Estrogen-induced changes in IGF-I, Myb family and MAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines.

Many studies have implicated numerous hormones, growth factors, cytokines and other signal transduction molecules in the pathogenesis of uterine leiomyoma. Estrogen and estrogen-related genes are thought to play a key role in the growth of uterine leiomyomas, but the molecular mechanisms are unclear. In an attempt to investigate various pathways that might be involved in estrogen-regulated uterine leiomyoma growth as well as to identify any novel effector genes, microarray studies comparing estrogen-treated uterine leiomyoma cells (UtLM) and normal myometrial cells to untreated cells were performed. Several genes were differentially expressed in estrogen treated UtLM cells, including insulin-like growth factor-I (IGF-I) and others potentially involved in the IGF-I signalling pathway, specifically genes for A-myb, a transcription factor which promotes cell cycle progression and for MKP-1, a dual specificity phosphatase that dephosphorylates mitogen-activated protein kinase. IGF-I and A-myb were up-regulated in estrogen-treated cells while MKP-1 was down-regulated. Two other cell cycle promoting genes, c-fos and myc, were also down-regulated in estrogen treated UtLM cells. These genes are typically up-regulated in response to estrogen in some cells, notably breast epithelial cells, yet consistently have lower expression levels in uterine leiomyoma tissue when compared to autologous myometrium. Our results demonstrate some novel genes that may play a role in the growth of uterine leiomyoma, strengthen the case for involvement of the IGF-I pathway in the response of UtLM to estrogen and corroborate evidence that uterine smooth muscle cells respond to estrogen with a different gene expression pattern than that seen in epithelial cells.

Charcoal enhancement of treatment for tricyclic-induced mania.

Induction of mania by tricyclic antidepressants (TCAs) is controversial, with indirect evidence for and against it. Unusual direct evidence of it was observed in a 77-year-old female patient having ingested an amitriptyline overdose. Mania developed while the TCA blood levels were high, and responded to a combination of charcoal and valproate. However, mania reappeared when charcoal was discontinued, and disappeared again when it was restarted. This time course suggests a therapeutic advantage for adding charcoal to valproate in treating tricyclic-induced mania. Presumably, charcoal might have removed a mania-inducing metabolite of amitriptyline. Moreover, repeated doses of oral activated charcoal accelerated the elimination of TCA from the blood stream to several times its original rate, which is consistent with interruption of the enterohepatic circulation. This enhanced elimination and improved outcome illustrate the value of repeated charcoal doses after TCA overdose, and suggest its use when mania develops in a patient who takes an antidepressant, at least amitriptyline or nortriptyline.

Long-term outcome after ECT for catatonic depression.

INTRODUCTION: This is the initial report of the course of major depression with catatonic features after hospitalization. METHOD: Telephone interviews and ratings were conducted 3-7 years after response to inpatient electroconvulsive therapy (ECT) for such catatonic depression. This was done for all 19 followable patients treated over a particular 4-year period. All had received left anterior right temporal brief-pulse ECT. Prior to data examination, we constructed rules to classify medications as antimelancholic. These rules led to the inclusion of lithium, tricyclics, bupropion, and venlafaxine in this antimelancholic classification and to the exclusion of selective serotonin reuptake inhibitors. RESULTS: Ten of the 13 patients discharged on antimelancholic medication (AMM) had good function on follow-up and no more than one rehospitalization. In contrast, none of the six patients in the other group had as good an outcome (p = 0.004, corrected chi2 = 8.26). The AMM group had no deaths, but three patients in the other group died of acute cardiopulmonary causes (p = 0.015). In most cases, catatonia and depression were not identified by informant interview on follow-up. DISCUSSION: ECT followed by AMM usually led to long-term outcome that was good and better than without such medication. Although benzodiazepines can acutely diminish catatonia, we found no relevant long-term study; accordingly, long-term benzodiazepine use in catatonia is speculative.

Validation of an arsenic sequential extraction method for evaluating mobility in sediments.

Arsenic (As) mobility and transport in the environment are strongly influenced by arsenic's associations with solid phases in soil and sediment. We have tested a sequential extraction procedure intended to differentiate the following pools of solid phase arsenic: loosely and strongly adsorbed As; As coprecipitated with metal oxides or amorphous monosulfides; As coprecipitated with crystalline iron (oxyhydr)oxides; As oxides; As coprecipitated with pyrite; and As sulfides. Additions of As-bearing phases to wetland and riverbed sediment subsamples were quantitatively recovered by the following extractants of the sequential extraction procedure: As adsorbed on goethite, 1 M NaH2PO4; arsenic trioxide (As2O3), 10 M HF; arsenopyrite (FeAsS), 16 N HNO3; amorphous As sulfide, 1 N HCI, 50 mM Ti-citrate-EDTA, and 16 N HNO3; and orpiment (As2S3), hot concentrated HNO3/H2O2. Wet sediment subsamples from both highly contaminated wetland peat and less As-rich sandy riverbed sediment were used to test the extraction procedure for intra-method reproducibility. The proportional distribution of As among extractant pools was consistent for subsamples of the wetland and for subsamples of the riverbed sediments. In addition, intermethod variability between the sequential extraction procedure and a single-step hot concentrated HNO3/H2O2 acid digestion was investigated. The sum of the As recovered in the different extractant pools was not significantly different than results for the acid digestion.

Adverse outcome with delay in identification of catatonia in elderly patients.

All three patients to show catatonia at a teaching veterans' hospital over a 1-year period were over 60 years old. Each experienced delays of 2-5 months in identification of catatonia and adverse events attributable to the delay (e.g., pulmonary embolus, physical restraint, pneumonia, mislabeling as "advanced dementia," Do Not Resuscitate orders, and death). These outcomes suggest that geriatric patients with unrecognized catatonia are at high risk for major adverse events.

Melancholic symptoms during concurrent olanzapine and fluoxetine.

The concomitant use of olanzapine and fluoxetine has been advocated for the treatment of various psychiatric disease states. We describe a case in which the combination of olanzapine and fluoxetine appears to have caused the psychopathology of melancholic depression requiring hospitalization in a 40-year-old female. Postulated mechanisms for this drug interaction, particularly CYP450 isoenzyme inhibition by fluoxetine, is discussed.

Efficiency of the stimulus characteristics of ECT.

OBJECTIVE: Greater ECT stimulus efficiency allows for a lower stimulus dose and should diminish the side effects of ECT. METHOD: Four different ECT stimuli of identical charge (average mC=2.5 times age) with pulse widths of 0.5 msec and 1 msec and frequencies of 30 Hz and 60 Hz, respectively, were compared for efficiency. The stimuli were applied in a balanced order to each of 24 subjects. Asymmetric bilateral electrode placement was used. RESULTS: Peak heart rates were higher with the 0.5-msec pulse width than the 1-msec pulse width. Seizure induction was more successful with the 0. 5-msec pulse width than the 1-msec pulse width. Stimulus frequency had no effect on heart rate or seizure induction. CONCLUSIONS: The pulse width of 0.5 msec is more efficient than the 1-msec pulse width. The "half-age" dose for the first bilateral ECT treatment is usually successful for subsequent ECTs when the 0.5-msec pulse width is used.

Resuscitation considerations to prevent pressure ulcers in trauma patients.

The success of a trauma resuscitation is often measured in short-term patient outcomes. To be a true success, the patient should also be protected from long-term problems that are easily preventable. Skin pressure ulcers are a real threat to trauma patients who are immobilized. Nurses involved in the initial care of these patients should be aware of the common causes of skin breakdown and how to prevent it.

Physiological response to ECT stimulus dose.

For a physiological effect to be useful to regulate the electrical stimulus dose used in electroconvulsive therapy (ECT), it must show sensitivity to the stimulus dose. In the analogy of using blood drug concentration to regulate drug dosage, this concentration must be sensitive to the dose. Accordingly, we examined the sensitivity of several physiological effects to ECT stimulus dose. Previously no substantial sensitivity of physiological effects was found when generally effective ECT methods were used. EEG post-ictal suppression, recruitment phase duration, wave form regularity and spike-and-wave frequencies, peak seizure heart rate (HR), and several types of seizure duration were measured with standard and higher dose stimuli given on separate days to 24 subjects. Left frontal to right temporal asymmetric bilateral stimulus placement was applied. Peak HR (P=0.007, t=2.7) and EEG recruitment phase duration (P=0.04, t=1.9) varied with stimulus dose, by 12 beats/min and 1.3 s, respectively. Only peak HR (P=0.02, t=2.2) varied with stimulus dose (by 6 beats/min) when subjects who showed only EEG seizure but no motor seizures were excluded. Subjects who maintained peak HR near their individual maximum values received fewer ECTs than other subjects (P=0.00003, t=5.20); this greater efficacy suggests that the peak HR reflects clinical efficacy as well as stimulus dose. In addition to EEG measurements, peak HR is a candidate to measure ECT seizure quality and provide feedback for stimulus dose regulation.

Variations of peak and baseline heart rates.

The heart rate (HR) rises rapidly with ECT seizure onset and falls with seizure termination. The peak HR is a potential reflection of the intensity of the seizure. Because it varies greatly among patients, comparison with a benchmark HR for each patient should be useful. By comparing variations in the peak and baseline HRs, this study aims to determine if the peak HR should be compared with the baseline. HRs were measured on all treatments for 24 subjects receiving asymmetric bilateral ECT, excluding treatments with motoric seizure duration under 18s or no EEG postictal suppression. The resulting mean variations within subjects were significantly larger for the baseline (7.7 bpm, 8.1%, SD 4.6 bpm, p = 0.004 2-tail, p = 3.2 than the peak HR (4.6 bpm, 3.0%, SD 2.4 bpm). This indicates that comparison of the peak HR with the baseline substantially increases random variations. There was a general absence of correlation between peak and baseline HRs; this reveals no rationale for subtraction of the baseline from the peak. An expression of the peak HR that allows comparisons between patients but avoids the baseline HR is the difference between the seizure peak HR and the highest peak HR seen during that patient's ECT course.

Endpoint of ECT-induced elevation in heart rate.

Changes in the heart rate during electroconvulsive therapy (ECT) reflect seizure activity at a deeper brain site than shown by electroencephalography and motoric activity. Accordingly, such changes may provide additional information that is helpful in the evaluation of treatment quality. One basic measurement of heart rate change is the duration of ECT-induced tachycardia. In a prospective study, the electrocardiographic ECT records of 24 patients were rated for the abruptness of the endpoint of the seizure-induced elevation in heart rate; 19 showed abrupt endpoints and 5 showed gradual endpoints. The baseline heart rate of patients with abrupt endpoints (88 SD [standard deviation] 10 beats/min) was significantly lower (p = 0.00001) than those with gradual endpoints (118 SD 12 beats/min). A threshold occurred at a baseline heart rate of 100 beats/min, with abrupt endpoints below and gradual endpoints above. The data suggest that patients with low baseline heart rates might be likely to show bradyarrhythmia during the treatment, and corresponding precautions might be considered.

Hypofrontal symptoms from olanzapine: a case report.

Olanzapine acutely induced disabling hypofrontal symptoms in a 31-year-old male. This occurred after 13 years of exposure to typical neuroleptics without such symptoms. Presumably, hypofrontal symptoms should limit the dose of atypical neuroleptics in some patients. Milder expressions of hypofrontal symptoms should be more common.