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F Hamilton

Publications and source records attributed to F Hamilton.

53 records · Page 3Linked to original sources

The effect of alveolar hypoxia on pulmonary vascular responsiveness in the conscious newborn lamb.

To determine the effect of alveolar hypoxia and consequent increased pulmonary vascular tone on the responsiveness of the neonatal pulmonary circulation, we studied the local pulmonary vascular effects of acetylcholine, bradykinin, and histamine in the normoxic and hypoxic newborn lamb. Right and left pulmonary flows were continuously monitored from chronically implanted electromagnetic flow probes, agents were injected into only one lung, and changes in the proportion of pulmonary blood flow directed to the injected lung (Qinj/QT) provided a measure of active local pulmonary vascular constriction or dilation. At maximally tolerated doses, hypoxia enhanced the dilatory effects of acetylcholine and diminished the constrictor effects of histamine but hypoxia had a minimal effect on the maximal dilatation induced by bradykinin. Hypoxia did appear to lower the threshold dose for bradykinin's effects. These results demonstrate that base-line conditions may qualitatively alter the responsiveness of the neonatal pulmonary circulation to several drugs. In these agents, increased base-line tone generally augmented dilatory effects and diminished constrictor effects. However, the lack of such an effect on the dilator response to a high dose of bradykinin suggests the possibility that hypoxic-induced changes in pulmonary vascular responsiveness may not be entirely passive. Further, these results do not support the hypothesis that hypoxic-induced vasoconstriction is mediated by decreased production of bradykinin.

Acetylcholine↗

Direct pulmonary vascular responses in the conscious newborn lamb.

Electromagnetic flow probes were placed around the right and left pulmonary arteries (RPA and LPA) of nine newborn lambs. Preliminary in vitro and in vivo experiments delineated the accuracy and limitations of this method of flow measurement and the value in vivo of a balloon occlusive zero. Six to nine days after surgery, catheters were placed in the aorta and a branch pulmonary artery permitting simultaneous measurements of RPA and LPA flow, pulmonary arterial pressure, and aortic pressure. Vasoactive agents were injected into one lung, and a shift in blood flow distribution reflected direct active vasoconstruction or vasodilation in that lung. With a normal arterial oxygen tension, acetylcholine had no direct effect on the pulmonary vessels, but indirectly lowered pulmonary resistance via its systemic effects. Histamine was a potent direct pulmonary vasoconstrictor, bradykinin was a weak direct dilator, norepinephrine was a direct constrictor, prostaglandin E1 was a direct dilator, and prostaglandin F2a was a direct constrictor. These results demonstrate the feasibility of isolating the direct pulmonary vascular effects of certain pharmacologic agents using a double pulmonary artery flow probe preparation, agents using a double pulmonary artery flow probe preparation, without the use of anesthetics or extracorporeal perfusion circuits.

Acetylcholine↗

The establishment of continuous macrophage cell lines from peripheal blood monocytes.

Peripheral blood monocytes were established in cultured from ten different animal species. Using a method of repeated medium changes, monolayers of cells developed from seven of these species. These cells had the following characteristics: they were glass and plastic adherent, phagocytic, possessed many vacuoles and pseudopodia, esterase-positive, exhibited complement and Fc receptors and could partake in antigen-specific immune induction of T cells. These characteristics classify the cells as macrophages. The monolayers could be serially passaged and used for virological and immunological assays.

Animals↗

The pulmonary vascular effects of three prostaglandin I2 analogs in conscious newborn lambs.

Pulmonary and systemic vascular effects of three stable prostaglandin (PG) I2 analogs were studied in normoxic and hypoxic conscious newborn lambs. The three agents were : (5E)-6a-carba-PGI2 (analog I); 9-deoxy-9 alpha, 6-nitrilo-PGF1 hydrochloride (analog II); and (2E,5S)-9-deoxy-5,9 alpha-epoxy-13,14-dihydro-delta 1-PGF1 (analog III). Each component was injected into either a branch pulmonary artery or the ascending aorta. Locally induced alterations in pulmonary vascular tone were assessed from changes in the ratio of blood flow to the injected lung over total flow (delta Qinj/Qt). Each compound was a systemic vasodilator, with thresholds from 1 to 3 micrograms/kg. However, analog III was without local pulmonary vasoactivity, and analog I was a pulmonary vasodilator only at the highest dose used (30 micrograms/kg) and in hypoxic lambs. Analog II, in contrast, was a pulmonary vasodilator in both hypoxic (threshold = 3 micrograms/kg) and normoxic (threshold = 10 micrograms/kg) lambs. Moreover, only analog II mimicked PGI2 during hypoxia by decreasing vascular resistance in the injected lung more than systemic resistance. These results demonstrate that PGI2 analogs are vasodilators with variable activity on the pulmonary and systemic circulations of the newborn lamb. Of the three analogs tested, only analog II resembles PGI2 in being more specific for the pulmonary as opposed to the systemic circulation. Analog II, however, is less active than PGI2 in this regard.

Animals↗

The replication of virulent and attenuated strains of African swine fever virus in porcine macrophages.

The replication of virulent and attenuated strains of African swine fever virus (ASFV) was studied in pure cultures of swine macrophages. To ensure complete destruction of the macrophage monolayers about 50--100 times more virulent ASFV was needed than attenuated virus although both isolates could be used to establish persistently infected cultures. Interferon did not appear to influence virus yields from such cultures. Fluorescent and electron microscopy studies of infected macrophages suggested that the cycle of infection of the two isolates was different.

African Swine Fever Virus↗

Pulmonary and systemic vascular responses to 6-keto-PGE1 in the conscious lamb.

6-Keto-PGE1 is a potent direct dilator of the pulmonary and systemic circulations of the newborn lamb under both normoxic and hypoxic conditions. Its threshold dose is similar to that of PGI2 and PGE1. Under hypoxia, 6-keto-PGE1 appears equally effective on the pulmonary and systemic circulations, while under normoxia it predominantly affects the systemic circulation.

Alprostadil↗

African swine fever virus replication in porcine lymphocytes.

Purified preparation of porcine lymphocytes were infected with three isolates of virulent African swine fever virus (ASFV). Electron microscopy showed the presence of small numbers of mature virus particles in degenerating cells. The titres of infective virus released were low and reached a maximum by 24 h after infection.

African Swine Fever Virus↗

Lysosomes in the pathogenesis of the renal necrosis of choline-deficient rats.

Previously published data from our laboratories led us to postulate that alterations in lysosomes may play a cardinal pathogenic role in the fatal renal necrosis of choline-deficient weanling rats. To explore this hypothesis further a series of five different experiments were carried out. In the first two experiments the effect of a "stabilizer" of the lysosomes, hydrocortisone, was studied; conversely, in the third and fourth experiments, the effect of a "labilizer," vitamin A, was studied. Finally, in the fifth experiment, the renal levels of a lysosomal enzyme, acid phosphatase, were evaluated biochemically. Results of the first two experiments revealed a protective effect of hydrocortisone while those of the third and fourth an aggravating effect of vitamin A. Results of the fifth experiment indicated lysosomal changes in the prenecrotic and early necrotic stages. These results along with those from our previous studies, support the concept that lysosomal alterations play an important pathogenic role in renal changes of choline-deficient weanling rats.

Acid Phosphatase↗

Capitation and insurance protection: how to protect against unpredictability.

Capitation contracting has created new challenges in the world of health care. The payment emphasis in a capitated environment concentrates on prepayment of services. Opportunities are created to control health care dollars by the physician or hospital group, but the potential downside must also be recognized. This article introduces the Provider Excess Loss (or "stop loss") insurance product and some of the main features of coverage. This insurance is specifically designed to protect providers in a capitated environment and is purchased by Physician Hospital Organizations (PHO), Independent Physician Associations (IPA), and physician-owned HMOs, among others. The emphasis is on collective purchasing. Focus on the main policy features-deductible options, allowable charges, and premium factors-should ensure a basic understanding of how coverage works and how to design coverage to make it fit the unique needs of each provider's risk.

Capitation Fee↗

Neonatal autoperfused working heart-lung preparation: assessment of factors determining survival.

The function and survival of the autoperfused working heart-lung preparation in the newborn period was studied in six newborn pigs (3 to 5 days old). Normothermic autoperfusion was maintained by a closed blood-primed circuit. Left ventricular afterload was determined by positioning the blood reservoir, and the venous return was adjusted to maintain a right atrial pressure of 6 to 8 mm Hg. Left ventricular function was assessed by a conductance catheter in the left ventricle and was determined by the slope of the end-systolic pressure-volume relationship. Left ventricular diastolic compliance was measured from the end-diastolic pressure-volume relationship. Serial measurements at 60, 120, 180, and 240 minutes showed no change in the end-systolic pressure-volume relationship, whereas there was a significant leftward shift of the end-diastolic pressure-volume relationship after 240 minutes (0.42 +/- 0.02 ml-1 to 0.66 +/- 0.04 ml-1, p less than 0.05). Cessation of effective cardiac function occurred at 268 +/- 10 minutes (+/- SEM). This followed progressive deterioration in pulmonary function based on measurement of arterial blood gases and peak airway resistance. This study shows the feasibility of maintaining systolic cardiac function in a newborn autoperfused working heart-lung preparation. Extended survival beyond 4 hours will require improved methods to preserve left ventricular diastolic function and especially pulmonary function.

Animals↗