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Biomedical subjects
Publications and source records attributed to M E Thompson.
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The importance of endogenous prostaglandins (PGs) in regulating CRF release was investigated by administering the PG synthesis inhibitor, indomethacin (Ind), in specific hypothalamic regions to adult female rats. Solid Ind pellets placed in the anterior hypothalamic area (AHA) significantly reduced the elevated levels of plasma corticosterone normally observed after the surgical stress of the stereotaxic procedure. Similar pellets placed in the hypothalamic median eminence region (ME) completely blocked the normal compensatory hypertrophy observed 48 h after unilateral adrenalectomy. Plasma corticosterone secretion in response to hemorrhage (1% b.w.) or laparotomy with intestinal manipulation (LAP) in dexamethasone pretreated rats was reduced by Ind pellets, or Ind in phosphate buffer (BUF), respectively, implanted 2 h prior to the stress. These data suggest that the PGs may be important in mediating CRF release in response to a variety of stimuli.
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Indomethacin (Ind) was administered to adult female rats to reduce endogenous prostaglandin (PG) synthesis in order to investigate the role of PGs in thyroid hormone secretin. This treatment markedly reduced thyroidal PGF levels (667.7 vs. 1822.1 pg/my, P less than .001). Although the plasma TSH concentrations were normal in the Ind-treated group (41.14 vs. 40.01 mug/100 ml), dramatic decreases were observed in plasma T3 (24.5 ca. 6.7 nf/100 ml, P less than .001) and T4 (5.6 vs. 0.7 mug/100 ml, P less than .001) levels...
The introduction of the ventricular inhibited pulse generator with the feature of rate hysteresis has been associated with a variety of rhythm disturbances, some causing serious concern. This pulse generator has two different pacing rates: (1) the automatic rate, which is the interval between two successive paced beats (usually 860 msec or 70/min), and (2) the hysteresis interval, which results in a 1,000 msec delay between a sensed cardiac contraction and the next pacemaker discharge. The hysteresis interval after a sensed signal may result in long pauses that may predispose to the development of serious cardiac arrhythmias. Two examples of this type of complication were recently observed. One patient had bigeminal rhythm with mechanically ineffective cardiac contractions and an effective cardiac rate of 35/min; he experienced dyspnea and weakness during these prolonged episodes. Another patient had repeated episodes of ventricular fibrillation. The cardiac arrhythmias were not controlled by antiarrhythmic agents, and both patients required replacement of the pulse generator. The proposed advantages of pulse generator hysteresis are (1) prolongation of battery life, and (2) maintenance of effective atrial transport; these advantages may be outweighed by undesirable cardiac arrhythmias that may be associated with this mode of pacemaker function. Rate hysteresis cardiac pacemakers should be reserved for patients having predominantly sinus rhythm without ventricular irritability. In patients with frequent ectopic ventricular activity, atrial fibrillation or high degree atrioventricular block, the rate hysteresis pacemaker offers no advantage over the conventional demand pacemaker. For patients with frequent ectopic ventricular activity not easily controlled by antiarrhythmic agents, consideration should be given to the use of a permanent demand pacemaker with external rate control, which may provide greater flexibility in arrhythmia management.
A longitudal study was carried out to separate the effects of treatment with diet from those of treatment with glibenclamide and phenformin on the oral glucose tolerance test (OGTT) plasma sugar and insulin levels in 118 patients with maturity-onset diabetes mellitus. Both drugs improved glucose tolerance and random blood sugar levels more than diet alone. The improved glucose tolerance with both drugs was due to a combination of a reduced fasting plasma sugar level and an improved tolerance to the glucose load. Treatment with glibenclamide increased insulin secretion but phenformin had no significant effect. Mean body weight fell slightly during phenformin administration, whereas a small but insignificant rise in patients receiving glibenclamide.
In order to determine whether endogenous prostaglandins (PGs) are involved in the secretion of thyrotropic hormone (TSH), we monitored plasma TSH levels in female rats receiving indomethacin (Ind) or aspirin (Asp) to inhibit PG synthesis. TSH secretion was induced by either exogenous thyrotropin-releasing hormone (TRH) or by throidectomy. On the basis of preliminary experiments, Ind was found to inhibit thyroid secretion directly. Subsequently, thyroidectomized rats receiving thyroxine (T4) replacement (2-4 mug/100 g BW/day) were used to avoid this complicating factor. These replacement regimens were judged to be adequate on the basis of the measurement of plasma triiodothyronine and T4 levels, and the lack of a compensatory rise in plasma TSH levels. Under these conditions, Ind significantly inhibited, but did not abolish, the TSH response to exogenous TRH (250 ng/100 g BW iv). Thyroidectomy-induced TSH secretion was abolished by Ind, and could be reversed upon cessation of Ind treatment. Aspirin was also found to inhibit significantly the compensatory TSH rise following thyroidectomy. These findings suggest that endogenous pituitary PGs mediate the stimulation of TSH secretion by TRH or by reduced feedback of thyroid hormones.
Oral glucose-tolerance test (O.G.T.T.) plasma sugar and insulin levels were measured in 118 newly diagnosed maturity-onset diabetic patients before and after treatment with diet alone for periods of 2 and 6 months. The results of glucose-tolerance tests carried out during treatment could be predicted from the initial test and the weight reduction between the tests. This prediction was not improved by the addition of further variables, including age, obesity, and plasma-insulin levels during the first test. The change in O.C.T.T. plasma-insulin between the first and second tests was predicted by the result of the initial tests, the improvement of glucose tolerance between the two tests, and the degree of weight reduction. 95% of the group achieved some improvement of glucose tolerance after 2 months of dietary treatment, and 59% of the group achieved adequate diabetic control by this time. It is concluded that treatment with diet alone should be the first-line management for patients with newly diagnosed maturity-onset diabetes mellitus.
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Selective autonomic blockade with intravenous propranolol, practolol, atropine, and combined atropine-propranolol was utilized to elucidate the role of the autonomic nervous system in the hemodynamic responses in young adult male volunteers to handgrip sustained at 30% of maximal voluntary contraction for 3 min. The initial 30 s of the tachycardia response was found to be mediated by withdrawal of vagal dominance, as evidenced by blockade of this response by prior atropinization. The mid and late portion of the heart rate response curve was demonstrated to be sympathetic in origin, since it was unaffected by atropine, but was suppressed by combined atropine-propranolol blockade. Sympathetic stimulation appears to be a secondary mechanism for increasing the heart rate, however, as it becomes operative only after the first mechanism of vagal withdrawal has been utilized. This was confirmed by the finding that beta adrenergic receptor blockade alone had little effect on the heart rate response curve. The pressor response to handgrip was accompanied by increased cardiac output and no change in calculated systemic vascular resistance. After propranolol, handgrip resulted in increased peripheral resistance and an equivalent rise in arterial pressure, but no increase in cardiac output. It was concluded that the increase in resistance was the result of sympathetically induced vasoconstriction. This response was shown to be independent of peripheral beta adrenergic receptor blockade by the use of practolol, a cardio-selective beta adrenergic receptor-blocking drug which caused identical hemodynamic responses to those observed after propranolol. Left ventricular ejection time (corrected for heart rate) was prolonged by handgrip. The increased afterload imposed on the left ventricle by sustained handgrip may explain the prolongation of ejection time index. Preejection period was prolonged by SHG after propranolol and shortened after atropine. In addition to confirming the previously defined role of the parasympathetic nervous system, this study delineates the role of the sympathetic nervous system in the heart rate and pressor responses to sustained handgrip.
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