Input: Seizure resulting from a venlafaxine overdose. OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40 - year - old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50 - mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.

Seizure

overdose

overdose

major depression

overdose

seizure

overdose

seizure

overdose

seizure

venlafaxine

venlafaxine

venlafaxine

venlafaxine

venlafaxine

venlafaxine

venlafaxine

venlafaxine

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

Seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

seizure

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose

venlafaxine

overdose


Input: Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus. The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.

nifedipine

tacrolimus

nifedipine

tacrolimus

tacrolimus

nifedipine

nifedipine

Nifedipine

creatinine

nifedipine

tacrolimus

hypertensive

nephrotoxicity

hypertension

tacrolimus

hypertensive

tacrolimus

hypertension

tacrolimus

hypertensive

tacrolimus

hypertension

tacrolimus

hypertensive

tacrolimus

hypertension

tacrolimus

hypertensive

tacrolimus

hypertension


Input: Sinus arrest associated with continuous - infusion cimetidine. The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40 - year - old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous - infusion cimetidine 50 mg / hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous - infusion cimetidine.

Sinus arrest

bradyarrhythmias

leukemia

cardiac disease

sinus arrest

arrhythmias

sinus arrest

cimetidine

cimetidine

cimetidine

cimetidine

ranitidine

cimetidine

cimetidine

Sinus arrest

cimetidine

sinus arrest

cimetidine

sinus arrest

cimetidine

Sinus arrest

cimetidine

sinus arrest

cimetidine

sinus arrest

cimetidine

Sinus arrest

cimetidine

sinus arrest

cimetidine

sinus arrest

cimetidine

Sinus arrest

cimetidine

sinus arrest

cimetidine

sinus arrest

cimetidine

Sinus arrest

cimetidine

sinus arrest

cimetidine

sinus arrest

cimetidine

bradyarrhythmias

cimetidine

bradyarrhythmias

cimetidine

bradyarrhythmias

cimetidine

bradyarrhythmias

cimetidine

bradyarrhythmias


Input: Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid. Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13 - 60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1. 19 (0. 08) (range 1. 01 - 1. 53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1 - 4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58. 3 (15. 9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

gall bladder stones

acromegaly

gall bladder stones

acromegalic

gall stones

gall stones

gall stone

gall stone

gall stones

gall stone disease

gall stones

octreotide

ursodeoxycholic acid

Octreotide

octreotide

cholesterol

cholesterol

cholesterol

cholesterol

cholesterol

ursodeoxycholic acid

UDCA

UDCA

cholesterol

octreotide

cholesterol

calcium

octreotide

gall bladder stones

octreotide

gall bladder stones

octreotide

gall stones

octreotide

gall stones

octreotide

gall stone

octreotide

gall stone

octreotide

gall stones

octreotide

gall stone disease

octreotide

gall stones

Octreotide

gall bladder stones

Octreotide

gall bladder stones

Octreotide

gall stones

Octreotide

gall stones

Octreotide

gall stone

Octreotide

gall stone

Octreotide

gall stones

Octreotide

gall stone disease

Octreotide

gall stones

octreotide

gall bladder stones

octreotide

gall bladder stones

octreotide

gall stones

octreotide

gall stones

octreotide

gall stone

octreotide

gall stone

octreotide

gall stones

octreotide

gall stone disease

octreotide

gall stones

octreotide

gall bladder stones

octreotide

gall bladder stones

octreotide

gall stones

octreotide

gall stones

octreotide

gall stone

octreotide

gall stone

octreotide

gall stones

octreotide

gall stone disease

octreotide

gall stones


Input: Cardiovascular complications associated with terbutaline treatment for preterm labor. Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.

Cardiovascular complications

preterm labor

cardiovascular complications

preterm labor

terbutaline

terbutaline

terbutaline

Cardiovascular complications

terbutaline

cardiovascular complications

terbutaline

Cardiovascular complications

terbutaline

cardiovascular complications


Input: Neurologic effects of subarachnoid administration of 2 - chloroprocaine - CE, bupivacaine, and low pH normal saline in dogs. The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2 - chloroprocaine - CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2 - chloroprocaine - CE (N = 20), low pH normal saline (pH 3. 0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2 - chloroprocaine - CE seven (35%) developed hind - limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3. 0 developed hind - limb paralysis. Of the 15 spinal cords of the animals that received 2 - chloroprocaine - CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3. 0), or normal saline did not show abnormal findings.

2 - chloroprocaine - CE

bupivacaine

2 - chloroprocaine - CE

bupivacaine

2 - chloroprocaine - CE

2 - chloroprocaine - CE

bupivacaine

2 - chloroprocaine - CE

bupivacaine

neurotoxicity

paralysis

paralysis

subpial necrosis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

paralysis

2 - chloroprocaine - CE

subpial necrosis

2 - chloroprocaine - CE

subpial necrosis

2 - chloroprocaine - CE

subpial necrosis

2 - chloroprocaine - CE

subpial necrosis

2 - chloroprocaine - CE

subpial necrosis


Input: Early adjuvant adriamycin in superficial bladder carcinoma. A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg / 50 ml) was administered intravesically within 24 h after transurethral resection of TA - T1 (O - A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side - effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side - effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow - up and in 72 patients followed for 2 - 3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor - free during the 2 - to 3 - year follow - up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.

adriamycin

Adriamycin

Adriamycin

bladder carcinoma

bladder carcinoma

carcinoma

carcinoma of the bladder

carcinoma of the bladder

carcinoma

bladder tumors

cystitis

tumors

tumor

adriamycin

cystitis

Adriamycin

cystitis

Adriamycin

cystitis


Input: Hyperkalemia associated with sulindac therapy. Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6. 1 to 6. 9 mEq / l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause - and - effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.

Hyperkalemia

Hyperkalemia

hyperkalemia

hyperkalemia

sulindac

indomethacin

sulindac

prostacyclin

sulindac

potassium

sulindac

potassium

sulindac

sulindac

indomethacin

Hyperkalemia

indomethacin

Hyperkalemia

indomethacin

hyperkalemia

indomethacin

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia

sulindac

Hyperkalemia

sulindac

Hyperkalemia

sulindac

hyperkalemia

sulindac

hyperkalemia


Input: Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics. This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha - adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.

Ventricular tachyarrhythmias

preterm labor

cardiovascular complications

hypotensive

tachycardia

ritodrine

ritodrine

ritodrine

ritodrine

potassium

ephedrine

phenylephrine

ritodrine

Ventricular tachyarrhythmias

ritodrine

Ventricular tachyarrhythmias

ritodrine

Ventricular tachyarrhythmias

ritodrine

Ventricular tachyarrhythmias


Input: Immunohistochemical, electron microscopic and morphometric studies of estrogen - induced rat prolactinomas after bromocriptine treatment. To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen - induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg / kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.

estrogen

bromocriptine

bromocriptine

estrogen

bromocriptine

bromocriptine

bromocriptine

bromocriptine

prolactinomas

prolactinoma

prolactinoma

prolactinoma

prolactinoma

prolactinoma

adenoma

estrogen

prolactinomas

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinomas

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma

estrogen

prolactinoma


Input: On two paradoxical side - effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action. Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue - specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.

prednisolone

prednisolone

prednisolone

Liver enlargement

muscle wastage

prednisolone

Liver enlargement

prednisolone

Liver enlargement

prednisolone

Liver enlargement

prednisolone

muscle wastage

prednisolone

muscle wastage

prednisolone

muscle wastage


Input: Possible intramuscular midazolam - associated cardiorespiratory arrest and death. Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.

midazolam

Midazolam hydrochloride

midazolam

midazolam

cardiorespiratory arrest

death

respiratory and cardiovascular depression

respiratory and cardiovascular depression

cardiovascular depression

cardiorespiratory arrest

death

midazolam

respiratory and cardiovascular depression

midazolam

respiratory and cardiovascular depression

Midazolam hydrochloride

respiratory and cardiovascular depression

Midazolam hydrochloride

respiratory and cardiovascular depression

midazolam

respiratory and cardiovascular depression

midazolam

respiratory and cardiovascular depression

midazolam

respiratory and cardiovascular depression

midazolam

respiratory and cardiovascular depression

midazolam

cardiorespiratory arrest

midazolam

cardiorespiratory arrest

Midazolam hydrochloride

cardiorespiratory arrest

Midazolam hydrochloride

cardiorespiratory arrest

midazolam

cardiorespiratory arrest

midazolam

cardiorespiratory arrest

midazolam

cardiorespiratory arrest

midazolam

cardiorespiratory arrest


Input: Serial epilepsy caused by levodopa / carbidopa administration in two patients on hemodialysis. Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high - flux dialyzer; both had been receiving a carbidopa / levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.

epilepsy

chronic renal failure

hallucinosis

seizures

levodopa / carbidopa

carbidopa / levodopa

vitamin B6

levodopa / carbidopa

epilepsy

carbidopa / levodopa

epilepsy


Input: Effect of L - alpha - glyceryl - phosphorylcholine on amnesia caused by scopolamine. The present study was carried out to test the effects of L - alpha - glycerylphosphorylcholine (L - alpha - GFC) on memory impairment induced by scopolamine in man. Thirty - two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L - alpha - GFC or placebo, p. o., and on the eleventh day either scopolamine or placebo, i. m. Before and 0. 5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.

L - alpha - glyceryl - phosphorylcholine

scopolamine

L - alpha - glycerylphosphorylcholine

L - alpha - GFC

scopolamine

L - alpha - GFC

scopolamine

scopolamine

amnesia

memory impairment

impairment of attention and memory

scopolamine

memory impairment

scopolamine

impairment of attention and memory

scopolamine

memory impairment

scopolamine

impairment of attention and memory

scopolamine

memory impairment

scopolamine

impairment of attention and memory

scopolamine

memory impairment

scopolamine

impairment of attention and memory


Input: Seizures induced by the cocaine metabolite benzoylecgonine in rats. The half - life (t1 / 2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0. 2 and 0. 4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE - Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine - induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE - Injected rats that did not have seizures had significantly more locomotor activity than cocaine - injected animals without seizures. The finding that cocaine - and BE - induced seizures differ in several respects suggests more than one mechanism for cocaine - induced seizures and emphasizes the importance of a cocaine metabolite, BE.

Seizures

seizures

strokes

seizures

seizure

seizures

seizures

seizures

death

death

seizure

seizures

seizures

seizures

seizures

cocaine

benzoylecgonine

cocaine

cocaine

cocaine

benzoylecgonine

BE

cocaine

BE

BE

cocaine

cocaine

BE

BE

cocaine

cocaine

BE

cocaine

cocaine

BE

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

benzoylecgonine

Seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizure

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizure

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

Seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizure

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizure

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

benzoylecgonine

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures

BE

Seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizure

BE

seizures

BE

seizures

BE

seizures

BE

seizures


Input: Protection against amphetamine - induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist. LY274614, 3SR, 4aRS, 6SR, 8aRS - 6 - [phosphonomethyl] decahydr oisoquinoline - 3 - carboxylic acid, has been described as a potent antagonist of the N - methyl - D - aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole - treated rats is reported. A single 18. 4 mg / kg (i. p.) dose of (+ / -) - amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK - 801, a non - competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose - dependent, being maximum at 10 - 40 mgkg (i. p.). A 10 mg / kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose - dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long - lasting in vivo effects in rats.

amphetamine

dopamine

amino acid

3SR, 4aRS, 6SR, 8aRS - 6 - [phosphonomethyl] decahydr oisoquinoline - 3 - carboxylic acid

N - methyl - D - aspartate

NMDA

glutamate

dopamine

amphetamine

iprindole

amphetamine

iprindole

dopamine

dopamine

dizocilpine

MK - 801

NMDA

NMDA

dopamine

amphetamine

amphetamine

dopamine

amphetamine

amphetamine

dopamine

methamphetamine

amphetamine

dopamine

NMDA

NMDA

neurotoxicity

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic

amphetamine

neurotoxicity

amphetamine

neurotoxic


Input: Neonatal pyridoxine responsive convulsions due to isoniazid therapy. A 17 - day - old infant on isoniazid therapy 13 mg / kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.

pyridoxine

isoniazid

isoniazid

pyridoxine

pyridoxine

isoniazid

convulsions

tuberculosis

clonic fits

fits

isoniazid

convulsions

isoniazid

clonic fits

isoniazid

fits

isoniazid

convulsions

isoniazid

clonic fits

isoniazid

fits

isoniazid

convulsions

isoniazid

clonic fits

isoniazid

fits


Input: Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction. Nitroglycerin has been shown to reduce ST - segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin - induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 + / - 6 to 85 + / - 6 mm Hg (P less than 0. 001), for 60 minutes. Left ventricular filling pressure decreased from 19 + / - 2 to 11 + / - 2 mm Hg (P less than 0. 001). SigmaST, the sum of ST - segment elevations in 16 precordial leads, decreased (P less than 0. 02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re - elevate mean arterial pressure to 106 + / - 4 mm Hg (P less than 0. 001) for 30 minutes, increased left ventricular filling pressure to 17 + / - 2 mm Hg (P less than 0. 05) and also significantly increased sigmaST (P less than 0. 05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.

phenylephrine

nitroglycerin

Nitroglycerin

nitroglycerin

nitroglycerin

phenylephrine

nitroglycerin

nitroglycerin

phenylephrine

phenylephrine

nitroglycerin

acute myocardial infarction

acute myocardial infarction

hypotension

myocardial infarctions

acute myocardial infarction

nitroglycerin

hypotension

Nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension

nitroglycerin

hypotension


Input: Elevation of ADAM10, ADAM17, MMP - 2 and MMP - 9 expression with media degeneration features CaCl2 - induced thoracic aortic aneurysm in a rat model. PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl (2)) - induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague - Dawley rats was exposed to 0. 5M CaCl (2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl (2) - treated, CaCl (2) - untreated (n = 12) and NaCl - treated aortic segments (n = 12) were collected for histological and molecular assessments. MMP - TIMP and ADAM mRNAs were semi - quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl (2) - treated, non - CaCl (2) - treated and NaCl - treated segments, aneurymal alteration (n = 6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n = 12, 100%) were demonstrated in CaCl (2) - treated segments. MMP - 2, MMP - 9, ADAM - 10 and ADAM - 17 mRNA levels were increased in CaCl (2) - treated segments (all p < 0. 01), with trends of elevation in CaCl (2) - untreated segments, as compared with NaCl - treated segments. Immunohistochemistry displayed significantly increased expressions of MMP - 2, MMP - 9, ADAM - 10 and ADAM - 17 (all p < 0. 01) in intima and media for CaCl (2) - treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl (2) exposure in rats, and demonstrates a significant elevation of expression of MMP - 2, MMP - 9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.

calcium chloride

CaCl (2)

CaCl (2)

NaCl

CaCl (2)

CaCl (2)

NaCl

CaCl (2)

CaCl (2)

NaCl

CaCl (2)

CaCl (2)

CaCl (2)

NaCl

CaCl (2)

CaCl (2)

thoracic aortic aneurysm

thoracic aortic aneurysm

TAA

arterial injury

TAA

TAA

thoracic aortic aneurysm

thoracic aortic aneurysm

TAA

TAA

TAA

calcium chloride

thoracic aortic aneurysm

calcium chloride

thoracic aortic aneurysm

calcium chloride

TAA

calcium chloride

TAA

calcium chloride

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

thoracic aortic aneurysm

CaCl (2)

TAA

CaCl (2)

TAA

CaCl (2)

TAA


Input: When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration. Twenty - three hours after heart transplantation, life - threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.

right heart failure

hypertensive

catecholamines

epinephrine

catecholamine

epinephrine

hypertensive


Input: Long - term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel. Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC - induced peripheral neuropathy in a randomized, placebo - controlled, double - blinded clinical and electro - diagnostic study. Forty - three ovarian cancer patients were available for analysis following six cycles of the same PAC - containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory - motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0. 011). Also the frequency of abnormal electro - diagnostic findings showed similarity between the two groups (G: 7 / 23 = 30. 4%; P: 6 / 20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.

glutamate

paclitaxel

paclitaxel

PAC

glutamate

amino acid

glutamine

PAC

glutamate

PAC

PAC

glutamate

glutamate

PAC

peripheral neurotoxicity

peripheral neuropathy

neurotoxicity

peripheral neuropathy

ovarian cancer

neurotoxicity

pain

peripheral neurotoxicity

paclitaxel

peripheral neurotoxicity

paclitaxel

peripheral neuropathy

paclitaxel

peripheral neuropathy

paclitaxel

peripheral neurotoxicity

paclitaxel

peripheral neurotoxicity

paclitaxel

peripheral neuropathy

paclitaxel

peripheral neuropathy

paclitaxel

peripheral neurotoxicity

PAC

peripheral neurotoxicity

PAC

peripheral neuropathy

PAC

peripheral neuropathy

PAC

peripheral neurotoxicity

PAC

peripheral neurotoxicity

PAC

peripheral neuropathy

PAC

peripheral neuropathy

PAC

peripheral neurotoxicity

PAC

peripheral neurotoxicity

PAC

peripheral neuropathy

PAC

peripheral neuropathy

PAC

peripheral neurotoxicity

PAC

peripheral neurotoxicity

PAC

peripheral neuropathy

PAC

peripheral neuropathy

PAC

peripheral neurotoxicity

PAC

peripheral neurotoxicity

PAC

peripheral neuropathy

PAC

peripheral neuropathy

PAC

peripheral neurotoxicity


Input: Attentional modulation of perceived pain intensity in capsaicin - induced secondary hyperalgesia. Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin - induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin - untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin - induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.

pain

hyperalgesia

pain

pain

hyperalgesia

pain

hyperalgesia

hyperalgesia

hyperalgesia

pain

capsaicin

capsaicin

capsaicin

capsaicin

capsaicin

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia

capsaicin

hyperalgesia


Input: Testosterone - dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt - sensitive rats. Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt - sensitive rats (DS), high - salt (HS) diet increases BP more in males than females. In contrast to the systemic renin - angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS - induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low - salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin - angiotensin system.

Testosterone

salt

salt

salt

salt

angiotensin

testosterone

salt

Testosterone

Testosterone

angiotensin

hypertension

renal injury

glomerular sclerosis

renal injury

hypertension

renal injury

salt

renal injury

salt

glomerular sclerosis

salt

renal injury

salt

renal injury

salt

renal injury

salt

glomerular sclerosis

salt

renal injury

salt

renal injury

salt

renal injury

salt

glomerular sclerosis

salt

renal injury

salt

renal injury

salt

renal injury

salt

glomerular sclerosis

salt

renal injury

salt

renal injury

salt

renal injury

salt

glomerular sclerosis

salt

renal injury

salt

renal injury


Input: Prenatal protein deprivation alters dopamine - mediated behaviors and dopaminergic and glutamatergic receptor binding. Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol - induced catalepsy or MK - 801 - induced locomotion were seen following PD. In addition, PD female rats showed increased (3) H - MK - 801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3) H - haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3) H - MK - 801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.

dopamine

apomorphine

amphetamine

haloperidol

MK - 801

H

MK - 801

H

haloperidol

dopamine

H

MK - 801

schizophrenia

schizophrenia

catalepsy

nutritional deficiency

schizophrenia

haloperidol

catalepsy

haloperidol

catalepsy


Input: mToR inhibitors - induced proteinuria: mechanisms, significance, and management. Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade - induced proteinuria.

proteinuria

chronic allograft nephropathy

proteinuria

proteinuria

proteinuria

glomerulosclerosis

proteinuria

rapamycin

sirolimus

sirolimus

sirolimus

sirolimus

rapamycin

proteinuria

rapamycin

proteinuria

rapamycin

proteinuria

rapamycin

proteinuria

rapamycin

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria


Input: Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol. Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen - induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid - induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL - R) and components of prolactin' s signaling pathway. To test the hypothesis that estrogen increases PRL - R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin - induced STAT5 activation. Lastly, we measured PRL - R and suppressor of cytokine signaling (SOCS - 1 and - 3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS - 1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL - R, SOCS - 3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS - 3 and CIS. Interestingly, estradiol also induced PRL - R, SOCS - 3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid - dependent manner. They also provide evidence for estradiol - dependent and brain region - specific regulation of PRL - R expression and signaling responses by prolactin.

ribonucleic acid

estradiol

estrogen

dopamine

sulpiride

estradiol

Sulpiride

steroid

Estradiol

estrogen

estradiol

sulpiride

estradiol

Sulpiride

Estradiol

estradiol

steroid

estradiol

hyperprolactinemic

Hyperprolactinemia

hyperprolactinemia

hyperprolactinemia

hyperprolactinemia

sulpiride

hyperprolactinemic

sulpiride

Hyperprolactinemia

sulpiride

hyperprolactinemia

sulpiride

hyperprolactinemia

sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemic

Sulpiride

Hyperprolactinemia

Sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemia

sulpiride

hyperprolactinemic

sulpiride

Hyperprolactinemia

sulpiride

hyperprolactinemia

sulpiride

hyperprolactinemia

sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemic

Sulpiride

Hyperprolactinemia

Sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemia

Sulpiride

hyperprolactinemia


Input: Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir. Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long - term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir - treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP - 1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage - like phenotype in the presence or absence of 1 nM 17beta - estradiol (E2), 100 nM progesterone or vehicle (0. 01% ethanol). Cells were then treated with 30 ng / ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte - derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.

cholesteryl ester

ritonavir

ritonavir

ritonavir

ritonavir

cholesteryl ester

cholesterol

ritonavir

17beta - estradiol

progesterone

ethanol

ritonavir

cholesteryl esters

ritonavir

Ritonavir

ritonavir

cholesteryl ester

ritonavir

premature atherosclerosis

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

Ritonavir

premature atherosclerosis

Ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion

ritonavir

premature atherosclerosis

ritonavir

atherosclerotic lesion


Input: Upregulation of brain expression of P - glycoprotein in MRP2 - deficient TR (-) rats resembles seizure - induced up - regulation of this drug efflux transporter in normal rats. PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood - brain barrier (BBB). MRP2 is absent in the transport - deficient (TR (-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2 - deficient rats with those in transport - competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P - glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR (-) rats compared with nonmutant (wild - type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR (-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR (-) rats. TR (-) rats exhibited a significant up - regulation of Pgp in brain capillary endothelial cells compared with wild - type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine - induced seizures in wild - type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR (-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR (-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR (-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp - enhancing events for this purpose.

seizure

seizures

injury to the brain

seizures

phenytoin

pilocarpine

phenobarbital

tariquidar

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures


Input: Use of chromosome substitution strains to identify seizure susceptibility loci in mice. Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine - induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A / J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine - induced seizures. Three hundred fifty - five adult male CSS mice, 58 B6, and 39 A / J were tested for susceptibility to pilocarpine - induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A / J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.

seizure

Seizure

seizure

seizures

temporal lobe epilepsy

seizure

seizures

seizures

seizures

seizure

temporal lobe epilepsy

pilocarpine

pilocarpine

pilocarpine

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy


Input: Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine. Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA - encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4. 8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA - encoded subunit of CCO (CCO - I) or a relative decrease in CCO - I when compared with nuclear - encoded subunits (CCO - IV and SDH - fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO - I, and in CCO activity.

epilepsy

Mitochondrial abnormalities

death

status epilepticus

temporal lobe epilepsy

mitochondrial abnormalities

pilocarpine

pilocarpine

pilocarpine

temporal lobe epilepsy

pilocarpine

temporal lobe epilepsy


Input: Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation. OBJECTIVES: Thrombotic microangiopathy is a well - known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1 - year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n = 25) performed during this interval. Pre - and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow - up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most - frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug - related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody - mediated rejection. We found that the most - frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).

thrombotic microangiopathy

Thrombotic microangiopathy

thrombotic microangiopathy

hemolytic uremic syndrome

thrombotic microangiopathy

thrombotic microangiopathy

thrombotic microangiopathy

thrombotic microangiopathy

antiphospholipid syndrome

systemic lupus erythematosus

hemolytic uremic syndrome

hemolytic uremic syndrome

toxicity

thrombotic microangiopathy

thrombotic microangiopathy

cyclosporine

cyclosporine

tacrolimus

cyclosporine

tacrolimus

cyclosporine

cyclosporine

thrombotic microangiopathy

cyclosporine

Thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

Thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

Thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

Thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy

cyclosporine

thrombotic microangiopathy


Input: Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose. Catecholamine - induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35 - year - old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.

left ventricular systolic and diastolic dysfunction

overdose

cardiomyopathy

myocardial dysfunction

overdose

myocardial stunning

left ventricular systolic and diastolic dysfunction

myocardial necrosis

epinephrine

Catecholamine

catecholamines

epinephrine

epinephrine

myocardial stunning

epinephrine

myocardial stunning


Input: Urinary bladder cancer in Wegener' s granulomatosis: risks and relation to cyclophosphamide. OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener' s granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener' s granulomatosis, 1969 - 95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case - control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener' s granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener' s granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2. 0, 95% confidence interval (CI) 0. 8 to 4. 9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7. 7, 95% CI 0. 9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener' s granulomatosis, and a history of bladder cancer was (non - significantly) twice as common as expected at the time of diagnosis of Wegener' s granulomatosis. CONCLUSION: The results indicate a dose - response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener' s granulomatosis.

Urinary bladder cancer

Wegener' s granulomatosis

bladder cancer

Wegener' s granulomatosis

Wegener' s granulomatosis

Cancer

bladder cancer

bladder cancer

bladder cancer

Wegener' s granulomatosis

bladder cancer

Wegener' s granulomatosis

bladder cancer

bladder cancer

Wegener' s granulomatosis

bladder cancer

Wegener' s granulomatosis

bladder cancer

Wegener' s granulomatosis

cyclophosphamide

cyclophosphamide

cyclophosphamide

cyclophosphamide

cyclophosphamide

cyclophosphamide

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

Urinary bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer

cyclophosphamide

bladder cancer


Input: L - arginine transport in humans with cortisol - induced hypertension. A deficient L - arginine - nitric oxide system is implicated in cortisol - induced hypertension. We investigate whether abnormalities in L - arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5 - day fixed - salt diet (150 mmol / d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L - arginine uptake was assessed in mononuclear cells incubated with L - arginine (1 to 300 micromol / L), incorporating 100 nmol / L [3H] - l - arginine for a period of 5 minutes at 37 degrees C. Forearm [3H] - L - arginine extraction was calculated after infusion of [3H] - L - arginine into the brachial artery at a rate of 100 nCi / min for 80 minutes. Deep forearm venous samples were collected for determination of L - arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323 + / - 43 to 1082 + / - 245 mmol / L, P < 0. 05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L - arginine transport into mononuclear cells (placebo vs active, 26. 3 + / - 3. 6 vs 29. 0 + / - 2. 1 pmol / 10 000 cells per 5 minutes, respectively, at an l - arginine concentration of 300 micromol / L) nor L - arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904 + / - 434 962 vs 2 013 910 + / - 770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L - arginine uptake is not affected by short - term cortisol treatment. We conclude that cortisol - induced increases in blood pressure are not associated with abnormalities in the l - arginine transport system.

L - arginine

cortisol

L - arginine

nitric oxide

cortisol

L - arginine

Hydrocortisone acetate

L - arginine

L - arginine

[3H] - l - arginine

[3H] - L - arginine

[3H] - L - arginine

L - arginine

cortisol

L - arginine

l - arginine

L - arginine

cortisol

L - arginine

cortisol

cortisol

l - arginine

hypertension

hypertension

increases in blood pressure

Hydrocortisone acetate

hypertension

Hydrocortisone acetate

hypertension

Hydrocortisone acetate

increases in blood pressure


Input: MR imaging with quantitative diffusion mapping of tacrolimus - induced neurotoxicity in organ transplant patients. Our objective was to investigate brain MR imaging findings and the utility of diffusion - weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow - up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35. 7%) had white matter abnormalities, 1 (7. 1%) had putaminal hemorrhage, and 8 (57. 1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80. 0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow - up images. The remaining 1 patient (20. 0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion - weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus - induced neurotoxicity.

tacrolimus

tacrolimus

tacrolimus

tacrolimus

neurotoxicity

neurologic complications

white matter abnormalities

putaminal hemorrhage

white matter abnormalities

cortical laminar necrosis

neurotoxicity

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities

tacrolimus

white matter abnormalities


Input: Octreotide - induced hypoxemia and pulmonary hypertension in premature neonates. The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high - risk premature neonates.

Octreotide

octreotide

hypoxemia

pulmonary hypertension

fistula

necrotizing enterocolitis

Pulmonary hypertension

fistula

Octreotide

pulmonary hypertension

Octreotide

Pulmonary hypertension

octreotide

pulmonary hypertension

octreotide

Pulmonary hypertension


Input: Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly. Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid - to late - gestation mouse embryos. We observed the exencephaly induced by 5 - azacytidine at embryonic day 13. 5 (E13. 5), let the embryos develop exo utero until E18. 5, and re - observed the same embryos at E18. 5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13. 5 and E18. 5. It was found that the transformation of exencephalic tissue was not simply size - dependent, and all cases of anencephaly at E18. 5 resulted from embryos with a large amount of exencephalic tissue at E13. 5. Microscopic observation showed the configuration of exencephaly at E13. 5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15. 5, and multiple modes of reduction in the exencephalic tissue at E18. 5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and / or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.

exencephaly

exencephaly

anencephaly

Anencephaly

exencephaly

exencephaly

exencephaly

anencephaly

exencephalic

exencephaly

exencephalic

exencephalic

anencephaly

exencephalic

exencephaly

hemorrhaging

exencephalic

exencephalic

exencephalic

exencephalic

circulatory failure

hemorrhaging

exencephalic

exencephaly

anencephaly

5 - azacytidine

5 - azacytidine

anencephaly

5 - azacytidine

Anencephaly

5 - azacytidine

anencephaly

5 - azacytidine

anencephaly

5 - azacytidine

anencephaly


Input: Acute cocaine - induced seizures: differential sensitivity of six inbred mouse strains. Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50 - 100 mg / kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A / J and SJL mice being most sensitive and C57BL / 6J most resistant. DBA / 2J, BALB / cByJ and NZW / LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A / J and C57BL / 6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine - induced seizures.

cocaine

cocaine

Cocaine

cocaine

cocaine

seizures

seizures

Seizure

seizure

seizure

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizure

cocaine

seizure

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizure

cocaine

seizure

cocaine

seizure

cocaine

seizures

Cocaine

seizures

Cocaine

seizures

Cocaine

Seizure

Cocaine

seizure

Cocaine

seizure

Cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizure

cocaine

seizure

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

Seizure

cocaine

seizure

cocaine

seizure

cocaine

seizures


Input: Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy. We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506 - associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross - react with cyclosporin A (CyA), an immuno - suppressive drug already known to induce MAHA.

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

tacrolimus

tacrolimus

corticosteroids

aspirin

dipyridamole

cyclosporin A

CyA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

tacrolimus

Microangiopathic hemolytic anemia

tacrolimus

microangiopathic hemolytic anemia

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

tacrolimus

Microangiopathic hemolytic anemia

tacrolimus

microangiopathic hemolytic anemia

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

tacrolimus

MAHA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA

Microangiopathic hemolytic anemia

microangiopathic hemolytic anemia

MAHA

MAHA

MAHA

MAHA

MAHA


Input: Variant ventricular tachycardia in desipramine toxicity. We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R - R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.

ventricular tachycardia

toxicity

ventricular tachycardia

toxicity

arrhythmia

ventricular tachycardia

ventricular tachycardia

desipramine

desipramine

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia

desipramine

ventricular tachycardia


Input: Desipramine - induced delirium at " subtherapeutic " concentrations: a case report. An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the " subtherapeutic " range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.

Desipramine

Desipramine

antidepressants

delirium

delirium

Delirium

Desipramine

delirium

Desipramine

delirium

Desipramine

Delirium

Desipramine

delirium

Desipramine

delirium

Desipramine

Delirium


Input: Mouse strain - dependent effect of amantadine on motility and brain biogenic amines. The effect of amantadine hydrochloride, injected i. p. in 6 increments of 100 mg / kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague - Dawley ICR and BALB / C, the black C57BL / 6 and the brown CDF - I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB / C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB / C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug - free period following the fourth amantadine treatment. Readministration of amantadine, after a drug - free overnight period, increased motility from respective saline control in all strains with exception of the BALB / C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3, 4 - dihydroxyphenylacetic acid in the BALB / C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB / C mice. The results suggest a strain - dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB / C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB / C mouse strain suggest a probable decrease of catecholamine turnover rate and / or metabolism by monoamine oxidase and a resulting increase in O - methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB / C mice.

amantadine

amines

amantadine hydrochloride

amines

Amantadine

amantadine

amantadine

amantadine

amantadine

amantadine

dopamine

3, 4 - dihydroxyphenylacetic acid

normetanephrine

amantadine

amantadine

amantadine

amines

catecholamine

norepinephrine

amantadine

depressed

suppression of motility

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine hydrochloride

suppression of motility

amantadine hydrochloride

behavioral depression

Amantadine

suppression of motility

Amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression

amantadine

suppression of motility

amantadine

behavioral depression


Input: No enhancement by phenobarbital of the hepatocarcinogenicity of a choline - devoid diet in the rat. An experiment was performed to test whether inclusion of phenobarbital in a choline - devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5 - week old male Fischer - 344 rats were fed for 7 - 25 months semipurified choline - devoid or choline - supplemented diets, containing or not 0. 06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline - supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline - devoid diet, and 17% and 30%, in rats fed the phenobarbital - containing choline - devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline - devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.

phenobarbital

choline

phenobarbital

choline

choline

choline

phenobarbital

choline

phenobarbital

choline

phenobarbital

choline

choline

phenobarbital

hepatocellular carcinomas

hepatocellular carcinoma

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas

choline

hepatocellular carcinomas

choline

hepatocellular carcinoma

choline

hepatocellular carcinomas


Input: Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina. The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms / min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 + / - 13 micrograms (mean + / - SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.

methylergonovine

methylergonovine

Methylergonovine

methylergonovine

variant angina

variant angina

chest pain

angina pectoris

variant angina

coronary spasm

spasm

spasm

variant angina

methylergonovine

coronary spasm

methylergonovine

coronary spasm

Methylergonovine

coronary spasm

methylergonovine

coronary spasm


Input: Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin - treated long - term survivors of childhood cancer. Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long - term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 + / - 5 years) treated from 1. 6 to 14. 3 years (median 5. 3) before this study with 27 to 532 mg / m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age - matched control subjects. Graded dobutamine infusions of 0. 5, 2. 5, 5 and 10 micrograms / kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms / kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end - systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin - treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End - systolic left ventricular posterior wall dimension at baseline for the doxorubicin - treated group was 11 + / - 1. 9 mm versus 13. 1 + / - 1. 5 mm for control subjects (p less than 0. 01). End - systolic left ventricular posterior wall dimension at the 5 - micrograms / kg per min dobutamine infusion for the doxorubicin - treated group was 14. 1 + / - 2. 4 mm versus 19. 3 + / - 2. 6 mm for control subjects (p less than 0. 01). (ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine

doxorubicin

Doxorubicin

doxorubicin

dobutamine

doxorubicin

doxorubicin

dobutamine

Dobutamine

doxorubicin

dobutamine

doxorubicin

dobutamine

doxorubicin

cancer

cardiomyopathy

cardiac damage

cancer

doxorubicin

cardiomyopathy

Doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy

doxorubicin

cardiomyopathy


Input: Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure. Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid - base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7. 05 to 7. 25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.

aminophylline

aminophylline

aminophylline

oxygen

carbon dioxide

aminophylline

aminophylline

ventricular fibrillation

respiratory failure

Cardiac arrhythmias

respiratory failure

cardiac disturbances

respiratory failure

ventricular fibrillation

respiratory failure

ventricular fibrillation

ventricular fibrillation

respiratory failure

hypoventilation

ventricular fibrillation

ventricular arrhythmias

respiratory failure

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation

aminophylline

ventricular fibrillation