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Biomedical subjects

R L Page

Publications and source records attributed to R L Page.

At least 91 records · Page 5Linked to original sources
PubMed1994

Evaluation of outpatients experiencing implantable cardioverter defibrillator shocks associated with minimal symptoms.

Patients receiving minimally symptomatic shocks from their implantable cardioverter defibrillators were studied prospectively using transtelephonic ECG loop monitoring. The time course to the first subsequent shock was evaluated. Twenty-nine consecutive patients who received a shock preceded by mild palpitations or no symptoms were given a transtelephonic ECG loop monitor and instructed to activate the monitor if a subsequent shock occurred. Kaplan-Meier analysis was used to quantitate the time to first shock during the study period. The point estimate +/- standard error of patients receiving a shock during the study period was 31% +/- 9% at 30 days, 41% +/- 9% at 60 days, and 60% +/- 9% at 120 days. The ECG was successfully transmitted in 7 of 13 patients who had shocks in the 60-day monitoring period, and demonstrated inappropriate shocks in 6 of 7. Determination of the cause of shock led to a change in subsequent management in all 7 patients. We conclude that the incidence of inappropriate shocks may be higher than estimated previously in patients with minimal symptoms prior to the shock. There are thousands of patients with implantable cardioverter defibrillators that have no storage function for treated tachycardias; transtelephonic ECG loop monitoring can determine the cause of implantable cardioverter defibrillator discharge in these patients, and the diagnosis is invaluable in their management.

Adolescent↗
PubMed1994

MR imaging and spectroscopy for prognostic evaluation in soft-tissue sarcomas.

PURPOSE: To enable prediction of tumor response to a particular treatment. MATERIALS AND METHODS: The authors studied the value of hydrogen-1 T2 and phosphorus-31 magnetic resonance (MR) spectroscopic metabolic determinations as indicators of prognosis in 20 humans and 10 dogs with soft-tissue sarcomas. All patients underwent combined fractionated radiation therapy and hyperthermia. Surgical resection of the entire tumor in humans allowed comparison of pretherapy T2 and MR spectroscopic parameters with subsequent histologic findings. Long-term clinical follow-up (no surgical intervention) was available with the dogs and allowed comparison of pretherapy pH with the duration of local relapse-free survival. RESULTS: A relationship exists between pretherapy pH and T2 and ultimate tumor necrosis in humans and pretherapy pH and time elapsed until local failure in dogs. CONCLUSION: MR imaging and spectroscopy could be useful in the prognosis of patients with soft-tissue sarcomas before therapy is initiated.

Adult↗
PubMed1994

Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.

BACKGROUND: Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown. METHODS AND RESULTS: Twenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymptomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P = .02). The ratio of the mean rates was 0.0 (0.0, 0.8). CONCLUSIONS: In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias.

Atrial Fibrillation↗
PubMed1994

PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody Fab fragment.

UNLABELLED: Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the 18F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. METHODS: The antibody fragment was labeled using the N-succinimidyl 8-[(4'-[18F]fluorobenzyl)amino]suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T1/2 beta = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. RESULTS: PET images demonstrated increased accumulation of 18F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10(-3)% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. CONCLUSIONS: These results, although preliminary, suggest that PET imaging of 18F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates.

Animals↗
PubMed1993

Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.

PURPOSE: To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. METHODS AND MATERIALS: Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C. Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. RESULTS: Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7 degrees C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30-35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. CONCLUSION: Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7 degrees C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma.

METHODS: Forty-nine dogs with spontaneously occurring osteosarcoma underwent limb-sparing surgery after preoperative therapy consisting of intra-arterial cisplatin alone or intra-arterial cisplatin in combination with doses of radiation from 20-40 Gy in 10 fractions. All resections were marginal, and the defect was repaired with a cortical allograft. RESULTS: Local tumor control was strongly influenced by the percent necrosis in the excised specimen. Overall, the estimated 1-year local recurrence rate was approximately 32% (by life-table estimate). Dogs with less than 75% necrosis had an estimated 1-year recurrence rate of 65%; those with greater than 75% necrosis had an estimated 1-year recurrence rate of 15% (P = 0.004, by log-rank test). Local recurrence was influenced by the radiation dose. Dogs receiving 28 Gy or less had an estimated 50% 1-year recurrence rate, and those receiving 32 Gy or more had an estimated 8% 1-year recurrence rate (P = 0.03, by log-rank test). Normal host bone more frequently became necrotic at doses of 36 Gy or more. CONCLUSIONS: Intra-arterial cisplatin in combination with moderate doses of radiation (32 Gy) can achieve a high percent tumor necrosis while maintaining host bone viability. Survival was limited by distant metastasis but was lengthened by treatment compared with some earlier findings.

Amputation, Surgical↗
PubMed1993

Development and characterization of an isolated and perfused tumor and skin preparation for evaluation of drug disposition.

The purpose of this study was to develop a model in which the regional pharmacokinetics of a drug in tumor and nontumorous tissue could be evaluated under a variety of physiological conditions. To this effect, the growth of a human choriocarcinoma cell line (JAR) was evaluated in pigs immunosuppressed with 25 mg cyclosporine/kg every 24 h. During an initial study, we demonstrated that suspensions containing approximately 3 million JAR cells with and without 1 million normal human fibroblasts injected s.c. into the inguinal region of pigs resulted in the growth of tumors consisting primarily of polygonal neoplastic cells. Multinucleate tumor cells, inflammatory cells, necrotic debris, and vascular endothelial cells were also present. Maximal tumor size was noted on day 12, after which time tumor regression occurred. The coinoculation of fibroblasts resulted in significantly larger tumors. Two single pedicle, axial pattern tubed flaps were created in the inguinal area of 4 pigs. JAR cells and fibroblasts were transplanted to one flap to allow for tumor formation. The other flap served as a nontumorous control. Both flaps were removed for perfusion with a physiological solution 11 days later. Glucose utilization, lactate concentrations, lactate dehydrogenase activities, and microscopic evaluation of skin samples were used to assess flap viability. All flaps remained viable for 8 h of perfusion. The only differences detected between nontumorous and tumor flaps was the initial perfusion pressure which was significantly lower in tumor flaps (P < 0.05). The isolated perfused tumor and skin flap is unique in that it consists of a tumor surrounded by normal tissue with an intact microvascular system and can be utilized to design regional pharmacokinetic studies describing drug distribution in tumor tissue.

Animals↗
PubMed1993

Effect of tumor presence on cisplatin and carboplatin: disposition in the isolated, perfused tumor and skin flap.

The purpose of this study was to evaluate the disposition of elemental platinum (Pt) derived from cisplatin (CDDP) or carboplatin (CBDCA) in the isolated, perfused tumor and skin flap (IPTSF). Flaps were perfused with either 3.0 micrograms CDDP/ml perfusion medium (n = 4 tumor, n = 4 control) or 15 micrograms CBDCA/ml (n = 4 tumor, n = 3 control) at a rate of 1 ml/min for 3 h. A 2-h (CDDP experiments) or 3-h (CBDCA experiments) washout phase using undosed medium was then performed. The disposition kinetics of free (ultrafilterable) Pt were characterized using a four-compartment physiologically relevant pharmacokinetic model. A tumor effect on the disposition of Pt was noted in that the Pt mass from CDDP in the central and mobile tissue compartments was greater in tumor flaps than in control flaps (P < 0.05). Similar trends were noted in CBDCA-treated flaps, but these were not significant. The Pt mass in the fixed tumor and non-tumor tissue compartments was significantly greater when Pt was derived from CDDP than when it was derived from CBDCA (P < 0.05). A linear relationship existed between the estimated micrograms of Pt in the flaps from both CDDP and CBDCA and the cross-sectional vascular resistance of the flaps at 30 (CDDP, r = 0.78; CBDCA, r = 0.89) and 60 min (CDDP, r = 0.65; CBDCA, r = 0.85) of perfusion. We conclude that the IPTSF is a useful model for evaluating the disposition of Pt drugs in tumor and non-tumor tissue and that tumor presence alters the disposition of CDDP.

Animals↗
PubMed1993

Utility of transtelephonic ECG monitoring in evaluating discharges from a third-generation implantable cardioverter defibrillator.

The authors report the case of a 60-year-old man with a third-generation implantable cardioverter defibrillator whose rate-sensing lead malfunction was diagnosed only after surface loop electrocardiographic (ECG) monitor recording. The stored R-R intervals suggested an irregular ventricular rhythm, but the loop ECG monitor demonstrated inappropriate shocks delivered during sinus rhythm.

Defibrillators, Implantable↗
PubMed1993

Radiofrequency catheter ablation of idiopathic recurrent ventricular tachycardia with right bundle branch block, left axis morphology.

Idiopathic ventricular tachycardia with right bundle branch block and left axis deviation morphology is a well described clinical syndrome. Previous studies have mapped the tachycardia focus to the inferior septal region at the base of the posterior papillary muscle of the left ventricle. We describe two typical cases in a 20-year-old man and 29-year-old woman in which the tachycardia focus was localized with endocardial mapping techniques. In both cases the ventricular tachycardia focus was ablated with application of radiofrequency current at the inferior septal region. There were no complications of the procedures. The patients remain asymptomatic over follow-up of 7 and 4 months, respectively.

Adult↗
PubMed1993

Changes in nocturnal oximetry after treatment of exacerbations in cystic fibrosis.

Sleep related arterial oxygen desaturation has been described in clinically stable young adults with cystic fibrosis. The incidence and severity of nocturnal oxygen desaturation in children during infective exacerbations and the changes that occur with treatment were examined. Forty five children with proved cystic fibrosis, median age 8.9 years, admitted to the Regional Cystic Fibrosis Unit underwent clinical evaluation, spirometry, and measurement of peak flow and nocturnal oxygen saturation on admission and after 10 days' treatment. There was a significant improvement in all the above measurements, with the averaged overnight saturation changing from a mean (SD) 92.7 (2.7)% to 94.3 (2.0)%, mean (SE) difference 1.58 (0.37). The time spent with a saturation 4% or more below their clinic value showed a marked improvement from 122 (152) minutes on the first night to 21 (30.7) on the second, mean (SE) difference 101 (22.4). Eight young children could not perform pulmonary function tests, all desaturated on the admission night. Nocturnal hypoxaemia is a common finding in young cystic fibrosis patients during infective exacerbations but improves with treatment. Overnight oximetry is simple to perform, well tolerated, and identifies patients with marked nocturnal desaturation.

Child↗
PubMed1993

Spontaneous occurrence of symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia in untreated patients.

BACKGROUND: Ambulatory outpatients (n = 150) with a history of paroxysmal supraventricular arrhythmia were studied to establish the characteristics of the first recurrence of symptomatic tachycardia (time to first recurrence, heart rate during tachycardia, and observed rhythm that was regular versus irregular) when no antiarrhythmic drug was being taken. Baseline variables were examined to assess their impact on time to first recurrence: index arrhythmia (paroxysmal atrial fibrillation [n = 37] versus paroxysmal supraventricular tachycardia [n = 113]), age (mean +/- SD, 43.3 +/- 16.1 years), female sex (n = 71), or presence of other heart or lung disease (n = 53). METHODS AND RESULTS: Transtelephonic monitoring of the ECG was used to document the rhythm during recurrences of symptomatic tachycardia. Time to first recurrence of symptomatic tachycardia and heart rate during tachycardia were measured, the observed rhythm was classified as irregular (consistent with paroxysmal atrial fibrillation) or regular (consistent with paroxysmal supraventricular tachycardia), and the hour of recurrence was recorded. Advancing age was significantly associated with a decreasing time to first recurrence (p < 0.001); the estimated increase in the hazard function was 25% with each 10 years of advancing age. After the effect of age was adjusted for, neither the classification of arrhythmia (p > 0.2), presence of other heart or lung disease (p > 0.8), nor sex (p > 0.9) was significantly associated with time to first recurrence. Among patients with paroxysmal supraventricular tachycardia, 6.5% had atrial fibrillation recorded at the next symptomatic arrhythmia; among patients with paroxysmal atrial fibrillation, 11.8% had a regular tachycardia recorded at the next symptomatic arrhythmia. There was a circadian pattern to the hour of occurrence of paroxysmal supraventricular tachycardia but not paroxysmal atrial fibrillation. CONCLUSIONS: Age is more important than other clinical variables, including the ECG classification of a paroxysmal supraventricular arrhythmia in predicting the occurrence of symptomatic arrhythmias. Arrhythmias documented by ECG during symptoms are often different from the arrhythmia documented at the time of referral, which may confound interpretation of antiarrhythmic drug effects.

Adult↗
PubMed1992

High-level expression of a heterologous protein in the milk of transgenic swine using the cDNA encoding human protein C.

Transgenic pigs were generated that produced human protein C in their milk at up to 1 g/liter. The gene construct was a fusion gene consisting of the cDNA for human protein C inserted into the first exon of the mouse whey acidic protein gene. These results demonstrate that the mouse whey acidic protein gene contains regulatory elements that can direct cDNA expression at high levels in the pig mammary gland. Recombinant human protein C that was produced at about 380 micrograms/ml per hr in transgenic pig milk possessed anticoagulant activity that was equivalent to that of protein C derived from human plasma. These studies provide evidence that gamma-carboxylation can occur at high levels in the mammary gland of a pig.

Animals↗
PubMed1992

ATP-MgCl2 increases cisplatin toxicity in the dog and rat.

The purpose of this study was to examine if ATP-MgCl2, an agent that protects against acute cisplatin toxicity in vitro, protected against cisplatin toxicity in vivo. Baseline renal function measurements were obtained on dogs (n = 12) and rats (n = 20) on day -1. Dogs were given 90 mg m-2 cisplatin (n = 5), 90 mg m-2 cisplatin and 50 mumol kg-1 ATP-MgCl2 (n = 5), or 90 mg m-2 cisplatin and 150 mumol kg-1 ATP-MgCl2 (n = 2), in a slow bolus i.v. injection on day 0. Rats were given 4 mg kg-1 cisplatin i.p. (n = 6) and 25 mumol kg ATP-MgCl2 (n = 8) i.v. or 4 mg kg-1 cisplatin i.p. and 25 mumol kg-1 ATP-MgCl2 (n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine clearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 mumol kg-1 ATP-MgCl2 and both dogs given 150 mumol kg-1 ATP-MgCl2 in addition to cisplatin developed acute anuric renal failure and were euthanatized prior to completion of the study. Rats given 4 mg kg-1 cisplatin and 25 mumol kg-1 ATP-MgCl2 had significantly increased blood urea nitrogen and serum creatinine after drug administration, compared to rats given cisplatin alone. The results indicated that ATP-MgCl2 worsened in vivo cisplatin renal toxicity in the dog and rat.

Acute Kidney Injury↗