A pilot study exploring the role of glucocorticoid receptor variants in primary biliary cirrhosis and primary sclerosing cholangitis

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) significant therapeutic effects of glucocorticoids have not been documented. The most important clinical problem in patients with these diseases is fatigue, which is occasionally invalidating. Abnormalities in the hypothalamo-pituitary-adrenal axis have been suggested as a cause of fatigue. Most effects of glucocorticoids are mediated by the glucocorticoid receptor (hGR alpha). Recently a causative role for a splicing variant of the glucocorticoid receptor (hGR beta) has been proposed in glucocorticoid resistance in asthma and ulcerative colitis, whereas another splicing variant (hGR P) might be associated with glucocorticoid-resistant haematological malignancies. The aims of the present pilot study were to assess abnormalities in glucocorticoid receptor expression and to relate these abnormalities to the development of fatigue and to disease activity and severity in autoimmune cholestatic liver disease. METHODS: Five fatigued and five nonfatigued patients with PBC or PSC were included, and the results were compared with healthy controls. RESULTS: The expression of hGR P was not different from controls, but hGR beta mRNA was significantly increased (p=0.02) and hGR alpha mRNA decreased (p=0.015). There were no significant differences between fatigued and nonfatigued patients. A significant negative correlation between the serum activity of alkaline phosphatase and hGR alpha and hGR P mRNA was found. CONCLUSION: Although there was no relation with fatigue, abnormalities in hGR expression appear to occur in patients with these diseases, and may play a role in its pathophysiology and the poor response to glucocorticoid treatment

The interpretation of the reasons for encounter ‘cough’ and ‘sadness’ in four international family medicine populations

Background This is a study of the relationships between common reasons for encounter and common diagnoses (episode titles) within episodes of care in family practice populations in four countries.Method Participating family doctors recorded details of all their patient contacts in an EoC structure using the International Classification of Primary Care, including RfEs presented by the patient, and the FDs’ diagnostic labels. The relationships between RfEs and episode titles were studied using Bayesian methods.Results The RfE ‘cough’ is a strong, reliable predictor for the diagnoses ‘cough’, ‘acute bronchitis’, ‘URTI’ and ‘acute laryngitis/tracheitis’ and a less strong, but reliable predictor for ‘sinusitis’, ‘pneumonia’, ‘influenza’, ‘asthma’, ‘other viral diseases’, ‘whooping cough’, ‘chronic bronchitis’, ‘wheezing’ and ‘phlegm’. The absence of cough is a weak but reliable predictor to exclude a diagnosis of ‘cough’, ‘acute bronchitis’ and ‘tracheitis’. Its presence allows strong, reliable exclusion of the diagnoses ‘gastroenteritis’, ‘no disease’ and ‘health promotion/prevention’, and less strong exclusion of ‘adverse effects of medication’. The RfE ‘sadness’ is a strong, reliable predictor for the diagnoses ‘feeling sad/depressed’ and ‘depressive disorder’. It is a less strong, but reliable predictor of a diagnosis of ‘acute stress reaction’. The absence of sadness is a weak but reliable predictor to exclude the symptom diagnosis ‘feeling sad/depressed’. Its presence does not support the exclusion of any diagnosis.Conclusions We describe clinically and statistically significant diagnostic associations observed between the RfEs ‘cough’ and ‘sadness’, presenting as a new problem in family practice, and all the episode titles in ICPC

The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene(DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 μg, 0.2 μg, 1 μg, 5 μg, and 20 μg. Buserelin was used in a 2 × 5 μg/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progest

Revisiting the concept of ‘chronic disease’ from the perspective of the episode of care model. Does the ratio of incidence to prevalence rate help us to define a problem as chronic?

Background This is a study of the epidemiology of acute and chronic episodes of care (EoCs) in the Transition Project in three countries. We studied the duration of EoCs for acute and chronic health problems and the relationship of incidence to prevalence rates for these EoCs.Method The Transition Project databases collect data on all elements of the doctor–patient encounter in family medicine. Family doctors code these elements using the International Classification of Primary Care.We used the data from three practice populations to study the duration of EoCs and the ratio of incidence to prevalence for common health problems.Results We found that chronic health problems tended to have proportionately longer duration EoCs, as expected, but also a lower incidence to prevalence rate ratio than acute health problems. Thus, the incidence to prevalence index could be used to define a chronic condition as one with a low ratio, below a defined threshold.Conclusions Chronic health problems tend to have longer duration EoCs, proportionately, across populations. This result is expected, but we found important similarities and differences which make defining a problem as chronic on the basis of time rather difficult. The ratio of incidence to prevalence rates has potential to categorise health problems into acute or chronic categories, at different ratio thresholds (such as 20, 30 or 50%). It seems to perform well in this study of three family practice populations, and is proposed to the scientific community for further evaluation

Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

BACKGROUND: General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. METHODS: We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted) top 10 percent during 1 year (1-year frequent attenders) or 3 years (persistent frequent attenders). All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC) were used to assess morbidity.First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. RESULTS: Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6%) were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6%) were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes). They received more prescriptions for psychotropic medication. CONCLUSION: One out of every seven 1-year-frequent attenders (15.4%) becomes a persistent frequent attender. Compared with non-frequent attenders, and 1-year frequent attenders, persistent frequent attenders consume more health care and are diagnosed not only with more somatic diseases but especially more social problems, psychiatric problems and medically unexplained physical symptoms

Defining frequent attendance in general practice

Background: General practitioners (GPs) or researchers sometimes need to identify frequent attenders (FAs) in order to screen them for unidentified problems and to test specific interventions. We wanted to assess different methods for selecting FAs to identify the most feasible and effective one for use in a general (group) practice. Methods: In the second Dutch National Survey of General Practice, data were collected on 375 899 persons registered with 104 practices. Frequent attendance is defined as the top 3% and 10% of enlisted patients in each one-year age-sex group measured during the study year. We used these two selections as our reference standard. We also selected the top 3% and 10% FAs (90 and 97 percentile) based on four selection methods of diminishing preciseness. We compared the test characteristics of these four methods. Results: Of all enlisted patients, 24 % did not consult the practice during the study year. The mean number of contacts in the top 10% FAs increased in men from 5.8 (age 15-24 years) to 17.5 (age 64-75 years) and in women from 9.7 to 19.8. In the top 3% of FAs, contacts increased in men from 9.2 to 24.5 and in women from 14 to 27.8. The selection of FAs becomes more precise when smaller age classes are used. All selection methods show acceptable results (kappa 0.849 - 0.942) except the three group method. Conclusion: To correctly identify frequent attenders in general practice, we recommend dividing patients into at least three age groups per se

Dizziness reported by elderly patients in family practice: prevalence, incidence, and clinical characteristics

Background: Although dizziness in elderly patients is very common in family practice, most prevalence studies on dizziness are community-based and include a study population that is not representative of family practice. The aim of this study was to investigate the prevalence and incidence of dizziness reported by elderly patients in family practice, to describe their final diagnoses as recorded by the family physician, and to compare the clinical characteristics of dizzy patients with those of non-dizzy patients. Methods: Data were obtained from the Second Dutch National Survey of General Practice, a prospective registration study which took place over a 12-month period in 2001. We developed a search strategy consisting of 15 truncated search terms (based on Dutch synonyms for dizziness), and identified all patients aged 65 or older who visited their family physician because of dizziness (N=3,990). We used the mid-time population as denominator to calculate the prevalence and incidence, and for group comparisons we used the Student's t and Chi-square test, and logistic regression analysis. Results: The one-year prevalence of dizziness in family practice in patients aged 65 or older was 8.3%, it was higher in women than in men, and it increased with age. In patients aged 85 or older the prevalence was similar for men and women. The incidence of dizziness was 47.1 per 1000 person-years. For 39% of the dizzy patients the family physicians did not specify a diagnosis, and recorded a symptom diagnosis as the final diagnosis. Living alone, lower level of education, pre-existing cerebrovascular disease, and pre-existing hypertension were independently associated with dizziness. Conclusions: Dizziness in family practice patients increases with age. It is more common in women than in men, but this gender difference disappears in the very old. Because a large proportion of dizzy elderly patients in family practice remains undiagnosed, it would be worthwhile to carry out more diagnostic research on dizziness in a family practice setting

TTA Processor Synthesis

Due to the decreasing feature size of VLSI technology, the amount of hardware which can be integrated into a single chip increases. As a result, future processor chips can execute tens of operations concurrently. Many applications can profit from these huge amounts of hardware parallelism by designing application specific processors. Two problems emerge however: 1) the design space gets large; it is difficult to chose a satisfactory solution, and 2) the design complexity increases and therefore design cycle gets too long. Solving these problems makes tools for automatic processor design necessary. In this paper we present such a tool. It generates processor layout for so called transport triggered processors. The processor configuration is largely parameterized. A working processor has already been produced using this generator. An important question concerns the quality of automatically generated designs: what do we pay in area and cycle time, when compared to a manual design? In orde..