Effect of potassium on urinary acidosis.
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Acidosis↗
Biomedical subjects
G D Phillips
Publications and source records attributed to G D Phillips.
Inhibition by methylprednisolone acetate suggests an indirect mechanism for TGF-B induced angiogenesis.
Angiogenesis induced by transforming growth factor beta (TGFB) implanted in the rabbit cornea is accompanied by an influx of inflammatory cells. To determine if the inflammatory cells are the mediators of the neovascularization, they were depleted by local administration of methylprednisolone acetate (MPA). Subconjunctival injections of 16 mg of MPA immediately following implantation of 50 ng of TGFB in the cornea prevented the inflammation and subsequent formation of capillaries. If the injections of MPA were delayed by 48 hr and the inflammatory cells were allowed to enter the cornea, angiogenesis occurred, demonstrating that MPA had no adverse effects on the ability of endothelial cells to form capillaries. These results confirm the hypothesis that TGFB induces angiogenesis indirectly by recruiting inflammatory cells capable of stimulating direct angiogenesis.
Animals↗
Induction of neointima formation by platelet derived angiogenesis fraction in a small diameter, wide pore, PTFE graft.
Enhancement of endothelialization and patency of a small diameter (2 mm), wide pore, PTFE graft was attempted by coating the luminal surface with a platelet derived angiogenesis fraction (PDAF) and implanting it in a rat model. PDAF was delivered to the grafts by combining it with a carrier polymer. PDAF-treated grafts were initially implanted in the retroperitoneum for 21 days followed by removal of one for histology and in situ end to side bypass to the infrarenal aorta for the other. Vascularized grafts were examined at 14 days for patency and 100 days for patency and histology. Significant differences were noted in transmural ingrowth of capillaries and tissue at 21 days post implantation in PDAF-treated versus untreated grafts. Similarly, near significance was noted in capillary ingrowth and significance was noted in tissue ingrowth at 100 days in PDAF-treated grafts. Despite favorable trends particularly early in the time course, no significant differences in graft patency, endothelialization, or hydroxyproline content was demonstrated between PDAF-treated and untreated grafts. Results of this preliminary study are encouraging for further study of PDAF-treated PTFE grafts and the potential that rapid vascularized neointima formation results improved in graft patency rates.
Animals↗
Initiation and pattern of angiogenesis in wound healing in the rat.
The object of this study was to examine the initiation and pattern of capillary growth associated with wound healing. Collagen sponges were implanted subcutaneously in the hind limbs of adult male rats to stimulate the formation of granulation tissue. Blood vessels of the hind limbs of euthanized rats were perfused with Mercox (an acrylic monomer) via the abdominal aorta at selected periods of time following sponge implantation. When the perfusate was completely cured, the sponge and parajacent tissues were excised and subsequently macerated by alternating immersion in 40% KOH and distilled water. Cast replicas of the vascular lumina were coated with gold and imaged by scanning electron microscopy. At 6 hr, punctate depressions at the periphery of the replicas of vein and venule lumina were noted. The depressions represented sites of leukocyte margination. By 24 hr, the depressions increased numerically, indicating a great increase in the sites of leukocyte margination. The number of these depressions decreased by 48 hr. Concomitantly, the depressions representing endothelial cell nuclei became more pronounced, indicating nuclear hypertrophy of these cells. In addition, capillary bud formation was initiated. At 72 hr, capillary buds were quite apparent and arose solely from venules. Between 7 and 14 days, replicas of capillary lumina were longer and formed an elaborate network, presumably by end-to-end, side-to-side, and end-to-side anastomoses. The network was formed circumferential to the sponge and then capillary sprouts entered the sponge's interstitial spaces.
Animals↗
The effect of inhaled ipratropium bromide alone and in combination with oral terfenadine on bronchoconstriction provoked by adenosine 5'-monophosphate and histamine in asthma.
The aim of this study was to investigate the effect of terfenadine, an antihistamine, 180 mg orally, the anticholinergic drug, ipratropium bromide (IB), 0.5 mg nebulized aerosol, the combination of these two drugs, and placebo tablets and aerosol on histamine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in a randomized, double-blind fashion. Airway response was evaluated as FEV1. After placebo, the geometric mean (GM) provocative concentration causing a 20% in FEV1 from the postsaline baseline value (PC20) for histamine and AMP was 0.63 and 5 mg/ml, respectively. Terfenadine displaced the FEV1 concentration-response curves obtained with both histamine (GM PC20 values increasing to 26.92 mg/ml) and AMP (GM PC20 values increasing to 26.7 mg/ml) to the right. IB had a small, but significant, protective effect against the fall in FEV1 produced by histamine and AMP, the GM PC20 values increasing to 1.69 and to 12.6 mg/ml, respectively. Terfenadine and IB in combination produced protection against histamine and AMP that was more than the production produced by either drug alone, the GM PC20 values increasing to 54.76 and 47.7 mg/ml, respectively. There was no correlation between degree of bronchodilatation induced by active treatments and concentration ratios for AMP or histamine. These data suggest that histamine release and vagal reflexes both contribute to AMP-induced bronchoconstriction in clinical asthma in man.
Adenosine Monophosphate↗
Reversed helper/suppressor T-lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and Pneumocystis carinii pneumonia.
Pneumocystis pneumonia (PCP) usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome (AIDS). Patients with solid tumors represent a very small fraction of the reported cases of PCP. Over an 18-month period, PCP was diagnosed in three patients who had received radiation and chemotherapy for breast cancer. In all three patients, there was no serologic or clinical evidence of AIDS. Direct staining of bronchoalveolar lavage fluid (BAL) revealed Pneumocystis carinii, and cellular analysis of BAL revealed an increased percentage of lymphocytes with reversed helper/inducer:suppressor/cytotoxic T-cell (CD4:CD8) ratio. Because decreased CD4:CD8 ratio in BAL is commonly accepted as findings consistent with hypersensitivity pneumonitis and AIDS, we conclude that similar findings in patients without AIDS are not specific for hypersensitivity pneumonitis, and P. carinii should be ruled out in the appropriate clinical setting.
Adult↗
Effect of a hay and a grain diet on the rate of hydrolysis of ochratoxin A in the rumen of sheep.
The hydrolysis of ochratoxin A (OA) and the corresponding formation of its hydrolysis product, alpha ochratoxin (O alpha), by ruminal digesta and in the rumen of hay-fed and grain-fed sheep were compared. Ruminal contents from sheep fed diets with hay or with grain hydrolyzed OA in vitro; the majority of the activity was associated with the particulate fraction of the ruminal contents. The rate of hydrolysis of OA by ruminal fluid that was adjusted to different pH values was not influenced (P greater than .6) by the pH of the samples (pH was from 5.5 to 7.0). Ruminal fluid obtained from hay-fed animals (pH 7.0) was able to hydrolyze OA in vitro and to produce the hydrolyzed product, O alpha, at a much greater rate (fivefold) than ruminal fluid obtained from grain-fed animals (pH 5.5) (P less than .01). Ochratoxin A was administered intraruminally at a concentration of .5 mg/kg of BW to hay-fed and grain-fed sheep. The half-lives for disappearance of OA from the rumen of sheep fed grain (normal feed intake, rumen pH 5.7), fed grain at a low level (30% of normal feed intake, pH 6.5), and fed hay (pH 7.1) were 3.6, 1.3, and .6 h, respectively. The results suggest that OA is hydrolyzed much faster in the rumen of sheep fed hay than in sheep fed grain, presumably because of the different ruminal microbial population, which in turn influenced the rate of hydrolysis of OA.
Animal Feed↗
Effect of a hay and a grain diet on the bioavailability of ochratoxin A in the rumen of sheep.
The role of the rumen and its contents in the detoxification of ochratoxin A (OA) was studied in sheep. The first experiment established that very little conversion of OA to alpha ochratoxin (O alpha) occurs systematically; 90 to 97% of the OA and metabolites was recovered as unaltered OA in the urine. Most of the small amount of O alpha recovered was also in the urine. In this experiment, two sheep were fasted and another two fed normally, but feed intake had no significant effect. In the second experiment, two sheep fed hay and two fed grain were dosed with OA at .5 mg/kg of BW into the rumen via a cannula. Recoveries, in urine and feces, accounted for 58 to 70% of the administered OA, but almost all (greater than 97%) was in the form of O alpha. About 76 to 92% of this O alpha was in the urine. Although excretion patterns and pharmacodynamics tended to differ with different diets, one of the sheep fed grain had very low intake and the results were equivocal. In the third experiment, eight sheep (four fed hay, four fed grain) were given a single intraruminal dose of OA (.5 mg/kg of BW). The disappearance of OA from the rumen and the corresponding formation of O alpha was much faster for hay-fed than for grain-fed sheep; the half-lives were .63 and 2.7 h for OA and .9 and 1.9 h for O alpha, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animal Feed↗
An angiogenic extract from skeletal muscle stimulates monocyte and endothelial cell chemotaxis in vitro.
The purpose of this study was to determine whether the extraction of skeletal muscle with a combination of ethanol and hydrochloric acid yields a product capable of stimulating angiogenesis. The resulting extract stimulated inflammation in the rabbit corneal assay, which was followed by capillary formation. In order to determine whether the observed angiogenesis was stimulated by a factor(s) acting directly on the endothelial cells versus a factor(s) recruiting macrophages that in turn release factors acting on endothelial cells, the muscle extract was tested for endothelial cell and monocyte chemotaxis activity in vitro. The muscle extract stimulated significant endothelial cell chemotaxis at concentrations between 94 and 750 micrograms of protein/ml and significant monocyte chemotaxis at concentrations between 8 and 75 micrograms of protein/ml. Polyacrylamide gel electrophoresis suggests that basic fibroblast growth factor and transforming growth factor-beta may be present in this acid/ethanol extract of skeletal muscle.
Animals↗
Non-invasive mechanical ventilation for acute respiratory failure.
The value of mechanical ventilation using intermittent positive pressure ventilation delivered non-invasively by nasal mask was assessed in six patients with life threatening exacerbations of chronic respiratory disease. Median (range) arterial oxygen and carbon dioxide tensions were 4.4 (3.5-7.2) kPa and 8.7 (5.5-10.9) kPa respectively, with four patients breathing air and two controlled concentrations of oxygen. The arterial oxygen tension increased with mechanical ventilation to a median (range) of 8.7 (8.0-12.6) kPa and the carbon dioxide tension fell to 8.2 (6.5-9.2) kPa. Four patients discharged after a median of 10 (8-17) days in hospital were well five to 22 months later. One died at four days of worsening sputum retention and another after five weeks using the ventilator for 12-16 hours each day while awaiting heart-lung transplantation. This technique of mechanical ventilation avoids endotracheal intubation and can be used intermittently. Hypercapnic respiratory failure can be relieved in patients with either restrictive or obstructive lung disease in whom controlled oxygen treatment results in unacceptable hypercapnia. Respiratory assistance can be tailored to individual need and undertaken without conventional intensive care facilities.
Acute Disease↗
Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma.
Bradykinin, a nonapeptide cleavage product of high molecular weight kininogen, is a potent bronchoconstrictor agonist in asthma; however, its mechanism of action is not known. Since bradykinin has been shown to stimulate mediator release from mast cells and augment the release of prostanoids, we have examined the effect of a selective histamine H1 receptor antagonist, terfenadine and a potent cyclooxygenase inhibitor, flurbiprofen on bronchoconstriction provoked by inhaled bradykinin in asthma. As a bronchial provocation procedure bradykinin challenge was repeatable to within 1 doubling dilution. In nine atopic asthmatic subjects, terfenadine 180 mg, when compared to placebo, increased the geometric mean provocation concentration of inhaled agonist required to reduce FEV1 by 20% of baseline (PC20) from 0.7 to greater than 22.9 mg/ml for histamine (P less than 0.01) and 0.3 to 0.5 mg/ml for bradykinin (P less than 0.01). In a further nine atopic asthmatics, flurbiprofen 150 mg when compared to placebo produced a small but significant protection of the airways against bradykinin, geometric mean PC20 increasing from 0.40 to 0.79 mg/ml (P less than 0.05). We conclude that bradykinin is a potent bronchoconstrictor agonist in asthma, being approximately 9.5 times more potent than histamine in molar terms. Pharmacological intervention with terfenadine and flurbiprofen led to a significant protection of the airways against the constrictor effect of bradykinin but the effect in each case was small. Thus, while histamine and prostanoids may contribute as mediators of bradykinin-induced bronchoconstriction, they are unlikely to account for the majority of the response.
Adult↗
Angiogenic activity in damaged skeletal muscle.
After a muscle is damaged, blood vessels spontaneously grow into the injured region as the muscle fibers regenerate. The stimulus for this vascular ingrowth is currently unknown. We hypothesized that the damaged muscle releases a factor(s) capable of stimulating this revascularization. To test this theory, extracts were prepared from rabbit hind limb muscles and incorporated into Hydron, a slow-release polymer. Pellets of the extract containing Hydron were implanted between the layers of the rabbit corneal stroma as an assay for angiogenic activity. The normally avascular corneas were examined 7 days after surgery for the presence of new blood vessels. Skeletal muscle-derived extract from rabbits elicited positive angiogenic responses in a dose-dependent manner. Four hundred to 500 micrograms of the skeletal muscle-derived extract were required to produce maximum vessel ingrowth. The control, Dulbecco's phosphate-buffered saline in Hydron, failed to stimulate neovascularization.
Angiogenesis Inducing Agents↗
Wound healing angiogenesis: indirect stimulation by basic fibroblast growth factor.
Basic fibroblast growth factor (bFGF) was tested for its ability to stimulate angiogenesis in vivo using the rabbit corneal assay. Basic FGF (50-1,000 ng) was incorporated into 10% Hydron, and 50-500 ng of bFGF were incorporated into 10% Elvax. Human serum albumin (HSA) (10 ng) and 50 ng of transforming growth factor-beta (TGF-beta) served as negative and positive controls. Pellets of the polymers containing test compounds were implanted in the rabbit cornea, examined daily, and after 7 days corneal angiogenesis was scored on a graded scale [(-) for no response and +4 for a maximum response]. Histologic analysis of the corneas was performed on days 2 and 7. Basic FGF (50-500 ng) in Hydron failed to stimulate significant angiogenesis, though it did induce angiogenesis accompanied by inflammation at the 1,000-ng dose. Basic FGF in Elvax elicited inflammation-associated +3 to +4 responses at all doses tested. New blood vessels did not form in response to HSA in Hydron or Elvax, while TGF-beta induced +4 angiogenesis accompanied by vigorous inflammation. In vivo release kinetics for bFGF in Hydron and Elvax were compared, and the release of bioactive bFGF from Hydron and Elvax was demonstrated in vitro. These results suggest that the bFGF and Elvax combination incites an inflammatory response which stimulates indirect angiogenesis, while the same concentrations of bFGF delivered in Hydron produced no inflammation or angiogenesis. Although bFGF alone is a potent mitogen for endothelial cells, it does not appear to directly stimulate in vivo angiogenesis.
Animals↗
The toxic effects of saline drinking water on young turkey poults.
Turkey poults were offered ad libitum a diet containing 2.5 g salt/kg and tap water containing, 0, 90 or 105 mn NaCl to drink from 1 to 12 d of age. 2. High mortality with oedbema and ascites occurred mainly from 5 to 8 d in poults given the saline solutions. Mortality seemed to be related to salt and water intakes. 3. Plasma and body composition indicated abnormal retention of salt and water in poults younger than 12 d of age offered hypotonic saline. 4. In a second experiment using the same diet poults were offered hypotonic saline (105 mn NaCl in tap water) from 5, 9 or 13 d of age. High mortality with oedema and ascites was only observed when saline was given from 5 or 9 d. 5. The results suggest that from about 5 to 10 d of age there is a relative functional renal insufficiency which causes susceptibility to the toxic effects of saline water.
Animals↗
Intensive care data--I: Computer controlled analysis.
A flexible, simple computer-controlled system for analysis of administrative and clinical data in intensive care is described. The system uses an interactive data input programme to facilitate data entry, an editor to correct errors, and the Statistical Package for the Social Sciences (SPSS) for data selection, retrieval and analysis. The system has the following features: data input is simple; large amounts of data can be handled rapidly and accurately; old data is readily available for comparison with new data and can be included in the present analysis; available statistical packages remove the need for a programmer; complex analyses are possible. The system has been successfully used for two years to provide administrative and clinical data which is pertinent to patient care.
Australia↗
Intensive care data--II: A new unit's first two years.
Intensive care units now exist in a large number of hospitals. They vary from one another in many respects, but have one thing in common--high running costs. There are few published reports in recent years of the workload, results and effectiveness of intensive care units. This paper presents data obtained from a new unit in 1977 and 1978, using a computer-controlled system of data storage and analysis. This has provided useful information of an administrative and clinical nature, and has enabled us to compare data from year to year, as well as allowing comparisons with data from other units. The potential exists for such a system to be useful in evaluating criteria for admission and termination of care, and for cost-effectiveness studies.
Adolescent↗
Factors affecting the voluntary intake of food by sheep. 1. The role of distension, flow-rate of digesta and propulsive motility in the intestines.
1. Twelve sheep fitted with abomasal cannulas were given ad lib. access to a diet of chopped lucerne (Medicago sativa) hay to a ascertain if the amount of digesta being transported by the intestines was limiting intake. If this was the situation, pumping a solution of the bulk-laxative methylcellulose (100 g/kg; MC) into the abomasum should have reduced intake in proportion to the mass of digesta attributable to the MC and associated water. In preliminary experiments faecal water and wet matter outputs increased by 6.2 and 7.4 g/g MC powder respectively. 2. The infusion of 2.95 kg MC/d did not affect food intake even though wet faecal output increased from a control value of 2.436 to 4.616 kg/d. The transit time of 51 Cr-EDTA through the intestines decreased only slightly during the infusion indicating that MC produced a marked increase in the mass of intestinal contents. Increasing the rate of infusion to 5.336 kg/d increased wet faecal output to 5.437 kg/d, did not change transit time but significantly decreased food intake presumably to protect the intestines from overdistension. After stopping the infusion, food intakes and faecal outputs returned to control values but transit time remained unchanged. The intake of chopped lucerne hay by sheep was not limited by the capacity of the small and large intestines to transport bulk as intake was maintained even through wet faecal output was doubled and the intestines apparently became markedly distended.
Animals↗