Stimulus titration and ECT dosing

The seizure threshold to electroconvulsive therapy (ECT) is defined entirely by the duration of the induced seizure, is multidetermined, and varies enormously with a wide variety of patient and treatment factors, including especially the parameters of the ECT stimulus. No consistent relationship has ever been detected between the clinical antidepressant response to ECT and either the threshold or the duration of the induced seizure.The stimulus titration method for determining the seizure threshold (titration-threshold dosing) was the central research tool used to reverse years of dogma by proving that the induced seizure of ECT is not alone sufficient to explain the therapeutic properties of ECT, and that the interaction between dosage and treatment electrode placement is critical in this regard. In clinical use, however, titration-threshold dosing has proven less than fully effective in optimizing the stimulus dose for ECT-better results are consistently obtained with age-based or fixed high-dose methods.The lack of a direct correlation between either seizure threshold or duration and clinical ECT response is an irremediable flaw of the titration-threshold method as clinically applied. New approaches are now called for in which ECT stimulus dosage is set and adjusted ("titrated") according to the clinical antidepressant response of the patient or to measurable correlates thereof: maximum sustained electroencephalogram (EEG) ictal power, EEG postictal suppression, induced interictal EEG delta activity, peak heart rate, maximum sustained EEG coherence, and postictal EEG coherence reduction, all of which have been found by various investigators to be related to the clinical antidepressant response to ECT.     

Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) does not antagonize orphaninFQ/nociceptin-induced prolactin release

The specificity of the orphaninFQ (OFQ)/nociceptin (N)-induced prolactin increase was determined in male and female rats by pretreating animals with different doses of [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2), a compound originally reported to be a specific OFQ/N antagonist. In addition, the effect of naloxone pretreatment on OFQ/N-induced prolactin release was examined to determine if OFQ/N's effects were mediated by opiate receptors. Furthermore, dose response studies using [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) only were performed to determine potential agonist activity of this drug. Finally, growth hormone (GH) levels were determined as an index of specificity of the prolactin response. Our results confirm previous findings that OFQ/N potently stimulates prolactin release and that a gender difference exists in the magnitude of the response, with females showing a much greater response than male rats. The endocrine response is specific because OFQ/N potently stimulated prolactin, but not GH secretion. The prolactin response is not mediated by actions at opiate receptors because naloxone did not inhibit OFQ/N's effects on prolactin release. However, [Phe(1)Psi(CH(2)-NH) Gly2]NC(1-13) NH(2) did not antagonize OFQ/N's effects on prolactin release. Indeed, this drug acted as a potent agonist. Demonstrating pharmacological specificity of OFQ/N's effects on prolactin release awaits the development of more selective, specific antagonists.     

The effect of inpatient hospice units on hospice use post-admission

The objective of this study was to determine whether having a hospice unit within the hospital increases the proportion of terminally ill patients who use hospice services (including home, nursing home, or inpatient hospice) post-admission. Using medical record data abstracted for 232 randomly selected patients with terminal cancer admitted to six community hospitals in Connecticut, we found that patients admitted to a hospital with a hospice unit were more likely to use hospice services (i.e., home hospice, nursing home hospice, or inpatient hospice) post-admission than patients admitted to a hospital without a hospice unit (unadjusted OR 5.7, 95% CI 3.1, 10.6). This effect persisted after adjusting for patient age, gender, marital status, documented discussions of prognosis, prior hospice use, and type of cancer.     

Comparison of mucosal and systemic humoral immune responses after transcutaneous and oral immunization strategies

In order to compare the ability of transcutaneous and oral immunization strategies to induce mucosal and systemic immune responses, we inoculated mice transcutaneously with cholera toxin (CT) or the non-toxic B subunit of cholera toxin (CtxB), or orally with Peru2(pETR1), an attenuated vaccine strain of Vibrio cholerae expressing CtxB. In addition, we also evaluated dual immunization regimens (oral inoculation with transcutaneous boosting, and transcutaneous immunization with oral boosting) in an attempt to optimize induction of both mucosal and systemic immune responses. We found that transcutaneous immunization with purified CtxB or CT induces much more prominent systemic IgG anti-CtxB responses than does oral inoculation with a vaccine vector strain of V. cholerae expressing CtxB. In comparison, anti-CtxB IgA in serum, stool and bile were comparable in mice either transcutaneously or orally immunized. Overall, the most prominent systemic and mucosal anti-CtxB responses occurred in mice that were orally primed with Peru2(pETR1) and transcutaneously boosted with CT. Our results suggest that combination oral and transcutaneous immunization strategies may most prominently induce both mucosal and systemic humoral responses.     

Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an eastern cooperative oncology group study

Chromosome 13 abnormalities (Delta13) have been associated with an unfavorable prognosis in patients with multiple myeloma (MM). The significance of this has been unresolved because of diverse methods of detection and heterogeneous groups of patients. We conducted a study of Delta13 in patients entered into the Eastern Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM (median follow-up of survivors >100 months) were studied for Delta13, using bone marrow samples obtained at study enrollment. We used interphase fluorescence in situ hybridization with the probes LSI13 (Rb)/D13S319 with simultaneous immunofluorescence detection of bone marrow plasma cells (PCs). We detected Delta13 in 176 of 325 (54%) evaluable patients. Patients with Delta13 were more likely to have a serum monoclonal protein at a concentration < or =1 g/dl (22 versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), gamma light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and be female (60 versus 50%; P = 0.087). The PC labeling index and Delta13 correlated (P = 0.03). Patients with Delta13 were less likely to respond to treatment (74 versus 63%; P = 0.041) and had a significantly shorter median overall survival (34.9 versus 51 months; P = 0.021). The association of Delta13 and survival remained an independent prognostic variable in a regression model. Among patients with Delta13, those receiving IFN had a worse overall survival that those not receiving the medication (P = 0.03). The presence of Delta13 is an important and independent adverse prognostic factor in newly diagnosed MM and is associated with specific biological features.     

Trends in use of adjuvant multi-agent chemotherapy and tamoxifen for breast cancer in the United States: 1975-1999

BACKGROUND: Understanding trends in the dissemination of findings from clinical research can help in estimating their population-level benefits. We evaluated trends in the use of adjuvant multi-agent chemotherapy, tamoxifen, and the combination of both treatments for early-stage breast cancer in the United States from 1975 through 1999. METHODS: Data on treatment of 217 508 patients diagnosed from 1975 through 1999 with stages I, II, and IIIA breast cancer were obtained from eight registries of the Surveillance, Epidemiology, and End Results (SEER) Program. Models of dissemination were developed from these data after adjustment based on information from a series of population-based Patterns of Care (POC) studies that randomly selected case patients from the SEER registries. The POC studies included 7116 patients diagnosed from 1987 through 1991 and in 1995 who were eliminated from the SEER data used in this analysis. RESULTS: The modeled disseminations were generally compatible with the POC-observed proportions of each treatment. The use of multi-agent chemotherapy was higher among premenopausal women, and the use of tamoxifen was higher among postmenopausal women. The use of multi-agent chemotherapy for postmenopausal women diagnosed with lymph node-positive stage II+ or stage IIIA cancer reached a peak in 1983 and then decreased through 1986, indicating its substitution with tamoxifen. After 1986, the combined use of multi-agent chemotherapy and tamoxifen increased for almost all stages and ages. After the early 1990s, tamoxifen use in postmenopausal women with stage II+ or stage III breast cancer declined. CONCLUSIONS: The observed dissemination patterns suggest that the results of clinical trials are disseminated fairly rapidly to community-based physicians and their patients.     

Low hemoglobin levels in children with in idiopathic growth hormone deficiency

Multiple lines of evidence have implicated the growth hormone (GH) axis in the regulation of erythropoiesis. To test the hypothesis that GH deficiency is associated with hematologic abnormalities, we analyzed pretreatment hemoglobin levels in 100 children with GH deficiency. Hemoglobin levels were decreased in children with GH deficiency compared with age-corrected norms.     

Comparison of sweat loss estimates for women during prolonged high-intensity running

PURPOSE: This study evaluated the error produced by four commonly used field estimates and two prediction equations of total body sweat loss. METHODS: Eight women distance runners were studied during a 30-km treadmill run (approximately 70% .VO(2max)) in a warm (30 degrees C T(db)) and a cool (14 degrees C T(db)) environment. Total sweat loss (TSL) was determined from changes in body mass corrected for fluid intake (FI), urine losses (UL), clothing (trapped sweat, TS), CO(2)-O(2) exchange (metabolic mass loss, MML), and respiratory water loss (RWL). TSL was compared with four estimates of sweat losses (often employed in the field) from body mass changes corrected for: a) FI only (F-1); b) FI and TS (F-2); c) FI and UL (F-3); or d) FI, TS, and UL (F-4). Two prediction equations were used also for comparison to TSL values. RESULTS: In the warm environment, F-1, F-3, and F-4 accurately estimated (0.2-6.9%; P > 0.05) TSL, whereas F-2 produced a large error (15.3%; P < 0.05). In the cool environment, all four estimates produced large errors (14-41%; P < 0.05). Both prediction equations markedly underestimated (20-22%) TSL in the warm environment and underestimated (41%) or overestimated (20%) TSL in the cool environment. CONCLUSION: TSL can be accurately estimated from changes in body mass using F-1, F-3, or F-4 methods in hot environments; however, none of the methods accurately estimated actual TSL values in a cool environment. Neither prediction equation provided accurate estimates of TSL in warm or cool conditions for women runners. These results illustrate the difficulty of accurately estimating and predicting sweat losses in the field.