PubMed Health⌕ Search

Biomedical subjects

M A Simmonds

Publications and source records attributed to M A Simmonds.

At least 55 records · Page 3Linked to original sources
PubMed1985

Antagonism of inhibitory amino acids by the steroid derivative RU5135.

The steroid derivative RU5135 has been tested for its ability to antagonize glycine and the gamma-aminobutyric acid (GABA) analogue muscimol on isolated preparations of rat optic nerve and cuneate nucleus, respectively. On the cuneate nucleus, RU5135 antagonized muscimol in a competitive manner with a pA2 value of 8.31. RU5135 shared a common site of action with bicuculline that was separate from the picrotoxin site. On the optic nerve, RU5135 antagonized glycine with a pA2 of 7.67. It shared a common site of action with strychnine.

Amino Acids↗
PubMed1985

A phase II study of Catrix-S in solid tumors.

Catrix-S is an acidic mucopolysaccharide complex derived from bovine tracheal cartilage. This material was administered by weekly subcutaneous injection (5.0-7.5 g/week) to nine patients with progressive metastatic malignancy. One complete response was seen in a patient with metastatic renal cell carcinoma to the lungs. Eight patients had progression of their disease. No undue toxicity and no consistent immunologic alteration was noted.

Antineoplastic Agents↗
PubMed1985

Phase II study of mitolactol in metastatic malignant melanoma.

The Central Pennsylvania Oncology Group conducted a phase II study of mitolactol in advanced metastatic melanoma to determine the overall survival rate and duration of response to this agent. The starting dose was 100 mg/m2/day orally. If no hematologic toxicity was noted on weekly blood cell counts, the dose was increased to 130 mg/m2/day on Day 35, and, if still tolerated, to 160 mg/m2/day on Day 70. Six of 25 evaluable patients (24%) had objective partial response. The median duration of response was 20 weeks, with a range of 10-66 weeks. Six of 25 patients (24%) had stable measurable disease, with a median duration of 9 weeks. The median survival from date of entry in this study was 21 weeks in responding or stable patients compared to 7 weeks in nonresponders. Hematologic toxicity was the dose-limiting factor. This study shows that mitolactol has moderate activity against advanced melanoma, and the drug deserves further study in combination with nonmyelotoxic drugs.

Adult↗
PubMed1984

Modulation of the GABA receptor complex by a steroid anaesthetic.

The interactions of a steroid anaesthetic, alphaxalone, with the GABA receptor-ionophore complex were investigated by two different experimental approaches. In the rat cuneate nucleus slice, alphaxalone (0.1-10 microM) potentiated depolarizing responses to superfused GABA and muscimol, but not those to glycine. The potentiating effect of alphaxalone was unaltered by the benzodiazepine antagonist Ro 15-1788. Alphaxalone (0.1-30 microM) also enhanced [3H]muscimol binding to rat brain membranes in the presence of Cl-ions; the enhancing effect on [3H]muscimol binding was abolished by Triton X-100. Analysis of binding curves for [3H]muscimol indicated that the steroid anaesthetic increases the affinity for [3H]muscimol of low affinity binding sites; this property is shared by pentobarbitone. The physiologically inactive beta-hydroxy isomer of the steroid was without activity in either of the experimental situations at 30 microM. It is suggested that alphaxalone and pentobarbitone share a common mode of action on the GABA system, which may be relevant to the mechanisms by which these drugs produce anaesthesia.

Anesthetics↗
PubMed1984

The rat gracile nucleus in vitro: I. Evidence for a GABA-mediated depolarisation of the dorsal column afferents.

The preparation and maintenance of a novel slice of the rat gracile nucleus is described. The slice includes both gracile nuclei as well as an intact afferent input from the dorsal columns. Extracellular recording revealed that a compound tract action potential (CAP) could be recorded from the gracile nucleus following stimulation of the ipsilateral dorsal column. The CAP was followed by slower field potentials which are thought to be dependent on synaptic activity. Four consequences of stimulating the dorsal columns were observed: (1) a subsequent CAP was conducted more rapidly along the afferents whether it travelled in an orthodromic or antidromic direction; (2) the amplitude of a subsequent orthodromic CAP was reduced; (3) the amplitude of a subsequent submaximal antidromic CAP was increased; and (4) a slow positive potential could be recorded from the dorsal columns. All 4 phenomena had comparable time-courses and were similarly sensitive to agents which reduce synaptic transmission. Pharmacological evidence indicated that all 4 phenomena were mediated by GABA. It is suggested that a GABA-mediated depolarization of the gracile afferents can be evoked in this slice.

Afferent Pathways↗
PubMed1984

The rat gracile nucleus in vitro: II. Field potentials and their conditioned depression.

The field potentials which follow the compound tract action potential recorded from the rat gracile nucleus in vitro were studied. The field potentials were evoked by stimulating the ipsilateral dorsal column. Depth profile experiments revealed that the negative (N) wave recorded near the dorsal surface of the nucleus inverted to a positive (P) wave deeper in the nucleus. The negative wave consisted of an initial spiky component (NA) which peaked at a latency of 2-5 ms and temporally corresponded with the firing of post-synaptic units. This wave was usually fused with a long slow wave which peaked at 8-10 ms and often lasted for over a second. This slow wave was composed of a relatively brief bicuculline-sensitive wave (NB) superimposed on a longer bicuculline-resistant wave (NC). All of these components could be distinguished in the P wave recorded deeper in the nucleus. The amplitude of the field potential was depressed following an identical preceding stimulus delivered to the dorsal columns. This conditioned depression of the field potential had a similar time-course to the field potential itself and, likewise, had both a bicuculline-sensitive and a bicuculline-resistant component. The depression of field potentials outlasted the depolarization of the gracile afferents indicating that post-synaptic mechanisms may be involved in this long-lasting phenomenon.

Afferent Pathways↗
PubMed1984

The rat gracile nucleus in vitro: III. Unitary spike potentials and their conditioned inhibition.

Unitary spike potentials were recorded from the gracile nucleus in vitro following stimulation of the ipsilateral dorsal column. All of the unitary spike potentials were thought to be post-synaptic in origin because of their latencies and their type of response pattern to increasing the stimulus strength from threshold. Two main classes of response pattern were observed which were analogous to those of the relay cell and interneurone recorded in vivo. A further type of response pattern was observed but its anatomical substrate was not deduced. When examining the unitary spike potentials evoked by the second of a pair of identical stimuli an increase in the latency and/or decrease in the number of spikes was observed. This inhibitory period consisted of an initial intense phase followed by a less intense and long-lasting phase. At conditioning intervals of less than 40 msec this inhibition was sensitive to bicuculline. Only 13% of the units encountered in this study were spontaneously active. The activity of these units was depressed following stimulation of the dorsal column. The same inhibitory phenomena observed to act on the field potentials in this slice also act on unitary spike potentials.

Action Potentials↗
PubMed1984

Nonmedical costs to patients and their families associated with outpatient chemotherapy.

One hundred thirty-nine patients receiving outpatient chemotherapy kept diaries of nonmedical expenses resulting from their disease and its treatment. Diaries were kept for both treatment and nontreatment weeks. Results showed that the mean cost to patients and their families for treatment weeks was $72.81, and for nontreatment weeks it was $45.88. Approximately 45% of these costs were out-of-pocket expenses, and 55% were wages lost. Transportation and food were the largest out-of-pocket expenses. Patients living at greater distance from treatment had higher out-of-pocket costs, and younger patients reported more wages lost. Fourteen percent of the patients were estimated to be spending more than 50% of their weekly incomes on nonmedical expenses, and these patients were found largely in the lower-income categories. A method is proposed for using these data to estimate total nonmedical expenses for different treatment regimens, and also for estimating cancer patients' total nonmedical costs nationally.

Adolescent↗
PubMed1984

Interactions of two phenylquinolines with picrotoxin and benzodiazepines in vivo and in vitro.

PK 8165 and PK 9084 are phenylquinolines with high affinity for the benzodiazepine binding site. Both phenylquinolines were proconvulsant in combination with subconvulsant doses of picrotoxin and pentylenetetrazole in mice. Both chlordiazepoxide (10 mg/kg) and the imidazodiazepine, RO 15-1788 (10 mg/kg) prevented these tonic-clonic convulsions. In vitro studies of rat cuneate nucleus indicated that the proconvulsant actions of PK 8165 and PK 9084 could be explained by their direct, albeit slightly different, interactions with the GABA-receptor complex. PK 8165 (100 microM) alone had no effect on responses to the GABA analogue muscimol, but enhanced the potency of picrotoxin as an antagonist of muscimol and reduced the potency of flurazepam as a potentiator of muscimol. PK 9084 (100 microM) alone caused a small antagonism of muscimol, but did not affect the potency of picrotoxin; flurazepam reversed the effect of PK 9084.

Animals↗
PubMed1984

Sleep apnea precipitated by pharyngeal surgery in a patient with myotonic dystrophy.

A patient was seen for evaluation of excessive daytime sleepiness, which was exacerbated following complications secondary to surgical reconstruction of the pharynx for a submucous cleft palate. She underwent recordings in the sleep laboratory and was found to have sleep apnea. Also, a thorough clinical and laboratory assessment established the diagnosis of myotonic dystrophy. Following tracheostomy, both the patient's sleep apnea and daytime hypersomnia were eliminated. Our case demonstrates that surgical procedures involving the upper airway should be approached with considerable caution in patients with myotonic dystrophy and only after the presence of associated sleep apnea has been carefully excluded. An original finding is the suggestion of a decrease in the number of T-cell lymphocytes in a patient with myotonic dystrophy.

Adult↗
PubMed1984

Symptomatic malignant melanoma of the gastrointestinal tract. Operative treatment and survival.

Malignant melanoma involving the gastrointestinal tract is a common autopsy finding in patients who die with this disease. Melanoma metastatic to bowel infrequently causes symptoms. Some investigators suggest that survival following the onset of gastrointestinal symptoms is very poor and, as a result, surgical intervention to relieve symptoms should be avoided. We reviewed the clinical courses of 15 consecutive patients with symptomatic malignant melanoma of the bowel who underwent resection alone or in combination with bypass of symptomatic intestinal lesions. There were no deaths within 30 days of operation; 14 patients obtained relief of intestinal symptoms; 11 patients survived a mean of 7.9 months; and four patients are alive 2, 7, 22, and 23 months after operation. These results suggest that operations to treat symptomatic intestinal melanoma provide reasonable palliation and survival for patients with this disease.

Adult↗
PubMed1983

The picrotoxin-like action of a convulsant benzodiazepine, Ro5-3663.

The potency and site of action of Ro5-3663 as a GABA antagonist were investigated in the rat cuneate slice in vitro. A Schild plot for Ro5-3663 was clearly non-linear but enabled a pA2 value of 3.97 to be calculated. Combination studies using the 'classical' GABA antagonists bicuculline and picrotoxin indicated that Ro5-3663 acted at a separate site from bicuculline, but may share a common site with picrotoxin.

Animals↗
PubMed1983

Variations in response of the GABA-picrotoxin-benzodiazepine receptor complex to flurazepam.

Two effects of flurazepam have been studied on electrophysiological responses to muscimol in a slice preparation of rat cuneate nucleus. Flurazepam potentiated the responses to muscimol and also reduced the antagonism of these responses by picrotoxin. Repeated series of experiments over a 3 year period showed significant variations in the potentiation of muscimol by flurazepam which were negatively correlated with the apparent reduction in picrotoxin potency. A more reproducible reduction in picrotoxin potency by flurazepam was obtained when the data were re-calculated to take account of the possibility that picrotoxin might antagonize the potentiating effect of flurazepam as well as the direct response to muscimol. The simplest explanation of this relationship is that flurazepam and picrotoxin mutually antagonize each others effects on the GABA system. The underlying cause of the variation in flurazepam effect remains unknown.

Animals↗
PubMed1983

Depolarizing responses to glycine, beta-alanine and muscimol in isolated optic nerve and cuneate nucleus.

Concentration-dependent depolarizations were evoked by glycine and beta-alanine 5 X 10(-4)-10(-2)M and by the gamma-aminobutyric acid (GABA) analogue, muscimol 10(-6)-10(-4)M. The maximal response to glycine was several-fold higher than that to muscimol on optic nerve but the reverse was found on the dorsal funiculus fibres in the cuneate nucleus. beta-Alanine evoked a similar maximal response to glycine on optic nerve but a considerably higher maximum than glycine in the cuneate nucleus. Strychnine was 19.5 times more potent as a glycine antagonist (pA2 = 6.58) than as a muscimol antagonist. Bicuculline was 156 times more potent as a muscimol antagonist than as a glycine antagonist. Other antagonists of muscimol, i.e. tubocurarine, picrotoxin and leptazol, and potentiators of muscimol, i.e. pentobarbitone and flurazepam, had little or no effect on responses to glycine. Responses to beta-alanine had pharmacological properties compatible with a mixed action on both GABA and glycine receptors. The rat isolated optic nerve appears to be a useful preparation for studying the pharmacology of the neuronal glycine receptor plus chloride ionophore complex.

Alanine↗
PubMed1983

Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro.

Some pharmacological properties of the GABAA receptor complex in the rat cuneate nucleus slice have been assessed from depolarization responses to the gamma-aminobutyric acid (GABA) analogue muscimol and antagonism of the responses by bicuculline and picrotoxin. Responses to muscimol were potentiated by the following drugs, in descending order of potency with regard to the concentrations required in the Krebs medium: (+/-)-5-(1,3-dimethylbutyl)-5-ethylbarbituric acid [+/-)-DMBB) = (+/-)-quinalbarbitone = (+/-)-pentobarbitone greater than (+/-)-methyl-phenobarbitone = (-)-methylphenobarbitone greater than butobarbitone = chlormethiazole greater than phenobarbitone greater than barbitone = (+)-methylphenobarbitone. Primidone and phenylethylmalonamide were inactive. Calculation of the concentrations likely to be present in membrane lipids for equal potentiations of muscimol revealed little difference between quinalbarbitone, pentobarbitone, phenobarbitone and barbitone. The effect of picrotoxin as a muscimol antagonist was selectively reduced only by DMBB, chlormethiazole, phenobarbitone and (-)-methylphenobarbitone in concentrations that caused only a modest potentiation of muscimol. It is suggested that a specific site of action in the GABAA receptor complex is involved in the reduction of picrotoxin effect and that this may be relevant to the anticonvulsant properties of chlormethiazole, phenobarbitone and (-)-methylphenobarbitone. The potentiation of muscimol by chlormethiazole and the barbiturates in general involves a distinctly different site that is less selective and this may underlie the hypnotic properties of these drugs.

Animals↗
PubMed1983

Mucin and fat emboli in mucinous carcinomas. Cause of hemorrhagic cerebral infarcts.

A patient with a mucin-producing carcinoma of the breast died after three weeks of progressive neurologic deterioration. At autopsy, numerous small hemorrhagic cerebral infarcts of varying ages were found. The infarcts were primarily located in arterial boundary zones of cerebral and cerebellar hemispheres. They were associated with numerous mucin and fat emboli. In any unexplained cerebral infarct in patients with mucin-producing carcinoma, mucin and fat emboli should be considered and searched for.

Adenocarcinoma, Mucinous↗