting, no evidence of serious toxicity was observed in serum chemistries or histopathologic sections at 21 days post-treatment. Experiments involving in vitro incubation of cisplatin in normal saline were performed as a function of saline temperature; these showed that the amount of reactive cisplatin metabolites formed increased linearly with temperature by approximately 30% from 38 degrees C to 44 degrees C. This study supports the hypothesis that, with IP temperature elevation, there is an increased rate of generation and retention of reactive metabolites of cisplatin in the peritoneal cavity relative to unheated controls. In spite of these differences in pharmacokinetics, no significant toxicity was encountered. This study provides a model for treatment of IP malignancy such as ovarian carcinoma with IP cisplatin and regional HT.

Animals↗

Recurrent pleural fibroma.

Pleural fibromata are rare tumours. We report a case of histologically proven pleural fibroma with later recurrence following resection. The case emphasizes the need for long-term review of patients with pleural fibromata.

Female↗

Atrial reentry around an anatomic barrier with a partially refractory excitable gap. A canine model of atrial flutter.

We have characterized, in dogs, a model of inducible regular atrial tachycardia that resembles atrial flutter. The model involves creating a Y-shaped lesion comprised of an intercaval incision and a connected incision across the right atrium. It is suitable for serial studies of the effects of pacing or antiarrhythmic drugs in chronically instrumented animals studied in the awake state for at least several months. The postoperative cycle length of the induced tachycardia varies from 143 to 188 msec, depending on the size of the dog. The tachycardia cycle length was consistent for each dog, and the rhythm--once induced--was very stable until terminated by pacing. The mechanism of the tachycardia was reentry due to circus movement based on the ability to induce and terminate it by premature impulses or overdrive, the ability to reset the tachycardia by single premature stimuli, the pattern of entrainment during overdrive stimulation, and the ability to terminate the tachycardia by interrupting the conduction pathway. The window of reset determined by the range of coupling intervals of premature stimuli that were able to enter and reset the tachycardia ranged from 56 to 82 msec. There appears to be incomplete recovery of excitability by the end of the excitable gap as evidenced by the fact that even late premature impulses that enter the reentrant circuit conduct more slowly than the tachycardia impulse, and because stimulation of muscarinic receptors that shortens the duration of the action potential and refractoriness also reduces the cycle length of the tachycardia. Epicardial and endocardial activation mapping during tachycardia showed the reentrant pathway does not merely encircle the lesion, particularly over the left atrial epicardium near the intercaval lesion. Rather, the impulse appears to travel around the atrial tissue just above the tricuspid ring, including a portion that travels through the right side of the lower intraatrial septum. Thus, the model involves circus movement around an anatomic barrier through normal tissue that contains no depressed segments. During the circus movement, there is a relatively long excitable gap during which there is incomplete recovery of excitability. This model should be useful for studies of the mechanism of antiarrhythmic drug action and the responses to premature stimulation in this particular subclass of reentrant rhythms, and for comparison with the behavior and responses of other forms of reentry.

Animals↗