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Biomedical subjects

G Simon

Publications and source records attributed to G Simon.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[Measurement of monocyte activation: perspectives in clinical application in the investigation of the diabetic patient].

Monocytes play a pivotal role in the complex processes of inflammation, immunologic responses and atherothrombosis. Clinical studies essentially reported an increased procoagulant activity in diabetes and coronary disease, suggesting an overexpression of tissue factor. This was further confirmed by the direct measurement of tissue factor on monocyte membrane by flow cytometry. Many receptors can be measured on monocytes by flow cytometry: beta 2 integrins (CD 11 a-b-c/CD 18) involved in adhesion, EPR-1 receptor, receptors for advanced glycation products, urokinase receptor U-PAR. Flow cytometry allows a cell analysis in whole blood. Modern methods allow a standardization of the procedures and a quantification of the number of sites expressed by the cell. However, the respect of preanalytical and analytical conditions is mandatory to obtain reliable data. Besides, clinical studies in diabetes should carefully define the subgroups of patients: type of diabetes, metabolic abnormalities, risk factors, infective complications.

Diabetes Mellitus↗
PubMed1999

[Platelet activation in cardiology: methods, indications and therapeutic perspectives].

Platelet activation and/or platelet reactivity have been reported to be associated with coronary heart disease. Whole blood flow cytometry allows to analyze platelets in their physiological environment, while other assays need platelet separation, susceptible to induce platelet modifications. But flow cytometric assay also have limitations. We studied preanalytical conditions in healthy volunteers, using two monoclonal antibodies directed against CD62 and CD63 (two specific markers of platelet degranulation), and two markers which recognize GPIIb/IIIa activation (PAC1 and bound fibrinogen). Preanalytical requirements were as follow: 1) whole blood samples need antagonists of platelet activation i.e., a mixture of theophylline, adenosine and dipyridamole, since artefactual platelet activation rapidly occurred in citrated whole blood, 2) whole blood should be immediately immunolabeled when samples arrived to laboratory, because fixation did not prevent artefactual time dependent activation, 3) the stability of immunolabeling was determined for each monoclonal antibody: paraformaldehyde as fixative solution was mandatory for both CD62 and CD63, whereas it enhanced bound fibrinogen and PAC1 expression, 4) platelets can be easily identified and gating on a dual scatter (forward scatter x side scatter) dot plot with no specified labeling. The whole blood flow cytometric assay must be standardized in future clinical studies, especially regarding to preanalytical requirements.

Adenosine↗
PubMed1999

Use of amoxicillin and amoxicillin-clavulanic acid and hospitalization for acute liver injury.

Increase of acute liver injury in patients taking amoxicillin-clavulanic acid (co-amoxiclav) as compared to those taking amoxicillin has been suggested. To further investigate the potential hepatotoxicity of the two drugs a historical cohort study was conducted in the Italian region of Friuli-Venezia Giulia. One hundred and eighteen potential cases of acute liver injury were identified through the regional hospital information system and medical records were reviewed for all of them. Overall, 12 cases of acute liver injury were identified: 3 cases occurred in the amoxicillin exposure category, 2 among co-amoxiclav group, and 7 in the non-use category. The adjusted estimate of the rate ratio was 5.7 (CI 95% 1.5-22.1) among users of amoxicillin alone and 6.2 (CI 95% 1.3-29.7) among users of co-amoxiclav.

Acute Disease↗
PubMed1998

[Chlamydia pneumoniae infection in patients with myocardial infarct and angina pectoris].

In a prospective open study we investigated Chlamydia pneumoniae infections in 36 consecutively admitted patients: 26 males, mean age 53.4 yr, range 36-70 yr, 10 females mean age 57.7 yr, range 47-70 yr, suffering myocardial infarction (24 acute, 2 previous) or angina pectoris (10). Antibody serum levels were measured by the immunefluorescent method and they were as follows: negative 5, low 12, medium/high 11, chronic infection 5, recent infection 3. The 3 cases considered as recent infections are described in detail.

Adult↗
PubMed1998

Assessing the feasibility of using computerized pharmacy refill data to monitor antidepressant treatment on a population basis: a comparison of automated and self-report data.

This article compares self-report and automated data as measures of dose and duration of antidepressant use in order to assess the feasibility of using automated pharmacy data in a disease management context. We used self-report and computerized refill data to identify two treatment failures-premature discontinuation of the medication and sub-optimal dosages-at time points 1 and 4 months after initiation of antidepressant therapy. The sources showed modest agreement regarding identification of current users at 1 month (kappa = .33); agreement was high at 4 months (kappa = .72). Agreement regarding dosage adequacy was also higher later in treatment, with kappas of .52 and .65 at 1 and 4 months, respectively. The two sources showed high agreement on an overall measure of acute phase treatment adequacy (kappa = .80). Data completeness was another outcome, with data on current users and overall treatment adequacy generally available from computerized files, data on dose less so. Automated pharmacy data appear to be a feasible means of monitoring treatment adequacy and quality of care as part of a disease management approach to improving care for populations of patients.

Antidepressive Agents↗
PubMed1998

A randomized controlled trial of CQI teams and academic detailing: can they alter compliance with guidelines?

BACKGROUND: The availability of clinical guidelines in isolation has generally failed to promote voluntary change in practice patterns. Accordingly, a randomized controlled trial was conducted to determine the effectiveness of academic detailing (AD) techniques and continuous quality improvement (CQI) teams in increasing compliance with national guidelines for the primary care of hypertension and depression. METHODS: Fifteen small group practices at four Seattle primary care clinics were assigned to one of three study arms--AD alone, AD plus CQI teams, or usual care. The activity of 95 providers and 4,995 patients was monitored from August 1, 1993, through January 31, 1996. Twelve-month baseline and study periods were separated by a six-month "wash-in" period during which training sessions were held. Changes in hypertension prescribing, blood pressure control, depression recognition, use of older tricyclics, and scores on the Hopkins Symptom Checklist depression scale were examined. RESULTS: Clinics varied considerably in their implementation of both the AD and the CQI team interventions. Across all sites, AD was associated with change in a single process measure, a decline in the percentage of depressives prescribed first-generation tricyclics (-4.7 percentage points versus control, p = 0.04). No intervention effects were demonstrated for CQI teams across all sites for either disease condition. Within the clinic independently judged most successful at implementing both change strategies, the use of CQI teams and AD in combination did increase the percentage of hypertensives adequately controlled (17.3 percentage points versus control, p = 0.03). SUMMARY AND CONCLUSIONS: The AD techniques and the CQI teams evaluated were generally ineffective in improving guideline compliance and clinical outcomes regarding the primary care of hypertension and depression.

Adult↗
PubMed1998

Effect of neonatal sympathectomy on the development of structural vascular changes in angiotensin II-treated rats.

BACKGROUND: In a previous study, we found that neonatal sympathectomy prevented the development of angiotensin II (ANG II)-induced hypertension but not the development of structural changes in small mesenteric arteries. OBJECTIVES: To investigate further the dissociation between hypertension and structural vascular changes in sympathectomized ANG II-treated rats by extending morphometric measurements to include all segments of the mesenteric arterial tree. METHODS: Neonatally sympathectomized and sham-sympathectomized male Sprague-Dawley rats, aged 34 months, were administered 200 ng/kg per min ANG II subcutaneously for 4 weeks. Sham-operated sympathectomized and sham-sympathectomized rats were controls. At the end of the treatment period the mesenteric circulation of rats was perfusion-fixed for morphometric measurements. RESULTS: Tail systolic blood pressure in ANG II-treated sham-sympathectomized rats increased by 47 mmHg (P < 0.001); the increase of systolic blood pressure (11 mmHg) in ANG II-treated sympathectomized rats did not attain statistical significance. Sympathectomy alone increased the lumen and reduced the wall : lumen ratio of first- and second-order branches of the superior mesenteric artery (hypotrophic outward remodeling). ANG II treatment increased the dimensions, wall thickness, and wall area of first- and second-order arteries (hypertrophic outward remodeling) and the wall : lumen ratio of small resistance arteries in sham-sympathectomized rats. Neonatal sympathectomy attenuated the development of structural changes in large arteries but had no effect on the development of structural changes in small arteries of ANG II-treated rats. CONCLUSION: Hypertension and sympathetic innervation appear to be contributing to the development of structural changes in large arteries of ANG II-treated rats because sympathectomy attenuated these changes. Structural changes in small arteries, on the other hand, appear to be due to a direct trophic effect of ANG II.

Angiotensin II↗
PubMed1998

Structural vascular changes in hypertension: role of angiotensin II, dietary sodium supplementation, blood pressure, and time.

The dose and time dependence of angiotensin II (Ang II) induced hypertension and structural vascular changes and the effect of dietary sodium supplementation on these relationships were investigated. Male Sprague-Dawley rats were treated with 50, 100, or 200 ng . kg-1 . min-1 Ang II subcutaneously for 4 or 12 weeks on normal sodium diet (0.7% NaCl) or with 50 ng . kg-1 . min-1 Ang II SC for 12 weeks on high sodium diet (2% NaCl). Additional rats were sham-operated and fed normal sodium (control rats) or high sodium diet. Plasma Ang II level of rats receiving 100 ng . kg-1 . min-1 Ang II for 4 weeks was 26+/-5 pg/mL (mean+/-SEM, n=7) compared with 11+/-2 pg/mL (n=15) in control rats (P<0.03). Lumen and external diameters of small (50 to 100 microm OD) and intermediate-size (100 to 150 microm OD) resistance arteries were measured in maximally dilated, pump-perfused (55 to 60 mm Hg), in situ fixed mesenteric vascular beds of rats, and wall-to-lumen ratios (W/L) were calculated. Large mesenteric arteries of rats treated with 100 ng . kg-1 . min-1 Ang II for 12 weeks were examined to distinguish hypertrophy from hyperplasia of vascular muscle. Tail systolic blood pressure (BP) and W/L of resistance arteries of Ang II treated rats increased in a dose-dependent manner. Treatment with 50 ng . kg-1 . min-1 Ang II for 12 weeks had no significant effect on BP but produced the same increase in W/L (+10%, n=8, P<0.06) as 100 ng . kg-1 . min-1 Ang II for 4 weeks (+9%, n=18, P<0.05) (time dependence). A 2% NaCl diet for 12 weeks had no significant effect on either BP or W/L, but in combination with 50 ng . kg-1 . min-1 Ang II, it increased systolic BP by 31 mm Hg (P<0.01) and W/L of small resistance arteries by 28% (P<0.01) (synergism). In rats treated with 100 ng . kg-1 . min-1 Ang II for 12 weeks, arterial smooth muscle cell thickness was increased without a change in the number of cell layers (hypertrophy). There was a dissociation between the average BP load (the area under the weekly systolic BP curve) of Ang II treated rats and the W/L of their mesenteric resistance arteries. Ang II induced hypertension and structural vascular changes are dose- and time-dependent and synergistically enhanced by dietary sodium supplementation. Dissociation between BP and vascular structure in Ang II treated rats suggests that a direct trophic effect of Ang II may contribute to the development of structural vascular changes.

Analysis of Variance↗
PubMed1998

The treated prevalence of bipolar disorder in a large staff-model HMO.

OBJECTIVE: The treated prevalence of bipolar disorder was examined in a large staff-model health maintenance organization (HMO) in western Washington state. METHODS: Automated data for all 294,284 adults enrolled in the HMO or treated by HMO providers were used to determine the number of patients treated for bipolar disorder between July 1, 1995, and June 30, 1996. Patients with bipolar disorder were identified using computerized records of inpatient diagnoses, outpatient visit diagnoses, and outpatient prescriptions of mood stabilizers. Validity of the identification procedure was confirmed by review of a random sample of outpatient records. RESULTS: The treated prevalence of bipolar disorder in the HMO was .42 percent. Somewhat higher treated-prevalence rates were found for women, younger enrollees, family members of HMO subscribers, enrollees in some of the individual plans within the HMO, and enrollees in the state's Basic Health Plan program for low-income residents. Of the 1,236 adults treated for bipolar disorder, 93 percent made at least one visit to specialty mental health services, and 86 percent received mood-stabilizing medications. Only a small percentage of the 1,236 patients received treatment with an antidepressant, an antipsychotic, or a benzodiazepine without having a mood stabilizer prescribed. CONCLUSIONS: The treated-prevalence rate found in this HMO population is higher than rates previously reported for prepaid health plans and lower than estimates from large population surveys. The majority of treated patients received specialty mental health services and treatment with mood-stabilizing medications.

Adult↗
PubMed1998

Sequencing analysis of forty-eight human image cDNA clones similar to Drosophila mutant protein.

We have sequenced 48 human IMAGE cDNA clones selected from the public EST database (dbEST) for their significant homology to Drosophila mutant genes. A dynamically updated analysis report was produced by BlastX and BlastN analysis searches in the latest databases available. This analysis led us to estimate the grade of similarity with homologous genes isolated in other species. Bottlenecks were detected in the sequencing process and here we have presented our problem-solving approach. We think the value of this full-length sequencing project is an enrichment of the sequence database information that is currently available to the human genome community.

Animals↗
PubMed1998

The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities.

BACKGROUND: This study reports the responses of patients with confirmed depressive illnesses to different treatments in the WHO Mental Disorders in General Health Care study, conducted in 15 cities around the world. AIM: To discover how depressions recognized by the doctor compare with unrecognized depressions, both in terms of the initial illnesses and their outcomes, and to compare the outcomes of those depressions treated with antidepressants with those treated with daytime sedatives. METHOD: The design of the study was naturalistic, in that physicians were free to treat patients however they wished. Patients with confirmed depressive illnesses were assigned to four groups: treatment with an antidepressant; treatment with a daytime sedative (usually a benzodiazepine); patients recognized as having depression by the physician but were not offered drug treatment; and patients unrecognized as having depression by their physician. RESULTS: Both groups receiving drugs had illnesses of equal severity, were demographically similar to one another, and had similar previous histories of depression. Those receiving antidepressants had significantly fewer overall symptoms and fewer suicidal thoughts than those treated with sedatives. By the end of one year, differences between the groups had disappeared: patients not given drugs had milder illnesses but did significantly better than those receiving drugs, both in terms of symptoms lost and their diagnostic status. Unrecognized depressions were less severe than recognized depressions, and had a similar course over the year. CONCLUSIONS: Patients receiving antidepressants were better in terms of overall symptoms and suicidal thoughts than those treated with sedatives at three months, but this advantage does not persist. Depression emerges as a chronic disorder at one-year follow-up--about 60% of those treated with drugs, and 50% of the milder depressions, still meet criteria for caseness. The study does not support the view that failure to recognize depression has serious adverse consequences, but, in view of the poor prognosis of depression, measures to improve compliance with treatment would appear to be indicated.

Adolescent↗
PubMed1997

Identification by shotgun sequencing, genomic organization, and functional analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.

We recently reported the isolation of two new members of the sulfatase gene family, arylsulfatase D (ARSD) and E (ARSE), located approximately 50 kb from each other in the Xp22.3 region. Mutation analysis indicated ARSE as the gene responsible for X-linked recessive chondrodysplasia punctata. Expression of the ARSE gene in COS cells resulted in a heat-labile arylsulfatase activity that was inhibited by warfarin. At the same time, we detected the presence of a 1.2-kb fragment located at approximately 60 kb from ARSD and ARSE with significant homology to these two genes, suggesting the existence of another sulfatase gene, arylsulfatase F (ARSF), in Xp22.3. We have used a combined approach of long-range genomic sequencing and screening of cDNA libraries to isolate the ARSF gene. Expression of the ARSF cDNA in COS cells resulted in a heat-labile arylsulfatase activity that is not inhibited by warfarin, supporting our hypothesis that only ARSE is specifically inhibited by warfarin and is most likely involved in warfarin embryopathy. Genomic analysis revealed that ARSF has an intron/exon organization highly similar to those of ARSD and ARSE, which is also shared by another Xp22.3 sulfatase gene, ARSC (arylsulfatase C, also known as steroid sulfatase), with the splice sites occurring at the same position in all four genes. The data obtained from sequence analysis and presented in this paper indicate that the ARSC, ARSD, ARSE, and ARSF genes are more similar to each other than to other members of the sulfatase gene family, supporting our hypothesis that they represent a subfamily of related proteins created through duplication events that occurred in an ancestral pseudoautosomal region.

Amino Acid Sequence↗
PubMed1997

Depressive symptoms and the cost of health services in HMO patients aged 65 years and older. A 4-year prospective study.

OBJECTIVE: To examine whether depressive symptoms in older adults contribute to increased cost of general medical services. DESIGN: A 4-year prospective cohort study. SETTING: Four primary care clinics of a large staff-model health maintenance organization (HMO) in Seattle, Wash. PATIENTS: A total of 5012 Medicare enrollees older than 65 years were invited to participate in the study; 2558 subjects (51%) were successfully enrolled. Non-participants were somewhat older and had a higher level of chronic medical illness. MAIN OUTCOME MEASURES: Depressive symptoms as measured by the Center for Epidemiological Studies Depression scale, which was administered as part of a mail survey at baseline, at 2 years, and at 4 years; and total cost of medical services from the perspective of the HMO. Data were obtained from the cost accounting system of the HMO. RESULTS: In this cohort of older adults, depressive symptoms were common, persistent, and associated with a significant increase in the cost of general medical services. This increase was seen for every component of health care costs and was not accounted for by an increase in specialty mental health care. The increase in health care costs remained significant after adjusting for differences in age, sex, and chronic medical illness. CONCLUSIONS: Depressive symptoms in older adults are associated with a significant increase in the cost of medical services, even after adjusting for the severity of chronic medical illness.

Aged↗