An update on diagnosis, treatment, and prevention of Clostridium difficile-associated disease

Clostridium difficile is an important cause of nosocomial morbidity and mortality and is implicated in recent epidemics. Data support the treatment of colitis with oral metronidazole in a dose of 1.0 to 1.5 g/d, with oral vancomycin as a second-line agent, not because its efficacy is questioned but because of environmental concerns. Nitazoxanide and other drugs are currently under intense study as alternatives. Treatment of asymptomatic patients is not recommended. Current management strategies appear to be increasingly ineffective, especially for patients who experience multiple recurrences. Biotherapy and vaccination are currently being explored as treatment options for patients who have recurrent disease. Greater attention should be paid to hospital infection control policies and restriction of broad-spectrum antibiotics.     

Invasive monitoring in patients with heart failure

The syndrome of heart failure is characterized by symptoms that are relatively insensitive and nonspecific. Physical diagnosis may be unreliable even in the hands of experienced clinicians, despite the presence of significantly elevated filling pressures or a significantly depressed cardiac output. Instrumentation and devices such as the insertion of a pulmonary artery catheter and the implantable hemodynamic monitor have a major role in the diagnosis and management of cardiovascular disease. They provide a means of measuring intracardiac pressures for point-in-time measurements (cardiac catheterization), short term in an acute situation (insertion of a pulmonary arterial catheter), and, more recently, a long-term assessment increasing our understanding of the nuances of the hemodynamic derangements associated with heart failure and other conditions. With improved ability to accurately assess and monitor filling pressures, clinicians can more precisely adjust therapy with the goal of improving patient symptoms and possibly outcomes.     

Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats

The present study was designed to evaluate the behavioral and neurochemical profiles of clozapine and risperidone in rats in a dose-dependent manner. Animals injected intraperitoneally (i.p.) with clozapine (2.5, 5.0 and 10.0 mg kg-1) or risperidone (1.0, 2.5 and 5.0 mg kg-1) were sacrificed 1 h later to collect brain samples. Hypolocomotive effects (home cage activity and catalepsy) were successively monitored in each animal after the drug or saline administration. Both drugs significantly (p < 0.01) decreased locomotor activity at high doses and in a dose-dependent manner. Maximum (100%) cataleptic potential was achieved at a high dose (5.0 mg kg-1) of risperidone. Neurochemical estimations were carried out by HPLC with electrochemical detection. Both drugs, at all doses, significantly (p < 0.01) increased the concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the striatum. Dihydroxyphenylacetic acid (DOPAC) levels increased in the striatum and decreased in the rest of the brain, particularly in clozapine-injected rats. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin, significantly (p < 0.01) decreased in the striatum. 5-Hydroxytryptamine (5-HT) was significantly (p < 0.01) increased by risperidone and decreased by clozapine in the rest of the brain. Striatal tryptophan (TRP) was significantly (p < 0.01) decreased by risperidone and increased in the rest of the brain. The striatal HVA/DA ratio increased and the 5-HT turnover rate remained unchanged in the rest of the brain. Results suggest that the affinity of the two drugs towards D2/5-HT1A receptors interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed.     

Three-dimensional nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells

The regulation of mouse embryonic stem cell (mESC) fate is controlled by the interplay of signaling networks that either promote self-renewal or induce differentiation. Leukemia inhibitory factor (LIF) is a cytokine that is required for stem cell renewal in mouse but not in human embryonic stem cells. However, feeder layers of embryonic fibroblasts are capable of inducing stem cell renewal in both cell types, suggesting that the self-renewal signaling pathways may also be promoted by other triggers, such as alternative cytokines and/or chemical or physical properties of the extracellular matrix (ECM) secreted by feeder fibroblasts. We have recently used a synthetic polyamide matrix (Ultra-Web) whose three-dimensional (3D) nanofibrillar organization resembles the ECM/basement membrane. Growth of mESCs on this nanofibrillar surface greatly enhanced proliferation and self-renewal in comparison with growth on tissue culture surfaces without nanofibers, despite the presence of LIF in both systems. Enhanced proliferation and self-renewal of the stem cells on nanofibrillar surfaces were correlated with the activation of the small GTPase Rac, the activation of phosphoinositide 3-kinase (PI3K) pathway, and the enhanced expression of Nanog, a homeoprotein required for maintenance of pluripotency. Inhibitors of PI3K reduced the expression level of Nanog in mESCs cultured on 3D nanofibrillar surfaces. These results provide support for the view that the three-dimensionality of the culture surface may function as a cue for the activation of Rac and PI3K signaling pathways, resulting in stem cell proliferation and self-renewal.     

Analytical evaluation of HgbA1c, microalbumin, CRP, and RF on Architect ci8200 integrated system and workflow performance evaluation using computer simulation

BACKGROUND: Recently, hemoglobin A1c (HgbA1c), microalbumin (MA), C-reactive protein (CRP) and rheumatoid factor (RF) have been introduced on high throughput general chemistry system. We evaluated analytical performance of these assays on an integrated clinical chemistry and immunoassay analyzer and studied the impact of testing these assays on these systems on the overall efficiency of the analyzer, via computer simulation. METHODS: The analytical performance was measured by determining precision, linearity and correlation of patient sample results with in-house testing methodology. MedModel simulation software is used to develop simulation model and process efficiency is determined by measuring turnaround times and resource utilization. RESULTS: Between-days CVs ranged from 8.59% for MA to 3.22% for HgbA1c level 1 controls. Less than 2% carryover for all 4 methods was observed on the integrated analyzer. For HgbA1c on HPLC analyzer, the minimum and maximum TAT for a batch of 50 samples was 3.78 and 160 min, respectively, while for the integrated system it was 28.2 and 35.1 min, respectively. Labor utilization for the 2 processes ranged from 3.21% to 3.75%. CONCLUSION: Chemistry module on an integrated system can be used to determine the HgbA1c and other serum proteins.     

Induction of neutralizing antibodies specific to dengue virus serotypes 2 and 4 by a bivalent antigen composed of linked envelope domains III of these two serotypes

There is no vaccine to prevent dengue fever, a mosquito-borne viral disease, caused by four serotypes of dengue viruses. In this study, which has been prompted by the emergence of dengue virus envelope domain III as a promising sub-unit vaccine candidate, we have examined the possibility of developing a chimeric bivalent antigen with the potential to elicit neutralizing antibodies against two serotypes simultaneously. We created a chimeric dengue antigen by splicing envelope domain IIIs of serotypes 2 and 4. It was expressed in Escherichia coli and purified to near homogeneity. This protein retains the antigenic identities of both its precursors. It elicited antibodies that could efficiently block host cell binding of both serotypes 2 and 4 of dengue virus and neutralize their infectivity (neutralizing antibody titers approximately 1:40 and ~1:80 for dengue virus serotypes 2 and 4, respectively). This work could be a forerunner to the development of a single envelope domain III-based tetravalent antigen.     

Acute respiratory failure with a single dose of quetiapine fumarate

OBJECTIVE: To report a case of acute respiratory failure after a single dose of quetiapine fumarate in an elderly patient with a history of chronic obstructive pulmonary disease (COPD). CASE SUMMARY: A 92-year-old woman with a history of COPD was admitted to the hospital with pneumonia. Her symptoms improved with antibiotics. Because of acute agitation and delirium, quetiapine 50 mg twice daily was started. After receiving the first dose, the woman developed acute respiratory failure and severe central nervous system depression. She required mechanical ventilation and supportive care in the intensive care unit (ICU). She had a full recovery within 24 hours. DISCUSSION: Quetiapine is an atypical antipsychotic that has been used successfully for the treatment of schizophrenia and bipolar disorder for many years. Recently, it has also been used to treat delirium and agitation. It has proven to be very safe, even in the elderly. In previously reported cases, serious adverse effects were seen in patients who ingested very high doses of quetiapine. Those patients required intubation and supportive care in the ICU. To our knowledge, as of January 19, 2006, this is the first case report of acute respiratory failure of such severity with one dose of quetiapine. Using the Naranjo probability scale, we conclude that the acute respiratory failure observed in this patient was probably related to quetiapine. CONCLUSIONS: This case suggests that quetiapine can have significant adverse effects even with a single 50 mg dose. Elderly patients, especially those with significant underlying pulmonary pathology, should be monitored closely when started on this medication.     

Seimisochromenes A and B: two new dihydroisochromenes from the endophytic fungus,Seimatosporium sp.

Two new dihydroisochromenes, named seimisochromenes A and B (1 and 2), were isolated from an endophytic fungus, Seimatosporium sp. The structures of seimisochromenes A and B have been determined from 1D (¹H and ¹³C NMR spectra) and 2D (COSY, HMQC, HMBC, and NOESY) NMR experiments.