Behavioral effects of L-alpha-methyltyrosine, an inhibitor of tyrosine hydroxylase.
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Amphetamine↗
Biomedical subjects
A Weissman
Publications and source records attributed to A Weissman.
Fetal acrania: five new cases and review of the literature.
Acrania is a lethal malformation in which there is an absence of the flat skull bones covering the brain. Five new cases are described, and a review of the English-language medical literature is presented. The sonographic differential diagnosis of acrania includes anencephaly, large cephalocele, osteogenesis imperfecta, and hypophosphatasia. The diagnosis of acrania can be established sonographically even in the first trimester if a large mass of disorganized brain tissue covered only by a thin membrane is detected.
Adult↗
On the definition of cannabinoids: botanical? chemical? pharmacological?
Cannabinoids (or presumed synonyms such as cannabinols or cannabis-like agents) have been variously defined in botanical, chemical, or pharmacological terms, with unfortunate consequences. Botanical definitions include inactive substances such as cannabigerol, as well as alkaloids and other secondary constituents of Cannabis sativa, but exclude synthetics such as levonantradol and nabilone. Chemical definitions include inactive close analogs of THC but exclude a growing number of substances structurally remote from THC that share its actions. Pharmacological definitions have depended on relatively nonspecific or vague behavioral endpoints. However, animal testing methodology has recently been developed that can identify and quantify agents that share THC's unique subjective effects. To avoid preexisting ambiquity in the word cannabinoids, the term cannabimimetics has been coined to include all such agents, regardless of origin or structure. Such a classification emphasizes research toward improved biological selectivity and therapeutic advance. While no totally noncannabimimetic agents with potent analgesic effects have yet been identified among derivatives of THC, selectivity has been uncovered for levonantradol, HHC (racemic-9-nor, 9-beta-OH-hexahydrocannabinol) and several structurally related compounds.
Animals↗
Discriminative stimulus properties of delta 9-tetrahydrocannabinol: mechanistic studies.
delta 9-Tetrahydrocannabinol (THC) produces a multiplicity of pharmacologic effects including analgesic, antiinflammatory, anticonvulsant, antidiarrheal, antiglaucoma, antihypertensive, and sedative effects. Efforts to elucidate the neurochemical systems mediating the THC effects have used these and related endpoints. However, animal models useful for evaluating the mechanisms by which THC produces its unique subjective effects have only recently been established. The use of drugs as discriminative stimuli provides a means for studying such mechanisms, since generalization data from this test closely correlate with subjective properties observed in clinical studies. The present study examined the ability of various drugs to mimic or block the cue produced by THC in rats. In animals trained to discriminate 3.2 mg/kg THC from vehicle, generalization occurred consistently with cannabinoids such as 11-OH-THC, HHC, and nabilone. Stereoselective generalization was also obtained with isomers of a potent analgesic, nantradol; potencies were consistent with results from other endpoints. In contrast, THC cueing was not produced by agents acting on adrenergic, cholinergic, serotonergic, GABAergic, or opiate systems. Similarly, a number of drugs previously reported to antagonize various nonunique effects of THC uniformly failed to block its subjective properties. These results indicate that the subjective properties of THC are mediated through as yet unidentified neurochemical systems.
Animals↗
GABA-like actions of levonantradol.
The interaction of levonantradol and its pharmacologically less active (+)-enantiomer with GABAergic mechanisms was studied in several in vivo systems: (1) rat cerebellar cGMP, based on the inverse relationship of GABAergic activity and cGMP levels; (2) convulsions elicited by 3-mercaptopropionic acid, an inhibitor of GABA synthesis; and (3) activated dopamine synthesis in rat striatum following blockade of dopamine receptors. Levonantradol decreased rat cerebellar cGMP content at low doses (1.0 mg/kg intraperitoneally) and antagonized elevation of cGMP levels by the GABA biosynthesis inhibitor isoniazid at even lower doses (0.32 mg/kg intraperitoneally); this activity pattern is suggestive of GABAergic activity. This conclusion is also supported by levonantradol's protection of mice against the convulsant effects of 3-mercaptopropionic acid, GABAergic agents are known to antagonize the enhanced dopamine synthesis and turnover that accompany dopamine receptor blockade by neuroleptics. Levonantradol (0.047 mg/kg intravenously) stereospecifically attenuated the elevated dopa accumulation induced by haloperidol. Levonantradol is at least 100-fold more active than THC in blocking isoniazid-induced elevation of cGMP levels in rat cerebellum or haloperidol-induced enhanced dopa accumulation in rat striatum.
3-Mercaptopropionic Acid↗
Selective and potent analgetics derived from cannabinoids.
Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (--)-9-nor-9 beta-hydroxyhexahydrocannabinol (HHC). A new grouping, the 1-methyl-4-phenylbutyloxy C-3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C-5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.
Analgesics↗
Facilitation of benzodiazepine binding by levonantradol.
Levonantradol enhanced binding of 3H-diazepam to rat cortical membranes. Scatchard analysis of this effect showed apparent KD and Bmax changes at 100 microM levonantradol and a KD decrease at 50 microM. Dextronantradol caused a similar enhancement, suggesting a lack of stereospecificity in vitro. Subsequently, levonantradol at pharmacologic doses (0.15 mg/kg subcutaneously) was found to enhance the binding of intravenous 3H-flunitrazepam to mouse brain. In contrast to the results in vitro, dextronantradol showed no enhancement of 3H-flunitrazepam binding at doses up to 15 mg/kg subcutaneously. This stereospecific interaction with benzodiazepine receptors in vivo suggests that levonantradol may facilitate the pharmacologic actions of benzodiazepines. Levonantradol, at doses of 0.32 and 3.2 mg/kg subcutaneously, which did not block the convulsant effect of pentylenetetrazol, enhanced both the potency and efficacy of diazepam in elevating the absolute threshold of pentylenetetrazol for eliciting clonic seizures. Consistent with its lack of facilitation of benzodiazepine binding, dextronantradol at 3.2 mg/kg, a dose without effect on pentylenetetrazol-induced convulsions, showed little or no enhancement of diazepam's anticonvulsant activity against the latter.
Animals↗
Penfluridol blockade of apomorphine: dependence of duration on species and endpoint.
Penfluridol, at relatively low doses, blocks apomorphine-elicited emesis in dogs and apomorphine-elicited floor pecking in pigeons for over a month. In mice tested for apomorphine-elicited hypothermia, and in rats tested for apomorphine-elicited chewing behavior, however, the anti-apomorphine activity of penfluridol does not persist for longer than 2-3 days even when high doses of penfluridol are given. In rabbits tested for apomorphine-induced hyperthermia and gnawing, on the other hand, penfluridol blocks apomorphine for about a week. Thus, of the 5 species tested, only in rabbits does the duration of penfluridol's anti-apomorphine action approximate the 1-week duration reported from human therapeutic trials. In mice given high-dose penfluridol apomorphine consistently elevates body temperatures, rather than exerts its usual hypothermic response. Conversely, in rabbits given penfluridol apomorphine tends slightly to decrease body temperatures, rather than exert its usual hyperthermic response.
Animals↗
Maternal and fetal digoxin-like immunoreactive factor in elective cesarean sections and spontaneous vaginal delivery.
The effect of mode of delivery on maternal and newborn plasma levels of total digoxin-like immunoreactive factor was evaluated. 32 healthy at term parturients with normal fetuses were studied. The cord blood level of digoxin-like immunoreactive factor of the 16 vaginally delivered infants was significantly higher than in the 16 matched controlled newborns delivered by an elective Cesarean section (1381 +/- 334 versus 1104 +/- 338 pg/ml, p less than 0.02). No differences were found between the maternal venous blood levels of digoxin-like immunoreactive factor of both study groups. The cord blood levels of this factor in the vaginal as well as the Cesarean section groups were significantly higher than the concentration in the corresponding maternal blood (p less than 0.001 and p less than 0.01, respectively). It is suggested that the changes in digoxin-like immunoreactive factor in the cord blood may reflect the stress of vaginal delivery on the fetus.
Adult↗
What it takes to validate behavioral toxicology tests: a belated commentary on the Collaborative Behavioral Teratology Study.
"Design Considerations in Screening for Behavioral Teratogens: Results of the Collaborative Behavioral Teratology Study" (CBTS) was an important conference whose proceedings were published in entirety in Neurobehavioral Toxicology and Teratology (7:532-822; 1985). The proceedings advocate that mandatory "behavioral teratology" testing be made part of regulations governing approval of new drugs and chemicals. This conclusion is unjustified either by the CBTS proceedings or by the present status of "behavioral teratology." First, there is little basis for accepting the validity of testing in developmental psychopharmacology, since so few agents acknowledged to lack the presumed toxic effects are explicitly identified and systematically tested. Second, findings from the CBTS itself can be construed as having indicated poor reliability: Amphetamine, the only drug examined in the CBTS, was selected for study expressly because of prior positive data, yet the study found it to be inactive. Third, the presumed "sensitivity" of behavioral measures is shown to be irrelevant. Fourth, and perhaps most important, the CBTS does not consider the public health risks of mandating nonvalid procedures within regulations. Drugs that are crucial both in therapy as scientific tools may not have been developed had regulations now advocated been in place at the time of their development.
Animals↗
Outcome of pregnancy in class A1 and A2 gestational diabetic patients delivered beyond 40 weeks' gestation.
The charts of all diabetic women and their infants delivered during the years 1983-1988 in our department were reviewed. The test group included consecutive gestational diabetic women class A1 (n = 65) and class A2 (n = 59), who delivered beyond 40 weeks of gestation. The mean gestational age at delivery was 40.90 weeks (range, 40.0 to 42.57) in class A1 and 40.49 weeks (range, 40.0 to 42.28) in class A2 patients. The first control group matched for age, parity, and presentation included 65 gestational diabetic patients class A1 and 59 A2 who delivered prior to 40 weeks' gestation. The second control group matched for age, parity, and presentation included 124 nondiabetic patients who delivered beyond 40 weeks of gestation (mean, 41.04 +/- 0.83 weeks). By allowing the pregnancies of gestational diabetic patients class A1 and class A2 to proceed beyond 40 weeks of gestation, we did not increase the incidence of perinatal mortality and morbidity rate. The cesarean section rate was low (10.76% in class A1 and 22.03% in class A2). We suggest that not only elective intervention prior to 40 weeks of gestation is to be avoided, but an attempt should be made to allow the gestational diabetics class A1 and class A2 to proceed to spontaneous labor.
Apgar Score↗
Sonographic nuchal markers for Down syndrome are more common but less ominous in gestations with a male fetus.
OBJECTIVE: A change in the normal male-to-female ratio has been reported in some autosomal trisomies (i.e., trisomy 21 or trisomy 18). The objective of the present study was to evaluate the male-to-female ratio in pregnancies with sonographic nuchal markers for Down syndrome. METHODS: The results of amniocenteses performed for isolated nuchal markers for Down syndrome were grouped by fetal sex and by maternal age. The male-to-female ratio in normal and trisomic gestations was compared. RESULTS: 584 fetal karyotypes were available for analysis. A significantly higher male-to-female ratio was observed. More affected gestations were observed in association with a female fetus. These differences were mainly attributed to the group of patients younger than 35 years that represents more than 80% of our study population. No difference was observed in pregnancies of patients older than 35 years of age. CONCLUSIONS: In patients younger than 35 years, sonographic nuchal markers for Down syndrome are more frequent (but apparently less ominous) in gestations with a male fetus. If the gender is known, counseling can be modified to include such differential risks.
Adult↗
White noise does not induce fetal sleep.
White noise has been shown to induce sleep in newborns. We sought to examine whether this type of sound will also induce a quiet state in the fetus. Twenty-two fetuses at 36-41 weeks of gestation were exposed to white noise during an active state. The sound was delivered for 5 min at an intensity of 100 dB. No significant change in fetal activity was noted following the sound.
Female↗
Ocular and systemic characteristics of Duane syndrome.
The clinical features of 63 patients with Duane syndrome are described in this report. All data in the study were gathered retrospectively except for measurements of vertical palpebral fissure and axial eye length, which were investigated prospectively. The following new aspects of the syndrome are emphasized: 1) In most cases with heterotropia, the angle of deviation was not large (< or = 25 prism diopters). 2) Visual acuity of 0.66 (20/30) or better was recorded in 94% of the affected eyes. 3) Smaller palpebral fissure (by 1 mm or more) of the affected eye was measured in primary position among 9 of 40 (22%) unilateral cases. 4) The axial length of the affected eye (mean, 22.8 +/- 0.6 mm) was not significantly different from the uninvolved eye. 5) Two cases of heterochromia iridis (3.2%) were found among the Duane syndrome patients. 6) A 4.8% prevalence of high-tone hearing loss was detected, in addition to 4.8% of sensorineural deafness.
Adolescent↗
The English romantics and modern psychology.
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History, Modern 1601-↗
[Improving intravenous cholangiography. Is re-injection vallid].
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Cholangiography↗
"Race-ethnicity": a dubious scientific concept.
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Acquired Immunodeficiency Syndrome↗
[Findings by baryum enema in granulomatous colitis and ileocolitis. A review based upon 60 cases (author's transl)].
Radiological aspects of colonic involvement in 60 patients whose disease has been followed up during several years are described. The typical radiological findings have been observed with their usual frequency. This study also confirmed the persistancy of the radiological findings in the chronic stage and the frequency of recurence in the two first years after surgery. Extension of disease has not been uncommon in the series, even without surgery. This progression was different, according to the initial location of disease: in the case of initial ileal lesion, extension occurred towards the adjacent caecum and right colon in sequence; in the case of initial colitis or ileocolitis lesion, extension occurred at a distance in other colonic segments.
Anal Canal↗