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Biomedical subjects

S A Robertson

Publications and source records attributed to S A Robertson.

18 recordsLinked to original sources

Postanesthetic recumbency associated with hyperkalemic periodic paralysis in a quarter horse.

Anesthesia and surgery in a Quarter Horse affected with hyperkalemic periodic paralysis resulted in euthanasia after 7 days of postoperative recumbency. Initial recovery was uneventful after extensive sinus surgery, but within 2 hours, the horse had severe muscle weakness. Plasma electrolyte concentrations were within the normal range during the period of recumbency. There was no clinical or laboratory evidence of severe muscle damage. Despite treatment with acetazolamide, isoproterenol, and intensive nursing, the horse was unable to stand for more than a few seconds and developed severe decubital ulcers. Ultrastructural examination revealed nemaline rods and swollen mitochondria in disrupted myofibers.

Anesthesia, General

Cytokines in rodent reproduction and the cytokine-endocrine interaction.

Insights derived from recent studies employing rodent models demonstrate that the synthesis of pluripotent cytokines is an important function of resident cells in the female reproductive tract. Through steroid hormone regulated secretion of these mediators, resident cells appear to coordinate the recruitment and action of leukocytes that are centrally implicated in the dramatic remodelling processes characteristic of reproductive events.

Animals

Tumor necrosis factor alpha in the human ovary: presence in follicular fluid and effects on cell proliferation and prostaglandin production.

OBJECTIVE: To examine the concentration of tumor necrosis factor alpha (TNF alpha) in human follicular fluid (FF) and its effects on cultured human granulosa-lutein cells. DESIGN: The concentration of TNF alpha in FF from hyperstimulated cycles and in conditioned media from cultured granulosa-lutein cells was measured by radioimmunoassay (RIA) and bioassay using L929 cells. The effects of recombinant human TNF alpha (rTNF alpha) on proliferation and production of progesterone (P) and prostaglandin (PG, PGE2, and PGF2 alpha) by cultured human granulosa-lutein cells were assessed. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program at Reproductive Medicine Unit, The Queen Elizabeth Hospital, Woodville, South Australia, Australia. PATIENTS: Twenty-five women undergoing IVF-ET for tubal factor infertility. RESULTS: The concentration of immunoreactive TNF alpha in FF was 0.36 +/- 0.02 microgram/L, and there were no significant correlations between levels of TNF alpha and steroids or FF volume. Bioactivity for TNF alpha was considerably less. Immunoreactive or bioactive TNF alpha was not detected in conditioned media from granulosa-lutein cell culture. Recombinant human TNF alpha dose-dependently stimulated proliferation of cultured granulosa-lutein cells as measured by incorporation of 3H-thymidine, but in contrast to earlier reports, we were not able to demonstrate any effect of rTNF alpha on basal or human chorionic gonadotropin-stimulated P accumulation during culture periods of up to 72 hours. The accumulation of both PGE2 and PGF2 alpha was dose-dependently increased by rTNF alpha during a 48-hour incubation period. Time course studies revealed that maximal levels of both PGE2 and PGF2 alpha were reached within 12 hours of culture. CONCLUSION: Immunoreactive and bioactive TNF alpha is present in FF. Tumor necrosis factor alpha may have a physiological role in stimulating proliferation of follicular cells and PG production at the time of ovulation and formation of the corpus luteum.

Cell Division

Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.

Animals

Uterine epithelial cells synthesize granulocyte-macrophage colony-stimulating factor and interleukin-6 in pregnant and nonpregnant mice.

Cytokine secretion by endometrial cells from estrous and mated mice was measured using specific bioassays. The granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) contents of uterine intraluminal fluid were elevated greater than 20-fold and 250-fold respectively following mating, and both cytokines were synthesized in abundance in vitro by uterine cells harvested at estrus and on Day 1 of pregnancy. Synthesis was not impaired in genetically lymphocyte-deficient nude, SCID, or beige mice. To determine the cellular origin of the cytokines, a panning technique employing monoclonal antibodies against a range of leukocyte and other lineage markers was used to isolate uterine cell subsets in vitro. These experiments identified glandular and/or luminal epithelial cells as the major source of GM-CSF and IL-6 in estrous and pregnant uteri. Stromal fibroblasts also synthesized IL-6, as did macrophages in mated mice. Epithelial cells harvested from midgestation uteri secreted GM-CSF and IL-6 in quantities similar to those of cells from estrous and mated mice. Bioactivities of both cytokines derived from epithelial cells were neutralized by specific antibodies, and size-exclusion chromatography of conditioned media from uterine cells revealed peaks of GM-CSF and IL-6 bioactivity with M(r) 23,000 and 23,000-26,000, respectively. Bioassay of luminal fluids and culture supernatants were negative for the cytokines interleukin-1, interleukin-2, interleukin-3, and tumor necrosis factor-alpha. These studies identify murine uterine epithelium as a potent source of the cytokines GM-CSF and IL-6, which we postulate have potentially important functions in pregnancy through actions on target cells in both the uterus and the conceptus.

Animals

Cardiopulmonary, anesthetic, and postanesthetic effects of intravenous infusions of propofol in greyhounds and non-greyhounds.

The cardiopulmonary, anesthetic, and postanesthetic effects of an IV infusion of the hypnotic agent propofol were assessed in 6 Greyhounds and 7 non-Greyhounds. After IM injection of acetylpromazine and atropine, a bolus injection of propofol sufficient to allow endotracheal intubation (mean +/- SEM = 4.0 +/- 0.3 mg/kg of body weight in Greyhounds; 3.2 +/- 0.1 mg/kg in non-Greyhounds) was administered, followed by continuous infusion at a rate of 0.4 mg/kg/min for 60 minutes, during which time dogs breathed 100% oxygen. In 23% of all dogs (3 of 13), apnea developed after initial bolus administration of propofol. Arterial blood pressure was well maintained in all dogs, but heart and respiratory rates were decreased significantly (P less than 0.05) during the infusion in Greyhounds. In Greyhounds, mild respiratory acidosis developed after 45 minutes, whereas arterial carbon dioxide tension was increased at all times after propofol administration in non-Greyhounds. In all dogs, PCV and total plasma proteins were unaffected by propofol. Rectal temperature decreased during treatment. Muscle tremors were observed in approximately 50% of dogs (in 3 of 6 Greyhounds and 3 of 7 non-Greyhounds) during and after infusion of propofol. Non-Greyhounds lifted their heads, assumed sternal recumbency, and stood 10 +/- 1, 15 +/- 3, and 28 +/- 5 minutes, respectively, after the end of the infusion; in Greyhounds, the corresponding times were 36 +/- 4, 43 +/- 6, and 63 +/- 7 minutes.

Anesthesia, Intravenous

Surgical treatment of perforating duodenal ulcer in a dog by use of modified choledochoduodenostomy and gastrojejunostomy.

Modified choledochoduodenostomy and gastrojejunostomy were used successfully to treat extensive duodenal ulceration and perforation in a dog. Concomitant pyometra, simultaneously managed by ovariohysterectomy, may have predisposed the dog to stress ulceration. Choledochoduodenostomy was performed by transplantation of the entire common bile duct and associated major duodenal papilla to a more distal duodenal location. An indwelling choledochostomy tube was used to stent the anastomotic site, externally divert bile flow, and allow postoperative cholangiography. Early postoperative complications included presumed metronidazole-induced neurotoxicosis, choledochostomy tube obstruction, and pancreatitis, all of which resolved within 2 weeks. The dog was clinically normal and medication (ranitidine and sucralfate) was discontinued 35 months later.

Animals

Granulocyte macrophage colony stimulating factor (GM-CSF) in the murine reproductive tract: stimulation by seminal factors.

The activity of GM-CSF during early pregnancy in the murine uterine lumen in vivo and in media conditioned by uterine cells in vitro has been assessed. GM-CSF was detected in uterine luminal fluid recovered by lavage on the morning after syngeneic mating (median level 5.7 CFUc U/uterus) and following mating with vasectomized (5.1 U/uterus) or allogeneic males (4.4 U/uterus), with significantly lesser (P less than 0.05) amounts recovered from the uteri of superovulated, mated mice. By contrast, GM-CSF was only detectable (greater than 0.5 U/uterus) in the luminal fluid of three of 22 unmated oestrous mice examined. No activity was detected in secretions from male accessory glands including seminal vesicle, epididymis, prostate and coagulating gland (less than 0.5 U/gland). GM-CSF was found at higher levels in supernatants from cell monolayers prepared by tryptic digest of the uteri of Day 1 mated mice than those from unmated oestrous mice (P less than 0.05). Little GM-CSF was detected in supernatants from ovariectomized mice. An alpha-GM-CSF polyvalent antibody neutralized the FD5/12 bioassay response confirming the identity of the lymphokine. The interleukins IL-2 and IL-3 were not detected in uterine luminal fluid nor in media conditioned by cell monolayers. We postulate that elevated uterine GM-CSF activity after mating is elicited by a non-sperm associated, non-MHC component of the ejaculate and synthesized by a hormone-responsive endometrial cell population. This cytokine may have an embryotrophic role or contribute to priming of the uterus for implantation.

Animals

Effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature in neonatal foals.

The effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature were investigated in six foals at 10 and 28 days of age. These variables were also measured in three foals at 19 days of age when saline alone was injected. Rectal temperature fell significantly after 30 mins in both groups of xylazine treated foals and was still depressed after 120 mins. Hypothermia did not occur in the saline control group. There was no significant change in blood glucose or plasma insulin concentrations during the 120 mins following either xylazine or saline administration and no significant differences between the three groups of foals. When foals were allowed to suckle after being away from their dams for 2 h, there was a significant (P less than 0.01) rise in plasma insulin levels in all the groups. Blood glucose showed a concomitant rise but this was only significant in the saline group. Unlike adults, intravenous xylazine (1.1 mg/kg) does not produce hypoinsulinaemia and hyperglycaemia in foals. This study suggests that the inhibition of insulin release from pancreatic beta-cells by xylazine, which in adults is alpha 2-adrenoceptor mediated, is immature or absent in foals under one month of age.

Animals

Metabolic and hormonal changes associated with arthroscopic surgery in the horse.

The effect of general anaesthesia and arthroscopic surgery on blood glucose and lactate, plasma non-esterified fatty acids, insulin, beta-endorphin and cortisol was investigated in seven horses. Animals were premedicated with xylazine and anaesthesia was induced with guaifenesin and sodium thiamylal and maintained with halothane vaporised in oxygen. Blood samples were collected in the pre-, intra- and post operative period. Induction of anaesthesia was associated with a transient hyperglycaemia and a significant rise in plasma insulin levels. Plasma insulin values fell during surgery but showed a significant increase post operatively. Surgery stimulated a small but significant rise in plasma beta-endorphin and cortisol values but these had returned to baseline values in the early post operative period. No changes in blood lactate were recorded.

Anesthesia, General

Cardiopulmonary effects of xylazine sedation in the foal.

Six healthy foals underwent instrumentation for measurement of the cardiopulmonary effects of sedation with 1.1 mg/kg bodyweight xylazine hydrochloride given intravenously. Responses to xylazine in foals at 10 and 28 days of age were not significantly different. Foals became sedate and markedly ataxic, and four of the six foals became recumbent. Heart rate decreased significantly but no arrhythmias were detected. Arterial blood pressure increased initially and then fell significantly below pre-injection values. Changes in respiratory airflow, upper airway obstruction and respiratory noise were noted in the initial 20 mins of sedation, after which respiratory rate fell, tidal volume increased, and minute volume decreased gradually. Arterial blood gas tensions and pH did not change significantly during the 120 mins following xylazine administration. Control studies showed no significant changes. All foals recovered uneventfully.

Airway Obstruction

The use of 5'-phospho-2 deoxyribocytidylylriboadenosine as a facile route to chemical aminoacylation of tRNA.

Methodology is described for the synthesis and chemical aminoacylation of the hybrid dinucleotide 5'-phospho-2'-deoxyribocytidylylriboadenosine (pdCpA). Ligation of aminoacylated pdCpA to a truncated amber suppressor tRNACUA (-CA) using T4 RNA ligase generates an aminoacylated suppressor tRNA which can be used for site-specific incorporation of unnatural amino acids into proteins. Both the ligation and in vitro suppression efficiencies are the same when either pCpA or pdCpA is used. The use of deoxycytidine simplifies the chemistry involved in the synthesis of the dinucleotide pCpA. In addition, these results demonstrate that ribocytidine is not required for recognition of the aminoacylated tRNA during protein synthesis.

Chromatography, High Pressure Liquid

Simple acid-base disorders.

The body regulates pH closely to maintain homeostasis. The pH of blood can be represented by the Henderson-Hasselbalch equation: pH = pK + log [HCO3-]/PCO2 Thus, pH is a function of the ratio between bicarbonate ion concentration [HCO3-] and carbon dioxide tension (PCO2). There are four simple acid base disorders: (1) Metabolic acidosis, (2) respiratory acidosis, (3) metabolic alkalosis, and (4) respiratory alkalosis. Metabolic acidosis is the most common disorder encountered in clinical practice. The respiratory contribution to a change in pH can be determined by measuring PCO2 and the metabolic component by measuring the base excess. Unless it is desirable to know the oxygenation status of a patient, venous blood samples will usually be sufficient. Metabolic acidosis can result from an increase of acid in the body or by excess loss of bicarbonate. Measurement of the "anion-gap" [(Na+ + K+) - (Cl- + HCO3-)], may help to diagnose the cause of the metabolic acidosis. Treatment of all acid-base disorders must be aimed at diagnosis and correction of the underlying disease process. Specific treatment may be required when changes in pH are severe (pH less than 7.2 or pH greater than 7.6). Treatment of severe metabolic acidosis requires the use of sodium bicarbonate, but blood pH and gases should be monitored closely to avoid an "overshoot" alkalosis. Changes in pH may be accompanied by alterations in plasma potassium concentrations, and it is recommended that plasma potassium be monitored closely during treatment of acid-base disturbances.

Acid-Base Equilibrium

The effect of 2,3-butanedione monoxime (BDM) on smooth muscle mechanical properties.

2,3-Butanedione monoxime (BDM) has been reported to selectively block crossbridge interaction in skeletal and cardiac muscle and BDM has been shown to cause a dose-dependent decrease in smooth muscle maximum tension development (Po). With the relatively recent descriptions of at least two functionally different types of crossbridges (those recruited early in contraction and then fairly rapidly--within 30% of the muscles' contraction time--replaced by very slowly-cycling or "latch" crossbridges), it became important to know whether BDM is a specific inhibitor of one type of crossbridge or the other. In this study it was shown that 7.5 mM BDM had an even greater affect on maximum shortening ability (delta Lmax) having decreased the tracheal smooth muscle delta Lmax by 47%. BDM treatment did not alter "transition time (tT; defined arbitrarily as the time in contraction at which a functionally significant number of slowly-cycling bridges have replaced rapidly-cycling bridges)" in tracheal smooth muscle. Velocity of shortening early in contraction i.e. prior to tT, was decreased by 48%, while velocity late in contraction i.e. post tT, was not decreased with BDM treatment. BDM caused a decrease in maximum load bearing capacity, or maximum force potential (MFP), at all times in contracting tracheal smooth muscle. This investigation supports the suggestion that BDM inhibits crossbridge cycling rate in smooth muscle. In particular BDM appears to specifically inhibit rapidly-cycling crossbridges or their control as it has no apparent affect on cycling rate of very slowly-cycling or "latch" crossbridges in tracheal smooth muscle.

Animals

Metabolic and hormonal responses to neuroleptanalgesia (etorphine and acepromazine) in the horse.

Administration of etorphine and acepromazine to horses was associated with an increase in haematocrit, blood glucose, blood lactate and plasma non-esterified fatty acids (NEFA). The rise in plasma NEFA was most striking following injection of the antagonist diprenorphine and could contribute to the production of cardiac arrhythmias. Plasma insulin was depressed at the end of surgery. These changes, plus profuse sweating, are indirect evidence of strong sympathetic stimulation. Plasma cortisol did not alter significantly due to wide individual variation. Venous blood pH fell, reflecting the rise in lactate and venous carbon dioxide tension.

Acepromazine

Some metabolic and hormonal changes associated with general anaesthesia and surgery in the horse.

Three different anaesthetic techniques were studied in normal, healthy Thoroughbred or Thoroughbred type horses. These were (a) acepromazine, thiopentone and suxamethonium; (b) acepromazine, glyceryl guaiacolate and a 'half-dose' of thiopentone; and (c) xylazine and ketamine. Anaesthesia was maintained with halothane vaporized in oxygen and nitrous oxide. All horses underwent either laryngeal or body surface surgery. Heart rate, packed cell volume, blood glucose and lactate, plasma non-esterified fatty acids, insulin and cortisol were measured before, during and after surgery. The greatest metabolic and hormonal changes occurred immediately after anaesthetic induction and were different in each group. The combination of acepromazine, glyceryl guaiacolate and a 'half-dose' of thiopentone was associated with the least change in the physiological and metabolic variables measured.

Anesthesia, General

Some personality correlates of time competence, temporal extension and temporal evaluation.

In a study of the relationship among three temporal dimensions, viz., competence, extension, and evaluation, and a number of personality variables including ego strength, external control, and dogmatism for 21 males and 19 females time competence and temporal evaluation related closely to a number of these variables while the relationship with extension was weak. The implications were discussed with reference to the value and validity of measures of temporal extension.

Anxiety

Suspected malignant hyperthermia after halothane anesthesia in a cat.

A 6 month old domestic shorthaired cat died of suspected malignant hyperthermia. Anesthesia was induced and maintained with halothane vaporized in oxygen and nitrous oxide, after acepromazine premedication. Before an incision was made, the cat's heart rate dropped from 140 to 90 beats/min concomitant with a drop in blood pressure. Glycopyrrolate administration resulted in severe ventricular tachycardia (340 beats/min). Halothane and nitrous oxide were discontinued and the surgery was abandoned. Lidocaine administration resulted in a normal sinus rhythm. In recovery, the cat was tachypneic and struggling, with a rectal temperature of 40.1 degrees C that quickly increased to 41.4 degrees C. While the cat was being cooled, cardiac dysrhythmias progressed to ventricular fibrillation that was not responsive to cardiorespiratory resuscitation. Blood specimens obtained while the cat was being cooled showed hyperkalemia (10.0 mEq/L) and increased serum creatine kinase activity (780 IU/L). There was extreme extensor rigidity (rigor mortis) within 5 min of cardiac arrest. Results of microscopic and electron microscopic examination of muscle showed occasional perivascular infiltrates of lymphocytes with infrequent perimysial and epimysial neutrophils and a few sarcomeres with streaming of Z-bands (suggesting a contracted state). Histochemical evaluation of skeletal muscle showed no significant difference between type I and type II fibers.

Anesthesia, General