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Biomedical subjects

J B Forrest

Publications and source records attributed to J B Forrest.

At least 37 records · Page 2Linked to original sources
PubMed1989

Autoradiographic study of smooth muscle cell proliferation in spontaneously hypertensive rats.

1. The rate of smooth muscle cell proliferation in age-matched 1-4-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was compared using autoradiography. 2. Labelling index, defined as labelled cells/sum of labelled and unlabelled cells x 1000, was obtained from perfusion-fixed superior mesenteric and large mesenteric arteries. 3. In the large mesenteric arteries, the smooth muscle cell labelling indices were similar between the SHR and WKY at all age groups, except at 1 week of age when the smooth muscle labelling index was higher in the SHR. 4. In the superior mesenteric arteries, labelling indices were similar between the rat strains at all age groups. 5. We conclude that, in the SHR, a rapid proliferation of smooth muscle cells in the large mesenteric arteries occurred during the first week of life. This resulted in a higher number of smooth muscle cell layers in the media of muscular arteries. 6. The increased proliferation may play a role in the subsequent development of hypertension in the SHR.

Animals↗
PubMed1989

Comparative pulmonary mechanics in the horse and the cow.

Pulmonary mechanics and lung volumes were measured in horses and cows to determine if differences in breathing pattern between the two species were due to differences in the mechanical properties of the lungs. Tidal volume (VT) was larger in the horses, while the respiratory rate (fR) and minute ventilation (VE) were higher in the cows. The horses often had a double peak in airflow during inspiration and, or, expiration, while the cows had a single peak during expiration. Measured lung volumes were larger in the horses and they had a higher dynamic lung compliance (Cdyn,L), although the static compliance of the lung, chest wall and respiratory system (Cst,L,Cst,w and Cst,rs respectively) did not appear to differ between the two species. The cows had a greater change in maximum transpulmonary pressure (delta PLmax) and an increased nonelastic work of breathing (Wb). However, the pulmonary resistance (RL) did not differ between the two species, thus the higher delta PLmax and Wb in the cows were most likely a function of their higher flow rates. Calculations of the rate of work of breathing (W) indicate that both species breathed at an fR above the minimum W. The fR in the horses was close to the fR predicted for the average minimum muscle force, but the fR in the cows was higher. As the differences in the mechanical properties of the lung do not explain the differences in flow pattern, nor adequately account for the higher fR in the cows, it is suggested that the differences in breathing pattern between the two species is due to differences in the chest wall, particularly the size and shape of the abdomen.

Animals↗
PubMed1989

Comparative ventilation and gas exchange in the horse and the cow.

Ventilation and gas exchange were studied in healthy, adult horses and cows, two large species with different lung structures and different breathing patterns. The oxygen uptake (VO2), carbon dioxide output (VCO2), respiratory rate (fR), minute ventilation (VE), alveolar ventilation (VA), alveolar oxygen pressure (PAO2), and VE/VO2 ratio were higher in the cows, while the tidal volume (VT) and physiological dead space (VD) were larger in the horses. The arterial blood gases, alveolar-arterial oxygen pressure difference (PAO2-PaO2) and VD/VT ratio did not differ between the two species. The higher VO2 in the cows was most likely due to the energy cost of standing, and possibly to a higher cost of digestion. The higher VE, VA, VE/VO2 and PAO2 were most likely secondary to the increased VO2 and the slightly higher respiratory exchange ratio (R) in the cows. In contrast to hypotheses based on allometric equations, the PAO2 of horses and cows did not appear to differ from that of smaller mammals. The VD was larger than that predicted from allometric equations, and even though the VD/VT ratio (0.50) was lower than the previously reported values for horses and cows, it was significantly larger than the predicted weight-independent value of 0.36. Re-examination of the data used to derive the equation for VD raised questions as to the validity of this equation, and it is suggested that caution be exercised in the use of allometric equations for prediction.

Animals↗
PubMed1988

Structural and reactivity alterations of the renal vasculature of spontaneously hypertensive rats prior to and during established hypertension.

The renal vasculature of Wistar Kyoto spontaneously hypertensive rats (SHR), prior to (4-5 week) and during established hypertension (21 week) and those of age-matched Wistar Kyoto normotensive rats (WKY) were morphometrically and pharmacologically studied. Under dilated conditions, the vascular resistances (RVR) of the isolated kidneys of young and adult SHR were similar to WKY. Morphometric measurements of renal vasculature indicated that the cross-sectional area of the intima and adventitia and its subcomponents were similar in adult SHR and WKY. With the exception of the preglomerular arterioles, all the renal arteries of adult SHR exhibited elevated cross-sectional quantities of total media, medial smooth muscle cells (SMCs), and extracellular space. Analysis of the SMCs indicated the presence of increased numbers of SMC layers and/or an increase in the SMC volume-to-surface area ratio in arteries sampled from adult SHR. Vascular contraction produced by infusing norepinephrine, BaCl2, angiotensin II, or by stimulating the renal nerves elevated the RVR to a greater degree in adult SHR than in WKY. The sensitivity of the renal vasculature to the various contractile agents was similar in adult SHR and WKY. When compared with WKY, prehypertensive SHR also exhibited increased cross-sectional quantities of arterial media and elevated amplitudes of RVR change in response to norepinephrine and renal nerve stimulation. However, the vascular contractile sensitivity to norepinephrine was reduced. Our results indicate that renovascular wall thickening and the hypercontractile reactivity associated with such a change precedes hypertension in SHR. In prehypertensive SHR, elevations in RVR might be counterbalanced by a decreased norepinephrine sensitivity. An increase in the norepinephrine contractile sensitivity and further vascular thickening with age could elevate the RVR and establish hypertension.

Animals↗
PubMed1988

Prenatal and postnatal hydralazine treatment does not prevent renal vessel wall thickening in SHR despite the absence of hypertension.

Previous studies in our laboratory have shown that the renal blood vessels of 21-week-old Wistar-Kyoto spontaneously hypertensive rats exhibited thicker vascular walls than age matched Wistar-Kyoto normotensive rats. Morphometric analysis of the relaxed renovasculature revealed an increase in the cross-sectional area of the media, which in most cases was associated with an increase in the number of smooth muscle cell layers. To test if these structural changes occur in the absence of raised blood pressure, hydralazine was administered to spontaneously hypertensive rats and normotensive controls prior to and during pregnancy (100 ml/l drinking water), and to the newborn males up to 21 weeks of age (16.9 mg/kg/day by gavage until weaning followed by 100 mg/l in the drinking water). Treated animals were compared with untreated rats. Treatment prevented hypertension development in spontaneously hypertensive rats but did not alter the structural changes found in untreated animals with hypertension. At 21 weeks of age, hydralazine-treated spontaneously hypertensive rats had similar wall-to-lumen area ratios, medial cross-sectional areas and numbers of medial smooth muscle layers as untreated hypertensive rats while these parameters were greater in treated and untreated spontaneously hypertensive rats than in either treated or untreated normotensive controls. Withdrawal of hydralazine from 26-week-old spontaneously hypertensive rats that had been treated in utero and postnatally and had normal blood pressures throughout life resulted in the rapid onset of hypertension. Our results show that renal vascular wall thickening in spontaneously hypertensive rats occurs in the absence of high blood pressure and therefore is not a secondary effect of raised blood pressure.

Animals↗
PubMed1985

Epidural morphine prophylaxis of postoperative pain: report of a double-blind multicentre study.

In a double-blind placebo-controlled trial, 154 subjects, having intraperitoneal surgery or Caesarean section, and 53 patients undergoing lower limb orthopaedic surgery, received epidural morphine, 5 mg in 10 ml 0.9 per cent NaCl, or placebo, 10 ml 0.9 per cent NaCl, intraoperatively to determine duration of action and efficacy in preventing postoperative pain. Epidural morphine gave significantly longer postoperative analgesia (greater than 11 h) than placebo (3-6 h) in both groups (p less than 0.05) and patients who received morphine required less postoperative analgesic. Obstetric subjects experienced longer pain relief (18.3 +/- 1.3 h) than patients undergoing non-obstetric intraperitoneal surgery (9.2 +/- 1.2 h) (p less than 0.001). Generally mild pruritus affected more than 40 per cent of those receiving morphine, but over 90 per cent of obstetric patients receiving morphine. Respiratory depression occurred in 2-7 per cent of subjects who received morphine; unpredictable in onset, it responded rapidly to naloxone. Epidural bupivacaine, if employed for the surgical procedure, appeared to prolong epidural morphine analgesia. We consider epidural morphine useful in preventing postoperative pain, but its use demands close observation of respiratory rate in a high density nursing area.

Adult↗
PubMed1984

Survival following orchiectomy for stage D adenocarcinoma of the prostate.

The survival of nonprivate and private patients following orchiectomy for stage D adenocarcinoma of the prostate was studied. While the private patients enjoyed a longer survival, their improved survival was found to be a function of an earlier presentation. Examination of the survival statistics with linear regression analysis suggested that survival following orchiectomy is a function of the age at the time of orchiectomy.

Adenocarcinoma↗
PubMed1984

Comparative effects of volatile anaesthetic agents and nitrous oxide on human leucocyte chemotaxis in vitro.

Infection following surgery is not uncommon. Human leucocytes play a vital role in the body's defense against infection. In order to decrease perioperative morbidity and mortality from infection, it is important to define the comparative effects of different anaesthetic agents on the leucocyte function. Therefore, the effect of equipotent concentrations (MAC 1) of isoflurane, enflurane, halothane, methoxyflurane and 70 per cent nitrous oxide, on the leucocyte chemotactic migration was investigated in vitro. The chemotactic migration of neutrophils and monocytes, with and without equilibration with MAC 1 concentrations of different volatile anaesthetics and 70 per cent nitrous oxide, was compared by using a modification of Boyden's method. Chemotactic migration of both cell types was unaffected by isoflurane, but a significant depression of chemotactic migration was observed with enflurane, halothane, methoxyflurane and nitrous oxide (p less than 0.05). The severity of depression of migration was maximal with nitrous oxide, followed by methoxyflurane, halothane and enflurane in order. It is concluded that equipotent concentrations of various anaesthetic agents produce different degrees of depression of leucocyte chemotactic migration in vitro.

Anesthesia, Inhalation↗
PubMed1984

Smooth muscle cell herniation in the contracted arterial wall of spontaneously hypertensive and normotensive rats.

Structural changes of blood vessels from hypertensive animals during contraction were studied using light and transmission microscopy. In the arteries, maximally contracted with norepinephrine, vacuoles were found in the media of three categories of mesenteric arteries from two age groups (10-12, 28-30 weeks) of spontaneously hypertensive (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. These vacuoles were related to contraction of the smooth muscle cells involving shape change, as they were absent in relaxed vessel walls, and also in muscles that underwent isometric contraction. In the SHR, the number of vacuoles/1,000 microns 2 of media was positively correlated with the degree of contraction of the vessels. Electron microscopic examination of these vacuoles showed that they were the result of herniation (or evagination) of smooth muscle cells into the intercellular space as well as into the neighbouring cells. When the number of herniae per unit cross-sectional area of the contracted media was used as the basis for comparison between SHR and WKY, we found no difference between the two strains of rats at 10-12 weeks of age. At 28-30 weeks, however, the number of herniae was significantly lower in the SHR as compared with age-matched WKY and younger SHR, suggesting that functional changes, that functional changes, probably related to the physical property of the plasma membrane in the smooth muscle cells, have taken place in older SHR.

Animals↗
PubMed1984

Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases.

In an attempt to establish the relevance of ciliary ultrastructure to the pathophysiologic aspects of respiratory tract disease, we compared quantitatively the ultrastructure and function of cilia from healthy subjects (atopic and nonatopic nonsmokers, asymptomatic smokers) and patients with a variety of respiratory diseases (cystic fibrosis, chronic rhinitis, bronchiectasis associated with hypogammaglobulinemia, chronic bronchitis) with cilia from patients with primary ciliary dyskinesia (PCD). In healthy subjects and patients with non-PCD respiratory disease, approximately 5% of the cilia evaluated had ultrastructural abnormalities. Ciliary beat frequency was significantly higher in the chronic rhinitis group (15.3 +/- 1.2 Hz) than in the other non-PCD groups, which were within the normal range (12.5 +/- 1.7 Hz), and in all non-PCD cases ciliary wave form was normal. In each of these groups, normal mucociliary transport had been previously demonstrated. By contrast, in patients with PCD, the proportion of cilia with ultrastructural abnormalities was significantly greater than in the normal subjects and those with non-PCD respiratory disease (p less than 0.0001). In addition, beat frequency was significantly reduced, ciliary wave form was grossly abnormal, and pulmonary and nasal mucociliary transport were virtually absent. These findings demonstrate the relevance of ciliary ultrastructural abnormalities to altered ciliary function and lend support to the primary role of the demonstrated abnormalities in the respiratory tract disease of PCD.

Adolescent↗
PubMed1984

Ciliary defects associated with the development of bronchopulmonary dysplasia. Ciliary motility and ultrastructure.

We have on several occasions studied the nasal respiratory epithelium of an infant with hyaline membrane disease that evolved into bronchopulmonary dysplasia and observed an association between the clinical status and naso-ciliary motion and ultrastructure. At 4 months of age, when the patient had significant respiratory disease, few cilia were present and they beat with a slow dyskinetic motion. The specimens contained primarily necrotic and squamous epithelial membranes; the occasional cilia present had swollen or ruptured membranes. Partial recovery of the epithelium was noted at 4.5 months, with 45% of the cilia having normal ultrastructure. The beat frequency was 15.2 +/- 1.5 Hz (mean +/- SD), and although some degree of dyskinesia was evident, primarily normal ciliary motion was observed. By 10 months of age, significant clinical improvement had occurred and the nasal epithelium had regenerated; 96% of the cilia had normal ultrastructure, and the ciliary beat frequency (12.4 +/- 1.2 Hz) and motion were normal.

Bronchopulmonary Dysplasia↗
PubMed1984

Trypan blue method for the identification of areas of damage to airway epithelium due to mechanical trauma.

A method has been developed for locating the regions of pulmonary epithelial damage due to mechanical trauma, based on the inability of the injured cells to exclude vital stains such as trypan blue. Scanning electron microscopy was used to confirm the sites, as well as the specific type of mechanical damage. The damaged area on rabbit tracheal epithelium due to gentle stroking was characterized by denudation of the ciliated epithelial cells, leaving only a layer of flat, non-ciliated cells. Repeated gentle stroking of the epithelial surface removed all the epithelial cells, exposing the underlying connective tissue layer. The trypan blue method provides a fast and sensitive means of locating damaged airway epithelium due to mechanical trauma. Because the dye is non-toxic, the repair process of the epithelium can also be studied, following the initial assessment of the extent of epithelial damage.

Animals↗
PubMed1983

The involvement of prostaglandins and thromboxanes in the response to pulmonary embolism in anaesthetized rabbits and isolated perfused lungs.

Embolisation of blood clots produced an increased pulmonary artery pressure in vitro and systemic hypotension in vivo. In control anaesthetized animals, systemic blood pressure fell by 44.9 +/- 28.0 mm Hg following embolisation and 40% of the animals died within 5 minutes of embolisation. Plasma concentrations of thromboxane B2 (TXB222222 2) and 6-keto-prostaglandin F 1 alpha (6-keto-PGF 1 alpha) were increased by 0.54 +/- 0.13 ng/ml and 0.41 +/- 0.25 ng/ml, respectively. Pretreatment of animals with aspirin (ASA), 5 mg/kg or 250 mg/kg, reduced the hypotensive response and the TXB 2 and 6-keto-PGF 1 alpha release. Embolisation of isolated lungs perfused with blood-free medium induced an increase in pulmonary artery pressure of 32.7 +/- 21.0 mm Hg and significantly increased the content of TXB 2 and 6-keto-PGF 1 alpha in the perfusate. Pretreatment of lungs with indomethacin, 10 micrograms/ml, reduced the mean pulmonary pressure response to embolisation to 10.6 +/- 4.9 mm Hg and blocked the appearance of TXB 2 in the perfusate. Embolisation with an agarose clot induced only a 2.58 +/- 0.8 mm Hg increase in pressure and no detectable TXB 2 release. These results indicate that embolisation of lungs with a blood clot induces the release of TXB 2 and 6-keto-PGF 1 alpha. The release of these mediators, the hemodynamic responses and mortality were blocked by ASA pretreatment.

6-Ketoprostaglandin F1 alpha↗