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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
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↗
PubMed1997

[How great is the risk of personal contact in the transmission of hepatitis C virus infection?].

The sexual, household and nosocomial transmission of Hepatitis C virus infection were studied in patients with HCV-RNA positive chronic active hepatitis, confirmed by PCR. Liver function tests and hepatitis C virus serology were performed in family members living in the same household of patients, sexual partners as well as members of the hospital environment in the Department of Hepatology. Fifty-three members of 27 families and 32 staff-members were examined. Quantitative HCR-RNA-PCR and virus serotype of anti-HCV (III.gen.) positive individuals were also identified. Two of the family members turned out to be anti-HCV positive. The husband in one of the married couples was treated for hepatitis of unidentified etiology in an Infectology Department four years ago. His wife was found to have chronic hepatitis C since two years. They both had C virus of serotype 1. The mother and daughter in another family suffered from von Willebrand factor deficiency syndrome. It was documented that they were infected by blood transfusion at different occasions. Their C virus serotypes were different. All the staff members of Hepatology Department were anti-HCV negative. These results confirmed the possibility of the non-parenteral transmission of hepatitis C virus, however, its incidence is very low.

Family↗
PubMed1997

Population-based care of depression: effective disease management strategies to decrease prevalence.

This paper reviews the concepts of population-based care and disease management of major depression. Population-based care and disease management strategies motivated by health care reform provide approaches for organizing health services to lower the prevalence of common medical and psychiatric illnesses in primary care populations. We apply these concepts to the organization of services for patients with major depression.

Cross-Sectional Studies↗
PubMed1997

Hematocrit as a predictor of significant injury after penetrating trauma.

A study was undertaken to determine if there are differences in hematocrit (HCT) during the initial evaluation of patients with and without significant visceral intrathoracic or intraabdominal injury after penetrating trauma and, if so, the predictive value of this parameter. Sixty consecutive adults with potentially significant penetrating trauma who presented to an urban municipal trauma center during a 10-week period were studied. Diagnostic variables were recorded for all patients at risk for significant injury, defined as intrathoracic or intraabdominal injury requiring surgical intervention. Patients were ultimately grouped on the basis of operative findings or observation to discharge. Acquired variables included vital signs, initial HCT (HCT-0), HCT at 15 minutes (HCT-15), HCT at 30 minutes (HCT-30), and fluid administered. Twenty-one patients had significant injuries (INJ), and 39 did not (NO-INJ). INJ patients had lower HCT values than NO-INJ on presentation (35% +/- 6% and 41% +/- 5%, respectively). At presentation, a low HCT was predictive of significant injury, but a normal HCT did not preclude injury. The changes in HCT from arrival to 15 minutes, between INJ and NO-INJ patients, were similar (-1.5% +/- 3% and -0.6% +/- 3% respectively). Only when the decrease in HCT was > or =6.5% from presentation measurements was it predictive of injury. During the first 15 minutes a decrease in HCT of > or =6.5% had a positive predictive value and specificity of 1.0. The change in HCT between 15 and 30 minutes was less useful. There was a large difference between the amounts of fluid given to injured and uninjured patients, which may have been responsible for some of the differences in HCT between the two groups. These results show that HCT may have some diagnostic utility during the early management of penetrating trauma. Presentation with an HCT below normal, or an early decrease in HCT, is an indicator of potential injury. Although many patients with serious internal injuries do not manifest large decreases early after presentation, those who do have a high probability of internal injury. The lower the HCT, or the greater the decrease, the greater the probability that a significant injury exists.

Abdominal Injuries↗
PubMed1997

Synergistic effect of angiotensin II and a high sodium diet on the vascular glycosaminoglycan synthesis of rats.

The effect of dietary sodium supplementation on angiotensin II (ANG II)-induced stimulation of vascular glycosaminoglycan (GAG) synthesis of rats was investigated. Measurements were performed both ex vivo and in vivo to validate the in vivo measurements and to estimate the relative contribution of intrinsic and extrinsic influences to ANG II-stimulated GAG synthesis in sodium-fed rats. Male Sprague-Dawley rats on normal (0.7% NaCl) and high sodium (4.0% NaCl) diets were infused with 100 ng/kg/min ANG II intraperitoneally for 48 h, or sham operated (controls). To measure tissue GAG synthesis, 35SO4 was added to the incubation medium (ex vivo) or injected intravenously into rats (in vivo). Systolic blood pressure of ANG II-treated rats on normal sodium diet was unchanged, but it increased by 13 mm Hg (P < .05) in the rats on the combined treatment of ANG II and a high sodium diet. ANG II or high sodium diet by itself had no effect on GAG synthesis. On the combined treatment, GAG synthesis of the aorta was increased by 17% (P < .05) when measured ex vivo, and by 38% (P < .01) when measured in vivo. In vivo, there was also increased GAG synthesis of mesenteric arteries (P < .01) and of vena cava (P < .02); GAG synthesis of nonvascular tissue (diaphragm, bladder, and kidney) was unchanged. The synergistic effect of ANG II treatment and high sodium diet on GAG synthesis appears to be, in part, arterial pressure independent and vascular tissue specific. The greater effect of combined treatment in vivo than ex vivo suggests that humoral or neural stimuli may be contributing to the interaction.

Angiotensin II↗
PubMed1997

Gender and cross-cultural differences in somatic symptoms associated with emotional distress. An international study in primary care.

BACKGROUND: Gender and cross-cultural differences in the association between somatic symptoms and emotional distress were investigated, using data from the World Health Organization Collaborative Project on Psychological Problems in General Health Care. METHODS: Data were collected at 15 centres in 14 countries around the world. At each centre, a stratified random sample of primary care attenders aged 15-65 years was assessed using, among other instruments, the 28-item General Health Questionnaire and the Composite International Diagnostic Interview-Primary Health Care Version. RESULTS: Females reported higher levels of somatic symptoms and emotional distress than males. A strong correlation between somatic symptoms and emotional distress was found in both sexes, with females reporting more somatic symptoms at each level of emotional distress. However, linear regression analysis showed that gender had no significant effect on level of somatic symptoms, when the effects of centre and emotional distress were controlled for. In both sexes, no specific pattern of association emerged between somatic symptom clusters and either anxiety or depression. Primary care attenders from less developed centres reported more somatic symptoms and showed greater gender differences than individuals from more developed centres, but inter-centre differences were small. Finally, gender was not a significant predictor of reason for consultation (somatic versus mental/behavioural symptoms), after controlling for levels of somatic symptoms and emotional distress as well as for centre effect. CONCLUSIONS: These data do not support the common belief that females somatize more than males or the traditional view that somatization is a basic orientation prevailing in developing countries. Instead, somatic symptoms and emotional distress are strongly associated in primary care attenders, with few differences between the two sexes and across cultures.

Adolescent↗
PubMed1997

A comparison between somatic symptoms with and without clear organic cause: results of an international study.

BACKGROUND: The aim of this study was to determine differences between patients attending primary-care clinics with somatic symptoms for which no organic cause can be found, and those with a clear organic basis for their complaints. METHODS: Physical and psychiatric morbidity was measured in 5447 subjects presenting for primary care in 14 countries. Subjects were recruited using a two-stage design from 26,969 consecutive attenders and 25,916 (96.5%) subjects were successfully screened using the General Health Questionnaire (GHQ-12). The response rate for the second-stage assessment was 63% and consisted of the Composite International Diagnostic Instrument adapted for use in primary care (CIDI-PHC), the 28-item GHQ, the Groningen Social Disability Schedule (GSDS) and GP ratings to assess physical psychiatric and social status. Patients who reached the threshold for the number of somatic symptoms (five or more symptoms) were then divided into two groups on the basis of whether their somatic symptoms were medically explained or not. RESULTS: The presence of somatic symptoms, irrespective of aetiology, was associated with increased social and psychiatric morbidity. In the case of non-medically explained symptoms there was a clear linear relationship while with medically explained symptoms psychiatric morbidity rose sharply in the presence of more than 11 symptoms. Patients who had five or more non-medically explained symptoms were significantly younger, had greater psychiatric morbidity, were at greater risk of harmful use of alcohol and reported greater social disability than those with a medical explanation for their somatic symptoms. Patients who had an excess of somatic symptoms in both categories had especially high rates of social and psychiatric morbidity. CONCLUSIONS: These results show a strong association between somatic symptoms irrespective of aetiology and psychiatric morbidity across disparate cultures.

Adolescent↗
PubMed1997

Effect of neonatal sympathectomy on development of angiotensin II-induced hypertension.

We tested, in the early stage of angiotensin II (ANG II)-induced hypertension, whether sympathectomy prevented the autopotentiation of vasoconstrictor responses by ANG II and, in the chronic, established phase of hypertension, whether the antihypertensive effect of sympathectomy, if any, was related to the prevention of structural vascular changes. Neonatally and sham-sympathectomized male Sprague-Dawley rats received 100 or 200 ng x kg(-1) x min(-1) ANG II intraperitoneally for 7-10 days or 200 ng x kg(-1) x min(-1) ANG II subcutaneously for 4 wk. Sham-treated sympathectomized and sham-sympathectomized rats were controls. Vasoconstrictor responses to ANG II, norepinephrine (NE), arginine vasopressin, and periarterial nerve stimulation were measured in the mesentery of rats, and thereafter, in the chronically treated rats, mesenteric resistance arteries were fixed in situ for morphometric measurements. In ANG II-treated sham-sympathectomized rats: 1) tail systolic blood pressure was unchanged after 7-10 days and increased by 23 mmHg at 4 wk (P < 0.001); 2) vasoconstrictor responses were selectively increased to ANG II (autopotentiation; P = 0.026) and nerve stimulation (P = 0.031) at 7-10 days and nonselectively increased to all stimuli at 4 wk (P < 0.05 to P < 0.01); and 3) after 4 wk, the wall-to-lumen ratio of resistance arteries was increased (P < 0.02). In ANG II-treated sympathectomized rats, there were no changes in systolic blood pressure or vasoconstrictor responses at either 7-10 days or 4 wk, but structural vascular changes developed to the same extent as in sham-sympathectomized ANG II-treated rats. Autopotentiation of vasoconstrictor responses appears to be due to an interaction between ANG II and the sympathetic nervous system, because it is prevented by sympathectomy. The dissociation of function and structure in the chronic stage of ANG II administration to sympathectomized rats suggests that structural vascular changes by themselves are insufficient to cause hypertension, but increased vascular reactivity or vasoconstrictor input is also needed.

Angiotensin II↗
PubMed1997

Synergistic vascular effects of dietary sodium supplementation and angiotensin II administration.

The hypertensinogenic action of dietary sodium supplementation was investigated in angiotensin II (ANG II)-treated rats. We hypothesized that high-sodium diet would potentiate ANG II-induced vasoconstriction and hypertension, including the development of structural vascular changes, through synergistic action with ANG II in stimulating sympathetic activity and vascular growth. Mesenteric vasoconstrictor responses to ANG II, norepinephrine (NE), arginine vasopressin (AVP), and periarterial nerve stimulation were measured in Sprague-Dawley rats after 7-10 days of the following treatments: 200 ng.kg-1.min-1 ip ANG II (n = 12), 4% NaCl diet (n = 11), ANG II + 4% NaCl diet (n = 7), and 0.7% NaCl diet (controls) (n = 15). Additional rats received 50 ng.kg-1.min-1 sc ANG II (n = 8), 2% NaCl diet (n = 9), ANG II + 2% NaCl diet (n = 6), or 0.7% NaCl diet (controls) (n = 10) for 12 wk. Systolic blood pressure (SBP) values were measured weekly for 4 wk and then every other week for 8 wk. Then, the wall-to-lumen ratio (W/L) of mesenteric resistance arteries (< 150 microns OD) was measured after in situ perfusion-fixation. After 7-10 days of treatment, there were no significant changes in SBP in any of the groups. High-sodium diet increased vasoconstrictor responses to ANG II (P < 0.01) and nerve stimulation (P < 0.02), but not to NE or AVP, and in combination with ANG II treatment further potentiated vasoconstrictor responses to ANG II (synergism). After 12 wk of treatment, ANG II increased W/L of small resistance arteries by 11% (P < 0.05) without a significant rise in SBP. ANG II and 2% NaCl diet in combination raised SBP by 36 mmHg (P < 0.01) and increased small artery W/L by 28% (P < 0.001) compared with values obtained in control rats. To test the specificity of the interaction between ANG II and high-sodium diet, all the experiments were repeated during phenylephrine (PE, 10 micrograms.kg-1.min-1 sc) treatment of rats. PE by itself or in combination with high-sodium diet had no effect on the measured parameters. Thus short-term administration of high-sodium diet appears to potentiate vasoconstrictor responses to ANG II by facilitating sympathetic neurotransmission, and long-term administration of high-sodium diet raises SBP by potentiating the trophic vascular effects of ANG II. The interaction appears to be specific to ANG II and is occurring on the vascular level.

Angiotensin II↗
PubMed1997

Collaborative management to achieve depression treatment guidelines.

Two models that integrate the psychiatrist into treatment of depression in primary care have been evaluated in randomized controlled trials. In the psychiatrist/primary care model, a psychiatrist alternated visits with a primary care physician to assist in the education and pharmacologic treatment of the patient. In the psychiatrist/psychologist team model, the psychiatrist worked with a team of psychologists to improve adherence to and effectiveness of antidepressant treatment, with psychologists also providing brief behavioral treatment in the primary care clinic. Findings with the psychiatry/primary care model are reported. It was found that the collaborative model was associated with improved adherence to treatment, increased patient satisfaction with depression care, and improved depression outcome compared with usual care by primary care physicians alone. Similar results were found in the study of the psychiatrist/psychologist collaborative care model. The success of these models indicates the appropriateness of a novel role for the psychiatrist and psychologist, i.e., that of collaboration with primary care physicians in care of the depressed patient in the primary care setting.

Antidepressive Agents↗