Input: Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism. Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2 - adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg / kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper - reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2 - adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.

Neuroinflammation

behavioral abnormalities

autism

Autism

neurodevelopmental disorder

deficits in communication and social skills

repetitive behaviors

autism

preterm labor

autism

behavioral abnormalities

autism

autism spectrum disorders

terbutaline

Terbutaline

terbutaline

terbutaline

terbutaline

terbutaline

terbutaline

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

Terbutaline

autism

Terbutaline

Autism

Terbutaline

autism

Terbutaline

autism

Terbutaline

autism

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

autism

terbutaline

Autism

terbutaline

autism

terbutaline

autism

terbutaline

autism


Input: Acute myocarditis associated with clozapine. OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20 - year - old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.

myocarditis

myocarditis

schizophrenia

myocarditis

Myocarditis

psychosis

clozapine

clozapine

clozapine

clozapine

clozapine

antidepressant

clozapine

clozapine

clozapine

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

myocarditis

clozapine

Myocarditis

antidepressant

myocarditis

antidepressant

myocarditis

antidepressant

myocarditis

antidepressant

Myocarditis


Input: Encephalopathy induced by levetiracetam added to valproate. BACKGROUND: We report on the manifestation of a levetiracetam (LEV) - induced encephalopathy. FINDINGS: A 28 - year - old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic - clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high - amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.

Encephalopathy

encephalopathy

idiopathic epilepsy

seizures

tonic - clonic seizures

impaired word fluency, psychomotor speed and working memory

seizure

levetiracetam

valproate

levetiracetam

LEV

LEV

valproate

VPA

LEV

levetiracetam

impaired word fluency, psychomotor speed and working memory

levetiracetam

impaired word fluency, psychomotor speed and working memory

LEV

impaired word fluency, psychomotor speed and working memory

LEV

impaired word fluency, psychomotor speed and working memory

LEV

impaired word fluency, psychomotor speed and working memory

valproate

impaired word fluency, psychomotor speed and working memory

valproate

impaired word fluency, psychomotor speed and working memory

VPA

impaired word fluency, psychomotor speed and working memory

valproate

Encephalopathy

valproate

encephalopathy

valproate

Encephalopathy

valproate

encephalopathy

VPA

Encephalopathy

VPA

encephalopathy

levetiracetam

Encephalopathy

levetiracetam

encephalopathy

levetiracetam

Encephalopathy

levetiracetam

encephalopathy

LEV

Encephalopathy

LEV

encephalopathy

LEV

Encephalopathy

LEV

encephalopathy

LEV

Encephalopathy

LEV

encephalopathy

levetiracetam

tonic - clonic seizures

levetiracetam

tonic - clonic seizures

LEV

tonic - clonic seizures

LEV

tonic - clonic seizures

LEV

tonic - clonic seizures

valproate

tonic - clonic seizures

valproate

tonic - clonic seizures

VPA

tonic - clonic seizures


Input: Norepinephrine signaling through beta - adrenergic receptors is critical for expression of cocaine - induced anxiety. BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine' s rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta - hydroxylase knockout (Dbh - / -) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine - induced anxiety. RESULTS: We found that cocaine dose - dependently increased anxiety - like behavior in control (Dbh + / -) mice, as measured by a decrease in open arm exploration. The Dbh - / - mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine - induced anxiety was also attenuated in Dbh + / - mice following administration of disulfiram, a dopamine beta - hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta - adrenergic receptor antagonist propranolol blocked cocaine - induced anxiety - like behavior in Dbh + / - and wild - type C57BL6 / J mice, while the alpha (1) antagonist prazosin and the alpha (2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta - adrenergic receptors is required for cocaine - induced anxiety in mice.

Norepinephrine

cocaine

Cocaine

cocaine

cocaine

dopamine

norepinephrine

NE

cocaine

cocaine

cocaine

Cocaine

disulfiram

dopamine

propranolol

cocaine

prazosin

yohimbine

cocaine

anxiety

anxiety

anxiety

anxiety

anxiety

anxiety

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

Cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety

cocaine

anxiety


Input: Clonidine for attention - deficit / hyperactivity disorder: II. ECG changes and adverse events analysis. OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention - deficit / hyperactivity disorder (ADHD). METHOD: In a 16 - week multicenter, double - blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0. 6 mg / day for clonidine and 60 mg / day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17. 5% versus 3. 4%; p =. 02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79. 4% versus 49. 2%; p =. 0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.

Clonidine

clonidine

methylphenidate

clonidine

methylphenidate

clonidine

methylphenidate

clonidine

methylphenidate

clonidine

clonidine

clonidine

methylphenidate

clonidine

clonidine

Clonidine

methylphenidate

clonidine

attention - deficit / hyperactivity disorder

attention - deficit / hyperactivity disorder

ADHD

ADHD

bradycardia

Drowsiness

ADHD

bradycardia

drowsiness

Clonidine

bradycardia

Clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

Clonidine

bradycardia

Clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia


Input: Thalidomide has limited single - agent activity in relapsed or refractory indolent non - Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B. Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed / refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1 - 2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1 - 4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12. 5% (95% confidence interval: 2. 6 - 32. 4%). Eleven patients progressed during therapy. Grade 3 - 4 adverse effects included myelosuppression, fatigue, somnolence / depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.

Thalidomide

Thalidomide

thalidomide

thalidomide

lenalidomide

non - Hodgkin lymphomas

Cancer

Leukemia

multiple myeloma

mantle cell lymphoma

lymphoplasmacytic lymphoma

tumour

lymphomas

myelosuppression

fatigue

somnolence

depressed mood

neuropathy

dyspnea

thromboembolic

lymphomas

Thalidomide

thromboembolic

Thalidomide

thromboembolic

thalidomide

thromboembolic

thalidomide

thromboembolic


Input: Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department. Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45 - year - old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.

epinephrine

cocaine

cocaine

epinephrine

priapism

Priapism

priapism

cocaine

priapism

cocaine

Priapism

cocaine

priapism

cocaine

priapism

cocaine

Priapism

cocaine

priapism


Input: Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats. The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO) - induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg / kg, s. c.) for 2 days at an interval of 24 h caused a significant (P < 0. 05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca + 2 ATPase level whereas there was a significant (P < 0. 05) decrease in body weight, endogenous antioxidants, Na + / K + ATPase and Mg + 2 ATPase levels. Administration of green tea (100 mg / kg / day, p. o.) and vitamin E (100 mg / kg / day, p. o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P < 0. 05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca + 2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na + / K + ATPase and Mg + 2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.

green tea

vitamin E

isoproterenol

green tea

vitamin E

isoproterenol

ISO

ISO

Ca

K

Mg

green tea

vitamin E

ISO

Ca

K

Mg

ISO

green tea

vitamin E

green tea

vitamin E

ISO

myocardial infarction

myocardial infarction

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction

ISO

myocardial infarction


Input: Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C. A 63 - year - old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha - 2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient' s ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha - 2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha - 2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.

ocular myasthenia

chronic hepatitis C

diplopia

chronic hepatitis C

CHC

ptosis on the right upper lid

restricted right eye movement

ocular myasthenia

CHC

pegylated interferon

ribavirin

pegylated interferon (IFN) alpha - 2b

ribavirin

acetylcholine

pegylated IFN alpha - 2b

ribavirin

pegylated IFN alpha - 2b

ribavirin

IFN

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

ribavirin

ocular myasthenia

pegylated interferon

ptosis on the right upper lid

pegylated interferon (IFN) alpha - 2b

ptosis on the right upper lid

pegylated IFN alpha - 2b

ptosis on the right upper lid

pegylated IFN alpha - 2b

ptosis on the right upper lid

IFN

ptosis on the right upper lid

ribavirin

ptosis on the right upper lid

ribavirin

ptosis on the right upper lid

ribavirin

ptosis on the right upper lid

ribavirin

ptosis on the right upper lid

pegylated interferon

restricted right eye movement

pegylated interferon (IFN) alpha - 2b

restricted right eye movement

pegylated IFN alpha - 2b

restricted right eye movement

pegylated IFN alpha - 2b

restricted right eye movement

IFN

restricted right eye movement

pegylated interferon

ocular myasthenia

pegylated interferon

ocular myasthenia

pegylated interferon (IFN) alpha - 2b

ocular myasthenia

pegylated interferon (IFN) alpha - 2b

ocular myasthenia

pegylated IFN alpha - 2b

ocular myasthenia

pegylated IFN alpha - 2b

ocular myasthenia

pegylated IFN alpha - 2b

ocular myasthenia

pegylated IFN alpha - 2b

ocular myasthenia

IFN

ocular myasthenia

IFN

ocular myasthenia

ribavirin

restricted right eye movement

ribavirin

restricted right eye movement

ribavirin

restricted right eye movement

ribavirin

restricted right eye movement


Input: The glycine transporter - 1 inhibitor SSR103800 displays a selective and specific antipsychotic - like profile in normal and transgenic mice. Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N - methyl - D - aspartate (NMDA) receptor produce schizophrenic - like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter - 1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co - agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic - like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK - 801) or transgenic mice (ie, NMDA Nr1 (neo - / -) and DAT (- / -)). Results showed that SSR103800 (10 - 30 mg / kg p. o.) blocked hyperactivity induced by the non - competitive NMDA receptor antagonist, MK - 801 and partially reversed spontaneous hyperactivity of NMDA Nr1 (neo - / -) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT (- / -)) knockout mice (10 - 30 mg / kg p. o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg / kg p. o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic - like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side - effect potential as compared with these latter drugs.

glycine

dopamine

glutamate

N - methyl - D - aspartate

NMDA

NMDA

NMDA

glycine

NMDA

glycine

NMDA

amphetamine

MK - 801

NMDA

NMDA

MK - 801

NMDA

amphetamine

dopamine

haloperidol

olanzapine

clozapine

aripiprazole

Schizophrenia

schizophrenic

hyperactivity

hyperactivity

hyperactivity

hyperactivity

hyperactivity

catalepsy

aripiprazole

catalepsy

haloperidol

catalepsy

olanzapine

catalepsy

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

MK - 801

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

clozapine

catalepsy


Input: Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia - induced hypotension. BACKGROUND: Vasopressor agents are used to correct anesthesia - induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S (c) O (2)) following anesthesia - induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0. 15 mg kg (- 1)) and propofol (2. 0 mg kg (- 1)), 13 patients received phenylephrine (0. 1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S (c) O (2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S (c) O (2). After administration of phenylephrine, MAP increased (51 + / - 12 to 81 + / - 13 mmHg; P < 0. 001; mean + / - SD). However, a 14% (from 70 + / - 8% to 60 + / - 7%) reduction in S (c) O (2) (P < 0. 05) followed with no change in CO (3. 7 + / - 1. 1 to 3. 4 + / - 0. 9 l min (- 1)). The administration of ephedrine led to a similar increase in MAP (53 + / - 9 to 79 + / - 8 mmHg; P < 0. 001), restored CO (3. 2 + / - 1. 2 to 5. 0 + / - 1. 3 l min (- 1)), and preserved S (c) O (2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S (c) O (2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.

Phenylephrine

ephedrine

phenylephrine

ephedrine

fentanyl

propofol

phenylephrine

ephedrine

phenylephrine

ephedrine

phenylephrine

ephedrine

reduces frontal lobe oxygenation

hypotension

hypotension

hypotension

stroke

a decrease in MAP, HR, SV, and CO

a decrease in MAP

a decrease in MAP, HR, SV, and CO

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

a decrease in MAP, HR, SV, and CO

fentanyl

a decrease in MAP

fentanyl

hypotension

fentanyl

a decrease in MAP, HR, SV, and CO

propofol

hypotension

propofol

hypotension

propofol

hypotension

propofol

a decrease in MAP, HR, SV, and CO

propofol

a decrease in MAP

propofol

hypotension

propofol

a decrease in MAP, HR, SV, and CO

Phenylephrine

reduces frontal lobe oxygenation

phenylephrine

reduces frontal lobe oxygenation

phenylephrine

reduces frontal lobe oxygenation

phenylephrine

reduces frontal lobe oxygenation

phenylephrine

reduces frontal lobe oxygenation


Input: A novel, multiple symptom model of obsessive - compulsive - like behaviors in animals. BACKGROUND: Current animal models of obsessive - compulsive disorder (OCD) typically involve acute, drug - induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD - like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e. g., win - shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD - like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease - like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.

obsessive - compulsive - like behaviors

obsessive - compulsive disorder

OCD

anxiety

OCD

anxiety

behavioral inflexibility

memory impairment

hoarding

corticostriatal dysfunction

OCD

OCD

OCD

psychiatric disorders

antidepressant

clomipramine

Clomipramine

Dopamine

serotonin

serotonin

clomipramine

memory impairment

Clomipramine

memory impairment

clomipramine

anxiety

clomipramine

anxiety

Clomipramine

anxiety

Clomipramine

anxiety

clomipramine

hoarding

Clomipramine

hoarding


Input: Late recovery of renal function in a woman with the hemolytic uremic syndrome. A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.

hemolytic uremic syndrome

hemolytic uremic syndrome

HUS

anuria

HUS

oliguria

HUS

hypertension

microangiopathic hemolytic anemia

oral contraceptives

heparin

dipyridamole

oral contraceptives

hemolytic uremic syndrome

oral contraceptives

hemolytic uremic syndrome

oral contraceptives

HUS

oral contraceptives

HUS

oral contraceptives

HUS


Input: Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine - induced myocardial injury in dogs. A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline - infused control animals (4, 957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12. 0 vs. 5. 0 mg. per 100 Gm. of fat - free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2, 682, 2, 803, and 3, 424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11. 2, 8. 3, and 8. 9 mg. per 100 Gm. of fat - free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.

acetylsalicylic acid

dipyridamole

hydrocortisone

epinephrine

epinephrine

epinephrine

radiocalcium

calcium

calcium chloride

calcium

calcium

radiocalcium

acetylsalicylic acid

dipyridamole

hydrocortisone

epinephrine

calcium

Acetylsalicylic acid

dipyridamole

hydrocortisone

myocardial injury

myocardial injury

myocardial infarction

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury

epinephrine

myocardial injury


Input: Changes in depressive status associated with topical beta - blockers. Depression and sexual dysfunction have been related to side effects of topical beta - blockers. We performed a preliminary study in order to determine any difference between a non selective beta - blocker (timolol) and a selective beta - blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0. 5% / 12h, suffering from depression diagnosed through DMS - III - R criteria, were included in the study. During the six - month follow up, depression was quantified through the Beck and Zung - Conde scales every two months. In a double blind cross - over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung - Conde scales (p < 0. 001 vs control). These results suggest that betaxolol could be less of a depression - inducer than timolol in predisposed patients.

depressive

Depression

sexual dysfunction

glaucomatous

depression

depression

depression

depression

timolol

betaxolol

timolol

timolol

betaxolol

timolol

timolol

depressive

timolol

Depression

timolol

depression

timolol

depression

timolol

depression

timolol

depression

timolol

depressive

timolol

Depression

timolol

depression

timolol

depression

timolol

depression

timolol

depression

timolol

depressive

timolol

Depression

timolol

depression

timolol

depression

timolol

depression

timolol

depression

timolol

depressive

timolol

Depression

timolol

depression

timolol

depression

timolol

depression

timolol

depression


Input: Long - term follow - up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report. The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g / m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty - eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi' s syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g / m2 of ifosfamide, a younger age (less than 2 1 / 2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

ifosfamide

ifosfamide

ifosfamide

ifosfamide, vincristine, and dactinomycin

IVA

cisplatin

creatinine

phosphate

phosphate

ifosfamide

ifosfamide

renal toxicity

malignant mesenchymal tumors

malignant mesenchymal tumors

Malignant Mesenchymal Tumor

tumor

glucosuria

proteinuria

aminoaciduria

renal abnormalities

toxicity

Fanconi' s syndrome

TDFS

toxicity

tumor

mesenchymal tumors

ifosfamide

Fanconi' s syndrome

ifosfamide

TDFS

ifosfamide

Fanconi' s syndrome

ifosfamide

TDFS

ifosfamide

Fanconi' s syndrome

ifosfamide

TDFS

ifosfamide

Fanconi' s syndrome

ifosfamide

TDFS

ifosfamide

Fanconi' s syndrome

ifosfamide

TDFS

ifosfamide

renal toxicity

ifosfamide

renal abnormalities

ifosfamide

renal toxicity

ifosfamide

renal abnormalities

ifosfamide

renal toxicity

ifosfamide

renal abnormalities

ifosfamide

renal toxicity

ifosfamide

renal abnormalities

ifosfamide

renal toxicity

ifosfamide

renal abnormalities


Input: Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine - induced hyperactivity in rats. Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine - induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine - induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague - Dawley rats tested in photocell cages. Nicotine (1. 0 mg / kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine - induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1 / D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine - induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.

dopamine

nicotine

nicotine

nicotine

dopamine

nicotine

dopamine

nicotine

Nicotine

nicotine

mecamylamine

hexamethonium

Nicotine

SCH 23390

raclopride

fluphenazine

PHNO

nicotine

SKF 38393

nicotine

nicotine

dopamine

hyperactivity

increase in locomotor activity

hyperactivity

hyperactivity

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

Nicotine

hyperactivity

Nicotine

increase in locomotor activity

Nicotine

hyperactivity

Nicotine

hyperactivity

Nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

Nicotine

hyperactivity

Nicotine

increase in locomotor activity

Nicotine

hyperactivity

Nicotine

hyperactivity

Nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

increase in locomotor activity

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity


Input: Neuropsychiatric side effects after the use of mefloquine. This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep - wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8, 000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13, 000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.

mefloquine

mefloquine

mefloquine

mefloquine

mefloquine

seizures

psychoses

anxiety neurosis

disturbances of sleep - wake rhythm

malaria

mefloquine

disturbances of sleep - wake rhythm

mefloquine

disturbances of sleep - wake rhythm

mefloquine

disturbances of sleep - wake rhythm

mefloquine

disturbances of sleep - wake rhythm

mefloquine

disturbances of sleep - wake rhythm

mefloquine

psychoses

mefloquine

psychoses

mefloquine

psychoses

mefloquine

psychoses

mefloquine

psychoses

mefloquine

anxiety neurosis

mefloquine

anxiety neurosis

mefloquine

anxiety neurosis

mefloquine

anxiety neurosis

mefloquine

anxiety neurosis

mefloquine

seizures

mefloquine

seizures

mefloquine

seizures

mefloquine

seizures

mefloquine

seizures


Input: Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization. Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2. 7 + / - 1. 9 vs. 3. 8 + / - 2. 2, P = 0. 03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues.

pain

pain

pain

pain

pain

pain

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain

lidocaine

pain


Input: Randomized, double - blind trial of mazindol in Duchenne dystrophy. There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12 - month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg / d) or placebo. The study was designed to have a power of greater than 0. 90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0. 05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF - I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol - treated patients gained less weight and height than placebo - treated patients, no significant effect on IGF - I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.

mazindol

mazindol

mazindol

Mazindol

mazindol

mazindol

mazindol

mazindol

mazindol

Mazindol

Duchenne dystrophy

weakness

Duchenne dystrophy

Duchenne dystrophy

weakness

decreased appetite

dry mouth

gastrointestinal symptoms

weakness

Duchenne dystrophy

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

Mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

mazindol

gastrointestinal symptoms

Mazindol

gastrointestinal symptoms

mazindol

dry mouth

mazindol

dry mouth

mazindol

dry mouth

Mazindol

dry mouth

mazindol

dry mouth

mazindol

dry mouth

mazindol

dry mouth

mazindol

dry mouth

mazindol

dry mouth

Mazindol

dry mouth

mazindol

decreased appetite

mazindol

decreased appetite

mazindol

decreased appetite

Mazindol

decreased appetite

mazindol

decreased appetite

mazindol

decreased appetite

mazindol

decreased appetite

mazindol

decreased appetite

mazindol

decreased appetite

Mazindol

decreased appetite


Input: Pentoxifylline (Trental) does not inhibit dipyridamole - induced coronary hyperemia: implications for dipyridamole - thallium - 201 myocardial imaging. Dipyridamole - thallium - 201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole - induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole - thallium - 201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open - chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7. 5, or 15 mg / kg i. v.) or theophylline (3 mg / kg i. v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7. 5 or 15 mm / kg i. v. pentoxifylline (p less than 0. 002). Neither dose of pentoxifylline significantly decreased the dipyridamole - induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0. 01). We conclude that pentoxyifylline does not inhibit dipyridamole - induced coronary hyperemia even at high doses.

Pentoxifylline

Trental

dipyridamole

dipyridamole

thallium

Dipyridamole

thallium

pentoxifylline

Trental

methylxanthine

pentoxifylline

dipyridamole

methylxanthines

theophylline

dipyridamole

thallium

dipyridamole

pentoxifylline

theophylline

Dipyridamole

pentoxifylline

pentoxifylline

dipyridamole

theophylline

pentoxyifylline

dipyridamole

hyperemia

peripheral vascular disease

intermittent claudication

hyperemia

hyperemia

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

Dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

dipyridamole

hyperemia

Pentoxifylline

intermittent claudication

Trental

intermittent claudication

pentoxifylline

intermittent claudication

Trental

intermittent claudication

pentoxifylline

intermittent claudication

pentoxifylline

intermittent claudication

pentoxifylline

intermittent claudication

pentoxifylline

intermittent claudication

pentoxyifylline

intermittent claudication


Input: Cause of death among patients with Parkinson' s disease: a rare mortality due to cerebral haemorrhage. Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson' s disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44. 1%), malignant neoplasms (11. 6%), heart diseases (4. 1%), cerebral infarction (3. 7%) and septicaemia (3. 3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0. 8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson' s disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.

death

Parkinson' s disease

cerebral haemorrhage

death

cerebral haemorrhage

Parkinson' s disease

death

pneumonia

bronchitis

neoplasms

heart diseases

cerebral infarction

septicaemia

Cerebral haemorrhage

death

deaths

death

cerebral haemorrhage

death

Parkinson' s disease

hypotensive

hypotensive

parkinsonian

levodopa

noradrenaline

levodopa

hypotensive

levodopa

hypotensive


Input: Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever. Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.

ribavirin

ribavirin

ribavirin

ribavirin

ribavirin

Argentine hemorrhagic fever

Argentine hemorrhagic fever

AHF

viremia

death

anemia

AHF

anemia

AHF

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia

ribavirin

anemia


Input: Dipyridamole - induced myocardial ischemia. Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole - induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary " steal " phenomenon may be the mechanism of the dipyridamole - induced ischemia observed.

Dipyridamole

dipyridamole

dipyridamole

dipyridamole

dipyridamole

myocardial ischemia

Angina

myocardial ischemia

coronary artery disease

ischemia

Dipyridamole

Angina

dipyridamole

Angina

dipyridamole

Angina

dipyridamole

Angina

dipyridamole

Angina


Input: Inhibition of immunoreactive corticotropin - releasing factor secretion into the hypophysial - portal circulation by delayed glucocorticoid feedback. Nitroprusside - induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin - releasing factor (irCRF) into the hypophysial - portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2 - h systemic corticosterone infusion in urethane - anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms / dl. Suppression of irCRF secretion in response to nitroprusside - induced hypotension is observed and occurs at a plasma corticosterone level between 8 - 12 micrograms / dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.

Nitroprusside

arginine vasopressin

oxytocin

corticosterone

urethane

arginine vasopressin

oxytocin

corticosterone

corticosterone

corticosterone

nitroprusside

corticosterone

hypotension

hypotension

Nitroprusside

hypotension

Nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension


Input: Noradrenergic involvement in catalepsy induced by delta 9 - tetrahydrocannabinol. In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9 - tetrahydrocannabinol (THC), the effect of pretreatment with 6 - hydroxydopamine (6 - OHDA) or with desipramine and 6 - OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6 - OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6 - OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6 - OHDA but not in rats treated with 6 - OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.

catalepsy

catalepsy

catalepsy

delta 9 - tetrahydrocannabinol

delta 9 - tetrahydrocannabinol

THC

6 - hydroxydopamine

6 - OHDA

desipramine

6 - OHDA

THC

6 - OHDA

desipramine

6 - OHDA

haloperidol

desipramine

6 - OHDA

6 - OHDA

THC

haloperidol

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

delta 9 - tetrahydrocannabinol

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy

THC

catalepsy


Input: Intracranial pressure increases during alfentanil - induced rigidity. Intracranial pressure (ICP) was measured during alfentanil - induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 + / - 1 mmHg, mean + / - SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu / kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7. 5 + / - 1. 0 mmHg, delta CVP 5. 9 + / - 1. 3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.

alfentanil

alfentanil

halothane

halothane

alfentanil

halothane

metocurine

alfentanil

alfentanil

rigidity

rigidity

somatic rigidity

rigidity

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

somatic rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

somatic rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

somatic rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

somatic rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

rigidity

alfentanil

somatic rigidity

alfentanil

rigidity

alfentanil

rigidity


Input: Adverse cardiac effects during induction chemotherapy treatment with cis - platin and 5 - fluorouracil. Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and / or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis - platin (80 - 120 mg / m2BSA) and 5 - FU (1000 mg / m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre - treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre - treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST - T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5 - FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.

cis - platin

5 - fluorouracil

cis - platin

5 - FU

5 - FU

head and neck carcinoma

esophageal carcinoma

cardiovascular disease

cardiotoxicity

cardiovascular disease

cardiotoxicity

chest pain

atrial fibrillation

ventricular fibrillation

sudden death

chest pain

tachyarrhythmia

cis - platin

cardiovascular disease

cis - platin

cardiovascular disease

cis - platin

cardiovascular disease

cis - platin

cardiovascular disease

5 - fluorouracil

ventricular fibrillation

5 - FU

ventricular fibrillation

5 - FU

ventricular fibrillation

5 - fluorouracil

chest pain

5 - fluorouracil

chest pain

5 - FU

chest pain

5 - FU

chest pain

5 - FU

chest pain

5 - FU

chest pain

5 - fluorouracil

atrial fibrillation

5 - FU

atrial fibrillation

5 - FU

atrial fibrillation

cis - platin

atrial fibrillation

cis - platin

atrial fibrillation

5 - fluorouracil

cardiovascular disease

5 - fluorouracil

cardiovascular disease

5 - FU

cardiovascular disease

5 - FU

cardiovascular disease

5 - FU

cardiovascular disease

5 - FU

cardiovascular disease

cis - platin

ventricular fibrillation

cis - platin

ventricular fibrillation

cis - platin

chest pain

cis - platin

chest pain

cis - platin

chest pain

cis - platin

chest pain


Input: Verapamil - induced carbamazepine neurotoxicity. A report of two cases. Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).

Verapamil

carbamazepine

carbamazepine

verapamil

calcium

verapamil

carbamazepine

carbamazepine

carbamazepine

neurotoxicity

neurotoxicity

Verapamil

neurotoxicity

Verapamil

neurotoxicity

verapamil

neurotoxicity

verapamil

neurotoxicity

verapamil

neurotoxicity

verapamil

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity

carbamazepine

neurotoxicity


Input: Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy. Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion - dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty - two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg / kg per dose, therapy was restarted with lower doses, usually 50 mg / kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause - and - effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg / kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg / kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg / kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg / kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.

auditory neurotoxicity

Visual and auditory neurotoxicity

Visual and auditory neurotoxicity

auditory neurotoxicity

anemia

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

permanent disability

auditory abnormality

toxicity

ototoxicity

toxicity

hearing loss

auditory dysfunction

deferoxamine

iron

deferoxamine

deferoxamine

deferoxamine

deferoxamine

deferoxamine

deferoxamine

deferoxamine

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

abnormal audiograms with deficits mostly in the high frequency range of 4, 000 to 8, 000 Hz

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity

deferoxamine

Visual and auditory neurotoxicity


Input: Flurbiprofen in the treatment of juvenile rheumatoid arthritis. Thirty - four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg / kg / day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.

Flurbiprofen

flurbiprofen

juvenile rheumatoid arthritis

juvenile rheumatoid arthritis

arthritis

tender joints

swelling

tenderness

morning stiffness

fecal occult blood

gastrointestinal (GI) bleeding

headache

abdominal pain

Flurbiprofen

headache

flurbiprofen

headache

Flurbiprofen

gastrointestinal (GI) bleeding

flurbiprofen

gastrointestinal (GI) bleeding

Flurbiprofen

abdominal pain

flurbiprofen

abdominal pain


Input: The correlation between neurotoxic esterase inhibition and mipafox - induced neuropathic damage in rats. The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N' - diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long - Evans male rats 1 hr post - exposure to various dosages of Mipafox (ip, 1 - 15 mg / kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14 - 21 days post - exposure. Those dosages (greater than or equal to 10 mg / kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg / kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.

neurotoxic

neuropathic damage

neuropathic damage

neurotoxic

neuropathy

neurotoxic

cord damage

cord damage

neuropathic damage

mipafox

Mipafox

N, N' - diisopropylphosphorodiamidofluoridate

organophosphate

Mipafox

Mipafox

Mipafox

mipafox

cord damage

mipafox

cord damage

Mipafox

cord damage

Mipafox

cord damage

N, N' - diisopropylphosphorodiamidofluoridate

cord damage

N, N' - diisopropylphosphorodiamidofluoridate

cord damage

Mipafox

cord damage

Mipafox

cord damage

Mipafox

cord damage

Mipafox

cord damage

Mipafox

cord damage

Mipafox

cord damage


Input: Cerebral infarction with a single oral dose of phenylpropanolamine. Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.

Cerebral infarction

seizures

intracerebral hemorrhage

neuropsychiatric symptoms

cerebral infarction

cerebral infarction

phenylpropanolamine

Phenylpropanolamine

PPA

amphetamine

PPA

phenylpropanolamine

neuropsychiatric symptoms

Phenylpropanolamine

neuropsychiatric symptoms

PPA

neuropsychiatric symptoms

PPA

neuropsychiatric symptoms

phenylpropanolamine

seizures

Phenylpropanolamine

seizures

PPA

seizures

PPA

seizures

phenylpropanolamine

Cerebral infarction

phenylpropanolamine

cerebral infarction

phenylpropanolamine

cerebral infarction

Phenylpropanolamine

Cerebral infarction

Phenylpropanolamine

cerebral infarction

Phenylpropanolamine

cerebral infarction

PPA

Cerebral infarction

PPA

cerebral infarction

PPA

cerebral infarction

PPA

Cerebral infarction

PPA

cerebral infarction

PPA

cerebral infarction

phenylpropanolamine

intracerebral hemorrhage

Phenylpropanolamine

intracerebral hemorrhage

PPA

intracerebral hemorrhage

PPA

intracerebral hemorrhage


Input: Treatment of psoriasis with azathioprine. Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.

psoriasis

psoriasis

cholestasis

fibrosis

liver damage

azathioprine

Azathioprine

azathioprine

azathioprine

fibrosis

Azathioprine

fibrosis

azathioprine

fibrosis

azathioprine

cholestasis

Azathioprine

cholestasis

azathioprine

cholestasis


Input: Maternal lithium and neonatal Ebstein' s anomaly: evaluation with cross - sectional echocardiography. Cross - sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein' s anomaly of the tricuspid valve was identified. In the other infant cross - sectional echocardiography provided reassurance that the infant did not have Ebstein' s anomaly. Cross - sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium - induced cardiac malformations.

lithium

lithium

lithium

lithium

Ebstein' s anomaly

Ebstein' s anomaly

Ebstein' s anomaly

cardiac malformations

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly

lithium

Ebstein' s anomaly


Input: Effects of training on the extent of experimental myocardial infarction in aging rats. The effects of exercise on the severity of isoproterenol - induced myocardial infarction were studied in female albino rats of 20, 40, 60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary - isoproterenols and minimum in the exercise - controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.

myocardial infarction

myocardial infarction

infarcts

myocardial infarction

isoproterenol

isoproterenols

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenols

myocardial infarction

isoproterenols

myocardial infarction

isoproterenols

myocardial infarction


Input: Effect of polyethylene glycol 400 on adriamycin toxicity in mice. The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high - dose and chronic low - dose - ADR - associated lethality. Light microscopic analysis showed a significant protection against ADR - induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.

polyethylene glycol 400

adriamycin

polyethylene glycol 400

PEG 400

adriamycin

ADR

PEG 400

ADR

ADR

ADR

toxicity

cardiac morphological alterations

L1210 leukemia

Ehrlich ascites tumor

adriamycin

cardiac morphological alterations

adriamycin

cardiac morphological alterations

ADR

cardiac morphological alterations

ADR

cardiac morphological alterations

ADR

cardiac morphological alterations

ADR

cardiac morphological alterations


Input: Intra - arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. Because of the rapid systemic clearance of BCNU (1, 3 - bis - (2 - chloroethyl) - 1 - nitrosourea), intra - arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty - six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg / sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast - enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18 - month survival rate of 42%. Twenty - four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra - arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.

BCNU

BCNU

1, 3 - bis - (2 - chloroethyl) - 1 - nitrosourea

BCNU

BCNU

BCNU

ethanol

malignant gliomas

malignant gliomas

astrocytomas

tumor

tumor

edema

astrocytomas

loss of vision

retinal vasculitis

visual loss

BCNU

retinal vasculitis

BCNU

retinal vasculitis

1, 3 - bis - (2 - chloroethyl) - 1 - nitrosourea

retinal vasculitis

BCNU

retinal vasculitis

BCNU

retinal vasculitis

BCNU

retinal vasculitis


Input: Blood pressure response to chronic low - dose intrarenal noradrenaline infusion in conscious rats. Sodium chloride solution (0. 9%) or noradrenaline in doses of 4, 12 and 36 micrograms h - 1 kg - 1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration - blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.

noradrenaline

Sodium chloride

noradrenaline

noradrenaline

noradrenaline

noradrenaline

noradrenaline

noradrenaline

noradrenaline

noradrenaline

hypertension

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension

noradrenaline

hypertension


Input: Age and renal clearance of cimetidine. In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high - pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6 - hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4. 8 + / - 2. 0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1. 9 microgram / ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1. 25 microgram / ml. Thus, high cimetidine levels alone do not always induce dementia.

cimetidine

cimetidine

cimetidine

creatinine

Cimetidine

cimetidine

cimetidine

cimetidine

creatinine

cimetidine

cimetidine

cimetidine

cimetidine

cimetidine

cimetidine

dementia

liver or kidney disease

liver or kidney disease

kidney disease

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

Cimetidine

dementia

Cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia

cimetidine

dementia


Input: Development of clear cell adenocarcinoma in DES - exposed offspring under observation. Two cases of clear cell adenocarcinoma of the vagina detected at follow - up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x - ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.

clear cell adenocarcinoma

clear cell adenocarcinoma of the vagina

clear cell adenocarcinoma

adenocarcinoma of the vagina

carcinoma

carcinoma

DES

diethylstilbestrol

DES

clear cell adenocarcinoma of the vagina

DES

adenocarcinoma of the vagina

diethylstilbestrol

clear cell adenocarcinoma of the vagina

diethylstilbestrol

adenocarcinoma of the vagina

DES

clear cell adenocarcinoma

DES

clear cell adenocarcinoma

diethylstilbestrol

clear cell adenocarcinoma

diethylstilbestrol

clear cell adenocarcinoma


Input: Phenobarbitone - induced enlargement of the liver in the rat: its relationship to carbon tetrachloride - induced cirrhosis. The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2. 2 g / dl, splenomegaly 2 - 3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone - primed rat was increased from 25% to 56% by giving the initial " calibrating " dose of carbon tetrachloride at the peak of the phenobarbitone - induced enlargement of the liver. At this point it was assumed that the cytochrome P450 / CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.

Phenobarbitone

carbon tetrachloride

carbon tetrachloride

phenobarbitone

carbon tetrachloride

phenobarbitone

phenobarbitone

carbon tetrachloride

phenobarbitone

enlargement of the liver

cirrhosis

cirrhosis of the liver

ascites

splenomegaly

atrophy

enlargement of the liver

Phenobarbitone

cirrhosis of the liver

phenobarbitone

cirrhosis of the liver

phenobarbitone

cirrhosis of the liver

phenobarbitone

cirrhosis of the liver

phenobarbitone

cirrhosis of the liver

carbon tetrachloride

cirrhosis of the liver

carbon tetrachloride

cirrhosis of the liver

carbon tetrachloride

cirrhosis of the liver

cirrhosis of the liver

carbon tetrachloride

cirrhosis of the liver

Phenobarbitone

enlargement of the liver

Phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver

phenobarbitone

enlargement of the liver


Input: Attenuation of the lithium - induced diabetes - insipidus - like syndrome by amiloride in rats. The effect of amiloride on lithium - induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium - induced diabetes - insipidus - like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium - treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.

lithium

amiloride

amiloride

lithium

lithium

LiCl

Amiloride

amiloride

lithium

lithium

lithium

lithium

amiloride

lithium

potassium

amiloride

lithium

amiloride

lithium

diabetes - insipidus - like syndrome

polydipsia

polyuria

diabetes - insipidus - like syndrome

polydipsia

polyuria

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome

lithium

diabetes - insipidus - like syndrome


Input: Safety and side - effects of alprazolam. Controlled study in agoraphobia with panic disorder. BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side - effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM - III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side - effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side - effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop - out rate was low. CONCLUSIONS: Alprazolam caused side - effects and adverse effects during treatment but many patients were willing to accept these.

alprazolam

benzodiazepines

alprazolam

alprazolam

alprazolam

alprazolam

Alprazolam

agoraphobia

panic disorder

panic disorder

agoraphobia

panic disorder

agoraphobia

depression

enuresis

aggression

irritability

impaired memory

weight loss

ataxia

alprazolam

ataxia

alprazolam

ataxia

alprazolam

ataxia

alprazolam

ataxia

alprazolam

ataxia

Alprazolam

ataxia

alprazolam

impaired memory

alprazolam

impaired memory

alprazolam

impaired memory

alprazolam

impaired memory

alprazolam

impaired memory

Alprazolam

impaired memory

alprazolam

enuresis

alprazolam

enuresis

alprazolam

enuresis

alprazolam

enuresis

alprazolam

enuresis

Alprazolam

enuresis

alprazolam

depression

alprazolam

depression

alprazolam

depression

alprazolam

depression

alprazolam

depression

Alprazolam

depression

alprazolam

weight loss

alprazolam

weight loss

alprazolam

weight loss

alprazolam

weight loss

alprazolam

weight loss

Alprazolam

weight loss


Input: Dup 753 prevents the development of puromycin aminonucleoside - induced nephrosis. The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg / kg per day. The results suggest a possible involvement of the renin - angiotensin system in the development of puromycin aminonucleoside - induced nephrosis.

Dup 753

puromycin aminonucleoside

blood nitrogen urea

puromycin aminonucleoside

Dup 753

losartan

angiotensin II

angiotensin

puromycin aminonucleoside

nephrosis

nephrotic syndromes

proteinuria

hypoalbuminemia

hypercholesterolemia

nephrosis

puromycin aminonucleoside

hypercholesterolemia

puromycin aminonucleoside

hypercholesterolemia

puromycin aminonucleoside

hypercholesterolemia

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

nephrotic syndromes

puromycin aminonucleoside

nephrotic syndromes

puromycin aminonucleoside

nephrotic syndromes

puromycin aminonucleoside

hypoalbuminemia

puromycin aminonucleoside

hypoalbuminemia

puromycin aminonucleoside

hypoalbuminemia


Input: Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction. In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0. 2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7. 05) or without (pH 4. 17) the addition of sodium bicarbonate (0. 03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.

Sodium bicarbonate

sodium bicarbonate

papaverine

phentolamine

prostaglandin E1

sodium bicarbonate

sodium bicarbonate

sodium bicarbonate

penile pain

erectile dysfunction

penile pain

penile pain

impotence

penile pain

penile pain

penile pain

phentolamine

penile pain

phentolamine

penile pain

phentolamine

penile pain

phentolamine

penile pain

phentolamine

penile pain

phentolamine

penile pain

prostaglandin E1

penile pain

prostaglandin E1

penile pain

prostaglandin E1

penile pain

prostaglandin E1

penile pain

prostaglandin E1

penile pain

prostaglandin E1

penile pain


Input: Prospective study of the long - term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients. This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300 - 1500 micrograms / day for a mean of 24. 2 + / - 13. 9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100 - micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long - term octreotide therapy of acromegalic patients.

octreotide

octreotide

octreotide

octreotide

octreotide

octreotide

gallstone

acromegalic

acromegaly

gallstones

acute cholecystitis

depressed

gallstones

gallstones

depressed

gallstones

cholecystitis

acromegalic

acromegalic

octreotide

acute cholecystitis

octreotide

acute cholecystitis

octreotide

acute cholecystitis

octreotide

acute cholecystitis

octreotide

acute cholecystitis

octreotide

acute cholecystitis

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstone

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones

octreotide

gallstones


Input: Improvement of levodopa - induced dyskinesia by propranolol in Parkinson' s disease. Seven patients suffering from Parkinson' s disease (PD) with severely disabling dyskinesia received low - dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta - blockers may improve levodopa - induced ballistic and choreic dyskinesia in PD.

levodopa

propranolol

propranolol

levodopa

dyskinesia

Parkinson' s disease

Parkinson' s disease

PD

dyskinesia

dyskinesia

parkinsonian

motor disability

dyskinesia

dystonia

dyskinesia

PD

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia


Input: Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex. Long - term intragastric application of the antiepileptic drug sodium valproate (Vupral " Polfa ") at the effective dose of 200 mg / kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (" valproate encephalopathy "). The first ultrastructural changes in structural elements of the blood - brain - barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann' s in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.

encephalopathy

neurological disorders

cerebellum damage

encephalopathy

necrosis

necrotic

hepatic damage

hyperammonemia

encephalopathy

valproate

sodium valproate

valproate

luminal

luminal

valproate

valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy

sodium valproate

encephalopathy

sodium valproate

encephalopathy

sodium valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy

valproate

encephalopathy


Input: Macula toxicity after intravitreal amikacin. BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha - haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6 / 24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.

toxicity

endophthalmitis

infarction

retinal toxicity

streptococcal endophthalmitis

Endophthalmitis

telangiectasis

retinal toxicity

ischaemia

retinal toxicity

amikacin

aminoglycosides

amikacin

amikacin

vancomycin

fluorescein

amikacin

ischaemia

amikacin

ischaemia

amikacin

ischaemia

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity

amikacin

retinal toxicity