Input: Is the treatment of scabies hazardous? Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at - risk groups, and give adequate warnings regarding potential toxicity.

scabies

scabies

toxic to the central nervous system

aplastic anaemia

toxicity

lindane

gamma benzene hexachloride

Lindane

lindane

lindane

lindane

aplastic anaemia

gamma benzene hexachloride

aplastic anaemia

Lindane

aplastic anaemia

lindane

aplastic anaemia

lindane

aplastic anaemia

lindane

toxic to the central nervous system

gamma benzene hexachloride

toxic to the central nervous system

Lindane

toxic to the central nervous system

lindane

toxic to the central nervous system

lindane

toxic to the central nervous system


Input: Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita. We report an undiagnosed case of myotonia congenita in a 24 - year - old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred.

masseter spasm

myotonia congenita

myotonia congenita

masseter spasm

suxamethonium

suxamethonium

masseter spasm

suxamethonium

masseter spasm


Input: Toxicity in rhesus monkeys following administration of the 8 - aminoquinoline 8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline (WR242511). INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long - acting MHb former could serve as a CN pretreatment. Using this rationale, the 8 - aminoquinoline WR242511, a potent long - lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3. 5 and / or 7. 0 mg / kg; a single male also received WR242511 orally (PO) at 7. 0 mg / kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2. 0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3. 5 or 7. 0 mg / kg), and 2 lethalities occurred (one IV and one PO) following the 7. 0 mg / kg dose. Myoglobinuria was also observed following the 7. 0 mg / kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally - treated animal. CONCLUSIONS: These data demonstrate direct and / or indirect drug - induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti - CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.

Toxicity

toxicity

poisoning

methemoglobinemia

hemoglobinuria

Myoglobinuria

liver and kidney toxicity

liver and kidney toxicity

kidney toxicity

toxicity

poisoning

toxicity

8 - aminoquinoline

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

8 - aminoquinoline

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

liver and kidney toxicity

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

liver and kidney toxicity

kidney toxicity

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

liver and kidney toxicity

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

hemoglobinuria

hemoglobinuria

hemoglobinuria

hemoglobinuria

hemoglobinuria

hemoglobinuria

hemoglobinuria

hemoglobinuria

8 - [(4 - amino - l - methylbutyl) amino] - 5 - (l - hexyloxy) - 6 - methoxy - 4 - methylquinoline

Myoglobinuria

Myoglobinuria

Myoglobinuria

Myoglobinuria

Myoglobinuria

Myoglobinuria

Myoglobinuria

Myoglobinuria


Input: Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss. Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone - burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss.

hearing loss

hearing loss

hearing loss

kanamycin

furosemide

furosemide

hearing loss

furosemide

hearing loss

furosemide

hearing loss

kanamycin

hearing loss

kanamycin

hearing loss

kanamycin

hearing loss


Input: The site of common side effects of sumatriptan. Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.

sumatriptan

sumatriptan

Atypical sensations

tingling or burning sensations

sunburn

sumatriptan

Atypical sensations

sumatriptan

tingling or burning sensations

sumatriptan

Atypical sensations

sumatriptan

tingling or burning sensations


Input: Tremor side effects of salbutamol, quantified by a laser pointer technique. OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low - priced method is needed. A new method using a commercially available, pen - shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a. m., 4 p. m. and 9 a. m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2 - kg weight until exhaustion. Inter - observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose - dependent way. Within healthy adults no age - dependency could be found (b = 0. 262 mm / year; P = 0. 72). There was no agreement between the questionnaire and tremor severity (r = 0. 093; P = 0. 53). Postural tremor showed no significant difference between the first and third session (P = 0. 07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0. 72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (< 12 years) a sensitive and reproducible method.

Tremor

tremor

Tremor

tremor

obstructive lung disease

tremor

tremor

tremor

tremor

Tremor

tremor

tremor

tremor

tremor

tremor

tremor

salbutamol

salbutamol

salbutamol

Salbutamol

salbutamol

Tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

Tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

salbutamol

tremor

Salbutamol

Tremor

Salbutamol

tremor

Salbutamol

Tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

Tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor

Salbutamol

tremor


Input: Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen - independent prostate cancer. STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen - independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50 - 80 years, with advanced androgen - independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg / m2 / week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4 - week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p = 0. 025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.

venous thromboembolism

prostate cancer

venous thromboembolism

VTE

prostate cancer

prostate cancer

toxicity

VTE

VTE

prostate cancer

VTE

docetaxel

thalidomide

docetaxel

thalidomide

docetaxel

thalidomide

docetaxel

docetaxel

docetaxel

thalidomide

thalidomide

docetaxel

thalidomide

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

venous thromboembolism

thalidomide

venous thromboembolism

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

thalidomide

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

venous thromboembolism

docetaxel

venous thromboembolism

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE

docetaxel

VTE


Input: Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM - 272. UM - 272 (N, N - dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain - induced ventricular tachycardias. Both anti - arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM - 272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4 - 12 times greater than for oral drug, suggesting the existence of an absorption - limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.

quaternary ammonium

UM - 272

UM - 272

N, N - dimethylpropranolol

ouabain

UM - 272

ventricular tachycardias

ventricular tachycardia

ouabain

ventricular tachycardias

ouabain

ventricular tachycardia


Input: Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome. Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30 - year old Caucasian man reported with abdominal pain and jaundice after 3 - day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life - threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.

thrombocytopenia

haemolytic anaemia

abdominal pain

jaundice

urinary tract infection

thrombocytopenia

haemolysis

petechiae

purpura

haemorrhages

bone marrow depression

thrombi

microangiopathies

thrombocytopenia

haemolytic anaemia

ciprofloxacin

ciprofloxacin

ciprofloxacin

ciprofloxacin

ciprofloxacin

petechiae

ciprofloxacin

purpura

ciprofloxacin

petechiae

ciprofloxacin

purpura

ciprofloxacin

petechiae

ciprofloxacin

purpura

ciprofloxacin

petechiae

ciprofloxacin

purpura

ciprofloxacin

jaundice

ciprofloxacin

jaundice

ciprofloxacin

jaundice

ciprofloxacin

jaundice

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

thrombocytopenia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

haemolytic anaemia

ciprofloxacin

abdominal pain

ciprofloxacin

abdominal pain

ciprofloxacin

abdominal pain

ciprofloxacin

abdominal pain


Input: Simvastatin - induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism. A 54 - year - old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.

Simvastatin

thyroxine

simvastatin

simvastatin

compartment syndrome

myonecrosis

hypothyroidism

hypothyroid

compartment syndrome

myonecrosis

arteriopathic

Simvastatin

compartment syndrome

Simvastatin

compartment syndrome

simvastatin

compartment syndrome

simvastatin

compartment syndrome

simvastatin

compartment syndrome

simvastatin

compartment syndrome


Input: Bile duct hamartoma occurring in association with long - term treatment with danazol. We report a case of bile duct hamartoma which developed in a patient who had been on long - term danazol treatment. Such patients should be under close follow - up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non - specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.

Bile duct hamartoma

Bile duct hamartoma

hamartoma

bile duct hamartoma

bile duct hamartoma

hamartoma

liver mass

danazol

danazol

danazol

Bile duct hamartoma

danazol

Bile duct hamartoma

danazol

bile duct hamartoma

danazol

bile duct hamartoma

danazol

Bile duct hamartoma

danazol

Bile duct hamartoma

danazol

bile duct hamartoma

danazol

bile duct hamartoma

danazol

hamartoma

danazol

hamartoma

danazol

hamartoma

danazol

hamartoma


Input: Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid. We report the case of a patient with amoxicillin - clavulanic acid - induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.

Granulomatous hepatitis

Granulomatous

hepatitis

hepatitis

granulomas

liver injury

cholestatic syndrome

granulomas

eosinophilia

combination of amoxicillin and clavulanic acid

amoxicillin - clavulanic acid

penicillin

amoxicillin

amoxicillin

clavulanic acid

combination of amoxicillin and clavulanic acid

Granulomatous hepatitis

combination of amoxicillin and clavulanic acid

hepatitis

combination of amoxicillin and clavulanic acid

hepatitis

combination of amoxicillin and clavulanic acid

liver injury

amoxicillin - clavulanic acid

Granulomatous hepatitis

amoxicillin - clavulanic acid

hepatitis

amoxicillin - clavulanic acid

hepatitis

amoxicillin - clavulanic acid

liver injury

combination of amoxicillin and clavulanic acid

Granulomatous

combination of amoxicillin and clavulanic acid

granulomas

combination of amoxicillin and clavulanic acid

granulomas

amoxicillin - clavulanic acid

Granulomatous

amoxicillin - clavulanic acid

granulomas

amoxicillin - clavulanic acid

granulomas

combination of amoxicillin and clavulanic acid

cholestatic syndrome

amoxicillin - clavulanic acid

cholestatic syndrome


Input: Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators. OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6 - year period revealed 14 patients with cocaine - related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0. 002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 + / - 6. 08 mm versus 11 + / - 5. 4 mm; P = 0. 05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0. 005) and age (P < 0. 007) were significant predictors of outcome for the patients with cocaine - related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.

Intracranial aneurysms

cocaine abuse

subarachnoid hemorrhage

cocaine abuse

aneurysms

ruptured aneurysms

cocaine abuse

subarachnoid hemorrhage

aneurysm

aneurysm

aneurysms

aneurysms

aneurysms

aneurysmal rupture

aneurysms

cocaine

cocaine

Cocaine

cocaine

ruptured aneurysms

cocaine

aneurysmal rupture

cocaine

ruptured aneurysms

cocaine

aneurysmal rupture

Cocaine

ruptured aneurysms

Cocaine

aneurysmal rupture


Input: Anti - epileptic drugs - induced de novo absence seizures. The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug - induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma - aminobutyric acid - transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug - induced de novo absence seizure is rare, pro - absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug - induced aggravation should be considered whenever an unexpected increase in seizure frequency and / or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug - induced absence seizures.

epileptic

absence seizures

absence epilepsy

absence seizure

absence epilepsy

absence seizure

absence seizure

seizure

seizure

absence epilepsy

epilepsy

absence seizures

carbamazepine

vigabatrin

gamma - aminobutyric acid

vigabatrin

absence seizures

vigabatrin

absence epilepsy

vigabatrin

absence seizure

vigabatrin

absence epilepsy

vigabatrin

absence seizure

vigabatrin

absence seizure

vigabatrin

absence epilepsy

vigabatrin

absence seizures

carbamazepine

absence seizures

carbamazepine

absence epilepsy

carbamazepine

absence seizure

carbamazepine

absence epilepsy

carbamazepine

absence seizure

carbamazepine

absence seizure

carbamazepine

absence epilepsy

carbamazepine

absence seizures


Input: Procainamide - induced polymorphous ventricular tachycardia. Seven cases of procainamide - induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q - T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q - T syndrome with polymorphous ventricular tachycardia.

Procainamide

procainamide

procainamide

procainamide

procainamide

procainamide

ventricular tachycardia

ventricular tachycardia

ventricular tachycardia

ventricular tachycardia

premature ventricular contractions

atrial flutter

Q - T prolongation

syncope

ventricular tachycardia

arrhythmia

arrhythmia

arrhythmia

ventricular fibrillation

ventricular tachycardia

prolonged Q - T syndrome

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

Procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia

procainamide

ventricular tachycardia


Input: Role of activation of bradykinin B2 receptors in disruption of the blood - brain barrier during acute hypertension. Cellular mechanisms which account for disruption the blood - brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis / release of bradykinin to activate B2 receptors in disruption of the blood - brain barrier during acute hypertension. Permeability of the blood - brain barrier was quantitated by clearance of fluorescent - labeled dextran before and during phenylephrine - induced acute hypertension in rats treated with vehicle and Hoe - 140 (0. 1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood - brain barrier during acute hypertension is not related to the synthesis / release of bradykinin to activate B2 receptors.

bradykinin

bradykinin

dextran

phenylephrine

Hoe - 140

Phenylephrine

dextran

bradykinin

hypertension

hypertension

hypertension

hypertension

hypertension

phenylephrine

hypertension

phenylephrine

hypertension

phenylephrine

hypertension

phenylephrine

hypertension

phenylephrine

hypertension

Phenylephrine

hypertension

Phenylephrine

hypertension

Phenylephrine

hypertension

Phenylephrine

hypertension

Phenylephrine

hypertension


Input: 5 - azacytidine potentiates initiation induced by carcinogens in rat liver. To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5 - azacytidine (5 - AzC) (10 mg / kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo [a] - pyrene (200 mg / kg), N - methyl - N - nitrosourea (60 mg / kg) and 1, 2 - dimethylhydrazine (1, 2 - DMH) (100 mg / kg). The initiated hepatocytes in the liver were assayed as the gamma - glutamyltransferase (gamma - GT) positive foci formed following a 2 - week selection regimen consisting of dietary 0. 02% 2 - acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5 - AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10 - 20 foci / cm2 in 5 - AzC and carcinogen - treated rats compared with 3 - 5 foci / cm2 in rats treated with carcinogen only. Administration of [3H] - 5 - azadeoxycytidine during the repair synthesis induced by 1, 2 - DMH further showed that 0. 019 mol% of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5 - AzC occurs during repair synthesis. In the absence of the carcinogen, 5 - AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma - GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.

5 - azacytidine

5 - azacytidine

5 - AzC

benzo [a] - pyrene

N - methyl - N - nitrosourea

1, 2 - dimethylhydrazine

1, 2 - DMH

2 - acetylaminofluorene

5 - AzC

5 - AzC

[3H] - 5 - azadeoxycytidine

1, 2 - DMH

cytosine

5 - AzC

5 - AzC

initiation induced by carcinogens

initiation of carcinogenic process

2 - acetylaminofluorene

initiation induced by carcinogens

2 - acetylaminofluorene

initiation of carcinogenic process

benzo [a] - pyrene

initiation induced by carcinogens

benzo [a] - pyrene

initiation of carcinogenic process

initiation induced by carcinogens

initiation of carcinogenic process

5 - azacytidine

initiation induced by carcinogens

5 - azacytidine

initiation of carcinogenic process

5 - azacytidine

initiation induced by carcinogens

5 - azacytidine

initiation of carcinogenic process

5 - AzC

initiation induced by carcinogens

5 - AzC

initiation of carcinogenic process

5 - AzC

initiation induced by carcinogens

5 - AzC

initiation of carcinogenic process

5 - AzC

initiation induced by carcinogens

5 - AzC

initiation of carcinogenic process

5 - AzC

initiation induced by carcinogens

5 - AzC

initiation of carcinogenic process

5 - AzC

initiation induced by carcinogens

5 - AzC

initiation of carcinogenic process

1, 2 - dimethylhydrazine

initiation induced by carcinogens

1, 2 - dimethylhydrazine

initiation of carcinogenic process

1, 2 - DMH

initiation induced by carcinogens

1, 2 - DMH

initiation of carcinogenic process

1, 2 - DMH

initiation induced by carcinogens

1, 2 - DMH

initiation of carcinogenic process

N - methyl - N - nitrosourea

initiation induced by carcinogens

N - methyl - N - nitrosourea

initiation of carcinogenic process


Input: Withdrawal - emergent rabbit syndrome during dose reduction of risperidone. Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal - emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal - emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin - dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.

Withdrawal - emergent rabbit syndrome

Withdrawal - emergent rabbit syndrome

emergent rabbit syndrome

Rabbit syndrome

RS

withdrawal - emergent RS

withdrawal - emergent RS

emergent RS

RS

withdrawal - emergent RS

withdrawal - emergent RS

emergent RS

RS

risperidone

risperidone

trihexyphenidyl

risperidone

serotonin

dopamine

serotonin

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

emergent rabbit syndrome

risperidone

Rabbit syndrome

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

emergent rabbit syndrome

risperidone

Rabbit syndrome

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

emergent rabbit syndrome

risperidone

Rabbit syndrome

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

withdrawal - emergent RS

risperidone

emergent RS

risperidone

RS

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

withdrawal - emergent RS

risperidone

withdrawal - emergent RS

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

withdrawal - emergent RS

risperidone

withdrawal - emergent RS

risperidone

Withdrawal - emergent rabbit syndrome

risperidone

withdrawal - emergent RS

risperidone

withdrawal - emergent RS


Input: Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram. Verapamil is an effective and relatively - safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta - blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil - related increase in platelet and / or vascular alpha 2 - adrenoreceptor affinity for catecholamines are discussed.

Verapamil

Verapamil

captopril

verapamil

verapamil

catecholamines

myocardial infarction

hypertensive

depression

myocardial infarction

hypertension

Verapamil

myocardial infarction

Verapamil

myocardial infarction

Verapamil

myocardial infarction

Verapamil

myocardial infarction

verapamil

myocardial infarction

verapamil

myocardial infarction

verapamil

myocardial infarction

verapamil

myocardial infarction


Input: Remission induction of meningeal leukemia with high - dose intravenous methotrexate. Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high - dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10 (- 5) mol / L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6, 000 mg / m2 for a period of one hour followed by an infusion of 1, 200 mg / m2 / h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg / m2 followed by 12 mg / m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10 (- 7) mol / L. The mean steady - state plasma and CSF methotrexate concentrations achieved were 1. 1 X 10 (- 3) mol / L and 3. 6 X 10 (- 5) mol / L, respectively. All 20 patients responded to this regimen, 16 / 20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High - dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.

meningeal leukemia

acute lymphoblastic leukemia

meningeal disease

toxicities

neutropenia

mucositis

seizures

transient hemiparesis

acute lymphoblastic leukemia

methotrexate

methotrexate

methotrexate

methotrexate

Leucovorin

methotrexate

methotrexate

bilirubin

methotrexate

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

transient hemiparesis

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

neutropenia

methotrexate

seizures

methotrexate

seizures

methotrexate

seizures

methotrexate

seizures

methotrexate

seizures

methotrexate

seizures

methotrexate

seizures

methotrexate

mucositis

methotrexate

mucositis

methotrexate

mucositis

methotrexate

mucositis

methotrexate

mucositis

methotrexate

mucositis

methotrexate

mucositis


Input: Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure. We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.

Hypersensitivity

leukemoid reaction

eosinophilia

erythroderma

renal failure

hypersensitivity

erythroderma

leukemoid reaction

eosinophilia

hyponatremia

renal failure

carbamazepine

carbamazepine

carbamazepine

carbamazepine

renal failure

carbamazepine

renal failure

carbamazepine

renal failure

carbamazepine

renal failure

carbamazepine

renal failure

carbamazepine

renal failure

carbamazepine

erythroderma

carbamazepine

erythroderma

carbamazepine

erythroderma

carbamazepine

erythroderma

carbamazepine

erythroderma

carbamazepine

erythroderma

carbamazepine

leukemoid reaction

carbamazepine

leukemoid reaction

carbamazepine

leukemoid reaction

carbamazepine

leukemoid reaction

carbamazepine

leukemoid reaction

carbamazepine

leukemoid reaction

carbamazepine

Hypersensitivity

carbamazepine

hypersensitivity

carbamazepine

Hypersensitivity

carbamazepine

hypersensitivity

carbamazepine

Hypersensitivity

carbamazepine

hypersensitivity

carbamazepine

hyponatremia

carbamazepine

hyponatremia

carbamazepine

hyponatremia


Input: The interpeduncular nucleus regulates nicotine' s effects on free - field activity. Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham - operated controls, lesions significantly (p < 0. 25) blunted the early (< 60 min) free - field locomotor hypoactivity caused by nicotine (0. 5 mg kg (- 1), i. m.), enhanced the later (60 - 120 min) nicotine - induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p < 0. 025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.

nicotine

kainic acid

nicotine

nicotine

choline

tyrosine

locomotor hypoactivity

hyperactivity

depression

nicotine

hyperactivity

nicotine

hyperactivity

nicotine

hyperactivity


Input: Assessment of a new non - invasive index of cardiac performance for detection of dobutamine - induced myocardial ischemia. BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine - induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP / dtejc) measurement, based on brachial artery flow changes, as compared to standard 12 - lead ECG, for detecting dobutamine - induced myocardial ischemia, using Tc99m - Sestamibi single - photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi - SPECT / dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP / dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP / dtejc during infusion of dobutamine in this group was severely impaired as compared to the non - ischemic group. dP / dtejc outcome was combined with the ECG results, giving an ECG - enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP / dtejc improved the sensitivity of the test and could be a cost - savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.

dobutamine

dobutamine

dobutamine

Tc99m - Sestamibi

Sestamibi

dobutamine

dobutamine

dobutamine

myocardial ischemia

myocardial ischemia

myocardial ischemia

ischemia

ischemia

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia

dobutamine

myocardial ischemia


Input: Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage. BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3 - 5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol / day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e. g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g / day in such patients and that their liver function should be monitored closely while being treated with paracetamol.

Acute liver failure

hepatotoxicity

liver failure

hepatotoxicity

liver failure

alcohol

paracetamol

alcohol

paracetamol

acetaminophen

alcohol

alcohol

paracetamol

paracetamol

paracetamol

alcohol

paracetamol

paracetamol

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

acetaminophen

hepatotoxicity

acetaminophen

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

hepatotoxicity

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

acetaminophen

liver failure

acetaminophen

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure

paracetamol

liver failure


Input: Cocaine related chest pain: are we seeing the tip of an iceberg? The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed.

Cocaine

cocaine

cocaine

cocaine

cocaine

cocaine

chest pain

chest pain

chest pain

chest pain

Cocaine

chest pain

Cocaine

chest pain

Cocaine

chest pain

Cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain

cocaine

chest pain


Input: Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir. OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72 - year - old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66, 680 U / L creatine kinase, 93 mg / dL blood urea nitrogen, 4. 6 mg / dL creatinine, 1579 U / L aspartate aminotransferase, and 738 U / L alanine aminotransferase. Simvastatin, amiodarone, and the patient' s human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient' s creatine kinase had dropped to 1695 U / L and creatinine was 3. 3 mg / dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.

rhabdomyolysis

acute renal failure

rhabdomyolysis

acute renal failure

human immunodeficiency virus

atrial fibrillation

coronary artery disease

hyperlipidemia

pain

fatigue

human immunodeficiency virus

rhabdomyolysis

simvastatin

amiodarone

atazanavir

simvastatin

amiodarone

atazanavir

simvastatin

amiodarone

atazanavir

creatine

blood urea nitrogen

creatinine

aspartate

alanine

Simvastatin

amiodarone

creatine

creatinine

simvastatin

Simvastatin

Amiodarone

atazanavir

statins

statins

pravastatin

fluvastatin

rosuvastatin

atorvastatin

simvastatin

lovastatin

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

amiodarone

acute renal failure

Amiodarone

acute renal failure

Amiodarone

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

atazanavir

acute renal failure

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

Simvastatin

rhabdomyolysis

statins

rhabdomyolysis

statins

rhabdomyolysis

statins

rhabdomyolysis

statins

rhabdomyolysis

statins

rhabdomyolysis

statins

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

rhabdomyolysis

simvastatin

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

Simvastatin

acute renal failure

Simvastatin

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

Simvastatin

acute renal failure

Simvastatin

acute renal failure

statins

acute renal failure

statins

acute renal failure

statins

acute renal failure

statins

acute renal failure

simvastatin

acute renal failure

simvastatin

acute renal failure

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

amiodarone

rhabdomyolysis

Amiodarone

rhabdomyolysis

Amiodarone

rhabdomyolysis

Amiodarone

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis

atazanavir

rhabdomyolysis


Input: Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group. PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty - six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin - based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25 - mg / m2 short intravenous (i. v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose - intensity (DI) was 20 mg / m2 / wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.

vinorelbine

vinorelbine

VNB

cisplatin

VNB

VNB

VNB

VNB

squamous cell esophageal carcinoma

Cancer

Cancer

squamous cell esophageal carcinoma

toxicity

toxicity

granulocytopenia

infection

deaths

peripheral neurotoxicity

esophageal squamous cell carcinoma

toxicity

vinorelbine

granulocytopenia

vinorelbine

granulocytopenia

VNB

granulocytopenia

VNB

granulocytopenia

VNB

granulocytopenia

VNB

granulocytopenia

VNB

granulocytopenia

vinorelbine

peripheral neurotoxicity

vinorelbine

peripheral neurotoxicity

VNB

peripheral neurotoxicity

VNB

peripheral neurotoxicity

VNB

peripheral neurotoxicity

VNB

peripheral neurotoxicity

VNB

peripheral neurotoxicity


Input: Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma. BACKGROUND: Cisplatin - based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty - five consecutive chemotherapy - naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 - 2 were treated with a combination of paclitaxel (135 mg / m (2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg / m (2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg / m (2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second - line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73. 5% of the patients (95% confidence interval [CI], 55. 6 - 87. 1%), including 4 complete responses (11. 7%). According to intention - to - treat, the overall response rate was 71. 4% (95% CI, 53. 7 - 85. 4%). After 154 courses of therapy, the median dose intensity was 131 mg / m (2) for paclitaxel (97. 3%), 117 mg / m (2) for cisplatin (97. 3%), and 1378 mg / m (2) for gemcitabine (86. 2%). World Health Organization Grade 3 - 4 neutropenia and thrombocytopenia occurred in 39. 9% and 11. 4% of patients, respectively. There was one treatment - related death. Nonhematologic toxicities were mild. After a median follow - up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin - based regimens.

Paclitaxel

cisplatin

gemcitabine

Cisplatin

paclitaxel

cisplatin

gemcitabine

paclitaxel

cisplatin

gemcitabine

paclitaxel

cisplatin

gemcitabine

paclitaxel

cisplatin

gemcitabine

cisplatin

nonsmall cell lung carcinoma

nonsmall cell lung carcinoma

NSCLC

toxicity

NSCLC

NSCLC

toxicity

toxicity

neutropenia

thrombocytopenia

death

toxicities

NSCLC

cisplatin

neutropenia

Cisplatin

neutropenia

cisplatin

neutropenia

cisplatin

neutropenia

cisplatin

neutropenia

cisplatin

neutropenia

cisplatin

neutropenia

Paclitaxel

thrombocytopenia

paclitaxel

thrombocytopenia

paclitaxel

thrombocytopenia

paclitaxel

thrombocytopenia

paclitaxel

thrombocytopenia

gemcitabine

neutropenia

gemcitabine

neutropenia

gemcitabine

neutropenia

gemcitabine

neutropenia

gemcitabine

neutropenia

Paclitaxel

neutropenia

paclitaxel

neutropenia

paclitaxel

neutropenia

paclitaxel

neutropenia

paclitaxel

neutropenia

gemcitabine

thrombocytopenia

gemcitabine

thrombocytopenia

gemcitabine

thrombocytopenia

gemcitabine

thrombocytopenia

gemcitabine

thrombocytopenia

cisplatin

thrombocytopenia

Cisplatin

thrombocytopenia

cisplatin

thrombocytopenia

cisplatin

thrombocytopenia

cisplatin

thrombocytopenia

cisplatin

thrombocytopenia

cisplatin

thrombocytopenia


Input: Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution. We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine - treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.

aponidine hydrochloride

apraclonidine

apraclonidine

apraclonidine

apraclonidine

ocular hypotensive

Decreases in systolic blood pressure

Conjunctival blanching

mydriasis

entropion

corneal abrasion

aponidine hydrochloride

ocular hypotensive

apraclonidine

ocular hypotensive

apraclonidine

ocular hypotensive

apraclonidine

ocular hypotensive

apraclonidine

ocular hypotensive

aponidine hydrochloride

mydriasis

apraclonidine

mydriasis

apraclonidine

mydriasis

apraclonidine

mydriasis

apraclonidine

mydriasis

aponidine hydrochloride

entropion

apraclonidine

entropion

apraclonidine

entropion

apraclonidine

entropion

apraclonidine

entropion

aponidine hydrochloride

corneal abrasion

apraclonidine

corneal abrasion

apraclonidine

corneal abrasion

apraclonidine

corneal abrasion

apraclonidine

corneal abrasion

aponidine hydrochloride

Conjunctival blanching

apraclonidine

Conjunctival blanching

apraclonidine

Conjunctival blanching

apraclonidine

Conjunctival blanching

apraclonidine

Conjunctival blanching


Input: Carmofur - induced organic mental disorders. Organic mental disorder was observed in a 29 - year - old female in the prognostic period after the onset of carmofur - induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM - III - R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur - induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.

Carmofur

carmofur

carmofur

organic mental disorders

Organic mental disorder

leukoencephalopathy

organic personality syndrome

frontal lobe syndrome

leukoencephalopathy

organic personality syndrome

structural damage to the frontal lobe

Carmofur

leukoencephalopathy

Carmofur

leukoencephalopathy

carmofur

leukoencephalopathy

carmofur

leukoencephalopathy

carmofur

leukoencephalopathy

carmofur

leukoencephalopathy

Carmofur

organic mental disorders

Carmofur

Organic mental disorder

carmofur

organic mental disorders

carmofur

Organic mental disorder

carmofur

organic mental disorders

carmofur

Organic mental disorder


Input: International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group. The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil - Perlongets) were evaluated in a double - blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7. 6%) than in the placebo group (4. 8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.

mexiletine

mexiletine

Mexitil - Perlongets

mexiletine

mexiletine

mexiletine

mexiletine

arrhythmia

myocardial infarction

deaths

tremor

gastrointestinal problems

mexiletine

tremor

mexiletine

tremor

Mexitil - Perlongets

tremor

mexiletine

tremor

mexiletine

tremor

mexiletine

tremor

mexiletine

tremor

mexiletine

gastrointestinal problems

mexiletine

gastrointestinal problems

Mexitil - Perlongets

gastrointestinal problems

mexiletine

gastrointestinal problems

mexiletine

gastrointestinal problems

mexiletine

gastrointestinal problems

mexiletine

gastrointestinal problems


Input: Regional localization of the antagonism of amphetamine - induced hyperactivity by intracerebral calcitonin injections. Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine - induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine - induced locomotor activity.

amphetamine

calcitonin

Calcitonin

calcitonin

amphetamine

calcitonin

calcitonin

calcitonin

calcitonin

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity


Input: Fatal intracranial bleeding associated with prehospital use of epinephrine. We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.

intracranial bleeding

allergic reaction

pulmonary edema

wheezing

respiratory distress

rash

cardiac arrest

subarachnoid hemorrhage

cardiac arrest

allergic reaction

hypertension

epinephrine

epinephrine

Epinephrine

epinephrine

intracranial bleeding

epinephrine

subarachnoid hemorrhage

epinephrine

intracranial bleeding

epinephrine

subarachnoid hemorrhage

Epinephrine

intracranial bleeding

Epinephrine

subarachnoid hemorrhage

epinephrine

cardiac arrest

epinephrine

cardiac arrest

epinephrine

cardiac arrest

epinephrine

cardiac arrest

Epinephrine

cardiac arrest

Epinephrine

cardiac arrest


Input: A case of massive rhabdomyolysis following molindone administration. Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.

rhabdomyolysis

Rhabdomyolysis

psychiatric

rhabdomyolysis

schizophrenic

rhabdomyolysis

acute renal failure

molindone

molindone

molindone

molindone

rhabdomyolysis

molindone

Rhabdomyolysis

molindone

rhabdomyolysis

molindone

rhabdomyolysis

molindone

rhabdomyolysis

molindone

Rhabdomyolysis

molindone

rhabdomyolysis

molindone

rhabdomyolysis

molindone

rhabdomyolysis

molindone

Rhabdomyolysis

molindone

rhabdomyolysis

molindone

rhabdomyolysis

molindone

acute renal failure

molindone

acute renal failure

molindone

acute renal failure


Input: Cardiovascular alterations in rat fetuses exposed to calcium channel blockers. Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40 - 5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40 - 5967 and verapamil.

Cardiovascular alterations

cardiovascular alterations

cardiovascular malformations

cardiovascular malformations

cardiovascular malformations

calcium

calcium

Ro 40 - 5967

calcium

calcium

nifedipine

diltiazem

verapamil

calcium

calcium

verapamil

nifedipine

Ro 40 - 5967

verapamil

verapamil

Cardiovascular alterations

verapamil

cardiovascular alterations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

verapamil

Cardiovascular alterations

verapamil

cardiovascular alterations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

verapamil

Cardiovascular alterations

verapamil

cardiovascular alterations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

verapamil

cardiovascular malformations

nifedipine

Cardiovascular alterations

nifedipine

cardiovascular alterations

nifedipine

cardiovascular malformations

nifedipine

cardiovascular malformations

nifedipine

cardiovascular malformations

nifedipine

Cardiovascular alterations

nifedipine

cardiovascular alterations

nifedipine

cardiovascular malformations

nifedipine

cardiovascular malformations

nifedipine

cardiovascular malformations

Ro 40 - 5967

Cardiovascular alterations

Ro 40 - 5967

cardiovascular alterations

Ro 40 - 5967

cardiovascular malformations

Ro 40 - 5967

cardiovascular malformations

Ro 40 - 5967

cardiovascular malformations

Ro 40 - 5967

Cardiovascular alterations

Ro 40 - 5967

cardiovascular alterations

Ro 40 - 5967

cardiovascular malformations

Ro 40 - 5967

cardiovascular malformations

Ro 40 - 5967

cardiovascular malformations


Input: Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine - resistant hepatitis B virus e antigen - positive and - negative strains. Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment - associated mutants with resistance to lamivudine (LAM) and / or HBeAg negativity. Replication - competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M / rtM204V) were generated on an HBeAg - positive and an HBeAg - negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM - resistant HBV mutants to the levels of wild - type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM - resistant clones. However, the concomitant occurrence of HBeAg negativity (PC / BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild - type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.

lamivudine

hepatitis B virus e antigen

lamivudine

LAM

HBeAg

LAM

HBeAg

HBeAg

HBsAg

LAM

HBsAg

LAM

HBeAg

LAM

LAM

nucleotide

adefovir

tenofovir

hepatitis B

HBsAg

hepatitis B

HBsAg

hepatitis B

hepatitis B virus e antigen

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B

HBeAg

hepatitis B


Input: The effects of sevoflurane on lidocaine - induced convulsions. The influence of sevoflurane on lidocaine - induced convulsions was studied in cats. The convulsive threshold (mean + / - SD) was 41. 4 + / - 6. 5 mg. l (- 1) with lidocaine infusion (6 mg. kg (- 1). min (- 1)), increasing significantly to 66. 6 + / - 10. 9 mg. l (- 1) when the end - tidal concentration of sevoflurane was 0. 8%. However, the threshold (61. 6 + / - 8. 7 mg. l (- 1)) during 1. 6% sevoflurane was not significant from that during 0. 8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1. 6% sevoflurane, and in 0. 8% and 1. 6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium - dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0. 8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21. 6 + / - 2. 2 to 19. 9 + / - 2. 5 mg. l (- 1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.

sevoflurane

lidocaine

sevoflurane

lidocaine

lidocaine

sevoflurane

sevoflurane

sevoflurane

sevoflurane

enflurane

sevoflurane

enflurane

sevoflurane

enflurane

lidocaine

Apamin

calcium

potassium

sevoflurane

Apamin

sevoflurane

lidocaine

convulsions

convulsions

convulsive

convulsive

convulsions

convulsive

convulsive

toxicity

depression

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive

lidocaine

convulsions

lidocaine

convulsive

lidocaine

convulsive


Input: Anti - oxidant effects of atorvastatin in dexamethasone - induced hypertension in the rat. 1. Dexamethasone (Dex) - induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2 -) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2 - production in various forms of hypertension. In the present study, we investigated whether 50 mg / kg per day, p. o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2 - in Sprague - Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg / kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg / kg per day, s. c.) or saline was started after 4 days in Ato - treated and non - treated rats and continued for 11 - 13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail - cuff method. Endothelial function was assessed by acetylcholine - induced vasorelaxation and phenylephrine - induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi - quantitative reverse transcription - polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 + / - 2 to 133 + / - 2 mmHg on Days 4 and Day 14, respectively (P < 0. 001). In the Ato + Dex group, SBP was increased from 113 + / - 2 to 119 + / - 2 mmHg on Days 4 to 14, respectively (P < 0. 001), but was significantly lower than SBP in the group treated with Dex alone (P < 0. 05). Endothelial - dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0. 05 and P < 0. 0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0. 0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex - treated SD rats.

atorvastatin

dexamethasone

Dexamethasone

Dex

nitric oxide

NO

superoxide

O2 -

Atorvastatin

Ato

NO

O2 -

Ato

NO

O2 -

Ato

Dexamethasone

Ato

acetylcholine

phenylephrine

Dex

Ato

Dex

Dex

Dex

Ato

Dex

superoxide

Dex

Ato

Dex

Ato

superoxide

Dex

hypertension

hypertension

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dexamethasone

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension

Dex

hypertension


Input: 99mTc - glucarate for detection of isoproterenol - induced myocardial infarction in rats. Infarct - avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct - avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc - glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol - induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc - glucarate administration the standardised heart uptake value S (h) UV was 4. 7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4. 4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.

99mTc - glucarate

isoproterenol

isoproterenol

glucaric acid

99mTc - glucarate

isoproterenol

isoproterenol

99mTc - glucarate

myocardial infarction

Infarct

myocardial infarction

infarction

infarct

myocardial infarction

infarct

cardiac infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

cardiac infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

cardiac infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

cardiac infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

cardiac infarction


Input: A randomized, placebo - controlled dose - comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer' s disease. OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer' s disease. METHOD: In a 6 - week random - assignment, double - blind, placebo - controlled trial (phase A), haloperidol, 2 - 3 mg / day (standard dose), and haloperidol, 0. 50 - 0. 75 mg / day (low dose), were compared in 71 outpatients with Alzheimer' s disease. For the subsequent 6 - week double - blind crossover phase (phase B), patients taking standard - or low - dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard - or low - dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard - dose haloperidol was efficacious and superior to both low - dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55% - 60%) than the low dose (25% - 35%) and placebo (25% - 30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low - dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2 - 3 mg / day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg / day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer' s disease patients with psychosis and disruptive behaviors.

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

haloperidol

psychosis

disruptive behaviors

Alzheimer' s disease

psychosis

disruptive behaviors

Alzheimer' s disease

Alzheimer' s disease

psychosis

psychomotor agitation

extrapyramidal signs

extrapyramidal signs

Alzheimer' s disease

psychosis

disruptive behaviors

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs

haloperidol

extrapyramidal signs


Input: Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin - induced renal damage. BACKGROUND: In man, differences in angiotensin - converting enzyme (ACE) levels, related to ACE (I / D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip - His - Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1. 5 mg / kg intravenously (i. v.) n = 18; controls, saline i. v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0. 62, P < 0. 01), renal interstitial alpha - smooth muscle actin (r = 0. 49, P < 0. 05), interstitial macrophage influx (r = 0. 56, P < 0. 05), interstitial collagen III (r = 0. 53, P < 0. 05), glomerular alpha - smooth muscle actin (r = 0. 74, P < 0. 01) and glomerular desmin (r = 0. 48, P < 0. 05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0. 22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin - induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.

adriamycin

angiotensin

adriamycin

Hip - His - Leu

adriamycin

adriamycin

adriamycin

adriamycin

renal damage

renal damage

proteinuria

Proteinuria

nephrotic

proteinuria

renal interstitial damage

focal glomerulosclerosis

proteinuria

focal glomerulosclerosis

renal damage

renal damage

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

proteinuria

adriamycin

Proteinuria

adriamycin

proteinuria

adriamycin

proteinuria


Input: Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study. Nearly 3. 2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg / kg / day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside - related renal failure, defined as at least a one - third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin - treated patients and 16 of 29 (55. 2%) of the gentamicin - treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.

nephrotoxicity

ototoxicity

nephrotoxicity

renal failure

renal failure

renal failure

renal failure

tobramycin

gentamicin

aminoglycoside

Gentamicin sulfate

tobramycin sulfate

gentamicin sulfate

tobramycin sulfate

aminoglycoside

tobramycin

gentamicin

gentamicin

tobramycin

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

Gentamicin sulfate

renal failure

Gentamicin sulfate

renal failure

Gentamicin sulfate

renal failure

Gentamicin sulfate

renal failure

gentamicin sulfate

renal failure

gentamicin sulfate

renal failure

gentamicin sulfate

renal failure

gentamicin sulfate

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

gentamicin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin sulfate

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure

tobramycin

renal failure


Input: Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine - induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats. The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg / kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2 - methyl - 6 - (phenylethynyl) pyridine (MPEP; 5 mg / kg ip), when administered five times immediately before each methamphetamine injection reversed the above - mentioned methamphetamine effects. A single MPEP (5 mg / kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg / kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg / kg sc) - induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50 - 100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine - induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine - induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.

MPEP

methamphetamine

dopamine

glutamate

methamphetamine

Methamphetamine

dopamine

2 - methyl - 6 - (phenylethynyl) pyridine

MPEP

methamphetamine

methamphetamine

MPEP

dopamine

dopamine

methamphetamine

veratridine

methamphetamine

MPEP

dopamine

MPEP

methamphetamine

MPEP

methamphetamine

dopamine

neurotoxicity

hyperthermia

hyperthermia

toxicity

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

Methamphetamine

hyperthermia

Methamphetamine

hyperthermia

Methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia


Input: Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open - label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C (max) of desipramine increased 3. 6 - and 1. 8 - fold when coadministered with cinacalcet. The t (1 / 2, z) of desipramine was longer when desipramine was coadministered with cinacalcet (21. 0 versus 43. 3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.

desipramine HCl

cinacalcet HCl

cinacalcet

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

cinacalcet

cinacalcet

cinacalcet

nausea

headache

desipramine HCl

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

cinacalcet HCl

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

desipramine HCl

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

cinacalcet HCl

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea


Input: Proteomic analysis of striatal proteins in the rat model of L - DOPA - induced dyskinesia. L - DOPA - induced dyskinesia (LID) is among the motor complications that arise in Parkinson' s disease (PD) patients after a prolonged treatment with L - DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6 - hydroxydopamine - lesion rat model of PD treated with saline, L - DOPA or bromocriptine using two - dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L - DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix - assisted laser desorption / ionization time - of - flight MS, atmospheric pressure matrix - assisted laser desorption / ionization and HPLC coupled tandem MS (LC / MS / MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta - crystalin, gamma - enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha - 2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.

L - DOPA

L - DOPA

L - DOPA

6 - hydroxydopamine

L - DOPA

bromocriptine

L - DOPA

dyskinesia

dyskinesia

LID

Parkinson' s disease

PD

LID

PD

LID

LID

LID

L - DOPA

dyskinesia

L - DOPA

dyskinesia

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

dyskinesia

L - DOPA

dyskinesia

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

dyskinesia

L - DOPA

dyskinesia

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

dyskinesia

L - DOPA

dyskinesia

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

dyskinesia

L - DOPA

dyskinesia

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID

L - DOPA

LID