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Biomedical subjects

D S Parsons

Publications and source records attributed to D S Parsons.

At least 73 records · Page 4Linked to original sources

Functional endoscopic sinus surgery in aviators with recurrent sinus barotrauma.

Recurrent sinus barotrauma in an aviator is difficult to treat successfully. Exacerbations frequently result in marked aviator discomfort, cycles of temporary restriction from aviation duties, or even permanent disqualification for flying duties. Medical management and standard sinus operations are often ineffective, seldom curative, and have a disappointing record in returning the aviator to flying duties. Detailed computerized tomographic scanning of the paranasal sinuses coupled with the functional endoscopic sinus surgery approach directs treatment at the causative pathology. Sinus ventilation is improved while making possible a return to active flight status without recurrence of sinus barotrauma. Initial experience with the functional endoscopic sinus surgery technique in such a patient population is reported. A discussion of recurrent sinus barotrauma, paranasal sinus anatomy, and the theory of endoscopic surgical management for sinus disease is included.

Adult↗

Third case of Pfeiffer-type cardiocranial syndrome.

We report on a third child with a newly recognized craniosynostosis syndrome involving the sagittal suture. Additional findings not related to the abnormal head growth include micrognathia with limited mouth opening, tracheobronchial anomalies, congenital heart defects, microphallus, cryptorchidism, and growth and mental retardation.

Abnormalities, Multiple↗

The role of cortical sympathetic ingrowth in the behavioral effects of nucleus basalis magnocellularis lesions.

Following cholinergic denervation of the neocortex by nucleus basalis magnocellularis (NBM) lesions, peripheral sympathetic fibers grow into the neocortex. Two experiments were performed to determine the behavioral effects of this neuronal rearrangement. Group I animals underwent training on a standard radial-8-arm maze task, while Group II animals learned a modified version (i.e. 4 arms baited). Following acquisition, NBM lesions were performed. Animals with lesions but without sympathetic ingrowth performed consistently better in both behavioral paradigms, than animals with NBM lesions and sympathetic ingrowth. These studies suggest that cortical sympathetic ingrowth can alter behavior and is detrimental to the learning of a spatial memory paradigm.

Acetylcholinesterase↗

Role of gender in the behavioral effects of peripheral sympathetic ingrowth.

Following cholinergic denervation of the hippocampal formation, peripheral sympathetic nerves originating from the superior cervical ganglia grow into the hippocampus. As gender is known to alter the anatomy of hippocampal sympathetic ingrowth, we assessed the effect of this variable on the behavioral recovery following ingrowth. Adult male or female rats were trained on a standard version of a radial-8-arm maze task until they reached a specific learning criterion. Animals from each sex then underwent one of three surgical procedures: sham surgery, medial septal lesions plus superior cervical ganglionectomy, or medial septal lesion plus sham ganglionectomy. Reacquisition of the maze was then assessed. Prior to surgery, male animals acquired the task significantly faster than female animals. Following surgery male and female rats recovered overall performance at similar rates. However, marked group differences were observed. In males, the control group recovered faster than the group with medial septal lesion plus ganglionectomy, which recovered faster than the medial septal lesion group. In females, the control group recovered faster than the medial septal lesion group, which in turn recovered faster than the medial septal ganglionectomy group. The results of this study clearly demonstrate that gender can influence the behavioral effects of hippocampal sympathetic ingrowth. We believe that this is the first report in which gender has been shown to alter the behavioral effect of a neuronal reorganization.

Animals↗

Recurrent respiratory papillomatosis: a 10 year study.

Sixty cases of recurrent respiratory papillomatosis in both children and adults treated over a 10 year period were reviewed. An unexpected finding was that nine of the 60 patients (15 per cent) had symptoms by two months of age; an earlier onset than previously described. The control rate was 66 per cent for paediatric onset patients and 44 per cent with adult onset; the former required more operations. No anaesthetic deaths or complications were encountered. Glottic webs were the only surgical complication. The findings confirm that there is no relationship between puberty and the rate of control or recurrence. The necessity for precise and comprehensive endoscopic examination of the upper aerodigestive tract using a range of endoscopes and rigid telescopes under general anaesthetic is emphasized.

Adolescent↗

Alterations in regulatory behaviors induced by medial septal lesions and superior cervical ganglionectomy.

Following medial septal (MS) lesions peripheral sympathetic fibers, originating from the superior cervical ganglia (SCG), grow into the hippocampus and habenula. To assess their effect on regulatory behaviors, body weight, and food and water consumption were studied under ad libitum and pharmacological stress conditions, after MS lesions, superior cervical ganglionectomy (Gx) or MS lesion + ganglionectomy (MSGx). Twenty-two animals completed the study: control (n = 7), MS lesion (n = 5), Gx (n = 6), MSGx (n = 4). No differences were observed preoperatively. Postoperatively, body weight fell but over time all groups gained weight. However, animals with MSGx were lighter than MS or Gx animals (which were equivalent), which in turn were lighter than controls (P less than 0.0001). Hypophagia was observed in the Gx and MSGx animals when compared to the MS and control groups (P less than 0.05), while hyperdipsia was seen in the MS and Gx groups (P less than 0.001). Administration of both 1 M NaCl and isoproterenol (25 micrograms/kg) increased drinking in all animals (P less than 0.001), with the MSGx group consuming significantly less than all others (P less than 0.025). Food intake increased following 2-deoxy-D-glucose (500 mg/kg) (P less than 0.0001), while epinephrine (120 micrograms/kg) treatment produced anorexia only in the MS group (P less than 0.05). Hyperthermia was found in the Gx and MSGx groups. The results of this study suggest that both the MS region and SCG contribute to the maintenance of normal regulatory behaviors, with combined loss of these neural systems resulting in severe disturbances, both qualitatively and quantitatively different from either MS lesion or Gx. Although the MS lesion group clearly regulated better than the MSGx group, it is unclear whether this is due to ingrowth or just the presence of the SCG.

Acetylcholinesterase↗

Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions.

To assess the potential usefulness of chronic acetylcholinesterase inhibition in the treatment of learning/memory disorders arising from central cholinergic deficient states, physostigmine was administered chronically to rats with medial septal lesions and the retention of a spatial/working memory task investigated. Three dose levels of physostigmine (0.025, 0.05, 0.075 mg/kg) were administered three times per day following medial septal lesions. Retention of a standard radial 8-arm maze task was assessed. Although the lesions transiently disrupted task performance, physostigmine therapy did not improve either daily performance or total recovery time. Our results suggest that chronic acetylcholinesterase inhibition is not effective in ameliorating the working memory deficits that occur after medial septal lesions.

Animals↗

Passive-avoidance learning after medial septal lesions: effect of experience and the peripheral sympathetic nervous system.

Prior studies from our laboratory suggest that peripheral sympathetic ingrowth, which occurs in the hippocampus following medial septal lesions, is detrimental to the reaquisition of a spatial learning/memory task. To assess the generality of this finding we studied step-through passive-avoidance learning in animals with a medial septal lesion with or without superior cervical ganglionectomy under two experimental conditions. In the first condition, in which no prior experience with the task occurred, animals with a lesion demonstrated facilitation of learning. In the second condition, in which animals received pretraining with no shock prior to surgical manipulation, the behavior of animals with the lesion was similar to that of controls. No effect of ganglionectomy or initial sympathetic ingrowth was found in either condition. The results suggest that the effects of medial septal lesions on passive avoidance behavior are determined by the experimental condition and that early peripheral sympathetic ingrowth does not contribute either in a detrimental or beneficial fashion to passive avoidance learning.

Animals↗

Pachyonychia congenita with laryngeal involvement.

Pachyonychia congenita (Jadassohn-Lewandowsky Syndrome) is a rare autosomal dominant disorder characterized by nail dystrophy, hyperkeratosis of the palms and soles, leukoplakia of the mucosa of the upper respiratory tract and anus, follicular keratoses especially about the knees and elbows, and palmar and plantar hyperhidrosis. We present a patient with pachyonychia congenita and an exophytic lesion in the larynx at the posterior commissure. He is the youngest of 4 family members with this disorder covering 3 generations. Each of the 4 patients also exhibited both oral leukoplakia compatible with the Jadassohn-Lewandowsky syndrome (Ikonograph Dermatol. Lab., 1 (1906) p. 29), and subcutaneous cysts of the face and scalp as described by Jackson and Lawler (Ann. Eugenics (1951) 142.

Adolescent↗

Effects of olsalazine in the jejunum of the rat.

Olsalazine (ADS) is the azo-linked dimer of 5-aminosalicylic acid (5-ASA). It is of value for the management of patients with ulcerative colitis but may be associated with increasing diarrhoea in a few. This study examines the effect of 5-ASA and ADS on small intestinal transport systems of the rat. Krebs-Ringer-bicarbonate solution was circulated through the lumen of a jejunal segment and the appearance of fluid, glucose and lactate on the serosal surface was shown to be linear over a two hour period. Addition of 5-ASA (10 mmol/l) or ADS (5 mmol/l and 10 mmol/l) caused a significant inhibition both of fluid transport (p less than 0.001), and of the appearance of glucose (p less than 0.001) and lactate (p less than 0.001 for 5 mmol/l and 10 mmol/l ADS, p less than 0.01 for 10 mmol/l 5-ASA). The uptake of glucose by rings of rat jejunum was shown to be markedly reduced by ADS. Experiments substituting glucose with either sucrose of 2-aminoisobutyric acid showed that ADS (5 mmol/l, 10 mmol/l) also inhibited the serosal appearance of fructose and the amino acid. These results show that 5-ASA and ADS, at concentrations which could be expected in the jejunum of patients receiving therapeutic doses, are able to inhibit small intestinal transport systems. The resulting increase in load on the diseased colon could be important for the pathogenesis of diarrhoea.

Aminoisobutyric Acids↗

Vascularly perfused frog lung: effects of metabolic conditions on adenine nucleotides and inorganic ions.

The metabolic activity of frog lung perfused through its vascular bed has been assessed by determining changes in metabolites in the perfusion medium and by measuring the adenine nucleotides, ions and water in the tissue after perfusion under a variety of conditions. The addition of respiratory inhibitors, CN- or antimycin A, reduced the adenylate energy charge when a glucose-free perfusate was used but not when glucose was present. CN- and anaerobiosis stimulated lactate production while iodoacetate reduced lactate production and the adenylate energy charge. The addition of fatty acids, glutamine or lactate to the perfusate had no effect on the adenylate energy charge or ionic contents. With plasma albumin depleted of fatty acids in the perfusate, there was an increased production of NH4+; this could be partially suppressed by the addition of butyrate or octanoate. Glutamine increased NH4+ production and lactate was consumed by the lung, indicating that both of these substrates are metabolized. The tissue levels of Na+ and K+ were remarkably resistant to ouabain, a concentration of 2 mmol X 1(-1) being required to produce significant reduction of K+ and increase in the tissue Na+; the contents of adenine nucleotides, Ca2+ and Mg2+ were unaffected. During April-June, the tissue ATP and adenylate energy charge appeared to be particularly sensitive to PO2 in the perfusate.

Adenine Nucleotides↗

Uptake of uric acid, xanthine and hypoxanthine by brush-border membrane vesicles from mouse small intestine.

Using mouse small intestine brush-border membrane vesicles virtually free of xanthine oxidase (EC 1.2.3.2) and free of uricase (EC 1.7.3.3) the uptake of the purines uric acid, xanthine and hypoxanthine have been studied. The sodium-dependent overshoot phenomenon shown to exist for the uptake into the vesicles for D-glucose and L-phenylalanine was not observed with the purines. However, the uptake of the three purines in the presence of NaCl or KCl was greater than the uptake in the presence of either NaSCN or mannitol. Although 12.9% of the xanthine uptake and 17.6% of the hypoxanthine uptake was attributed to binding to the membranes, almost all the uric acid uptake was due to transport into an osmotically active space. The apparent intravesicular volume, calculated after 60 min incubation, for the three purines was consistently greater than the values obtained with D-glucose, L-glucose and L-phenylalanine equilibration, suggesting slow continuing penetration of purines associated with swelling or an apparent accumulation of purines within the vesicles associated with normal vesicle volume.

Animals↗

Absorption and metabolism of fructose by rat jejunum.

The absorption and metabolism of fructose was investigated in the vascularly perfused jejunum of fructose-fed rats. With 10 mM-glutamate and 10 mM-fructose in the lumen, the viability of the tissue is maintained and fructose is absorbed and utilized at high rates. With 28 mM-fructose in the lumen, glucose appears in the vascular bed. With 10 mM- or 28 mM-fructose in the presence of 10 mM- or mM-glucose in the lumen, the fructose absorption is decreased. From 10 mM- or 28 mM-sucrose in the lumen, fructose uptake is also less than from the equivalent concentration of free fructose. The rate of appearance of fructose in the vascular bed is independent of the source of fructose from which it is derived. In the presence of glucose, either free or as sucrose, there is a marked decrease in the utilization of fructose, defined as the difference between that absorbed by the jejunum and that transported unchanged into the vascular bed. In all cases about half of the carbohydrate absorbed from the lumen is converted into lactate, most of which is secreted into the blood. The absorption of glucose and the rate of vascular appearance of glucose from glucose in the lumen are about 1.5 times greater than those of fructose from fructose in the lumen. It is concluded: firstly, that fructose uptake from the lumen of rat jejunum is determined by its concentration and by the demand for it as a fuel for the intestine, a demand that is severely decreased in the presence of glucose; secondly, that in the vascularly perfused jejunum there is no evident kinetic advantage for uptake of fructose or glucose from sucrose rather than from free monosaccharide in the lumen; thirdly, that some fructose can be converted into glucose.

Animals↗

Absorption and metabolism of allopurinol and oxypurinol by rat jejunum in vitro: effects on uric acid transport.

The transport and metabolism of allopurinol and oxypurinol have been examined in a preparation of adult rat jejunum in vitro. When present in the lumen (50-500 mumol/l) allopurinol appeared in the serosal secretions at lower concentrations, together with its metabolite oxypurinol and an unidentified substance. Oxypurinol in the lumen (1.4-430 mumol/l) was transported into the serosal secretions and at luminal concentrations below approximately 150 mumol/l was concentrated in the secretions. The transport of oxypurinol into serosal secretions was greater than that of allopurinol. Allopurinol and oxypurinol decreased the appearance of urate, in the serosal secretions and the luminal fluid, by an amount which was greater than the concomitant increase in oxypurines; they increased the rate constant of the mono-exponential washout of endogenous urate and induced purine secretion into the lumen. The transport of uric acid from the lumen into the serosal secretions was inhibited by allopurinol and oxypurinol. With allopurinol the specific radioactivity (14C) of urate in the serosal secretions approached that in the lumen; with oxypurinol the specific radioactivity was approximately 70% that in the lumen. There was no evidence for the uphill movement of urate from the lumen.

Allopurinol↗

Introductory remarks on the brush border.

The specialized surface of the luminal border of small intestinal epithelial cells was first described by J. Henle in 1837 and for many years controversy raged about the nature of this region. Was it a plate rendered porous by perforating canals or was it composed of an array of rods with their long axes normal to the surface? Because the diameter of the microvilli was below the limits of resolution by optical microscopy, the arguments could not be settled until the region had been observed under the electron microscope in 1950. In 1961, the brush border membrane (also known as the free border or microvillus membrane) was separated for biochemical study and results on transport using vesicles were first described in 1973. The increase in surface area due to the microvilli is about 40 times and the surface: volume 'ratio' for a single microvillus is 4 X 10(5) cm-1, about 20 times that for an erythrocyte. An important but unresolved question concerns the relationships between transporter proteins in the membrane and proteins that have digestive functions; the physiological role of the glycocalyx is not yet resolved.

Animals↗

Shuttlebox self-stimulation in the rat: an anatomical analysis and the effect of morphine with two current levels.

A shuttlebox paradigm was used to train rats to turn electrical stimulation ON and OFF by crossing back and forth in a stabilimeter cage. Two experiments are presented. In the first experiment a threshold current level was used in testing four electrode sites: the lateral hypothalamic area (LHA), lateral septal nucleus (LSN), periaqueductal grey (PAG), and the mesencephalic reticular formation (MRF). In the second experiment, a suprathreshold current level was used to explore two electrode sites: the PAG and the MRF. Stimulation with electrodes in the MRF produced an aversive behavioral response; animals shuttled mainly to turn electrical stimulation OFF. At the other electrode sites, both rewarding and aversive properties were apparent: animals shuttled to turn the stimulation ON as well as OFF. Systemic morphine (10 mg/kg) injections nonselectively increased both average ON and OFF times for the three rewarding sites (minimum p less than 0.05) at the threshold current level. Systemic morphine injections (10 mg/kg) in animals stimulated at a suprathreshold current level in the PAG selectively increased time spent with stimulation ON (p less than 0.05) as opposed to time spent with stimulation OFF. No significant behavioral change due to morphine was seen in the aversive MRF at either current level. Animal behavior also was found to vary as a function of site of stimulation (p less than 0.05). The use of suprathreshold currents appears necessary to produce selective reward facilitation effects of morphine such as those found in the PAG or LHA.

Animals↗

Application of high performance liquid chromatography to study transport and metabolism of nucleic acid derivatives by rat jejunum in vitro: endogenous washout.

A procedure is described for maintaining segments of rat jejunum in vitro in a steady state of fluid and solute absorption for periods of up to 2 h so that the secretion of endogenous and exogenous nucleic acid derivatives across the serosa may be followed. Methods of high performance liquid chromatography for the separation and measurement of some nucleic acid derivatives are also described. These procedures are applied to investigate three endogenous components found in the washout into the serosal secretions. The kinetics of the washout are, in each case, mono-exponential and the effects of pre-feeding, of pre-feeding a glucose solution and of the diabetic state on the washouts have been investigated. One of the components of the washout is uric acid, the initial pool size of which varies from 13-22 mumol/g dry wt. of jejunum. Negligible amounts of derivatives of endogenous origin appear in the lumen.

Animals↗