PubMed Health⌕ Search

Biomedical subjects

P J Hoopes

Publications and source records attributed to P J Hoopes.

At least 55 records · Page 3Linked to original sources
PubMed1987

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↗
PubMed1986

Lateral hermaphroditism and seminoma in a dog.

A 3.6-year-old female Collie was found to have a functionally active ovary and an azospermic testis containing several seminomas. The bitch had had 3 irregular estrous cycles. An ovariohysterectomy was performed, and the histopathologic diagnosis was lateral hermaphroditism and seminoma. Canine intersexes generally have been thought not to have estrous cycles. However, as evidenced in this case, estrous activity can occur. From this report, it is suggested that bitches having irregular estrous cycles should be evaluated for intersexuality.

Animals↗
PubMed1986

Temperature measurements in normal and tumor tissue of dogs undergoing whole body hyperthermia.

Temperature was measured in the left ventricle, aorta, liver, brain, lung, bone marrow, kidney, and spontaneous solid tumors in dogs undergoing whole body hyperthermia in a radiant heat device. Rectal temperature was found to be a satisfactory indicator of systemic arterial temperature during plateau temperature conditions but rectal temperature underestimated arterial temperature during heating and overestimated it during cooling. Lung temperature, based on small airway temperature, was the same as rectal temperature during plateau temperature conditions. Liver and brain temperatures were slightly higher (0.1-0.2 degree C) than rectal temperature during the plateau phase. During plateau temperature conditions, kidney temperature measurements were higher than rectal temperature when one site/kidney was measured but were lower than rectal temperature when two sites/kidney were measured suggesting invasive thermometry may have affected measured temperature values. Tibial marrow temperature was greater than rectal temperature during heating but fell below rectal temperature during plateau temperature conditions by as much as 1.3 degree C. Femoral marrow temperature was below rectal during heating but gradually exceeded it during steady state conditions, by 0.1-0.4 degree C. Temperature in solid tumors was variable, sometimes exceeding (0.6 degree C) and sometimes being less (1.8 degree C) than rectal temperature.

Animals↗
PubMed1985

Isoeffect curves for radiation-induced cardiomyopathy in the dog.

Canine hearts were irradiated with a range of total doses given in 2, 3, or 4 Gy per fraction. Echocardiography was done before irradiation and at 3 and 6 months after irradiation. Histologic analyses were done of tissues taken at necropsy 6 months after irradiation. The percentage vascular component in the ventricles decreased with increasing total doses. The connective tissue component increased at lower doses and then decreased at higher doses. There was more fibroblastic proliferation and collagen production in the lower dose range and there may have been more cell killing by the higher doses. There was some evidence of myocardial hypertrophy at higher doses, which would have caused an apparent decrease in the connective tissue component. In either case, surviving fibroblasts would be expected to continue proliferating and producing collagen. At longer time intervals after irradiation the connective tissue component would likely continue to increase as observed clinically. That increase would be proportional to dose, but might not be closely related to initial killing of fibroblasts. Many factors such as changes in blood supply, continued loss of myocardium, and other stresses on the heart could influence the degree of fibrosis at later times. A relationship of response to cell killing appeared to exist based on alpha/beta ratios that were less than 3 Gy whether determined at the mid-range or for the greatest response of vasculoconnective tissues. Alpha/beta ratios ranged from 2.7 to 5 Gy for increases in diastolic wall thickness of the left ventricle at 3 and 6 months after irradiation. The low alpha/beta ratios reflect relatively steep isoeffect curves and have important implications for use of coarser fractionation schedules for treatment volumes that include the heart. The risk of cardiac damage could be significantly increased.

Animals↗
PubMed1985

The pathogenesis of radiation nephropathy in the dog.

Canine kidneys were biopsied at 2-week intervals from 3 to 13 weeks after a single 15-Gy dose of intraoperatively delivered 6 MeV electrons to determine the pathogenesis and dose-limiting tissue for radiation nephropathy. The data suggest that the dose and time after irradiation determine the dose-limiting tissue. The early functional survival of canine kidneys appeared to be dependent on parenchymal cell killing. Histologic changes in epithelial cells were seen as early as 3 weeks after irradiation. The parenchyma decreased to 50% of the preirradiation volume by 9 weeks but repopulated to near normal by 11 weeks. A second wave of depopulation, possibly due to perivascular fibrosis, was evident at 13 weeks. Previous investigators have demonstrated progressively extensive changes in renal vessels after irradiation. In this study, permanent vascular damage was seen at 3 weeks; however, most early changes in vessel walls proved to be temporary and probably resulted from atrophic vasoconstriction following parenchymal depopulation. Vessel dimensions returned to near normal as the parenchyma repopulated; however, a "histohematic barrier" created by progressively increasing perivascular fibrosis may cause a reduction in oxygen and nutrient support of the parenchyma and permanent loss of renal function.

Animals↗
PubMed1984

Idiopathic hemorrhagic pericardial effusion in eight dogs.

Idiopathic hemorrhagic pericardial effusion was diagnosed in 8 dogs. The patients were typically males of large or giant breeds and a wide age range was represented. In all dogs clinical features of acute or chronic cardiac tamponade and right-sided heart failure were present. The pericardial effusion in each case was identified by thoracic radiography, electrocardiography, and echocardiography. Cytologic examination of the fluid did not allow differentiation from hemorrhagic effusions caused by neoplasia. Bacterial and fungal cultures were negative in 5 dogs. In 6 cases, a presumptive diagnosis was based on the absence of cardiac masses on 2-dimensional echocardiography, contrast pericardiography, or both. The condition was managed successfully by partial pericardiectomy in 5 cases. The definitive diagnosis in each case was established by gross cardiac examination at surgery or necropsy and by histologic examination of tissues. Blood vessels and lymphatics of the parietal and visceral pericardia appeared to be the primary targets of the disease process.

Animals↗
PubMed1981

Extrahepatic biliary carcinomas in Asiatic bears.

Extrahepatic biliary carcinomas occurred in 2 Asiatic bears at the National Zoological Park in Washington, D.C. The tumors were associated with ascites in both cases and jaundice in 1 and metastasized widely. Neither bear had gallstones. Microscopically, the tumors were infiltrative, scirrhous adenocarcinomas that produced varying amounts of mucin. A genetic predisposition and change from the natural diet were factors proposed to contribute to the development of this neoplasm.

Animals↗
PubMed1978

Suppurative arthritis in an infant orangutan.

A 12-day-old male orangutan (Pongo pygmaeus) was removed from its mother because of oral ulcers and reluctance to suckle. Close examination revealed ulcerations extended to the mandibular bone. Staphylococcus aureus was cultured from the oral lesions. Despite intensive antibiotic therapy, the infection progressed to septicemia, with suppurative arthritis of the left coxofemoral and right radiohumeral joints. Treatment included removal of synovial exudate by aspiration, indwelling drains, and arthrotomy. Antibiotics were administered systemically and by joint irrigation. The infant responded well to the treatment, which lasted for approximately 2 months.

Ampicillin↗
PubMedDate not supplied

Hyperthermia induced pathophysiology of the central nervous system.

This review is focused on the pathophysiology of the central nervous system (CNS) associated with mild-to-moderate hyperthermia (body temperature > 37 degrees C but <40 degrees C) induced thermal stress in Human cases as well as whole body hyperthermia (WBH) in animal studies. Pathological changes can be observed in the nerve cells and glial cells in Humans following mild-to-moderate thermal exposure. On the other hand, morphological changes in the axons, nerve cells, glial cells and vascular endothelium is seen at the cellular and the molecular levels in rats subjected to heat exposure at 38 degrees C for 4 h (body temperature > 40 degrees C but <42 degrees C). This effect depends on the age of the animals and their prior thermal experiences. Taken together, heat stress induced hyperthermia, once believed to be non-toxic in the mammalian CNS, do produce specific alterations in the CNS that may have long-term behavioural, physiological and neuropathological consequences. The probable mechanism(s) underlying hyperthermia induced brain pathology is discussed.

Animals↗
PubMedDate not supplied

Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia.

This paper is one of several in this Special Issue of the International Journal of Hyperthermia that discusses the current state of knowledge about the human health risks of hyperthermia. This special issue emanated from a workshop sponsored by the World Health Organization in the Spring of 2002 on this topic. It is anticipated that these papers will help to establish guidelines for human exposure to conditions leading to hyperthermia. This comprehensive review of the literature makes it clear that much more work needs to be done to clarify what the thresholds for thermal damage are in humans. This review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature are provided as well as a detailed discussion about the underlying assumptions that go into these calculations. There are few in vivo papers examining the type and extent of damage that occurs in the lower temperature range for hyperthermic exposures (e.g. 39-42 degrees C). Therefore, it is clear that estimation of thermal dose to effect at these thermal exposures is less precise in that temperature range. In addition, there are virtually no data that directly relate to the thermal sensitivity of human tissues. Thus, establishment of guidelines for human exposure based on the data provided must be done with significant caution. There is detailed review and presentation of thermal thresholds for tissue damage (based on what is detectable in vivo). The data are normalized using thermal dosimetric concepts. Tables are included in an Appendix Database which compile published data for thresholds of thermal damage in a variety of tissues and species. This database is available by request (contact MWD or PJH), but not included in this manuscript for brevity. All of the studies reported are for single acute thermal exposures. Except for brain function and physiology (as detailed in this issue by Sharma et al) one notes the critical lack of publications examining effects of chronic thermal exposures as might be encountered in occupational hazards. This review also does not include information on the embryo, which is covered in detail elsewhere in this volume (see article by Edwards et al.) as well as in a recent review on this subject, which focuses on thermal dose.

Animals↗
PubMedDate not supplied

Intraoperative irradiation of 16 spontaneously occurring canine neoplasms.

Sixteen dogs with malignant neoplasms were treated with intraoperative radiation therapy after surgical debulking. Fractionated external beam radiation therapy was given postoperatively to 11 dogs. Healing of surgical incisions was uncomplicated in 14 dogs. When the ureters or urinary bladder were included in the irradiation field, they became stenotic and fibrotic. Urinary incontinence and secondary renal injury were common. Local tumor control was poor regardless of site or tumor type.

Animals↗
PubMedDate not supplied

The effect of air cooling on the radial temperature distribution of a single microwave hyperthermia antenna in vivo.

Canine skeletal muscle was heated with a single microwave antenna within a brachytherapy catheter driven at 2000 MHz. The radial, steady-state temperature distribution was measured with and without air cooling of the antenna, as produced by room temperature air flowing in the catheter at 7.5 l/min. The axial temperature distribution was also measured with air cooling. In the antenna junction plane the area heated to a given temperature increased by a factor of four with air cooling when the same antenna temperature was enforced. With the same maximum temperature enforced, the area would increase by a factor of 2.5 with air cooling. The axial temperature distribution was not compromised by air cooling.

Air↗
PubMedDate not supplied

Analysis and testing of a concentric ring applicator for ultrasound hyperthermia with clinical results.

A planar ultrasound transducer was modified by etching concentric circles on one surface of a piezoelectric ceramic to create four rings. The 10 cm diameter transducer had four active rings and an unenergized centre. The transducer housing was designed to be completely immersed in fluid, suitable for intraoperative hyperthermia. The transducer was resonant at 1.0 MHz and was tested in a water tank and in an acoustic absorbing medium where the steady-state temperatures were measured. A comparison between a single 10 cm element and the concentric ring modification with all rings at equal power density showed the performance to be nearly identical. In vivo experiments in canine thigh verified the phantom predictions as individual rings were energized. Theoretical intensity calculations were made and compared favourably to water tank test results. Clinical hyperthermia treatments for chest wall and head and neck tumours showed that the temperature distribution could be highly modified by adjusting the power to individual rings while holding the transducer stationary. Automated temperature mapping parallel to the transducer face was used to compare a single element applicator to the concentric ring applicator in clinical treatments on the same lesion. The concentric ring applicator was radially adjustable and was found to be advantageous in lowering the central peak temperatures and flattening the temperature distribution in tumours. A comparison between the single element clinical and operating room series showed that when pain is removed as a treatment limiting factor, higher central tumour temperatures are possible and more of the tumour volume achieves therapeutic temperatures. The concentric ring design improves the temperature distribution such that the higher central temperatures will not be necessary.

Evaluation Studies as Topic↗
PubMedDate not supplied

Pattern of response to interstitial hyperthermia and brachytherapy for malignant intracranial tumour: a CT analysis.

Interstitial microwave hyperthermia in combination with iridium-192 brachytherapy has been administered to 23 cases of malignant brain tumours in a phase one clinical trial to assess the feasibility and safety of this treatment. In order to quantify the acute and long-term response of tumour and surrounding brain to this treatment, a morphometric computed tomography scan analysis was performed in 18 evaluable patients. Volumes defined by the outer margin of the contrast-enhancing rim, by the hypodense necrotic region within the enhancing rim and by the surrounding hypodensity region were calculated from computer measurements. Hyperthermia equipment performance (HEP) was calculated for the evaluation of heating. After the treatments, the volume of the inner hypodensity region decreased in seven patients and the volume increased in 11 patients. In five patients, the outer margin of the contrast-enhancing lesion showed an initial increase in volume followed by a decrease and in these patients higher HEP and longer survival were observed significantly. The volume of the surrounding hypodensity region varied following treatments, but in most instances, the region subsequently increased in the interval immediately prior to death. Contribution of heat effect to these changes are discussed and the significance of aggressive heating, which provides transient opening of blood brain barrier, is shown.

Adult↗
PubMedDate not supplied

Performance of an adaptive MIMO controller for a multiple-element ultrasound hyperthermia system.

A prototype adaptive automatic control algorithm was implemented to regulate temperatures measured at several points in a tumour by adjusting the power applied to several ultrasound transducers. The goal was to control the temperatures under the elements of a mosaic applicator individually without any priori knowledge of which probes are under which elements. The control algorithm was devised for clinical applications where the position of each probe with respect to the heat sources is difficult to determine precisely. Instead, the program 'learns' the relationship between the inputs (power levels) and the outputs (temperatures) automatically. Based on the observed transfer function relating the power at m sources to the temperatures n probes, where n and m are not necessarily the same, a new method was used to implement a feedback controller. This method simplifies the design of the controller for a multiple-input/multiple-output (MIMO) system, while taking into account the coupling that may exist between the various elements of the system. As a result of using an adaptive scheme, the regulator continuously tracks changes in the system, such as blood flow variations or patient motion, by modifying its control parameters. The algorithm performance has been tested in simulations as well as experiments in dog thigh and a perfused kidney model.

Algorithms↗
PubMedDate not supplied

Effect of phase modulation on the temperature distribution of a microwave hyperthermia antenna array in vivo.

Perfused, canine skeletal muscle and the brain tumour of a cancer patient were heated with an array of four parallel, interstitial antennas placed on the corners of a 2-cm square and driven at 915 MHz. The temperature distributions along the axial and diagonal catheters were measured with equal-phase driving of the antennas and with several time-varying schemes of driving phase differences among the antennas. When equal-phase driving was replaced by a rotating scheme of 90 degrees driving phase differences, the tissue area in the junction plane heated above a normalized index temperature of 0.6 increased by a factor of about 1.25. With a rotating phase of 135 degrees, the same area increased by a factor of about 1.6. The axial temperature distribution was not affected significantly by driving phase.

Animals↗
PubMedDate not supplied

Initial in vivo experience with EIT as a thermal estimator during hyperthermia.

Thermal imaging experiments using electrical impedance tomography (EIT) have been conducted during hyperthermia treatments delivered to two human patients and one animal subject. Coplanar and circumferential arrays of 16 and 32 tin-plated copper electrodes etched on a 0.005" polyimide sheet were used to inject 12.5 KHz current patterns of increasing sinusoidal spatial frequencies and subsequent potential distributions were recorded at each electrode site. Image reconstruction was achieved with a finite element method and difference images of conductivity changes during the course of treatment were formed. An assumed linear relationship (2%/degree C increase) between tissue impedance change and temperature change was used to produce thermal images of the treatment field in patients whereas an empirically measured nonlinear relationship obtained from excised tissue samples was applied retrospectively in the animal subject case. Reconstructed conductivity changes are shown to be possible given electrical data measured in vivo during hyperthermia delivery with conventional equipment (spiral microstrip applicator at 433 MHz). These correlated well with direct temperature measurements and demonstrated quantitative levels of agreement to the extent that estimated temperature accuracies were approximately 1.5 degrees C; although large errors (> 5 degrees C) did exist. This work suggests that EIT is a potentially useful tool for hyperthermia treatment monitoring and assessment. The relationship between tissue impedance and temperature is complex and confounds the ability to make simple correlations between conductivity and temperature changes. Further, study is required to discern whether this will ultimately limit EIT as a thermal estimator or whether it will lead to more fundamental uses of impedance as an indicator of thermal effect.

Aged↗