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Biomedical subjects

J E Comaty

Publications and source records attributed to J E Comaty.

At least 19 recordsLinked to original sources
PubMed1999

Clinical outcome to clozapine treatment in chronic psychiatric inpatients.

1. A review of the medical records in a state psychiatric hospital was conducted to evaluate the clinical efficacy of the atypical antipsychotic, clozapine. 2. Using the Brief Psychiatric Rating Scale (BPRS), four groups of schizophrenic inpatients (n = 59) were operationally defined: Nonresponders (< 20% decrease from pre-drug baseline); Short-term Pharmacological Responders (20% decline, but not sustained); Long-term Pharmacological Responders (maintained a 20% decline) and Clinical Responders (maintained a 20% decline and achieved a BPRS < or = 36; the criterion of Kane et al. 1988). 3. There were 7 NRs, 13 STPRs, 21 LTPRs and 18 CRs 4. The STPR, LTPR and CR groups improved significantly within the first month of treatment and reached a 20% decrease in BPRS by 3 months. CRs required 5 months to attain a BPRS < or = 36. These criteria were reached at the same average doses (about 300-400 mg/day). 5. The proportion of CRs (30%) in this retrospective, naturalistic study, is remarkably close to the results of the definitive study by Kane et al. 1988. These results are also consistent with many of the controlled research studies of clozapine in hospitalized, treatment refractory psychiatric patients.

Adult↗
PubMed1990

Is maintenance antiparkinsonian treatment necessary?

The authors designed a three-phase prospective trial in which only those patients who developed an acute, neuroleptic-induced extrapyramidal side effect (EPSE) received benztropine (BZ) at 2 mg i.m. and then 1 mg p.o. b.i.d. for 2 days after their symptoms were rated for severity and type (Preparatory Phase 1). They were then randomly assigned under double-blind conditions to continue BZ or be switched to placebo for 8 days (Experimental Phase 2). Finally in Phase 3 (Followup), all patients continued on placebo in a single-blind design until Day 30. If the patient re-experienced an acute EPSE that was of sufficient severity to require immediate BZ administration, he or she was rated, treated, and then dropped from the study. EPSE scores and dropout rates did not differ in Phase 2 between the placebo- and BZ-treated groups. Implications for the continuation, cessation, or intermittent use of antiparkinsonian (AP) drugs are discussed.

Adult↗
PubMed1989

Trifluoperazine plasma levels and clinical response.

The authors studied 36 acutely psychotic inpatients who were diagnosed as having either a schizophrenic (N = 30) or other psychotic (N = 6) disorder. After a washout phase averaging 18 days, all patients were placed on trifluoperazine 5 mg orally twice a day. Plasma levels of trifluoperazine were obtained on days 11 and 15 of treatment and then compared with clinical response. After 2 weeks of treatment an inverted U-shaped relationship was found between change scores on the Brief Psychiatric Rating Scale and trifluoperazine plasma levels.

Adult↗
PubMed1988

The effect of diagnosis and age on the DST: a metaanalytic approach.

The authors present new data on the results of the pretreatment Dexamethasone Suppression Test (DST) in 164 drug-free inpatients, as well as on the effects of age on postdexamethasone cortisol values. Nonsuppression rates were 18% in schizophrenic patients (n = 44), versus 46% in patients with a major depression (n = 56). In addition, a significant correlation was found between age and the 4:00 PM postdexamethasone cortisol value among the depressed patients (r = 0.33). The authors then applied a metaanalysis to summarize 25 other studies that have addressed the schizophrenia/major depression dichotomy as it relates to the DST outcome. Nonsuppression rates were consistently different in schizophrenic patients (19%) when compared to patients with a major depression (51%) or normal controls (7%). These differences were highly significant as measured by the Mantel-Haenszel chi-square statistic. A metaanalysis applied to a series of correlations obtained from 14 other studies reporting an age/postdexamethasone cortisol relationship in affective patients indicated a modest, but significant correlation (r = 0.24) in a total of 1284 patients (p less than 1 x 10(-8)).

Adolescent↗
PubMed1988

A comparison of thiothixene with chlorpromazine in the treatment of mania.

High potency neuroleptics have been advocated for acute mania because their side effect profile may allow for a more rapid dose escalation and symptom resolution. Low potency neuroleptics have also been advocated because their sedative properties might better calm the acutely agitated manic patient. The authors tested these hypotheses using a double-blind design comparing thiothixene with chlorpromazine in 29 manic patients on a standard dose of lithium. They found that thiothixene and chlorpromazine produced identical rates and degree of improvement, that side effect profiles differed for each drug but did not affect overall clinical response, and that most patients had a good response on much lower than expected doses. The implications for less aggressive use of neuroleptics to treat mania are discussed.

Adult↗
PubMed1979

Phenothiazine effect on gastrointestinal tract function.

Clinical evidence indicates that phenothiazines, specifically chlorpromazine (CPZ), used extensively in the treatment of patients with mental and/or neurologic disorders produce an ileus characterized by pseudoobstruction with an extended barium transit time of eight to ten days. Postoperatively, these patients have a protracted ileus, lasting from ten to fourteen days. In our present study we investigated the mechanism of action by which phenothiazines block gastrointestinal tract function as well as the possible reversal of this effect by pharmacologic agents. Guinea pigs were injected intraperitoneally with CPZ at a dose of 30 mg/kg/day for five to seventeen days. This caused deleterious effects in the gastrointestinal tract, such as cessation of peristalsis of small intestine and colon, and marked distension of the cecum. In vitro pharmacologic studies were performed on the electrically stimulated longitudinal muscle-myenteric plexus of the guinea pigs. We found that phenothiazines interfered with the neuromuscular mechanism of the intestine, as exemplified by a lack of response to electrical current stimulation. The effect was protracted, lasting at least 24 hours. These effects were reversed by the administration of the anticholinesterase, physostigmine (PGM), provided the block was less than 80 per cent. The paralytic ileus produced was similar to that found in man.

Animals↗
PubMed1978

Effect of lithium chloride on electrically stimulated guinea-pig longitudinal muscle-myenteric plexus.

Lithium chloride, in the concentration range of 10(-4)M to 10(-2)M, increases the height of electrically induced contractions of guinea-pig longitudinal muscle-myenteric plexus preparation. Higher concentrations of the salt cause a progressive block of contractions. Sodium chloride shows no augmentation of contraction height, but concentrations above 10(-2)M only cause block of contractions. Inhibition of contractions by LiCl exactly parallels inhibition of responses of the tissue to exogenous acetylcholine (ACh); thus, the site of action is considered to be directly on the muscle. Sodium chloride causes insignificant inhibition of responses to exogenous ACh. Guinea-pigs injected chronically with high doses of LiCl (2 months, 5 mEq/kg show no stimulatory effect on LiCl in vitro, only inhibition. This finding suggests that tolerance to at least some of the actions of LiCl may occur upon chronic administration, particularly if the dose used is very high.

Acetylcholine↗
PubMed1976

Mechanism of morphine block of electrical activity in ganglia of Auerbach's plexus.

A study was made of the effect of morphine on electrical activity within single ganglia of Auerbach's plexus of guinea pig longitudinal muscle-myenteric plexus as monitored by means of external electrodes. Morphine produces a concentration dependent block of single spike activity. This effect is competitively antagonized by naloxone. The ED50 for morphine effect is about 7 X 10(-7) M. Naloxone and dextrorphan have no effect on electrical activity. Acetylcholine in the concentration range of 10(-7)--10(-5) M augments electrical activity of ganglia. Morphine has little if any effect on the enhanced stimulation produced by acetylcholine thus indicating that the drug does not act directly upon the ganglion. Our results suggest that a specific opiate receptor is present on the preganglionic nerve terminals and that morphine and other opiates block ganglionic transmission by inhibiting the release of preganglionic acetylcholine.

Acetylcholine↗
PubMed1976

Block of electrically induced contractions of guinea pig longitudinal muscle by prostaglandin synthetase and receptor inhibitors.

Inhibitors of prostaglandin synthetase as well as prostaglandin receptor inhibitors block electrically induced contractions of the longitudinal muscle of the guinea pig ileum. This blockade is selectivety reversed by some prostaglandins, particularly those of the E series. There is a very close parallel between the potency with which the synthetase inhabitors block transmission and inhibit the enzyme. That blockade is actually accompanied by inhibition of synthesis of PG was shown by inhibition of arachidonic acid contractions of the tissue by indomethacin. The inhibition of transmission by indomethacin involves block of acetylcholine release as shown by direct assay and by the fact that physostigmine can reverse the block. Physostigmine also reverses block of transmission by prostaglandin receptor inhibitors and by morphine but not that produced by chlorpromazine or papaverine. Other evidence for a presynaptic site of action for the synthetase and PG receptor inhibitors is indicated by lack of effect of blocking concentrations on response of the tissue to exogenous acetylcholine. That prostaglandin reverses block of transmission by a presynaptic effect was shown by lack of reversal of atropine and papaverine inhibition of electrically induced contractions; both of these drugs produce this effect directly on the smooth muscle. These results are compatible with the previous postulate that a prostaglandin system, comprised of prostaglandin, its synthesizing enzyme and its receptor, is directly involved with the release of acetylcholine in the ileum.

Acetylcholine↗