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Biomedical subjects

H E Ward

Publications and source records attributed to H E Ward.

At least 19 recordsLinked to original sources
PubMed1999

Depression in the medical setting: biopsychological interactions and treatment considerations.

This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Corticotropin-releasing factor and defensive withdrawal: inhibition of monoamine oxidase prevents habituation to chronic stress.

There is growing evidence for a role of extrahypothalamic corticotropin-releasing factor (CRF) in the pathogenesis of anxiety. A modified form of the defensive withdrawal test was used to test the anxiogenic effects of acute administration of intracerebroventricular (1 microg, i.c.v.) CRF in adult male rats. Habituation to the mild stress of daily handling and subcutaneous (s.c.) saline injection over 2-6 weeks abolished the anxiogenic effects of exogenous CRF. At 6 weeks this habituation also resulted in attenuation of baseline withdrawal behavior. CRF receptor binding was significantly decreased in the amygdala of chronically handled animals and may have been responsible for this habituation phenomenon. Comparison of rats treated with the monoamine oxidase (MAO) inhibitor, phenelzine [3 mg/kg, s.c., daily for 2-6 weeks] to the saline-treated groups revealed a failure to habituate to the chronic handling, as the baseline withdrawal (after injection of artificial CSF) by the phenelzine-treated animals was not different from the baseline withdrawal by unhandled rats. In comparison to rats treated chronically with saline, phenelzine treatment enhanced the anxiogenic effect of CRF. In summary, habituation to a mild chronic stress decreased baseline defensive withdrawal. Intraventricular administration of CRF produced an anxiogenic response as measured in the defensive withdrawal test, which was lost through exposure to mild chronic stress. Two or 6 weeks of daily handling and SC saline injection caused a downregulation of CRF receptors in the amygdala, which could account for the behavioral habituation and the loss of CRF-induced defensive withdrawal. Phenelzine treatment concurrent with mild chronic stress prevented habituation and maintained the anxiogenic effect of CRF in spite of the downregulation of CRF receptors in the amygdala.

Amygdala↗
PubMed1998

Psychiatric morbidity in endocrine disorders.

Psychiatric disturbances are frequently observed during the course of endocrine disorders. This article discusses the history, current knowledge, assessment, and treatment of psychiatric morbidity in endocrine disorders. The primary focus is on biologic links between psychiatric symptoms and endocrine dysfunction. Psychiatric disorders associated with abnormalities of the pituitary, thyroid, parathyroids, adrenals, and gonads are discussed as well as the chronic illness of diabetes mellitus.

Endocrine System Diseases↗
PubMed1997

Hyaluronan in radiation-induced lung disease in the rat.

We have used a previously described model of bilateral radiation-induced lung disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the role of hyaluronan in this process. Hyaluronan was measured in the bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma irradiation or sham irradiation. Four weeks after irradiation, during peak alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was in the intra-alveolar edema fluid but was not increased in the alveolar walls; hyaluronan, measured by high-performance liquid chromatography, also was not elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis (6 to 20 weeks). The administration of methylprednisolone significantly decreased the alveolitis, including the increase in hyaluronan in the alveolar space and serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of inflammation and cannot be used as a serum marker to predict the onset of radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does not appear to be a necessary precursor in the evolution of radiation fibrosis.

Animals↗
PubMed1995

Prenatal stress increases corticotropin-releasing factor (CRF) content and release in rat amygdala minces.

Corticotropin-releasing factor (CRF) is a neuropeptide found throughout the central nervous system that has a proposed role in modulating emotional and behavioral states, including stress and anxiety. The amygdala, which is important in the control of emotional and autonomic responses to stress, contains CRF nerve terminals, CRF cell bodies, and CRF receptors. In rats, exposure to prenatal stress results in offspring that display a hyperemotional state and increased anxiety. In this study the effects of prenatal stress on CRF release was measured in amygdala minces (1 mm3) obtained from adult (8-16 weeks of age) male offspring of dams subjected to daily saline injection (0.1 ml, s.c.) from gestational day 14 to 21. CRF release from amygdala was time- and calcium-dependent, and stimulated by KCl-induced depolarization. Depolarization-induced CRF release was significantly increased by 42% from the amygdala of prenatally stressed offspring versus controls. Prenatally stressed offspring also showed a 49% increase in CRF levels in the amygdala. The increased amounts of CRF released in response to depolarization were likely the consequence of increased tissue content of CRF, as fractional release under basal or KCl-stimulated conditions was not different in the prenatal stress group versus control. This suggests that a long-lasting up-regulation of the CRFergic neurotransmission may occur in the amygdala, which may be important in the generation of hyperemotional offspring after exposure to prenatal stress.

Amygdala↗
PubMed1993

The pulmonary response to sublethal thoracic irradiation in the rat.

An animal model of radiation-induced lung disease was established using male Wistar rats given sublethal bilateral thoracic irradiation (15 Gy). The rats were studied for up to 20 weeks and compared to sham-irradiated controls. Three distinct syndromes were identified. Two weeks after irradiation there was an increase in wet lung weight without an increase in dry lung weight. Interstitial edema was confirmed ultrastructurally, but aside from minor abnormalities of endothelial cells, both capillary and alveolar basement membranes were intact and there was no alveolar protein leak. At 4 weeks after irradiation, there was an abrupt increase in both wet and dry lung weights, as well as intra-alveolar macrophages, lymphocytes, polymorphs, and protein. These changes persisted for periods of up to 8 weeks. Electron microscopy at 4 weeks revealed prominent interstitial edema and severe endothelial cell damage. There was patchy thickening of the cytoplasm of type I cells as well as some cells which appeared to be transforming from type II to type I cells, suggesting previous epithelial denudation. Mast cell density increased in perivascular and peribronchial areas from 4 weeks, and this and parenchymal mast cell density peaked at 7 weeks. The total collagen content of the lungs (determined biochemically) rose by up to 50% above control values from 5 weeks after irradiation, the bulk of the increase having occurred by 12 weeks. Further increases up to 20 weeks were similar to that seen in growing control animals. Collagen deposition (as defined by electron microscopy and Picrosirius polarization) was prominent in peribronchial and perivascular areas in all animals, but in alveolar walls it was increased severalfold above controls by 20 weeks after irradiation. In summary, this model provides sequential changes of interstitial edema, alveolitis, and interstitial fibrosis which can be studied independently. The temporal relationship between the appearance of mast cells and increased collagen deposition supports the hypothesis that mast cells are intimately related to the development of fibrosis.

Animals↗
PubMed1993

The effect of steroids on radiation-induced lung disease in the rat.

We have used a model of bilateral radiation-induced lung disease in the rat to study the effects of corticosteroids. This model is characterized by interstitial edema at 2 weeks after radiotherapy followed by florid alveolitis with an alveolar protein leak which peaks at 4 weeks. Mast cell density peaks at 7 weeks, and there is a progressive increase in lung collagen (fibrosis) from 5 to 20 weeks. Intraperitoneal corticosteroids or saline were given at the time of irradiation or sham irradiation (protocol 1), every second day during weeks 3 and 4 (protocol 2), or three times weekly during weeks 3 to 8 (protocol 3). In protocol 1, steroids protected the lung from interstitial edema at 2 weeks, delayed the alveolitis without reducing its intensity, and significantly reduced the alveolar protein leak. However, radiation fibrosis was not reduced at 20 weeks. Longer steroid administration (protocol 2) suppressed the alveolar protein leak and delayed and significantly reduced the severity of the inflammatory cell response. Although the tissue mast cell and fibrotic responses were suppressed during and for at least 3 weeks after steroids, the ultimate fibrotic reaction was the same in both irradiated groups. In protocol 3, steroids suppressed the alveolitis and delayed the rise in tissue mast cell density, but did not affect the fibrotic response at 20 weeks. These studies suggest that steroids can suppress the alveolitis provided they are used throughout the period of alveolitis. Although they also delay the tissue mast cell response to radiation, the ultimate fibrosis is not altered. This provides further evidence for the dissociation of alveolitis and fibrosis after lung irradiation and has potential implications for management of radiation-induced lung disease in humans.

Animals↗
PubMed1993

Selenium deficiency augments the pulmonary toxic effects of oxygen exposure in the rat.

Selenium (Se) is a component of the antioxidant enzyme glutathione peroxidase (GSHPx). We wanted to determined whether Se deficiency predisposes to pulmonary O2 toxicity. Sixteen weanling rats were fed a Se-free diet (Se-). Sixteen rats fed the same diet had drinking water supplemented with 400 micrograms.l-1 sodium selenite (Se+). After 5 weeks, rats were killed after exposure to either 95% O2 or air for 36 h. Se concentration in blood, lung, liver, heart, muscle and spleen, and blood GSHPx activity were higher in Se+ than in Se- groups. Pulmonary oedema developed in both O2-exposed groups, but was more severe in Se-O2 group than in the Se+O2 group, as judged by the presence of pleural effusions (7 out of 8 versus 0 out of 8), elevated lavage protein concentration (173 +/- 17 versus 120 +/- 14 micrograms.ml-1), and higher wet/dry weight ratio (W:D) (5.8 +/- 0.07 versus 5.4 +/- 0.07). W:D correlated inversely with lung Se content in O2-exposed rats. Both O2-exposed groups had a reduction in the amount of less aggregated lavage phospholipid (PL) compared with the Se+air group. However, the Se-O2 group had increased total PL, because of an increase in more aggregated PL. We conclude that Se deficiency exacerbates pulmonary injury in O2-exposed rats, and that O2 toxicity is associated with an altered physical form of alveolar surfactant.

Animals↗
PubMed1992

Effect of artificial ventilation and anaesthesia on surfactant turnover in rats.

We have tested the hypothesis that breathing releases pulmonary surfactant via distortion of the alveolar type II cell. Gas exchange was maintained in the anaesthetized rat by applying high frequency (10 Hz) oscillations (HFO) to the chest wall; this resulted in apnoea within two to three breaths. After instrumentation under anaesthesia for 30 min, rats were infused with [3H]choline and [14C]choline, and we compared the tubular myelin-rich (PLalv-1) and -poor (PLalv-2) alveolar phospholipids and the microsomal and lamellar body phospholipids (PLlb) together with their specific activities after three forms of ventilation for 90 min: HFO (group 1), conventional mechanical ventilation (group 2) and spontaneous breathing (group 3). Group 4 was killed after surgical instrumentation and in group 5 the lungs were removed immediately after induction of anaesthesia. Groups 1-3 did not differ in any measured variable. Groups 1-4, which were anaesthetized for 30-120 min, had a lower PLalv-2 than did group 5. In contrast, PLlb was greater in groups 1-3, which were anaesthetized for 120 min, than in groups 4 and 5. In conclusion, we have successfully maintained normal gas exchange during complete apnoea by applying external HFO in rats for periods up to 90 min. Compared to mechanically ventilated or spontaneously breathing anaesthetized rats, surfactant turnover was unaltered by HFO, despite a markedly reduced tidal volume. However, the barbiturate anaesthetic itself appeared to inhibit surfactant turnover. We suggest that distortion of the type II cell may be the stimulus for surfactant release at tidal volumes above resting values.

Anesthesia↗
PubMed1991

Structure of a human pulmonary acinus.

The structure of the human pulmonary acinus has been described infrequently. The aim of the study was to determine the branching pattern of respiratory bronchioles and alveolar ducts in a human acinus from the peripheral part of the lung, where space constraints may have affected airway branching patterns. The lungs were obtained from an 18 year old victim of a motor vehicle accident and fixed in inflation under a pressure of 25 cm H2O. A block was cut from the lower edge of the right lower lobe and embedded in plastic. Serial sections were cut and the branching pattern of airways subtended by a terminal bronchiole were followed. The acinus was bounded on two sides by pleura and on the remaining sides by connective tissue septa. The terminal bronchiole divided into two respiratory bronchioles, each of which gave rise to four systems of alveolar ducts. Between successive systems of alveolar ducts the respiratory bronchioles continued as single airways, becoming progressively more alveolated towards the periphery but not subtending further branches of respiratory bronchioles. The duct systems became less complex towards the periphery, near to the edge of the lung. The total volume of the acinus was similar to that found in previous studies. This branching pattern has not been described previously in a human acinus.

Adolescent↗
PubMed1988

The effect of L-glutamic acid on airway function and reactivity in the rabbit.

The ingestion of monosodium glutamate in sensitive individuals has been reported to cause severe asthma. We therefore studied the effects of L-glu on airway function and histamine (H) responsiveness in the rabbit. Histamine dose response curves (HDR's) were performed by measuring total lung resistance (RL) after inhalation of saline and increasing concentrations of H (1-30 mg/ml). The concentration of H producing a 20% increase in RL (PC20H) was obtained by interpolation. To assess the effects of L-glu, 8 rabbits were infused with L-glu (0.2 g/kg/hr) or saline in random order (14 days apart) for 4 hours followed by an HDRC. To look at possible late effects, a repeat HDRC was also performed in 6 rabbits 12 hours after completion of the L-glu infusion. In order to see whether rabbits rendered hyperresponsive responded to L-glu, the above protocol was performed in 7 rabbits following the inhalation of 3 micrograms of the activated complement fragment C5a des Arg. The L-glu infusions increased the plasma levels approx. ten-fold (mean +/- SEM 0.119 +/- 0.012 base-line, 1.272 +/- 0.061 mmol/l post infusion). L-glu did not increase the PC20H or baseline RL in either the normal rabbits at 4 or 12 hours or in the C5a des Arg treated rabbits at 4 hours. It is concluded that L-glu does not cause bronchoconstriction or an increase in airway responsiveness to H in the rabbit.

Administration, Inhalation↗
PubMed1988

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.

Adult↗
PubMed1988

Deferoxamine infusion does not inhibit bleomycin-induced lung damage in the rat.

It has been proposed that the pneumonitis and subsequent lung fibrosis induced by bleomycin occurs when bleomycin is complexed with ferrous iron and oxygen. In order to see whether chelation of free iron reduced tissue damage induced by intratracheal bleomycin, deferoxamine (DFO) was administered by continuous subcutaneous infusion to overcome its rapid renal excretion. Thirty-three rats received DFO and 30 rats received an equivalent volume of saline by 7-day infusion pumps. Three days after commencement of infusion, half of each group received intratracheal bleomycin, the remainder received intratracheal saline. Three weeks after intratracheal injection, the rats were killed and their lungs were removed for histologic and morphometric assessment and collagen estimation. When compared with animals given intratracheal saline, both bleomycin-treated groups had significant evidence of lung toxicity, but DFO was not protective. Similarly, DFO infusion did not reduce the elevation in collagen concentration (bleomycin/saline, 49 +/- 3.6; bleomycin/DFO, 49.8 +/- 4.1; saline/saline, 39.6 +/- 3.9; saline/DFO, 43.4 +/- 3.8 mg.g-1 wet lung weight) or total lung collagen (bleomycin/saline, 29.9 +/- 6.3; bleomycin/DFO, 33.7 +/- 1.8; saline/saline, 15.5 +/- 2.2; saline/DFO, 17.8 +/- 1.9 mg.left lung-1) induced by bleomycin. This lack of effect was not due to iron contamination of the DFO in the pump or to loss of chelation capacity of DFO, at least for as long as 6 days after pump implantation. No DFO was detected in homogenized lung tissue (limits of detection of assay was 8 x 10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Failure of systemic N-acetyl cysteine to protect the rat lung against bleomycin toxicity.

In order to see whether systemically administered N-acetyl cysteine (NAC) could protect the lung from bleomycin lung injury, 24 rats were given a constant subcutaneous infusion of NAC (mean 195 mg.kg-1.day-1) for 7 days while 23 rats were given a similar volume of saline. Two days after the start of infusion, half of each group received an endotracheal injection of bleomycin and the other half received a similar volume of saline. All animals were killed 7 days after intratracheal injection and their lungs were prepared for wet-weight to dry-weight ratio (W:D) and morphometric assessment of histological changes. In animals given intratracheal saline, NAC infusion had no effect on weight gain, W:D or morphometry compared to those animals given saline infusions. However, all bleomycin-treated animals had obvious evidence of lung damage. Compared to either group of animals treated with intratracheal saline, the bleomycin-treated groups gained less weight (p less than 0.001), had a higher W:D (p less than 0.001) and an increase in the volume densities of alveolar and duct walls (p less than 0.001), intra-alveolar cells (p less than 0.05) and consolidation (p less than 0.001). There were no significant differences between the two bleomycin-treated groups in any parameter measured. It is concluded that administration of NAC by a constant subcutaneous infusion was not protective against bleomycin lung injury.

Acetylcysteine↗
PubMed1985

Ventilation by external high-frequency oscillation in cats.

Eight anesthetized tracheostomized cats were placed in an 8.2-liter airtight chamber with the trachea connected to the exterior. Thirty-two combinations of high-frequency oscillations (HFO) (0.5-30 Hz; 25-100 ml) were delivered for 10 min each in random order into the chamber. Arterial blood gas tensions during oscillation were compared with control measurements made after 10 min of spontaneous breathing without oscillation when the mean arterial PCO2 (PaCO2) was 30.1 Torr. Ventilation due to spontaneous breathing (Vs) and oscillation (Vo) were derived from the chamber pressure trace and a pneumotachograph, respectively. As the oscillation frequency increased, oscillated tidal volume (Vo) decreased from a mean of 39 (0.5 Hz) to 3.3 ml (30 Hz) when 100 ml was delivered to the chamber. From 6-25 Hz, apnea occurred with Vo less than estimated respiratory dead space (VD); the minimum effective Vo/VD ratio was 0.37 +/- 0.05. Although Vo was maximal at 10 Hz at each oscillation volume, the lowest PaCO2 occurred at 2-6 Hz, and arterial PO2 rose as expected during hypocapnia. Above 10 Hz, PaCO2 was determined by Vo and was independent of frequency, whereas at lower frequencies, PaCO2 was related to Vo; below 6 Hz, PaCO2 varied inversely with the calculated alveolar ventilation. As oscillations became more effective, both PaCO2 and Vs fell progressively and were highly correlated; apnea occurred when PaCO2 was reduced by a mean of 4.5 Torr. Mean chamber pressure remained near zero up to 15 Hz, indicating functional residual capacity did not change. We conclude that externally applied HFO can readily maintain gas exchange in vivo, with Vo less than VD at frequencies over 2 Hz.

Animals↗
PubMed1984

Alveolar type I and type II cells.

The alveolar epithelium comprises two main cell types: the alveolar type I and alveolar type II cell. The type I cell is a complex branched cell with multiple cytoplasmic plates that are greatly attenuated and relatively devoid of organelles; these plates represent the gas exchange surface in the alveolus. On the other hand, the type II cell acts as the "caretaker" of the alveolar compartment. It responds to damage of the vulnerable type I cell by dividing and acting as a progenitor cell for both type I and type II cells. In addition, it synthesises, stores and releases pulmonary surfactant into the alveolar hypophase, where it acts to optimise conditions for gas exchange.

Animals↗