Conformational studies by dynamic NMR. 73.(1) conformational enantiomers of cyclohexene oxide in the solid state
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Journal Article↗
Biomedical subjects
G Simon
Publications and source records attributed to G Simon.
Different structural vascular changes in angiotensin II-treated and cold-stressed rats.
The role of the renin-angiotensin and sympathetic nervous system in the pathogenesis of structural vascular changes in experimental hypertension was investigated by comparing the effect of angiotensin II (ANG II) administration and of sympathetic stimulation by cold stress on the structure and composition of mesenteric arteries of rats. Adult male Sprague-Dawley rats were administered subcutaneously 100 ng/kg per min ANG II or exposed to 5 degrees C cold overnight for 12 weeks. Sham-operated rats were controls. At the end of treatment, the mesenteric circulation of rats was perfusion-fixed for morphometric measurements by light microscopy and volume density measurements by point counting on electron micrographs. Tail systolic blood pressure of ANG II-treated rats increased by 37 mm Hg at week 2 and remained elevated for the rest of the experiment. The systolic BP of cold-stressed rats measured at room temperature did not change. These findings were confirmed by direct measurement of mean arterial pressure in free-moving rats. Compared to control rats, medial thickening of large and small arteries in ANG II-treated and cold-stressed rats was the main finding of this study. Thickening of the media in the two treated groups of rats appeared to be due to hypertrophy of vascular muscle, as indicated by the increased width of smooth muscle cells. Loose matrix (interstitial fluid compartment) was increased in media of large arteries of ANG II-treated rats, and collagen was increased in the outer media of arteries of cold-stressed rats. Measurements of compositional changes in addition to morphometric changes are needed to detect differences in the pathogenesis of structural vascular changes in the various forms of hypertension.
Angiotensin II↗
Quality adjusted life years in older adults with depressive symptoms and chronic medical disorders.
We used data from a 4-year prospective study of 2,558 primary care patients age 65 and older in a large staff model health maintenance organization to examine the association of clinically significant depressive symptoms and eight other chronic medical conditions with quality adjusted life years (QALYs). We developed linear regression models to examine the association of clinically significant depressive symptoms as defined by a score of 16 or greater on the Center for Epidemiological Studies Depression Scale and eight common chronic medical disorders at baseline with QALYs over the 4-year study period. Estimates of QALYs were derived from Quality of Well-Being Scale scores at baseline, at 2-year follow-up, and at 4-year follow-up. Individuals with clinically significant depressive symptoms at baseline had significantly lower QALYs over the 4-year study period than nondepressed subjects, even after adjusting for differences in age, gender, and the eight other chronic medical conditions. In terms of the entire study population, only arthritis and heart disease were more strongly associated with QALYs than depression.
Aged↗
A look to the past, directions for the future.
This article represents the history of primary care and behavioral health integration at Group Health Cooperative (GHC) over the last decade, and foreshadows probable futures for this work into the next decade. To build from a logical progression, the article responds to a series of questions: 1. Why integrate primary care and behavioral health? 2. What has been done so far and how well has it worked? 3. Keeping the end in mind, what's the idealized picture of integration for the future? 4. How to get from here to there? What will help or hinder the effort? and 5. Again, why make these efforts to integrate?
Behavioral Medicine↗
Are there detectable differences in quality of care or outcome of depression across primary care providers?
OBJECTIVE: The objective of this work was to determine whether there are detectable differences among primary care physicians in measures of quality of care or clinical outcome for depressed patients during the first 2 months of treatment with antidepressant medication. METHODS: We studied 1,599 depressed primary care patients initiating antidepressant treatment from 63 family physicians in 4 primary care clinics of a staff-model health maintenance organization. Patients were interviewed 6 to 8 weeks after initiating antidepressant medication with a telephone structured interview that included the Structural Clinical Interview for DSM-IV Diagnoses (SCID). Automated databases of the HMO were used to examine 3 quality-of-care measures: (1) the percentage of patients who had a refill of their antidepressant by 6 weeks, (2) the percentage of patients who had a return visit by 3 weeks, and (3) the percentage of patients having a return visit by 6 weeks. The percentage of patients in each primary care physician panel who had > or =4 persistent DSM-IV depressive symptoms at 6 to 8 weeks was the main clinical outcome variable. To adjust for case-mix differences between physician panels, patient age, gender, and medical comorbidity were controlled for in the analyses. Two covariates were used to adjust for differences in patients' clinical severity: self-report of > or =2 prior depressive episodes and an SCID diagnosis of major depression during the patient's worst episode in the last 2 years. Physician age, gender, and part-time versus full-time practice were also used as covariates. RESULTS: The wide observed range of variability in quality-of-care and clinical outcome measures by physician practice decreased markedly in the statistical model that controlled for patient-level covariates and differences in the number of patients seen per provider. We did not detect differences in physician practice for the percentage of patients who had a return visit by 3 or 6 weeks, the percentage of patients who had a refill of their antidepressant prescription by 6 weeks, or the percentage of patients with an adverse clinical outcome of depression. CONCLUSIONS: We did not find important differences in measures of quality of care or patient outcomes by physician. These results may have implications for the use of physician profiling and other forms of physician report cards.
Adolescent↗
Care for depression in HMO patients aged 65 and older.
OBJECTIVE: To examine treatment for depression among older adults in a large staff model health maintenance organization (HMO). DESIGN: A 4-year prospective cohort study (1989-1993). SETTING: Four primary care clinics of a large staff model HMO in Seattle, Washington. PATIENTS: A total of 2558 Medicare enrollees aged 65 and older. MAIN OUTCOME MEASURES: Treatment of depression was defined as primary care visits resulting in depression diagnoses, use of antidepressant medications, or specialty mental health services. MAIN RESULTS: The older adults in our sample had low rates of treatment for depression, ranging from 4 to 7% in the entire sample and from 12 to 25% among those with probable depressive disorders. Predictors of treatment included female gender, severity, and persistence of depressive symptoms, and severity of comorbid medical illness. Even when patients were treated for depression, the intensity of treatment was very low. Overall likelihood of treatment for depression increased somewhat from 1989 to 1993, but among those treated, the rate of adequate antidepressant use remained below 30%. CONCLUSIONS: There is still considerable need to improve care for older adults with depression in primary care.
Aged↗
The TorR high-affinity binding site plays a key role in both torR autoregulation and torCAD operon expression in Escherichia coli.
In the presence of trimethylamine N-oxide (TMAO), the TorS-TorR two-component regulatory system induces the torCAD operon, which encodes the TMAO respiratory system of Escherichia coli. The sensor protein TorS detects TMAO and transphosphorylates the response regulator TorR which, in turn, activates transcription of torCAD. The torR gene and the torCAD operon are divergently transcribed, and the short torR-torC intergenic region contains four direct repeats (the tor boxes) which proved to be TorR binding sites. The tor box 1-box 2 region covers the torR transcription start site and constitutes a TorR high-affinity binding site, whereas box 3 and box 4 correspond to low-affinity binding sites. By using torR-lacZ operon fusions in different genetic backgrounds, we showed that the torR gene is negatively autoregulated. Surprisingly, TorR autoregulation is TMAO independent and still occurs in a torS mutant. In addition, this negative regulation involves only the TorR high-affinity binding site. Together, these data suggest that phosphorylated as well as unphosphorylated TorR binds the box 1-box 2 region in vivo, thus preventing RNA polymerase from binding to the torR promoter whatever the growth conditions. By changing the spacing between box 2 and box 3, we demonstrated that the DNA motifs of the high- and low-affinity binding sites must be close to each other and located on the same side of the DNA helix to allow induction of the torCAD operon. Thus, prior TorR binding to the box 1-box 2 region seems to allow cooperative binding of phosphorylated TorR to box 3 and box 4.
Bacterial Proteins↗
Peroxynitrite-induced apoptosis involves activation of multiple caspases in HL-60 cells.
In this study, we show that caspases 2, 3, 6, and 7 were activated during peroxynitrite-induced apoptosis in human leukemia HL-60 cells and that processing of these caspases was accompanied by cleavage of poly(ADP-ribose) polymerase and lamin B. Treatment of cells with DEVD-fluoromethyl ketone (FMK), a selective inhibitor for caspase 3-like proteases, resulted in a marked diminution of apoptotic cells. VAVAD-FMK, an inhibitor of caspase 2, partially inhibited the apoptotic response to peroxynitrite. However, selective inactivation of caspase 6 by VEID-FMK did not affect apoptosis rates. These data suggest that caspase 3-like proteases and caspase 2, but not caspase 6, are required for peroxynitrite-induced apoptosis in this cell type. Moreover, we demonstrate that peroxynitrite treatment stimulated activation of caspases 8 and 9, two initial caspases in the apoptotic signaling pathway, and preincubation of cells with their inhibitor, IETD-FMK, inhibited activation of caspase 3-like proteases and caspase 2 at the concentration that prevents the apoptosis. These observations, together, suggest that caspase 8 and/or caspase 9 mediates activation of caspase 3-like proteases and caspase 2 during the apoptosis induced by peroxynitrite in HL-60 cells.
Apoptosis↗
Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin.
The purpose of this study was to assess the percutaneous absorption of nonylphenol (NP) and the nonylphenol ethoxylates, NPE-4 and NPE-9, in human, porcine and rat skin. In vitro studies with the NPEs were conducted for 8 h in flowthrough diffusion cells using topical solutions of 0.1, 1.0 and 10% in PEG-400 or 1% in water (NPE-9 only). NP absorption was assessed as a 1% solution in PEG-400. All compounds were 14C ring-labeled and radioactivity in perfusate was monitored over time. Skin deposition was measured at the termination of the experiment. Absorption into perfusate and total penetration (compound absorbed plus compound sequestered in skin) were calculated. Absorption of NPE-4, NPE-9 and NP was similar across all species at less than 1% of the applied dose over 8 h. Penetration was generally below 5% of applied dose, the majority located in the stratum corneum. In all species and for both NPEs, the fraction of dose absorbed was highest for the lowest applied dose. Absorptions expressed as actual mass absorbed over 8 h were similar (approximately 0.3 microg/cm2) across all concentrations. Penetration, but not absorption, was greater from a water vehicle compared to a PEG-400 vehicle, particularly in rat skin. These studies suggest that NP, NPE-4 and NPE-9 were minimally absorbed across skin from all three species. Fractional absorption was concentration-dependent, making the actual absorbed flux constant across all doses.
Animals↗
Depression management programs
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Journal Article↗
Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial.
BACKGROUND: Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects, many patients treated with antidepressant medications by primary care physicians have persistent symptoms. METHODS: A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were randomized to a collaborative care intervention (n = 114) or usual care (n = 114) by the primary care physician. Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment. Follow-up assessments were completed at 1, 3, and 6 months by a telephone survey team blinded to randomization status. RESULTS: Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls. Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months. CONCLUSIONS: A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants, satisfaction with care, and depressive outcomes compared with usual care.
Antidepressive Agents↗
Prolonged elevation of insulin content in the unicellular tetrahymena after insulin treatment: induction of insulin production or storage?
In the unicellular organism, Tetrahymena, the first encounter with an exogeneously given hormone results in hormonal imprinting. This causes an increase of the binding capacity of receptors and the production of the appropriate hormone in the progeny generations of the treated cell. In the present experiments the quantity (using radioimmunoassay) and localization (using confocal laser scanning microscopy) of the immunologically insulin-like material (hereafter insulin) were studied for 10 days after 4 h or 24 h 10(-6) M insulin treatment (hormonal imprinting). Forty-eight hours after both insulin treatments a high quantity of insulin was present in the cells. This value was also significantly increased after 96 h. After 8 days the difference to the control was significant only in the 24 h treated group. Confocal microscopy (using antibody to pig insulin) localized insulin in the cell body. The oral field contained extremely high quantities of the endogeneous hormone. Insulin treatment (after 48 and 96 h) caused an elevation of insulin content in general, and specific accumulation in the posterior sections of the cell, around the nucleus and in the periphery were observed. Ten days after both treatments only the peripheral region of the cell body and the ciliary row contained more insulin than the control. This means that after insulin treatment the quantity of insulin increases for a lengthy time period which is followed by the expression of insulin in the peripheral region. Insulin contained by Tetrahymena 48 h after imprinting stimulated glucose uptake of rat diaphragm.
Animals↗
Typologies of anxiety, depression and somatization symptoms among primary care attenders with no formal mental disorder.
BACKGROUND: Typologies of anxiety, depression and somatization symptoms were investigated in individuals with no formal mental disorders, making no a priori assumptions about symptom distribution and inter-relationship. METHOD: The subjects were 1617 adult primary care attenders from the WHO Collaborative Project on Psychological Problems in General Health Care, with at least three symptoms of anxiety, depression and/or somatization, but with no formal ICD-10 disorders. Analyses were based on the grade of membership model, a multivariate statistical procedure exploring indistinct boundaries between disease categories and preserving the heterogeneity of clinical picture within each category. RESULTS: Six prototype categories (or pure types) best described the structure of symptoms included in analyses. Pure type I included the full set of somatization symptoms. Pure type II was characterized by most anxiety and depression symptoms. Pure type III resembled generalized anxiety disorder. Pure type IV consisted of individuals reporting sporadic symptoms of anxiety, depression or somatization. Pure type V defined individuals with sleep problems. Finally, pure type VI was characterized by anxiety symptoms, including panic-like symptoms. CONCLUSIONS: These findings provide support to the existence of a mixed anxiety-depression category crossing the diagnostic boundaries of current anxiety and depression disorders. Moreover, criteria of anxiety and somatization disorders may be re-examined to assess whether lower diagnostic thresholds can be identified that both preserve the symptom profile and clinical features of current diagnostic categories and allow for a better characterization of individuals with substantial psychopathology though not meeting the high symptom thresholds required for a diagnosis of formal mental disorders.
Adolescent↗
Onset of disability in depressed and non-depressed primary care patients.
BACKGROUND: While cross-sectional and longitudinal studies have consistently found depressive illness and disability to be related, understanding whether depression leads to subsequent onset of disability is limited. METHODS: In the context of the multi-centre international WHO Collaborative Study on Psychological Problems in General Health Care, we followed prospectively consulting non-elderly primary care patients who were essentially disability free at baseline but who differed in baseline depression status, comprising 1051 patients free of physical disability at baseline including 14% depression; 914 free of social disability including 9% depression. Depression status was assessed with the CIDI; patient-reported physical disability with the MOS physical functioning scale and social disability with the BDQ role functioning and number of disability days measures; investigator-rated social disability with the Occupational section of Groningen Social Disability schedule; and the treating physicians rated the severity of physical illness. RESULTS: In patients essentially disability free at baseline, depressive illness resulted in a 1.5-fold (at 3 months) and a 1.8-fold (at 12 months) increase in risk of onset of physical disability, after controlling for physical disease severity. Depressive illness also resulted in a 2.2-fold (at 3 months) and a 23-fold (at 12 months) increase in risk of onset of social disability, after controlling for physical disease severity, physical disability and onset of physical disability. CONCLUSIONS: Among non-elderly primary care patients, depressive illness is associated with onset of physical disability and shows an even stronger association with onset of social disability.
Adolescent↗
The prescribing of psychotropic drugs by primary care physicians: an international collaborative study.
Psychotropic drugs play a major role in primary care management of mental disorders. This study expands the existing data on prescribing practices using data from a 15-center, primary care epidemiologic survey. Questions to be addressed include the following: Which clinical and nonclinical factors are related to the prescribing of psychotropic drugs by primary care physicians? How do prescribing patterns vary across primary care centers? At each center, primary care patients were screened using the General Health Questionnaire, and a stratified random sample completed a standardized diagnostic assessment. For each patient completing the diagnostic assessment, the treating primary care physician provided data on clinical diagnosis and medications prescribed. Study results indicated that 11.5% of all practice attenders, 51.7% of cases who received a diagnosis of mental disorders by a physician, and 27.6% of cases who received a diagnosis using the Composite International Diagnostic Interview were treated with psychotropic medication because of their psychologic problems. Anxiolytics, hypnotics, and antidepressants each accounted for approximately 20% of all prescriptions. Prescription rates increased with the prominence of psychologic complaints, severity of mental disorder, severity of social disability, female gender, age older than 40 years, lower education, unemployment, and marital separation. Rates and type of drugs also varied among specific mental disorders; 19.3% of patients with brief recurrent depression but 55.0% with agoraphobia got any psychotropic drug. Antidepressant drugs were prescribed in 7.7% of anxiety disorders compared with 31.9% of depressive disorders. There were large differences between international centers. When comparing client-type centers with clinic-type centers, overall prescription rates were similar (51.2 vs. 52.9%), but significant differences were observed with respect to psychotropic polypharmacy (12.6% client, 6.3% clinic), tranquilizer medication (24.2 client, 32.9% clinic), and antidepressant medication (17.3 client, 8.9% clinic). Psychotropic drugs have an important role in the treatment of mental disorders by general practitioners. Prescription is associated with a number of clinical but also nonclinical factors that must be recognized when guidelines for international use are to be published. Recognition of mental disorders and selection of specific drug classes are important areas in which medical practice needs improvement.
Adult↗
Patterns of care for depressed older adults in a large-staff model HMO.
The authors examined automated pharmacy and visit data for 502 members of a large-staff model health maintenance organization (HMO) who had been diagnosed with depression and started on antidepressants by their primary-care providers. Older patients (age >/=60; n=110) were less likely than younger adults (age 18-59, n=110) to receive adequate doses of antidepressant medications for 30 or 90 days. Older adults were also less likely than younger adults to receive more than two primary-care visits for depression in the 12 weeks after receiving a new antidepressant prescription and were less likely to receive specialty mental health care in the 6 months after receiving a new antidepressant prescription.
Adolescent↗
Current trends in medical mycology.
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Humans↗
Free and total platelet glycoprotein IIb/IIIa measurement in whole blood by quantitative flow cytometry during and after infusion of c7E3 Fab in patients undergoing PTCA.
A quantitative flow cytometry assay was used to evaluate the ex vivo kinetics of c7E3 Fab platelet effect in 16 patients undergoing PTCA treated with abciximab and compared with aggregometry assay. Immunolabeling of platelets was directly assessed on whole blood, using in parallel two monoclonal antibodies (Mabs) raised against GPIIIa, Mab1, the binding of which is inhibited by c7E3 Fab, and Mab2, the binding of which is not affected by c7E3 Fab. We found a severe and sustained inhibition of both GPIIb/IIIa receptors and platelet functions. The inter-individual variation in response to abciximab was low. A significant transient increase at H24 and H48 in the binding of Mab2 was found as an unexpected result, and confirmed in vitro. Results demonstrate that flow cytometry is a reliable method in agreement with aggregation. In addition, our results show that it is a standardized tool and a time-saving technique.
Abciximab↗