mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile technology.

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Respiratory medicine curriculum in Portuguese family medicine training: A Delphi study.

BACKGROUND: Respiratory diseases (RD) constitute a significant part of the workload of family physicians. There is no consensus on what family doctors should know in this area but established methods for achieving consensus may help to overcome this. OBJECTIVES: The purpose of the study was to obtain a national consensus on the required knowledge and skills in respiratory medicine for family medicine trainees after vocational training. METHODS: A Delphi study was conducted via e-mail with a diverse panel of experts. We developed a Learning Curriculum Framework (LCF) with 399 items adapted from the Royal Australasian College of Physicians - Respiratory Medicine Advanced Training Curriculum. The LCF was submitted to the experts in two rounds for consensus. Consensus was considered for items that had an agreement of 80% in the classifications above 4 on a scale of importance that ranged from 1 (not important) to 5 (very important). RESULTS: Consensus was obtained for 159 items (38.8%). These included structure and function of the respiratory tract (0.6%), presenting problems (21.4%), diagnosis (7.5%), interventions and prevention (11.3%), COPD-emphysema (12.6%), tumours (3.1%), infections (10.7%), tuberculosis (5.7%), HIV (1.3%), thromboembolic disease (2.5%), pleural-pulmonary disease (3.1%), pregnancy (0.6%) and sleep disorders (3.8%). Items on iatrogenic diseases and respiratory research did not reach consensus. CONCLUSIONS: Consensus on the respiratory medicine curriculum may contribute to further development of the vocational training curriculum in Portugal. This approach may help teachers in other countries in Europe to develop curricula for respiratory medicine and other areas of general practice.

Direct evidences of enhanced Ga interdiffusion in InAs vertically aligned free-standing nanowires.

Direct evidences of enhanced Ga interdiffusion in InAs free-standing nanowires grown at moderate temperatures by molecular beam epitaxy on GaAs (111)B are presented in this work. Scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction measurements in coplanar and grazing incidence geometries show that nominally grown InAs NWs are actually made of an In0.86Ga0.14As alloy. Unlike typical vapor-liquid-solid growth, these nanowires are formed by diffusion-induced growth combined with strong interdiffusion from substrate material. Based on the experimental results, a simple nanowire growth model accounting for the Ga interdiffusion is also presented. This growth model could be generally applicable to the molecular beam heteroepitaxy of III-V nanowires.

Reduction of testosterone synthesis after high dose interleukin-2 therapy of metastatic cancer.

We have investigated the effect of high dose iv bolus interleukin-2 (IL-2) therapy on sex hormone and adrenal steroid concentrations in six men treated for metastatic renal cell carcinoma or malignant melanoma. Blood concentrations of testosterone, 17 beta-estradiol, LH, FSH, cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) were measured before and after a 5-day course of IL-2 therapy. Cortisol levels rose and DHEA-S decreased insignificantly. DHEA declined, reaching a nadir (P less than 0.001) on day 6, and testosterone decreased significantly on day 2 and reached a nadir on day 6 (P less than 0.0001). Concentrations of both steroids then gradually rose. Estradiol rose on day 4 (P less than 0.001) and then declined. Neither LH nor FSH was affected significantly, although there was a rise in the mean level of LH after IL-2 therapy. Our results suggest that high dose IL-2 therapy in men affects both adrenal and testicular androgen production without inhibiting pituitary trophic hormone secretion. These effects of IL-2 on plasma sex steroids may be the result of cytokines stimulated by IL-2 therapy, rather than direct responses to IL-2.

Association between coagulation factors VII and X with triglyceride rich lipoproteins.

The association between the concentration of different plasma lipoproteins and plasma factor VII (F VII) was analysed by isolating plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) lipoproteins and assessing their in vitro interaction with F VII by immunoenzyme assay using peroxidase labelled anti-factor VII immunoglobulins to determine whether F VII coagulant activity is prognostic for cardiovascular mortality. F VII bound to triglyceride rich lipoproteins, the fixation being stronger on chylomicrons and VLDL fractions than on LDL fractions. In our experiments HDL did not bind to F VII. The fixation of coagulation factor X (FX) tested by the same method is comparable with that of F VII. The nature of this fixation seemed to arise from hydrophobic interaction as calcium was not necessary and the use of Tween 20 inhibited the interaction. The binding of factors VII and X was increased when lipids were previously treated by phospholipase C and the interaction seemed to be completely dependent on the lipid part of the lipoproteins. Hyrophobic fixation is a possible mechanism of interaction of plasma lipoproteins and F VII and X, and it may be of importance in the covariance of triglyceride concentrations and the activity of vitamin K dependent coagulation factors.

Oleic acid inhibits cholesteryl esterase and cholesterol utilization for testosterone synthesis in mouse Leydig cells.

We have observed that nonesterified fatty acids (NEFA) inhibit testosterone synthesis in response to luteinizing hormone (LH) in mouse Leydig cells, possibly by affecting cholesterol utilization or endogenous concentrations. We have now studied the influence of oleic acid (OA) on the cellular content of cholesterol, hydrolysis of cholesterol esters, and steroidogenesis in isolated mouse Leydig cells. OA (700 micromol/L added with fatty acid-free [FAF] albumin, 3 g/dL) significantly (P<.025) reduced testosterone production in response to LH (10 ng/mL), total cholesterol concentrations of Leydig cells and the culture medium, and cholesteryl esterase activity in the cytosol and mitochondria. We also studied the effects of OA on steroidogenesis and cellular cholesterol concentrations after treatments to increase cellular cholesterol. OA at lower concentrations (5 micromol/L with albumin, 0.1 g/dL) or low-density lipoprotein ([LDL] 4 micrograms protein/mL) increased cellular cholesterol (P<.01) without affecting basal steroidogenesis. These treatments failed to reverse the inhibitory (P<.05) effect of OA on testosterone synthesis following LH stimulation, but did significantly (P<.01) increase cellular cholesterol. In summary, OA appears to inhibit testosterone synthesis by inhibiting cholesteryl esterase activity.

Direct and indirect effects of murine interleukin-2, gamma interferon, and tumor necrosis factor on testosterone synthesis in mouse Leydig cells.

It was recently observed that treatment of patients with a high dosage of human interleukin (IL-2) resulted in suppression of plasma concentrations of testosterone. A murine model was developed to assess the direct and indirect effects of murine IL-2 and the secondarily released cytokines, gamma interferon (INF gamma), and tumor necrosis factor (TNF alpha), on testosterone production in isolated Leydig cells. Pretreatment for 24 hours with IL-2 (100 to 500 IU/ml) or INF gamma (100 to 1000 IU/ml) significantly decreased testosterone production in response to luteinizing hormone (LH; P < 0.02 and 0.005, respectively). The combinations of INF gamma with either TNF alpha or IL-2 produced enhanced suppressive effects on Leydig cell testosterone production. Steroidogenic precursors (22-hydroxycholesterol, 17 alpha-hydroxypregnenolone, and dehydroepiandrosterone) restored testosterone secretion to control levels after preincubation with INF gamma or TNF alpha. In contrast, the inhibition of testosterone synthesis produced by either IL-2 or INF gamma plus TNF alpha could be reversed by 17 alpha-hydroxypregnenolone and dehydroepiandrosterone, but not by 22-hydroxycholesterol (P < 0.01). Dibutyryl cyclic adenosine monophosphate was also ineffective in reversing the inhibitory effects of these cytokines on synthesis. Although IL-2 directly inhibited synthesis in isolated Leydig cells, it stimulated testosterone production (P < 0.005) in minced murine testes. This suggests that IL-2 releases regulatory factors from other cells that were able to overcome the direct inhibitory effect of IL-2. This stimulatory effect was not caused by INF gamma and TNF alpha because INF gamma alone or with TNF alpha inhibited (P < 0.005) testosterone production in minced testes.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison between two common methods for measuring Giardia lamblia susceptibility to antiparasitic drugs in vitro.

In this study a comparison between two different methods for measuring the susceptibility of Giardia lamblia trophozoites to metronidazole and albendazole is performed. Modifications of Meloni's method, based on the loss of adherence of parasites to surfaces, and the Hill method, based on the loss of parasite division capacity, are compared. A logistic model was used to calculate the inhibitory concentrations IC(10), IC(50) and IC(90) that were further compared using the respective standard errors. The results obtained, after contact of parasites with the antiparasitic drugs for 24h, show that the adherence method is more sensitive than the multiplication method for low and moderate inhibitory concentrations of albendazole. Conversely for metronidazole the multiplication method seems to be more sensitive for high inhibitory concentrations of the drug. For screening the IC(50), both methods seem to be effective, however, the inhibition of adherence method have even better performance for the benzimidazole like drugs.

[Antithrombotic therapy in the elderly patient]. / Terapêutica antitrombótica no doente idoso.

In 1994 there were about 100,000 deaths in Portugal (99.621), most of these (43%) were caused by cardiocirculatory and cerebrovascular diseases. A revision about antithrombotic therapy in the elderly is completely justified by the importance of these numbers. In respect to oral anticoagulant therapy, special attention is given to its use in atrial fibrillation concerning the actual therapeutic levels. The current recommendations point to the use of INR levels inferior to those usually used. An INR superior to 2.0-3.0 is only used in the case of valvular mechanical prosthesis. Particular importance is given to the problem of therapeutic induction, mentioning the principal causes of fluctuation of dose/response to oral anticoagulants in the elderly, with special attention to the possible alterations of vitamin K metabolism and the therapeutic interference. Finally, we specify the hemorrhagic complications of this kind of antithrombotic treatment, and give the recommended measures for a practical action for patients with a high level of INR with or without hemorrhages. Concerning heparin therapy, an explanation of the action of heparin and the principal differences between standard heparin and low molecular weight heparins are presented. In the elderly, we point out the secondary effects, such as hemorrhages, thrombocytopenia induced by heparin and osteoporosis. The usual measures for its minimization are related to the recommended dose and type of heparin administered. Finally, we approach the problem of the antiplatelet therapy. The current knowledge is reviewed concerning its use in primary prevention and the minimum dose of aspirin that seems to be effective. The use of aspirin in primary prevention, even if it is not well specified, can be proposed, in a minimum dose, in the elderly with high vascular risk (among other associated factors). However, some particular cases must be studied because an identical clinical attitude cannot be accepted for all patients. The minimum effective dose of aspirin is now also known to be significantly inferior to the one that has been used. With the possible exceptions of atrial fibrillation and valvular prosthesis, aspirin seems to be effective in doses of approximately 75 to 150 mg/day. Other possibilities of antiplatelet therapy, are also analysed, with emphasis on platelet receptor inhibitors and metabolic inhibitors, even if their indications not yet been have completely established.

[Antithrombin III. Physiologic, physiopathologic and laboratory aspects]. / Antitrombina III. Aspectos fisiológicos, fisiopatológicos e laboratoriais.

Hemostatic control is based in a delicate balance between the activities of activator enzymes and their inhibitors, each one depending on a large number of proteins. Plasma Antithrombin III (ATIII) is one of the most important coagulation inhibitors and the fundamental enzyme for the therapeutical action of heparin. In the last years it was well established that ATIII deficiency accounts for a thrombotic state and inefficiency of heparin therapy. In this work, the authors review the biology of ATIII including its biochemical nature, its physiology, physiopathology and mechanism of action, analysing the implications of its deficiency. The authors draw the attention on clinical and laboratory studies that analyse the prevalence and importance of congenital and acquired deficiency of ATIII, in relation to the prevalence of venous thrombosis. Finally, the laboratory methods applied to the study of ATIII and to the biological control of heparin therapy are described with emphasis on the importance of the ATIII concentrates on this type of treatment. Also the fundamental aspects of heparin resistance are specially mentioned.

[Platelet antigens: immunology and immuno-allergology]. / Les antigènes plaquettaires: immunologie et immunoallergologie.

Platelet immunology allows the understanding of clinical findings in a genetic and serologic basis. Blood platelets bear common antigens and same specific antigens, classified in five groups (HPA 1 to 5), that are localized on membrane glycoproteins Ia, Ib alpha, IIb and IIIa. Antiplatelet autoimmunization is generally due to IgG antibodies against membrane complexes IIb/IIIa or Ib/lX. Antiplatelet alloimmunization, clinically resulting in Posttransfusion Purpura and Neonatal Thrombocytopenia is more frequently associated with anti-IIb/IIIa antibodies, either anti-HPA-1a or HPA-1b. Finally, platelet participation in immunoallergic reactions is discussed, focusing both platelet activation by allergen itself and platelet recruitment by other inflammatory cells.

[Antiphospholipid immunization syndrome and thrombosis]. / Síndrome de imunização antifosfolipídica e trombose.

The designation of Antiphospholipid Syndrome was first applied by Harris in 1987, to a clinical status characterized by the detection of anticardiolipin and/or lupus anticoagulant with clinical thromboembolic manifestations. Recent advances in its study has shown that the inducing antigen is really a complex of phospholipid and protein. Therefore, it became clear that there is a need for a protein cofactor to the formation and action of antiphospholipid antibodies (APL). The authors present a detailed revision of the nature and specificity of APL, described as its proteic counterpart. Their action is surely conditioned by the specific protein involved with phospholipids, as it may be with Beta 2-Glycoprotein 1, Prothrombin, Protein c and s, Anexin V and the association of plasminogen and t-PA. The isotype of immunoglobulins is also very heterogeneous, since it was detected as IgG as well as IgA and IgM immunoglobulins. Furthermore, they can coexist in the same patient and with no clear relationship with thromboembolic manifestations. These aspects demonstrate well the greater variability that is found in these patients in relation to clinical and laboratory manifestations of the disease. For laboratory diagnosis, micro ELISA systems were developed, allowing the identification of antiphospholipid immunoglobulins with relative specificity and accuracy. Finally, the most frequent clinical expression is described, emphasising the pitfalls of clinical and laboratory diagnosis of the antiphospholipid syndrome.

[Complementary internship of clinical pathology in hematology]. / Internato complementar de patologia clínica em hematologia.

The correct practice of specialized Clinical Pathology is dependent on the acquired aptitude and capacity gained by residents during their specialization. So, the adopted program for residents must be practical and detailed, obviously exceeding the simple and routine execution of laboratory methods and techniques. In this paper the authors describe a scheme for the Clinical Pathology residents practical program in hematology. The program is applied to a central laboratory (Hospital de Santa Maria - Lisboa). This scheme describes the basic principles for orientation of residents: systematic learning and training of laboratory technology, acquisition of experience in organization and valorizing this activity, introduction to methods and practice of quality control and administration of laboratory activity. Methodological studies and valorization are adapted to its clinical and technical specifications. Furthermore, specialization must include other theoretical and practical activities, which are in fact essential to systematization, organization and consolidation or residents knowledge. We schematized the discussion of technical reports, conception and discussion of investigation protocols and active participation in scientific meetings in this field. Responsibility for the execution of practical scientific work and for the presentation of the final report are fundamental to assess the experience and knowledge that has been acquired and simultaneously to give a mean of self criticism and perfectionism. In fact, this last aspect must be a part of the discussion and conclusion of the final report. In this paper, all these particularities are presented and the methods for their effective use are suggested in detail.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evolution of the concept of heath center in the context of the new National Health Service Act and the development of health administration at the local level]. / Evolução do conceito de centro de Saúde no âmbito do novo estatuto do S.N.S. e a criação do nível local de Administração de Saúde.

The authors consider the recently passed about the Portuguese health system reform, namely bills Laws 48/90 and 10/93 (the Bases for Health Law and the National Health Service Act) and they existing some contradictions between the two Laws. In this paper the authors try to adopt point out legislation, mainly the Bases for Health Law from August 24, 1990, as a standard for the conceptualization of a model. One of the proposals in this law, the Health Area, is examined according to the functional contents expressed therein. The authors then probe the concept further, suggesting a local health administration function, at in a Health Area and aimed based a population of about 30,000 inhabitants (from 10 to 50 thousand) and headed by a local Health Administration. The duties and the functional and organizational structure of this body are defined; suggestions for its composition are also advanced. Considering the organizational structure, the authors suggest some services to be supervised by the Local Health Administration: a Public Health Service, a Secretariat and Accounting Service, a Social Service and other. The new concept of Health Center, as the primary care providing unit, is introduced, as is the idea of a Family Medicine Unit, whose functions, definition and scope are proposed.

Isolation, excystation and axenization of Giardia lamblia isolates: in vitro susceptibility to metronidazole and albendazole.

From 53 samples of human faeces containing Giardia lamblia cysts, 18 isolates were successfully excysted in vitro, and cultivated axenically in TYI-S-33 modified medium. The in vitro effects of metronidazole and albendazole on these isolates were evaluated by the trophozoite adherence inhibition method. The IC50 was between 2.4 and 11.5 micro M for metronidazole and 0.027 and 0.192 micro M for albendazole. These IC50 values were similar to those found for the ATCC 30888 and 30957 reference isolates. All isolates were susceptible to the antiparasitic drugs tested. These results suggest that resistance of G. lamblia to metronidazole and albendazole does not seem to be a significant problem in our population.

The distribution of endocrine cell types of the gastrointestinal mucosa in genetically diabetic (db/db) mice.

BACKGROUND/AIMS: Genetically diabetic (db/db) mice are a model for non-insulin-dependent diabetes in humans. The gastrointestinal tracts in 12-week-old db/db and nondiabetic control (db/+) mice were studied with particular emphasis on the endocrine cells. METHODS: Immunocytochemical and quantification techniques were used to localize and determine the number of cells containing serotonin and various regulatory peptides. RESULTS: In the antrum, the gastrin- and serotonin-immunoreactive cells were increased in number. In the large intestine, the enteroglucagon and the peptide tyrosine-immunoreactive cells were increased in number, whereas there were fewer serotonin-immunoreactive cells. There were also fewer somatostatin-immunoreactive cells in most gastrointestinal regions. In diabetic mice, the intestine was longer and its mucosa thicker than in control mice. CONCLUSIONS: The results indicate that the genetic diabetic (db/db) condition exerts a significant influence on the gastrointestinal tract and on the endocrine cell systems studied. The observed alterations may reflect the effect of indirect factors rather than the diabetes per se.