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Biomedical subjects

D Ingram

Publications and source records attributed to D Ingram.

At least 91 records · Page 5Linked to original sources

Heterogeneity of the rabbit collecting tubule: localization of mineralocorticoid hormone action to the cortical portion.

This study was designed to examine the sodium, potassium, and chloride transport rates across the cortical and outer medullary collecting tubule and to localize the action of mineralocorticoid hormone. Rabbit collecting tubules were dissected from the cortex (CCT), the outer stripe of the outer medulla (OMCT0), or the inner stripe of the outer medulla (OMCTi). From normal rabbits, the transepithelial voltage was -20.8 +/- 2.7 mV in CCT, -4.2 +/- 1.4 mV in OMCT0, and +10.6 +/- 2.3 mV in OMCTi. From DOCA-treated rabbits, only the CCT voltage was different (-42.9 mV). Net sodium absorption across the CCT increased ith DOCA-treatment from 23 +/- 5 to 54 +/- 8 pEq . mm-1 . min-1, whereas net potassium secretion increased from 15 +/- 2 to 43 +/- 5 pEq . min-1 . min-1. Net chloride absorption was significant only in DOCA-treated rabbits. The OMCTi, in contrast, displayed no net transport of sodium, potassium, or chloride and had a lower rate coefficient for sodium efflux than did the CCT. DOCA treatment had no effect on any transport rate measured in this segment. The OMCT0 has small potassium secretion, which did not increase with DOCA treatment. The collecting tubule is heterogeneous along its length with respect to ion transport. Mineralocorticoid-hormone-sensitive sodium absorption is present predominantly, if not exclusively, in the cortical collecting tubule.

Animals↗

An evaluation of the clinical potential of a comprehensive model of human respiration in artificially ventilated patients.

1. We have investigated the feasibility of accurately simulating the respiratory function of artificially ventilated patients, using a computer model of the respiratory system. Twelve patients artificially ventilated after uncomplicated cardiac bypass surgery was studied. 2. The basic information required to simulate individual ventilated subjects was measured or derived. A program was written to enable key model parameters to be adjusted automatically to match model predictions to these clinical measurements. On completion of this matching procedure all the variables computed by the model were compared with patient values (measured or derived) and their accuracy was assessed. 3. The matching algorithm successfully optimized parameters of the model representing metabolic activity, tissue respiratory quotient, venous admixture, physiological dead space and total body bicarbonate to match measured values for oxygen consumption, carbon dioxide production, Pa, O2, PaCO2, and arterial HCO3- respectively. Other variables compared arise from the solution of equations within the model and correlation between model and patient values is generally good (r greater than 0.9). However, values of Pv-, O2 correlate less well (r = 0.85). Factors affecting the accuracy of patient simulation are discussed and some deficiencies analysed. 4. The creation of an accurate, steady-state representation of a patient by the model opens up the possibility of using it interactively as an aid to clinical management. Some possible future developments of the technique are discussed.

Blood↗

'MacDope': a simulation of drug disposition in the human body: applications in clinical pharmacokinetics.

1 We have described a novel approach to absorption, distribution, metabolism and elimination of drugs in which the patient is described using 23 Patient Factors and drugs by up to 50 Drug Factors. Kinetic behavior of a drug results from the interaction of patient and drug factors according to equations describing an eight compartment model. In this model non-linear processes (protein binding, hepatic drug metabolism and renal tubular transport) are handled by derivations of the law of mass action which have been generalised to permit the consequences of multiple drugs interacting at single macromolecular sites to be correctly calculated. 2 The mathematical description of this model is provided in a companion paper and solution of the equations is only possible using a digital computer. The computer programme is provided with an interactional format which makes operation independent of mathematical skills. Patients are defined by age, sex, height and weight with, or without, organ dysfunction; the programme then generates appropriate factors. Drug enters the system when a prescription is type on the keyboard and required Drug Factors are then retrieved from the disc flies. Drug concentrations in plasma or body fluids are given as simple graphs as a function of time, or in tabular form. 3 Any of the Patient or Drug Factors may be altered before, or during a run and up to three drugs may be simulated at one time thus permitting certain kinetic interactions to be examined. The scope of the simulator is illustrated using aspirin: pH dependent gastric absorption, first-order conversion of aspirin to salicylate, partly first order and partly saturable hepatic metabolism of salicylate, and the complex renal handling of this drug are all represented. Interaction of phenytoin with salicylate has been examined quantitatively to suggest limited clinical relevance for the observed displacement of phenytoin from serum albumin. The use of the simulator in a short course of pharmacokinetics is briefly described.

Aspirin↗

Controlled trial of intermittent aerosol therapy with sodium 2-mercaptoethane sulphonate in cystic fibrosis.

Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug, sodium-2-mercaptoethane sulphonate (Mistabron, UCB Pharmaceutical Division, Brussels, Belgium), with inhaled iso-osmolar hypertonic saline. As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy, both when compared with a control period, and with iso-osmolar saline results. Subjective measurements by diary card failed to show any changes. No significant changes were found in five patients with no measurable sputum production. The inhalations were given after physiotherapy and were well tolerated. There were no significant side effects. The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality, and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis.

Adolescent↗

Inversion of subject NP and Aux in children's questions.

Bellugi has proposed a stage of language acquisition in which children invert subject NP and Aux in yes-no but not wh questions. It was proposed that this stage would be found in a sampling of questions from young children. Cross-sectional samples of questions were collected from young children between 2:0 and 3:11. The results did not bear out this expectation. Based on percentages of inversion, none showed this stage. The results are discussed in terms of the importance of frequency in determining stages of acquisition and the use of children's data as psychological evidence for linguistic rules.

Child, Preschool↗

Recurrent biliary calculi due to non-absorbable cystic duct ligatures.

A non-absorbable cystic duct ligature may migrate into the common bile duct and act as a nidus for recurrent stone formation. Four case histories are presented and the problem is discussed. This sequel may be prevented by the use of absorbable sutures to ligate the cystic duct, thereby reducing the number of patients facing the hazards of recurrent biliary surgery.

Adult↗

Immunochemical studies of 5-bromodeoxyuridine.

Specific antibodies for BrdUrd and IdUrd have been produced and characterized by immunochemical studies. Studies as determined by hapten-inhibition showed a cross reactivity of less than 0.001% to thymidine, and no cross reactivity to bromodeoxycytidine, uridine or methyl cytosine. The equilibrium constant determination for anti-BrdU and IdUrd was 4.2 x 10(8)M-1. Unfractionated antiserum, produced under the conditions herein described, can be employed for the specific cytological detection of DNA replication.

Animals↗

A procedure for dissociating Ayre scrape samples.

The dissociation of cervical cell suspensions after various chemical and enzymatic treatments was monitored by using the Centrifugal Cytology rotor to produce glutaraldehyde-fixed dispersions on conventional microscope slides and subsequent Pap staining. A special program was written in RPG II to record and analyze the results of the dissociation experiments in terms of white blood cells and the true cervical cells ("other cells"), and the degree of dissociation and recovery of both classes of cells. Since accurate differential counts on the untreated Ayre scrapes were difficult, the samples were syringed gently to break up the large or adventitious clumps. Cumulated results from control preparations indicate that the white blood cells and "other cells" are composed respectively of 92 and 63% single cells. The cells were further dissociated by: dissolving the cervical mucin sequentially with dithiothreitol and iodoacetic acid; depolymerizing the nucleohistone gel with ribonuclease; solubilizing the desmosomes with EDTA; removing the remaining cellular agglutinins with Varidase; and finally mechanical dispersion by hypertonic shock. The optimum procedure for dissociation involves the use of ribonuclease, dithiothreitol, iodoacetic acid EDTA, Varidase and sucrose shock. The white blood cells are now monodisperse and 81% of the "other cells" are found as single cells. If nuclear separation by two diameters is considered sufficient 98% of the "other cells" are single. The slide preparations are now sufficiently good that a scanning system is feasible.

Autoanalysis↗

Optimization of the binding of dissociated exfoliated cervico-vaginal cells to glass microscope slides.

In order to monitor the development of a cell dissociation technique, it was essential to utilize the Centrifugal Cytology rotor to produce glutaraldehyde-fixed even cellular dispersions. The Cytology rotor has been improved to insure rapid alignment with the centrifugal field during both acceleration and deceleration, and the fixative is now delivered to the surface of the slide. The dissociation of the cells results in a loss of their adhesion to glass slides. Three bonding agents were tested: (a) Poly-L-Lysine; (b) Mayer's albumin fixative; (c) positively charging the slides with a silicone coating. The results with 65% albumin-coated slides were clearly superior to the other two. The addition of a postfixation step of 95% ethanol/4% polyethylene glycol did not significantly affect the recovery of the cells, but did eliminate some unevenness in the Centrifugal Cytology preparations, flattened the cells and expedited the procedure.

Albumins↗

Continuous monitoring of arterial oxygen tension using a catheter-tip polarographic electrode in infants.

An oxygen electrode mounted in the tip of an umbilical artery catheter was used in 36 newborn infants with severe respiratory illnesses, 28 of whom survived. Thirty-seven electrodes were used. The median age at insertion was 4 hours (range, 30 minutes to 122 hours). Three electrodes failed to work and they were removed or replaced, and two could not be properly evaluated. Thirty-two electrodes functioned satisfactorily for 10 to 190 hours (mean, 75 hours) after a one-point calibration against blood sampled through the catheter. Twenty-two did not need recalibrating before they were removed after 10 to 190 hours (mean, 88 hours. Four of the remaining ten electrodes were recalibrated once after 33 to 97 hours and then functioned until removed 15 to 55 hours later. The other six electrodes failed after 32 to 105 hours (mean, 49 hours). Complications were few. A total of 356 arterial blood samples, obtained after the initial calibration and before any recalibration was necessary, gave a correlation coefficient of 0.93 (P less than .0001) against an independent system for measuring arterial oxygen tension (Pao2) (Radiometer Type E.5046 oxygen electrode). We conclude that the catheter-tip electrode is a safe and reliable instrument for continuously recording Pao2 in newborn infants which much simplifies the management of serious respiratory illnesses.

Arteries↗

Continuous positive airway pressure and mechanical ventilation by facemask in newborn infants.

During a nine-month period 24 newborn infants were treated with continuous positive airway pressure (CPAP) or mechanical ventilation delivered through a facemask. The mask was held in place in a way that minimised trauma and distortion of the head. The median birth weight of the infants was 1096 g and their median gestational age 29 weeks. The usual reason for treatment was hyaline membrane disease or recurrent apnoea due to inadequate control of breathing. Twenty-one of the infants survived. The technique was simple to apply and complications were minimal. We suggest that it may have advantages over other methods of applying CPAP or mechanical ventilation to infants mildly affected by respiratory illnesses and that it should be useful in avoiding endotracheal intubation or reducing the length of time that infants with more serious illnesses are intubated.

Female↗