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Biomedical subjects

C Jaffe

Publications and source records attributed to C Jaffe.

At least 19 recordsLinked to original sources

Secretory process regularity monitors neuroendocrine feedback and feedforward signaling strength in humans.

The present experiments examine the neuroregulatory hypothesis that the degree of sample-by-sample regularity of hormone output by an interlinked hypothalamopituitary target-organ system monitors the strength of feedback and/or feedforward signaling. To test this postulate and assess its generality, we implemented a total of nine thematically complementary perturbation experiments. In particular, we altered feedback or feedforward signaling selectively in two distinct neuroendocrine systems; namely, the growth hormone (GH) insulin-like growth factor type I (IGF-I) and the luteinizing hormone-testosterone axes. Four experimental paradigms comprised preferential reduction vs. enhancement of IGF-I or testosterone feedback signal strength; and, conversely, five others entailed selective attenuation vs. augmentation of GH-releasing hormone and gonadotropin-releasing hormone feedforward signal intensity. In these independent interventions, quantitation of subordinate (nonpulsatile) secretory pattern reproducibility via the approximate entropy statistic unmasked salient changes (P values typically <10(-3)) in the conditional regularity of serial hormone output with high consistency (96-100%). In particular, approximate entropy quantified degradation of secretory subpattern orderliness under either muted feedback restraint or heightened feedforward drive. Assuming valid interpretation of the biological constraints imposed, these experimental observations coincide with earlier reductionist mathematical predictions, wherein increased irregularity of coupled parameter output mirrors attenuated feedback and/or augmented feedforward coupling within an integrative system.

Fasting↗

Transition state theory without time-reversal symmetry: chaotic ionization of the hydrogen atom

We present the first application of transition state theory to a system that evolves from an initial to a final state without time-reversal symmetry. The problem studied is the chaotic ionization of a hydrogen atom in crossed electric and magnetic fields. The stable manifolds of the transition state reveal a fractal tiling which connects the geometrical properties of the tiling to the ionization rate, leading to a theoretical explanation for the computational and experimental observation of "prompt" and "delayed" electrons in this problem.

Journal Article↗

Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial.

Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.

Adolescent↗

Treatment satisfaction compared with outcome in severe dual disorders.

This paper examines patient (N = 75) ratings of treatment satisfaction and outcome for severely mentally ill dually diagnosed outpatients participating in long-term integrated dual focus treatment. In addition, it compares these ratings with case manager ratings of patient outcome over a one year period. Satisfaction ratings ranged from very good to excellent. Combined means of several outcomes ratings indicated that most patients rated themselves as improved. Satisfaction with over-all care and with case management was significantly, though weakly (r = .3 and .31, respectively, p < .05), related to patient ratings of overall outcome. While most patients rated that they had improved, satisfaction with treatment was only weakly related to either patient or case manager rated clinical outcomes. These findings indicate the relatively independent relationship of satisfaction with treatment outcome and caution against over generalizing the meaning of treatment satisfaction measures.

Adult↗

Leishmania tropica: the identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease.

Few experimental studies on Leishmania tropica have been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, for L. tropica infections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific for L. tropica, was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophages in vitro and by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates of L. tropica were nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections using L. tropica metacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates of L. tropica were compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease.

Agglutination Tests↗

A brief medical necessity scale for mental disorders: reliability, validity, and clinical utility.

Managed care organizations (MCOs) use the concept of "medical necessity" to decide whether a prescribed treatment is warranted for a given medical condition. Because mental disorders lack the objective disease criteria common to medical illness, behavioral health administrators need a validated means to identify and quantify the severity of "medically important" aspects of mental disorders. The authors developed and tested a brief medical necessity scale for mental disorders in 205 patients presenting for initial evaluation. The scale had a factor structure with four subscales; good internal consistency, interrater reliability, and concurrent and predictive validity; and modest ability to identify patients requiring hospitalization and, in hospitalized patients, those requiring involuntary hospitalization. The authors propose use of the scale to better clarify decisions about level of care assignments and to better assess patient characteristics predictive of good outcome.

Adult↗

A pilot study comparing severely and persistently mentally ill opiate-addicted patients in dual-diagnosis treatment with patients in methadone maintenance.

The authors describe a severely and persistently mentally ill (SPMI) opiate-addicted (OA) patient sample (n = 43) in a dual-diagnosis outpatient treatment program by demographic, clinical, and treatment characteristics and compare these with other dually diagnosed SPMI patients in the same treatment center (n = 297). Also, those SPMI/OA patients with physiological dependence (n = 20) were compared with a matched sample of OA patients in traditional methadone maintenance (n = 20). The authors then present a clinical evaluation of treatment course and outcome for the SPMI/OA patients (n = 43) and discuss implications from these pilot data.

Adult↗

The relationship of patient-administered outcome assessments to quality of life and physician ratings: validity of the BASIS-32.

The reliability and validity of a patient-administered version of the Behavior and Symptom Identification Scale (BASIS-32) was compared to the original interviewer-administered version. The construct validity of BASIS-32 subscales was assessed by examining their relationship with functional and satisfaction quality of life and physician ratings of functional and clinical status. A total of 361 acute psychiatric inpatients were given a self-administered BASIS-32, nurse-administered Lehman's Quality of Life Interview (QOLI), and Psychiatrist Assessment Form at admission and discharge. The original factor structure, internal consistency reliability, discriminant validity, and sensitivity to change were replicated. The patient-administered BASIS-32 is equally as reliable and valid as the interview. Construct validity analyses revealed that functional and satisfaction QOLI indices were moderately related to the BASIS-32 in the hypothesized directions. All satisfaction scales were associated with significantly less severity. Physician ratings were only mildly related to the subscales. The BASIS-32 used in outcome assessments with inpatients provides important and unique perspectives on functional and clinical status that are not tapped by clinician-rated assessments.

Inpatients↗

Psychiatric status, quality of life, and level of care as predictors of outcomes of acute inpatient treatment.

OBJECTIVE: The study examined the role of five types of variables--demographic characteristics, psychiatric status, functional quality of life, satisfaction with quality of life, and level of care--in predicting key outcomes of inpatient treatment. METHODS: Multivariate canonical regression and univariate multiple regression models were constructed using data from 1,053 inpatients at a public hospital in Washington State. The models were used to predict length of stay, change in symptom severity during hospitalization, psychiatrists' ratings of patients' insight into their illness at discharge, patients' global satisfaction with life, and rehospitalization within 18 months. Hierarchical stepwise procedures were used to select variables that were significant predictors of outcomes. RESULTS: All five classes of predictors were related to the outcomes. The roles of demographic characteristics and diagnoses were minimal. Previous hospitalization and severity of symptoms at admission were strong predictors of psychiatric status. Indicators of functional quality of life and satisfaction with quality of life explained significant variance in all models after accounting for the other classes of predictors. Frequency of family visits was the strongest functional quality-of-life predictor, relating to positive outcomes. Pretreatment satisfaction with life was a significant predictor of most outcomes, and increased satisfaction was associated with positive outcomes. CONCLUSIONS: Patients' quality of life before psychiatric inpatient treatment predicted treatment outcomes independently of psychiatric status, demographic characteristics, and level-of-care variables. Prospective studies are needed to predict outcomes using multidimensional constructs.

Adolescent↗

Sleeping beauty.

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Adaptation, Psychological↗

Structure of Leishmania lipophosphoglycan: inter- and intra-specific polymorphism in Old World species.

The most abundant surface macromolecule on the promastigote stage of leishmanial parasites is a polymorphic lipophosphoglycan (LPG). We have elucidated the structures of two new LPGs, from Leishmania tropica (LRC-L36) and L. aethiopica (LRC-L495), and investigated the nature of intra-specific polymorphism in the previously characterized LPG of L. major (LRC-L456 and -L580). These molecules contain a phosphoglycan chain, made up of repeating PO4-6Gal beta 1-4Man units and a conserved hexaglycosyl-phosphatidylinositol membrane anchor. Extensive polymorphism occurs in the extent to which the LPG repeat units are substituted with different glycan side chains. The L. tropica LPG is the most complex LPG characterized to date, as most of the repeat units are substituted with more than 19 different glycan side chains. All of these side chains, including the novel major glycans, Arap beta 1-3Glc beta 1- and +/- Arap beta 1-2Glc beta 1-4[+/- Arap beta 1-2]Glc beta 1-, are linked to the C-3 position of the backbone disaccharide galactose. In contrast, the L. aethiopica LPG repeat units are partially substituted (35%) with single alpha-mannose residues that are linked, unusually, to the C-2 position of the mannose in the backbone disaccharide. Polymorphism is also evident in the spectrum of alpha-mannose-containing oligosaccharides that cap the non-reducing terminus of the phosphoglycan chains of these LPGs. Finally, analysis of the L. major LPGs showed that, while some strains contain LPGs which are highly substituted with side chains of beta Gal, Gal beta 1-3Gal beta 1- and Arap beta 1-2Gal beta 1-3Gal beta 1-, the LPGs of other strains (i.e L. major LRC-L456) are essentially unsubstituted. Recent studies have shown that the LPG side chains and cap structures can mediate promastigote attachment to a number of different receptors along the midgut of the sandfly vector. The possible significance of LPG polymorphism on the ability of these parasites to infect a number of different sandfly vectors is discussed.

Animals↗

Exclusion of aortic tear in the unstable trauma patient: the utility of transesophageal echocardiography.

OBJECTIVE: The goal of this study was to investigate the value of biplanar transesophageal echocardiography (TEE) as a screening tool for aortic tear in unstable trauma patients. METHODS: During a 1-year period, a prospective trial to exclude aortic tear was conducted at a level I trauma center. Ten of 53 patients (19%) sustaining severe blunt thoracic trauma were deemed too unstable to undergo safe transport to aortography and underwent TEE. Mechanism of injury was motor vehicle crash in eight patients and pedestrians struck in two. Patients had a mean Injury Severity Score = 34 (range, 17 to 59) and mean age = 43 years (range, 18 to 77). Indications for aortic tear evaluation were chest x-ray findings in seven and mechanism of injury alone in three. Patients were not transportable because of hemodynamic instability in five individuals, severe unstable head injury in three individuals, and unstable cervical spine fracture in two individuals. RESULTS: Transesophageal echocardiography was performed in the emergency department in one instance, in the operating room in one instance, and in the surgical intensive care unit in the remaining eight instances. Patients underwent the procedure less than 8 hours after admission in seven and more than 48 hours after admission in three. One patient had a complication during TEE (ventricular dysrhythmias). In one of ten patients, TEE was positive. This patient required medical management (beta-blockade) for aortic tear until severe hypoxia secondary to pulmonary contusion improved after 36 hours. Repair of aortic tear was then successfully performed. CONCLUSIONS: The TEE procedure is valuable in identifying aortic injury in high-risk trauma patients who are too unstable to undergo transport to the aortography suite.

Accidents, Traffic↗

Being a midwife.

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Humans↗