Input: Nicotine antagonizes caffeine - but not pentylenetetrazole - induced anxiogenic effect in mice. RATIONALE: Nicotine and caffeine are widely consumed licit psychoactive drugs worldwide. Epidemiological studies showed that they were generally used concurrently. Although some studies in experimental animals indicate clear pharmacological interactions between them, no studies have shown a specific interaction on anxiety responses. OBJECTIVES: The present study investigates the effects of nicotine on anxiety induced by caffeine and another anxiogenic drug, pentylenetetrazole, in mice. The elevated plus - maze (EPM) test was used to evaluate the effects of drugs on anxiety. METHODS: Adult male Swiss Webster mice (25 - 32 g) were given nicotine (0. 05 - 0. 25 mg / kg s. c.) or saline 10 min before caffeine (70 mg / kg i. p.) or pentylenetetrazole (15 and 30 mg / kg i. p.) injections. After 15 min, mice were evaluated for their open - and closed - arm time and entries on the EPM for a 10 - min session. Locomotor activity was recorded for individual groups by using the same treatment protocol with the EPM test. RESULTS: Nicotine (0. 05 - 0. 25 mg / kg) itself did not produce any significant effect in the EPM test, whereas caffeine (70 mg / kg) and pentylenetetrazole (30 mg / kg) produced an anxiogenic effect, apparent with decreases in open - arm time and entry. Nicotine (0. 25 mg / kg) pretreatment blocked the caffeine - but not pentylenetetrazole - induced anxiety. Administration of each drug and their combinations did not produce any effect on locomotor activity. CONCLUSIONS: Our results suggest that the antagonistic effect of nicotine on caffeine - induced anxiety is specific to caffeine, instead of a non - specific anxiolytic effect. Thus, it may extend the current findings on the interaction between nicotine and caffeine.

Nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

nicotine

caffeine

pentylenetetrazole

nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

pentylenetetrazole

nicotine

caffeine

caffeine

nicotine

caffeine

anxiety

anxiety

anxiety

anxiety

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety


Input: Long term hormone therapy for perimenopausal and postmenopausal women. BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long - term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non - indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double - blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta - analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year' s use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long - term oestrogen - only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long - term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long - term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year - old women taking combined continuous HT and 1637 taking oestrogen - only HT, versus similar - sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short - term use appears to be relatively safe for healthy younger women.

menopausal symptoms

cardiovascular disease

osteoporosis

dementia

heart disease

venous thromboembolism

stroke

transient ischaemic attacks

breast cancer

colorectal cancer

ovarian cancer

endometrial cancer

gallbladder disease

dementia

fractures

venous thromboembolism

stroke

breast cancer

gallbladder disease

stroke

gallbladder disease

fractures

colon cancer

dementia

cardiovascular disease

venous thromboembolism

venous thromboembolism

chronic disease

oestrogens

progestogens

oestrogen

oestrogen

progestogens

gallbladder disease

progestogens

gallbladder disease

progestogens

gallbladder disease

oestrogens

dementia

oestrogens

dementia

oestrogens

dementia

oestrogen

dementia

oestrogen

dementia

oestrogen

dementia

oestrogen

dementia

oestrogen

dementia

oestrogen

dementia

oestrogens

venous thromboembolism

oestrogens

venous thromboembolism

oestrogens

venous thromboembolism

oestrogens

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogen

venous thromboembolism

oestrogens

cardiovascular disease

oestrogens

cardiovascular disease

oestrogen

cardiovascular disease

oestrogen

cardiovascular disease

oestrogen

cardiovascular disease

oestrogen

cardiovascular disease

oestrogens

gallbladder disease

oestrogens

gallbladder disease

oestrogens

gallbladder disease

oestrogen

gallbladder disease

oestrogen

gallbladder disease

oestrogen

gallbladder disease

oestrogen

gallbladder disease

oestrogen

gallbladder disease

oestrogen

gallbladder disease

progestogens

venous thromboembolism

progestogens

venous thromboembolism

progestogens

venous thromboembolism

progestogens

venous thromboembolism

oestrogens

stroke

oestrogens

stroke

oestrogens

stroke

oestrogen

stroke

oestrogen

stroke

oestrogen

stroke

oestrogen

stroke

oestrogen

stroke

oestrogen

stroke

progestogens

cardiovascular disease

progestogens

cardiovascular disease

progestogens

breast cancer

progestogens

breast cancer

progestogens

stroke

progestogens

stroke

progestogens

stroke

progestogens

dementia

progestogens

dementia

progestogens

dementia

oestrogens

breast cancer

oestrogens

breast cancer

oestrogen

breast cancer

oestrogen

breast cancer

oestrogen

breast cancer

oestrogen

breast cancer


Input: Drug - induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10 - year period. BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug - induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin - clavulanate accounting for the 12. 8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P <. 0001), and had the worst outcome (Cox regression, P <. 034). Indeed, the incidence of liver transplantation and death in this group was 11. 7% if patients had jaundice at presentation, whereas the corresponding figure was 3. 8% in nonjaundiced patients (P <. 04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4. 1 - 151; P <. 0001), hepatocellular damage (OR = 7. 9; 95% CI: 1. 6 - 37; P <. 009), and higher baseline plasma bilirubin value (OR = 1. 15; 95% CI: 1. 09 - 1. 22; P <. 0001). CONCLUSIONS: Patients with drug - induced hepatocellular jaundice have 11. 7% chance of progressing to death or transplantation. Amoxicillin - clavulanate stands out as the most common drug related to DILI.

Drug - induced liver injury

drug - induced liver injury

DILI

DILI

liver damage

cholestatic

DILI

jaundice

fulminant hepatic failure

jaundice

DILI

amoxicillin - clavulanate

bilirubin

Amoxicillin - clavulanate

amoxicillin - clavulanate

Drug - induced liver injury

amoxicillin - clavulanate

drug - induced liver injury

amoxicillin - clavulanate

DILI

amoxicillin - clavulanate

DILI

amoxicillin - clavulanate

liver damage

amoxicillin - clavulanate

DILI

amoxicillin - clavulanate

DILI

Amoxicillin - clavulanate

Drug - induced liver injury

Amoxicillin - clavulanate

drug - induced liver injury

Amoxicillin - clavulanate

DILI

Amoxicillin - clavulanate

DILI

Amoxicillin - clavulanate

liver damage

Amoxicillin - clavulanate

DILI

Amoxicillin - clavulanate

DILI

amoxicillin - clavulanate

jaundice

amoxicillin - clavulanate

jaundice

Amoxicillin - clavulanate

jaundice

Amoxicillin - clavulanate

jaundice


Input: Morphological evaluation of the effect of d - ribose on adriamycin - evoked cardiotoxicity in rats. The influence of d - ribose on adriamycin - induced myocardiopathy in rats was studied. Adriamycin in the cumulative dose of 25 mg / kg evoked fully developed cardiac toxicity. D - ribose in the multiple doses of 200 mg / kg did not influence ADR cardiotoxicity.

d - ribose

adriamycin

d - ribose

adriamycin

Adriamycin

D - ribose

ADR

cardiotoxicity

myocardiopathy

cardiac toxicity

cardiotoxicity

adriamycin

myocardiopathy

adriamycin

myocardiopathy

Adriamycin

myocardiopathy

ADR

myocardiopathy


Input: In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin - induced nephrotoxicity: protection by erdosteine. The aims of this study were to examine vancomycin (VCM) - induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM - induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i. p.) with 200mgkg (- 1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N - acetyl - beta - d - glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM - induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM - treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM - induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM - induced kidney damage both at the biochemical and histological levels.

vancomycin

erdosteine

vancomycin

VCM

oxygen

erdosteine

VCM

VCM

VCM

erdosteine

VCM

Erdosteine

VCM

malondialdehyde

MDA

superoxide

Erdosteine

VCM

MDA

VCM

Erdosteine

VCM

VCM

erdosteine

Erdosteine

VCM

erdosteine

VCM

nephrotoxicity

renal impairment

renal tubular injury

nephrotoxicity

atrophy

desquamation

necrosis

nephrotoxicity

kidney damage

vancomycin

nephrotoxicity

vancomycin

renal impairment

vancomycin

renal tubular injury

vancomycin

nephrotoxicity

vancomycin

nephrotoxicity

vancomycin

kidney damage

vancomycin

nephrotoxicity

vancomycin

renal impairment

vancomycin

renal tubular injury

vancomycin

nephrotoxicity

vancomycin

nephrotoxicity

vancomycin

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage

VCM

nephrotoxicity

VCM

renal impairment

VCM

renal tubular injury

VCM

nephrotoxicity

VCM

nephrotoxicity

VCM

kidney damage


Input: Does domperidone potentiate mirtazapine - associated restless legs syndrome? There is now evidence to suggest a central role for the dopaminergic system in restless legs syndrome (RLS). For example, the symptoms of RLS can be dramatically improved by levodopa and dopamine agonists, whereas central dopamine D2 receptor antagonists can induce or aggravate RLS symptoms. To our knowledge, there is no previous report regarding whether domperidone, a peripheral dopamine D2 receptor antagonist, can also induce or aggravate symptoms of RLS. Mirtazapine, the first noradrenergic and specific serotonergic antidepressant (NaSSA), has been associated with RLS in several recent publications. The authors report here a depressed patient comorbid with postprandial dyspepsia who developed RLS after mirtazapine had been added to his domperidone therapy. Our patient started to have symptoms of RLS only after he had been treated with mirtazapine, and his RLS symptoms resolved completely upon discontinuation of his mirtazapine. Such a temporal relationship between the use of mirtazapine and the symptoms of RLS in our patient did not support a potentiating effect of domperione on mirtazapine - associated RLS. However, physicians should be aware of the possibility that mirtazapine can be associated with RLS in some individuals, especially those receiving concomitant dopamine D2 receptor antagonists.

domperidone

mirtazapine

levodopa

dopamine

dopamine

domperidone

dopamine

Mirtazapine

mirtazapine

domperidone

mirtazapine

mirtazapine

mirtazapine

domperione

mirtazapine

mirtazapine

dopamine

restless legs syndrome

restless legs syndrome

RLS

RLS

RLS

RLS

RLS

postprandial dyspepsia

RLS

RLS

RLS

RLS

RLS

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

Mirtazapine

restless legs syndrome

Mirtazapine

restless legs syndrome

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

Mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

restless legs syndrome

mirtazapine

restless legs syndrome

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS

mirtazapine

RLS


Input: Antiandrogenic therapy can cause coronary arterial disease. AIM: To study the change of lipid metabolism by antiandrogen therapy in patients with prostate cancer. MATERIALS AND METHODS: We studied with a 2. 5 years follow - up the changes in plasma cholesterols (C), triglycerides (TG), lipoproteins (LP), and apolipoproteins (Apo) B - 100, A - I, and A - II pro fi les in 24 patients of mean age 60 years with low risk prostate cancer (stage: T1cN0M0, Gleason score: 2 - 5) during treatment with cyproterone acetate (CPA) without surgical management or radiation therapy. RESULTS: Significant decreases of HDL - C, Apo A - I and Apo A - II and an increase of triglyceride levels in VLDL were induced by CPA. After a period of 2. 5 years on CPA treatment, four patients out of twenty - four were found to be affected by coronary heart disease. CONCLUSIONS: Ischaemic coronary arteriosclerosis with an incidence rate of 16. 6% as caused by prolonged CPA therapy is mediated through changes in HDL cholesterol, Apo A - I and Apo A - II pro fi les, other than the well - known hyperglyceridemic effect caused by estrogen.

coronary arterial disease

prostate cancer

prostate cancer

coronary heart disease

coronary arteriosclerosis

hyperglyceridemic effect

cholesterols

C

triglycerides

TG

cyproterone acetate

CPA

triglyceride

CPA

CPA

CPA

cholesterol

estrogen

cyproterone acetate

hyperglyceridemic effect

CPA

hyperglyceridemic effect

CPA

hyperglyceridemic effect

CPA

hyperglyceridemic effect

CPA

hyperglyceridemic effect

cyproterone acetate

coronary arterial disease

cyproterone acetate

coronary arteriosclerosis

CPA

coronary arterial disease

CPA

coronary arteriosclerosis

CPA

coronary arterial disease

CPA

coronary arteriosclerosis

CPA

coronary arterial disease

CPA

coronary arteriosclerosis

CPA

coronary arterial disease

CPA

coronary arteriosclerosis


Input: 5 - Fluorouracil cardiotoxicity induced by alpha - fluoro - beta - alanine. Cardiotoxicity is a rare complication occurring during 5 - fluorouracil (5 - FU) treatment for malignancies. We herein report the case of a 70 - year - old man with 5 - FU - induced cardiotoxicity, in whom a high serum level of alpha - fluoro - beta - alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5 - FU (1000 mg / day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng / ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5 - FU. As the precordial pain in this patient was considered to have been due to 5 - FU - induced cardiotoxicity, the administration of 5 - FU was abandoned. Instead, oral administration of S - 1 (a derivative of 5 - FU), at 200 mg / day twice a week, was instituted, because S - 1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5 - FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng / ml, the same as the value measured on the first day of S - 1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S - 1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5 - FU - induced cardiotoxicity. S - 1 may be administered safely to patients with 5 - FU - induced cardiotoxicity.

5 - Fluorouracil

alpha - fluoro - beta - alanine

5 - fluorouracil

5 - FU

5 - FU

alpha - fluoro - beta - alanine

FBAL

5 - FU

FBAL

5 - FU

5 - FU

5 - FU

5 - FU

dihydropyrimidine

5 - FU

FBAL

FBAL

FBAL

5 - FU

5 - FU

cardiotoxicity

Cardiotoxicity

malignancies

cardiotoxicity

colon cancer

precordial pain

right bundle branch block

precordial pain

precordial pain

cardiotoxicity

cardiac symptoms

cardiotoxicity

cardiotoxicity

5 - Fluorouracil

precordial pain

5 - Fluorouracil

precordial pain

5 - Fluorouracil

precordial pain

5 - fluorouracil

precordial pain

5 - fluorouracil

precordial pain

5 - fluorouracil

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - FU

precordial pain

5 - Fluorouracil

right bundle branch block

5 - fluorouracil

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block

5 - FU

right bundle branch block


Input: The influence of the time interval between monoHER and doxorubicin administration on the protection against doxorubicin - induced cardiotoxicity in mice. PURPOSE: Despite its well - known cardiotoxicity, the anthracyclin doxorubicin (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX - induced cardiac damage presumably results from the formation of free radicals by DOX. Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system. The semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed cardioprotection against DOX - induced cardiotoxicity through its radical scavenging and iron chelating properties. Because of the relatively short final half - life of monoHER (about 30 min), it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER. Therefore, the aim of the present study was to investigate this possible effect. METHODS: Six groups of 6 BALB / c mice were treated with saline, DOX alone or DOX (4 mg / kg i. v.) preceded by monoHER (500 mg / kg i. p.) with an interval of 10, 30, 60 or 120 min. After a 6 - week treatment period and additional observation for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for light microscopy, after which cardiomyocyte damage was evaluated according to Billingham (in Cancer Treat Rep 62 (6): 865 - 872, 1978). Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group (P < 0. 001). RESULTS: The number of damaged cardiomyocytes was 9. 6 - fold (95% CI 4. 4 - 21. 0) higher in mice treated with DOX alone than that in animals of the control group. The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1. 6 to 2. 8 (mean 2. 2, 95% CI 1. 2 - 4. 1, P = 0. 019). The mean protective effect by adding monoHER before DOX led to a significant 4. 4 - fold reduction (P < 0. 001, 95% CI 2. 3 - 8. 2) of abnormal cardiomyocytes. This protective effect did not depend on the time interval between monoHER and DOX administration (P = 0. 345). CONCLUSION: The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX.

monoHER

doxorubicin

doxorubicin

doxorubicin

DOX

DOX

DOX

oxygen

flavonoid

monohydroxyethylrutoside

monoHER

DOX

iron

monoHER

monoHER

DOX

monoHER

DOX

DOX

monoHER

DOX

DOX

DOX

monoHER

monoHER

DOX

monoHER

DOX

monoHER

DOX

cardiotoxicity

cardiotoxicity

cardiac damage

cardiotoxicity

cardiomyocyte damage

Cancer

cardiac damage

doxorubicin

cardiomyocyte damage

doxorubicin

cardiomyocyte damage

doxorubicin

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage

DOX

cardiomyocyte damage


Input: Clinical evaluation of adverse effects during bepridil administration for atrial fibrillation and flutter. BACKGROUND: Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. METHODS AND RESULTS: Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63 + / - 12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66 + / - 11% and 40 + / - 6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow - up of 20 months. There was marked QT prolongation greater than 0. 55 s in 13 patients, bradycardia less than 40 beats / min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. CONCLUSION: Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients.

bepridil

Bepridil hydrochloride

Bpd

Bpd

Bpd

potassium

Bpd

atrial fibrillation and flutter

atrial fibrillation

atrial fibrillation and flutter

atrial fibrillation

AF

atrial flutter

AFL

torsade de pointes

Tdp

AF

AFL

QT prolongation

bradycardia

dizziness

fatigue

QT prolongation

Tdp

Tdp

hypokalemia

Tdp

Tdp

bepridil

QT prolongation

bepridil

QT prolongation

Bepridil hydrochloride

QT prolongation

Bepridil hydrochloride

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

Bpd

QT prolongation

bepridil

torsade de pointes

bepridil

Tdp

bepridil

Tdp

bepridil

Tdp

bepridil

Tdp

bepridil

Tdp

Bepridil hydrochloride

torsade de pointes

Bepridil hydrochloride

Tdp

Bepridil hydrochloride

Tdp

Bepridil hydrochloride

Tdp

Bepridil hydrochloride

Tdp

Bepridil hydrochloride

Tdp

Bpd

torsade de pointes

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

torsade de pointes

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

torsade de pointes

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

torsade de pointes

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

Bpd

Tdp

bepridil

bradycardia

Bepridil hydrochloride

bradycardia

Bpd

bradycardia

Bpd

bradycardia

Bpd

bradycardia

Bpd

bradycardia

bepridil

dizziness

Bepridil hydrochloride

dizziness

Bpd

dizziness

Bpd

dizziness

Bpd

dizziness

Bpd

dizziness

bepridil

fatigue

Bepridil hydrochloride

fatigue

Bpd

fatigue

Bpd

fatigue

Bpd

fatigue

Bpd

fatigue

potassium

torsade de pointes

potassium

Tdp

potassium

Tdp

potassium

Tdp

potassium

Tdp

potassium

Tdp


Input: Enhanced isoproterenol - induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen. We have previously shown that a permanent deficiency in the brain renin - angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta - adrenoceptor (beta - AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+ dP / dt (max)) in the TGR than in the Sprague - Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt / 100 g body wt, 0. 28 + / - 0. 004 vs. 0. 24 + / - 0. 004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta - AR and upregulation of LV beta - AR kinase - 1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the beta - AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (- 9. 9 + / - 1. 7% vs. - 18. 1 + / - 1. 5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to beta - AR agonist - induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.

isoproterenol

angiotensin

isoproterenol

Iso

Iso

Iso

metoprolol

atropine

cardiac hypertrophy

LV hypertrophy

LV hypertrophy

cardiac inotropic

hypertrophy

isoproterenol

cardiac hypertrophy

isoproterenol

LV hypertrophy

isoproterenol

LV hypertrophy

isoproterenol

cardiac hypertrophy

isoproterenol

LV hypertrophy

isoproterenol

LV hypertrophy

Iso

cardiac hypertrophy

Iso

LV hypertrophy

Iso

LV hypertrophy

Iso

cardiac hypertrophy

Iso

LV hypertrophy

Iso

LV hypertrophy

Iso

cardiac hypertrophy

Iso

LV hypertrophy

Iso

LV hypertrophy


Input: Drug - induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. BACKGROUND: Drug - induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose - dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug - drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5 - year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0. 50 second ((1 / 2)) or longer was 16. 2% compared with 0% in 80 control subjects. Six patients (3. 6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0. 20; P <. 01). Multivariate regression analysis allowed attribution of 31. 8% of QTc variability to methadone dose, cytochrome P - 450 3A4 drug - drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P - 450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.

long QT syndrome

long QT syndrome

QT interval prolongation

QT prolongation

torsades de pointes

hypokalemia

QT interval prolongation

QT prolongation

Long QT syndrome

methadone

Methadone

methadone

methadone

methadone

methadone

methadone

methadone

methadone

methadone

methadone

methadone

methadone

Methadone

potassium

methadone

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

Methadone

long QT syndrome

Methadone

long QT syndrome

Methadone

QT interval prolongation

Methadone

QT prolongation

Methadone

QT interval prolongation

Methadone

QT prolongation

Methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome

Methadone

long QT syndrome

Methadone

long QT syndrome

Methadone

QT interval prolongation

Methadone

QT prolongation

Methadone

QT interval prolongation

Methadone

QT prolongation

Methadone

Long QT syndrome

methadone

long QT syndrome

methadone

long QT syndrome

methadone

QT interval prolongation

methadone

QT prolongation

methadone

QT interval prolongation

methadone

QT prolongation

methadone

Long QT syndrome


Input: Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function. Loss of endothelial cell - derived nitric oxide (NO) in hypertension is a hallmark of arterial dysfunction. Experimental hypertension created by the removal of NO, however, involves mechanisms in addition to decreased arterial vasodilator activity. These include augmented endothelin - 1 (ET - 1) release, increased sympathetic nervous system activity, and elevated tissue oxidative stress. We hypothesized that increased venous smooth muscle (venomotor) tone plays a role in Nomega - nitro - L - arginine (LNNA) hypertension through these mechanisms. Rats were treated with the NO synthase inhibitor LNNA (0. 5 g / L in drinking water) for 2 weeks. Mean arterial pressure of conscious rats was 119 + / - 2 mm Hg in control and 194 + / - 5 mm Hg in LNNA rats (P < 0. 05). Carotid arteries and vena cava were removed for measurement of isometric contraction. Maximal contraction to norepinephrine was modestly reduced in arteries from LNNA compared with control rats whereas the maximum contraction to ET - 1 was significantly reduced (54% control). Maximum contraction of vena cava to norepinephrine (37% control) also was reduced but no change in response to ET - 1 was observed. Mean circulatory filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30, 100, and 300 micromol kg (- 1), IV) did not change arterial pressure in control rats but caused a dose - dependent decrease in LNNA rats (- 18 + / - 8, - 26 + / - 15, and - 54 + / - 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a significantly greater fall in LNNA hypertensive rats (76 + / - 9 mm Hg) compared with control rats (35 + / - 10 mm Hg). Carotid arteries, vena cava, and sympathetic ganglia from LNNA rats had higher basal levels of superoxide compared with those from control rats. These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension.

hypertension

hypertension

arterial dysfunction

hypertension

hypertension

hypertension

hypertensive

hypertension

nitric oxide

NO

nitric oxide

NO

NO

Nomega - nitro - L - arginine

LNNA

NO

LNNA

LNNA

norepinephrine

LNNA

norepinephrine

LNNA

LNNA

superoxide

tempol

LNNA

hexamethonium

LNNA

LNNA

superoxide

NO

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertensive

nitric oxide

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertensive

NO

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertension

nitric oxide

hypertensive

nitric oxide

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertensive

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertensive

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertensive

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertension

NO

hypertensive

NO

hypertension


Input: Association of DRD2 polymorphisms and chlorpromazine - induced extrapyramidal syndrome in Chinese schizophrenic patients. AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine - induced EPS in schizophrenic patients. METHODS: We identified seven SNP (single nucleotide polymorphism) (- 141Cins > del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson - Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of - 141Cins > del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.

chlorpromazine

chlorpromazine

chlorpromazine

chlorpromazine

extrapyramidal syndrome

schizophrenic

Extrapyramidal syndrome

EPS

schizophrenia

EPS

schizophrenic

schizophrenic

EPS

EPS

schizophrenia

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

extrapyramidal syndrome

chlorpromazine

Extrapyramidal syndrome

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS

chlorpromazine

EPS


Input: Physical training decreases susceptibility to subsequent pilocarpine - induced seizures in the rat. Regular motor activity has many benefits for mental and physical condition but its implications for epilepsy are still controversial. In order to elucidate this problem, we have studied the effect of long - term physical activity on susceptibility to subsequent seizures. Male Wistar rats were subjected to repeated training sessions in a treadmill and swimming pool. Thereafter, seizures were induced by pilocarpine injections in trained and non - trained control groups. During the acute period of status epilepticus, we measured: (1) the latency of the first motor sign, (2) the intensity of seizures, (3) the time when it occurred within the 6 - h observation period, and (4) the time when the acute period ended. All these behavioral parameters showed statistically significant changes suggesting that regular physical exercises decrease susceptibility to subsequently induced seizures and ameliorate the course of experimentally induced status epilepticus.

pilocarpine

pilocarpine

seizures

epilepsy

seizures

seizures

status epilepticus

seizures

seizures

status epilepticus

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus


Input: Tonic dopaminergic stimulation impairs associative learning in healthy subjects. Endogenous dopamine plays a central role in salience coding during associative learning. Administration of the dopamine precursor levodopa enhances learning in healthy subjects and stroke patients. Because levodopa increases both phasic and tonic dopaminergic neurotransmission, the critical mechanism mediating the enhancement of learning is unresolved. We here probed how selective tonic dopaminergic stimulation affects associative learning. Forty healthy subjects were trained in a novel vocabulary of 45 concrete nouns over the course of 5 consecutive training days in a prospective, randomized, double - blind, placebo - controlled design. Subjects received the tonically stimulating dopamine - receptor agonist pergolide (0. 1 mg) vs placebo 120 min before training on each training day. The dopamine agonist significantly impaired novel word learning compared to placebo. This learning decrement persisted up to the last follow - up 4 weeks post - training. Subjects treated with pergolide also showed restricted emotional responses compared to the PLACEBO group. The extent of' flattened' affect with pergolide was related to the degree of learning inhibition. These findings suggest that tonic occupation of dopamine receptors impairs learning by competition with phasic dopamine signals. Thus, phasic signaling seems to be the critical mechanism by which dopamine enhances associative learning in healthy subjects and stroke patients.

impairs associative learning

stroke

impaired novel word learning

stroke

dopamine

dopamine

levodopa

levodopa

dopamine

pergolide

dopamine

pergolide

pergolide

dopamine

dopamine

dopamine

pergolide

impairs associative learning

pergolide

impaired novel word learning

pergolide

impairs associative learning

pergolide

impaired novel word learning

pergolide

impairs associative learning

pergolide

impaired novel word learning


Input: Minocycline - induced vasculitis fulfilling the criteria of polyarteritis nodosa. A 47 - year - old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C - reactive protein (CRP). Neither myeloperoxidase - nor proteinase - 3 - antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline - induced vasculitis satisfying the criteria. Differential diagnosis for drug - induced disease is invaluable even for patients with classical polyarteritis nodosa.

Minocycline

minocycline

minocycline

minocycline

vasculitis

polyarteritis nodosa

palmoplantar pustulosis

fever

myalgias

polyneuropathy

testicular pain

polyarteritis nodosa

vasculitis

polyarteritis nodosa

Minocycline

polyarteritis nodosa

Minocycline

polyarteritis nodosa

Minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa

minocycline

polyarteritis nodosa


Input: Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation. BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV - related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter. RESULTS: At a median follow - up of 14. 1 months, the overall recurrence rate in the 51 patients was 3. 9% (2 / 51). The overall patient survival was 88. 3%, and 82. 4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57. 1% (4 / 7) and 62. 5% (5 / 8) of HBV - DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.

hepatitis B

hepatitis B

hepatitis B

hepatitis B

hepatitis B

cirrhotic diseases

lamivudine

lamivudine

HBsAg

lamivudine

HBeAg

Lamivudine

HBeAg

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B


Input: Anticonvulsant effect of eslicarbazepine acetate (BIA 2 - 093) on seizures induced by microperfusion of picrotoxin in the hippocampus of freely moving rats. Eslicarbazepine acetate (BIA 2 - 093, S - (-) - 10 - acetoxy - 10, 11 - dihydro - 5H - dibenzo / b, f / azepine - 5 - carboxamide) is a novel antiepileptic drug, now in Phase III clinical trials, designed with the aim of improving efficacy and safety in comparison with the structurally related drugs carbamazepine (CBZ) and oxcarbazepine (OXC). We have studied the effects of oral treatment with eslicarbazepine acetate on a whole - animal model in which partial seizures can be elicited repeatedly on different days without changes in threshold or seizure patterns. In the animals treated with threshold doses of picrotoxin, the average number of seizures was 2. 3 + / - 1. 2, and average seizure duration was 39. 5 + / - 8. 4s. Pre - treatment with a dose of 30 mg / kg 2h before picrotoxin microperfusion prevented seizures in the 75% of the rats. Lower doses (3 and 10mg / kg) did not suppress seizures, however, after administration of 10mg / kg, significant reductions in seizures duration (24. 3 + / - 6. 8s) and seizure number (1. 6 + / - 0. 34) were found. No adverse effects of eslicarbazepine acetate were observed in the behavioral / EEG patterns studied, including sleep / wakefulness cycle, at the doses studied.

eslicarbazepine acetate

BIA 2 - 093

picrotoxin

Eslicarbazepine acetate

BIA 2 - 093

S - (-) - 10 - acetoxy - 10, 11 - dihydro - 5H - dibenzo / b, f / azepine - 5 - carboxamide

carbamazepine

CBZ

oxcarbazepine

OXC

eslicarbazepine acetate

picrotoxin

picrotoxin

eslicarbazepine acetate

seizures

seizures

seizure

seizures

seizure

seizures

seizures

seizures

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizure

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizure


Input: Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Chinese herbal medicine preparations are widely available and often regarded by the public as natural and safe remedies for a variety of medical conditions. Nephropathy caused by Chinese herbs has previously been reported, usually involving the use of aristolochic acids. We report a 23 - year - old woman who developed acute renal failure following prolonged use of a proprietary Chinese herbal slimming pill that contained anthraquinone derivatives, extracted from Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the concomitant intake of a non - steroidal anti - inflammatory drug, diclofenac. Renal pathology was that of hypocellular interstitial fibrosis. Spontaneous renal recovery occurred upon cessation of the slimming pills, but mild interstitial fibrosis and tubular atrophy was still evident histologically 4 months later. Although a causal relationship between the use of an anthraquinone - containing herbal agent and renal injury remains to be proven, phytotherapy - associated interstitial nephropathy should be considered in patients who present with unexplained renal failure.

Acute renal failure

Nephropathy

acute renal failure

renal injury

fibrosis

fibrosis

atrophy

renal injury

nephropathy

renal failure

anthraquinones

Chinese herbal

Chinese herbs

aristolochic acids

Chinese herbal

anthraquinone

diclofenac

anthraquinone

diclofenac

Acute renal failure

diclofenac

acute renal failure

diclofenac

renal injury

diclofenac

renal injury

Chinese herbal

Acute renal failure

Chinese herbal

acute renal failure

Chinese herbal

renal injury

Chinese herbal

renal injury

Chinese herbs

Acute renal failure

Chinese herbs

acute renal failure

Chinese herbs

renal injury

Chinese herbs

renal injury

Chinese herbal

Acute renal failure

Chinese herbal

acute renal failure

Chinese herbal

renal injury

Chinese herbal

renal injury


Input: Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in ifosfamide nephropathy. Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO) and putatively responsible for renal damage following anti - tumor therapy with IFO. Depletion of sulfhydryl (SH) groups has been reported from cell culture, animal and clinical studies. In this work the effect of CAA on human proximal tubule cells in primary culture (hRPTEC) was investigated. Toxicity of CAA was determined by protein content, cell number, LDH release, trypan blue exclusion assay and caspase - 3 activity. Free thiols were measured by the method of Ellman. CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular thiols and an increase in necrosis markers. CAA but not acrolein inhibited the cysteine proteases caspase - 3, caspase - 8 and cathepsin B. Caspase activation by cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The effects of CAA on cysteine protease activities and thiols could be reproduced in cell lysate. Acidification, which slowed the reaction of CAA with thiol donors, could also attenuate effects of CAA on necrosis markers, thiol depletion and cysteine protease inhibition in living cells. Thus, CAA directly reacts with cellular protein and non - protein thiols, mediating its toxicity on hRPTEC. This effect can be reduced by acidification. Therefore, urinary acidification could be an option to prevent IFO nephropathy in patients.

Chloroacetaldehyde

sulfhydryl

thiol

ifosfamide

Chloroacetaldehyde

CAA

ifosfamide

IFO

IFO

sulfhydryl

SH

CAA

CAA

trypan blue

thiols

CAA

thiols

CAA

acrolein

cysteine

cisplatin

CAA

CAA

CAA

cysteine

thiols

CAA

thiol

CAA

thiol

cysteine

CAA

thiols

IFO

nephropathy

renal damage

tumor

Toxicity

necrosis

necrosis

toxicity

nephropathy

ifosfamide

nephropathy

ifosfamide

renal damage

ifosfamide

nephropathy

ifosfamide

nephropathy

ifosfamide

renal damage

ifosfamide

nephropathy

IFO

nephropathy

IFO

renal damage

IFO

nephropathy

IFO

nephropathy

IFO

renal damage

IFO

nephropathy

IFO

nephropathy

IFO

renal damage

IFO

nephropathy


Input: Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine - induced status epilepticus in the adult rat. Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine - induced status epilepticus. The number of hilar neurons immunoreactive for Prox - 1, a granule - cell - specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.

pilocarpine

pilocarpine

pilocarpine

status epilepticus

status epilepticus

seizures

status epilepticus

status epilepticus

status epilepticus

seizures

seizures

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus


Input: A prospective, open - label trial of galantamine in autistic disorder. OBJECTIVE: Post - mortem studies have reported abnormalities of the cholinergic system in autism. The purpose of this study was to assess the use of galantamine, an acetylcholinesterase inhibitor and nicotinic receptor modulator, in the treatment of interfering behaviors in children with autism. METHODS: Thirteen medication - free children with autism (mean age, 8. 8 + / - 3. 5 years) participated in a 12 - week, open - label trial of galantamine. Patients were rated monthly by parents on the Aberrant Behavior Checklist (ABC) and the Conners' Parent Rating Scale - Revised, and by a physician using the Children' s Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: Patients showed a significant reduction in parent - rated irritability and social withdrawal on the ABC as well as significant improvements in emotional lability and inattention on the Conners' Parent Rating Scale - - Revised. Similarly, clinician ratings showed reductions in the anger subscale of the Children' s Psychiatric Rating Scale. Eight of 13 participants were rated as responders on the basis of their improvement scores on the Clinical Global Impressions scale. Overall, galantamine was well - tolerated, with no significant adverse effects apart from headaches in one patient. CONCLUSION: In this open trial, galantamine was well - tolerated and appeared to be beneficial for the treatment of interfering behaviors in children with autism, particularly aggression, behavioral dyscontrol, and inattention. Further controlled trials are warranted.

galantamine

galantamine

galantamine

galantamine

galantamine

autistic disorder

autism

autism

autism

irritability

headaches

autism

aggression

behavioral dyscontrol

inattention

galantamine

headaches

galantamine

headaches

galantamine

headaches

galantamine

headaches

galantamine

headaches


Input: Randomized comparison of olanzapine versus risperidone for the treatment of first - episode schizophrenia: 4 - month outcomes. OBJECTIVE: The authors compared 4 - month treatment outcomes for olanzapine versus risperidone in patients with first - episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age = 23. 3 years [SD = 5. 1]) with first - episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2. 5 - 20 mg / day) or risperidone (1 - 6 mg / day). RESULTS: Response rates did not significantly differ between olanzapine (43. 7%, 95% CI = 28. 8% - 58. 6%) and risperidone (54. 3%, 95% CI = 39. 9% - 68. 7%). Among those responding to treatment, more subjects in the olanzapine group (40. 9%, 95% CI = 16. 8% - 65. 0%) than in the risperidone group (18. 9%, 95% CI = 0% - 39. 2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1. 4 (95% CI = 1. 2 - 1. 6) with risperidone and 1. 2 (95% CI = 1. 0 - 1. 4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17. 3% (95% CI = 14. 2% - 20. 5%) with olanzapine and 11. 3% (95% CI = 8. 4% - 14. 3%) with risperidone. Body mass index at baseline and at 4 months was 24. 3 (95% CI = 22. 8 - 25. 7) versus 28. 2 (95% CI = 26. 7 - 29. 7) with olanzapine and 23. 9 (95% CI = 22. 5 - 25. 3) versus 26. 7 (95% CI = 25. 2 - 28. 2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

risperidone

olanzapine

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

risperidone

olanzapine

Olanzapine

olanzapine

schizophrenia

schizophrenia

schizophrenia

schizophreniform disorder

schizoaffective disorder

parkinsonism

akathisia

Extrapyramidal symptom

weight gain

weight gain

weight gain

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain

Olanzapine

weight gain

Olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

Olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain


Input: Early paracentral visual field loss in patients taking hydroxychloroquine. OBJECTIVE: To review the natural history and ocular and systemic adverse effects of patients taking hydroxychloroquine sulfate who attended an ophthalmic screening program. DESIGN: Retrospective study. RESULTS: Records of 262 patients who were taking hydroxychloroquine and screened in the Department of Ophthalmology were reviewed. Of the 262 patients, 14 (18%) of 76 who had stopped treatment at the time of the study experienced documented adverse effects. Systemic adverse effects occurred in 8 patients (10. 5%) and ocular adverse effects, in 5 (6. 5%). Thirty - five patients (13. 4%) had visual field abnormalities, which were attributed to hydroxychloroquine treatment in 4 patients (1. 5%). Three of the 4 patients were taking less than 6. 5 mg / kg per day and all patients had normal renal and liver function test results. CONCLUSIONS: The current study used a protocol of visual acuity and color vision assessment, funduscopy, and Humphrey 10 - 2 visual field testing and shows that visual field defects appeared before any corresponding changes in any other tested clinical parameters; the defects were reproducible and the test parameters were reliable. Patients taking hydroxychloroquine can demonstrate a toxic reaction in the retina despite the absence of known risk factors. Screening, including Humphrey 10 - 2 visual field assessment, is recommended 2 years after the initial baseline and yearly thereafter.

visual field loss

visual field abnormalities

visual field defects

hydroxychloroquine

hydroxychloroquine sulfate

hydroxychloroquine

hydroxychloroquine

hydroxychloroquine

hydroxychloroquine

visual field loss

hydroxychloroquine

visual field abnormalities

hydroxychloroquine

visual field defects

hydroxychloroquine sulfate

visual field loss

hydroxychloroquine sulfate

visual field abnormalities

hydroxychloroquine sulfate

visual field defects

hydroxychloroquine

visual field loss

hydroxychloroquine

visual field abnormalities

hydroxychloroquine

visual field defects

hydroxychloroquine

visual field loss

hydroxychloroquine

visual field abnormalities

hydroxychloroquine

visual field defects

hydroxychloroquine

visual field loss

hydroxychloroquine

visual field abnormalities

hydroxychloroquine

visual field defects


Input: Peri - operative atrioventricular block as a result of chemotherapy with epirubicin and paclitaxel. A 47 - year - old woman presented for mastectomy and immediate latissimus dorsi flap reconstruction having been diagnosed with carcinoma of the breast 6 months previously. In the preceding months she had received neo - adjuvant chemotherapy with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been apparently uncomplicated and she had maintained a remarkably high level of physical activity. She was found to be bradycardic at pre - operative assessment but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing instituted in the peri - operative period. We discuss how evidence - based guidelines would not have been helpful in this case, and how chemotherapy can exhibit substantial cardiotoxicity that may develop over many years. We suggest that patients who have received chemotherapy at any time should have a pre - operative electrocardiogram even if they are asymptomatic.

atrioventricular block

carcinoma of the breast

bradycardic

atrioventricular block

cardiotoxicity

epirubicin

paclitaxel

epirubicin

paclitaxel

Taxol

cyclophosphamide

cyclophosphamide

atrioventricular block

cyclophosphamide

atrioventricular block

paclitaxel

atrioventricular block

paclitaxel

atrioventricular block

paclitaxel

atrioventricular block

paclitaxel

atrioventricular block

Taxol

atrioventricular block

Taxol

atrioventricular block

epirubicin

atrioventricular block

epirubicin

atrioventricular block

epirubicin

atrioventricular block

epirubicin

atrioventricular block


Input: Risks and benefits of COX - 2 inhibitors vs non - selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study. OBJECTIVES: The risk of acute myocardial infarction (AMI) with COX - 2 inhibitors may offset their gastrointestinal (GI) benefit compared with non - selective (NS) non - steroidal anti - inflammatory drugs (NSAIDs). We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX - 2 inhibitors, NS - NSAIDs and acetaminophen. METHODS: We conducted a retrospective cohort study using administrative data of patients > or = 65 years of age who filled a prescription for NSAID or acetaminophen during 1999 - 2002. Outcomes were compared using Cox regression models with time - dependent exposures. RESULTS: Person - years of exposure among non - users of aspirin were: 75, 761 to acetaminophen, 42, 671 to rofecoxib 65, 860 to celecoxib, and 37, 495 to NS - NSAIDs. Among users of aspirin, they were: 14, 671 to rofecoxib, 22, 875 to celecoxib, 9, 832 to NS - NSAIDs and 38, 048 to acetaminophen. Among non - users of aspirin, the adjusted hazard ratios (95% confidence interval) of hospitalization for AMI / GI vs the acetaminophen (with no aspirin) group were: rofecoxib 1. 27 (1. 13, 1. 42), celecoxib 0. 93 (0. 83, 1. 03), naproxen 1. 59 (1. 31, 1. 93), diclofenac 1. 17 (0. 99, 1. 38) and ibuprofen 1. 05 (0. 74, 1. 51). Among users of aspirin, they were: rofecoxib 1. 73 (1. 52, 1. 98), celecoxib 1. 34 (1. 19, 1. 52), ibuprofen 1. 51 (0. 95, 2. 41), diclofenac 1. 69 (1. 35, 2. 10), naproxen 1. 35 (0. 97, 1. 88) and acetaminophen 1. 29 (1. 17, 1. 42). CONCLUSION: Among non - users of aspirin, naproxen seemed to carry the highest risk for AMI / GI bleeding. The AMI / GI toxicity of celecoxib was similar to that of acetaminophen and seemed to be better than those of rofecoxib and NS - NSAIDs. Among users of aspirin, both celecoxib and naproxen seemed to be the least toxic.

COX - 2 inhibitors

COX - 2 inhibitors

non - steroidal anti - inflammatory drugs

COX - 2 inhibitors

acetaminophen

acetaminophen

aspirin

acetaminophen

rofecoxib

celecoxib

aspirin

rofecoxib

celecoxib

acetaminophen

aspirin

acetaminophen

aspirin

rofecoxib

celecoxib

naproxen

diclofenac

ibuprofen

aspirin

rofecoxib

celecoxib

ibuprofen

diclofenac

naproxen

acetaminophen

aspirin

naproxen

celecoxib

acetaminophen

rofecoxib

aspirin

celecoxib

naproxen

acute myocardial infarction

AMI

AMI

GI bleeding

AMI

AMI

GI bleeding

AMI

toxicity

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

non - steroidal anti - inflammatory drugs

GI bleeding

non - steroidal anti - inflammatory drugs

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

COX - 2 inhibitors

acute myocardial infarction

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

acute myocardial infarction

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

acute myocardial infarction

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

non - steroidal anti - inflammatory drugs

acute myocardial infarction

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI


Input: Quinine - induced arrhythmia in a patient with severe malaria. It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120 / 80 mmHg, pulse rate 100 x / minute, regular. On admission, laboratory examination showed Plasmodium falciparum (+ + + +), total bilirubin 8. 25 mg / dL, conjugated bilirubin 4. 36 mg / dL, unconjugated bilirubin 3. 89 mg / dL, potassium 3. 52 meq / L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg / 8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x / minute, trigemini, constant type - - sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5% / 24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x / minute and on the third day ECG was normal, potassium level was 3. 34 meq / L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti - arrhythmic property, although it also pro - arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro - arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases.

Quinine

quinine

bilirubin

bilirubin

bilirubin

potassium

quinine

dextrose

quinine

lidocaine

dextrose

potassium aspartate

Quinine

quinine

potassium

Quinine

quinidine

quinine

arrhythmia

severe malaria

severe malaria

jaundice

arrhythmia

premature ventricular contraction

fever

chill

vomiting

jaundice

severe malaria

jaundice

vomitus

diarrhea

tinnitus

loss of hearing

palpitation

premature ventricular contraction

PVC

sinoatrial block

PVC

arrhythmic

arrhythmic

arrhythmias

arrhythmia

PVC

arrhythmic

heart diseases

electrolyte disorder

hypokalemia

vomiting

diarrhea

malaria

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC


Input: Penicillamine - related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities. Wilson' s disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson' s disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc - ECD - SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow - up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side - effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson' s disease patient in which penicillamine - related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson' s disease. Since most of Wilson' s disease penicillamine - treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson' s disease therapy, and in particular to differentiate specific therapies for different Wilson' s disease phenotypes.

Penicillamine

zinc acetate

copper

copper

penicillamine

zinc acetate

zinc acetate

penicillamine

zinc acetate

penicillamine

lichenoid dermatitis

Wilson disease

anxiety

Wilson' s disease

toxicity

hepatic, neurologic and psychiatric disorders

hepatic, neurologic and psychiatric disorders

neurologic and psychiatric disorders

psychiatric disorders

Wilson' s disease

chronic liver disease

anxiety

depression

lichenoid dermatitis

Wilson' s disease

Wilson' s disease

Wilson' s disease

skin lesion

Wilson' s disease

Wilson' s disease

Penicillamine

lichenoid dermatitis

Penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis

penicillamine

lichenoid dermatitis


Input: A dramatic drop in blood pressure following prehospital GTN administration. A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient' s observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient' s condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold - Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold - Jarisch reflex as the cause and manage the patient accordingly.

drop in blood pressure

chest pain

chest pain

drop in blood pressure

syncopal episode

GTN

oxygen

glyceryl trinitrate

GTN

GTN

atropine sulphate

oxygen

drop in blood pressure

oxygen

drop in blood pressure

GTN

drop in blood pressure

GTN

drop in blood pressure

glyceryl trinitrate

drop in blood pressure

glyceryl trinitrate

drop in blood pressure

GTN

drop in blood pressure

GTN

drop in blood pressure

GTN

drop in blood pressure

GTN

drop in blood pressure


Input: Acute encephalopathy and cerebral vasospasm after multiagent chemotherapy including PEG - asparaginase and intrathecal cytarabine for the treatment of acute lymphoblastic leukemia. A 7 - year - old girl with an unusual reaction to induction chemotherapy for precursor B - cell acute lymphoblastic leukemia (ALL) is described. The patient developed acute encephalopathy evidenced by behavioral changes, aphasia, incontinence, visual hallucinations, and right - sided weakness with diffuse cerebral vasospasm on magnetic resonance angiography after the administration of intrathecal cytarabine. Vincristine, dexamethasone, and polyethylene glycol - asparaginase were also administered before the episode as part of induction therapy. Neurologic status returned to baseline within 10 days of the acute event, and magnetic resonance angiography findings returned to normal 4 months later.

Acute encephalopathy

cerebral vasospasm

acute lymphoblastic leukemia

acute lymphoblastic leukemia

ALL

acute encephalopathy

aphasia

incontinence

visual hallucinations

weakness

cerebral vasospasm

PEG - asparaginase

cytarabine

cytarabine

Vincristine

dexamethasone

polyethylene glycol - asparaginase

cytarabine

cerebral vasospasm

cytarabine

cerebral vasospasm

cytarabine

cerebral vasospasm

cytarabine

cerebral vasospasm

Vincristine

cerebral vasospasm

Vincristine

cerebral vasospasm

Vincristine

weakness

dexamethasone

weakness

cytarabine

aphasia

cytarabine

aphasia

PEG - asparaginase

visual hallucinations

polyethylene glycol - asparaginase

visual hallucinations

cytarabine

visual hallucinations

cytarabine

visual hallucinations

dexamethasone

aphasia

cytarabine

incontinence

cytarabine

incontinence

PEG - asparaginase

weakness

polyethylene glycol - asparaginase

weakness

PEG - asparaginase

incontinence

polyethylene glycol - asparaginase

incontinence

dexamethasone

incontinence

Vincristine

aphasia

Vincristine

visual hallucinations

dexamethasone

visual hallucinations

Vincristine

incontinence

cytarabine

weakness

cytarabine

weakness

PEG - asparaginase

aphasia

polyethylene glycol - asparaginase

aphasia

PEG - asparaginase

cerebral vasospasm

PEG - asparaginase

cerebral vasospasm

polyethylene glycol - asparaginase

cerebral vasospasm

polyethylene glycol - asparaginase

cerebral vasospasm

dexamethasone

cerebral vasospasm

dexamethasone

cerebral vasospasm


Input: Comparison of valsartan / hydrochlorothiazide combination therapy at doses up to 320 / 25 mg versus monotherapy: a double - blind, placebo - controlled study followed by long - term combination therapy in hypertensive adults. BACKGROUND: One third of patients treated for hypertension attain adequate blood pressure (BP) control, and multidrug regimens are often required. Given the lifelong nature of hypertension, there is a need to evaluate the long - term efficacy and tolerability of higher doses of combination anti - hypertensive therapies. OBJECTIVE: This study investigated the efficacy and tolerability of valsartan (VAL) or hydrochlorothiazide (HCTZ) - monotherapy and higher - dose combinations in patients with essential hypertension. METHODS: The first part of this study was an 8 - week, multicenter, randomized, double - blind, placebo controlled, parallel - group trial. Patients with essential hypertension (mean sitting diastolic BP [MSDBP], > or = 95 mm Hg and < 110 mm Hg) were randomized to 1 of 8 treatment groups: VAL 160 or 320 mg; HCTZ 12. 5 or 25 mg; VAL / HCTZ 160 / 12. 5, 320 / 12. 5, or 320 / 25 mg; or placebo. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) were analyzed at the 8 - week core study end point. VAL / HCTZ 320 / 12. 5 and 320 / 25 mg were further investigated in a 54 - week, open - label extension. Response was defined as MSDBP < 90 mm Hg or a > or = 10 mm Hg decrease compared to baseline. Control was defined as MSDBP < 90 mm Hg compared with baseline. Tolerability was assessed by monitoring adverse events at randomization and all subsequent study visits and regular evaluation of hematology and blood chemistry. RESULTS: A total of 1346 patients were randomized into the 8 - week core study (734 men, 612 women; 924 white, 291 black, 23 Asian, 108 other; mean age, 52. 7 years; mean weight, 92. 6 kg). All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8 - week study, with each monotherapy significantly contributing to the overall effect of combination therapy (VAL and HCTZ, P < 0. 001). Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo (all, P < 0. 001). The mean reduction in MSSBP / MSDBP with VAL / HCTZ 320 / 25 mg was 24. 7 / 16. 6 mm Hg, compared with 5. 9 / 7. 0 mm Hg with placebo. The reduction in MSSBP was significantly greater with VAL / HCTZ 320 / 25 mg compared with VAL / HCTZ 160 / 12. 5 mg (P < 0. 002). Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy. The incidence of hypokalemia was lower with VAL / HCTZ combinations (1. 8% - 6. 1%) than with HCTZ monotherapies (7. 1% - 13. 3%). The majority of adverse events in the core study were of mild to moderate severity. The efficacy and tolerability of VAL / HCTZ combinations were maintained during the extension (797 patients). CONCLUSIONS: In this study population, combination therapies with VAL / HCTZ were associated with significantly greater BP reductions compared with either monotherapy, were well tolerated, and were associated with less hypokalemia than HCTZ alone.

valsartan

hydrochlorothiazide

valsartan

VAL

hydrochlorothiazide

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

VAL

HCTZ

HCTZ

VAL

HCTZ

VAL

HCTZ

HCTZ

hypertensive

hypertension

hypertension

hypertensive

essential hypertension

essential hypertension

hypokalemia

hypokalemia

hydrochlorothiazide

hypokalemia

hydrochlorothiazide

hypokalemia

hydrochlorothiazide

hypokalemia

hydrochlorothiazide

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia

HCTZ

hypokalemia


Input: Succimer chelation improves learning, attention, and arousal regulation in lead - exposed rats but produces lasting cognitive impairment in the absence of lead exposure. BACKGROUND: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb - exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure. OBJECTIVES: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning. RESULTS: Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb - exposed children. Succimer treatment of the Pb - exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen. CONCLUSIONS: These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb - exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals.

Succimer

lead

lead

lead

Pb

Pb

Pb

succimer

Pb

Pb

Succimer

Pb

Pb

succimer

Pb

Pb

Pb

succimer

Pb

succimer

Pb

cognitive impairment

Pb poisoning

impairments in learning, attention, inhibitory control, and arousal regulation

impairments in learning

impairments in learning, attention, inhibitory control, and arousal regulation

cognitive and affective dysfunction

cognitive and affective dysfunction

affective dysfunction

cognitive deficits

Succimer

cognitive impairment

Succimer

cognitive and affective dysfunction

Succimer

cognitive and affective dysfunction

Succimer

cognitive deficits

succimer

cognitive impairment

succimer

cognitive and affective dysfunction

succimer

cognitive and affective dysfunction

succimer

cognitive deficits

Succimer

cognitive impairment

Succimer

cognitive and affective dysfunction

Succimer

cognitive and affective dysfunction

Succimer

cognitive deficits

succimer

cognitive impairment

succimer

cognitive and affective dysfunction

succimer

cognitive and affective dysfunction

succimer

cognitive deficits

succimer

cognitive impairment

succimer

cognitive and affective dysfunction

succimer

cognitive and affective dysfunction

succimer

cognitive deficits

succimer

cognitive impairment

succimer

cognitive and affective dysfunction

succimer

cognitive and affective dysfunction

succimer

cognitive deficits

lead

impairments in learning, attention, inhibitory control, and arousal regulation

lead

impairments in learning

lead

impairments in learning, attention, inhibitory control, and arousal regulation

lead

impairments in learning

lead

impairments in learning, attention, inhibitory control, and arousal regulation

lead

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning

lead

impairments in learning, attention, inhibitory control, and arousal regulation

lead

impairments in learning, attention, inhibitory control, and arousal regulation

lead

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation

Pb

impairments in learning, attention, inhibitory control, and arousal regulation