Input: Hypercalcemia, arrhythmia, and mood stabilizers. Recent findings in a bipolar patient receiving maintenance lithium therapy who developed hypercalcemia and severe bradyarrhythmia prompted the authors to conduct a retrospective study of bipolar patients with lithium - associated hypercalcemia. A printout of all cases of hypercalcemia that presented during a 1 - year period was generated. After eliminating spurious hypercalcemias or those associated with intravenous fluids, the authors identified 18 non - lithium - treated patients with hypercalcemias related to malignancies and other medical conditions (group A) and 12 patients with lithium - associated hypercalcemia (group B). Patients in group B were not comparable to those in group A, as the latter were medically compromised and were receiving multiple pharmacotherapies. Thus, two control groups were generated: group C1, which included age - and sex - comparable lithium - treated bipolar normocalcemic patients, and group C2, which included bipolar normocalcemic patients treated with anticonvulsant mood stabilizers. The electrocardiographic (ECG) findings for patients in group B were compared with those of patients in groups C1 and C2. It was found that these groups did not differ in their overall frequency of ECG abnormalities; however, there were significant differences in the frequency of conduction defects. Patients with hypercalcemia resulting from medical diseases and bipolar patients with lithium - associated hypercalcemia had significantly higher frequencies of conduction defects. Patients in group A had significant mortality at 2 - year follow - up (28%), in contrast to zero mortality in the other three groups. The clinical implications of these findings are discussed.

Hypercalcemia

arrhythmia

bipolar

hypercalcemia

bradyarrhythmia

bipolar

hypercalcemia

hypercalcemia

hypercalcemias

hypercalcemias

malignancies

hypercalcemia

bipolar

bipolar

hypercalcemia

bipolar

hypercalcemia

lithium

lithium

lithium

lithium

lithium

lithium

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

Hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemias

lithium

hypercalcemias

lithium

hypercalcemia

lithium

hypercalcemia

lithium

hypercalcemia


Input: Attenuation of nephrotoxicity by a novel lipid nanosphere (NS - 718) incorporating amphotericin B. NS - 718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS - 718 with that of Fungizone (amphotericin B - sodium deoxycholate; D - AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS - 718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D - AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D - AmB 3 mg / kg but not in those given the same dose of NS - 718. Histopathological examination of the kidney showed tubular necrosis in D - AmB - treated rats but no change in NS - 718 - treated rats. Amphotericin B concentrations in the kidney in NS - 718 - treated rats were higher than those in D - AmB - treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS - 718 attenuates the nephrotoxicity of amphotericin B.

nephrotoxicity

toxicity

toxicity

tubular necrosis

nephrotoxicity

amphotericin B

amphotericin B

Fungizone

amphotericin B - sodium deoxycholate

D - AmB

amphotericin B

D - AmB

urea

creatinine

D - AmB

D - AmB

Amphotericin B

D - AmB

amphotericin B

amphotericin B

amphotericin B - sodium deoxycholate

tubular necrosis

D - AmB

tubular necrosis

D - AmB

tubular necrosis

D - AmB

tubular necrosis

D - AmB

tubular necrosis

D - AmB

tubular necrosis


Input: Patterns of sulfadiazine acute nephrotoxicity. Sulfadiazine acute nephrotoxicity is reviving specially because of its use in toxoplasmosis in HIV - positive patients. We report 4 cases, one of them in a previously healthy person. Under treatment with sulfadiazine they developed oliguria, abdominal pain, renal failure and showed multiple radiolucent renal calculi in echography. All patients recovered their previous normal renal function after adequate hydration and alcalinization. A nephrostomy tube had to be placed in one of the patients for ureteral lithiasis in a single functional kidney. None of them needed dialysis or a renal biopsy because of a typical benign course. Treatment with sulfadiazine requires exquisite control of renal function, an increase in water ingestion and possibly the alcalinization of the urine. We communicate a case in a previously healthy person, a fact not found in the recent literature. Probably many more cases are not detected. We think that a prospective study would be useful.

sulfadiazine

Sulfadiazine

sulfadiazine

sulfadiazine

acute nephrotoxicity

acute nephrotoxicity

toxoplasmosis

oliguria

abdominal pain

renal failure

renal calculi

ureteral lithiasis

sulfadiazine

renal calculi

Sulfadiazine

renal calculi

sulfadiazine

renal calculi

sulfadiazine

renal calculi

sulfadiazine

acute nephrotoxicity

sulfadiazine

acute nephrotoxicity

Sulfadiazine

acute nephrotoxicity

Sulfadiazine

acute nephrotoxicity

sulfadiazine

acute nephrotoxicity

sulfadiazine

acute nephrotoxicity

sulfadiazine

acute nephrotoxicity

sulfadiazine

acute nephrotoxicity


Input: Downbeat nystagmus associated with intravenous patient - controlled administration of morphine. IMPLICATIONS: This case documents a patient who developed dizziness with downbeating nystagmus while receiving a relatively large dose of IV patient - controlled analgesia morphine. Although there have been case reports of epidural morphine with these symptoms and signs, this has not been previously documented with IV or patient - controlled analgesia morphine.

Downbeat nystagmus

dizziness

downbeating nystagmus

morphine

morphine

morphine

morphine

morphine

dizziness

morphine

dizziness

morphine

dizziness

morphine

dizziness

morphine

Downbeat nystagmus

morphine

downbeating nystagmus

morphine

Downbeat nystagmus

morphine

downbeating nystagmus

morphine

Downbeat nystagmus

morphine

downbeating nystagmus

morphine

Downbeat nystagmus

morphine

downbeating nystagmus


Input: Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction. The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg / kg), amiodarone (10 and 30 mg / kg), and placebo twice daily for 7 days, with a 3 - week washout between consecutive treatments. Heart rate (HR), mean arterial pressure (MBP), positive rate of increase of left ventricular pressure (+ LVdP / dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise - induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, + LVdP / dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose - dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise - induced tachycardia and, at the highest dose, decreased the isoproterenol - induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function.

dronedarone

amiodarone

dronedarone

amiodarone

amiodarone

dronedarone

amiodarone

isoproterenol

dronedarone

amiodarone

dronedarone

amiodarone

isoproterenol

dronedarone

amiodarone

dronedarone

myocardial infarction

myocardial infarction

tachycardia

tachycardia

arrhythmias

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia


Input: Phase 2 trial of liposomal doxorubicin (40 mg / m (2)) in platinum / paclitaxel - refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. BACKGROUND: Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum - resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg / m (2) q 4 weeks) being severe erythrodysesthesia (" hand - foot syndrome ") and stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well - defined patient population with platinum / paclitaxel - refractory disease. METHODS AND MATERIALS: Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum / paclitaxel - refractory disease (stable or progressive disease following treatment with these agents or previous objective response < 3 months in duration) were treated with liposomal doxorubicin at a dose of 40 mg / m (2) q 4 weeks. RESULTS: A total of 49 patients (median age: 60; range 41 - 81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1 - 6). Six (12%) and 4 (8%) patients experienced grade 2 hand - foot syndrome and stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin administered on this protocol was 2 (range: 1 - 12). Four of 44 patients (9%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. CONCLUSION: This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand - foot syndrome) than the standard FDA - approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well - defined platinum - and paclitaxel - refractory ovarian cancer.

doxorubicin

platinum

paclitaxel

doxorubicin

Doxil

platinum

doxorubicin

platinum

paclitaxel

platinum

paclitaxel

doxorubicin

doxorubicin

doxorubicin

platinum

paclitaxel

ovarian and fallopian tube cancers

ovarian and fallopian tube cancers

fallopian tube cancers

carcinoma of the peritoneum

ovarian cancer

toxicity

erythrodysesthesia

hand - foot syndrome

stomatitis

ovarian or fallopian tube cancers

ovarian or fallopian tube cancers

fallopian tube cancers

peritoneal carcinoma

hand - foot syndrome

stomatitis

diarrhea

toxicity

stomatitis

hand - foot syndrome

ovarian cancer

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

Doxil

stomatitis

Doxil

stomatitis

Doxil

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

stomatitis

doxorubicin

diarrhea

doxorubicin

diarrhea

Doxil

diarrhea

doxorubicin

diarrhea

doxorubicin

diarrhea

doxorubicin

diarrhea

doxorubicin

diarrhea

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

Doxil

erythrodysesthesia

Doxil

hand - foot syndrome

Doxil

hand - foot syndrome

Doxil

hand - foot syndrome

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

erythrodysesthesia

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome

doxorubicin

hand - foot syndrome


Input: Efficacy of olanzapine in acute bipolar mania: a double - blind, placebo - controlled study. The Olanzipine HGGW Study Group. BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four - week, randomized, double - blind, parallel study. A total of 115 patients with a DSM - IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg / d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young - Mania Rating Scale (Y - MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y - MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine - treated patients demonstrated a statistically significant greater mean (+ / - SD) improvement in Y - MRS total score than placebo - treated patients (- 14. 8 + / - 12. 5 and - 8. 1 + / - 12. 7, respectively; P <. 001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine - treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =. 02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo - treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine - treated patients had a statistically significant greater mean (+ / - SD) weight gain than placebo - treated patients (2. 1 + / - 2. 8 vs 0. 45 + / - 2. 3 kg, respectively) and also experienced more treatment - emergent somnolence (21 patients [38. 2%] vs 5 [8. 3%], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

olanzapine

Olanzipine

olanzapine

olanzapine

Olanzapine

Olanzapine

olanzapine

Olanzapine

bipolar mania

bipolar mania

bipolar disorder

manic

Mania

Extrapyramidal Symptom

EPS

EPSs

weight gain

somnolence

bipolar mania

olanzapine

somnolence

Olanzipine

somnolence

olanzapine

somnolence

olanzapine

somnolence

Olanzapine

somnolence

Olanzapine

somnolence

olanzapine

somnolence

Olanzapine

somnolence

olanzapine

weight gain

Olanzipine

weight gain

olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain

Olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain


Input: The effect of pupil dilation with tropicamide on vision and driving simulator performance. PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high - and low - contrast visual acuity (HCVA and LCVA), Pelli - Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV - - a test of visual attention) was also undertaken. The mean differences in the pre - and post - dilatation measurements were tested for statistical significance at the 95% level using one - tail paired t - tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended.

pupil dilation

pupil dilation

pupil dilation

Pupillary dilation

Pupillary dilation

tropicamide

tropicamide

tropicamide

pupil dilation

tropicamide

pupil dilation

tropicamide

pupil dilation

tropicamide

Pupillary dilation

tropicamide

Pupillary dilation

tropicamide

pupil dilation

tropicamide

pupil dilation

tropicamide

pupil dilation

tropicamide

Pupillary dilation

tropicamide

Pupillary dilation


Input: A case of isotretinoin embryopathy with bilateral anotia and Taussig - Bing malformation. We report a newborn infant with multiple congenital anomalies (anotia and Taussig - Bing malformation) due to exposure to isotretinoin within the first trimester. In this paper we aim to draw to the fact that caution is needed when prescribing vitamin A - containing drugs to women of childbearing years.

isotretinoin embryopathy

anotia

Taussig - Bing malformation

anotia

Taussig - Bing malformation

isotretinoin

vitamin A

isotretinoin

Taussig - Bing malformation

isotretinoin

Taussig - Bing malformation

isotretinoin

anotia

isotretinoin

anotia

isotretinoin

isotretinoin embryopathy


Input: Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo - controlled, double - blind crossover study. The aim of the study was to evaluate the potential role for a selective alpha1 - adrenoceptor agonist in the treatment of urinary stress incontinence. A randomised, double - blind, placebo - controlled, crossover study design was employed. Half log incremental doses of intravenous methoxamine or placebo (saline) were administered to a group of women with genuine stress incontinence while measuring maximum urethral pressure (MUP), blood pressure, heart rate, and symptomatic side effects. Methoxamine evoked non - significant increases in MUP and diastolic blood pressure but caused a significant rise in systolic blood pressure and significant fall in heart rate at maximum dosage. Systemic side effects including piloerection, headache, and cold extremities were experienced in all subjects. The results indicate that the clinical usefulness of direct, peripherally acting sub - type - selective alpha1 - adrenoceptor agonists in the medical treatment of stress incontinence may be limited by associated piloerection and cardiovascular side effects.

methoxamine

methoxamine

Methoxamine

stress incontinence

urinary stress incontinence

stress incontinence

a significant rise in systolic blood pressure

headache

stress incontinence

methoxamine

a significant rise in systolic blood pressure

methoxamine

a significant rise in systolic blood pressure

Methoxamine

a significant rise in systolic blood pressure

methoxamine

headache

methoxamine

headache

Methoxamine

headache


Input: Toleration of high doses of angiotensin - converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival. BACKGROUND: Treatment with angiotensin - converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high - compared with low - dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double - blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium - dose lisinopril (12. 5 or 15. 0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high - (35. 0 or 32. 5 mg OD) or low - dose (5. 0 or 2. 5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0. 30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4. 2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2. 0%) or because of renal dysfunction or hyperkalemia (2. 3%). Doses in more than 90% of randomized patients in the high - and low - dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27. 1% of the high - and 30. 7% of the low - dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, < 120 mm Hg; creatinine, > or = 132. 6 micromol / L [> or = 1. 5 mg / dL]; age, > or = 70 years; and patients with diabetes) generally tolerated the high - dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.

angiotensin - converting enzyme inhibitors

Lisinopril

angiotensin - converting enzyme (ACE) inhibitors

lisinopril

Lisinopril

ACE inhibitor

lisinopril

ACE inhibitor

ACE inhibitor

creatinine

ACE inhibitor

heart failure

heart failure

CHF

CHF

CHF

hypotension

renal dysfunction

hypotension

renal dysfunction

hyperkalemia

diabetes

CHF

Lisinopril

renal dysfunction

Lisinopril

renal dysfunction

lisinopril

renal dysfunction

lisinopril

renal dysfunction

Lisinopril

renal dysfunction

Lisinopril

renal dysfunction

lisinopril

renal dysfunction

lisinopril

renal dysfunction

Lisinopril

hyperkalemia

lisinopril

hyperkalemia

Lisinopril

hyperkalemia

lisinopril

hyperkalemia

Lisinopril

hypotension

Lisinopril

hypotension

lisinopril

hypotension

lisinopril

hypotension

Lisinopril

hypotension

Lisinopril

hypotension

lisinopril

hypotension

lisinopril

hypotension


Input: Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse. OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. METHODS: Twenty - three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7. 5 mg / kg with ethanol (1 g / kg) as an IV infusion (C + E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. RESULTS: Two of eight dogs in the C + E group experienced cardiovascular collapse. The most dramatic hemodynamic changes occurred after each cocaine bolus in the C + E and C only groups; however, persistent hemodynamic changes occurred in the C + E group. Peak CE levels were associated with a 45% (SD + / - 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0. 05), a 56% (SD + / - 23%, 95% CI = 32% to 80%) decrease in dP / dt (max) (p <. 006), and a 23% (SD + / - 15%, 95% CI = 7% to 49%) decrease in SVO (2) (p < 0. 025). Ventricular arrhythmias were primarily observed in the C + E group, in which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS: Cocaine and ethanol in combination were more toxic than either substance alone. Co - administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.

Cocaine

ethanol

cocaethylene

cocaethylene

CE

cocaine

ethanol

CE

cocaine

ethanol

cocaine

ethanol

cocaine

ethanol

cocaine

CE

Cocaine

ethanol

cocaethylene

cardiotoxity

cocaine and ethanol abuse

cocaine and ethanol abuse

ethanol abuse

abuse of cocaine and ethanol

abuse of cocaine

abuse of cocaine and ethanol

cardiac toxicity

cardiotoxicity

cardiovascular collapse

decrease in cardiac output

Ventricular arrhythmias

ventricular tachycardia

cardiac toxicity

myocardial depression

ethanol

ventricular tachycardia

ethanol

ventricular tachycardia

ethanol

ventricular tachycardia

ethanol

ventricular tachycardia

ethanol

ventricular tachycardia

ethanol

ventricular tachycardia

Cocaine

ventricular tachycardia

cocaine

ventricular tachycardia

cocaine

ventricular tachycardia

cocaine

ventricular tachycardia

cocaine

ventricular tachycardia

cocaine

ventricular tachycardia

Cocaine

ventricular tachycardia

cocaethylene

decrease in cardiac output

cocaethylene

decrease in cardiac output

CE

decrease in cardiac output

CE

decrease in cardiac output

CE

decrease in cardiac output

cocaethylene

decrease in cardiac output


Input: Worsening of Parkinsonism after the use of veralipride for treatment of menopause: case report. We describe a female patient with stable Parkinson' s disease who has shown a marked worsening of her motor functions following therapy of menopause related symptoms with veralipride, as well as the improvement of her symptoms back to baseline after discontinuation of the drug. We emphasize the anti - dopaminergic effect of veralipride.

Parkinsonism

Parkinson' s disease

veralipride

veralipride

veralipride

veralipride

Parkinsonism

veralipride

Parkinson' s disease

veralipride

Parkinsonism

veralipride

Parkinson' s disease

veralipride

Parkinsonism

veralipride

Parkinson' s disease


Input: Viracept and irregular heartbeat warning. A group of doctors in Boston warn that the protease inhibitor Viracept may cause an irregular heart beat, known as bradycardia, in people with HIV. Bradycardia occurred in a 45 - year - old male patient who was Viracept in combination with other anti - HIV drugs. The symptoms ceased after switching to another drug combination.

Viracept

Viracept

Viracept

irregular heartbeat

irregular heart beat

bradycardia

Bradycardia

Viracept

bradycardia

Viracept

Bradycardia

Viracept

bradycardia

Viracept

Bradycardia

Viracept

bradycardia

Viracept

Bradycardia


Input: Frequency of appearance of myeloperoxidase - antineutrophil cytoplasmic antibody (MPO - ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO - ANCA and clinical manifestations. OBJECTIVE: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO - ANCA) - positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO - ANCA in these cases was suspected of being related to PTU because the titres of MPO - ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO - ANCA and vasculitis during PTU therapy, or on the incidence of MPO - ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease. PATIENTS: We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO - ANCA, and for the development vasculitis after starting PTU therapy. Twenty - nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23. 6 months (range: 3 - 37 months). MEASUREMENTS: MPO - ANCA was measured at intervals of 2 - 6 months. RESULTS: Before treatment, the MPO - ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U / ml). Three (4. 1%) of the 73 patients were positive for MPO - ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO - ANCA titres transiently increased to 12. 8 and 15. 0 U / ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO - ANCA titre increased to 204 U / ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO - ANCA titre decreased to 20. 7 U / ml by 4 months after discontinuing PTU. CONCLUSIONS: PTU therapy may be related to the appearance of MPO - ANCA, but MPO - ANCA does not appear to be closely related to vasculitis.

Graves' disease

vasculitis

Graves' disease

vasculitis

Graves' disease

Graves' disease

hyperthyroidism

Graves' disease

vasculitis

Graves' disease

vasculitic disorders

fever

oral ulcers

polyarthralgia

vasculitis

propylthiouracil

propylthiouracil

PTU

PTU

PTU

PTU

PTU

PTU

PTU

PTU

PTU

PTU

PTU

propylthiouracil

fever

propylthiouracil

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

PTU

fever

propylthiouracil

polyarthralgia

propylthiouracil

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

PTU

polyarthralgia

propylthiouracil

oral ulcers

propylthiouracil

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers

PTU

oral ulcers


Input: Prevalence of heart disease in asymptomatic chronic cocaine users. To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age - matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0. 01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0. 055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0. 11 and 0. 02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients.

heart disease

heart disease

coronary artery disease

abnormal left ventricular filling

coronary artery or myocardial disease

coronary artery or myocardial disease

myocardial disease

cocaine

cocaine

cocaine

cocaine

cocaine

coronary artery disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery disease

cocaine

coronary artery or myocardial disease

cocaine

coronary artery or myocardial disease

cocaine

myocardial disease

cocaine

myocardial disease

cocaine

myocardial disease

cocaine

myocardial disease


Input: Cardioprotective effects of Picrorrhiza kurroa against isoproterenol - induced myocardial stress in rats. The cardioprotective effect of the ethanol extract of Picrorrhiza kurroa rhizomes and roots (PK) on isoproterenol - induced myocardial infarction in rats with respect to lipid metabolism in serum and heart tissue has been investigated. Oral pre - treatment with PK (80 mg kg (- 1) day (- 1) for 15 days) significantly prevented the isoproterenol - induced myocardial infarction and maintained the rats at near normal status.

isoproterenol

ethanol

isoproterenol

isoproterenol

myocardial infarction

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction


Input: Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long - QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. BACKGROUND: This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl - sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. METHODS AND RESULTS: Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl - Sotalol preferentially prolonged action potential duration (APD) in M cells dose - dependently (1 to 100 micromol / L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0. 1 to 10 micromol / L but shortened them at 30 micromol / L. Unlike dl - sotalol, azimilide (> 3 micromol / L) increased epicardial APD markedly, causing a diminished TDR. Although both dl - sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl - sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol / L) increased APD more than dl - sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. CONCLUSIONS: This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.

ventricular tachycardia

long - QT syndrome

torsade de pointes

TdP

QT prolongation

TdP

QT prolongation

QT prolongation

TdP

TdP

QT prolongation

sotalol

azimilide

Sotalol

Azimilide

sotalol

azimilide

sotalol

azimilide

sotalol

azimilide

sotalol

sotalol

long - QT syndrome

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

Sotalol

long - QT syndrome

Sotalol

QT prolongation

Sotalol

QT prolongation

Sotalol

QT prolongation

Sotalol

QT prolongation

sotalol

long - QT syndrome

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

long - QT syndrome

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

long - QT syndrome

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

long - QT syndrome

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

QT prolongation

sotalol

torsade de pointes

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

TdP

Sotalol

torsade de pointes

Sotalol

TdP

Sotalol

TdP

Sotalol

TdP

Sotalol

TdP

sotalol

torsade de pointes

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

torsade de pointes

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

torsade de pointes

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

torsade de pointes

sotalol

TdP

sotalol

TdP

sotalol

TdP

sotalol

TdP


Input: Prenatal cocaine exposure and cranial sonographic findings in preterm infants. PURPOSE: Prenatal cocaine exposure has been linked with subependymal hemorrhage and the formation of cysts that are detectable on cranial sonography in neonates born at term. We sought to determine if prenatal cocaine exposure increases the incidence of subependymal cysts in preterm infants. METHODS: We retrospectively reviewed the medical records and cranial sonograms obtained during a 1 - year period on 122 premature (< 36 weeks of gestation) infants. Infants were categorized into 1 of 2 groups: those exposed to cocaine and those not exposed to cocaine. Infants were assigned to the cocaine - exposed group if there was a maternal history of cocaine abuse during pregnancy or if maternal or neonatal urine toxicology results were positive at the time of delivery. RESULTS: Five of the 122 infants were excluded from the study because of insufficient medical and drug histories. The incidence of subependymal cysts in the 117 remaining infants was 14% (16 of 117). The incidence of subependymal cysts in infants exposed to cocaine prenatally was 44% (8 of 18) compared with 8% (8 of 99) in the unexposed group (p < 0. 01). CONCLUSIONS: We found an increased incidence of subependymal cyst formation in preterm infants who were exposed to cocaine prenatally. This result is consistent with results of similar studies in term infants.

cocaine

cocaine

cocaine

cocaine

cocaine

cocaine

cocaine

cocaine

preterm infants

hemorrhage

cysts

subependymal cysts

subependymal cysts

cysts

preterm infants

premature (< 36 weeks of gestation) infants

cocaine abuse

subependymal cysts

subependymal cysts

cysts

subependymal cysts

subependymal cysts

cysts

subependymal cyst

subependymal cyst

cyst

preterm infants

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cysts

cocaine

cysts

cocaine

subependymal cyst

cocaine

cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cysts

cocaine

subependymal cyst

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

preterm infants

cocaine

premature (< 36 weeks of gestation) infants

cocaine

preterm infants


Input: Thalidomide neuropathy in patients treated for metastatic prostate cancer. We prospectively evaluated thalidomide - induced neuropathy using electrodiagnostic studies. Sixty - seven men with metastatic androgen - independent prostate cancer in an open - label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3 - month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.

Thalidomide

thalidomide

androgen

thalidomide

Thalidomide

thalidomide

thalidomide

neuropathy

prostate cancer

neuropathy

prostate cancer

neuropathy

Neuropathy

peripheral neuropathy

Thalidomide

peripheral neuropathy

thalidomide

peripheral neuropathy

thalidomide

peripheral neuropathy

Thalidomide

peripheral neuropathy

thalidomide

peripheral neuropathy

thalidomide

peripheral neuropathy


Input: Overexpression of copper / zinc - superoxide dismutase protects from kanamycin - induced hearing loss. The participation of reactive oxygen species in aminoglycoside - induced ototoxicity has been deduced from observations that aminoglycoside - iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu / Zn - superoxide dismutase (h - SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h - SOD1 in inner ear tissues of transgenic C57BL / 6 - TgN [SOD1] 3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg / kg body weight / day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin - treated group was 45 - 50 dB higher than in saline - injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside - induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.

copper

zinc

superoxide

kanamycin

oxygen

aminoglycoside

aminoglycoside

iron

superoxide

Cu

Zn

superoxide

kanamycin

kanamycin

kanamycin

superoxide

aminoglycoside

hearing loss

ototoxicity

ototoxicity

ototoxicity

ototoxicity

kanamycin

hearing loss

kanamycin

hearing loss

kanamycin

hearing loss

kanamycin

hearing loss


Input: Prednisone induces anxiety and glial cerebral changes in rats. OBJECTIVE: To assess whether prednisone (PDN) produces anxiety and / or cerebral glial changes in rats. METHODS: Male Wistar rats were studied and 3 groups were formed (8 rats per group). The moderate - dose group received 5 mg / kg / day PDN released from a subcutaneous implant. In the high - dose group, implants containing PDN equivalent to 60 mg / kg / day were applied. In the control group implants contained no PDN. Anxiety was assessed using an open field and elevated plus - maze devices. The number of cells and cytoplasmic transformation of astrocytes and microglia cells were assessed by immunohistochemical analyses. RESULTS: Anxiety was documented in both groups of PDN treated rats compared with controls. The magnitude of transformation of the microglia assessed by the number of intersections was significantly higher in the PDN groups than in controls in the prefrontal cortex (moderate - dose, 24. 1; high - dose, 23. 6; controls 18. 7; p < 0. 01) and striatum (moderate - dose 25. 6; high - dose 26. 3; controls 18. 9; p < 0. 01), but not in hippocampus. The number of stained microglia cells was significantly higher in the PDN treated groups in the prefrontal cortex than in controls (moderate - dose, 29. 1; high - dose, 28. 4; control, 17. 7 cells per field; p < 0. 01). Stained microglia cells were significantly more numerous striatum and hippocampus in the high - dose group compared to controls. CONCLUSION: Subacute exposure to PDN induced anxiety and reactivity of microglia. The relevance of these features for patients using PDN remains to be elucidated.

Prednisone

prednisone

PDN

PDN

PDN

PDN

PDN

PDN

PDN

PDN

PDN

anxiety

anxiety

Anxiety

Anxiety

anxiety

Prednisone

anxiety

Prednisone

anxiety

Prednisone

Anxiety

Prednisone

Anxiety

Prednisone

anxiety

prednisone

anxiety

prednisone

anxiety

prednisone

Anxiety

prednisone

Anxiety

prednisone

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety

PDN

anxiety

PDN

anxiety

PDN

Anxiety

PDN

Anxiety

PDN

anxiety


Input: Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix. BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg / m (2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty - nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion - related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and / or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand - foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.

carboplatin

doxorubicin

carboplatin

doxorubicin

carboplatin

doxorubicin

Doxil

doxorubicin

carboplatin

doxorubicin

squamous cell carcinoma of the cervix

squamous cell carcinoma

carcinoma of the cervix

cervical carcinoma

squamous cell cervical carcinoma

squamous cell cervical carcinoma

cervical carcinoma

toxicity

toxicity

myelosuppression

neutropenia

anemia

thrombocytopenia

neutropenic fever

neutropenic

fever

toxicity

nausea

emesis

fatigue

mucositis

stomatitis

constipation

weight loss

hand - foot syndrome

skin reactions

cervical carcinoma

doxorubicin

neutropenia

doxorubicin

neutropenic fever

doxorubicin

neutropenic

doxorubicin

neutropenia

doxorubicin

neutropenic fever

doxorubicin

neutropenic

doxorubicin

neutropenia

doxorubicin

neutropenic fever

doxorubicin

neutropenic

Doxil

neutropenia

Doxil

neutropenic fever

Doxil

neutropenic

doxorubicin

neutropenia

doxorubicin

neutropenic fever

doxorubicin

neutropenic

doxorubicin

neutropenia

doxorubicin

neutropenic fever

doxorubicin

neutropenic

doxorubicin

constipation

doxorubicin

constipation

doxorubicin

constipation

Doxil

constipation

doxorubicin

constipation

doxorubicin

constipation

carboplatin

neutropenia

carboplatin

neutropenic fever

carboplatin

neutropenic

carboplatin

neutropenia

carboplatin

neutropenic fever

carboplatin

neutropenic

carboplatin

neutropenia

carboplatin

neutropenic fever

carboplatin

neutropenic

carboplatin

neutropenia

carboplatin

neutropenic fever

carboplatin

neutropenic

carboplatin

thrombocytopenia

carboplatin

thrombocytopenia

carboplatin

thrombocytopenia

carboplatin

thrombocytopenia

doxorubicin

mucositis

doxorubicin

mucositis

doxorubicin

mucositis

Doxil

mucositis

doxorubicin

mucositis

doxorubicin

mucositis

carboplatin

emesis

carboplatin

emesis

carboplatin

emesis

carboplatin

emesis

doxorubicin

weight loss

doxorubicin

weight loss

doxorubicin

weight loss

Doxil

weight loss

doxorubicin

weight loss

doxorubicin

weight loss

carboplatin

fatigue

carboplatin

fatigue

carboplatin

fatigue

carboplatin

fatigue

doxorubicin

skin reactions

doxorubicin

skin reactions

doxorubicin

skin reactions

Doxil

skin reactions

doxorubicin

skin reactions

doxorubicin

skin reactions

doxorubicin

anemia

doxorubicin

anemia

doxorubicin

anemia

Doxil

anemia

doxorubicin

anemia

doxorubicin

anemia

doxorubicin

nausea

doxorubicin

nausea

doxorubicin

nausea

Doxil

nausea

doxorubicin

nausea

doxorubicin

nausea

carboplatin

skin reactions

carboplatin

skin reactions

carboplatin

skin reactions

carboplatin

skin reactions

carboplatin

constipation

carboplatin

constipation

carboplatin

constipation

carboplatin

constipation

doxorubicin

fatigue

doxorubicin

fatigue

doxorubicin

fatigue

Doxil

fatigue

doxorubicin

fatigue

doxorubicin

fatigue

carboplatin

nausea

carboplatin

nausea

carboplatin

nausea

carboplatin

nausea

doxorubicin

emesis

doxorubicin

emesis

doxorubicin

emesis

Doxil

emesis

doxorubicin

emesis

doxorubicin

emesis

carboplatin

mucositis

carboplatin

mucositis

carboplatin

mucositis

carboplatin

mucositis

carboplatin

weight loss

carboplatin

weight loss

carboplatin

weight loss

carboplatin

weight loss

doxorubicin

thrombocytopenia

doxorubicin

thrombocytopenia

doxorubicin

thrombocytopenia

Doxil

thrombocytopenia

doxorubicin

thrombocytopenia

doxorubicin

thrombocytopenia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia

carboplatin

anemia


Input: Antimicrobial - induced mania (antibiomania): a review of spontaneous reports. The authors reviewed reported cases of antibiotic - induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic - induced mania. Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA). Twenty - one reports of antimicrobial - induced mania were found in the literature. There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin. The WHO reported 82 cases. Of these, clarithromycin was implicated in 23 (27. 6%) cases, ciprofloxacin in 12 (14. 4%) cases, and ofloxacin in 10 (12%) cases. Cotrimoxazole, metronidazole, and erythromycin were involved in 15 reported manic episodes. Cases reported by the FDA showed clarithromycin and ciprofloxacin to be the most frequently associated with the development of mania. Statistical analysis of the data would not have demonstrated a significant statistical correlative risk and was therefore not undertaken. Patients have an increased risk of developing mania while being treated with antimicrobials. Although this is not a statistically significant risk, physicians must be aware of the effect and reversibility. Further research clearly is required to determine the incidence of antimicrobial - induced mania, the relative risk factors of developing an antimicrobial - induced manic episode among various demographic populations, and the incidence of patients who continue to have persistent affective disorders once the initial episode, which occurs while the patient is taking antibiotics, subsides. The authors elected to name this syndrome " antibiomania. "

mania

antibiomania

manic

mania

mania

manic

mania

mania

mania

manic

antibiomania

clarithromycin

isoniazid

erythromycin

amoxicillin

clarithromycin

ciprofloxacin

ofloxacin

Cotrimoxazole

metronidazole

erythromycin

clarithromycin

ciprofloxacin

ciprofloxacin

mania

ciprofloxacin

antibiomania

ciprofloxacin

manic

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

manic

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

manic

ciprofloxacin

antibiomania

ciprofloxacin

mania

ciprofloxacin

antibiomania

ciprofloxacin

manic

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

manic

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

mania

ciprofloxacin

manic

ciprofloxacin

antibiomania

Cotrimoxazole

mania

Cotrimoxazole

antibiomania

Cotrimoxazole

manic

Cotrimoxazole

mania

Cotrimoxazole

mania

Cotrimoxazole

manic

Cotrimoxazole

mania

Cotrimoxazole

mania

Cotrimoxazole

mania

Cotrimoxazole

manic

Cotrimoxazole

antibiomania

metronidazole

mania

metronidazole

antibiomania

metronidazole

manic

metronidazole

mania

metronidazole

mania

metronidazole

manic

metronidazole

mania

metronidazole

mania

metronidazole

mania

metronidazole

manic

metronidazole

antibiomania

isoniazid

mania

isoniazid

antibiomania

isoniazid

manic

isoniazid

mania

isoniazid

mania

isoniazid

manic

isoniazid

mania

isoniazid

mania

isoniazid

mania

isoniazid

manic

isoniazid

antibiomania

ofloxacin

mania

ofloxacin

antibiomania

ofloxacin

manic

ofloxacin

mania

ofloxacin

mania

ofloxacin

manic

ofloxacin

mania

ofloxacin

mania

ofloxacin

mania

ofloxacin

manic

ofloxacin

antibiomania

amoxicillin

mania

amoxicillin

antibiomania

amoxicillin

manic

amoxicillin

mania

amoxicillin

mania

amoxicillin

manic

amoxicillin

mania

amoxicillin

mania

amoxicillin

mania

amoxicillin

manic

amoxicillin

antibiomania

clarithromycin

mania

clarithromycin

antibiomania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

antibiomania

clarithromycin

mania

clarithromycin

antibiomania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

antibiomania

clarithromycin

mania

clarithromycin

antibiomania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

mania

clarithromycin

mania

clarithromycin

mania

clarithromycin

manic

clarithromycin

antibiomania

erythromycin

mania

erythromycin

antibiomania

erythromycin

manic

erythromycin

mania

erythromycin

mania

erythromycin

manic

erythromycin

mania

erythromycin

mania

erythromycin

mania

erythromycin

manic

erythromycin

antibiomania

erythromycin

mania

erythromycin

antibiomania

erythromycin

manic

erythromycin

mania

erythromycin

mania

erythromycin

manic

erythromycin

mania

erythromycin

mania

erythromycin

mania

erythromycin

manic

erythromycin

antibiomania


Input: Levodopa - induced ocular dyskinesias in Parkinson' s disease. Levodopa - induced ocular dyskinesias are very uncommon. Usually they occur simultaneously with limb peak - dose choreatic dyskinesias. We report on a patient with leftward and upward deviations of gaze during the peak effect of levodopa, and hypothesize that a severe dopaminergic denervation in the caudate nucleus is needed for the appearance of these levodopa - induce ocular dyskinesias.

Levodopa

Levodopa

levodopa

levodopa

ocular dyskinesias

Parkinson' s disease

ocular dyskinesias

choreatic dyskinesias

ocular dyskinesias

Levodopa

ocular dyskinesias

Levodopa

ocular dyskinesias

Levodopa

ocular dyskinesias

Levodopa

ocular dyskinesias

Levodopa

ocular dyskinesias

Levodopa

ocular dyskinesias

levodopa

ocular dyskinesias

levodopa

ocular dyskinesias

levodopa

ocular dyskinesias

levodopa

ocular dyskinesias

levodopa

ocular dyskinesias

levodopa

ocular dyskinesias


Input: A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross - over trial. Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non - steroidal anti - inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross - over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses / day of 50 mg DCF or 2. 5 mg / 24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side - effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, - 12. 8 + / - 17. 9; DCF, - 18. 9 + / - 16. 6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, - 12. 8 + / - 17. 9; DFC, - 18. 9 + / - 16. 6 and after two hours: GTN, - 23. 7 + / - 20. 5; DFC, - 59. 7 + / - 17. 9, p = 0. 0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache - - attributed to its use - - became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.

glyceryl trinitrate

diclofenac

prostaglandins

nitric oxide

NO

glyceryl trinitrate

GTN

NO

diclofenac

DCF

DCF

GTN

DCF

GTN

GTN

DCF

DCF

GTN

GTN

GTN

GTN

DCF

GTN

GTN

DCF

dysmenorrhea

dysmenorrhea

dysmenorrhea

dysmenorrhea

pain

pelvic pain

Low back pain

Headache

headache

dysmenorrhea

glyceryl trinitrate

Headache

glyceryl trinitrate

headache

glyceryl trinitrate

Headache

glyceryl trinitrate

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache

GTN

Headache

GTN

headache


Input: Temocapril, a long - acting non - SH group angiotensin converting enzyme inhibitor, modulates glomerular injury in chronic puromycin aminonucleoside nephrosis. The purpose of the present study was to determine whether chronic administration of temocapril, a long - acting non - SH group angiotensin converting enzyme (ACE) inhibitor, reduced proteinuria, inhibited glomerular hypertrophy and prevented glomerulosclerosis in chronic puromycin aminonucleoside (PAN) - induced nephrotic rats. Nephrosis was induced by injection of PAN (15mg / 100g body weight) in male Sprague - Dawley (SD) rats. Four groups were used, i) the PAN group (14), ii) PAN / temocapril (13), iii) temocapril (14) and iv) untreated controls (15). Temocapril (8 mg / kg / day) was administered to the rats which were killed at weeks 4, 14 or 20. At each time point, systolic blood pressure (BP), urinary protein excretion and renal histopathological findings were evaluated, and morphometric image analysis was done. Systolic BP in the PAN group was significantly high at 4, 14 and 20 weeks, but was normal in the PAN / temocapril group. Urinary protein excretion in the PAN group increased significantly, peaking at 8 days, then decreased at 4 weeks, but rose again significantly at 14 and 20 weeks. Temocapril did not attenuate proteinuria at 8 days, but it did markedly lower it from weeks 4 to 20. The glomerulosclerosis index (GSI) was 6. 21% at 4 weeks and respectively 25. 35% and 30. 49% at 14 and 20 weeks in the PAN group. There was a significant correlation between urinary protein excretion and GSI (r = 0. 808, p < 0. 0001). The ratio of glomerular tuft area to the area of Bowman' s capsules (GT / BC) in the PAN group was significantly increased, but it was significantly lower in the PAN / temocapril group. It appears that temocapril was effective in retarding renal progression and protected renal function in PAN neprotic rats.

Temocapril

angiotensin

puromycin aminonucleoside

temocapril

angiotensin

puromycin aminonucleoside

PAN

PAN

PAN

PAN

temocapril

temocapril

Temocapril

PAN

PAN

temocapril

PAN

Temocapril

PAN

PAN

PAN

temocapril

temocapril

PAN

glomerular injury

nephrosis

proteinuria

hypertrophy

glomerulosclerosis

nephrotic

Nephrosis

proteinuria

glomerulosclerosis

neprotic

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

PAN

proteinuria

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

Nephrosis

puromycin aminonucleoside

neprotic

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

Nephrosis

puromycin aminonucleoside

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic

PAN

nephrosis

PAN

Nephrosis

PAN

neprotic


Input: Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants. We report three cases of severe hypoxaemia after ibuprofen administration during a randomised controlled trial of prophylactic treatment of patent ductus arteriosus with ibuprofen in premature infants born at less than 28 weeks of gestation. Echocardiography showed severely decreased pulmonary blood flow. Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that investigators involved in similar trials pay close attention to pulmonary pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.

Pulmonary hypertension

hypoxaemia

patent ductus arteriosus

Hypoxaemia

hypoxaemia

ibuprofen

ibuprofen

ibuprofen

nitric oxide

ibuprofen

ibuprofen

Pulmonary hypertension

ibuprofen

Pulmonary hypertension

ibuprofen

Pulmonary hypertension

ibuprofen

Pulmonary hypertension

ibuprofen

hypoxaemia

ibuprofen

Hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

Hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

Hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

hypoxaemia

ibuprofen

Hypoxaemia

ibuprofen

hypoxaemia


Input: Hyponatremia and syndrome of inappropriate anti - diuretic hormone reported with the use of Vincristine: an over - representation of Asians? PURPOSE: This retrospective study used a pharmaceutical company' s global safety database to determine the reporting rate of hyponatremia and / or syndrome of inappropriate secretion of anti - diuretic hormone (SIADH) among vincristine - treated patients and to explore the possibility of at - risk population subgroups. METHOD: We searched the Eli Lilly and Company' s computerized adverse event database for all reported cases of hyponatremia and / or SIADH as of 1 November 1999 that had been reported during the use of vincristine. RESULTS: A total of 76 cases of hyponatremia and / or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1. 3 / 100, 000 treated patients. The average age of patients was 35. 6 + / - 28. 3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data suggest that Asian patients may be at increased risk of hyponatremia and / or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event.

Hyponatremia

syndrome of inappropriate anti - diuretic hormone

hyponatremia

syndrome of inappropriate secretion of anti - diuretic hormone

SIADH

hyponatremia

SIADH

hyponatremia

SIADH

leukemia

lymphoma

hyponatremia

SIADH

SIADH

Vincristine

vincristine

vincristine

vincristine

vincristine

vincristine

Vincristine

syndrome of inappropriate anti - diuretic hormone

Vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

Vincristine

SIADH

Vincristine

SIADH

Vincristine

SIADH

Vincristine

SIADH

Vincristine

SIADH

vincristine

syndrome of inappropriate anti - diuretic hormone

vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

syndrome of inappropriate anti - diuretic hormone

vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

syndrome of inappropriate anti - diuretic hormone

vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

syndrome of inappropriate anti - diuretic hormone

vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

syndrome of inappropriate anti - diuretic hormone

vincristine

syndrome of inappropriate secretion of anti - diuretic hormone

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

vincristine

SIADH

Vincristine

Hyponatremia

Vincristine

hyponatremia

Vincristine

hyponatremia

Vincristine

hyponatremia

Vincristine

hyponatremia

vincristine

Hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

Hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

Hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

Hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

Hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia

vincristine

hyponatremia


Input: Delayed toxicity of cyclophosphamide on the bladder of DBA / 2 and C57BL / 6 female mouse. The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA / 2) but not in a resistant strain (C57BL / 6) when both were treated with a single 300 mg / kg dose of cyclophosphamide (CY). Inbred DBA / 2 and C57BL / 6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7 - 10 days. After 30 days of CY injection ulcerous and non - ulcerous forms of chronic cystitis appeared in 86% of DBA / 2 mice but only in 4% of C57BL / 6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA / 2 mice than in C57BL / 6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA / 2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA / 2 mice causes a bladder pathology that is not observed in C57BL / 6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the disease.

toxicity

toxicity

haemorrhagic

cystitis

cystitis

cystitis

cystitis

toxicity

interstitial cystitis

cyclophosphamide

cyclophosphamide

CY

CY

CY

CY

CY

cyclophosphamide

haemorrhagic

cyclophosphamide

haemorrhagic

CY

haemorrhagic

CY

haemorrhagic

CY

haemorrhagic

CY

haemorrhagic

CY

haemorrhagic

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

cyclophosphamide

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis

CY

cystitis


Input: High - dose 5 - fluorouracil / folinic acid in combination with three - weekly mitomycin C in the treatment of advanced gastric cancer. A phase II study. BACKGROUND: The 24 - hour continuous infusion of 5 - fluorouracil (5 - FU) and folinic acid (FA) as part of several new multidrug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective, with low toxicity. In a previous phase II study with 3 - weekly bolus 5 - FU, FA and mitomycin C (MMC) we found a low toxicity rate and response rates comparable to those of regimens such as ELF, FAM or FAMTX, and a promising median overall survival. In order to improve this MMC - dependent schedule we initiated a phase II study with high - dose 5 - FU / FA and 3 - weekly bolus MMC. PATIENTS AND METHODS: From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24 - hour 5 - FU 2, 600 mg / m (2) preceded by 2 - hour FA 500 mg / m (2) for 6 weeks, followed by a 2 - week rest period. Bolus MMC 10 mg / m (2) was added in 3 - weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male / female ratio 20 / 13; median age 57 (27 - 75) years; median WHO status 1 (0 - 2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow - up was 11. 8 months (range of those surviving: 2. 7 - 11. 8 months). RESULTS: 32 patients were evaluable for response - complete remission 9. 1% (n = 3), partial remission 45. 5% (n = 15), no change 27. 3% (n = 9), progressive disease 15. 1% (n = 5). Median overall survival time was 10. 2 months [95% confidence interval (CI): 8. 7 - 11. 6], and median progression - free survival time was 7. 6 months (95% CI: 4. 4 - 10. 9). The worst toxicities (%) observed were (CTC - NCI 1 / 2 / 3): leukopenia 45. 5 / 18. 2 / 6. 1, thrombocytopenia 33. 3 / 9. 1 / 6. 1, vomitus 24. 2 / 9. 1 / 0, diarrhea 36. 4 / 6. 1 / 3. 0, stomatitis 18. 2 / 9. 1 / 0, hand - foot syndrome 12. 1 / 0 / 0. Two patients developed hemolytic - uremic syndrome (HUS). CONCLUSIONS: High - dose 5 - FU / FA / MMC is an effective and well - tolerated outpatient regimen for AGC (objective response rate 54. 6%). It may serve as an alternative to cisplatin - containing regimens; however, it has to be considered that possibly HUS may occur.

5 - fluorouracil

folinic acid

mitomycin C

5 - fluorouracil

5 - FU

folinic acid

FA

5 - FU

FA

mitomycin C

MMC

MMC

5 - FU

FA

MMC

5 - FU

FA

MMC

5 - FU

FA

MMC

cisplatin

gastric cancer

gastric cancer

AGC

toxicity

toxicity

AGC

AGC

AGC

toxicities

leukopenia

thrombocytopenia

vomitus

diarrhea

stomatitis

hand - foot syndrome

hemolytic - uremic syndrome

HUS

AGC

HUS

folinic acid

vomitus

folinic acid

vomitus

FA

vomitus

FA

vomitus

FA

vomitus

FA

vomitus

FA

vomitus

folinic acid

thrombocytopenia

folinic acid

thrombocytopenia

FA

thrombocytopenia

FA

thrombocytopenia

FA

thrombocytopenia

FA

thrombocytopenia

FA

thrombocytopenia

mitomycin C

diarrhea

mitomycin C

diarrhea

MMC

diarrhea

MMC

diarrhea

MMC

diarrhea

MMC

diarrhea

MMC

diarrhea

folinic acid

stomatitis

folinic acid

stomatitis

FA

stomatitis

FA

stomatitis

FA

stomatitis

FA

stomatitis

FA

stomatitis

mitomycin C

thrombocytopenia

mitomycin C

thrombocytopenia

MMC

thrombocytopenia

MMC

thrombocytopenia

MMC

thrombocytopenia

MMC

thrombocytopenia

MMC

thrombocytopenia

5 - fluorouracil

vomitus

5 - fluorouracil

vomitus

5 - FU

vomitus

5 - FU

vomitus

5 - FU

vomitus

5 - FU

vomitus

5 - FU

vomitus

mitomycin C

leukopenia

mitomycin C

leukopenia

MMC

leukopenia

MMC

leukopenia

MMC

leukopenia

MMC

leukopenia

MMC

leukopenia

mitomycin C

hemolytic - uremic syndrome

mitomycin C

HUS

mitomycin C

HUS

mitomycin C

hemolytic - uremic syndrome

mitomycin C

HUS

mitomycin C

HUS

MMC

hemolytic - uremic syndrome

MMC

HUS

MMC

HUS

MMC

hemolytic - uremic syndrome

MMC

HUS

MMC

HUS

MMC

hemolytic - uremic syndrome

MMC

HUS

MMC

HUS

MMC

hemolytic - uremic syndrome

MMC

HUS

MMC

HUS

MMC

hemolytic - uremic syndrome

MMC

HUS

MMC

HUS

5 - fluorouracil

diarrhea

5 - fluorouracil

diarrhea

5 - FU

diarrhea

5 - FU

diarrhea

5 - FU

diarrhea

5 - FU

diarrhea

5 - FU

diarrhea

folinic acid

diarrhea

folinic acid

diarrhea

FA

diarrhea

FA

diarrhea

FA

diarrhea

FA

diarrhea

FA

diarrhea

5 - fluorouracil

hemolytic - uremic syndrome

5 - fluorouracil

HUS

5 - fluorouracil

HUS

5 - fluorouracil

hemolytic - uremic syndrome

5 - fluorouracil

HUS

5 - fluorouracil

HUS

5 - FU

hemolytic - uremic syndrome

5 - FU

HUS

5 - FU

HUS

5 - FU

hemolytic - uremic syndrome

5 - FU

HUS

5 - FU

HUS

5 - FU

hemolytic - uremic syndrome

5 - FU

HUS

5 - FU

HUS

5 - FU

hemolytic - uremic syndrome

5 - FU

HUS

5 - FU

HUS

5 - FU

hemolytic - uremic syndrome

5 - FU

HUS

5 - FU

HUS

5 - fluorouracil

stomatitis

5 - fluorouracil

stomatitis

5 - FU

stomatitis

5 - FU

stomatitis

5 - FU

stomatitis

5 - FU

stomatitis

5 - FU

stomatitis

5 - fluorouracil

leukopenia

5 - fluorouracil

leukopenia

5 - FU

leukopenia

5 - FU

leukopenia

5 - FU

leukopenia

5 - FU

leukopenia

5 - FU

leukopenia

5 - fluorouracil

thrombocytopenia

5 - fluorouracil

thrombocytopenia

5 - FU

thrombocytopenia

5 - FU

thrombocytopenia

5 - FU

thrombocytopenia

5 - FU

thrombocytopenia

5 - FU

thrombocytopenia

folinic acid

leukopenia

folinic acid

leukopenia

FA

leukopenia

FA

leukopenia

FA

leukopenia

FA

leukopenia

FA

leukopenia

mitomycin C

vomitus

mitomycin C

vomitus

MMC

vomitus

MMC

vomitus

MMC

vomitus

MMC

vomitus

MMC

vomitus

mitomycin C

stomatitis

mitomycin C

stomatitis

MMC

stomatitis

MMC

stomatitis

MMC

stomatitis

MMC

stomatitis

MMC

stomatitis

folinic acid

hemolytic - uremic syndrome

folinic acid

HUS

folinic acid

HUS

folinic acid

hemolytic - uremic syndrome

folinic acid

HUS

folinic acid

HUS

FA

hemolytic - uremic syndrome

FA

HUS

FA

HUS

FA

hemolytic - uremic syndrome

FA

HUS

FA

HUS

FA

hemolytic - uremic syndrome

FA

HUS

FA

HUS

FA

hemolytic - uremic syndrome

FA

HUS

FA

HUS

FA

hemolytic - uremic syndrome

FA

HUS

FA

HUS

5 - fluorouracil

hand - foot syndrome

5 - fluorouracil

hand - foot syndrome

5 - FU

hand - foot syndrome

5 - FU

hand - foot syndrome

5 - FU

hand - foot syndrome

5 - FU

hand - foot syndrome

5 - FU

hand - foot syndrome

folinic acid

hand - foot syndrome

folinic acid

hand - foot syndrome

FA

hand - foot syndrome

FA

hand - foot syndrome

FA

hand - foot syndrome

FA

hand - foot syndrome

FA

hand - foot syndrome

mitomycin C

hand - foot syndrome

mitomycin C

hand - foot syndrome

MMC

hand - foot syndrome

MMC

hand - foot syndrome

MMC

hand - foot syndrome

MMC

hand - foot syndrome

MMC

hand - foot syndrome


Input: Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1 - infected children treated with indinavir. BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well - documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir - related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1 - infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady - state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir. RESULTS: The cumulative incidence of persistent sterile leukocyturia (> or = 75 cells / micro L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin / creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels > 50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5. 6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve > 19 mg / L x h or a peak serum level of indinavir > 12 mg / L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin / creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months. CONCLUSIONS: Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of > 50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir - associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age < 5. 6 years, an area under the curve of indinavir > 19 mg / L x h, and a C (max) > 12 mg / L.

leukocyturia

impaired renal function

human immunodeficiency virus type 1 - infected

nephrotoxicity

human immunodeficiency virus type 1 - infected

leukocyturia

leukocyturia

hematuria

leukocyturia

leukocyturia

leukocyturia

leukocyturia

nephrotoxicity

leukocyturia

leukocyturia

leukocyturia

impairment of the renal function

nephrolithiasis

nephrotoxicity

leukocyturia

indinavir

indinavir

indinavir

indinavir

creatinine

creatinine

indinavir

indinavir

creatinine

creatinine

creatinine

indinavir

indinavir

creatinine

creatinine

indinavir

creatinine

Indinavir

indinavir

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

Indinavir

impaired renal function

Indinavir

nephrotoxicity

Indinavir

nephrotoxicity

Indinavir

impairment of the renal function

Indinavir

nephrotoxicity

indinavir

impaired renal function

indinavir

nephrotoxicity

indinavir

nephrotoxicity

indinavir

impairment of the renal function

indinavir

nephrotoxicity

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

indinavir

hematuria

Indinavir

hematuria

indinavir

hematuria


Input: Utility of troponin I in patients with cocaine - associated chest pain. Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine - associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. OBJECTIVE: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. METHODS: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule - in protocol that included serial sampling of creatine kinase (CK), CK - MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK - MB MI (CK - MB > or = 8 ng / mL with a relative index [(CK - MB x 100) / total CK] > or = 4, cardiac death, and significant coronary disease (> or = 50%). RESULTS: Of the 246 admitted patients, 34 (14%) met CK - MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI - positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK - MB criteria for MI, and the other had a peak CK - MB level of 13 ng / mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK - MB MI and cTnI and were not significantly different. CONCLUSIONS: Most patients with cTnI elevations meet CK - MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK - MB for diagnosing necrosis in patients with cocaine - associated chest pain and suspected MI.

cocaine

cocaine

cocaine

cocaine

creatine

cocaine

chest pain

myocardial necrosis

myocardial infarction

MI

chest pain

chest pain

MI

MI

MI

cardiac death

coronary disease

MI

MI

cardiac death

MI

MI

necrosis

chest pain

MI

cocaine

myocardial infarction

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

myocardial infarction

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

myocardial infarction

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

myocardial infarction

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

myocardial infarction

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI

cocaine

MI


Input: Acute interstitial nephritis due to nicergoline (Sermion). We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50 - year - old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i. e. arthralgia and fever) and laboratory findings (i. e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline - associated AIN.

interstitial nephritis

interstitial nephritis

AIN

fever

acute renal failure

retinal vein occlusion

fever

skin rash

arthralgia

fever

eosinophilia

renal failure

AIN

AIN

nicergoline

Sermion

nicergoline

Sermion

nicergoline

bendazac lysine

nicergoline

nicergoline

methylprednisolone

nicergoline

nicergoline

eosinophilia

Sermion

eosinophilia

nicergoline

eosinophilia

Sermion

eosinophilia

nicergoline

eosinophilia

nicergoline

eosinophilia

nicergoline

eosinophilia

nicergoline

eosinophilia

nicergoline

renal failure

Sermion

renal failure

nicergoline

renal failure

Sermion

renal failure

nicergoline

renal failure

nicergoline

renal failure

nicergoline

renal failure

nicergoline

renal failure

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

Sermion

interstitial nephritis

Sermion

interstitial nephritis

Sermion

AIN

Sermion

AIN

Sermion

AIN

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

Sermion

interstitial nephritis

Sermion

interstitial nephritis

Sermion

AIN

Sermion

AIN

Sermion

AIN

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

nicergoline

interstitial nephritis

nicergoline

interstitial nephritis

nicergoline

AIN

nicergoline

AIN

nicergoline

AIN

nicergoline

fever

nicergoline

fever

nicergoline

fever

Sermion

fever

Sermion

fever

Sermion

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

Sermion

fever

Sermion

fever

Sermion

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

fever

nicergoline

arthralgia

Sermion

arthralgia

nicergoline

arthralgia

Sermion

arthralgia

nicergoline

arthralgia

nicergoline

arthralgia

nicergoline

arthralgia

nicergoline

arthralgia


Input: Neuroleptic malignant syndrome complicated by massive intestinal bleeding in a patient with chronic renal failure. A patient with chronic renal failure (CRF) developed neuroleptic malignant syndrome (NMS) after administration of risperidone and levomepromazine. In addition to the typical symptoms of NMS, massive intestinal bleeding was observed during the episode. This report suggests that NMS in a patient with CRF may be complicated by intestinal bleeding and needs special caution for this complication.

Neuroleptic malignant syndrome

bleeding

chronic renal failure

chronic renal failure

CRF

neuroleptic malignant syndrome

NMS

NMS

bleeding

NMS

CRF

bleeding

risperidone

levomepromazine

risperidone

Neuroleptic malignant syndrome

risperidone

neuroleptic malignant syndrome

risperidone

NMS

risperidone

NMS

risperidone

NMS

levomepromazine

Neuroleptic malignant syndrome

levomepromazine

neuroleptic malignant syndrome

levomepromazine

NMS

levomepromazine

NMS

levomepromazine

NMS


Input: Blood brain barrier in right - and left - pawed female rats assessed by a new staining method. The asymmetrical breakdown of the blood - brain barrier (BBB) was studied in female rats. Paw preference was assessed by a food reaching test. Adrenaline - induced hypertension was used to destroy the BBB, which was evaluated using triphenyltetrazolium (TTC) staining of the brain slices just after giving adrenaline for 30 s. In normal rats, the whole brain sections exhibited complete staining with TTC. After adrenaline infusion for 30 s, there were large unstained areas in the left brain in right - pawed animals, and vice versa in left - pawed animals. Similar results were obtained in seizure - induced breakdown of BBB. These results were explained by an asymmetric cerebral blood flow depending upon the paw preference in rats. It was suggested that this new method and the results are consistent with contralateral motor control that may be important in determining the dominant cerebral hemisphere in animals.

Adrenaline

triphenyltetrazolium

TTC

adrenaline

TTC

adrenaline

hypertension

seizure

Adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension


Input: Carvedilol protects against doxorubicin - induced mitochondrial cardiomyopathy. Several cytopathic mechanisms have been suggested to mediate the dose - limiting cumulative and irreversible cardiomyopathy caused by doxorubicin. Recent evidence indicates that oxidative stress and mitochondrial dysfunction are key factors in the pathogenic process. The objective of this investigation was to test the hypothesis that carvedilol, a nonselective beta - adrenergic receptor antagonist with potent antioxidant properties, protects against the cardiac and hepatic mitochondrial bioenergetic dysfunction associated with subchronic doxorubicin toxicity. Heart and liver mitochondria were isolated from rats treated for 7 weeks with doxorubicin (2 mg / kg sc / week), carvedilol (1 mg / kg ip / week), or the combination of the two drugs. Heart mitochondria isolated from doxorubicin - treated rats exhibited depressed rates for state 3 respiration (336 + / - 26 versus 425 + / - 53 natom O / min / mg protein) and a lower respiratory control ratio (RCR) (4. 3 + / - 0. 6 versus 5. 8 + / - 0. 4) compared with cardiac mitochondria isolated from saline - treated rats. Mitochondrial calcium - loading capacity and the activity of NADH - dehydrogenase were also suppressed in cardiac mitochondria from doxorubicin - treated rats. Doxorubicin treatment also caused a decrease in RCR for liver mitochondria (3. 9 + / - 0. 9 versus 5. 6 + / - 0. 7 for control rats) and inhibition of hepatic cytochrome oxidase activity. Coadministration of carvedilol decreased the extent of cellular vacuolization in cardiac myocytes and prevented the inhibitory effect of doxorubicin on mitochondrial respiration in both heart and liver. Carvedilol also prevented the decrease in mitochondrial Ca (2 +) loading capacity and the inhibition of the respiratory complexes of heart mitochondria caused by doxorubicin. Carvedilol by itself did not affect any of the parameters measured for heart or liver mitochondria. It is concluded that this protection by carvedilol against both the structural and functional cardiac tissue damage may afford significant clinical advantage in minimizing the dose - limiting mitochondrial dysfunction and cardiomyopathy that accompanies long - term doxorubicin therapy in cancer patients.

Carvedilol

doxorubicin

doxorubicin

carvedilol

doxorubicin

doxorubicin

carvedilol

doxorubicin

calcium

doxorubicin

Doxorubicin

carvedilol

doxorubicin

Carvedilol

Ca

doxorubicin

Carvedilol

carvedilol

doxorubicin

cardiomyopathy

cardiomyopathy

mitochondrial dysfunction

toxicity

mitochondrial dysfunction

cardiomyopathy

cancer

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

Doxorubicin

cardiomyopathy

Doxorubicin

cardiomyopathy

Doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy