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Biomedical subjects

R D Hamilton

Publications and source records attributed to R D Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1987

Drug sensitivity of ten human tumor cell lines compared to mouse leukemia (L1210) cells.

L1210 leukemia cells, because of their rapid growth rate in suspension culture and high growth fraction, are ideally suited to screen in vitro for cytotoxic compounds. Although L1210 cells may mimic rapidly growing tumors, they have not been effective in selecting agents active against slow growing solid tumors. We expected that cell lines originating from human solid tumors, because of their slower growth rate and lower S phase fraction, would be more drug resistant than L1210. Therefore, we compared ten human tumor cell lines (5 melanomas, 4 colon carcinomas and 1 small cell lung carcinoma) to L1210 growth inhibition by 9 antitumor drugs. Not one human tumor cell line was consistently more resistant to all nine drugs than L1210 when the cells were exposed to drugs for about 2 doubling times. The drug sensitivity of 2 cell lines (L1210 and SK MEL 28) was again determined after a short term (2 hr) exposure and using growth inhibition and cell survival as end points. For both end points these two cell lines exhibited a random pattern of sensitivity to the drugs tested. Cell kill showed an order of sensitivity different than growth inhibition. The implication of these findings for drug-screening is discussed.

Animals↗
PubMed1987

Blockade of 'alveolar' and airway reflexes by local anesthetic aerosol in dogs.

To determine whether local anesthetic aerosol could selectively block a reflex thought to originate from the alveoli, two small particle bupivacaine aerosols (mass median diameters 1.0 and 1.7 micron) were administered on separate occasions to spontaneously breathing anesthetized dogs. Both aerosols resulted in a small but statistically significant increase in VT and one produced an increase in f. The pulmonary chemoreflex to right heart injection of capsaicin, the cough reflex and the Hering-Breuer inflation reflex were unaffected. The ability of a large particle aerosol (mass median diameter 4.8 micron) to block these reflexes was also assessed. This aerosol produced a progressive slowing and deepening of breathing which was maximal after 20 min of aerosol inhalation. Ten min of this aerosol attenuated the pulmonary chemoreflex and abolished the cough and inflation reflexes; 20 min abolished all reflexes. These had recovered by about 1 h after aerosol. Intravenous bupivacaine had no effect on breathing or any reflex. We conclude that a local anesthetic aerosol can block reflexes arising from the alveoli, but not selectively.

Aerosols↗
PubMed1987

Aerosol anesthesia increases hypercapnic ventilation and breathlessness in laryngectomized humans.

The effect of local anesthetic aerosol inhalation on the ventilatory response and the sensation of breathlessness to CO2 rebreathing was studied in seven healthy male subjects with permanent tracheal stomas after laryngectomy for carcinoma. Inhalation of bupivacaine aerosol sufficient to abolish the cough reflex to mechanical probing below the carina increased the ventilatory response to CO2 in six of seven subjects compared with saline control. This was achieved by an increase in both respiratory frequency (f) and tidal volume (VT) in four subjects, f in one subject, and VT in one subject. All subjects reported that they were more breathless on rebreathing after bupivacaine aerosol. The six subjects who recorded breathlessness with a visual analog scale (VAS) indicated its onset at a lower minute ventilation (VE) and gave higher VAS scores for equivalent levels of VE after threshold. We conclude that the enhanced CO2 sensitivity and breathlessness on rebreathing after airway anesthesia results from altered lower airway receptor discharge.

Aged↗
PubMed1986

Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: evidence for pulmonary chemosensitivity.

The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 micrograms/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a 'raw, burning' feeling, occurred 3-4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 micrograms/kg) produced paroxysmal coughing 3.9 s after a central injection. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8 micron), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.

Bupivacaine↗
PubMed1986

Entry and competition in the home health care industry.

Home health care is the fastest growing segment in the health care industry today. This article provides an understanding of the home health industry and a template of analysis that can be applied to other industries of interest to the health care strategist. The Porter model is used as the basis of this analysis.

Economic Competition↗
PubMed1986

Strategic planning: a balanced view of a balanced portfolio.

The application of portfolio analysis to strategic planning in health care organizations is presented. The practical use of this approach is demonstrated through a case example. Advantages and disadvantages of the approach are delineated.

Hospital Planning↗
PubMed1985

The effect of airway anaesthesia on the control of breathing and the sensation of breathlessness in man.

The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 micron), was studied in 12 normal subjects. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal PCO2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

Adult↗
PubMed1985

Orally induced adjuvant-like arthritis in the rat.

Adjuvant-like arthritis was produced in Sprague-Dawley rats during 14 days of oral administration of 2-amino-5-bromo-6-(3-fluorophenyl)-4(3H)-pyrimidinone. Inflammatory changes about and in the hindlimb joints were similar to those described by Pearson for adjuvant-induced polyarthritis. Lymphoid hyperplasia, elevation of serum IgG levels, and localization of fluorescein-labeled globulin in disseminated inflammatory lesions implicate an immunologic effect. Rats treated twice weekly for 64 days developed lymphocytic thyroiditis and showed less inflammation in the joints.

Administration, Oral↗
PubMed1982

Comparison between circulating interferon and drug levels following administration of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) to different animal species.

Using a high-performance liquid chromatographic assay, these studies attempted to correlate circulating levels of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) with the serum interferon response induced in mice, cats, dogs, cattle, and rabbits. The order of greatest sensitivity for interferon induction by ABPP was mice greater than cats greater than dogs greater than cattle greater than rabbits. Experiments to date indicate that the circulating drug levels associated with a detectable interferon response were 10-15 microgram/ml (mice), 15-30 micrograms/ml (cats and dogs), and 30-50 micrograms/ml (cattle). Whereas rabbits produced large amounts (greater than 10(4) units/ml) of interferon when induced with Newcastle disease virus, we could not demonstrate unequivocally that rabbits were induced by ABPP even when circulating drug levels reached 50 micrograms/ml, or greater. We also observed differences in the pharmacokinetics of ABPP in the different species which may contribute to the differences described for the interferon responses. The data point out the need for cautious selection of animal models for preclinical efficacy evaluation and cautious extrapolation of data from preclinical studies to eventual clinical evaluation.

Administration, Oral↗
PubMed1980

Neurogenic respiratory failure: a 5-year experience using implantable phrenic nerve stimulators.

During the past 5 years, 20 phrenic nerve stimulators have been implanted in 11 patients who were ventilator dependent because of neurogenic respiratory failure. Ten patients had traumatic spinal cord lesions; the remaining patient suffered from a progressive demyelinating disease. There was no operative mortality. Complications included 1 stimulator malfunction and 1 pneumothorax. In spite of adjacent tracheostomies, there were no infections or wound complications. Of the 20 stimulators implanted, 13 initially produced good diaphragmatic function, 2 had fair function, and 5 had little or not function. Three patients became completely independent of their ventilators; 6 became partially independent, thus simplifying nursing care. There were no late complications. As of December, 1979, 7 patients had benefited or were continuing to benefit from phrenic nerve stimulation.

Adolescent↗
PubMed1980

Acquired hemophilia, meningioma, and diphenylhydantoin therapy.

A patient is reported in whom a meningioma of the lateral one-third of the sphenoid ridge was completely removed and long-term prophylaxis for seizures with diphenylhydantoin was prescribed. One and a half years later, a powerful inhibitor developed that specifically neutralized Factor VIII, the antihemophilic factor, and caused an acquired state of hemophilia. The 4-month hemorrhagic disorder was characterized initially by painless hematuria and later by intracerebral and extradural hematomas at the operative site of the previously excised meningioma. Despite the transfusion of massive quantities of concentrates of clotting factors, and the surgical evacuation of the recurrent hematomas on two occasions, the localized bleeding could not be staunched and the patient died. The types of inhibitors that cause acquired hemophilia and their modes of treatment are examined. Although it is possible that the Factor VIII inhibitor in this patient was induced by the meningioma, most previously reported tumors associated with acquired hemophilia have had an immunological basis. The most probable explanation for the acquired hemophilia in this patient was an inhibitor to Factor VIII from an autoantibody induced by the long-term use of diphenylhydantoin.

Factor VIII↗
PubMed1979

Bronchial reactivity in Western red cedar induced asthma.

A patient with Western red cedar induced asthma is described. The diagnosis was confirmed by a bronchial challenge with Western red cedar saw dust and the subsequent prolonged bronchial reactivity changes were measured using histamine inhalation tests.

Asthma↗