[Insulin pens filled in advance are better than rechargeable ones according to patients with diabetes].
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Disposable Equipment↗
Biomedical subjects
E Mikkelsen
Publications and source records attributed to E Mikkelsen.
Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons.
The authors used buspirone, a new anxiolytic agent that has a low side effect profile, to treat 14 developmentally disabled individuals who demonstrated anxiety as well as aggressive and self-injurious behaviors. Nine of the 14 individuals responded favorably to the drug. The authors present case reports for 3 of the responders and discuss the clinical implications of buspirone therapy.
Adjustment Disorders↗
Nimodipine treatment of subarachnoid hemorrhage.
In a pilot study of 6 patients with subarachnoid hemorrhage caused by a ruptured intracranial (grade IV (Hunt and Hess) aneurysm the hemodynamics and plasma-nimodipine concentrations have been observed during a 3-week period of treatment. We found that 3 patients developed reversible hypotension during the nimodipine treatment and that the hypotension tendency could be related to the plasma-nimodipine level and not to a more or less severe sensitivity to nimodipine. Repeated measurements of blood pressure, plasma-nimodipine and regional cerebral blood flow (rCBF) are necessary for the purpose of obtaining the optimum treatment and for evaluating the effect of treatment.
Adult↗
Open trial effects of beta-blockers on speech and social behaviors in 8 autistic adults.
We began open trials of beta-blockers, as adjunctive medication, in eight consecutive autistic adults. The immediate result across all patients was a rapid diminution in aggressivity (Ratey et al., 1987). As time on the drug increased, subtler changes in speech and socialization emerged. While results of open trials must be interpreted with caution, these changes were significant and lasting. We speculate that these effects may be the result of a lessening of the autistic individual's state of hyperarousal. As the individual becomes less anxious, defensive and dearousing behaviors are relinquished and more social and adaptive behaviors appear. There is a concomitant improvement in language, though it is unclear whether lost skills are recouped or new ones developed. Further research is indicated.
Adult↗
Autism: the treatment of aggressive behaviors.
Eight consecutive cases of adults with the diagnosis of early infantile autism and who were treated with a betablocker are presented. Each had been on various and multiple drug, educational, and behavioral regimens to help control aggressive and self-abusive behavior. Most had been institutionalized from an early age, and a broad range of IQs and speech capacities are represented. Results show the betablockers to have a remarkable effect potentiating measurable diminution in previously intractable aggressive behavior and in many cases the decrease or withdrawal of their neuroleptic.
Adrenergic beta-Antagonists↗
Comparison of effects of a new dihydropyridine, Bay K 8644, and nifedipine on spontaneous mechanical activity in rat portal vein.
In isolated portal veins from rats, Bay K 8644 (methyl-1, 4-dihydro-2, 6-dimethyl-3-nitro-4 (2-trifluoromethyl-phenyl) pyridine-5-carboxylate) increased the spontaneous mechanical activity in low but not in high concentrations. The Bay K 8644-induced increase in spontaneous mechanical activity was abolished in Ca-free medium and restored by readdition of Ca. Nifedipine abolished the augmenting effect of Bay K 8644 on the spontaneous mechanical activity; this effect of nifedipine could be eliminated by further increasing the concentration of Bay K 8644. The results are consistent with the conclusion that in rat portal vein, Bay K 8644 increases the entry of extracellular Ca by a mechanism antagonistic to that of nifedipine and in high concentration has a Ca-entry blocking effect.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
A novel 1,4 dihydropyridine, BAY K 8644, with contractile effects on vascular smooth muscle.
The effect of a new 1,4-dihydropyridine derivative, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate, BAY K 8644, was studied on isolated thoracic aortae obtained from male Wistar-Kyoto rats. In rat aorta BAY K 8644 had dual actions as the compound induced contractions in the concentration range 10(-8)-10(-5)M and relaxation at higher concentrations. In low concentrations (10(-8)M) BAY K 8644 increased the contractile response to both noradrenaline and potassium and shifted the concentration response curves to the left while in high concentrations BAY K 8644 (10(-4)M) had a relaxant effect on preparations precontracted by potassium. The contractile response to BAY K 8644 was resistant to wash out in drug free medium but was totally abolished in Ca-free medium. Re-addition of Ca restored the contractile response in a concentration dependent manner. BAY K 8644, 10(-6)M, shifted the Ca-concentration response curve in high potassium solution to the left and increased the maximal response. Phentolamine or propranolol had no effect neither on the contractile nor on the relaxant effect of BAY K 8644. The findings suggest that BAY K 8644 acts mainly by increasing the transmembrane influx of Ca in the vascular smooth muscle cells, and that this effect could be opposite to that of nifedipine. However, in high concentrations BAY K 8644 also seems to have a Ca-entry blocking effect.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Effects of light and BAY K 8644, a new 1,4-dihydropyridine, on mechanical responses of rat thoracic aorta.
The effect of day light and ultraviolet radiation (360 nm) on mechanical responses to BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(-2-trifluoromethylphenyl)-py ridine- 5 -carboxylate), potassium (K+) and noradrenaline (NA) of rat aorta rings was investigated. The contractile response to BAY K 8644 (10(-6)M) obtained before and after exposure of the BAY K 8644 stock solution to ultraviolet radiation was unchanged and equal to that of K+, 125 mM. Ultraviolet radiation and day light did not affect responses evoked by K+ (125 mM) and NA (1.8 X 10(-5)M). In contrast to this both types of light relaxed vessels contracted by BAY K 8644 (10(-6)M). The light induced relaxations were reversible, unaffected by addition of propranolol (3 X 10(-6)M) and could not be eliminated by washing the preparations repeatedly with Krebs solution. In vessels contracted by K+ (125 mM) and NA (1.8 X 10(-5)M) ultraviolet radiation induced a reversible relaxation in the presence of BAY K 8644. BAY K 8644 (10(-4)M) and nifedipine (10(-8)M) relaxed preparations contracted by K+. Nifedipine (10(-6)M) totally relaxed preparations contracted by BAY K 8644 (10(-6)M). Ultraviolet radiation eliminated the relaxant effect of nifedipine and decreased the relaxant effect of BAY K 8644 (10(-4)M). The results indicate that BAY K 8644 is more light-stable than nifedipine and that BAY K 8644 sensitized the vascular smooth muscle to ultraviolet radiation as well as day light. Consequently this should be taken into account when BAY K 8644 is studied.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Studies on the effect of histamine in isolated human pulmonary arteries and veins.
The effect of histamine (0.01-200 microM) was studied in isolated human pulmonary vessels. Histamine induced concentration dependent contractions in both arteries and veins. In veins the maximal response to histamine was lower than in arteries. Histamine and 2-methyl-histamine had a dual action in both arteries and veins clearly demonstrated in vessels precontracted with potassium. In these vessels histamine and 2-methyl-histamine induced relaxation at low concentrations and contractions at high concentrations. Veins were more sensitive to the relaxant effect of histamine than arteries. Mepyramine eliminated the dual action of 2-methyl-histamine and histamine and unveiled a mepyramine resistant relaxation at the highest histamine concentrations used which was resistant to the effect of cimetidine and metiamide. The H2 receptor agonist dimaprit (10-400 microM) induced a slight relaxation in both arteries and veins that could be eliminated by metiamide (100 microM). The results show that histamine has a dual action in human pulmonary vessels which includes a contractile effect mediated via H1 receptors and a relaxant response partly mediated through H1 receptors and partly via unspecific mechanisms. However, an H2 mediated relaxant effect cannot be excluded.
Aged↗
Effects of two new Ca-entry blockers bepridil and nitrendipine on isolated vessels.
The effects of nitrendipine and bepridil were studied in isolated rings of human crural veins contracted by noradrenaline (NA) or potassium (K). Both drugs had a concentration dependent inhibitory effect on active tone and shifted the NA and K concentration-response curves to the right in a non-parallel manner and reduced the maximum contractile response. Both drugs had a more potent inhibitory effect on K than on NA-induced contractions. Nitrendipine was far more potent in inhibiting the K-induced contractions than bepridil while the drugs were equipotent in inhibiting NA-induced contractions. Human veins were less sensitive than rat aorta to the inhibitory effect of nitrendipine. In contrast to nitrendipine the effect of bepridil was gradual and slow in onset. The inhibitory effect of both drugs was strong and long-lasting and resistant to washout procedures. Both drugs effectively eliminated spontaneous mechanical activity and reduced K-induced contractions in rat portal veins. The results support that nitrendipine and bepridil are effective vasodilators in arteries as well as in veins. The main action of both nitrendipine and bepridil seems to be attributed to an inhibitory effect on cellular Ca-entry.
Adult↗
Regional differences in the response of isolated human vessels to vasoactive substances.
1. Crural, mesenteric and pulmonary vessels obtained during surgery were studied. Isometric tension was recorded and contractions were induced by potassium 127 mM (K), noradrenaline 18 microM (NA), prostaglandin F2 alpha 2.9 microM (F2 alpha), ergotamine 3.8 microM (Erg) or digoxin 1.0 microM (Dig). 2. Spontaneous myogenic activity was only observed in pulmonary veins. F2 alpha induced spontaneous activity in mesenteric arteries. 3. In all types of vessels, except in mesenteric arteries, the response to K+ had a greater amplitude than contractions developed by NA. Erg induced a slowly developing contraction in mesenteric veins but no contraction in mesenteric arteries. Dig induced a long-lasting monophasic response in arteries and a biphasic response in the veins. 4. After immersion for 30 min in a Ca-free medium the amplitudes to both NA and K+ were significantly reduced. The veins were more susceptible to the effects of Ca-deprivation than the arteries.
Digoxin↗
Effects of nifedipine on isolated human pulmonary vessels.
The effects of the Ca-blocker nifedipine on the contractile response to K and NA in isolated human pulmonary vessels were studied. Specimens of macroscopically normal pulmonary vessels, obtained from patients undergoing surgery for lungtumours were carefully dissected and cut into rings. The results suggest that nifedipine, by blocking the entry of extracellular calcium, inhibits K-induced contractions in isolated pulmonary vessels. The effect is more pronounced on K than on NA-induced response in both the pulmonary arteries and veins.
Adult↗
Aortic coarctation: the in vitro response to noradrenaline, potassium and prostaglandin F2 alpha in intercostal arteries.
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Adult↗
Renal effects of acute calcium blockade with nifedipine in hypertensive patients receiving beta-adrenoceptor-blocking drugs.
The effects on blood pressure and renal function of a single 20-mg sublingual dose of nifedipine were investigated in 10 patients with mild to moderate arterial hypertension insufficiently treated on beta-blocker monotherapy. Nifedipine induced a prompt and marked reduction of both systolic and diastolic blood pressure (average maximal reduction 30/22 mm Hg, P less than 0.001). Despite the beta blockade, heart rate rose 25%. Only insignificant increments of glomerular filtration (RVR) was markedly reduced (P less than 0.001). Urinary excretion rate of albumin and beta-2 microglobulin rose after nifedipine, reflecting changes in glomerular as well as tubular function. Mean blood pressure seemed to be a major determinant of the excretion of proteins. There was a marked increase in the excretion of sodium after nifedipine and urine volume rose from a mean of 8.2 +/- 1.3 to 12.5 +/- 1.8 ml/min (P less than 0.01). The changes in sodium excretion rate correlated with the renal hemodynamic changes. Uric acid excretion rate rose remarkably after nifedipine and the magnitude of the changes seemed intimately related to the basal level of RVR. The results indicate that nifedipine therapy may be advantageous in patients whose hypertension is insufficiently controlled with beta blockers alone. Renal blood flow is maintained and there is a desirable diuretic action and enhancement of uric acid excretion.
Adult↗
Comparison of the effects of a new vasodilator pinacidil and nifedipine on isolated blood vessels.
In isolated human crural veins studied in vitro pinacidil (0.038-380 microM) caused a concentration-related inhibition of noradrenaline, 18 microM (NA) and 127 mM K+-induced contractions. Pinacidil was more potent in inhibiting the NA-contraction than that induced by K+, whereas the reverse was seen for nifedipine. At the highest concentrations greater inhibitions of the NA-induced contractions could be obtained with pinacidil than with nifedipine. The inhibitory effect of pinacidil on the K+-induced contractions was eliminated during a 1 hr wash-out period. In contrast to this, the inhibitory effect of nifedipine could not be eliminated during 4 hrs repeated wash-out. Pinacidil was completely devoid of inhibitory effect on 45Ca net influx in rat aorta, whereas nifedipine caused a significant reduction of influx. The results indicate that both pinacidil and nifedipine are effective vasodilatators in human vessels. Pinacidil seems to be more effective in NA-induced contractions than does nifedipine. The mechanism of action of pinacidil cannot be attributed to an inhibitory effect on cellular calcium entry.
Adult↗
Are isolated femoral resistance vessels or tail arteries good models for the hindquarter vasculature of spontaneously hypertensive rats?
We have investigated the extent to which the properties of small arteries from the hindquarters of spontaneously hypertensive rats (SHRs) are consistent with the characteristics of perfused SHR hindquarter preparations (for which the relaxed vascular resistance, the reactivity and the sensitivity are reported to be increased). We have therefore compared the in vitro morphological and pharmacological properties of a femoral resistance vessel (i.d. ca 200 microns) and of the tail artery (i.d. ca 600 microns) from SHRs with those from control Wistar-Kyoto rats (WKYs). When relaxed, for any given wall tension, the internal circumference of the SHR resistance vessels was reduced, but that of the SHR tail artery was normal. When activated with 10 microM noradrenaline, the SHR resistance vessels had an increased calcium sensitivity, but the calcium sensitivity of the SHR tail arteries was normal. However, the maximum response of both types of SHR vessels was such that the vessels would have been able to contract against increased transmural pressure. The noradrenaline sensitivity of the SHR resistance vessels was normal but the SHR tail arteries had a decreased sensitivity. The results suggest that the femoral resistance vessel is in general a better model for the hindquarter vasculature than the tail artery.
Animals↗
Different reactivity and structure of the prestenotic and poststenotic aorta in human coarctation. Implications for baroreceptor function.
In eight humans with coarctation, fresh aortic tissue was examined pharmacodynamically. In four of these patients, and in 12 additional patients, the aorta above and below the coarctation was studied morphologically and compared with eight control aortas. By in vitro stimulation with potassium (127 mM), noradrenaline (18 microM), and prostaglandin F2 alpha (28 microM), postcoarctational aortic ring preparations showed a significantly greater contractility than precoarctational rings (p less than 0.05). Volumetric analysis showed significantly more collagen (P less than 0.01) and les smooth muscle mass (p less than 0.01) in the aorta above than below the coarctation. No significant differences were found between sections from the arch and distal to the ligamentum arteriosum in the normal aortas. We conclude that the precoarctational aortic wall is more rigid than the postcoarctational wall. This may influence baroreceptors in the upper vascular bed in such a way as to tolerate a higher pressure. This would explain the preoperative proximal hypertension, the paradoxic hypertension and the frequent lack of normalization of blood pressure postoperatively.
Adolescent↗
Treatment with verapamil reduces blood pressure and tends to normalize vascular responsiveness and ion transport in the spontaneously hypertensive rat.
Spontaneously hypertensive rats (n = 7) were treated with verapamil in the drinking water (0.9 g/L) for a 5-month period. Blood pressure and heart weight in these animals were significantly lower than in a control group of rats (n = 7) receiving tap water. Aortic preparations from spontaneously hypertensive rats treated with verapamil showed less dependency on extracellular calcium in isometric tension studies than did aortae from control rats. Net uptake of 22Na and 45Ca in the presence of ouabain was significantly lower in verapamil-treated aortae than in aortae from control spontaneously hypertensive rats. The results indicate that treatment with verapamil is an effective antihypertensive regimen in spontaneously hypertensive rats and furthermore may tend to normalize vascular responsiveness and ion transport.
Animals↗