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Biomedical subjects

K A Hardy

Publications and source records attributed to K A Hardy.

At least 19 recordsLinked to original sources
PubMed1996

Noninvasive clearance of airway secretions.

Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases or airway malacia. Use of positive pressure to maintain airway patency in these children allows cephalad clearance of secretions. Patients with segmental atelectasis, particularly related to asthma, may benefit from intrapulmonary percussive ventilator, positive expiratory pressure, or PDPV. Prevention of postoperative atelectasis is particularly well suited to positive expiratory pressure, which is not as painful as techniques using oscillations. Neurologically abnormal patients who are unable to cooperate with any active method are also treated using intrapulmonary percussive ventilator, PDPV, and suctioning, if necessary. Musculoskeletal abnormalities, muscular dystrophies, myasthenia gravis, poliomyelitis, or other similar diseases require stabilization of bellows function. Optimizing ventilation in patients with such abnormalities may require positive pressure ventilation either during sleep or continuously. Externally applied pressure, such as with the In-Exsufflator or the cyclically inflated pneumatic belt, can augment the patient's own efforts and is sometimes helpful. Normalizing the vital capacity and functional residual capacity typically helps to improve the ability to cough and clear secretions. Assisted cough devices or maneuvers are described in other papers by Bach and Hill. Not all patients who have weak muscles require nocturnal or continuous support, and may benefit from positive expiratory pressure mask treatments. Further studies are sorely needed for this population. Long-term controlled trials are urgently needed to help establish the best types of treatment for patients with CF and bronchiectasis. Such studies will become more complicated by the introduction of new treatments, such as DNase and other therapies that alter secretions, and may begin to change mucociliary or cough clearance. The selection of appropriate outcome measures is central to studying these questions, and it is unclear which are the most important. (ABSTRACT TRUNCATED)

Drainage↗
PubMed1994

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.

Animals↗
PubMed1994

Experimental simulation of proton space radiation environments: a dosimetric perspective.

Three-dimensional dose calculation techniques developed for radiotherapy treatment planning were used to calculate dose distributions from unidirectional, planar rotational and omnidirectional incident radiation (experimental proton beams and solar flares). The calculations predicted regions of high dose within primate heads exposed to 55-MeV protons, supporting the postulate of radiation-induced brain tumors within this population. Comparisons among predicted doses to the human head from solar flares of three different energies demonstrated differences between unidirectional and omnidirectional irradiation in the space environment. The results can be used to estimate dose distributions based on a) limited phantom measurements, or b) nonuniformly incident radiation in orbit; both situations are difficult to replicate under laboratory exposure conditions.

Animals↗
PubMed1991

A review of the USAF/NASA proton bioeffects project: rationale and acute effects.

Ionizing radiation represented one of the important hazards facing the first manned lunar mission. A combined USAF/NASA project was conducted from 1963 through 1969 to estimate the relative biological effectiveness (RBE) of the radiations of space. Approximately 2000 primates (Macaca mulatta) and 5000 mice were irradiated with protons and electromagnetic radiations. The proton energies studied were selected to be representative of the proton spectrum in space. Much of the project was concerned with the use of cyclotrons for proton irradiations and with dosimetry. Biological measurements included clinical findings, physiological changes, hematological changes, histopathology, and mortality. When allowance was made for variation of response as a consequence of depth-dose distribution, the RBE for protons was approximately 1. This was anticipated from earlier theoretical studies and radiation therapy in humans with high-energy charged-particle beams.

Acute Disease↗
PubMed1991

Dosimetry methods used in the studies of the effects of protons on primates: a review.

In a program to determine the acute and long-term effects of the space radiation environment, a series of primate irradiations was conducted from 1964 through 1969 by the USAF School of Aerospace Medicine. The animals were exposed total-body to protons, electrons, and X rays. The doses assigned were either body midline or body entrance geometrically averaged across the exposure field depending on the degree of penetration (total or partial body) of the radiation used. A 10-cm-diameter unit-density cylinder was used as an appropriate model for the animal in the determination of the body doses. The physical dosimetry methods used at the time of the irradiations are reviewed.

Animals↗
PubMed1990

Pediatric pulmonary disease: assessment with high-resolution ultrafast CT.

High-resolution computed tomography (HRCT) is widely used to assess pulmonary parenchymal disease in adults. The authors used ultrafast CT with 3-mm collimation and a 100-msec scan time to obtain HRCT scans in 36 children (mean age, 49.4 months). Clinical diagnoses included normal lungs (n = 6), cystic fibrosis (n = 12), obliterative bronchiolitis (n = 6), idiopathic pulmonary hemosiderosis (n = 2), and other lung diseases (n = 10). The HRCT scans and chest radiographs were reviewed separately in blinded fashion. Pulmonary parenchymal abnormalities were categorized into interstitial, airspace, and airway processes. Nine patients with normal chest radiographs had abnormal HRCT scans. In five other patients, the extent of abnormal lung parenchyma was considerably greater on HRCT scans than on chest radiographs. HRCT scans allowed accurate characterization of the type of lung process in 24 of 30 patients when compared with clinical or biopsy findings. Early HRCT findings in cystic fibrosis included lobular air trapping, bronchial wall thickening, and centrilobular nodules. The use of cine CT with high-resolution techniques is feasible in children too young or too sick to hold their breath. HRCT may enable early detection and characterization of pulmonary disease and depiction of the extent of lung abnormality.

Bronchiolitis Obliterans↗
PubMed1989

Mechanics and energetics of breathing in newly diagnosed infants with cystic fibrosis: effect of combined bronchodilator and chest physical therapy.

Response to bronchodilator (BD) and chest physical therapy (CPT) was evaluated in newly diagnosed infants with cystic fibrosis (n = 13; age, 6.9 +/- 1.5 SE months) who were asymptomatic for lung disease at the time of the study. Lung function was assessed from the mechanics and energetics of breathing prior to and following combined BD and CPT. After therapy, respiratory rate, tidal volume, minute ventilation, and pulmonary compliance were not statistically different from values under baseline conditions. In contrast, there was a significant decrease in pulmonary resistance (-34%; P less than 0.05) and the resistive work of breathing (-26%; P less than 0.05) following the combined treatment. The effect of combined BD and CPT in decreasing the resistive respiratory load may be related to relief of subclinical bronchospasm, reduction in mucosal edema, and mobilization of mucous secretions.

Bronchodilator Agents↗
PubMed1988

Obliterative bronchiolitis in children.

Clinical, radiologic and histologic features of obliterative bronchiolitis (OB) in children were reviewed to define features helpful in early recognition. All autopsies (n = 2,897), lung biopsies (n = 244), and medical records of children followed at St. Christopher's Hospital for Children (SCHC) between 1960 and 1985 were screened. Nineteen cases of OB were confirmed using radiologic and histologic criteria. Twelve patients were diagnosed during life, and ten survived. Seven were diagnosed post mortem. OB should be considered when persistent respiratory signs and symptoms follow acute pneumonia, aspiration is known or suspected, areas of hyperlucency are seen on chest radiograph, or respiratory failure with overaeration is unresponsive to therapy. Diagnostic studies include ventilation-perfusion scan, bronchography and lung biopsy. Sequelae include dyspnea on exertion, obstructive lung disease, bronchiectasis, persistent atelectasis, and hyperlucent lung syndrome. Recognition and supportive treatment during the acute and chronic phases may improve the functional status of these patients.

Adolescent↗
PubMed1987

Evaluation of domperidone as a modifier of gamma-radiation-induced emesis.

The D2 antidopaminergic drug domperidone was evaluated, singly and in combination with synthetic adrenocorticoid and an H2 antihistamine, for its ability to reduce the acute emetic effects of 60Co whole-body radiation. Random-source adult male dogs were fasted 12 hr, fed a standard meal, injected 44 min later, and irradiated 47 min after that. Four groups of dogs were irradiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim + Thi), and dexamethasone + domperidone + cimetidine (Dex + Dom + Cim). Drug quantities given the dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 kg, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset and offset times and number of episodes were recorded. The Dom group had more emetic episodes than any other. The Dex + Dom + Cim combination significantly raised the emetic threshold while maintaining episodes at a low incidence.

Animals↗
PubMed1986

Occurrence of brain tumors in rhesus monkeys exposed to 55-MeV protons.

Twenty-year observation of monkeys exposed to single doses of high energy protons simulating solar particles revealed that the most prevalent fatal cancers were brain tumors in the group of animals exposed to 55-MeV protons. Of 72 animals (50 males and 22 females) receiving 0.25 to 8.0 Gy total body surface dose, nine developed fatal tumors classified as grade IV astrocytoma or glioblastoma multiforme. The latent period for tumor development ranged from 14 months to 20 years, with a median of 5 years. Doses associated with the tumors were 4.0 to 8.0 Gy. Eight males and one female were affected. Depth-dose determinations suggest that the high incidence of cerebral neoplasia is associated with the Bragg Peak energy distribution of the 55-MeV protons. Comparison of the tumor incidence with that in humans with brain exposures incidental to radiotherapy indicates a high biological effectiveness compared with gamma radiation. Studies are in progress to attempt to replicate the results in rodents and establish a dose-response curve for proton-induced brain tumors.

Animals↗
PubMed1986

Animal studies of life shortening and cancer risk from space radiation.

The U.S. Air Force study of the delayed effects of single, total body exposures to simulated space radiation in rhesus monkeys is now in its 21st year. Observations on 301 irradiated and 57 age-matched control animals indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be expressed as a logarithmic function of the dose. The primary causes of life shortening are cancer and endometriosis (an abnormal proliferation of the lining of the uterus in females). Life shortening estimates permit comparison of the risk associated with space radiation exposures to be compared with that of other occupational and environmental hazards, thereby facilitating risk/benefit decisions in the planning and operational phases of manned space missions. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.

Animals↗
PubMed1986

Pseudomonas cepacia in the hospital setting: lack of transmission between cystic fibrosis patients.

Possible mechanisms of transmission of Pseudomonas cepacia in hospitalized patients with cystic fibrosis were examined. Twelve patients were colonized with P. cepacia prior to admission (group 1), and 15 patients were not (group 2). Daily contact occurred between both groups. Sputum cultures were obtained from all patients at admission and discharge, and 3 and 6 months after discharge in group 2 patients. Environmental cultures included cough plates, settle plates, spirometry tubing, stethoscopes, sinks, wall outlets, and hands of patients, physicians, nurses, and respiratory therapists. Specimens were plated on a P. cepacia-selective medium. All group 1 patients remained colonized with P. cepacia at discharge. None of the group 2 patients acquired P. cepacia during hospitalization or follow-up. P. cepacia was recovered from three of 151 environmental cultures; two of these were presumably patient related. P. cepacia contamination of pulmonary function equipment, wall outlets, hands, and stethoscopes was not documented. We conclude that transient aerosol environmental contamination is uncommon and restricted to the immediate patient environment.

Adolescent↗
PubMed1985

Pseudomonas cepacia colonization in patients with cystic fibrosis: risk factors and clinical outcome.

During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christopher's Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome.

Adolescent↗
PubMed1985

Performance following a 500-675 rad neutron pulse.

A three-light, three-lever discrete avoidance behavioral task was initiated to study the effects of a 500-675 rad neutron pulse upon performance. Eight primates performed the task for 4 h (3.5 h postexposure) on exposure day and for 4 h on each of 3 d postexposure. For the exposure day, five subjects had a decrease in correct responses, seven had increased reaction times, and six experienced productive emesis within 3.5 hours postexposure. Although the performance degradations were not severe, these data suggest that the performance of time critical tasks could be significantly impaired.

Animals↗
PubMed1985

Retrograde amnesia produced by electron beam exposure: causal parameters and duration of memory loss.

The production of retrograde amnesia (RA) upon electron beam exposure has been investigated. RA production was evaluated using a single-trial avoidance task across a 10(4) dose range for 10-, 1-, and 0.1-microsecond pulsed exposures. The dose-response curve obtained at each pulse duration showed significant RA production. The most effective dose range was 0.1-10 rad at a dose rate of 10(6) rad/sec. By employing a 10 rad (10(6) rad/sec) pulse, a memory loss of the events occurring in the previous 4 sec was demonstrated. The conclusion was that the RA effect might be due to sensory system activation which provided a novel stimulus that masked previous stimuli.

Amnesia↗
PubMed1984

In utero exposure to microwave radiation and rat brain development.

Timed-pregnancy rats were exposed in a circular waveguide system starting on day 2 of gestation. The system operated at 2,450 MHz (pulsed waves; 8 microseconds PW; 830 pps). Specific absorption rate (SAR) was maintained at 0.4 W/kg by increasing the input power as the animals grew in size. On day 18 of gestation the dams were removed from the waveguide cages and euthanized; the fetuses were removed and weighed. Fetal brains were excised and weighed, and brain RNA, DNA and protein were determined. Values for measured parameters of the radiated fetuses did not differ significantly from those of sham-exposed fetuses. A regression of brain weight on body weight showed no micrencephalous fetuses in the radiation group when using as a criterion a regression line based on two standard errors of the estimate of the sham-exposed group. In addition, metrics derived from brain DNA (ie, cell number and cell size) showed no significant differences when radiation was compared to sham exposure. We conclude that 2,450-MHz microwave radiation, at an SAR of 0.4 W/kg, did not produce significant alterations in brain organogenesis.

Animals↗
PubMed1984

Prevention of radiation emesis in dogs by combinations of drugs.

Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H2 antihistamine, Pro as an H1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were: 167 mg/m2 i.v. for Cim; 13.9 mg/m2 i.m. for Pro; and 5.6 mg/m2 i.m. for Thi. These doses were calculated on a mg/m2 basis to approximate doses for an average human (1.8 m2) of 300 mg Cim, 25 mg Pro, and 10 mg Thi. Exposure was to 60Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED50) was calculated using an up-and-down procedure. The ED50 (95% confidence limits) were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi.

Animals↗