The hypnotic actions of alpha 2-adrenoceptor agonists.
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Adrenergic alpha-Agonists↗
Biomedical subjects
S Feldman
Publications and source records attributed to S Feldman.
Anesthetists, nurses and pre-operative visiting.
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Child↗
Pacemaker dependency after coronary artery bypass.
A retrospective study was carried out on 36 patients (33 males and 3 females) to determine the incidence of VVI pacemaker dependency following coronary artery bypass surgery. Pacemaker dependency was defined as the presence of pacemaker activity when pacing rate was programmed at 50 beats/min and/or when no hemodynamic adequate rhythm was present during pulse generator replacement. The patients were divided into two groups: (group I) 26 patients with complete atrioventricular (AV) block developing in the early postoperative period. In most of them a pacemaker was implanted up to 3 weeks following surgery (range 2 days to 1 year); (group II) ten patients in whom the indication for pacemaker implantation was sick sinus syndrome with sinus arrest and/or tachy-bradycardia. These patients underwent pacemaker implantation at varying periods of time following surgery (range 12 days to 4 years). Unipolar endocardial leads with VVI programmable pacemakers were implanted in all patients included in this study. Mean follow-up time was 3 years. In group I the pacemaker dependency rate was 65%, whereas in group II it was 30% throughout the follow-up period. It is concluded that the low incidence of pacemaker dependency in patients who undergo pacemaker implantation after coronary bypass surgery necessitates frequent evaluation in the nondependent patient, in order to reassess the need for the pacemaker before pulse generator replacement. Such reassessment should probably include prolonged ambulatory monitoring as well as invasive evaluation of the conduction system, if avoidance of pulse generator replacement is considered.
Aged↗
Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency.
Fertility was evaluated in 53 female patients with late-onset adrenal hyperplasia (LAH) due to 21-hydroxylase deficiency. The majority of patients (n = 33) were seen for isolated postpubertal hirsutism, 9 patients consulted for sterility, and 11 for irregular menstrual cycles. At the time of diagnosis, the ages of patients ranged from 15-40 yr (mean +/- SD, 24.6 +/- 5.2). No patient had major signs of virilization. The plasma 17-hydroxyprogesterone level was higher than normal in all patients (26.8 +/- 18.9 nmol/L; range, 3.4-139.4) and dramatically increased to 140.1 +/- 80.6 nmol/L (range, 35.2-324.2) after ACTH treatment. Plasma androgen levels were high (testosterone, 3.25 +/- 2.03 nmol/L; delta 4-androstenedione, 13.65 +/- 5.60 nmol/L). Plasma basal and LHRH-stimulated values were normal for FSH and high for LH. Basal and TRH-stimulated plasma PRL levels were normal. Among these 53 LAH patients, only 20 desired a pregnancy. These had a total of 38 pregnancies. Ten patients became pregnant before the diagnosis of LAH and without any treatment; they had a total of 18 pregnancies, 12 of which were successful. Moreover, 19 normal pregnancies without any spontaneous abortion were carried to term by 14 of 16 hydrocortisone-treated patients. One patient needed the association of one cure of clomiphene citrate. Hypofertility in LAH patients seems, therefore, to be relative. Its mechanism is hormonal, with anovulation or dysovulation, due to the continuous steroid feedback of adrenal origin on the hypothalamo-pituitary axis. Hydrocortisone is the appropriate treatment in most cases, reducing adrenal androgen overproduction and relieving hypothalamic-pituitary gonadotropin function, thereby making possible cyclic ovarian activity and ovulations.
17-alpha-Hydroxyprogesterone↗
Relative importance of urinary sulfate and net acid excretion as determinants of calciuria in normal subjects.
In normal subjects fed western-mixed diets, in the fasting state, 39.6% of the variance of calciuria is accounted for by net acid excretion and 4% by sulfaturia. In the postprandial period, net acid accounts for 6.9% and sulfaturia for 11.8% of the variance of calciuria. As expected, after a load of ammonium chloride, net acid excretion exceeded the importance of sulfaturia (36.2% vs. 8.4%) and the opposite was observed after DL-methionine load (1.5% and 46.2%). A group of normal subjects fed vegetarian diets was also investigated. The excretion of the three variables measured were significantly reduced in this group when compared with that of the former group. In the fasting state the variance of calciuria was accounted mainly by net acid excretion (85.7%). In the postprandial state net acid (4.9%) and sulfate (2.2%) had much less importance as determinants of calciuria. It is concluded that in spite of their metabolic relationship, net acid and sulfate excretions are independent determinants of calciuria. The relative importance of each variable changes as a function of metabolic circumstances.
Acids↗
Adenocarcinoma in situ of the uterine cervix.
OBJECTIVE: To assess the diagnostic accuracy of cervical conization in women with adenocarcinoma in situ and to determine whether a select group of women could be managed by conization alone without hysterectomy. METHODS: We retrospectively reviewed 40 cases of cervical adenocarcinoma in situ diagnosed on cervical conization. RESULTS: Cervical conization revealed adenocarcinoma in situ alone in 15 women. Twenty-five women had adenocarcinoma in situ coexisting with squamous dysplasia (23) or microinvasive squamous cell carcinoma (two). Twenty-two women underwent hysterectomy after cone biopsy. Adenocarcinoma in situ was detected in the hysterectomy specimen in one of 12 women with uninvolved cone margins, versus seven of ten women with involved margins (P = .006); two of these seven women also had foci of invasive adenocarcinoma in the hysterectomy specimen. Conization was the only treatment for 18 selected women with adenocarcinoma in situ and uninvolved margins; all were relapse-free after a median interval of 3 years (range 1.5-5). CONCLUSIONS: Women with cervical adenocarcinoma in situ diagnosed by conization who have positive margins are at high risk of residual adenocarcinoma in situ and moderate risk of occult invasive adenocarcinoma; expectant management is not warranted. However, a cone biopsy with uninvolved margins can reliably guide subsequent therapy. Selected young women who desire preservation of fertility and have uninvolved margins probably can be managed by conization alone, but further study is required to establish the safety of this approach.
Adenocarcinoma↗
Effect of 6-hydroxydopamine and 5,7-dihydroxytryptamine on tissue uptake and cell nuclear retention of corticosterone in the rat hypothalamus.
Previous studies have shown that norepinephrine and serotonin can modulate the glucocorticoid (GC) binding capacity in the hippocampus. The aim of the present study was to evaluate the role of these neurotransmitters in regulating GC receptors in the hypothalamus. Injection of the neurotoxin 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle (VNAB) and 5,7-dihydroxytryptamine (5,7-DHT) into the raphe nuclei caused a marked depletion in norepinephrine and serotonin, respectively, in the paraventricular nucleus (PVN) and mediobasal hypothalamus (MBH). The injection of these neurotoxins did not change the basal levels of ACTH and corticosterone. Injection of 6-OHDA into the VNAB caused a significant reduction in the cell nuclear binding of corticosterone in the PVN but not in the MBH. Conversely, injection of 5,7-DHT into the raphe nuclei caused a significant reduction in cell nuclear binding of corticosterone in the MBH but did not affect binding in the PVN. These results demonstrate that at least part of the nuclear corticosteroid receptors in the PVN and MBH are differentially regulated by the noradrenergic and serotonergic systems.
5,7-Dihydroxytryptamine↗
A controlled trial of acyclovir for chickenpox in normal children.
BACKGROUND: Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS: To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS: The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS: Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.
Acyclovir↗
Effect of hypothalamic norepinephrine depletion on median eminence CRF-41 content and serum ACTH in control and adrenalectomized rats.
In this study we examined the role of the noradrenergic innervation of the hypothalamus on the adrenalectomy-induced changes in median eminence (ME) CRF-41 and serum ACTH. 6-Hydroxydopamine (6-OHDA), the catecholaminergic neurotoxin, or vehicle was injected into the ventral noradrenergic bundle of male rats. One week later animals underwent adrenalectomy or sham operation and were sacrificed 18 or 120 h later. In sham-operated rats 6-OHDA did not affect ME CRF-41 content or serum ACTH. In vehicle-injected adrenalectomized rats ACTH was increased approximately 3-fold at 18 h and almost 6-fold at 120 h. At 18 h CRF-41 content was markedly depleted (reduced approximately 20-fold) but by 120 h CRF-41 content had partially recovered and was about 70% of control animals. In adrenalectomized animals, 6-OHDA lesions caused a complete inhibition of the increase in serum ACTH both at 18 h and at 120 h. Pretreatment with 6-OHDA partially attenuated the drastic reduction in ME CRF-41 content following adrenalectomy at 18 h. However, at 120 h, the neurotoxin prevented the recovery of CRF-41 following adrenalectomy. These results suggest that intact norepinephrine innervation to the hypothalamus is necessary for the increased production of ACTH following adrenalectomy and that its interruption interferes with both the adrenalectomy-induced ME CRF-41 reduction and subsequent recovery.
Adrenalectomy↗
Differential recovery of adrenocortical responses to neural stimuli following administration of 5,7-dihydroxytryptamine into the hypothalamus.
In view of the role of serotonin in adrenocortical regulation, the effects of depletion of hypothalamic serotonin, using localized injections of the neurotoxin 5,7-dihydroxytryptamine into the hypothalamic paraventricular nucleus, on the rise in plasma corticosterone following afferent neural stimulation, were studied. The neurotoxin caused a significant reduction (p less than 0.001) in hypothalamic serotonin content of about 50% during the first month and about 30% up to two months later. Basal and ether stress-induced rises in plasma corticosterone levels were unaffected at all times after this treatment, but responses to stimulation of the sciatic nerve were reduced for up to four weeks (p less than 0.01), recovering at later times. Responses to photic and acoustic stimuli were almost entirely prevented up to four weeks following the treatment (p less than 0.001) but showed a gradual recovery to full, or almost full, adrenocortical responses at eight weeks, following acoustic and photic stimulation respectively. These results demonstrate a differential recovery of the adrenocortical responses, following the neurotoxin injection and indicate that different neural modalities require different 5-HT concentrations in the PVN for the expression of a full adrenocortical response.
5,7-Dihydroxytryptamine↗
Depletion of hypothalamic norepinephrine and serotonin enhances the dexamethasone negative feedback effect on adrenocortical secretion.
The role of norepinephrine (NE) and serotonin (5-HT) in the negative feedback effect of dexamethasone (DEX) on the adrenocortical response to ether stress was investigated. Injection of the catecholamine neurotoxin, 6-hydroxydopamine, into the ventral noradrenergic bundle or the paraventricular nucleus of the hypothalamus (PVN) which produced a very significant depletion in hypothalamic NE content enhanced the negative feedback effect of DEX. Injection of the 5-HT neurotoxin, 5,7-dihydroxytryptamine, into the raphé nuclei or PVN, which caused a depletion of hypothalamic 5-HT, produced a similar effect on the adrenocortical response to DEX. The degree of negative feedback may be viewed as a balance of neural stimulatory and glucocorticoid influences of the hypothalamus. Thus the removal of the stimulatory effects of NE and 5-HT on adrenocortical secretion, by the neurotoxic lesions, enhanced the inhibitory influence of DEX.
5,7-Dihydroxytryptamine↗
Catecholaminergic projections to tuberoinfundibular neurones of the paraventricular nucleus: III. Effects of adrenoceptor agonists and antagonists.
Stimulation of the ventral noradrenergic ascending bundle (VNAB) at low frequencies (0.5/5 Hz) excited the majority (37/46, 80%) of single paraventricular nucleus (PVN) tuberoinfundibular neurones, with high frequency (50 Hz) trains of stimuli reversing the direction of the response to inhibition for 7/16 (44%) of these excited cells. Iontophoretic application of noradrenaline, or the alpha 1-adrenoceptor agonist 1-phenylephrine, increased the spontaneous electrical activity of most of the cells tested (94% and 72%), whilst application of the alpha 1-antagonist, ergotamine reduced the spontaneous activity of 44% of the cells tested and prevented the excitation following VNAB stimulation for 84% of the cells examined. Application of the beta-adrenoceptor antagonist, propranolol, increased the spontaneous activity of 77% of cells and prevented the inhibitory PVN neuronal responses following high frequency VNAB stimulation of 94% of the cells, often reversing the response to excitation similar to that observed following low frequency VNAB stimulation. The alpha 2-adrenoceptor antagonist, tolazoline, was found to evoke mixed responses from the cells examined but a trend towards a suppression of spontaneous activity and potentiation of VNAB stimulation-evoked responses was observed. The alpha 2-adrenoceptor agonist, clonidine, elicited an initial excitation from the majority of cells tested, with most of the cells then exhibiting an inhibition, either with or without continued application. Excitatory responses following stimulation of the sciatic nerve were recorded from the majority of cells (82.5%) and ergotamine was able to suppress this response for all four cells so tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Afferent Pathways↗
Serologic follow-up of children with sickle cell disease immunized with a Haemophilus influenzae type b conjugate vaccine during early infancy.
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Anemia, Sickle Cell↗
Clonidine--a horse or an ass?
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Anesthesia↗
Comparative inactivation of isepamicin, amikacin, and gentamicin by nine beta-lactams and two beta-lactamase inhibitors, cilastatin and heparin.
This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikacin and gentamicin when exposed to different beta-lactams, beta-lactamase inhibitors, and heparin. The aminoglycosides (5, 10, 20, and 50 micrograms/ml) were incubated in human serum with ampicillin, azlocillin, aztreonam, carbenicillin, ceftazidime, piperacillin, and ticarcillin (100 and 600 micrograms/ml) and with clavulanate, cilastatin, 1:1 imipenemcilastatin, oxacillin, and sulbactam (20 and 120 micrograms/ml) for 48 h at 37 degrees C. Aminoglycoside concentrations were measured by fluorescence polarization immunoassay (FPI) after 0, 8, and 48 h of incubation and by radial diffusion bioassay after 48 h of incubation. Each of the three aminoglycosides was also added to whole blood containing either heparin (100 U/ml) or 0.5% EDTA as a control and assayed after 6 h by FPI. The degree of inactivation of isepamicin by the beta-lactams was significantly less than that by amikacin (P less than 0.003) and gentamicin (P less than 0.0002) when determined by bioassay. Piperacillin, carbenicillin, and azlocillin produced the greatest amount of inactivation, and cilastatin and oxacillin produced the least. A similar pattern was observed when the degree of inactivation was measured by FPI. A significant difference in the degree of inactivation was noted between isepamicin and gentamicin (P less than 0.003 at 8 h and P less than 0.006 at 48 h) but not between isepamicin and amikacin (P greater than 0.7 at 8 h and P greater than 0.08 at 48 h). Aminoglycoside determinations by FPI were not influenced by the presence of heparin. In summary, isepamicin was found to be at least as stable as amikacin against inactivation by beta-lactam compounds and beta-lactamase inhibitors. Heparin (100 U/ml) did not influence aminoglycoside determinations by FPI.
Amikacin↗
Managed psychiatric care.
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Cost Control↗
Neural control of adrenocortical secretion.
A variety of neural sensory stimuli as well as the stimulation of extrahypothalamic structures can produce an increase in ACTH and corticosterone (CS) secretion. This effect is mediated, at least partially, by corticotropin releasing factor (CRF)-41. Experiments involving stimulation, brain lesions and hypothalamic deafferentations have demonstrated that the mechanisms responsible for this activation are not uniform and the effects of the various modalities are mediated by different pathways. In addition to the anterior hypothalamic input, which plays an important role in the mediation of the adrenocortical responses, the medial forebrain bundle as well as a medial posterior hypothalamic input are also essential for the activation of the hypothalamo-pituitary-adrenocortical axis for some neural modalities. Norepinephrine (NE) seems to have a facilitatory effect on these mechanisms as depletion of hypothalamic NE blocks the rise in serum CS following both peripheral and central neural stimuli. This effect is mediated by alpha 1 and alpha 2 adrenoceptors, the role of beta receptors being unclear. NE palsy also an important role in the early and late changes of CRF-41 content in the median eminence and serum ACTH following adrenalectomy.
Adrenocorticotropic Hormone↗
[24-hour lung function in asthmatic patients: chrono-optimal theophylline therapy as once-daily Euphylong administration vs conventional twice-daily administration].
In this study we examined the efficacy and pharmacokinetics of a new chrono-optimized theophylline sustained release preparation for once-daily dosing in the evening for treating bronchial asthma. In a randomized, open crossover study, Euphylong (administered once daily at 2000 hours) was compared with the same dose of a reference preparation (subdivided into two equal doses taken at 800 and 2000 hours). Administration and dosage were in accordance with prior determination of clearance. The patients were outpatients during the first six days of every phase, whereas for the following 24-hour measurement period they were admitted as inpatients for measuring the requisite pharmacokinetic and pharmacodynamic data (PEF, FEV1, PEF 25 = 75, FVC). The theophylline levels remained practically constant for 24 hours under conventional theophylline treatment with twice-daily administration. In contrast, the variations of the theophylline serum levels and the night levels were higher after once-daily dosage of Euphylong, and the daytime levels and especially at the end of the dosage interval were lower. Compared with the standard profile without medication, both sustained release preparations improved the airway obstruction significantly and comparably during a 24-hour period. However, in the early morning hours between 200 and 600 both PEF and FEV1 were significantly higher under Euphylong. Between the improvement of PEF and FEV1 and the theophylline serum concentrations there was a significant correlation between 200 and 600 under Euphylong only. It is concluded that the treatment of asthma with the chrono-optimized once-daily theophylline preparation Euphylong over night is more effective than treatment with a conventional preparation in twice-daily dosage.
Adult↗