Health outcomes: of means and ends.
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Biomedical subjects
Publications and source records attributed to D Freeman.
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The relationship between apparent faking of cognitive impairment (as detected by such "malingering" tests as 15-item Memorization and Dot Counting) and faking of psychiatric symptoms has not been investigated formally. In addition, no empirical literature is available on the relationship between personality traits and faking of cognitive symptoms. Of 154 subjects who claimed "stress" psychiatric injury, 12% appeared to be faking cognitive impairment; 4.5% failed the 15-item Memorization Test, and 10% failed the Dot Counting task. Faking of cognitive symptoms occurred in only 23% of subjects who were faking/exaggerating psychological symptoms on the MCMI. Malingering test failure was associated with significant elevations on MCMI personality scales, although this appeared to be an artifact of attempts to fake/exaggerate on the MCMI, rather than a reflection of "true" personality traits.
Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.
The amino-terminal fragments of human PTH [hPTH-(1-34)] and PTH-related peptide [PTHrP-(1-34)] appear to be equipotent in several rodent models. However, continuous i.v. infusions of these peptides to young human volunteers suggested that a 10-fold higher molar dose of PTHrP was required to produce comparable circulating levels of the peptide and biochemical responses similar to PTH. As PTHrP has a wide variety of target tissues in mammalian species and may, therefore, play a paracrine, rather than an endocrine, hormonal role in vivo, we evaluated whether enhanced metabolic clearance of injected PTHrP might explain its apparently reduced potency as a PTH-like hormone. Ten healthy subjects [age, 25 +/- 9 (+/- SD) yr] received in random order either hPTH-(1-34) or hPTHrP-(1-34) given by bolus i.v. injections in a dose of 10.7 nmol. Measurements of plasma immunoreactive peptide indicated a comparable volume of distribution for each, but the apparent t1/2 (8.3 +/- 1.6 min) and plasma clearance (4.0 +/- 1.4 L/min) for hPTHrP were significantly (P < 0.05) accelerated compared to those of hPTH (t1/2, 10.2 +/- 0.5 min; clearance, 2.0 +/- 0.4 L/min). Peak plasma cAMP levels were 9-fold lower in response to hPTHrP (29.5 +/- 19 vs. 190 +/- 63 pmol/L; P < 0.01), and increases in urinary cAMP excretion were 5-fold lower (2.1 +/- 1.1 vs. 11.2 +/- 3.7 nmol/mmol creatinine; P < 0.01). No major differences were observed in the urinary excretion of phosphate, calcium, or sodium between the two peptides. Although hPTHrP-(1-34) has a 2-fold higher MCR than hPTH-(1-34), this may not explain the more than 5-fold lower plasma or urinary cAMP response to PTHrP in humans. The comparable effects of PTH and PTHrP on urinary phosphate, calcium, and sodium may indicate a non-cAMP-dependent pathway for these responses, although the intracellular pool of cAMP generated to either peptide, and thus the local target tissue response, could not be estimated in the present study.
MHC class-II-negative astrocytes prevented from intracellular antigen (Ag) processing induce myelin basic protein (MBP)-specific short-term T cell lines to proliferate. This process results from the ability of the T cells themselves to take up, process, and present Ag to each other. The Ag-presenting function of the T cells occurred in the absence of any conventional antigen-presenting cell (APC), was independent of their T cell receptor specificity, was sensitive to chloroquine, and was prevented by anti-class-II MHC antibody. Both native and HPLC-purified MBP were effective in stimulating T cell lines, and there was no obvious benefit in using either enzymatically digested or synthetic peptide preparations of the Ag. Furthermore, the Ag-presenting T cells could take up, reutilize, and re-present Ag adsorbed to the surface of histoincompatible astrocytes. Responding T cells activated by Ag-presenting T cells in the absence of other conventional APC were fully encephalitogenic upon transfer to syngeneic recipients. These results have relevance for understanding pathogenetic mechanisms in T cell-mediated autoimmunity in the central nervous system.
Parent and child reports were examined to study how epidemiological researchers can best use the information provided to describe childhood psychopathology. As part of a multisite methodologic study of mental disorders in children, a probability sample (N = 248) of children aged 9 to 17 years from the San Juan metropolitan area was selected. This sample was enriched with 74 clinic cases. Both parents and children were administered the DISC.2. Results showed that prevalence estimates were influenced by the informant. The clinicians' diagnosis is more concordant with children's reports of depression and with parents' reports of disruptive disorders. Parents and children provided unique information when interviewed with a structured psychiatric interview about child psychopathology. Their unique perspectives contributed to the observed discordance that emerged when DISC parent and DISC child results are compared. Combining the two perspectives with a simple "OR" rule at the symptom level did not seem to capture the unique perspectives.
We evaluated a rapid monoclonal antibody theophylline assay for two reasons: (a) to determine its specificity with respect to the possible confounding influence of a structurally related xanthine, enprofylline, and (b) to assess its accuracy relative to high-performance liquid chromatography (HPLC). Blood samples were taken from 233 patients who had been randomized in double-blind fashion to receive either oral theophylline (n = 117) or enprofylline (n = 116) for the treatment of chronic reversible obstructive airways disease. Monoclonal antibody assays (MAAs) were performed in 10 clinical sites by 10 trained paramedical technicians. Three patients, who actually received enprofylline but not theophylline, had MAA theophylline values of > or = 3.2 micrograms/ml, giving a specificity of 97%. HPLC determination of simultaneous blood samples confirmed that theophylline levels were in fact < 3.2 micrograms/ml and that theophylline was not being taken surreptitiously. Good correlation was observed between MAA and HPLC in patients taking theophylline (y = 1.07 x + 0.36; r = 0.93; standard error of the estimate (SEE) = 1.93). However, there was wide variability from technician to technician such that r values for individual sites ranged from 0.67 to 0.99. Based on the overall correlation, the prediction of an individual HPLC value from an individual MAA value had broad 95% confidence limits: when the MAA value was 10 micrograms/ml, the predicted HPLC value was 9.19 +/- 3.32; when MAA = 15 micrograms/ml; HPLC = 13.19 +/- 3.33; and when MAA = 20 micrograms/ml; HPLC = 17.19 +/- 3.36.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To present the expected appearance of the irradiated larynx and neck as seen at computed tomography (CT). MATERIALS AND METHODS: Sixty-one patients with primary squamous cell carcinoma of the larynx or hypopharynx were treated with radiation therapy. All patients underwent CT before and after treatment. RESULTS: Expected changes include symmetric thickening of the epiglottis, aryepiglottic folds, and false cords and increased attenuation of the paralaryngeal fat. The posterior pharyngeal wall tends to thicken and its mucosa enhances; retropharyngeal space edema is common. Glottic changes include increased attenuation of the paraglottic fat planes and thickening of the anterior and posterior commissures. Subglottic changes include thickening of the mucosa and submucosa. Soft-tissue changes include skin and platysmal thickening, as well as reticulation and increased attenuation of the subcutaneous and deeper fat. CONCLUSION: Familiarization with expected radiologic changes is essential for interpretation of CT images of the irradiated larynx so that such changes are not mistaken for signs of persistent or recurrent tumor.
PURPOSE: To evaluate the computed tomographic (CT) appearance of laryngeal tumors treated with radiation therapy and the ability of CT to depict persistent or residual tumor. MATERIALS AND METHODS: Sixty-one patients with primary squamous cell carcinoma of the larynx or hypopharynx were treated with definitive radiation therapy. CT was performed in all patients before and after treatment. RESULTS: In 32 of 41 patients with cancer controlled at the primary site, CT showed complete resolution of tumor, whereas in 10 of 14 patients in whom radiation therapy failed, there was minimal or no reduction in tumor. In a subpopulation of patients who underwent repeat imaging, 18 of 19 with tumor controlled at the primary site had complete resolution of tumor. Overall, in four of 13 patients with 50%-75% reduction in tumor size or persistent substantial asymmetry at CT, therapy eventually failed at the primary site. CONCLUSION: Lesions that are reduced by 50% or less at 4-month follow-up CT are highly suspicious for treatment failure. Repeat CT studies every 4 months is recommended in addition to careful clinical follow-up.
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Most insulin-like growth factor-I (IGF-I) in blood is found in complex with IGF binding protein-3 (IGFBP-3). An additional association of IGFBP-3 with an acid-labile subunit is thought to severely limit its ability to cross the vascular endothelium. However, it is not clear whether IGFBP-3 which is not complexed to acid-labile subunit can gain access to tissues and contribute to the transcapillary transport of IGF-I. We have investigated the concentration time profile of 125I-labelled recombinant, non-glycosylated human IGFBP-3 in the rat circulation, its appearance within various organs, urine, and in peritoneal lavage fluid. Radiolabelled IGFBP-3 was administered as a single infusion over 1 min into the catheterized jugular vein of male Wistar rats. Blood was sampled from the femoral artery, and urine by cannulation of the bladder for up to 3 h. The peritoneal cavity was cannulated to allow for the collection of lavage fluid. In a separate series of animals various organs were collected up to 3 h following administration of 125I-labelled IGFBP-3, and the content of radiolabel estimated by gamma spectrometry. Radiolabelled IGFBP-3 was rapidly cleared from the circulation initially (half-life 25 min), however from 70 min life to 3 h the levels of radiolabel remained constant. Neutral gel filtration on Sephadex G200 revealed that 1 h following administration the majority of the [125I]IGFBP-3 existed within a complex of 100-120 kDa, likely to represent an association with the acid-labile subunit. Radioactivity was detected in urine within 30 min of IGFBP-3 administration, was maximally present at 60 min, but declined thereafter. A proportion of the radiolabel in urine represented degraded protein fragments of IGFBP-3, although only 8% of the administered radiolabel was excreted within urine over 3 h. Within 10 min of entry into blood 125I-labelled IGFBP-3 was found within peritoneal lavage fluid. Most of the radiolabel was accumulated within the kidneys, liver, stomach and intestine up to 3 h after administration. However, while the hepatic and renal content were maximal after 30 min, stomach content continued to rise over 1 h, and stabilized at 15% of administered dose for up to 3 h. The results suggest that when not in complex with the acid-labile subunit, IGFBP-3 can rapidly cross capillary endothelia from blood to extravascular compartments. While kidney and liver are likely sites of excretion and degradation, a substantial proportion of IGFBP-3 is also accumulated by gastrointestinal tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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Four children with major sickle hemoglobinopathies developed severe pneumococcal infection. Three had sickle cell hemoglobin C (Hb SC) disease and one had sickle cell anemia (Hb SS). In three instances, there was a fatal outcome. The authors' experience with these cases leads them to question whether any patient with a major sickle hemoglobinopathy should be excluded from receiving prophylactic penicillin or if outpatient management with long-acting cephalosporin treatment in the sickle cell patient with suspected sepsis is appropriate therapy.
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This report examines the extent to which an educational component enhanced the efficacy of a community outreach program in reducing HIV transmission behaviors among injecting drug users (IDUs). The experimental enhancement comprised three group educational sessions where detailed information on HIV risk and protective behaviors was conveyed, protective behaviors were shown and practiced, and a problem solving perspective guided discussion of serostatus results. Substantial risk reduction in behaviors were prospectively measured. However, IDUs assigned on a random basis to the enhanced intervention showed no significant differences in levels of risk reduction when compared to those assigned to the standard-only intervention. The chronic and intensive use of injected drugs among the IDUs studied and their high level of HIV infection suggest the need of interventions geared to maximize the utilization of health care services and enhance the supportive functions of familial and social networks of IDUs.
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