Efavirenz as a psychotropic drug.

OBJECTIVE: Antiretroviral drugs are the mainstay of treatment for human immunodeficiency virus (HIV) infection. Lifelong highly active antiretroviral therapy (HAART) is indicated to prevent disease progression to acquired immunodeficiency syndrome (AIDS). Efavirenz was a first-line component of HAART across the world for many years. The purpose of this article is to review the psychotropic properties of efavirenz, which are the most important adverse events associated with the drug and commonly result in treatment discontinuation. MATERIALS AND METHODS: A PubMed search was conducted using efavirenz as a search term, which returned 4655 results. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included in the narrative review. RESULTS: Acute exposure to efavirenz may cause profound perceptual disturbances (delusions and hallucinations) whereas chronic exposure may be associated with abnormal dreams and other sleep disturbances, anxiety, depressed mood and suicidality. It may also be abused as a hallucinogen, especially in individuals with a history of poly-substance abuse. Recent research indicates that efavirenz directly affects monoaminergic neurotransmission and may partially substitute for psychedelic drugs, such as lysergic acid diethylamide (LSD). Efavirenz acts as a serotonin 5-HT2A receptor antagonist, a serotonin-dopamine reuptake inhibitor, an inhibitor of monoamine oxidase (MAO) and a vesicular monoamine transporter 2 (VMAT2) inhibitor, which are mechanisms common with many psychotropic drugs. Efavirenz interacts with many of the same molecular targets as the empathogen methylendioxymethamphetamine (MDMA), but the effects of the 2 drugs may differ. CONCLUSIONS: The exact mechanism of action of efavirenz as a psychotropic drug remains unclear and future studies should focus on evaluating whether prolonged exposure could lead to irreversible side effects.

Spontaneous intracranial hypotension: clinical and neuroimaging findings in six cases with literature review.

Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches.

Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls.

OBJECTIVES: This study was conducted to assess the role of pelvic ultrasound variables in discriminating between normal girls and girls with different forms of sexual precocity, and to establish reliable cut-off limits of pelvic ultrasound measurements for differentiating between these conditions. METHODS: Eighty-eight girls with different forms of sexual precocity (23 with premature thelarche, 15 with premature pubarche and 50 with central precocious puberty) were enrolled. All diagnoses were based on clinical examination with confirmation using the gonadotropin-releasing hormone-stimulation test. Additionally, 81 prepubertal girls, aged 0-10 years, were included as a control group. For statistical analysis and to facilitate comparisons, the groups were subdivided by age intervals (0-6, > 6-8 and > 8-10 years). All subjects underwent pelvic ultrasound examination for the measurement of uterine length, uterine volume, ovarian volume and the anteroposterior diameter at the fundus divided by the anteroposterior diameter at the cervix (fundal/cervical ratio, (F/C)). Finally, the morphological appearance of the ovaries was assessed. RESULTS: Patients with central precocious puberty had significantly higher values for all the ultrasound variables (with the exception of uterine length in the 1-6-year age group) in comparison to normal girls. Patients with premature thelarche and patients with premature pubarche showed similar pelvic ultrasound parameters to those of normal girls. Ovarian volume was the best parameter for identifying patients with central precocious puberty (a cut-off of 3.04 cm(3) had a sensitivity of 100% and a specificity of 97.1% for age interval 0-6 years, a cut-off of 3.35 cm(3) had a sensitivity of 100% and a specificity of 89.5% for age interval > 6-8 years, and a cut-off of 4.46 cm(3) had a sensitivity of 80.8% and a specificity of 88.5% for age interval > 8-10 years). Uterine length was the best parameter for distinguishing between patients with central precocious puberty and patients with premature thelarche (a cut-off of 3.185 cm had a sensitivity of 85.7% and a specificity of 91.7% for age interval 0-6 years, and a cut-off of 3.83 cm had a sensitivity of 82.4% and a specificity of 90.9% for age interval > 6-8 years). CONCLUSIONS: Ultrasound examination of the uterus and ovaries could serve as a complementary tool for the diagnosis of central precocious puberty and, consequently, for the early initiation of appropriate treatment.

MRI evaluation of diastematomyelia and associated abnormalities.

Fourteen children were studied with a 1Tesla scanner to assess the role of magnetic resonance (MR) imaging in the recognition and evaluation of diastematomyelia and associated abnormalities. With MRI divided spinal cord was well imaged in its entire craniocaudal extent. Fibrous bands or bony septum when it contained a marrow cavity, were also well depicted. Direct visualization of the spinal cord itself is probably the most rewarding feature of MR imaging compared with other more conventional techniques. MR imaging demonstrated associated syringohydromyelia, segmentation anomalies, scoliosis, low position of the conus medularis and intradural lipoma that they were not detected with other radiologic studies.

Radiation doses to paediatric patients up to 5 years of age undergoing micturating cystourethrography examinations and its dependence on patient age: a Monte Carlo study.

The effective dose received by children up to 5 years of age from micturating cystourethrography (MCU) examinations was estimated in this study. The MCU examination consisted of 5 radiological views, 2 anteroposterior (AP) and three oblique (OBL) views. Entrance surface doses (ESD) were measured with thermoluminescent dosimeters for 30 children. The average ESD values per view varied from 0.34 mGy up to 0.57 mGy. In order to calculate the organ and effective doses, Monte Carlo MCNP-4A radiation transport simulation code was used. It was applied to three mathematical phantoms representing newborn, 1 and 5 year old children and all the patients were classified in those three groups. The effective dose conversion factors (C(f)) were calculated as the ratio of effective dose over the entrance dose. The C(f) factors decrease as the children's age increases. Children simulated by a newborn mathematical phantom, had C(f) factors almost double those represented by a 1-year-old mathematical phantom. For children simulated by a 5 year old phantom, the C(f) factors for AP and OBL views were almost the same. This was true for both male and female patients. The mean effective dose per view for male and female patients was found to be E=0.16 mSv. The effective dose per examination for male patients was E=0.86+/-0.31 mSv and E=0.76+/-0.28 mSv for female patients.

Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases.

PURPOSE: To determine the efficacy, tolerability, and safety of concurrent temozolomide and radiotherapy in patients with previously untreated brain metastases. PATIENTS AND METHODS: Fifty-two patients with brain metastases from solid tumors were randomized to oral temozolomide (75 mg/m(2)/d) concurrent with 40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4 weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and radiotherapy continued temozolomide therapy (200 mg/m(2)/d) for 5 days every 28 days for an additional six cycles. The primary end points were radiologic response and neurologic symptom evaluation. RESULTS: The objective response rate was significantly (P =.017) improved in patients receiving temozolomide and radiotherapy versus radiotherapy alone. Among 24 patients assessable for response in the temozolomide group, 23 (96%) of 24 responded, including nine (38%) patients with a complete response and 14 (58%) patients with a partial response. With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including seven (33%) complete responses and seven (33%) partial responses. There was marked neurologic improvement in the group receiving temozolomide, and the proportion of patients requiring corticosteroids 2 months after treatment was lower in the temozolomide group compared with radiotherapy alone (67% v 91%, respectively). Daily temozolomide concurrent with radiotherapy was generally well tolerated; however, grade >or= 2 nausea (48% v 13%, P =.13) and vomiting (32% v 0%, P =.004) were significantly increased in the temozolomide group. Hematologic toxicity was predictable and reversible. CONCLUSION: Temozolomide is safe, and a significant improvement in response rate was observed when administered in combination with radiotherapy in patients with previously untreated brain metastases. A larger randomized trial is warranted to verify these results.