A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography–tandem mass spectrometry

BackgroundWe describe a fully-automated turbulent-flow liquid chromatography–tandem mass spectrometry method for the detection of tricyclic antidepressant drugs (amitriptyline, desipramine, imipramine, and nortriptyline) in serum.MethodsHuman serum and an internal standard were injected directly onto a Cyclone-P online solid-phase extraction (SPE) column (0.5 × 50 mm). Following removal of serum proteins and other components the analytes were transferred to a Hypersil Gold C-18 (50 × 3 mm) analytical column. Elution occurred with a gradient of water and acetonitrile each with 0.1% formic acid. Analytes were ionized and detected over a 3.5 min analysis time by electrospray-ionization mass spectrometry with selected reaction monitoring (SRM). Matrix effects were well-characterized and carryover, precision, linearity, recovery and limits of detection and quantitation were evaluated.ResultsThe simple and complex precision CVs for all compounds were ≤ 16%. The limits of detection and quantitation for all drugs were ≤ 3 ng/ml and < 20 ng/ml, respectively. Recoveries were between 97 and 114%. Slopes for method comparison plots were all > 0.96. Proficiency testing materials had values within 2 SDI of peer group means for all drugs.ConclusionBased on validation data, this is a specific, sensitive fully-automated method for rapid quantitation of tricyclic antidepressants in serum.     

A July Spike in Fatal Medication Errors: A Possible Effect of New Medical Residents

BACKGROUND  

Each July thousands begin medical residencies and acquire increased responsibility for patient care. Many have suggested that these new medical residents may produce errors and worsen patient outcomes—the so-called “July Effect;” however, we have found no U.S. evidence documenting this effect.     

Discussion of fertility preservation with newly diagnosed patients: oncologists’ views

Introduction Although physician discussion with patients regarding fertility preservation (FP) options prior to cancer treatment can provide important information for survivors concerning their future fertility, little is known about the extent to which physicians discuss FP with patients. This qualitative study sought to identify current physician FP communication practices and determine factors that may impact communication efforts regarding FP. Materials and methods Qualitative data were collected using semi structured interviews with 16 physicians practicing at a major cancer center in the South. Results All providers were board certified in medical oncology, radiation oncology or surgical oncology. The main factors that emerged from qualitative analysis included distinct variations in quality of discussion about FP, knowledge of FP resources, attitudes, practice behaviors and perceptions of patient characteristics. Discussion While most physicians discussed potential fertility loss as a side effect of cancer treatment, few provided information to patients about preserving fertility. Patient characteristics such as gender and cancer site may impact the discussion, as well as system factors such as costs of procedures and access to FP resources. Education and training for physicians about FP options for cancer patients, particularly females, may promote discussion of FP. In addition, system barriers related to availability and affordability of FP resources must also be addressed. Implications for cancer survivors Physicians should consider providing patients with timely, understandable information related to their FP options, prior to the administration of treatment. Such discussions may lead to improved quality of life for individuals as they transition from patients to survivors.     

Antenatal Screening for Congenital Infection with Rubella, Cytomegalovirus and Toxoplasma

Summary: The sera of 3,463 pregnant women were screened, at the first antenatal visit, for antibodies to rubella, cytomegalovirus (CMV) and Toxoplasma gondii. Rubella antibodies were detected in 97.5%, CMV antibodies in 71% and toxoplasma antibodies in 45% of women. Asymptomatic toxoplasmosis occurred during pregnancy in 3 of 609 (0.5%) and primary CMV infection in 5 of 338 (1.5%) initially seronegative women whose sera were retested at the end of their pregnancies. The observed incidence of toxoplasmosis was similar to that calculated on the basis of the age-related prevalence of antibodies found in this study. On the basis of these observations it is estimated that congenital toxoplasmosis and congenital CMV infection due to primary maternal infection each occurs in up to 2/1,000 infants in this community. Very few of these infants have obvious abnormalities at birth, but follow-up studies elsewhere have shown that many of them suffer significant long-term sequelae.     

The acceptability and behavioral effects of antibiotic prophylaxis for syphilis prevention

BACKGROUND AND OBJECTIVES: Use of preexposure antibiotic prophylaxis for syphilis control has been limited by concerns about acceptability and adverse behavioral effects. GOAL: The goal was to determine whether persons at high risk for syphilis accept antibiotic prophylaxis and if so, whether they subsequently increase their risky behavior. STUDY DESIGN: We gave a prospective cohort of persons either: 1) single doses of benzathine penicillin, azithromycin, and cefixime; or 2) a single dose of cefixime and 3 doses of azithromycin given biweekly. RESULTS: Of 268 persons approached, 186 (69%) agreed to participate, 174 were treated, and 125 (72%) were located for follow up. Four weeks and 4 months after enrollment, participants reported reductions in the number of sex partners. At 4 months, 1% had acquired gonorrhea, 5% had acquired chlamydia, and none had acquired syphilis. CONCLUSION: Antibiotic prophylaxis for syphilis was acceptable and not followed by increases in risky behavior. Larger trials of preexposure antibiotic prophylaxis of core group members to control syphilis outbreaks should be undertaken.     

Long-term potentiation is increased in the CA1 area of the hippocampus of APP(swe/ind) CRND8 mice

The present study reports changes in synaptic function and plasticity [long-term potentiation (LTP)] in a recently developed mouse model of Alzheimer's disease (CRND8 line) harboring a double amyloid precursor protein mutation (APP(swe/ind)). In 9-week-old preplaque transgenic (Tg) mice brain slices, basal synaptic function in the hippocampal CA1 area was unchanged. Only one of three different LTP induction protocols revealed early influence of genotype on synaptic plasticity. By 20 weeks of age, there were numerous plaques in the hippocampus from Tg mice associated with more robust evidence for genotype-related effects in synaptic function. Field potential maximum slope was consistently decreased and LTP was increased, irrespective of the stimulation protocol used. In addition, there was clear evidence of increased synaptic excitability in Tg mice. Furthermore, the maximum amplitude of evoked IPSCs was decreased whereas the maximum amplitude of evoked EPSCs was increased in 20-week-old Tg mice. Collectively, these results suggest a number of APP genotype-related changes in the fine-tuning of the CA1 area circuitry, some of which are likely to contribute to the pathology-dependent effects on LTP observed in CRND8 mice.     

Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat

Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke occurs. One unique therapy that may improve functional recovery after stroke is blockade of the neurite inhibitory protein Nogo-A with the monoclonal antibody IN-1, through enhancement of neuroanatomical plasticity from uninjured areas of the central nervous system. In the present study, we combined IN-1 treatment with an ischemic lesion (permanent middle cerebral artery occlusion) to determine the effect of Nogo-A neutralization on cortical plasticity and functional recovery. We report here that, following ischemic stroke and treatment with IN-1, adult rats demonstrated functional recovery on a forelimb-reaching task and new cortico-efferent projections from the opposite, unlesioned hemisphere. These results support the efficacy of Nogo-A blockade as a treatment for ischemic stroke and implicate plasticity from the unlesioned hemisphere as a mechanism for recovery.     

Experience facilitates vomeronasal and olfactory influence on Fos expression in medial preoptic area during pheromone exposure or mating in male hamsters

Chemosensory stimuli are essential for mating in male hamsters but either main olfactory or vomeronasal input is sufficient in sexually experienced males. Activation in central chemosensory pathways and medial preoptic area, after stimulation with female chemosignals or after mating, was estimated by counting neurons expressing Fos protein in experienced and naive males, with or without vomeronasal organ lesions. Regions counted included main and accessory olfactory bulbs, corticomedial amygdala, bed nucleus stria terminalis and medial preoptic area. Chemosensory stimulation was more effective in activating medial preoptic area in experienced than in naive males. In experienced males with vomeronasal organs removed, main olfactory input was as effective in activating medial preoptic area as was the combination of main and accessory input available to intact animals. As previously reported, the main olfactory input remaining after vomeronasal lesions in naive males was poorly effective in activating medial preoptic area, and these animals had impaired mating behavior. The change in access of chemosensory input to medial preoptic area after experience suggests that an experience-dependent synaptic modulation in this pathway, perhaps in the amygdala, may underlie some changes in mating behavior with experience.     

Effect of Endotoxin on the Ultrastructure of Liver and Blood Cells of Hamsters

The liver has been identified as one of the main target organs in fatal endotoxic shock (Fine, 1967). The present study was undertaken to study the ultrastructural changes induced in the liver and formed elements of the blood contained in liver sinusoids 30 min. and 24 hr after intracardial injection of an LD₅₀ dose of Escherichia coli endotoxin. No changes were detectable after 30 min., but after 24 hr: (1) the hepatic cells were extensively vesiculated; (2) the arrangement of the lining cells was grossly disturbed leaving wide gaps so that the lumen communicated freely with the space of Disse; and (3) the formed elements were all altered. Platelets were no more than “balloons” containing an abnormally light cytoplasm and a few vesicles. White cells had wide perinuclear zones, and red cells were aggregated. Such severe and extensive damage could be expected to result in liver disfunction, and likely inability of the cells to recover and regenerate. The damage could have resulted from direct action of endotoxin, from release of 5-HT, lysosomal enzymes and possibly other substances from platelets and other cells, or from ischaemia. Possibly all three were involved.