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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

Antibiotic prescription in italian children: a population-based study in Friuli Venezia Giulia, north-east Italy.

UNLABELLED: Comprehensive information on prescription patterns of antibiotics in Italy is scarce. This study describes the use of systemic antibiotics in children according to age and sex in Friuli Venezia Giulia, north-east Italy. A pharmacological prescription database was used to identify individual prescriptions provided to all 0-15-y-old resident children (n = 140,630) during 1998. Overall, 124,383 prescriptions were identified. The prescription rate was highest in the 3-6 y olds, with 1491 antibiotic prescriptions per 1,000 children per year. Antibiotics were prescribed for 52% of infants, 57.2% of toddlers and 62% of preschool children. Twenty-nine percent of the prescriptions were for cephalosporins, 27% for macrolides and 24% for broad-spectrum penicillins. Prescription rates were much higher than in other countries such as Denmark, with more antibiotic courses prescribed for more children at all ages. Prescriptions from general practitioners and family paediatricians often included second-line antibiotics (e.g. cephalosporins and macrolides) or antibiotics that have not been approved for community-acquired paediatric infections (e.g. quinolones). CONCLUSION: The development of regional guidelines for antibiotic use in children should be urgently recommended.

Adolescent↗

Breastfeeding by objectives.

BACKGROUND: In many countries, the rates of breastfeeding fall far short of those recommended. National plans to promote breastfeeding are badly needed. We describe the results of a breastfeeding promotion programme planned by objectives and financial penalties in a small region of Italy. METHODS: This observational study was conducted in all the maternity hospitals and immunisation clinics of the six local health authorities of Friuli Venezia Giulia, in the northeast of Italy. The regional health authority included breastfeeding in its annual plans for 1998 and 1999, and asked local health authorities to develop local workplans and targets. A financial penalty was contemplated for local health authorities not achieving objectives and targets. The rates of exclusive, predominant and complementary breastfeeding were measured at birth and at 16-19 weeks of age. Data were collected, using standard definitions and methods, at discharge from hospitals and at the time of the second mandatory immunisation. RESULTS: All local health authorities and hospitals set up a breastfeeding reporting system in 1998 and defined breastfeeding promotion activities for 1999. The rate of exclusive breastfeeding at discharge and at 16-19 weeks increased significantly between 1998 and 1999, with a corresponding reduction of complementary breastfeeding. CONCLUSION: Financial penalties may contribute to the promotion of exclusive breastfeeding.

Birth Rate↗

Importance of the nasal-to-cervical relationship to the profile in rhinoplasty surgery.

There is general agreement that when discussing surgery with the prospective rhinoplasty patient, one may also include discussion of the chin because of the important interrelationship between these two regions. It is apparent that on the profile-lateral view, the four prominences-the forehead, nose, chin, and neck-balance and complement one another. The cervical region, the fourth dimension, was examined to estimate the aesthetic significance of the nasal-to-cervical relationship and to determine the implications to rhinoplasty surgery. Part I of the study was a survey to test the hypothesis that the cervical region affects the perceived impression of the nose. Four standard facial-profile black-and-white photographs were chosen to represent varying degrees of nasal dorsum hump and cervical ptosis problems. Using computer-altering software, only the cervical regions were altered to create a pair of photographs for each of the four profiles: one with a youthful-looking non-ptotic cervical region, the other with a ptotic aged-looking cervical region. Raters were asked to give their first-impression opinions of which nose subjectively appeared "better." Raters consistently (84 percent of the time) chose the nose on the faces with the less ptotic neck as being better. Therefore, a less ptotic neck improved the perceived appearance of the nose. Part II was a retrospective chart review of the rhinoplasty patients of a single surgeon by independent raters. To estimate the aesthetic significance of the nasal-to-cervical relationship, the proportion of patients undergoing rhinoplasty surgery who could have potentially benefited from a youth-restoring neck procedure was determined. Criteria originally described by Ellenbogen and Karlin for judging the results of youth-restoring neck procedures were used as relative indications for neck surgery. An average of 27.2 percent of the patients did not have visible criteria and therefore by definition had relative indications for neck-rejuvenating procedures when undergoing rhinoplasty surgery. As demonstrated in part I of the study, improving the neck could improve the perceived results of the rhinoplasty. Part III of the study validated the Ellenbogen and Karlin criteria. The present authors found that the original criteria were probably based on female patients, that male and older patients had more indications for surgery, and that there was significant interrater agreement with the youthful criteria. In summary, the authors established that a strong nasal-to-cervical relationship exists whereby the perceived appearance of the nose is affected by the neck. The significance of this relationship to rhinoplasty surgery was determined, and it was found that more than 27 percent of rhinoplasty patients could obtain better perceived nasal results with a concomitant neck-rejuvenating procedure. Consequently, discussing neck-rejuvenating procedures with the rhinoplasty patient is valuable.

Adolescent↗

Structural vascular changes in hypertension: role of angiotensin II, dietary sodium supplementation, and sympathetic stimulation, alone and in combination in rats.

Elevated circulating angiotensin (Ang) II levels, dietary sodium, and sympathetic stimulation are recurrent themes of hypertension research, but their in vivo interaction in physiologically meaningful doses has not been adequately investigated. In this study, the interaction of a subpressor dose of Ang II (50 ng. kg(-1). min(-1) SC), 2% NaCl diet, and sympathetic stimulation in the form of overnight cold exposure was investigated in the development of hypertension and of structural vascular changes in male Sprague-Dawley rats. There were 8 experimental groups: sham operation and treatment (control), Ang II, 2% NaCl diet, cold exposure (5 degrees C), Ang II plus 2% NaCl diet, Ang II plus cold exposure, cold exposure plus 2% NaCl diet, and Ang II plus 2% NaCl diet plus cold exposure (triple treatment). For each group, the duration of treatment was 12 weeks. Morphometric measurements of maximally dilated, in situ fixed, second-order (250 to 320 microm OD), intermediate-size (100 to 150 microm OD), and small (50 to 100 microm OD) mesenteric arteries were performed, and wall-to-lumen ratios (W/L) were calculated. During the 12-week study, the blood pressure (BP) load (the area under the systolic BP curve) of rats receiving the combined treatment of Ang II and 2% NaCl diet was increased (P:<0.05), and that of rats receiving the combined treatment of cold exposure and 2% NaCl diet was decreased (P:<0.05); there were no BP changes in the remaining groups of rats. The most pronounced changes among groups occurred in W/L of small resistance arteries. The W/L of small arteries increased in Ang II-treated (P:<0.01) and in cold-stressed rats (P:<0.01). The effect of Ang II was potentiated by the addition of a 2% NaCl diet. In contrast, the addition of 2% NaCl diet to cold stress reduced the W/L of small arteries (P:<0.01). No other positive or negative synergism occurred among groups, including the rats receiving triple treatment. The findings confirm the potentiation of the hypertensinogenic and vascular trophic effects of Ang II by a high-sodium diet but do not provide evidence for synergism between Ang II and sympathetic stimulation. The finding of hypotension and reduced W/L of small resistance arteries in rats receiving the combined treatment of cold stress and high-sodium diet is unique because there are few known nonpharmacological vascular "hypotrophic" stimuli. The ultimate test of the hypertensinogenic potential of pressor stimuli alone or in combination is their long-term administration in physiologically meaningful doses to experimental animals.

Analysis of Variance↗

Small-cell lung cancer.

The management of small-cell lung cancer (SCLC) evolved rapidly through the 1980s, but has stalled since then. The relative roles of surgery and radiotherapy in this former systemic disease have been worked out well. The chemotherapy of SCLC has progressed less rapidly. This article discusses the latest developments in each modality of treatment of SCLC and summarizes current treatment strategies.

Carcinoma, Small Cell↗

ASTI: a guideline-based drug-ordering system for primary care.

Existing computer-based ordering systems for physicians provide effective drug-centered checks but offer little assistance for optimizing the overall patient-centered treatment strategy. Evidence-based clinical practice guidelines have been developed to disseminate state-of-the-art information concerning treatment strategy but these guidelines are poorly used in routine practice. The ASTI project aims to design a guideline-based ordering system to enable general practitioners to avoid prescription errors and to improve compliance with best therapeutic practices. The " critic mode " operates as a background process and corrects the physician's prescription on the basis of automatically triggered elementary rules that account for isolated guideline recommendations. The " guided mode " directs the physician to the best treatment by browsing a comprehensive guideline knowledge base represented as a decision tree. A first prototype, applied to hypertension, is currently under development.

Decision Support Systems, Clinical↗

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↗

What is critical renal artery stenosis? Implications for treatment.

Renovascular disease due to progressive atherosclerotic renal artery stenosis is being diagnosed with increasing frequency in the elderly. At what degree of renal artery stenosis should intervention be recommended is not clear. To answer this question, unilateral or bilateral activation of the renin-angiotensin system or its absence were detected by captopril-stimulated renal vein renin measurements in 49 hypertensive patients, aged 63 years, with normal or near-normal renal function (serum creatinine concentration < or =2.0 mg/dL), and the information was matched against radiographic measurements of the extent of renal artery stenosis. With few exceptions, unilateral or bilateral hypersecretion of renin was associated with 80% or greater reduction of renal artery lumen diameter. In contrast, normal secretion or suppression of renin production in a kidney contralateral to an ischemic one was associated with either normal caliber renal artery or renal artery stenosis less than 80%. These findings suggest that renal artery stenosis less than 80% should be monitored rather than treated because improvement of renal function and amelioration of hypertension are not expected unless the renin-angiotensin system has been activated in the affected kidney. Renoprotection by early intervention is uncertain because progression of renal artery stenosis is unpredictable. Normal captopril-stimulated renal vein renin measurements in hypertensive patients obviate the need for further work-up or interventional therapy of renovascular disease.

Aged↗

Why are patients prescribed psychotropic drugs by general practitioners? Results of an international study.

BACKGROUND: There has been growing interest in factors that might influence the prescription of psychotropic drugs in general practice. METHOD: This was a multi-centre study using a two-phase stratified sampling strategy in primary care facilities from 14 different countries to determine factors associated with the prescription of psychotropic drugs. RESULTS: A total of 1763 consecutive GP attenders aged between 16 and 65 years of age were recruited. Although antidepressants were used more for depressive disorders and anxiolytics for patients with anxiety, the differential diagnosis was otherwise not an important factor in prescribing behaviour. Antidepressants and anxiolytics were prescribed twice as frequently in client centred clinics following a 'personal physician model' as opposed to non-client centred settings, where care was less personalized. The reverse was true of hypnotics (adjusted odds ratio of 0.5). General practitioners with a positive view of their undergraduate psychiatric training and who had had further postgraduate experience in the speciality were significantly less likely to prescribe medication, and if they did they were more likely to use antidepressants. Older patients were significantly more likely to be prescribed psychotropic medication. Several other patient factors emerged when individual classes of medication were considered; these included the loss of a spouse and the absence of physical ill health in the case of antidepressants, and female sex, fewer years of schooling and unemployment in the case of anxiolytics. CONCLUSIONS: Social, health care and GP factors are at least as important as clinical features in the prescription and choice of psychotropic medication.

Adult↗

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↗

Predictors of outcome in a primary care depression trial.

OBJECTIVE: Previous treatment trials have found that approximately one third of depressed patients have persistent symptoms. We examined whether depression severity, comorbid psychiatric illness, and personality factors might play a role in this lack of response. DESIGN: Randomized trial of a stepped collaborative care intervention versus usual care. SETTING: HMO in Seattle, Wash. PATIENTS: Patients with major depression were stratified into severe (N = 149) and mild to moderate depression (N = 79) groups prior to randomization. INTERVENTIONS: A multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and primary care physician. MEASUREMENTS AND MAIN RESULTS: Patients with more severe depression had a higher risk for panic disorder (odds ratio [OR], 5.8), loneliness (OR, 2.6), and childhood emotional abuse (OR, 2.1). Among those with less severe depression, intervention patients showed significantly improved depression outcomes over time compared with those in usual care (z = -3.06, P<.002); however, this difference was not present in the more severely depressed groups (z = 0.61, NS). Although the group with severe depression showed differences between the intervention and control groups from baseline to 3 months that were similar to the group with less severe depression (during the acute phase of the intervention), these differences disappeared by 6 months. CONCLUSIONS: Initial depression severity, comorbid panic disorder, and other psychosocial vulnerabilities were associated with a decreased response to the collaborative care intervention. Although the intervention was appropriate for patients with moderate depression, individuals with higher levels of depression may require a longer continuation phase of therapy in order to achieve optimal depression outcomes.

Adult↗

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↗