Input: Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain. In acute pain models, N - methyl - D - aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail - withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail - withdrawal procedures. In males, the non - competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose - and time - dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually - dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.

NMDA

morphine

capsaicin

N - methyl - D - aspartate

NMDA

morphine

capsaicin

NMDA

dextromethorphan

morphine

morphine

dextromethorphan

NMDA

morphine

pain

acute pain

acute pain

pain

acute pain

hyperalgesia

acute pain

acute pain

pain

acute pain

capsaicin

hyperalgesia

capsaicin

hyperalgesia


Input: Development of proteinuria after switch to sirolimus - based immunosuppression in long - term cardiac transplant patients. Calcineurin - inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long - term cardiac transplant patients were switched from cyclosporine to Srl - based IS. Concomitant IS consisted of mycophenolate mofetil + / - steroids. Proteinuria increased significantly from a median of 0. 13 g / day (range 0 - 5. 7) preswitch to 0. 23 g / day (0 - 9. 88) at 24 months postswitch (p = 0. 0024). Before the switch, 11. 5% of patients had high - grade proteinuria (> 1. 0 g / day); this increased to 22. 9% postswitch (p = 0. 006). ACE inhibitor and angiotensin - releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42. 5 vs. 64. 1, p = 0. 25), whereas patients who developed high - grade proteinuria showed decreased renal function at the end of follow - up (median 39. 6 vs. 29. 2, p = 0. 125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi / ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

proteinuria

renal dysfunction

nephrotoxic

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

renal dysfunction

sirolimus

sirolmus

Srl

Srl

Srl

cyclosporine

Srl

mycophenolate mofetil

steroids

ACE inhibitor

angiotensin - releasing blocker

ARB

Srl

Srl

ACEi

ARB

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

sirolmus

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria

Srl

proteinuria


Input: Synthesis of N - pyrimidinyl - 2 - phenoxyacetamides as adenosine A2A receptor antagonists. A series of N - pyrimidinyl - 2 - phenoxyacetamide adenosine A (2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K (i) = 0. 4 nM), selectivity (A (1) / A (2A) > 100), and efficacy (MED 10 mg / kg p. o.) in the rat haloperidol - induced catalepsy model for Parkinson' s disease.

N - pyrimidinyl - 2 - phenoxyacetamides

adenosine

N - pyrimidinyl - 2 - phenoxyacetamide

adenosine

haloperidol

catalepsy

Parkinson' s disease

haloperidol

catalepsy


Input: Methamphetamine - induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial - specific fractalkine receptor (CX3CR1) as an important mediator of MPTP - induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH - induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild - type controls. The effects of METH in CX3CR1 knockout mice were not gender - dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP - microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal - resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.

Methamphetamine

Methamphetamine

METH

dopamine

DA

MPTP

DA

METH

MPTP

DA

METH

METH

METH

DA

METH

METH

METH

METH

METH

neurotoxicity

neurodegeneration

CNS damage

neurotoxicity

neurotoxicity

neurotoxicity

neurotoxicity

Methamphetamine

neurodegeneration

Methamphetamine

CNS damage

Methamphetamine

neurodegeneration

Methamphetamine

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

METH

neurodegeneration

METH

CNS damage

MPTP

neurodegeneration

MPTP

CNS damage

MPTP

neurodegeneration

MPTP

CNS damage


Input: Recovery of tacrolimus - associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient - - case report and review of the literature. TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight - and - a - half - yr - old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.

tacrolimus

everolimus

TAC

TAC

methylprednisolone

TAC

everolimus

brachial neuritis

Neurotoxicity

encephalopathy

headaches

seizures

neurological deficits

myelitis

brachial plexitis

tacrolimus

brachial neuritis

tacrolimus

brachial plexitis

TAC

brachial neuritis

TAC

brachial plexitis

TAC

brachial neuritis

TAC

brachial plexitis

TAC

brachial neuritis

TAC

brachial plexitis


Input: Valvular heart disease in patients with Parkinson' s disease treated with pergolide. Course following treatment modifications. Valvular heart abnormalities have been reported in patients with Parkinson' s disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case - control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n = 10 patients). Controls were age - and sex - matched non - PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3. 1; 95% IC: 1. 1 - 8. 8) and mitral regurgitation (OR: 10. 7; 95% IC: 2. 1 - 53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n = 2. 4 + / - 0. 7) and the sum of regurgitation grades (n = 2. 8 + / - 1. 09) were higher (p = 0. 008 and p = 0. 006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12 / 30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p = 0. 01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non - ergot dopamine agonists.

Valvular heart disease

Parkinson' s disease

Valvular heart abnormalities

Parkinson' s disease

PD

valvular heart abnormality

PD

PD

PD

aortic regurgitation

mitral regurgitation

PD

valvular regurgitation

heart failure

valvular heart disease

heart failure

valve regurgitation

PD

pergolide

pergolide

pergolide

pergolide

pergolide

pergolide

pergolide

Pergolide

pergolide

dopamine

pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

aortic regurgitation

Pergolide

aortic regurgitation

pergolide

aortic regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

pergolide

mitral regurgitation

Pergolide

mitral regurgitation

pergolide

mitral regurgitation


Input: Adverse effects of topical papaverine on auditory nerve function. BACKGROUND: Papaverine hydrochloride is a direct - acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II / III - V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre - papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.

papaverine

Papaverine hydrochloride

papaverine

papaverine

papaverine

papaverine

papaverine

papaverine

papaverine

papaverine

papaverine

papaverine

vasospasm

cranial nerve dysfunction

vasospasm

vasospasm

sensorineural hearing loss

vasospasm

adverse effect on the proximal eighth nerve

cranial nerve deficits

papaverine

adverse effect on the proximal eighth nerve

Papaverine hydrochloride

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

adverse effect on the proximal eighth nerve

papaverine

sensorineural hearing loss

Papaverine hydrochloride

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss

papaverine

sensorineural hearing loss


Input: Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis. A 61 - year - old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15. 6 to 2. 8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12. 8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.

proteinuria

acute renal failure

focal segmental glomerulosclerosis

nephrotic syndrome

focal segmental glomerulosclerosis

acute renal failure

proteinuria

acute renal failure

bisphosphonate

alendronate

steroid

bisphosphonate

alendronate sodium

alendronate

creatinine

bisphosphonates

alendronate

acute renal failure

alendronate

acute renal failure

alendronate

acute renal failure

alendronate sodium

acute renal failure

alendronate sodium

acute renal failure

alendronate sodium

acute renal failure

alendronate

acute renal failure

alendronate

acute renal failure

alendronate

acute renal failure

alendronate

proteinuria

alendronate

proteinuria

alendronate sodium

proteinuria

alendronate sodium

proteinuria

alendronate

proteinuria

alendronate

proteinuria


Input: Serum - and glucocorticoid - inducible kinase 1 in doxorubicin - induced nephrotic syndrome. Doxorubicin - induced nephropathy leads to epithelial sodium channel (ENaC) - dependent volume retention and renal fibrosis. The aldosterone - sensitive serum - and glucocorticoid - inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug / g body wt) was injected intravenously into gene - targeted mice lacking SGK1 (sgk1 (- / -)) and their wild - type littermates (sgk1 (+ / +)). Doxorubicin treatment resulted in heavy proteinuria (> 100 mg protein / mg crea) in 15 / 44 of sgk1 (+ / +) and 15 / 44 of sgk1 (- / -) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1 (+ / +) mice. Urinary sodium excretion reached signficantly lower values in sgk1 (+ / +) mice (15 + / - 5 mumol / mg crea) than in sgk1 (- / -) mice (35 + / - 5 mumol / mg crea) and was associated with a significantly higher body weight gain in sgk1 (+ / +) compared with sgk1 (- / -) mice (+ 6. 6 + / - 0. 7 vs. + 4. 1 + / - 0. 8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1 (- / -) mice than in sgk1 (+ / +) mice leading to uremia and a reduced median survival in sgk1 (- / -) mice (29 vs. 40 days in sgk1 (+ / +) mice). In conclusion, gene - targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.

doxorubicin

Doxorubicin

sodium

aldosterone

doxorubicin

Doxorubicin

aldosterone

sodium

urea

nephrotic syndrome

nephropathy

volume retention

fibrosis

fibrosis

volume retention

fibrosis

nephrotic syndrome

proteinuria

nephrotic syndrome

ascites

lipidemia

hypoalbuminemia

nephrotic

weight gain

nephrotic syndrome

uremia

volume retention

fibrosis

nephrotic syndrome

doxorubicin

ascites

Doxorubicin

ascites

doxorubicin

ascites

Doxorubicin

ascites

doxorubicin

lipidemia

Doxorubicin

lipidemia

doxorubicin

lipidemia

Doxorubicin

lipidemia

doxorubicin

proteinuria

Doxorubicin

proteinuria

doxorubicin

proteinuria

Doxorubicin

proteinuria

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic

doxorubicin

nephrotic syndrome

doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic

Doxorubicin

nephrotic syndrome

Doxorubicin

nephrotic syndrome

doxorubicin

hypoalbuminemia

Doxorubicin

hypoalbuminemia

doxorubicin

hypoalbuminemia

Doxorubicin

hypoalbuminemia


Input: Severe and long lasting cholestasis after high - dose co - trimoxazole treatment for Pneumocystis pneumonia in HIV - infected patients - - a report of two cases. Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV - infected individuals, is generally treated with high doses of co - trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV - infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co - trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co - trimoxazole treatment, therapy of patient 2 was switched early.

cholestasis

Pneumocystis pneumonia

HIV - infected

Pneumocystis pneumonia

PCP

opportunistic infection

HIV - infected

HIV - infected

intrahepatic cholestasis

liver abscess

PCP

co - trimoxazole

co - trimoxazole

co - trimoxazole

co - trimoxazole

co - trimoxazole

intrahepatic cholestasis

co - trimoxazole

intrahepatic cholestasis

co - trimoxazole

intrahepatic cholestasis

co - trimoxazole

intrahepatic cholestasis


Input: Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients. BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI) - based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999 - 2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein: creatinine ratios, an estimate of grams of proteinuria / day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty - eight patients (24%) developed increased proteinuria from baseline during their post - transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic - range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre - existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.

proteinuria

nephrotoxicity

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

proteinuria

nephrotic

proteinuria

Proteinuria

proteinuria

proteinuria

Proteinuria

sirolimus

Sirolimus

sirolimus

sirolimus

sirolimus

sirolimus

sirolimus

creatinine

sirolimus

sirolimus

sirolimus

sirolimus

Sirolimus

sirolimus

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

Proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

Proteinuria

Sirolimus

proteinuria

Sirolimus

proteinuria

Sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria

sirolimus

proteinuria

sirolimus

proteinuria

sirolimus

Proteinuria


Input: Comparative cognitive and subjective side effects of immediate - release oxycodone in healthy middle - aged and older adults. This study measured the objective and subjective neurocognitive effects of a single 10 - mg dose of immediate - release oxycodone in healthy, older (> 65 years), and middle - aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy - one participants completed 2 separate study days and were blind to medication condition (placebo, 10 - mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P <. 01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P <. 01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age - interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10 - mg dose of immediate - release oxycodone are similar to those observed for middle - aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle - aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.

oxycodone

oxycodone

oxycodone

oxycodone

oxycodone

oxycodone

pain

declines in simple and sustained attention, working memory, and verbal memory

declines in simple and sustained attention

declines in simple and sustained attention, working memory, and verbal memory

chronic pain

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention, working memory, and verbal memory

oxycodone

declines in simple and sustained attention

oxycodone

declines in simple and sustained attention

oxycodone

declines in simple and sustained attention

oxycodone

declines in simple and sustained attention

oxycodone

declines in simple and sustained attention

oxycodone

declines in simple and sustained attention


Input: Normalizing effects of modafinil on sleep in chronic cocaine users. OBJECTIVE: The purpose of the present study was to determine the effect of morning - dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine - dependent participants were randomly assigned to receive modafinil, 400 mg (N = 10), or placebo (N = 10) every morning at 7: 30 a. m. for 16 days in an inpatient, double - blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11: 30 a. m., 2: 00 p. m., and 4: 30 p. m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow - wave sleep time in cocaine - dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow - wave sleep time, total sleep time, and sleep latency in cocaine - dependent and healthy participants revealed a normalizing effect of modafinil in cocaine - dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning - dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.

modafinil

cocaine

modafinil

cocaine

cocaine

modafinil

cocaine

modafinil

cocaine

modafinil

cocaine

modafinil

cocaine

Modafinil

modafinil

cocaine

cocaine

daytime sleepiness

daytime sleepiness

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness

cocaine

daytime sleepiness


Input: Efficacy and safety of asenapine in a placebo - and haloperidol - controlled trial in patients with acute exacerbation of schizophrenia. Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double - blind 6 - week trial, 458 patients with acute schizophrenia were randomly assigned to fixed - dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (- 16. 2) and haloperidol (- 15. 4) than placebo (- 10. 7; both P < 0. 05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (- 21. 3 and - 19. 4, respectively) and haloperidol (- 20. 0) than placebo (- 14. 6; all P < 0. 05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment - related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.

asenapine

haloperidol

Asenapine

asenapine

asenapine

haloperidol

asenapine

haloperidol

asenapine

haloperidol

asenapine

asenapine

haloperidol

asenapine

haloperidol

asenapine

haloperidol

schizophrenia

schizophrenia

manic

bipolar I disorder

psychotic

schizophrenia

Extrapyramidal symptoms

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

Asenapine

Extrapyramidal symptoms

Asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms

asenapine

Extrapyramidal symptoms

asenapine

extrapyramidal symptoms


Input: Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis. BACKGROUND / AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte - associated molecules nephrin, a - actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a - actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a - actinin was unchanged.

puromycin aminonucleoside

puromycin aminonucleoside

nephrosis

proteinuria

nephrosis

proteinuria

proteinuria

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

proteinuria

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis

puromycin aminonucleoside

nephrosis


Input: Twin preterm neonates with cardiac toxicity related to lopinavir / ritonavir therapy. We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir / ritonavir therapy, a boosted protease - inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir / ritonavir in the immediate neonatal period.

cardiac toxicity

human immunodeficiency virus infection

heart block

dilated cardiomyopathy

bradycardia

lopinavir / ritonavir

lopinavir / ritonavir

lopinavir / ritonavir

lopinavir / ritonavir

dilated cardiomyopathy

lopinavir / ritonavir

dilated cardiomyopathy

lopinavir / ritonavir

dilated cardiomyopathy

lopinavir / ritonavir

heart block

lopinavir / ritonavir

heart block

lopinavir / ritonavir

heart block

lopinavir / ritonavir

bradycardia

lopinavir / ritonavir

bradycardia

lopinavir / ritonavir

bradycardia


Input: Learning of rats under amnesia caused by pentobarbital. Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg / kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain - dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.

amnesia

amnesia

memory dissociation

pentobarbital

pentobarbital

pentobarbital

pentobarbital

pentobarbital

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia

pentobarbital

amnesia


Input: Angiosarcoma of the liver associated with diethylstilbestrol. Angiosarcoma of the liver occurred in a 76 - year - old man who had been treated for a well - differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.

Angiosarcoma of the liver

Angiosarcoma

Angiosarcoma of the liver

Angiosarcoma of the liver

Angiosarcoma

Angiosarcoma of the liver

adenocarcinoma of the liver

adenocarcinoma

adenocarcinoma of the liver

Angiosarcoma

intraarterial lesions

tumors

diethylstilbestrol

diethylstilbestrol

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

adenocarcinoma of the liver

diethylstilbestrol

adenocarcinoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

Angiosarcoma of the liver

diethylstilbestrol

adenocarcinoma of the liver

diethylstilbestrol

adenocarcinoma of the liver

diethylstilbestrol

Angiosarcoma

diethylstilbestrol

Angiosarcoma

diethylstilbestrol

Angiosarcoma

diethylstilbestrol

Angiosarcoma

diethylstilbestrol

Angiosarcoma

diethylstilbestrol

Angiosarcoma


Input: Role of xanthine oxidase in dexamethasone - induced hypertension in rats. 1. Glucocorticoid - induced hypertension (GC - HT) in the rat is associated with nitric oxide - redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone - induced hypertension (dex - HT). 3. Thirty male Sprague - Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 + / - 2 - 126 + / - 3 mmHg; P < 0. 001) and decreased thymus (P < 0. 001) and bodyweights (P " < 0. 01). Allopurinol decreased serum urate from 76 + / - 5 to 30 + / - 3 micromol / L (P < 0. 001) in saline and from 84 + / - 13 to 28 + / - 2 micromol / L in dex - treated (P < 0. 01) groups. 6. Allopurinol did not prevent dex - HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC - HT in the rat.

xanthine

dexamethasone

nitric oxide

xanthine

dexamethasone

dex

dexamethasone

dex

allopurinol

allopurinol

dex

urate

Dex

Allopurinol

urate

dex

Allopurinol

dex

allopurinol

hypertension

hypertension

HT

hypertension

HT

increased SBP

decreased thymus (P < 0. 001) and bodyweights

HT

hypertension

HT

dexamethasone

decreased thymus (P < 0. 001) and bodyweights

dexamethasone

decreased thymus (P < 0. 001) and bodyweights

dex

decreased thymus (P < 0. 001) and bodyweights

dexamethasone

decreased thymus (P < 0. 001) and bodyweights

dex

decreased thymus (P < 0. 001) and bodyweights

dex

decreased thymus (P < 0. 001) and bodyweights

Dex

decreased thymus (P < 0. 001) and bodyweights

dex

decreased thymus (P < 0. 001) and bodyweights

dex

decreased thymus (P < 0. 001) and bodyweights

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

increased SBP

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

increased SBP

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dex

hypertension

dex

hypertension

dex

HT

dex

hypertension

dex

HT

dex

increased SBP

dex

HT

dex

hypertension

dex

HT

dexamethasone

hypertension

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dexamethasone

increased SBP

dexamethasone

HT

dexamethasone

hypertension

dexamethasone

HT

dex

hypertension

dex

hypertension

dex

HT

dex

hypertension

dex

HT

dex

increased SBP

dex

HT

dex

hypertension

dex

HT

dex

hypertension

dex

hypertension

dex

HT

dex

hypertension

dex

HT

dex

increased SBP

dex

HT

dex

hypertension

dex

HT

Dex

hypertension

Dex

hypertension

Dex

HT

Dex

hypertension

Dex

HT

Dex

increased SBP

Dex

HT

Dex

hypertension

Dex

HT

dex

hypertension

dex

hypertension

dex

HT

dex

hypertension

dex

HT

dex

increased SBP

dex

HT

dex

hypertension

dex

HT

dex

hypertension

dex

hypertension

dex

HT

dex

hypertension

dex

HT

dex

increased SBP

dex

HT

dex

hypertension

dex

HT


Input: Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5 - HT2 receptors. Previous clinical studies have proposed that risperidone' s pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so - called' atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I] IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug - induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5 - HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.

risperidone

haloperidol

Risperidone

dopamine

serotonin 5 - HT2

risperidone

risperidone

risperidone

haloperidol

risperidone

haloperidol

haloperidol

risperidone

risperidone

haloperidol

risperidone

psychotic symptoms

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

Risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

risperidone

Drug - induced parkinsonism

haloperidol

Drug - induced parkinsonism

haloperidol

Drug - induced parkinsonism

haloperidol

Drug - induced parkinsonism

haloperidol

Drug - induced parkinsonism

haloperidol

Drug - induced parkinsonism


Input: Simvastatin - ezetimibe - induced hepatic failure necessitating liver transplantation. Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3 - hydroxy - 3 - methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin - ezetimibe. We describe a 70 - year - old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg / day to simvastatin 10 mg - ezetimibe 40 mg / day. The patient' s lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work - up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work - up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate - to - severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2 - year follow - up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin - ezetimibe - induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe - induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin - ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.

Simvastatin - ezetimibe

statin

ezetimibe

simvastatin - ezetimibe

simvastatin

simvastatin 10 mg - ezetimibe 40 mg

simvastatin

Simvastatinezetimibe

escitalopram

Ezetimibe

uridine diphosphate

simvastatin hydroxy acid

simvastatin

simvastatin - ezetimibe

simvastatinezetimibe

simvastatin

ezetimibe

simvastatin - ezetimibe

hepatic failure

hepatotoxic

fulminant hepatic failure

hepatotoxicity

depression

hepatotoxicity

drug toxicity

hepatotoxicity

liver failure

hepatotoxicity

hepatotoxicity

Simvastatin - ezetimibe

hepatotoxic

Simvastatin - ezetimibe

hepatotoxicity

Simvastatin - ezetimibe

hepatotoxicity

Simvastatin - ezetimibe

hepatotoxicity

Simvastatin - ezetimibe

hepatotoxicity

Simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxic

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxic

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxicity

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxicity

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxicity

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxicity

simvastatin 10 mg - ezetimibe 40 mg

hepatotoxicity

Simvastatinezetimibe

hepatotoxic

Simvastatinezetimibe

hepatotoxicity

Simvastatinezetimibe

hepatotoxicity

Simvastatinezetimibe

hepatotoxicity

Simvastatinezetimibe

hepatotoxicity

Simvastatinezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxic

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatinezetimibe

hepatotoxic

simvastatinezetimibe

hepatotoxicity

simvastatinezetimibe

hepatotoxicity

simvastatinezetimibe

hepatotoxicity

simvastatinezetimibe

hepatotoxicity

simvastatinezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxic

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

simvastatin - ezetimibe

hepatotoxicity

Simvastatin - ezetimibe

fulminant hepatic failure

simvastatin - ezetimibe

fulminant hepatic failure

simvastatin 10 mg - ezetimibe 40 mg

fulminant hepatic failure

Simvastatinezetimibe

fulminant hepatic failure

simvastatin - ezetimibe

fulminant hepatic failure

simvastatinezetimibe

fulminant hepatic failure

simvastatin - ezetimibe

fulminant hepatic failure


Input: Oral manifestations of " meth mouth ": a case report. AIM: The aim of the documentation of this clinical case is to make clinicians aware of " meth mouth " and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (" meth mouth "), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30 - year - old Caucasian woman presented with dental pain, bad breath, and self - reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient' s medical and dental histories along with radiographic and clinical findings lead to a diagnosis of " meth mouth. " Although three different dental treatment modalities (either conventional or implant - supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.

meth mouth

meth mouth

cardiac dysrhythmias

hypertension

hallucinations

violent behavior

xerostomia

caries

meth mouth

tooth wear

pain

bad breath

carious lesions

carious episodes

meth mouth

meth mouth

Methamphetamine

methamphetamine

methamphetamine

methamphetamine

methamphetamines

Methamphetamine

caries

Methamphetamine

carious lesions

Methamphetamine

carious episodes

methamphetamine

caries

methamphetamine

carious lesions

methamphetamine

carious episodes

methamphetamine

caries

methamphetamine

carious lesions

methamphetamine

carious episodes

methamphetamine

caries

methamphetamine

carious lesions

methamphetamine

carious episodes

methamphetamines

caries

methamphetamines

carious lesions

methamphetamines

carious episodes


Input: Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy. Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.

Thyroxine

thyroxine

thyrotoxicosis

Eating disorders

drug abuse

eating disorders

eating disorders

thyrotoxicosis

Thyroxine

thyrotoxicosis

Thyroxine

thyrotoxicosis

thyroxine

thyrotoxicosis

thyroxine

thyrotoxicosis


Input: Attenuation of methamphetamine - induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment. Immunological activation has been proposed to play a role in methamphetamine - induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro - inflammatory and inflammatory factor, treatment in modulating the methamphetamine - induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine - elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine - induced striatal dopamine and 3, 4 - dihydroxyphenylacetic acid depletions in a dose - dependent manner. As the most potent dose (1 mg / kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine - induced striatal dopamine and 3, 4 - dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg / kg) attenuated local methamphetamine infusion - produced dopamine and 3, 4 - dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine - induced nigrostriatal dopamine neurotoxicity.

methamphetamine

lipopolysaccharide

methamphetamine

lipopolysaccharide

methamphetamine

dopamine

Lipopolysaccharide

methamphetamine

lipopolysaccharide

methamphetamine

dopamine

3, 4 - dihydroxyphenylacetic acid

lipopolysaccharide

methamphetamine

methamphetamine

dopamine

3, 4 - dihydroxyphenylacetic acid

lipopolysaccharide

methamphetamine

dopamine

3, 4 - dihydroxyphenylacetic acid

lipopolysaccharide

methamphetamine

lipopolysaccharide

methamphetamine

dopamine

neurotoxicity

dopaminergic terminal damage

neurotoxicity

hyperthermia

neurotoxicity

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia

methamphetamine

hyperthermia


Input: Effect of converting enzyme inhibition on the course of adriamycin - induced nephropathy. The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich - Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short - term studies showed that enalapril reduced arterial blood pressure (101 + / - 2 vs. 124 + / - 3 mm Hg, group 2 vs. 1, P less than 0. 05) and glomerular capillary pressure (54 + / - 1 vs. 61 + / - 2 mm Hg, P less than 0. 05) without reducing albuminuria (617 + / - 50 vs. 570 + / - 47 mg / day) or GFR (1. 03 + / - 0. 04 vs. 1. 04 + / - 0. 11 ml / min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0. 35 + / - 0. 08 ml / min at 4 months, 0. 27 + / - 0. 07 ml / min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0. 86 + / - 0. 15 ml / min at 4 months, 0. 69 + / - 0. 13 ml / min at 6 months, both P less than 0. 05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats. (ABSTRACT TRUNCATED AT 250 WORDS)

adriamycin

enalapril

adriamycin

adriamycin

enalapril

enalapril

enalapril

adriamycin

enalapril

Enalapril

nephropathy

nephrosis

albuminuria

albuminuria

renal injury

nephrosis

albuminuria

glomerular sclerosis

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

albuminuria

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis

adriamycin

nephrosis


Input: Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy. BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K - and the A - variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K - variant being the most frequent. The duration of apnea was 5 - 15 min compared with 3 - 5. 3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT.

apnea

apnea

apnea

apnea

apnea

succinylcholine

succinylcholine

succinylcholine

succinylcholine

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea

succinylcholine

apnea


Input: Ketamine sedation for the reduction of children' s fractures in the emergency department. BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency - department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children' s fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5. 3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level - I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety - nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board - certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children' s Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty - six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty - two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children' s Hospital of Eastern Ontario Pain Scale was 6. 4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety - nine percent (sixty - eight) of the sixty - nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long - term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children' s fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one - on - one monitoring is used and board - certified physicians skilled in airway management are directly involved in the care of the patient.

Ketamine

ketamine

ketamine

Ketamine hydrochloride

ketamine

Ketamine

Ketamine

fractures

fractures

fracture

dislocation

trauma

pain

Pain

fracture

dislocation

Pain

pain

fracture

fracture

nausea

emesis

nausea

clumsiness

ataxic movements

dysphoric reaction

hallucinations

fractures

Ketamine

nausea

Ketamine

nausea

ketamine

nausea

ketamine

nausea

ketamine

nausea

ketamine

nausea

Ketamine hydrochloride

nausea

Ketamine hydrochloride

nausea

ketamine

nausea

ketamine

nausea

Ketamine

nausea

Ketamine

nausea

Ketamine

nausea

Ketamine

nausea

Ketamine

emesis

ketamine

emesis

ketamine

emesis

Ketamine hydrochloride

emesis

ketamine

emesis

Ketamine

emesis

Ketamine

emesis

Ketamine

clumsiness

Ketamine

ataxic movements

ketamine

clumsiness

ketamine

ataxic movements

ketamine

clumsiness

ketamine

ataxic movements

Ketamine hydrochloride

clumsiness

Ketamine hydrochloride

ataxic movements

ketamine

clumsiness

ketamine

ataxic movements

Ketamine

clumsiness

Ketamine

ataxic movements

Ketamine

clumsiness

Ketamine

ataxic movements


Input: Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders. The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow - up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27 - 73), median disease duration 50 months (range 9 - 178) and median follow - up period of patients 13. 8 months (range 5 - 27) were enrolled in this study. Lamivudine therapy was started 3 - 7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT: 122 IU / l, AST: 111 IU / l, tenth patient: ALT: 294 IU / l, AST: 274 IU / l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow - up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow - up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.

lamivudine

lamivudine

hepatitis B virus surface antigen

HBs Ag

HBs Ag

lamivudine

Lamivudine

Lamivudine

lamivudine

rheumatologic disorders

rheumatologic disease

rheumatologic diseases

hepatitis B

abnormal liver function

hepatitis B virus surface antigen

hepatitis B

HBs Ag

hepatitis B

HBs Ag

hepatitis B


Input: Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital. BACKGROUND: TEE is a semi - invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni - and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65 + / - 16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4. 3 + / - 1. 9 mg and 0. 28 + / - 0. 2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16. 4 + / - 6. 1 minutes and 60 + / - 9%, respectively. Mild hypoxia (SO2 < 90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5. 8%) due to hypoxia caused by MZ use. Transient hypotension (SAP < 90mmHg) occurred in 1 patient (0. 7%). The multivariate analysis showed that severe MR, MP (EF < 45%) and high doses of MZ (> 5mg) were associated with events (p < 0. 001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.

Midazolan

MZ

Flumazenil

FL

MZ

MZ

MZ

MZ

FL

MZ

MZ

stroke

myocardiopathy

MP

mitral regurgitation

MR

hypoxia

hypoxia

airway obstruction

hypoxia

hypotension

MR

MP

MP

MR

Midazolan

hypoxia

Midazolan

hypoxia

Midazolan

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia

MZ

hypoxia


Input: Effects of calcium channel blockers on bupivacaine - induced toxicity. The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine - induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i. e. 2 and 10 mg / kg / i. p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg / kg / i. p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic - induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine - induced convulsions; this effect was less pronounced with bepridil.

calcium

bupivacaine

calcium

bupivacaine

calcium

diltiazem

verapamil

bepridil

bupivacaine

calcium

bupivacaine

calcium

bupivacaine

bepridil

toxicity

toxicity

convulsions

bupivacaine

convulsions

bupivacaine

convulsions

bupivacaine

convulsions

bupivacaine

convulsions

bupivacaine

convulsions


Input: Selegiline - induced postural hypotension in Parkinson' s disease: a longitudinal study on the effects of drug withdrawal. OBJECTIVES: The United Kingdom Parkinson' s Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson' s disease (PD) randomized to receive 10 mg selegiline per day and L - dopa compared with those taking L - dopa alone. Recently, we found that therapy with selegiline and L - dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head - up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head - up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L - dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non - selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.

Selegiline

selegiline

L - dopa

L - dopa

selegiline

L - dopa

selegiline

selegiline

selegiline

selegiline

selegiline

selegiline

selegiline

L - dopa

amphetamine

metamphetamine

postural hypotension

Parkinson' s disease

Parkinson' s Disease

Parkinson' s disease

PD

systolic orthostatic hypotension

orthostatic hypotension

PD

systolic orthostatic hypotension

PD

orthostatic hypotension

Orthostatic hypotension

reduced the supine systolic and diastolic blood pressures

orthostatic hypotension

Selegiline

postural hypotension

Selegiline

systolic orthostatic hypotension

Selegiline

orthostatic hypotension

Selegiline

systolic orthostatic hypotension

Selegiline

orthostatic hypotension

Selegiline

Orthostatic hypotension

Selegiline

reduced the supine systolic and diastolic blood pressures

Selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension

selegiline

postural hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

systolic orthostatic hypotension

selegiline

orthostatic hypotension

selegiline

Orthostatic hypotension

selegiline

reduced the supine systolic and diastolic blood pressures

selegiline

orthostatic hypotension


Input: Explicit episodic memory for sensory - discriminative components of capsaicin - induced pain: immediate and delayed ratings. Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long - term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0. 05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0 - 100) digitized at 1 / s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose - dependent flare (p < 0. 001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p < 0. 001), regardless of whether first - time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p < 0. 01, duration: p < 0. 05). Correlation with rating recall after one week was best when first - time ratings were requested as late as one day after injection (R (2) = 0. 79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.

capsaicin

capsaicin

Capsaicin

capsaicin

pain

Pain

pain

pain

pain

pain

Pain

pains

pain

pain

Pain

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pains

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pains

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain

Capsaicin

pain

Capsaicin

Pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

Pain

Capsaicin

pains

Capsaicin

pain

Capsaicin

pain

Capsaicin

Pain

Capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pains

capsaicin

pain

capsaicin

pain

capsaicin

Pain

capsaicin

pain


Input: Reversibility of captopril - induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension. We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre - treatment levels soon after cessation of the drug. This indicates reversibility in captopril - induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.

captopril

captopril

captopril

captopril

renal insufficiency

renovascular hypertension

hypertension

sudden deterioration of renal function

renal failure

captopril

sudden deterioration of renal function

captopril

sudden deterioration of renal function

captopril

sudden deterioration of renal function

captopril

sudden deterioration of renal function


Input: Liver disease caused by propylthiouracil. This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.

Liver disease

chronic active (aggressive) hepatitis

liver disease

propylthiouracil

propylthiouracil

propylthiouracil

chronic active (aggressive) hepatitis

propylthiouracil

chronic active (aggressive) hepatitis


Input: Capsaicin - induced muscle pain alters the excitability of the human jaw - stretch reflex. The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw - stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short - latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.

Capsaicin

Capsaicin

muscle pain

temporomandibular disorders

muscle pain

nociceptive muscle

pain

pain

pain

painful muscle

muscle pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain

Capsaicin

pain


Input: Repetitive transcranial magnetic stimulation for levodopa - induced dyskinesias in Parkinson' s disease. In a placebo - controlled, single - blinded, crossover study, we assessed the effect of " real " repetitive transcranial magnetic stimulation (rTMS) versus " sham " rTMS (placebo) on peak dose dyskinesias in patients with Parkinson' s disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1, 800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician - assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low - frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.

levodopa

dyskinesias

Parkinson' s disease

dyskinesias

Parkinson' s disease

PD

PD

dyskinesias

dyskinesia

dyskinesia

dystonia

dyskinesia

PD

dyskinesias

PD

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesia

levodopa

dyskinesias


Input: Disulfiram - like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France. Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram - like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59 - year - old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55 - year - old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram - like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.

Disulfiram

hydrogen cyanamide

Hydrogen cyanamide

aldehyde

acetaldehyde

alcohol

disulfiram

hydrogen cyanamide

Dormex

hydrogen cyanamide

alcohol

alcohol

Dormex

disulfiram

alcohol

Dormex

flushing of the face

tachycardia

dyspnea

flushing

tachycardia

arterial hypotension

alcohol

arterial hypotension

alcohol

arterial hypotension

alcohol

arterial hypotension

alcohol

arterial hypotension

alcohol

flushing of the face

alcohol

flushing

alcohol

flushing of the face

alcohol

flushing

alcohol

flushing of the face

alcohol

flushing

alcohol

flushing of the face

alcohol

flushing

hydrogen cyanamide

arterial hypotension

Hydrogen cyanamide

arterial hypotension

hydrogen cyanamide

arterial hypotension

Dormex

arterial hypotension

hydrogen cyanamide

arterial hypotension

Dormex

arterial hypotension

Dormex

arterial hypotension

alcohol

dyspnea

alcohol

dyspnea

alcohol

dyspnea

alcohol

dyspnea

hydrogen cyanamide

tachycardia

hydrogen cyanamide

tachycardia

Hydrogen cyanamide

tachycardia

Hydrogen cyanamide

tachycardia

hydrogen cyanamide

tachycardia

hydrogen cyanamide

tachycardia

Dormex

tachycardia

Dormex

tachycardia

hydrogen cyanamide

tachycardia

hydrogen cyanamide

tachycardia

Dormex

tachycardia

Dormex

tachycardia

Dormex

tachycardia

Dormex

tachycardia

hydrogen cyanamide

dyspnea

Hydrogen cyanamide

dyspnea

hydrogen cyanamide

dyspnea

Dormex

dyspnea

hydrogen cyanamide

dyspnea

Dormex

dyspnea

Dormex

dyspnea

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

alcohol

tachycardia

hydrogen cyanamide

flushing of the face

hydrogen cyanamide

flushing

Hydrogen cyanamide

flushing of the face

Hydrogen cyanamide

flushing

hydrogen cyanamide

flushing of the face

hydrogen cyanamide

flushing

Dormex

flushing of the face

Dormex

flushing

hydrogen cyanamide

flushing of the face

hydrogen cyanamide

flushing

Dormex

flushing of the face

Dormex

flushing

Dormex

flushing of the face

Dormex

flushing


Input: Repeated trimipramine induces dopamine D2 / D3 and alpha1 - adrenergic up - regulation. Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5 - hydroxytryptamine, nor does it induce beta - adrenergic down - regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1 - adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i. p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5 - hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d - amphetamine, quinpirole and (+) - 7 - hydroxy - dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d - amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1 - adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1 - adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.

trimipramine

dopamine

Trimipramine

TRI

antidepressant

imipramine

noradrenaline

5 - hydroxytryptamine

antidepressant

TRI

antidepressants

TRI

TRI

reserpine

5 - hydroxytryptophan

TRI

d - amphetamine

quinpirole

dopamine

d - amphetamine

apomorphine

TRI

phenylephrine

clonidine

antidepressants

TRI

dopamine

antidepressants

antidepressant

hypothermia

hyperactivity

aggressiveness

d - amphetamine

hyperactivity

d - amphetamine

hyperactivity

reserpine

hypothermia

trimipramine

hyperactivity

Trimipramine

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

TRI

hyperactivity

quinpirole

hyperactivity


Input: Ranitidine - induced acute interstitial nephritis in a cadaveric renal allograft. Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine - induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.

Ranitidine

Ranitidine

ranitidine

interstitial nephritis

interstitial nephritis

interstitial nephritis

Ranitidine

interstitial nephritis

Ranitidine

interstitial nephritis

Ranitidine

interstitial nephritis

Ranitidine

interstitial nephritis

Ranitidine

interstitial nephritis

Ranitidine

interstitial nephritis

ranitidine

interstitial nephritis

ranitidine

interstitial nephritis

ranitidine

interstitial nephritis


Input: Late, late doxorubicin cardiotoxicity. Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg / m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one - half years after receiving 580 mg / m2 which apparently represents late, late cardiotoxicity.

doxorubicin

adriamycin

cardiotoxicity

Cardiac toxicity

Cardiomyopathy

cardiomyopathy

cardiotoxicity

doxorubicin

Cardiomyopathy

doxorubicin

cardiomyopathy

adriamycin

Cardiomyopathy

adriamycin

cardiomyopathy


Input: Acetazolamide - induced nephrolithiasis: implications for treatment of neuromuscular disorders. Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long - term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.

Acetazolamide

acetazolamide

acetazolamide

nephrolithiasis

neuromuscular disorders

nephrolithiasis

paralysis

myotonia

renal calculi

renal calculus

calculus

Nephrolithiasis

Acetazolamide

renal calculi

Acetazolamide

renal calculus

acetazolamide

renal calculi

acetazolamide

renal calculus

acetazolamide

renal calculi

acetazolamide

renal calculus