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Biomedical subjects

A Fisher

Publications and source records attributed to A Fisher.

At least 217 records · Page 12Linked to original sources

Effects of the cholinotoxin, AF64A, on neuronal trace-metal distribution in the rat hippocampus and neocortex.

Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxin which is specific for cholinergic nerve terminals. Besides its effects on elements of the acetylcholine system, we observed that, after 2 and 8 days, a single 20-nmol intracerebroventricular dose altered the Timm's staining of certain regions of the central nervous system and reduced the tissue levels of trace metals. In the hippocampal formation, there was a considerable decrease in the staining of the neuropil of the stratum radiatum and stratum oriens, which contain cholinergic nerve terminals. A reduction in staining was also demonstrated in the perikarya of cortical pyramidal cells. The diminished trace-metal level in both regions was confirmed by quantitative measurements of zinc and copper levels. A similar reduction was not observed at a lower dose (8 nmol) of the cholinotoxin. The results led to the conclusion that AF64A may cause the decrease of the trace-metal content of the postsynaptic neurons through an indirect mechanism.

Animals↗

A controllable artificial afterload for isolated heart studies.

This paper presents an artificial afterload, based on the Westerhof model, for use in isolated heart preparations. The system has adjustable elements representing peripheral resistance and total arterial compliance, together with a fixed element representing aortic impedance. It is controlled by a computer in a manner which incorporates feed forward and feedback techniques. The system maintains constant 'arterial' pressure in the face of large excursions of the flow through it. It can be programmed to change this pressure in a dynamic fashion. The time taken to recover from large changes in flow and to reset the pressure is at most 3 S. Absolute values of peripheral resistance are easily obtained without any knowledge of the actual flow being required. Tests of the system demonstrate its stability and rapid transient characteristics.

Biomedical Engineering↗

Cholinergic lesion of the striatum impairs acquisition and retention of a passive avoidance response.

Significant impairments in the acquisition and retention of a step-down passive avoidance task were found in rats with striatal lesions induced by the cholinergic neurotoxin AF64A. No significant differences between control and AF64A-injected rats were found in sensitivity to electric shock or in various measures of spontaneous locomotor activity. Striatal choline acetyltransferase (CAT) activity was significantly decreased in AF64A-treated rats compared with controls, whereas glutamic acid decarboxylase (GAD) activities were not. Furthermore, there were no significant differences between groups in activities of CAT and GAD in either the cortex or the hippocampus, results that support the specificity of the lesion to the striatum. The passive avoidance deficits found in these rats after intrastriatal injection of AF64A support a role for the striatal cholinergic system in complex behavioral processes.

Animals↗

Plasma morphine concentrations and clinical effects after thoracic extradural morphine or diamorphine.

Twenty-seven patients undergoing thoracotomy received either morphine sulphate 2 mg or diamorphine hydrochloride 2 mg by thoracic extradural injection for postoperative analgesia. Arterial plasma morphine concentrations were measured by specific radioimmunoassay, and the analgesic, respiratory and biochemical effects noted. The plasma morphine concentrations were significantly greater after extradural diamorphine than after extradural morphine in the first 30 min after injection. The maximum increase in plasma morphine concentration was significantly (P less than 0.02) greater after extradural diamorphine, and mean peak values occurred at 5 and 10 min for diamorphine and morphine, respectively. There were significant decreases in respiratory rate and plasma cortisol concentration with maximum effects between 90 and 180 min after the extradural injection. The analgesia produced by these doses was inadequate. The role of lipophilicity is discussed.

Adult↗

Definitive irradiation of T1-T4N0 larynx cancer.

The use of definitive irradiation in T1-T4N0 larynx cancer was reviewed in 236 patients at Rush-Presbyterian-St. Luke's Medical Center in Chicago. Recurrence-free survival for all stages was 86% at five years. Ultimate recurrence-free survival, including successful surgical salvage, was 91% at five years. The data described herein and the literature reviewed support the recommendation for definitive radiation therapy for T1 and T2N0 larynx cancer of any site. T3 lesions may also be reasonably treated with radiation therapy initially, reserving surgery for salvage. However, more data are needed to accurately identify the T3 larynx cancer patients most suited for radiation therapy.

Adult↗

Antenatal education: does it improve the quality of labour and delivery?

Of 196 nulliparous women who delivered in a two month period, 78 percent had attended antenatal education classes. The mothers who did not attend antenatal classes consisted of significantly more Maori and Pacific Island mothers, they were younger, smoked more, had a lower socioeconomic status and fewer were married. The group who went to antenatal education classes had a significantly longer second stage in labour and required more forceps assistance during delivery compared to non-attenders. These results remained for the polynesian mothers, when they were analysed separately and the differences in age and socioeconomic status were no longer present. There was no difference in the type of pain relief required during childbirth by the attenders or non-attenders. We found no evidence that attending antenatal education classes will ensure an easy and less complicated childbirth.

Age Factors↗

Histologic reaction to a new microsurgical suture in rabbit reproductive tissue.

A newly introduced coated polyglactin suture was compared with a polyglycolic acid suture following microsurgical repair of standard rabbit uterine incisions. The degree of inflammatory response and tissue fibrosis for each suture was scored, and the results were compared. At 30 days, an inflammatory response was noted in both groups, with a greater response noted in the polyglycolic acid group. At 90 days, the inflammatory response and tissue fibrosis at the site of repair was evident in both groups, with no significant difference between the groups. The previously reported difference between these two absorbable suture materials in their earlier formulations could not be demonstrated in rabbit reproductive tissue. If an absorbable suture is used for tubal surgery, the choice can be made on considerations other than tissue reactivity.

Animals↗

Differing effects of pectin, cellulose and lignin on stool pH, transit time and weight.

Randomized cross-over studies were undertaken to determine the effects of daily dietary supplements of pectin (12 g/d), cellulose (15 g/d) and lignin (12 g/d) on stool characteristics of healthy volunteers. Detailed dietary records were kept throughout the study. Stool collections over 48 h were used to determine mean stool pH and weight. The single stool transit time was measured using radio-opaque markers. Pectin did not significantly alter the mean stool pH, transit time or 24 h wet weight. Cellulose lowered the mean stool pH from 6.38 to 6.12, decreased mean stool transit time by 27% and increased mean wet stool weight by 57%. Lignin lowered the mean pH from 6.34 to 6.25, decreased the stool transit time by 20% and increased stool weight by 27% but these changes were not statistically significant. These findings have shown that individual fibre components have different colonic metabolic effects and support the view that associations between dietary fibre intakes and diseases such as colorectal cancer should be evaluated with regard to the type of fibre components consumed.

Adult↗

Primary position upbeating nystagmus. A variety of central positional nystagmus.

We report a collaborative study of 11 patients with upbeat nystagmus in the primary position of gaze. In most cases the nystagmus behaved in accordance with Alexander's Law; in 3 patients convergence enhanced the nystagmus. Lateral gaze was without effect in 7 instances. Static tilt to prone and supine positions altered the characteristics of the nystagmus in 7 patients. The effects were variable and, in one case, there was reversal of the direction of the nystagmus to downbeating. There was pathological or radiological confirmation of lesions in the pontomedullary junction (2 cases) and the pontomesencephalic junction (2 cases). The findings support previous reports that primary position upbeat nystagmus occurs predominately with intra-axial brainstem lesions. There is one report of its occurrence with an intrinsic cerebellar lesion. Modification of the amplitude of upbeat nystagmus by tilt of the head with respect to gravity in the majority of patients implies an otolith-related component in the genesis of the nystagmus.

Adult↗

Selective presynaptic cholinergic neurotoxicity following intrahippocampal AF64A injection in rats.

Compound AF64A, ethylcholine mustard aziridinium ion (0.4-8 nmol) was stereotaxically administered into rat dorsal hippocampus, and neurochemical changes were determined 5 days later. AF64A treatment, over an almost 10-fold dose range, resulted in a significant (up to 70%) decline in choline acetyltransferase activity. In the same tissue samples, Na+-dependent choline transport activity was also lowered, with most decreases ranging between 10 and 50% of controls; however, there was no significant correlation (r = 0.39) between these two parameters. Acetylcholinesterase activity was not affected by AF64A treatment when assayed by either histochemical or enzymatic methods. AF64A reduced acetylcholine levels by 43%, but did not alter norepinephrine content or serotonin uptake. These results demonstrate that AF64A can induce a specific, long-term reduction of cholinergic presynaptic biochemical markers in rat hippocampus. Thus, AF64A can serve as a useful new tool to study the cholinergic system and as an important agent to help develop animal models representing disorders of central cholinergic hypofunction.

Acetylcholine↗

Selective inhibition of peripheral cholinergic transmission in the cat produced by AF64A.

The neuropharmacologic effects of ethylcholine aziridinium ion, AF64A, were studied in cats, using various physiological techniques, to ascertain its synaptic site of action and to determine whether it may act as a cholinergic specific neurotoxin in vivo. Nictitating membrane contractions elicited by preganglionic nerve stimulation (1-16 Hz) were diminished in a dose-dependent manner after injection of AF64A into the carotid artery. Contractions due to injection of l-norepinephrine, tetramethylammonium or acetylcholine were not changed. Postganglionic action potentials from the superior cervical ganglion evoked by preganglionic stimulation were also abolished by AF64A, whereas the postganglionic firing produced by tetramethylammonium was unchanged. Neither the nictitating membrane nor ganglionic responses on the contralateral side of the animal were affected by AF64A treatment. In the same animals, twitch tension in the tongue produced by stimulation of the ipsilateral hypoglossal nerve (1-16 Hz) was gradually reduced and in most experiments completely blocked by AF64A. Repetitive stimulation of either the autonomic or somatic nerves at high frequencies (greater than 10 Hz) magnified and accelerated the onset of neurotoxic effects of AF64A. The suppression of ganglionic and neuromuscular transmission by AF64A was irreversible during the course of the experiments (12-18 hr). From these results, we can conclude that AF64A produces in the peripheral nervous system a longlasting inhibition of cholinergic transmission, without interfering with adrenergic transmission. Moreover, because AF64A did not block the postganglionic responses elicited by cholinergic nicotinic and muscarinic agonists, the inhibitory effects of AF64A must be mediated by a presynaptic action on cholinergic nerve terminals.

Acetylcholine↗

Cooperative interaction among cell surface sites: evidence in support of the surface adsorption theory of cellular electrical potentials.

Resting potentials were studied in frog sartorius muscles equilibrated in Ringer solutions that contained various concentrations of K+. Cells in solutions that contained near-zero K+ showed a rise in potential followed by a slow decline over about 70 hours that paralleled the loss of cellular K+ in exchange for Na+. When these cells were placed in 2.5 mM K+, the re-gain of the potential occurred much more rapidly than the re-gain of cellular K+. Thus, there was no consistent relation between resting potential and concentration of intracellular K+. When cells were immersed in solutions containing 100 mM Na+ and K+ at concentrations of 2.5 mM and greater, there was a semi-logarithmic relation between potential and [K+]ex, in which potential declined as [K+]ex increased. However, when cells were equilibrated in [K+]ex below 2.5 mM, the potential peaked and then declined as [K+]ex decreased. The results are readily explained by the surface adsorption model of the cellular potential, in which the potential is determined simply by the nature of the fixed surface charges that interact with one another in a cooperative manner. The peak and decline of the potential with decreasing [K+]ex below 2.5 mM mirrors the autocooperative shift in the affinity of the surface charged sites from one that favors K+ over Na+ strongly to one that favors K+ over Na+ less strongly.

Animals↗

Dietary intakes and stool characteristics of patients with the irritable bowel syndrome.

Detailed dietary records were obtained from 30 women with the irritable bowel syndrome and 25 healthy, asymptomatic women. Stool transit times and wet stool weights were measured. Analysis of the dietary data revealed no significant difference between energy, protein, fat, carbohydrate, or total fiber intakes. Total dietary fiber intake was 17 g/day in the irritable bowel group and 18 g/day in the control group, but vegetable fiber intake was significantly lower in the patients (6.6 g/day) than the controls (8.2 g/day). Cereal and fruit fiber were comparable for both groups as were the stool transit times and wet stool weights. These results do not support the hypothesis that symptoms of the irritable bowel syndrome are directly related to total or cereal fiber depletion.

Adolescent↗