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PubMed1996

HIV viral dynamics.

BACKGROUND: Elucidation of the underlying rapid turnover of virus and HIV infected cells in vivo was perhaps the most informative and exciting discovery in HIV and AIDS research in the last few years. This observation, based on the rapid drop in virus load following antiviral drug therapy promises to change significantly the way we view important aspects of interaction of the virus and its host. As a result, the paradigm for HIV infection has shifted from considering the long period of clinical latency as one of viral inactivity, to viewing it as an active steady state of constant virus replication and cell death. This period should also be viewed as an integral part of the disease process, not simply a prolog to frank AIDS. METHODS: Here, I discuss the theoretical basis of the steady state model of HIV infection as well as its important consequences for understanding and controlling HIV pathogenesis. These include the significance of genetic variation and the establishment and evolution of the virus quasispecies, the evolution of resistance of the virus to antiviral therapy, and the theoretical and practical significance of virus load measurements. Emphasis is on discussion of recent developments as well as areas where our understanding still has significant gaps.

Antiviral Agents↗
PubMed2004

DNA vaccines against human immunodeficiency virus type 1 in the past decade.

This article reviews advances in the field of human immunodeficiency virus type 1 (HIV-1) and AIDS vaccine development over the last decade, with an emphasis on the DNA vaccination approach. Despite the discovery of HIV-1 and AIDS in humans nearly 20 years ago, there is no vaccine yet that can prevent HIV-1 infection. The focus has shifted toward developing vaccines that can control virus replication and disease progression by eliciting broadly cross-reactive T-cell responses. Among several approaches evaluated, the DNA-based modality has shown considerable promise in terms of its ability to elicit cellular immune responses in primate studies. Of great importance are efforts aimed at improvement of the potency of this modality in the clinic. The review discusses principles of DNA vaccine design and the various mechanisms of plasmid-encoded antigen presentation. The review also outlines current DNA-based vaccine strategies and vectors that have successfully been shown to control virus replication and slow disease progression in animal models. Finally, it lists recent strategies that have been developed as well as novel approaches under consideration to enhance the immunogenicity of plasmid-encoded HIV-1 antigen in various animal models.

AIDS Vaccines↗
PubMed1999

[Equipment and aids in trotting races].

During the last years, trotting races met with massive criticism, because some of the numerous items of equipment were not to be reconciled with animal protection. In March 1998, the Trotting Association (HVT), as well as the list of authorized equipment. The so-called "positive list" includes harnesses, bridles, bits, auxiliary reins, driving reins, whips and other aids, among other things brushing boots, ear-muffs and head-pole. Especially criticized items are submitted to an assessment according to the present animal protection law. Moreover, possibilities are shown to make positive conditions in the surrounding area of the trotter more transparent, for instance horse keeping and training management, and to underline them in order to improve the reputation of the trotting sport.

Animal Welfare↗
PubMed1995

A direct approach for correcting AIDS incidence: variance formula and comparison with other methods.

We present a direct approach for correcting the acquired immunodeficiency syndrome (AIDS) incidence data for reporting delays, based on a non-parametric method for the analysis of right truncated data. We show that the proposed method when applied for grouped data is equivalent to three other published methods. We give a simple formula for the variance of the estimated AIDS incidence. Both estimator and variance are assessed in a simulation study. It is important for the estimation of AIDS incidence in the last quarter of the period under consideration to use month rather than quarter or half-year as the time unit for the analyses. The method is illustrated using data from the United States Centers for Disease Control.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Medical diagnosis: are expert systems needed?

An evaluation of the pitfalls of computer-aided diagnosis during the last ten years seems to show that increased emphasis on real clinical problems as well as increased use of medical knowledge are required. Since such an approach could fit into the 'expert system' framework, one should expect new developments in that research field to occur soon. However, expert systems can also be designed along the same concepts as previous models of diagnostic reasoning presumably with the same shortcomings.

Diagnosis, Computer-Assisted↗
PubMed1990

Protozoan infections.

Protozoan infections, against which immunity is predominantly T cell mediated, are likely to be more severe in patients with the acquired immune deficiency syndrome (AIDS) than in immunocompetent hosts. Leishmaniasis, toxoplasmosis and cryptosporidiosis are examples, the last two being particularly common in AIDS patients. Cerebral toxoplasmosis almost always results from recrudescence of latent infections acquired earlier in life. Depletion of T-helper (CD4+) lymphocytes enables bradyzoites to survive if released from cysts in the brain of patients. In the absence of immune pressure bradyzoites revert to tachyzoites and multiply to cause a rapidly developing, necrotizing encephalitis which needs immediate treatment. AIDS patients, especially those who are negative for antibodies to Toxoplasma, should avoid cats, the source of oocysts, and undercooked meat which may contain tissue cysts, as primary infections may become systemic. Cryptosporidium infections are more likely to be primary infections. Sources of infection are other people, farm animals and pets and there is a significant risk from contaminated domestic water supplies. As infections cause a life-threatening secretory diarrhoea in AIDS patients, for which there is not satisfactory treatment at present, such patients should take steps to minimize the risk of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Selective impairment of retrieving people's names: a category specific disorder?

A patient with an extremely long-standing low grade glioma affecting the left temporal lobe is described. The patient was almost entirely unable to retrieve the names of current personalities, although in other respects identification was unimpaired and nominal functions were only mildly inefficient. In particular geographical features and historical figures were generally appropriately named. The problem was equally severe whether naming was to confrontation, from description or by generation. A similarly severe impairment was also found for the retrieval of new words that had come into the language in the last twenty years (eg. aids). The impairment of retrieving people's names was interpreted in terms of a long-standing inability to form new associations between meaning and phonological word-forms.

Amnesia↗
PubMedDate not supplied

A retrieval system for the selection and statistical analysis of clinical data.

Within the last years computer-aided clinical documentation has provided researchers and administrators with very large volumes of data for research. User-friendly retrieval tools are needed when processing these clinical databases. Clinical researchers require applications by means of which steps in selection and analysis can be performed in an iterative process. During the deduction of statistical parameters from routinely collected data a number of problems occur that do not appear in the analysis of data gathered within clinical studies. Unlike clinical studies, routine data have complex structures and must first be formatted and above all temporally synchronized. In this paper we will describe the medical retrieval system ArchiMed developed at the Vienna General Hospital. A main objective in the design of this system was to support a joint evaluation of data from clinical studies and routinely collected data. The retrieval system comprises the main functions: Selection of Patients; Selection and Joining of Variables; and Statistical Analysis.

Databases, Factual↗
PubMed2006

The advent of international 'mail-order' egg donation.

The rising demand and increasing scarcity of donor oocytes in developed countries have led to some fertility clinics sourcing oocyte donors from abroad, particularly from poorer countries, in what is referred to as 'transnational' or 'international' oocyte donation. In a further new 'twist' to this scheme, frozen sperm of the recipient's male partner is exported abroad through courier mail and is used to fertilise donor oocytes in a foreign clinic to produce embryos, which are then cryopreserved and imported back by mail for transfer to the woman. There are numerous ethical concerns with regards to such means of procuring donor oocytes. First, there is an issue of exploiting economically underprivileged women in poorer countries and disproportionate gains on the part of medical doctors and fertility clinics. Second, there is a question of abdication of responsibility for the donor's welfare on the part of the fertility doctor who takes charge of the recipient's treatment abroad if oocyte donors were to develop severe ovarian hyperstimulation syndrome. Third, the issue of responsibility and accountability becomes even more contentious if congenital defects were to appear in offsprings born from transnational oocyte donation or in the case of transmission of communicable diseases such as hepatitis B, syphilis and AIDS to the recipient. Last, cost savings from the lower prescription price of fertility drugs in economically less-developed countries may not be passed down to the oocyte recipient but instead be exploited to boost the already substantial profit margin of fertility clinics and doctors.

Commerce↗
PubMed2006

Phytochrome structure and signaling mechanisms.

Phytochromes are a widespread family of red/far-red responsive photoreceptors first discovered in plants, where they constitute one of the three main classes of photomorphogenesis regulators. All phytochromes utilize covalently attached bilin chromophores that enable photoconversion between red-absorbing (P(r)) and far-red-absorbing (P(fr)) forms. Phytochromes are thus photoswitchable photosensors; canonical phytochromes have a conserved N-terminal photosensory core and a C-terminal regulatory region, which typically includes a histidine-kinase-related domain. The discovery of new bacterial and cyanobacterial members of the phytochrome family within the last decade has greatly aided biochemical and structural characterization of this family, with the first crystal structure of a bacteriophytochrome photosensory core appearing in 2005. This structure and other recent biochemical studies have provided exciting new insights into the structure of phytochrome, the photoconversion process that is central to light sensing, and the mechanism of signal transfer by this important family of photoreceptors.

Models, Molecular↗
PubMed1993

Circulating endothelial giant cells permissive for human cytomegalovirus (HCMV) are detected in disseminated HCMV infections with organ involvement.

Giant cells fully permissive for human cytomegalovirus (HCMV) were found to circulate, at a variable proportion, in peripheral blood of 21 out of 25 immunocompromised patients with disseminated HCMV infection. Circulating endothelial giant cells (EGC) were identified by a specific monoclonal antibody of endothelial origin and shown to express immediate-early, early, and late viral proteins. Immunostaining patterns of different viral proteins were comparable to those detected in vitro in cultured human umbilical vein endothelial cells. EGC counts > 10 were associated with high levels (> 100) of HCMV viremia and antigenemia, as well as with an overt clinical syndrome in transplanted patients, and to an untreated long lasting organ localization in AIDS patients. On the other hand, EGC counts were < 10 during disseminated HCMV infections of both transplant recipients with no apparent organ syndrome and AIDS patients with recent organ involvement. In tissue sections from AIDS patients, infected endothelial cells were found to progressively enlarge till detaching from the small vessel wall and entering blood stream. HCMV-infected EGC represent a new systemic parameter suitable for the diagnosis of HCMV organ involvement and for the study of the pathogenesis of disseminated infections.

AIDS-Related Opportunistic Infections↗
PubMed2004

An assessment of health needs of chronic low back pain patients from general practice.

The perceived health needs of 50 chronic low back pain patients were explored within an interview procedure. Patients described symptom and treatment histories, the problems they encountered living with back pain and their severity. Problems as goals for recovery were prioritized. The last two tasks were aided by the use of a Problem Board. Interviews were analysed both quantitatively and qualitatively. Results indicated that the use of this patient-centred procedure could be helpful in outlining individual concerns, translatable into recovery goals for intervention, regardless of concurrent medical treatment. Implications of this approach for individual needs assessment in chronic conditions and for planning service development are discussed.

Adaptation, Psychological↗
PubMed1991

Antitumor activity of chemical modified natural compounds.

Search of new activity substances starting from chemotherapeutic agents, continuously appears in international literature. Perhaps this search has been done more frequently in the field of antitumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of super computers and emergence of computer net systems, will open new avenues to rational drug design" (Portoghese, P. S., J. Med. Chem. 1989, 32, 1). Unknown pharmacological active compounds synthetized by plants can be found even without this electronic devices, as traditional medicine has pointed out in many countries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inhibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplastic drugs will be examined, particularly those done by Brazilian researches.

Animals↗
PubMed1986

[Clinico-pharmacological study of a new Russian anti-angina preparation dinitrosorbilong].

Eighty patients with ischemic heart disease and stable angina pectoris of effort were examined for the efficacy of dinitrosorbilong (DNL), a new long-acting drug based on isosorbide dinitrate (ID). The anti-ischemic effect of DNL appraised with the aid of repeated exercise lasted about 8h, which was on the average 4 h longer as compared with the duration of the anti-ischemic effect of ID tablets. The regular intake of DNL favoured an appreciable decrease in the number of angina pectoris attacks making it possible to lower nitroglycerin consumption. DNL was well tolerated by the patients.

Administration, Oral↗
PubMed1997

[New developments and trends in adenovirus research].

Adenovirus infections have been associated with a variety of disorders of the respiratory, ocular, gastrointestinal and urogenital systems. In the last fifteen years, special attention has been given to the adenoviral infections in immunocompromised host, transplant recipients, cancer patients and AIDS patients. Adenoviruses in these patients can cause severe, often generalized illness, with high fatality rate. Data suggest a specific role for adenoviruses in AIDS pathogenesis. From AIDS patients many new and intermediate adenovirus serotypes could be isolated. Considerable effort should be devoted to this area of research in the coming years to understand the molecular mechanism of the interaction between AIDS and adenoviruses. In the last few years recombinant adenoviruses have been widely used as gene delivery vectors in experiments both with curative and preventive purposes. Adenovirus vectors have been used in the experimental gene therapy of genetic disorders, of immuno- and molecular therapy of a variety of cancers. The combination of recombinant adenovirus technology with chemotherapy (pro drug system) seems to be promising, as well as the specific destruction of tumor cells with modified, not recombinant adenoviruses. An the other hand, recombinant adenoviruses appear to be attractive candidates for vaccination against the infectious diseases, too. The current tendency is the construction of second-generation vectors which serve better the different purposes. Potential improvements could be the construction of targated vector by the modification of viral cell-tropism and the suppression of the immune response of the host organism directed against the vector and the vector virus infected cells.

Acquired Immunodeficiency Syndrome↗
PubMed1976

[Critical observations on changes in gamma-glutamyl-transpepdidase in hepatopathies].

The behaviour of gamma-glutamyl transpeptidase was compared with other serum enzyme activities and functional parameters in a carefully selected and relatively extensive series of patients with liver disease, including alcoholics, in an investigation of the underlying pathogenesis and its clinical expression. Reference. to the literature and to personal data showed that increased gamma-glutamyl transpeptidase levels could be attributed to enzyme induction (caused by drugs or alcohol), liver damage in the broad sense, and intra- or extrahepatic cholestasis. These causes were individually predominant, or nearly so, on occasions, though their concomitance was more common. High levels, however, were not pathognomonic for a given disease. In alcoholism, they were highly indicative, especially if accompanied by GLD changes. They were a virtually constant, early, and typical finding in intra- and extra-hepatic cholestasis, and tended to persist for a time after the resolution of icterus. Lastly, they were an aid in the early diagnosis of aggressive hepatitis and liver cancer.

Alkaline Phosphatase↗
PubMed2002

Acquired immunodeficiency syndrome in Brazil.

AIM: To describe the acquired immunodeficiency syndrome (AIDS) epidemic in Brazil and analyze the impact of federal government measures addressing the problem since its onset. METHOD: Retrospective review of AIDS epidemic data from its onset in 1980 up to the last published data in June 2001. RESULTS: AIDS was first reported in Brazil in 1980. By 1988, all 27 Brazilian states had diagnosed cases, and until June 2000 more than half of Brazilian municipalities had recorded at least one case of the disease. The AIDS incidence reached its peak between 1996 and 1997 (14.7 per 100,000 population), and then declined between 1998 and 2000 to 9 per 100,000 population. In the last two decades, the proportion of deaths has been also significantly reduced. These were not random events, but reflected the efficiency of the program implemented by the Brazilian Health Ministry's Coordination on Sexually Transmitted Diseases and AIDS. The program includes an epidemiological surveillance modeling system, which records cases from several regular epidemiological bulletins; national network of diagnosis and monitoring of HIV-infected individuals (ill or not); highly active antiretroviral therapy available free to all patients; mother-infant protection program; educational programs on condom use; the introduction of the female condom; development of AIDS studies in different areas to provide practical solutions; constant preoccupation about drug costs accounting for the patent breaking; and national production of many drugs currently in use. CONCLUSION: Well-planned and implemented national program against AIDS can significantly reduce the burden of this disease to the population.

Acquired Immunodeficiency Syndrome↗