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Biomedical subjects

R L Page

Publications and source records attributed to R L Page.

At least 109 records · Page 6Linked to original sources
PubMed1992

Treatment of supraventricular tachycardias with transcatheter delivery of radiofrequency current.

Medical therapy for the treatment of supraventricular tachycardias is frequently ineffective and associated with significant side effects, whereas curative surgical approaches have generally been limited by their considerable morbidity and cost. Greater understanding of the mechanisms underlying supraventricular tachycardias has improved our ability to precisely map endocardial areas critical to arrhythmogenesis. Advances in catheter ablation techniques and particularly the use of radiofrequency current to generate thermal energy for ablation have resulted in dramatic success rates for curative catheter ablation. This review examines the physics of radiofrequency current ablation and its application to the treatment of atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia, and arrhythmias associated with the Wolff-Parkinson-White syndrome. The limitations, risks, and cost-effectiveness of this technique relative to medical and surgical approaches are also evaluated.

Catheter Ablation↗
PubMed1992

Evaluation of systems for collection of porcine zygotes for DNA microinjection and transfer.

Crossbred gilts and sows (n=116) were used for the collection of 1-cell zygotes for DNA microinjection and transfer. Retrospectively, estrus synchronization and superovulation schemes were evaluated to assess practicality for zygote collection. Four synchronization and superovulation procedures were used: 1) sows were observed for natural estrous behavior; 1000 IU human chorionic gonadotrophin (hCG) was administered at the onset of estrus (NAT); 2) cyclic gilts were synchronized with 17.6 mg altrenogest (ALT)/day for 15 to 19 days followed by superovulation with 1500 IU pregnant mares serum gonadotropin (PMSG) and 500 IU hCG (LALT); 3) gilts between 11 and 16 days of the estrous cycle received 17.6 mg ALT for 5 to 9 days and PMSG and hCG were used to induce superovulation (SALT); and 4) precocious ovulation was induced in prepubertal gilts with PMSG and hCG (PRE). A total of 505 DNA microinjected embryos transferred into 17 recipients produced 7 litters and 50 piglets, of which 8 were transgenic. The NAT sows had less (P < 0.05) ovarian activity than gilts synchronized and superovulated by all the other procedures. Synchronization treatments with PMSG did not differ (P > 0.05) in the number of corpora hemorrhagica or unovulated follicles, but SALT and PRE treaments had higher ovulation rates than LALT (24.7 +/- 2.9, 24.3 +/- 1.8 vs 11.6 +/- 2.7 ovulations; X +/- SEM). The SALT and PRE treatments yielded 12.3 +/- 2.6 and 17.7 +/- 1.7 zygotes. Successful transgenesis was accomplished with SALT and PRE procedures for estrus synchronization and superovulation.

Journal Article↗
PubMed1992

Use of nitroprusside to increase tissue temperature during local hyperthermia in normal and tumor-bearing dogs.

The present study investigates the effects of nitroprusside, a potent vasodilating agent, on tissue temperature during local hyperthermia in five normal and five tumor-bearing dogs. Caudal thigh muscles were heated in normal dogs and muscle temperatures were recorded during hyperthermia. Tumor-bearing dogs received two hyperthermia treatments during a course of radiation therapy. Temperatures were recorded in tumor and surrounding normal tissues. Mean arterial pressure was decreased by approximately 40-45% during nitroprusside infusion and was associated with a compensatory increase in heart rate and increases in tissue temperature. In normal dogs, muscle temperatures increased an average of 1.7 degrees C with nitroprusside administration. When nitroprusside was administered at the beginning of local hyperthermia to induce step-down heating, approximately 48% of the measured positions in caudal thigh muscle achieved a temperature greater than or equal to 43 degrees C, sufficient to induce step-down heating, during the hyperthermia episode. In tumor-bearing dogs, there was a significant increase in tumor and normal tissue temperatures during nitroprusside administration. Estimated T90 and T50 descriptors increased by 0.9 degrees C and 1.6 degrees C, respectively, for tumor tissue and by 0.4 degrees C and 1.2 degrees C, respectively, for normal tissue. Despite the increase in normal tissue temperatures no toxicity was observed in these dogs. Nitroprusside may be a useful agent for manipulation of tumor temperatures during the entire hyperthermia treatment or for a short time period at the initiation of treatment to induce step-down heating.

Animals↗
PubMed1992

Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Administration, Oral↗
PubMed1992

In vitro development of zygotes from prepubertal gilts after microinjection of DNA.

The effect of pronuclear microinjection of DNA and culture in excised mouse oviducts on the development of porcine zygotes was assessed in this study. Precocious ovulation was induced in prepubertal gilts with pregnant mare's serum gonadotrophin and hCG. Zygotes received either pronuclear microinjection of buffer alone, buffer containing a DNA construct, or no microinjection. Zygotes were cultured in vitro in either modified Krebs-Ringer bicarbonate medium (KRB) for 144 h or in mouse oviduct (MO) explant culture with KRB for 48, 72, 96, or 120 h. Pronuclear microinjection of DNA resulted in a lower (P less than .05) cleavage index (CI) than did buffer or no microinjection (CI 2.16 +/- .10 vs 2.80 +/- .13 and 2.93 +/- .10). The CI loss was greatest for DNA-injected zygotes at the two-cell stage of development. Coculture of zygotes in MO resulted in a higher CI (P less than .01) than did culture in KRB. Culture in MO for 72 h was the most beneficial system compared with MO for 48, 96, or 120 h (P less than .05; CI 3.25 +/- .12 vs 2.66 +/- .18, 2.79 +/- .14, and 2.40 +/- .14, respectively). Microinjection of DNA, not merely the mechanical procedure, was detrimental to early zygote development and may be the cause of low pregnancy rates.

Animals↗
PubMed1992

Relationship between quantitative tumor scintigraphy and time to metastasis in dogs with osteosarcoma.

Parameters that predict tumor aggressiveness or response to therapy are potentially useful in selecting the most appropriate treatment. In theory, the biologic aggressiveness of an untreated bone tumor may be reflected in bone scan parameters. The purpose of this study was to assess the usefulness of bone scintigraphy as a predictive indicator of subsequent metastasis in 25 dogs with primary osteosarcoma. Dogs received radiotherapy and/or intra-arterial cisplatin prior to limb-sparing surgery. Quantitative bone scintigraphy of the tumor was performed prior to treatment (25 dogs) and following treatment but prior to limb-sparing surgery (22 dogs). All dogs developed metastasis at a median time of 202 days (range, 41-444 days) after initiation of treatment. A statistically significant relationship was identified between time to metastasis and: (1) the radiographic tumor area, (2) the pretreatment ratio of mean counts per pixel in tumor-to-adjacent nontumor bone (T/NTT), and (3) the pre:post-treatment T/NTT. Larger tumor area and high pretreatment tumor activity were associated with earlier metastasis. Tumors characterized by greater decreases in scintigraphic uptake after treatment were associated with earlier metastasis. These data suggest that osteosarcomas with high pretreatment mean counts per pixel signify aggressive tumors subject to early metastasis.

Animals↗
PubMed1991

Acute blindness associated with intracranial tumors in dogs and cats: eight cases (1984-1989).

Rostral and middle cranial fossa tumors affecting the optic chiasm and resulting in acute visual deficits were diagnosed in 7 dogs and 1 cat. Blindness and dilated nonresponsive pupils were the primary signs in all animals. Other concurrent neurologic deficits were either absent or were equivocal. Behavioral changes, including signs of depression and lethargy, were noticed in 1 dog and the cat subsequent to the onset of blindness. Retinal function was assessed as normal by electroretinography in all animals. The histologic necropsy diagnosis was pituitary carcinoma in 1 dog and the cat and paranasal sinus carcinoma with intracranial extension in 1 dog. A cytologic diagnosis of polycentric lymphosarcoma affecting the optic chiasm was diagnosed in 1 dog. In the remaining 4 dogs, results of computed tomographic imaging or endocrine function testing suggested pituitary gland neoplasia. Four dogs were treated with cobalt-60 radiation or chemotherapy. There was partial return of visual function in only 1 of the dogs treated with radiation.

Acute Disease↗
PubMed1991

Percent tumor necrosis as a predictor of treatment response in canine osteosarcoma.

The percent tumor necrosis was determined in 200 dogs with spontaneously occurring osteosarcoma. One hundred dogs had no treatment before amputation or death. One hundred other dogs were treated with either radiation therapy alone (n = 23), intraarterial (IA) cisplatin alone (n = 16), intravenous (IV) cisplatin alone (n = 6), radiation therapy plus IA cisplatin (n = 47), or radiation therapy plus IV cisplatin (n = 8). Eighty-nine of these 100 dogs had their tumors resected 3 weeks after the end of therapy (6 weeks after the initiation of therapy) and replaced with a cortical bone allograft. Dogs with preoperative treatment were evaluated for local tumor control and time to metastasis. The mean percent tumor necrosis in untreated osteosarcoma was 26.8%. The mean percent tumor necrosis for dogs receiving radiation only, IA cisplatin only, and IV cisplatin only was 81.6%, 49.1% and 23.8%, respectively. The mean percent tumor necrosis for dogs receiving radiation therapy plus IA cisplatin or radiation therapy plus IV cisplatin was 83.7% and 78.2%, respectively. There was no significant difference between percent tumor necrosis in untreated osteosarcoma compared with those receiving IV cisplatin, but there was a significant increase in percent tumor necrosis with all other treatments. A mathematic model for the effect of cisplatin and radiation dose was developed using multiple regression analysis. The radiation dose calculated to cause at least 80% tumor necrosis was 42.2 Gy (95% confidence interval [CI], 38.0 to 47.6 Gy) when radiation was given alone and 28.1 Gy (95% CI, 21.3 to 36.6 Gy) when radiation was combined with IA cisplatin. Areas of viable tumor tended to be most frequent adjacent to the articular cartilage and in the joint capsule. Percent tumor necrosis was strongly predictive for local tumor control; 28 of 32 dogs with greater than 80% tumor necrosis had local control, and only eight of 29 dogs with less than 79% tumor necrosis had local control (P = 0.0047). There was no correlation between percent tumor necrosis and time to metastasis.

Animals↗
PubMed1991

Dose response to inhaled salbutamol in chronic obstructive airways disease.

High dose inhaled salbutamol is increasingly used in the management of chronic obstructive airways disease. To determine the range of doses to achieve optimal bronchodilatation and the proportion of patients requiring high dose therapy we have studied 23 patients with chronic obstructive airways disease. Cumulative dose responses were measured to six incremental doses of salbutamol (0.2 to 1.2 mg) delivered by metered dose inhaler. Results were analysed by polynomial regression to calculate the smallest dose required to produce 90% maximal bronchodilatation in each patient. While 5/23 (22%) required greater than 1 mg the majority, 14/23 (61%), achieved 90% maximal bronchodilation with salbutamol 0.6 mg or less. The 8 patients with severe airflow limitation (FEV1 less than or equal to 1 litre) showed a similar pattern of response. We conclude that in chronic obstructive airways disease there are wide individual variations in the dose of inhaled salbutamol producing 90% maximal bronchodilatation with only a minority requiring high dose therapy.

Administration, Inhalation↗
PubMed1991

Effect of continuous enhanced vagal tone on atrioventricular nodal and sinoatrial nodal function in humans.

A constant intravenous infusion of phenylephrine (0.74 +/- 0.41 micrograms/kg/min) was given to 10 patients to cause a continuous augmentation in reflex vagal tone. After the infusion, the diastolic blood pressure increased from 76 +/- 7 to 89 +/- 11 mm Hg (p less than 0.01). The sinus cycle length and atrial-His (AH) interval were measured, and incremental atrial pacing was performed before and during phenylephrine infusion until atrioventricular (AV) nodal block was achieved. For each patient, the AV nodal function curve (i.e., the AH interval plotted as a function of the atrial pacing cycle length) was compared during both the control state and phenylephrine infusion; the AH intervals during each condition at chosen short (AHS) and long (AHL) cycle lengths were compared. The sinus cycle length increased during phenylephrine infusion from 941 +/- 294 to 1,115 +/- 347 msec (p = 0.013). The AH interval during sinus rhythm was not significantly prolonged (77 versus 82 msec, p = NS). The shortest atrial pacing cycle length yielding 1:1 AV nodal conduction increased during phenylephrine infusion from 412 +/- 120 to 575 +/- 211 msec (p less than 0.01). Of note, the degree of sinus cycle length prolongation did not correlate with the degree of prolongation in the shortest atrial pacing cycle length yielding 1:1 AV nodal conduction. The AV nodal function curve was shifted markedly to the right and only slightly upward.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of time of cisplatin administration on its toxicity and pharmacokinetics in dogs.

Cisplatin (90 mg/m2) was administered in a 5-minute bolus IV infusion to dogs at 8 AM (n = 6) or 4 PM (n = 6). Blood and urine samples were collected over a 4-hour period for statistical moment pharmacokinetic analysis. Mean urinary excretion rate of total platinum was increased, whereas mean plasma residence time of ultrafilterable platinum was decreased, in the group treated at 4 PM (PM group), compared with those treated at 8 AM (AM group). Over a 2-week postinfusion-monitoring period, both groups of dogs developed decreases in creatinine clearance, urine/serum osmolality ratio (UOsm/SOsm), specific gravity, and increase in BUN, serum creatinine concentration, urine gamma-glutamyltranspeptidase/urine creatinine ratio (UGGT/UCr), fractional excretion of magnesium, and fractional excretion of phosphate. Urine specific gravity and UOsm/SOsm were significantly decreased, whereas UGGT/UCr and BUN were significantly increased in the AM group, compared with the PM group. The time of administration had a significant effect on the pharmacokinetics of cisplatin, which resulted in significant differences in cisplatin-induced renal toxicosis.

Animals↗
PubMed1991

Effect of a passive heat and moisture exchanger on esophageal temperature in tumor-bearing dogs during whole-body hyperthermia.

The effect of a passive heat and moisture exchanger on tracheal and large airway temperature, as reflected by esophageal temperature at the thoracic inlet, was determined for 12 anesthetized and ventilated tumor-bearing dogs undergoing whole-body hyperthermia at 42 C. Delivered thermal dose to the esophagus and rectum during 120 minutes of whole-body hyperthermia was quantified as the thermal dose summary measure EQ43. The heat and moisture exchanger significantly increased esophageal EQ43 from 7.3 minutes to 12.1 minutes. Esophageal EQ43, however, remained lower than rectal EQ43. Although use of a heat and moisture exchanger improved esophageal temperature during whole-body hyperthermia, presumably through improved airway temperature, additional methods will be necessary to increase esophageal and airway temperature to the target value of 42 C.

Animals↗
PubMed1990

Nonuniform alteration of cis-diamminedichloroplatinum(II) tissue distribution in dogs with whole body hyperthermia.

The purpose of this study was to investigate the pharmacokinetics and tissue disposition of cisplatin (CDDP) in euthermic and hyperthermic dogs to determine if hyperthermic alteration of tissue CDDP concentration is uniform. Eighteen female beagle dogs received 20, 50, or 80 mg/m2 CDDP by constant infusion for 60 min under normothermic or hyperthermic conditions (n = 3/subgroup). Blood, plasma, and ultrafiltered plasma samples were collected during the infusion. At termination of infusion, animals were immediately sacrificed, all major tissues were collected, and platinum levels were determined by atomic absorption spectroscopy. Platinum concentrations in all blood fractions of hyperthermic dogs tended to be lower than those of normothermic dogs. The correlation between dose and blood area under the concentration-time curve was linear at both temperatures. Each tissue concentration was normalized for that individual dog's blood area under the curve. The ratio of relative extraction at 42 degrees C to that at 37 degrees C were compared for each tissue. Values of 1.0 were interpreted as indicating uniform relative tissue extraction at each temperature. Values of greater than 2.0 were obtained in lung and ileum, while values of greater than 1.5 were obtained in liver, adrenal, stomach, colon, duodenum, spleen, and pancreas. Values of less than 1.0 were obtained in skin and superficial lymph nodes. These results indicate that hyperthermia significantly alters the pattern of CDDP tissue disposition in a nonuniform manner and that pharmacokinetic data obtained at one temperature, e.g., areas under the curve, cannot be used to directly predict tissue concentrations at another temperature.

Animals↗
PubMed1990

Transient glomerulonephropathy associated with primary erythrocytosis in a dog.

Proteinuria (urine protein/creatinine ratio, 13.6) resolved after control of primary erythrocytosis in a dog. Hydroxyurea and doxorubicin administration and phlebotomy were used initially to manage erythrocytosis. Remission was maintained for approximately 2 years. Glomerulonephropathy, characterized by absence of routine histologic or immunofluorescent changes and ultrastructural evidence of basement membrane deterioration and podocyte fusion, was documented. These lesions may have been a result of hypoxia and/or hyperviscosity secondary to erythrocytosis.

Animals↗
PubMed1990

Radiotherapy prior to cortical allograft limb sparing in dogs with osteosarcoma: a dose response assay.

Twenty-one dogs with spontaneously occurring appendicular osteosarcoma were given preoperative radiation therapy prior to a limb sparing procedure using a cortical allograft. Radiation doses were randomly assigned, ranged from 36-52 Gy in 4 Gy intervals, and were given in 10 equally-sized fractions on a M, W, F schedule. Seventeen of the 21 dogs underwent the limb sparing procedure approximately 3 weeks after completion of radiation therapy. Local tumor recurrence was documented in 4 of 17 dogs at mean and median times of 5.5 and 5.8 months, respectively, after initiation of radiation therapy. Three of 4 recurrences were in anatomic regions with sparse adjacent soft tissue which precluded wide excision. Complications were significant. Fixation device failure occurred in 9 of 17 dogs and was associated with host bone necrosis, muscle thinning and fibrosis of vessels and nerves in irradiated normal tissue. Incidence of host bone necrosis was directly related to radiation dose (Kendall's statistic, p = 0.005). Metastasis occurred in all 21 dogs. Mean and median times to metastasis in these dogs were 5.1 and 4.0 months, respectively, after initiation of radiation therapy. Local tumor control rates and survival times were higher in dogs developing allograft infection suggesting that infection acted as an immunostimulant. All local failures occurred in dogs that did not develop allograft infection and median survival times for uninfected versus infected dogs were 5 and 11 months, respectively (logrank test, p = 0.029). Increased tumor radiopacity following radiation therapy was significantly related to survival. Median survival in dogs whose tumors were characterized by decreased, unchanged or increased opacity after radiation therapy were 3.5 and 14 months, respectively (logrank test, p = 0.014). Based on the results of our study, radiation therapy can not be recommended as part of limb sparing treatments for patients with osteosarcoma at doses and dose per fraction values similar to those used herein.

Animals↗