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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 775 records · Page 43Linked to original sources

The effect of monoamine oxidase inhibitors compared with classical tricyclic antidepressants on learned helplessness paradigm.

The present study investigated the effect of monoamine oxidase inhibitors, nialamide which is a non specific monoamine oxidase inhibitor (MAOI), toloxatone which is a A type MAOI and L-deprenyl which is a B type MAOI compared with classical tricyclic antidepressants (clomipramine, desipramine and imipramine), on the escape deficit induced by inescapable shocks (learned helplessness paradigm). Rats were first exposed to inescapable shock pretreatment (60 shocks, 15 sec duration, 0.8 mA, every minute + 15 sec) and 48 h later, shuttle box training (30 trials/day, 15 min.) was initiated in order to evaluate interference effect. Rats with inescapable shocks exhibited escape and avoidance deficits when tested for subsequent responding in a shuttle-box. Daily i.p. injections of nialamide (8 and 16 mg/kg), toloxatone (16 and 32 mg/kg), L-deprenyl (32 and 64 mg/kg) and tricyclic antidepressants (clomipramine: 16 and 32 mg/kg, desipramine: 16 and 24 mg/kg, imipramine: 16 and 32 mg/kg) eliminated escape deficits. In rat exposed to inescapable shocks and treated with L-deprenyl (16 mg/kg/day), nialamide (32 mg/kg/day) or toloxatone (64 mg/kg/day), avoidance responses are significantly increased as compared with non drugged rats preexposed to inescapable shocks. These data extend previous results bearing on the similarity of action of MAOI and tricyclic antidepressants in learned helplessness paradigm (Sherman et al., 1982) and are in agreement with data obtained in other animal models of depression.

Animals↗

Evaluation of out-patient counselling compared with general practitioner care following overdoses.

In a randomized prospective treatment study, 80 overdose patients (not requiring intensive psychiatric intervention) received either brief out-patient counselling or were returned to the care of their general practitioners with advice on management. There was little difference in outcome between the two groups. However, two sub-groups of patients benefited more from out-patient counselling than from general practitioner care, these were: (a) women, and (b) patients with dyadic problems. Counselling following overdoses should be focused on groups of patients such as these who are most likely to benefit from it. Further work is needed to identify treatment approaches that will help other groups who take overdoses, especially men.

Adult↗

Classification of neuroleptics--zotepine.

Neuroleptic classifications try to take account of both biological effects (interaction with different neurotransmitters, selectivity of action on dopaminergic structures or dopaminergic subclasses of receptors) and clinical effects (sedative properties, efficacy on positive or negative symptomatology of schizophrenia, antimanic effect). Zotepine blocks mainly dopaminergic, 5-HT 2 and alpha 1 receptors. It should therefore be expected to have sedative properties in humans and to be effective against mania and the positive symptoms of schizophrenia.

Animals↗

Interaction of whole-body hyperthermia and irradiation in the treatment of AKR mouse leukemia.

Whole-body hyperthermia (WBH) to 41-42 degrees C combined with fractionated total-body irradiation (TBI) was studied in mice with transplanted AKR leukemia. Mice treated with both TBI and WBH survived longer than mice treated with either modality alone. From other groups of similarly treated mice the spleens were removed, weighed, and assayed for their content of leukemic colony-forming units (CFU) by injecting single-cell suspensions into normal syngeneic recipients. Using this methodology it was determined that the thermal enhancement ratio for WBH combined with TBI was 1.6, and that enhanced killing of leukemia cells occurred irrespective of the sequence of WBH and TBI. Data are presented which relate variables, such as duration of WBH or heating time to target temperature, to the response of neoplastic disease. The implications of these preclinical findings to clinical trials are discussed.

Animals↗

Time course of vagal effects studied in clinical electrocardiograms.

We consider the transient effects of brief bursts of vagal stimulation on cardiac excitation and conduction as manifested in the clinical electrocardiogram. We hypothesize that such vagal effects may be more frequent than commonly recognized and that they may account for some types of arrhythmias that are commonly ascribed to other mechanisms. We first briefly review the direct chronotropic and dromotropic effects of brief vagal stimulus bursts in animals and man. We next consider the effects of brief vagal bursts on heart period in various arrhythmias in man, particularly ventriculophasic sinus arrhythmia with various degrees of A-V block, and various patterns of A-V dissociation. We illustrate these points with numerous clinical ECGs from our patient population, and with other cases from the literature. We next consider the effects of brief vagal bursts on A-V conduction time, and illustrate this with clinical cases of: (a) prolongation of A-V conduction after premature beats, (b) 'supernormal' A-V conduction, (c) Wenckebach periodicities, and (d) alternation of A-V conduction times. We review the evidence that brief vagal bursts are generated in vivo, and are a naturally occurring reflex phenomenon. We therefore suggest that such brief vagal effects should perhaps be considered more commonly when ascribing mechanisms to some complex and often difficult to interpret arrhythmias.

Animals↗

Interaction of brief sympathetic stimuli and heart period on atrial contractile force.

We studied the dynamic interaction between the independent effects of sympathetic stimuli and heart period on atrial contractile force with three experiments: 1) we measured the inotropic response to brief sympathetic stimuli when the heart was paced; this represented the pure sympathetic effect on contractile force. 2) We measured the responses to identical stimuli when the heart was not paced; this represented the effect of the combined influences. 3) We measured the contractile responses to the identical sequences of changing cycle lengths that were recorded (expt 2) but in the absence of sympathetic activity; this represented the pure effect of changing cardiac cycle length on contractile force. We subtracted the paced from the unpaced responses. This difference represented the linear elimination of the pure sympathetic effect from the combined responses. We then compared this difference with the responses to changing cycle lengths that were measured in the absence of sympathetic activity (expt 3). The values were not equal from 2.5 through 22.5 s after the stimulus of experiment 1 of the protocol above. We performed a similar comparison after expressing the results in the frequency domain. The values were significantly different for most of the frequency spectrum where the greatest power was concentrated. We therefore conclude that there is a significant interaction between the effects of sympathetic activity and changing heart periods, and this interaction determines the resultant inotropic state on any specific beat.

Animals↗

Time course of systolic loading is an important determinant of ventricular relaxation.

We studied the dependency of left ventricular relaxation on the timing of an abrupt increase in systolic load. In 10 canine isolated heart-lung preparations, a load step of 15 mmHg was imposed at specific intervals throughout systole, and the time of loading was defined as the interval from the R wave to the completion of the load step (R-load interval). Preload was held constant. The right atrium was paced at a cycle length of 450 ms. The decay of left ventricular pressure during isovolumic relaxation was described by a single exponential time constant (Texp). Load effects on isovolumic relaxation were expressed as a percent change in Texp as compared with Texp of the beat preceding the load intervention. Loads imposed early in systole consistently prolonged Texp [mean delta Texp = +17.01 +/- 1.64% (SE) for R-load intervals less than or equal to 120 ms]. Load changes late in systole consistently abbreviated Texp [mean delta Texp = -9.49 +/- 0.86% (SE) for R-load intervals greater than or equal to 130 ms]. The transition from augmentation to diminution of Texp always occurred when the R-load interval was 120-130 ms. The mean time interval of electromechanical systole for the test beats was not significantly different (P greater than or equal to 0.05) from that of the control beats [R-load intervals less than or equal to 120: test = 247.0 +/- 27.8 (SD) ms; control = 246.6 +/- 26.8 (SD) ms] [R-load intervals greater than or equal to 130: test = 243.3 +/- 29.1 (SD) ms; control = 243.8 +/- 28.4 (SD) ms].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Thyroid function and reversal by antidepressant drugs of depressive-like behavior (escape deficits) in rats.

Several investigations have suggested that a special relationship exists between thyroid function and affective disorders and/or therapeutic response to antidepressants. The present study shows that the reversal by clomipramine, desipramine, imipramine and nialamide of depressive-like behavior in rats (escape deficits produced by previous exposure to uncontrollable stress) was markedly attenuated in hypothyroid rats (propylthiouracil, 0.05% in the drinking water). Conversely, the effect of these same antidepressants was significantly hastened in euthyroid rats given daily triiodothyronine. This supports the notion of intricate thyroid/CNS interactions in the mechanisms of action of antidepressant drugs.

Animals↗

Adoptively transferred immunity persists in human marrow graft recipients.

This study was designed to determine if antibodies (Abs) to recall antigens (Ags) were produced after bone marrow transplantation (BMT). Sera from marrow recipients (recipients) were tested for Abs to recall Ags post-grafting, and T and B cells from recipients were tested for their ability to produce anti-tetanus toxoid antibody (anti-TT) using in vitro biosynthesis assays. Neither the donors nor recipients received booster immunizations with recall Ags before or after BMT. Serum Ab titers to tetanus toxoid (TT), diphtheria toxoid (DT), and measles virus (MV) were in the normal range for the majority of 235 short-term recipients (less than 100 days postgrafting) and for the majority of 149 long-term (greater than 6 months postgrafting) recipients. Anti-TT was produced in vitro by peripheral blood lymphocytes (PBL) from 6 of 14 long-term recipients after TT stimulation. In another system, purified B cells from 9 of 21 long-term recipients also produced anti-TT after Epstein-Barr virus (EBV) stimulation. The presence of Ab titers to TT, DT, and MV in the serum of recipients and the production of in vitro anti-TT by T and B cells from recipients show that Ag-specific memory was transferred via the marrow inoculum. These data show that adoptively transferred immunity persists in recipients for years postgrafting.

Antibody-Producing Cells↗

The human c-myc exon 1 product: preparation of antisera and analysis of its expression.

We investigated the coding capacity of the previously reported open reading frame (ORF) of the human c-myc exon 1. By in vitro translation assay, we found that exon 1 ORF was translated into a 20-kd protein (p20 protein). In order to obtain antisera raised against the p20 protein, we constructed a plasmid vector which expressed most of the exon 1 ORF as a 25-kd (P25) protein in Escherichia coli. Polyclonal antisera raised against this P25 protein specifically precipitated a chimeric protein which contained exon 1-related amino acid sequences. We used these antisera to test for the existence of an exon 1 product in human cells. In the human cell lines tested, these antisera have failed so far to detect any exon 1-related proteins. However, exon 1-related proteins were detected with the anti-p20 antisera in quail embryonic cells (QEC) transfected by human c-myc recombinants constructed to express such proteins, but were expressed at low levels compared with the human c-myc protein also expressed in the transfected QEC. Our results suggest that secondary structure of the mRNA could be responsible for the low expression of the exon 1 product in QEC.

Animals↗