Seizure freedom from recurrent insular low-grade glioma following laser interstitial thermal therapy.

Pediatric low-grade gliomas (LGGs) are found in approximately 1-3% of patients with childhood epilepsy that is often medically refractory. Magnetic resonance guided laser interstitial thermal therapy (MRgLITT) is a minimal access technique FDA-approved since 2007 to ablate soft tissue lesions including brain tumors and seizure foci in children. The authors describe the case of an 11-year-old boy who presented with focal right-sided seizures and was found to have a growing left insular mass determined to be a WHO grade II diffuse astrocytoma. After the initial open resection using frontotemporal craniotomy with transsylvian approach, gross total resection was achieved; however, the tumor recurred, as did the seizures. Six months postoperatively, the patient underwent laser ablation with MRgLITT for the recurrent tumor with complete removal. At both 1- and 6-months post re-operation, he has remained seizure free. MRgLITT management of LGG allows for both successfully reducing tumor burden and the amelioration of secondary seizures.

Surveying colloid sedimentation by coplanar waveguides.

By using coplanar waveguides, direct access to the dielectric properties of aqueous solutions of polystyrene beads with different diameters from 330 nm to 10 µm is provided. The relative variation of the transmission parameter with respect to water is monitored, ranging from [Formula: see text] obtained for a 9.5% solution with 330 nm diameter beads to ∼22% for 10 µm diameter particles at the same concentration. To highlight its applicability in biosensing, the technique was further employed to survey the clustering between biotin and streptavidin-coated beads. The transmission parameter displays a ∼50% increase for mixtures containing nine volumes of biotin and one volume of streptavidin-modified beads (4.5 ng µl(-1) of streptavidin) and reaches ∼400% higher values when equal volumes of biotin and streptavidin-coated beads (22.5 ng µl(-1) of streptavidin) were mixed.

Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo.

BACKGROUND: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. METHODS: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. RESULTS: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: -2.40, placebo: -1.97; LS mean change difference (95% confidence interval) = -0.43 (-0.82, -0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). CONCLUSIONS: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials.

Comparative safety and tolerability of duloxetine vs. pregabalin vs. duloxetine plus gabapentin in patients with diabetic peripheral neuropathic pain.

OBJECTIVE: The safety and tolerability of three treatments for diabetic peripheral neuropathic pain (DPNP) were compared. METHODS: A 12-week, randomized, open-label study confirming the non-inferiority of duloxetine (N = 138) vs. pregabalin (N = 134) and the combination of duloxetine plus gabapentin (N = 135) as the primary outcome was previously published. Patients had an inadequate pain response to a stable dose of gabapentin (≥ 900 mg/day) for ≥ 5 weeks prior to study enrolment. Data from that study were assessed in this current analysis for a detailed report of safety and tolerability. RESULTS: Completion rates did not differ significantly between the groups. Discontinuation because of adverse events was significantly greater in the duloxetine (19.6%) vs. pregabalin group (10.4%; p = 0.04); no differences emerged between the duloxetine vs. duloxetine plus gabapentin (13.3%) groups (p = 0.19) or pregabalin vs. duloxetine plus gabapentin groups (p = 0.57). Adverse event rates varied: nausea, insomnia, hyperhidrosis and decreased appetite were reported significantly more often in patients treated with duloxetine vs. patients treated with pregabalin (each p ≤ 0.01); insomnia significantly more in patients treated with duloxetine vs. duloxetine plus gabapentin (p = 0.01); peripheral oedema significantly more in patients treated with pregabalin vs. duloxetine and duloxetine plus gabapentin (p ≤ 0.001 each) and nausea, hyperhidrosis, decreased appetite and vomiting significantly more in patients treated with duloxetine plus gabapentin vs. pregabalin (each p ≤ 0.05). At end-point, weight change differed significantly among treatment groups: patients in the pregabalin group on average gained weight (1.0 ± 0.04 kg); while, patients in the duloxetine and duloxetine plus gabapentin groups on average lost weight (-2.39 ± 0.04 and -1.06 ± 0.04 kg, respectively) (pregabalin vs. duloxetine, p ≤ 0.001; pregabalin vs. duloxetine plus gabapentin, p ≤ 0.001; duloxetine vs. duloxetine plus gabapentin, p = 0.01). CONCLUSION: Duloxetine, pregabalin and duloxetine plus gabapentin were generally safe and tolerable for the treatment of DPNP.

Twisted bi-layer graphene: microscopic rainbows.

Blue, pink, and yellow colorations appear from twisted bi-layer graphene (tBLG) when transferred to a SiO2 /Si substrate (SiO2 = 100 nm-thick). Raman and electron microscope studies reveal that these colorations appear for twist angles in the 9-15° range. Optical contrast simulations confirm that the observed colorations are related to the angle-dependent electronic properties of tBLG combined with the reflection that results from the layered structure tBLG/100 nm-thick SiO2 /Si.

Frequency and outcomes of painful physical symptoms in a naturalistic population with major depressive disorder: an analysis of pooled observational studies focusing on subjects aged 65 years and over.

AIMS: To estimate the frequency of painful physical symptoms (PPS) in elderly subjects (≥ 65 years) with major depressive disorder (MDD) in real-world clinical conditions and to establish whether PPS are associated with poor depression outcomes, including more severe depression and worse health-related quality of life (HRQoL). METHODS: Observational studies of MDD that included assessment of PPS and elderly subjects were screened. Measures of PPS were based on the Somatic Symptom Inventory (SSI) or Visual Analogue Scale (VAS). Data from a variety of depressive symptom severity and HRQoL scales were used. Analysis cohorts were based on age [aged ≥ 65 years (elderly) or < 65 years (younger)] and/or PPS status (presence or absence); five subsets were used to examine specific outcomes in matched elderly subjects. RESULTS: Data from seven studies (representing 26 countries) were collated. Of the 11,477 subjects, 14% were aged ≥ 65 years and 71% were classified as having PPS (PPS+). PPS were more frequent in elderly subjects (74% vs. 70% of younger subjects) and were positively associated with being female and Hispanic, and negatively associated with being East Asian in the elderly. The presence of PPS was associated with more severe clinical symptomatology and comparatively poorer HRQoL in elderly subjects. CONCLUSIONS: PPS, although frequent in younger MDD patients, were slightly more frequent in elderly MDD patients and associated with comparatively poorer clinical and functional outcomes. As elderly patients report somatic symptoms more readily than emotional symptoms, physicians should consider depression in addition to physical causes when PPS are present.

The impact of etched trenches geometry and dielectric material on the electrical behaviour of silicon-on-insulator self-switching diodes.

Hole electrical transport in a p-doped nanochannel defined between two L-shape etched trenches made on a silicon-on-insulator substrate is investigated using a TCAD-Medici simulator. We study the impact of the etched trenches' geometry and dielectric filling materials on the current-voltage characteristics of the device. Carrier accumulation on frontiers defined by the trenches causes a modulation of the hole density inside the conduction channel as the bias voltage varies and this gives rise to a diode-like characteristic. For a 1.2 µm-long channel, plots of the electric field distribution show that a nonlinear transport regime is reached at a moderate reverse and forward bias of ± 2 V. Plots of the carrier velocity along the conduction channel show that holes remain hot for a few hundreds of nm outside the nanometre-wide channel, at a bias of ± 10 V. Filling the etched trenches with a high-κ dielectric material gives rise to a lower threshold voltage, V(th). A similar decrease of V(th) is also achieved by reducing the longitudinal and/or the transverse trench width. Our simulation results provide useful design guidelines for future integrated self-switching-diode-based circuits.

Attributes of response in depressed patients switched to treatment with duloxetine.

BACKGROUND: This study was designed to assess clinical and functional outcomes associated with switching to duloxetine treatment in patients with major depressive disorder (MDD) experiencing emotional and painful physical symptoms in their current episode. METHODS: In this 8-week, multinational, multicentre, single-arm, open-label clinical trial, 242 MDD patients were switched to duloxetine 60 mg/day after selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) treatment. The primary analysis compared mean change from baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) interference score between initial responders [≥ 50% reduction from baseline on the 17-item Hamilton Depression Rating Scale (HAMD(17)) Maier subscale] and initial non-responders after 4 weeks. Initial responders continued with duloxetine 60 mg/day. Initial non-responders received duloxetine 120 mg/day for the remaining 4 weeks. Depression, pain, anxiety and functional outcomes were also compared after 8 weeks. RESULTS: BPI-SF interference decreased from baseline in initial responders (n = 108) and initial non-responders (n = 85) after 4 weeks of duloxetine treatment, with greater reductions in initial responders [BPI-SF mean difference in reduction: 1.01 (95% CI 0.42-1.61); p < 0.001]. Reductions in pain interference favouring initial responders were also apparent after 8 weeks [0.68 (95% CI: 0.03-1.33); p = 0.042]. Depression, pain, anxiety and function improved over 8 weeks across patient groups. CONCLUSIONS: Elements of core mood and pain are important residual symptoms following poor treatment response in MDD. Early improvement in these symptoms after switching to duloxetine indicated an increased chance of functional recovery.

Duloxetine 60 mg/day for the prevention of depressive recurrences: post hoc analyses from a recurrence prevention study.

OBJECTIVE: To assess the efficacy of duloxetine 60 mg/day in the prevention of depressive recurrence in patients with major depressive disorder (MDD). METHODS: Patients having at least three episodes of MDD in the past 5 years received open-label (OL) duloxetine 60-120 mg/day for up to 34 weeks. Patients meeting response criteria were then randomised to either duloxetine or placebo for up to 52 weeks of double-blind maintenance treatment. Only patients taking duloxetine 60 mg/day during the OL phase, and randomised to either duloxetine (remained on 60 mg/day dose) or placebo, were included in this post hoc analysis. The primary outcome measure was time to recurrence of a major depressive episode. The 17-item Hamilton Rating Scale for Depression (HAMD(17)) was used to evaluate depressive symptomatology. Global and physical functioning and pain were also assessed. Safety and tolerability were assessed via analysis of treatment-emergent adverse events (TEAEs), vital signs and weight. RESULTS: A total of 124 patients were randomised to duloxetine 60 mg/day (n = 64) or placebo (n = 60). Time to depressive recurrence was significantly longer in duloxetine-treated patients compared with placebo-treated patients (p = 0.001). During the double-blind maintenance phase, 31.7% of placebo-treated patients experienced a depressive recurrence compared with 12.5% of duloxetine-treated patients (p = 0.004). The HAMD(17) total score and most of its subscales as well as the Clinical Global Impression of Severity (CGI-S), significantly worsened in the placebo group compared with the duloxetine 60 mg/day group. There were no significant differences between treatment groups in TEAEs, discontinuations because of adverse events, vital signs or weight. CONCLUSIONS: Treatment with duloxetine 60 mg/day was associated with a longer time to depressive recurrence and a significantly lower recurrence rate compared with placebo.

Association between painful physical symptoms and clinical outcomes in East Asian patients with major depressive disorder: a 3-month prospective observational study.

AIMS: Reports from non-Asian populations indicate that painful physical symptoms (PPS) are associated with poorer clinical and functional outcomes in major depressive disorder (MDD). The purpose of this study is to report comparative changes in disease severity, treatment patterns and quality of life observed in East Asian patients with MDD, with and without PPS, as assessed prospectively over a 3-month observation period. METHODS: This observational study enrolled 909 patients with MDD in psychiatric care settings in China, Hong Kong, Korea, Malaysia, Singapore and Taiwan. Patients were classified as PPS positive (PPS+) or negative (PPS-) based on mean modified Somatic Symptom Inventory scores of >or= 2 or < 2 respectively. The Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD(17)) determined depression severity; a visual analogue scale (VAS) determined pain severity; and the EuroQoL (EQ-5D) assessed well-being after 3 months observation. RESULTS: Of the 909 enrollees, 355/471 (75.4%) of PPS+ patients and 363/438 (82.9%) of PPS- patients completed the study (p = 0.006). PPS+ patients improved less than PPS- patients on depression, pain and quality of life measures during the study (HAMD(17) p < 0.001, CGI-S p < 0.001, VAS p = 0.008 and EQ-5D p = 0.004). Fewer PPS+ patients (46.5%) achieved remission compared with PPS- patients (69.4%, p < 0.001). CONCLUSION: As the presence of PPS is associated with poorer outcomes in East Asian MDD patients, clinical management should aim to address both the mental and PPS associated with MDD.

Utilization of Observational Data as a Proxy Cohort for Comparison Purposes with Open-Label Study Results: An Example from Alzheimer's Disease.

BACKGROUND: Randomized placebo-controlled trials in the development of disease-modifying treatments for Alzheimer's disease are typically of short duration (12-18 months), and health economic modeling requires extrapolation of treatment effects beyond the trial period. OBJECTIVES: To investigate whether observational data can be used to extrapolate data from open-label trials, we compared outcomes (cognition, function, behavior) over 36 months for patients with mild Alzheimer's disease dementia in the GERAS observational study (proxy for placebo control) with those of the mild Alzheimer's disease population on active treatment (solanezumab) in two 18-month randomized placebo-controlled trials (EXPEDITION and EXPEDITION2) and the additional 18-month open-label extension study (EXPEDITION-EXT). DESIGN AND SETTING: Analysis of longitudinal data from patients with mild Alzheimer's disease dementia in the GERAS observational study (conducted in France, Germany and the United Kingdom) and the EXPEDITION program (conducted in Europe, North America, South America, Asia and Australia). PARTICIPANTS: European and North American community-living patients, aged ≥55 years, with probable Alzheimer's disease dementia and their caregivers. Mild Alzheimer's disease dementia was defined as a Mini-Mental State Examination score of 20-26 in EXPEDITION and 21-26 in GERAS. INTERVENTION: Active treatment in both randomized placebo-controlled trials and the open-label extension study was intravenous solanezumab 400 mg every 4 weeks. Patients in GERAS were receiving treatment as part of standard care. MEASUREMENTS: Between-group differences for changes from baseline over 36 months in cognitive function, ability to perform activities of daily living, and behavioral and psychological symptoms of dementia were assessed using models stratified by propensity score. RESULTS: At baseline, patients and caregivers participating in GERAS were significantly older than those in the EXPEDITION studies, and the GERAS patient cohort had fewer years of education and a shorter time since diagnosis of Alzheimer's disease. The baseline mean Mini-Mental State Examination score of the GERAS cohort was significantly higher (indicating better cognition) than that of patients receiving placebo or active treatment in the pooled EXPEDITION studies Baseline functional ability scores were significantly lower for the GERAS cohort, indicating poorer functioning. Propensity score stratification achieved a good balance in the baseline variables between GERAS and the two EXPEDITION arms. Over 18 months, least squares mean changes from baseline in outcome measures were similar in the GERAS cohort and the pooled placebo groups from the randomized controlled trials. Also, the 18-month results for the comparison between the GERAS cohort and the pooled active treatment groups from the randomized controlled trials were generally similar to those reported for the comparison with the control group in the randomized trial. Comparison of active treatment (EXPEDITION-EXT) and observational study (GERAS, as proxy control) results over 36 months of the open-label trial showed a significantly smaller decline in activities of daily living (instrumental and basic) in the active treatment group, reflecting better functioning, but no between-group differences at 36 months for cognitive function or behavioral and psychological symptoms of dementia. CONCLUSIONS: Comparing results from clinical trials and observational studies (real-world data) may be a useful methodological approach for informing long-term outcomes in Alzheimer's disease drug development and could be used to inform health economic modeling. Further research using this methodological approach is needed.

Electrical detection of DNA hybridization: three extraction techniques based on interdigitated Al/Al2O3 capacitors.

Based on interdigitated aluminum electrodes covered with Al(2)O(3) and silver precipitation via biotin-antibody coupled gold nano-labels as signal enhancement, three complementary electrical methods were used and compared to detect the hybridization of target DNA for concentrations down to the 50 pM of a PCR product from cytochrome P450 2b2 gene. Human hepatic cytochrome P450 (CYP) enzymes participate in detoxification metabolism of xenobiotics. Therefore, determination of mutational status of P450 gene in a patient could have a significant impact on the choice of a medical treatment. Our three electrical extraction procedures are performed on the same interdigitated capacitive sensor lying on a passivated silicon substrate and consist in the measurement of respectively the low-frequency inter-electrodes capacitance, the high-frequency self-resonance frequency, and the equivalent MOS capacitance between the short-circuited electrodes and the backside metallization of the silicon substrate. This study is the first of its kind as it opens the way for correlation studies and noise reduction techniques based on multiple electrical measurements of the same DNA hybridization event with a single sensor.

Correlation between Cognition and Function across the Spectrum of Alzheimer's Disease.

BACKGROUND: Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer's disease (AD). OBJECTIVES: To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD. DESIGN: Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations. SETTING: Post-hoc analysis from existing databases. PARTICIPANTS: Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer's Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects). MEASUREMENTS: Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset. RESULTS: The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression. CONCLUSIONS: This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.

Dislocation-mediated relaxation in nanograined columnar palladium films revealed by on-chip time-resolved HRTEM testing.

The high-rate sensitivity of nanostructured metallic materials demonstrated in the recent literature is related to the predominance of thermally activated deformation mechanisms favoured by a large density of internal interfaces. Here we report time-resolved high-resolution electron transmission microscopy creep tests on thin nanograined films using on-chip nanomechanical testing. Tests are performed on palladium, which exhibited unexpectedly large creep rates at room temperature. Despite the small 30-nm grain size, relaxation is found to be mediated by dislocation mechanisms. The dislocations interact with the growth nanotwins present in the grains, leading to a loss of coherency of twin boundaries. The density of stored dislocations first increases with applied deformation, and then decreases with time to drive additional deformation while no grain boundary mechanism is observed. This fast relaxation constitutes a key issue in the development of various micro- and nanotechnologies such as palladium membranes for hydrogen applications.

Gastrointestinal effects of nonsteroidal anti-inflammatory therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of many conditions including rheumatoid arthritis, osteoarthritis, gouty arthritis, the joint and muscle discomfort associated with systemic lupus erythematosus, and other musculoskeletal disorders. Yet, their benefits, which are believed to be a result of their ability to inhibit cyclooxygenase-2 (COX-2), are accompanied by considerable toxicity. NSAIDs' untoward effects are attributed to their inhibition of the constitutively expressed enzyme cyclooxygenase-1 (COX-1), with attendant suppression of the synthesis of prostanoids, substances that mediate key homeostatic functions. Side effects include suppression of hemostasis through inhibition of platelet aggregation, adverse effects in patients with heart failure and cirrhosis, and those with certain renal diseases, as well as complicating antihypertensive therapies involving diuretics or beta-adrenoceptor blockade. Perhaps most importantly, NSAIDs disrupt the gastrointestinal mucosal-protective and acid-limiting properties of prostaglandins, frequently leading to upper gastrointestinal erosions and ulceration, with possible subsequent hemorrhage and perforation. These complications can be reduced through identification of patients at risk, with circumspect use of NSAIDs, careful functional monitoring, and, in the case of gastrointestinal toxicity, co-administration of such agents as misoprostol or omeprazole. However, these strategies introduce complexity into the treatment paradigm. Moreover, side effects and adverse events may be significantly reduced through the use of COX-2-specific inhibitors, new agents that alleviate pain and inflammation without the liability for adverse events caused by COX-1 inhibition.

Ventricular arrhythmias during pulmonary artery catheterization in the intensive care unit. Prospective study.

The balloon-tipped, flotation pulmonary artery catheter is frequently utilized in the management of intensive care unit patients. Advanced ventricular arrhythmias (three or more consecutive premature ventricular contractions) have been reported in 25 to 68 percent of intensive care unit patients undergoing catheterizations. A group of 56 intensive care unit patients who received a pulmonary artery catheter were prospectively studied to determine the incidence of catheter-induced arrhythmias and the time required for catheterization. The mean age of the patients was 69.8 +/- 11 years. Indications for catheterization included septic shock (n = 10), congestive heart failure (n = 8), hypovolemia (n = 12), respiratory failure (n = 2), preoperative cardiac evaluation (n = 20), and miscellaneous (n = 4). Advanced ventricular arrhythmias were recorded in seven of the 56 patients (12.5 percent), the longest arrhythmia being a run of seven consecutive premature ventricular contractions. No patient required treatment with lidocaine for their arrhythmias and all arrhythmias resolved with catheter movement. The mean time of catheterization for the 56 patients was 175.9 seconds (SD 263.2), and was not significantly different for patients with or without arrhythmias. There was no statistical difference in catheterization times or incidence of arrhythmias between critically ill patients and the preoperative patients. It is concluded that pulmonary artery catheterization can be performed in critically ill patients with a lower incidence of arrhythmias than has previously been reported. The decreased incidence of arrhythmias may be secondary to the decreased catheterization times.

Rapid tranquilization with olanzapine in acute psychosis: a case series.

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.

'Domino' liver transplantation combined with multivisceral transplantation.

Transplantation of the liver contemporaneously with another organ from the same donor is thought to confer an immunologic advantage. The latter is particularly desirable in intestinal transplantation because of the propensity of the intestinal graft to early and late rejections and because in some cases it may facilitate the operation. In clinical practice, shortage of liver grafts constrains liver transplantation to cases in which there is coexisting end stage liver disease.

Bronchoscopy in diffuse lung disease: evaluation by open lung biopsy in nondiagnostic transbronchial lung biopsy.

Transbronchial lung biopsy through the flexible bronchoscope is used widely for the diagnosis of diffuse lung disease; however, a significant number of specimens obtained by the bronchoscopic 2-mm biopsy forceps will reveal nonspecific findings, eg, interstitial fibrosis or nonspecific pneumonitis. Such a report may be an accurate reflection of the presence of idiopathic pulmonary fibrosis or nonspecific pneumonitis, but may merely indicate that the true diagnosis has been missed. We retrospectively studied 38 patients with diffuse lung disease whose transbronchial lung biopsies yielded nonspecific abnormalities. Subsequently, these patients were subjected to open lung biopsies. Nineteen of the 38 patients (50%) had a specific diagnosis made by open lung biopsy. The diagnoses included bronchiolitis obliterans, alveolar proteinosis, metastatic carcinoma, lymphoma, tuberculosis, and bronchioloalveolar cell carcinoma. Although transbronchial lung biopsy is useful in the diagnosis of many diffuse lung diseases, it is not a replacement for open lung biopsy. When nonspecific findings by transbronchial lung biopsy do not correlate with the clinical picture, open lung biopsy should be performed.