The GABA receptor-chloride ion channel protein complex.
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Biomedical subjects
Publications and source records attributed to G Smith.
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Ethanol (2 gm/kg of maternal body weight administered in four equal doses of 0.5 gm/kg over 5 hours) was infused intravenously into nine chronically prepared pregnant ewes between 124 and 137 days' gestation. The data demonstrated a dose-response relationship between fetal arterial ethanol concentrations and the incidence of fetal breathing movements. Suppression of normal fetal electrocortical activity occurred at a low ethanol concentration and returned to control values at a time of very high arterial ethanol concentrations. This experimental model of a binge drinking episode further supports the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.
Glycosaminoglycans (GAG) were extracted from the connective tissue of 15 dental cysts, 2 dentigerous cysts and 7 keratocysts, and separated electrophoretically and chromatographically. Hyaluronic acid (dental, 2.38; dentigerous, 3.98; keratocyst, 3.19 micrograms uronic acid/mg lyophilized tissue) was the major GAG detected, with lesser amounts of heparin (dental, 1.70; dentigerous, 1.95; keratocyst, 1.80 micrograms uronic acid/mg lyophilized tissue) and chrondroitin-4-sulphate (dental, 1.33; dentigerous, 2.85; keratocyst, 1.37 micrograms uronic acid/mg lyophilized tissue). It is suggested that enzymic release of these GAGs allows their diffusion into the luminal fluid where they may contribute to expansile cyst growth.
A characteristic electrophoretic pattern of glycosaminoglycans from fluid aspirates of the postoperative maxillary cyst has been observed. This pattern, in which hyaluronic acid and heparan sulfate are the predominant glycosaminoglycans (with lesser amounts of chondroitin-4-sulfate) may faciliate preoperative diagnosis of this lesion.
The construction and use of mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta is discussed. Simulated field trials implemented by deterministic mathematical models currently share with actual field trials the disadvantage that they convey no information concerning the risk associated with the net return demonstrated by the trial. This has important implications when it is necessary to rank disease control strategies in order of usefulness.
1. Diltiazem at doses of 2.5, 25, and 50 mg/kg caused a reduction of minute ventilation of hamsters over a 60 min period compared to saline administration. 2. The decrease of ventilation was due to a fall in frequency of breathing, but predominantly due to a decrease of tidal volume. 3. The pattern of metabolic response of hamsters to diltiazem was different to the ventilatory response--but metabolic rate was decreased in all animals receiving diltiazem by 60 min compared to pregavage values.
The population biology of the parasitic phase of the Haemonchus contortus life-cycle is discussed within the context of a mathematical model of those processes which regulate population density. Parasite death is assumed to be attributable to at least three processes: failure of the 3rd-stage larvae (L3) to exsheath following ingestion, failure to become established following exsheathment (immune exclusion), and mortality of 4th- and 5th-stage worms on the mucosal surface. The proportion of worms which avoid immune exclusion is a declining sigmoidal function of the duration of infection, at least under conditions of continual exposure to L3 larvae. Under the same conditions, the death rate of 4th- and 5th-stage worms can be modelled as an increasing linear function of the host's experience of 3rd-stage larvae. The model provides a good description of the worm burdens observed during the course of a long-term trickle infection experiment even though a priori arguments indicate that it would be an inadequate representation of events in the field.
A double-blind, randomized, parallel-group study compared the analgesic efficacy of a single oral dose of 500 mg diflunisal, 60 mg codeine, 500 mg diflunisal plus 60 mg codeine given as separate agents, and placebo in 161 patients with moderate to severe postoperative pain. Standard subjective measures were used to evaluate analgesia. Eight-hour sum of pain intensity differences and total pain relief scores for all active treatments were significantly better than were those for placebo (p less than 0.05). Diflunisal plus codeine performed the best followed by diflunisal, codeine, and placebo. Diflunisal plus codeine was better than placebo from 1 1/2 to 8 hours (p less than 0.01), better than codeine from 1 1/2 to 6 hours (p less than 0.05), and better than diflunisal alone from 1/2 to 1 1/2 hours (p less than 0.05) for most measures of analgesia. Factorial analysis demonstrated a significant early codeine effect and a significant diflunisal effect throughout. No significant treatment group differences were observed regarding adverse effects. Our data demonstrate that diflunisal plus codeine is generally well tolerated and provides analgesia superior to that of diflunisal or codeine alone in the treatment of moderate to severe postoperative pain.
While the cognitive deficits of Alzheimer's disease are considered related to a cholinergic deficit, no attempt has yet been made to test the hypothesis that the characteristic regional cerebral blood flow (rCBF) pattern of Alzheimer's disease may also relate to such a deficit. We therefore measured rCBF using the [133Xe] inhalation technique in 15 young normal subjects before and after induction of reversible cholinergic blockade with scopolamine at doses of 6.1 and 7.3 micrograms/kg i.v. Significant cognitive impairment was observed at both doses, while rCBF changes occurred only at the higher dose. Global CBF was significantly reduced 25 min after scopolamine. The pattern of regional change in CBF was not similar to Alzheimer's disease. Rather than a focal parietotemporal deficit as seen in Alzheimer's disease, we observed a predominantly frontal reduction in flow of about 20%. These results suggest that the frontal but not the parietotemporal deficits seen in several dementing conditions may be related to cholinergic dysfunction.
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The morphine hydrogel suppository (MHS), a monolithic sustained release rectal preparation, has been developed and evaluated in three pilot studies. Two release profiles have been prepared. The first, MHS(B), has a high initial release rate followed by a constant release for the remainder of a 12-h period. The second, MHS(S), has the same constant release rate for 12 h. MHS(B) is intended to attain and maintain analgesic or near analgesic plasma concentrations of morphine, and MHS(S) to maintain that concentration for successive 12-h periods. The pilot studies suggest that MHS may be of value in the management of postoperative pain.
Aztreonam, the first available monobactam, was used to treat 38 episodes of serious infection presumed or proven to be due to aerobic Gram-negative bacteria. On 15 occasions it was used empirically in combination with other antibiotics and on 23 occasions as therapy specifically directed against Gram-negative pathogens. Thirty-six Gram-negative infections were documented (including 23 septicaemias) and 35 of them were clinically cured by aztreonam. Likewise 35 of the 36 aerobic Gram-negative pathogens were eradicated. Both of the failures (one clinical and one microbiological were Salmonella infections). No major toxicity was seen but there were five superinfections (four due to Streptococcus faecalis). The results indicate that aztreonam is a useful alternative to the aminoglycosides or the broad-spectrum beta-lactam antibiotics for the treatment of severe Gram-negative infections.
Ileal prostaglandin (PGs) biosynthesis was compared in female rats in normal mild hemorrhage (exposed to mild hypotension, reperfusion, and maintenance on hyperalimentation for 5 days) and control groups (instrumentation and hyperalimentation without hemorrhage). Tissue PG levels were analyzed by radiochromatographic analysis of microsomal membrane fractions prepared from the ileum in each group. Total cyclooxygenase activity in the normal and control groups was modest, with low levels of 6-keto-PGF1 alpha, PGE2, PGF2 alpha, thromboxane B2, PGA2, and PGD2 being produced. Hemorrhage, reperfusion, and maintenance on hyperalimentation for 5 days markedly induced total cyclooxygenase activity in the female rat ileum. Ileal microsomal membrane fractions obtained from the mild hemorrhage group synthesized levels of individual PGs three- to seven-fold higher than the normal or control groups, with 6-keto- PGF1 alpha (breakdown product of prostacyclin), PGE2, and PGA2 demonstrating the highest levels of biosynthesis. These data suggest that the gastrointestinal tract could serve as a source for the elevated PGs known to occur in various shock models.
A nondestructive method of constructing the three-dimensional refractive index profile of crystalline lenses is presented. The technique is based on earlier work in which the refractive index profile is deduced from measuring the refraction of a set of light rays that traverse the lens in a particular plane. However, the present approach requires fewer assumptions about the form of the refractive index profile so that the deduced results are less likely to reflect preconceived notions about the form of the refractive index distribution. An accurate model for the bovine crystalline lens has been constructed with the present approach. Without further adjustable parameters, our three-dimensional model of the lens refractive index profile is able to predict accurately the refraction of meridional rays that traverse the lens in the sagittal plane. Preliminary data on human lenses are also presented.
A double-blind investigation was undertaken to compare the efficacy of nalbuphine and fentanyl in the prevention of pain after day case termination of pregnancy. Forty patients were allocated randomly to receive nalbuphine 0.25 mg/kg or fentanyl 1.5 micrograms/kg immediately before induction of anaesthesia. The patients completed scores for pain and nausea, and performed a reaction time test to assess recovery. An observer assessed patient appearance at 1, 2 and 4 hours postoperatively. Patients who received nalbuphine had significantly lower pain scores at 1 hour (p less than 0.01) and 2 hours (p less than 0.05) and required significantly (p less than 0.05) less postoperative analgesia. No significant differences were found between the groups for incidence of nausea or for observer assessment of appearance. There was some evidence of psychomotor impairment at 2 hours in the nalbuphine group. Freedom from Controlled Drug Act regulations and improved analgesia with nalbuphine, render it more satisfactory for day case surgery than the more commonly used fentanyl.
The catecholamine and cardiovascular responses to laryngoscopy and tracheal intubation were studied in 20 patients who underwent elective gynaecological surgery and who were allocated randomly to receive either practolol 10 mg or saline intravenously prior to induction of anaesthesia. Anaesthesia was induced with fentanyl and thiopentone; atracurium was administered and the lungs were ventilated artificially with 67% nitrous oxide in oxygen. Tracheal intubation was performed when muscle relaxation was adequate. Arterial pressure, heart rate, plasma noradrenaline and adrenaline concentrations were measured before and after tracheal intubation. A significant increase in catecholamine concentrations occurred in both groups in response to tracheal intubation but the magnitude of the increase in adrenaline was greater in the practolol group. There were no significant differences in arterial pressure or heart rate changes between the groups. We conclude that pretreatment with practolol is of no value in the attenuation of the hypertensive response to direct laryngoscopy and tracheal intubation in previously normotensive patients.
Plasma catecholamine concentrations were measured in 12 patients who had bilateral bat-ear surgery following infiltration of each ear with 2 ml 2% lignocaine with adrenaline 1:100,000. Venous blood samples were withdrawn before and at set intervals after infiltration. Plasma adrenaline concentration increased from 0.8 pmol/ml to a peak of 2.2 pmol/ml at 2 minutes after infiltration; this is an increase of 175%. There was no significant change in plasma noradrenaline concentration.
Parents of 63 North American girls with Rett syndrome filled out retrospective questionnaires in a project of the International Rett Syndrome Association, a parent group. No consistent pattern was revealed of possible etiological factors related to environmental insults; however, additional information gathered supported a genetic etiology. The survey included one pair of identical twins and one child with consanguineous parents. There were 46 male sibs and 34 female sibs. These data weigh against any theory relating etiology to a gene on the X chromosome which is lethal to males in utero. Figures were gathered on a number of clinical items. These were: onset of symptoms between 6 and 18 months of age, 83%; autistic withdrawal, 73%; never walked independently, 23%; hyperventilators with abdominal swelling, 63%; night laughter, 83%. The average age of walking of those who walked was 19 months and the average onset of seizure disorders was between 3 1/2 and 4 years of age. This paper ends by discussing the limitations of a parent questionnaire.