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Biomedical subjects

J Shelton

Publications and source records attributed to J Shelton.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cutting thread at flexible endoscopy.

BACKGROUND: New thread-cutting techniques were developed for use at flexible endoscopy. A guillotine was designed to follow and cut thread at the endoscope tip. A new method was developed for guiding suture cutters. Efficacy of Nd: YAG laser cutting of threads was studied. Experimental and clinical experience with thread-cutting methods is presented. METHODS: A 2.4 mm diameter flexible thread-cutting guillotine was constructed featuring two lateral holes with sharp edges through which sutures to be cut are passed. Standard suture cutters were guided by backloading thread through the cutters extracorporeally. A snare cutter was constructed to retrieve objects sewn to tissue. Efficacy and speed of Nd: YAG laser in cutting twelve different threads were studied. RESULTS: The guillotine cut thread faster (p < 0.05) than standard suture cutters. Backloading thread shortened time taken to cut thread (p < 0.001) compared with free-hand cutting. Nd: YAG laser was ineffective in cutting uncolored threads and slower than mechanical cutters. Results of thread cutting in clinical studies using sewing machine (n = 77 cutting episodes in 21 patients), in-vivo experiments (n = 156), and postsurgical cases (n = 15 over 15 years) are presented. CONCLUSIONS: New thread-cutting methods are described and their efficacy demonstrated in experimental and clinical studies.

Animals↗
PubMed1995

Suppression of anti-thyrocyte autoreactivity by the lymphocytes of normal fetal lambs.

We have devised an experimental strategy to determine whether the developing immune system of normal fetal animals can spontaneously acquire the capacity to inhibit autoimmune responses by its cells as it matures. Whilst the existence of cells with the capacity to exert negative regulation and to curtail autoimmune responses has been demonstrated previously in response to the experimental induction of these responses, the relevance of such regulatory processes to the prevention of overt autoimmunity in normal animals has not been established. We have produced pairs of identical twin fetal lambs by splitting blastocysts and have subsequently deprived one of each pair of exposure to thyroid-specific antigens by surgical thyroidectomy before development of immunological self recognition. Thyroidectomized fetuses developed T lymphocytes autoreactive against self thyrocytes. However, their normal, identical co-twins were found to acquire a class of T lymphocytes with the capacity to block anti-thyrocyte autoreactive cells from the thyroidectomized fetal co-twin. Blocking of anti-thyroid autoreactivity required preliminary contact between these normal T lymphocytes and the target thyrocytes. Substitution of an allograft of fetal thyroid tissue for a fetal lamb's own thyroid gland failed to prevent the development of autoreactivity against autologous thyrocytes by the recipient's lymphocytes. However, the reactivity of those lymphocytes against thyrocytes from the specific allogeneic thyroid donor was markedly curtailed.

Animals↗
PubMed1995

Muscle atonia is triggered by cholinergic stimulation of the basal forebrain: implication for the pathophysiology of canine narcolepsy.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep-related symptoms, such as cataplexy. The exact pathophysiology underlying the disease is unknown but may involve central cholinergic systems. It is known that the brainstem cholinergic system is activated during REM sleep. Furthermore, REM sleep and REM sleep atonia similar to cataplexy can be triggered in normal and narcoleptic dogs by stimulating cholinergic receptors within the pontine brainstem. The pontine cholinergic system is, therefore, likely to play a role in triggering cataplexy and other REM-related abnormalities seen in narcolepsy. The other cholinergic system that could be involved in the pathophysiology of narcolepsy is located in the basal forebrain (BF). This system sends projections to the entire cerebral cortex. Since acetylcholine release in the cortex is increased both during REM and wake, the basocortical cholinergic system is believed to be involved in cortical desynchrony. In the current study, we analyzed the effect of cholinergic compounds injected into the forebrain structures of narcoleptic and control dogs. We found that carbachol (a cholinergic agonist) injected into the BF triggers cataplexy in narcoleptic dogs while it increases wakefulness in control dogs. Much higher doses of carbachol bilaterally injected in the BF were, however, shown to trigger muscle atonia even in control dogs. These results suggest that a cholinoceptive site in the BF is critically implicated in triggering muscle atonia and cataplexy. Together with similar results previously obtained in the pontine brainstem, it appears that a widespread hypersensitivity to cholinergic stimulation may be central to the pathophysiology of canine narcolepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of 5-HT1A receptor agonists and antagonists on canine cataplexy.

Pharmacological studies using a canine model of narcolepsy have demonstrated that adrenergic rather than serotonergic or dopaminergic uptake inhibition is the primary mode of action of antidepressants on cataplexy, a pathological manifestation of rapid eye movement (REM) sleep atonia that occurs in narcolepsy. This result is in line with the known involvement of adrenergic systems in the regulation of REM sleep. However, the lack of anticataplectic effects of selective serotonergic compounds was puzzling as serotonergic neurons of the dorsal raphe nuclei are known to decrease activity during the REM sleep in a manner similar to the adrenergic neurons of the locus coeruleus. To further explore the role of serotonergic systems, we tested the effect on canine cataplexy of six 5-HT1A agonists and five 5-HT1A antagonists. Results indicate that 5-HT1A agonists significantly suppress cataplexy in correlation with their in vitro affinities to the canine central 5-HT1A receptors. Anticataplectic effects were, however, accompanied by various behavioral changes, such as flattened body posture, increased panting and agitation. In contrast, the selective 5-HT1A antagonist did not aggravate cataplexy, although a 5-HT1A antagonist was able to block the anticataplectic effect of a 5-HT1A agonist. These results suggest that the anticataplectic effects of 5-HT1A agonists are truly mediated by 5-HT1A receptor stimulation. It is, however, likely that anticataplectic effects occur due to the behavioral side effects rather than the direct involvement of this receptor subtype in the regulation of cataplexy. Further studies are therefore necessary to address the question of whether these 5-HT1A agonists hold promise in the pharmacological treatment of human cataplexy.

Animals↗
PubMed1995

Comparative effects of modafinil and amphetamine on daytime sleepiness and cataplexy of narcoleptic dogs.

The effects of modafinil and amphetamine on daytime sleep (polysomnographic recordings) and cataplexy (the food-elicited cataplexy test) were compared using the narcoleptic canine model. Results indicate that both modafinil (5 and 10 mg/kg body weight i.v.) and amphetamine (100 and 200 micrograms/kg i.v.) increase wakefulness and reduce slow-wave sleep in control and narcoleptic dogs. In contrast, the results of cataplexy testing demonstrate that amphetamine (2.5-160 micrograms/kg i.v.), but not modafinil (0.125-8.0 mg/kg i.v.) significantly suppresses canine cataplexy. These results suggest that the pharmacological property of modafinil is distinct from amphetamine. Results of polysomnographic recordings also demonstrate that narcoleptic dogs slept significantly more during the daytime than control dogs and required very high doses (10 mg/kg i.v. modafinil; 200 micrograms/kg i.v. amphetamine) of stimulants to reduce their level of sleepiness to that of control dogs. This finding is consistent with the data collected in human narcolepsy and validates the use of this canine model for the screening of stimulant compounds.

Amphetamine↗
PubMed1993

Memory performance during the Amytal test in patients with non-temporal lobe epilepsy.

PROBLEM: The amobarbital (Amytal) sodium test has been considered an indispensable tool in the presurgical examination of patients for epilepsy surgery. However, the accuracy of the Amytal test for predicting memory deficits, especially the amnestic syndrome, has been questioned. METHOD: The Amytal test was administered bilaterally to three groups of patients with epilepsy: temporal lobe (n = 76), frontal lobe (n = 25), and primary generalized (n = 8). Each injected hemisphere for each patient was graded pass or fail for its ability to support memory. RESULTS: The percentages of hemispheres that failed the Amytal test were 31% for the temporal lobe group, 32% for the frontal lobe group, and 56% for the primary generalized group. CONCLUSIONS: The Amytal test may be a sensitive measure of memory dysfunction. However, the high percentage of failures remains at variance with the rare incidence of the amnestic syndrome, suggesting a low specificity for this test.

Adolescent↗
PubMed1993

Desmethyl metabolites of serotonergic uptake inhibitors are more potent for suppressing canine cataplexy than their parent compounds.

Our series of pharmacological studies on canine narcolepsy has suggested that the adrenergic systems are more critically involved in the regulation of cataplexy than the serotonergic and dopaminergic systems. This, however, is an apparent contradiction to data obtained in human patients, which show that chronic oral administration of serotonergic uptake inhibitors, such as clomipramine, zimelidine and fluoxetine, is effective in reducing cataplexy. To explore this discrepancy, we have assessed the anticataplectic effects of various serotonergic uptake inhibitors and their active desmethyl metabolites on canine cataplexy. We found that the anticataplectic effect of the desmethyl metabolites, which are usually more potent for in vitro adrenergic uptake inhibition, was more potent and developed more rapidly than the effect of the parent compounds. Furthermore, the anticataplectic potency was positively correlated to the adrenergic uptake inhibition and was negatively correlated with serotonergic uptake inhibition among the 10 compounds tested. These results are consistent with our hypothesis of a preferential involvement of the adrenergic system in the control of cataplexy. Our results also suggest that the anticataplectic effect of "selective" serotonergic uptake inhibitors in human narcolepsy might be mediated by their less selective active metabolites.

Analysis of Variance↗
PubMed1985

Serum antibodies to LDH-C4.

Human sera from the WHO Reference Bank were tested by a liquid phase radioimmunoassay for antibodies to the sperm-specific form of lactate dehydrogenase (LDH-C4; LDH-X). Modestly elevated levels of antibodies were detected in about 10% of infertile males and females and in about 20% of vasectomized males, as well as in a few cases in other categories. The occurrence of this anti-LDH-C4 activity was without overt correlation with other anti-sperm antibody assays. The primary advantage of the radioimmunometric assay is its absolute specificity for a sperm antigen. These findings lend support to contraceptive vaccine development based on LDH-C4 antigenicity.

Animals↗
PubMed1985

Oxygen binding and stability properties of Hb Santa Ana (beta 88 Leu----Pro).

Hb Santa Ana (beta 88 Leu----Pro) was found at a level of 30% of total hemoglobin in red cells from a patient with congenital hemolytic anemia. Since no detailed functional studies of this hemoglobin have been done previously, we determined oxygen equilibrium curves of red cell suspensions, hemolysates, and isolated Hb Santa Ana. The P50 values obtained were 22.5 mm Hg (37 degrees C, pH 7.4) for red cell suspensions (normal mean = 27.0 mm Hg), 10.0 mm Hg (25 degrees C, pH 7.0) for hemolysate (normal = 13.5 mm Hg), and 1.3 mm Hg (25 degrees C, pH 7.0) for isolated Hb Santa Ana. Measurements of mechanical stability of Hb Santa Ana showed that the oxy-form of this hemoglobin was 10 times more unstable than that of Hb S and 100 times more unstable than that of Hb A. The deoxy-form of Hb Santa Ana was as unstable as its oxy-form, indicating that no stabilization (R----T conversion) takes place upon the deoxygenation of Hb Santa Ana.

Anemia, Hemolytic, Congenital↗
PubMed1983

The Food and Drug Administration and medroxyprogesterone acetate. What are the issues?

In 1978, the Food and Drug Administration denied approval of the three-month injectable contraceptive depot medroxyprogesterone acetate for use in the United States. This decision goes against the advice of the FDA's own scientific advisory panels, as well as the rulings of the World Health Organization and the drug regulation institutions of more than 70 developed and developing countries. In response to protest from the manufacturer of depot medroxyprogesterone acetate and from many health professionals, the FDA took the unusual step of scheduling a public board of inquiry to review its decision in January 1983. Reviewing the scientific literature on the risks and benefits of depot medroxyprogesterone acetate, we find no reason to deny depot medroxyprogesterone acetate approval, provided that studies of its possible side effects are continued and that women use it only after having made an informed choice between this and other methods of contraception.

Delayed-Action Preparations↗
PubMed1982

Impaired angiotensin-induced drinking in spontaneously hypertensive rats.

The drinking response during the 30 minutes following intracerebro-ventricular injection of angiotensin II (AII) (1 to 200 ng) was compared in male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto control rats (WK). SHR drank significantly less than WK at the 10, 50 and 100 ng doses. In contrast, responses to intracerebroventricular carbachol and intraperitoneal hypertonic saline were not different between SHR and WK. These agents are believed to induce drinking by mechanisms independent of angiotensin. Binding of I125-labelled AII to particles prepared from the hypothalamus, thalamus, septum and midbrain (HTSM) region was measured in one month old male and two month old female SHR and their respective age matched WK controls. No differences were found in binding between SHR and WK of either sex. These data demonstrate an impairment of drinking responses in the SHR which seem to be specific for angiotensin. This finding supports the hypothesis that the CNS angiotensin system might be abnormal in these animals.

Angiotensin II↗
PubMed1981

The risk of childbearing re-evaluated.

To determine the completeness of reporting of maternal deaths after live born deliveries in Georgia for 1975 and 1976, we matched death certificates with corresponding birth certificates for women of reproductive age. For these two years, more intensive searching led to our finding a minimum of a 27 per cent higher number of maternal deaths than that found by routine death certificate surveillance. When the delivery-death interval was not restricted to 42 days, use of the record linkage method led to a 50 per cent increase in reporting of maternal deaths. We recommend that special efforts be made to obtain more complete reporting of all pregnancy-related deaths and that completeness of reporting be periodically evaluated for all states.

Adolescent↗
PubMed1978

Bumetanide and frusemide: a comparison of dose-response curves in healthy men.

1 Log dose-responses for the loop diuretics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as regards urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46:1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20:1 reported when the drugs are used at high dosage in patients with renal failure.

Adult↗
PubMed1978

The influence of sodium and potassium supplements on the diuretic responses to frusemide administration in normal subjects.

1 Twelve normal subjects received (1) normal diet, (2) normal diet with 100 mmol supplementary sodium chloride and (3) normal diet with 96 mmol supplementary potassium chloride, each for 10 days, in a balanced cross-over study according to a Latin Square design. At the end of each study period, the subjects received 80 mg frusemide orally. Each study period was separated from the other by 10 days. 2 Changes in urinary electrolyte excretion occurred within the first four days of each dietary period then remained constant, with significant differences in urinary Na/K ratio between the dietary regimes. 3 Between-subject correlations, using the mean values over the three study periods, demonstrated significant associations between plasma uric acid and urinary Na/K ratio and between plasma prolactin and urinary potassium excretion. 4 Urinary potassium excretion and Na/K ratio following frusemide were influenced significantly by alteration of diet but there was no change in sodium excretion. 5 Between-subject correlations of pretreatment variables with diuretic response, using the mean values over the three study periods, demonstrated significant associations between both pretreatment urinary Na/K ratio and plasma uric acid and respectively the urinary potassium excretion and urinary Na/K ratio in response to frusemide. 6 While the response to frusemide was altered by short-term changes in dietary sodium and potassium, the difference was less than expected from observations in two populations with customary diets differing in similar manner.

Adult↗
PubMed1977

Spironolactone and canrenoate-K: relative potency at steady state.

Relative dose ratios of the mineralocorticoid antagonists spironolactone (100 mg and 200 mg daily) and canrenoate-K (200 mg daily) at steady state were defined in six healthy subjects with fludrecortisone as the mineralocorticoid agonist. The urine log 10 Na/K responses during spironolactone treatments were consistent with the law of mass action. The potency of canrenoate-K was 0.68 (95% C.L. 0.53 to 0.89) that of spironolactone on a weight basis. Approximately 72% of the renal antimineralocorticoid activity of spironolactone could attributed to the metabolite canrenone. The results at steady state are contrasted with those of a previously study comparing single doses of spironolactone and canrenoate-K.

Administration, Oral↗