Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of the rare juvenile form of Kearns-Shy syndrome with progressive external ophthalmoplegia and lid ptosis, carditis, skeletal muscle weakness, seizures, mental subnormality, short stature, EEG abnormality and deafness is presented. Electromyography revealed a myopathic pattern. Histochemical studies on quadriceps biopsy specimens showed atrophy of type II fibers and "ragged-red fibers." On electron microscopy these muscle cells were seen to contain an increased amount of glycogen particles and abnormal mitochondria were increased in number and size. It is of interest that abrupt deterioration of neurological findings such as seizures, mental subnormality, speech disturbance and deafness was present in our case. Computed tomographic scanning showed progressive changes of cerebral atrophy, low density of cerebral white matter and basal ganglia calcification, which were well associated with the clinical deterioration. A review of the literature also indicated that some patients with this syndrome showed abrupt neurological deterioration in childhood. Involvement of the central nervous system in this syndrome has to be considered as the cause of sudden deterioration and death in childhood.
 ...
PMID:Neurologic deterioration with progressive CT changes in a child with Kearns-Shy syndrome. 648 80

A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Structure-activity relationships are described. Minor structural modifications of 4 were sufficient to strongly attenuate activity. For example, changing one phenyl group to a 2-thienyl, cyclohexyl, or 3,4-dimethoxyphenyl group greatly reduced activity. Replacing both phenyl groups by 4-chlorophenyl groups also dissipated activity. The bisethanol functionality was not essential for activity (q.v. 17-19 in Table I). Although 17-19 compared well with 4 in the TBZ assay, only 19 (like 4) showed a satisfactory profile in the maximal electroshock seizure threshold test.
 ...
PMID:Structure-activity studies on antidepressant 2,2-diarylethylamines. 674 90

The effects of naloxone or thyrotropin releasing hormone (TRH) upon neurologic outcome were evaluated in gerbil models of cerebral ischemia. Following temporary bilateral carotid occlusion, hypotension was transiently reversed by these endorphin antagonists. However, neither drug altered time to awaken, time to death, or the severity of neurologic signs (ptosis, movement, retracted paws, circling, righting reflexes, seizures, or opisthotonus) when evaluated by a blinded rater. Hot plate escape and roto-rod performance were also unaltered by naloxone or TRH; TRH, but not naloxone, increased respiratory rates. Thus, the transient improvement of cardiorespiratory function produced by these drugs is unrelated to the morbidity and mortality associated with temporary cerebral ischemia in the gerbil. Additional studies evaluating the effects of naloxone or TRH upon neurologic outcome following permanent unilateral carotid occlusion also failed to show any therapeutic effects of these drugs. Both morphine and TRH exacerbated the effects of ischemia. Of gerbils which developed neurologic impairment, the deficit was usually ipsilateral to the occluded carotid. Collectively, these results indicate that neither naloxone nor TRH prevents ischemic deficits in the gerbil. Further studies with different cerebral ischemia models in other species are required to clarify the possible therapeutic effects of these drugs in experimental stroke.
 ...
PMID:Naloxone or TRH fails to improve neurologic deficits in gerbil models of "stroke". 681

A nine-week-old Caucasian male presented with right ptosis and right exotropia due to a third cranial nerve palsy. Symmetrical macular lesions and a paramacular hyperpigmented lesion with overlying vitreous cells in the left eye were compatible with congenital toxoplasmosis. Computer tomography demonstrated calcifications in the periventricular and midbrain regions where the oculomotor nerve exits the brainstem. The diagnosis was confirmed by the toxoplasma indirect fluorescent antibody titer greater than 1:2048 for the infant and greater than 1:512 for the mother. Treatment was instituted with pyrimethamine, sulfadiazine and folinic acid. Neurologic sequelae included a right hemiparesis, infantile seizures, and generalized developmental delay. A Mueller's muscle resection (RUL) combined with 9-mm recession of the right lateral rectus and 7-mm resection of the right medial rectus muscles produced minimal ptosis and right exotropia one year later. the child now prefers to fix with the right eye and a vertical nystagmus is evident in the left eye. To our knowledge this is the first reported case of an infant with noncomitant strabismus due to congenital toxoplasma cranial nerve involvement. The finding of an acquired third cranial nerve palsy accompanied by progressive neurologic sequelae warrants consideration of congenital toxoplasmosis.
 ...
PMID:Congenital toxoplasmosis associated with acquired oculomotor nerve (CN III) palsy. 717 24

A series of (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepines and (+/-)-4,5-dihydro-4-phenyl-1H-1,3-benzodiazepines was synthesized as part of a program to develop novel psychotropics. Of these compounds, (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (10a, HRP 543) emerged as a potential antidepressant. In in vivo mouse tests (inhibition of tetrabenazine-induced ptosis and potentiation of yohimbine toxicity) which are predictive of antidepressant-like activity, 10a is comparable to amitriptyline. The similarity is also maintained in vitro, as both 10a and amitriptyline inhibit norepinephrine and serotonin uptake into rat brain synaptosomes. No significant inhibition of rat brain monoamine oxidase A or B was found with 10a, nor did the compound potentiate tryptamine-induced seizures. On chronic administration, the number of cortical beta-adrenergic receptor sites was similarly reduced by 10a and desipramine. The anticholinergic activity of clinically useful antidepressants, such as amitriptyline, is a proposed cause of side effects which reduce patient compliance. In contrast to the tricyclics, 10a apparently lacks anticholinergic activity, as evidenced in vitro by negligible displacement of [3H]quinuclidinyl benzylate from rat brain muscarinic receptors and in vivo by insignificant antagonism of the cholinergic stimulation produced by physostigmine or oxotremorine. These data suggest that 10a may be clinically useful as a novel nontricyclic antidepressant which is devoid of anticholinergic side-effect liability. Further evaluation of 10a in nonrodent species is in progress.
 ...
PMID:(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 1. Synthesis and evaluation of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and analogues as potential antidepressant agents. 720 Jan 44

4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a mixture of cis- and trans-4-(dimethylamino)spiro[cyclohexane-1,1'(3'H)-isobenzofuran]-3'-ones (1a,b), which were separated by fractional crystallization. Addition of aryllithium or aryl Grignard reagents to 1a,b and formic acid reduction afforded cis- and trans-4-(dimethylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofurans] 3a-f, which were converted to secondary amine analogues 5a-e. Tentative stereochemical assignments are based on chemical arguments and are supported by 13C NMR chemical shift data. Marked inhibition of tetrabenazine-induced ptosis is a property of most antidepressants, and significant antitetrabenazine activity is observed for several of these compounds. Optimal antitetrabenazine activity is associated with the cis-3'-phenyl series, and the cis secondary amine 5a is approximately twice as potent as the cis tertiary amine 3a. The various compounds are relatively weak with respect to potentiation of L-5-hydroxytryptophan-induced seizures.
 ...
PMID:Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, 13C NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives. 724 20

The prognosis for 45,X/46,XX mosaicism diagnosed prenatally has yet to be established. We report our experience with 12 patients in whom prenatal diagnosis of 45,X/46,XX mosaicism was detected by amniocentesis for advanced maternal age or decreased maternal serum alpha-feto protein and compared them with 41 45,X/46,XX patients diagnosed postnatally. The girls in the prenatal group range in age from 3 mo to 10 years. All have had normal linear growth. Four had structural anomalies including: ASD (n = 1); ptosis and esotropia (n = 1); labial fusion (n = 1); and urogenital sinus, dysplastic kidneys, and hydrometrocolpos (n = 1). Gonadotropins were measured in seven; one had elevated luteinizing hormone/FSH at 3 mo of age. One has developmental delay and seizures as well as ophthalmologic abnormalities. None would have warranted karyotyping for clinical suspicion of Turner syndrome. The prevalence of 45,X/46,XX mosaicism is 10-fold higher among amniocenteses than in series of postnatally diagnosed individuals with Turner syndrome, which suggests that most individuals with this karyotype escape detection and that an ascertainment bias exists toward those with clinically evident abnormalities. The phenomenon of a milder phenotype for the prenatal group is similar to that observed for 45,X/46,XY diagnosed prenatally. Prenatal counseling for 45,X/46,XX in the absence of such ultrasound abnormalities as hydrops fetalis should take into account the expectation of a milder phenotype (except, possibly, with respect to developmental delay) than that of patients ascertained postnatally. The same does not hold true for 45,x diagnosed prenatally.
 ...
PMID:Prenatal diagnosis of 45,X/46,XX mosaicism and 45,X: implications for postnatal outcome. 766 95

Cardio-facio-cutaneous (CFC) syndrome consists of heart defects, a characteristic facial appearance, ectodermal abnormalities, growth retardation and developmental delay. The authors report two children with this condition, drawing particular attention to the neurological manifestations. The neurological features are neuro-opthalmological findings such as strabismus, ptosis and nystagmus, cortical atrophy, ventriculomegaly, mental retardation, seizures and hypotonia. These manifestations may allow differentiation of CFC from Noonan syndrome, which shares many of the physical features, but not these neurological features.
 ...
PMID:Cardio-facio-cutaneous (CFC) syndrome: neurological features in two children. 768 72

The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.
 ...
PMID:General pharmacology of the putative cognition enhancer linopirdine. 777 41

A meta-analysis of pregnancy complications and behavioral risk factors associated with infant low birth weight during adolescent pregnancy was undertaken using the published literature. Studies were included which 1) utilized a clearly defined sample of teenagers 2) provided numeric data on complications 3) included a control or comparison group. Many behavioral risk factors (smoking, drinking and drug use) appeared to be less prevalent among teenage gravidas, particularly when the young women were ethnic minorities. Teenagers enrolled in comprehensive programs of prenatal care showed a diminished risk of pregnancy-induced hypertension (PIH) in comparison to those enrolled in traditional care programs. The summary relative risk for PIH with comprehensive prenatal care was 0.59. Current publications indicated a slight, but not statistically significant, recent diminution in risk of anemia for those with young maternal age (Summary Relative Risk = 0.80). There was no overall increase in risk of anemia with young maternal age (Summary Relative Risk = 1.13). The overall relative risk for the eight controlled clinical studies reporting information on maternal anemia was 2.00 for a significant overall association between anemia and young maternal age, both currently in developing countries and in the past in the developed world. Apart from disproportion in young black women, other complications of labor and delivery where the relative risk was at least 10% higher in teenagers compared with mature women included fever, seizures, and, for whites, fetal distress. Rates at least 10% lower included those for placenta previa, precipitous labor, breech or malpresentation, and, for blacks, cord prolapse and complications of anaesthesia. Overall, the summary relative risk showed a diminution in preterm delivery with comprehensive care, after adjustment for study and time (Summary Relative Risk = 0.81). The published literature suggests that prenatal care regiments which provide social and behavioral services along with medical care could improve both the health of the mother and the outcome of her pregnancy.
 ...
PMID:Prenatal care and maternal health during adolescent pregnancy: a review and meta-analysis. 781 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>