Recent advances in our understanding of viral hepatitis involve the discovery and further characterization of the hepatitis C virus and the interferon treatment of patients with chronic viral hepatitis. Liver cirrhosis and primary hepatocellular carcinoma can develop after some years of disease. Interferon is the only effective treatment, which may improve symptoms and prognosis in some patients. Long-term responses with termination of viral replication are seen in 40% of patients with hepatitis B and 15-25% of patients with hepatitis C. In some patients complete elimination of the virus occurs. Higher response rates are achievable in subgroups of patients with favourable prognostic constellations. Patients have to be informed about side-effects and risks of interferon therapy. Treatment in uncomplicated cases is performed on an outpatient basis. The present paper reviews diagnosis, indications, contraindications and practical considerations concerning interferon treatment in patients with chronic viral hepatitis.
Acellular vaccines against pertussis could be developed because various virulence factors of B. pertussis have been characterized. Acellular pertussis vaccines should retain the efficacy but have lower side effects, as compared to the conventional whole-cell vaccine. Lacking any correlate of antibacterial resistance, the efficacy of the vaccines had to be tested in large field trials. Such trials have been conducted and are being conducted in various European and in one African country. These trials used different designs, and various different vaccines were tested. All available efficacy data show that acellular pertussis vaccine can effectively protect against typical pertussis. It also seems probable that the efficacy of vaccines, which contain more than two pertussis components may be better than a vaccine containing pertussis toxoid or pertussis toxoid with filamentous hemagglutinin. A three-component acellular pertussis vaccine has been licensed for use in primary vaccination in infants in Germany in early 1995.
Using pulsed-field gel electrophoresis, DNA fingerprints of eleven Legionella pneumophila isolates of serogroup 2 were generated. It was shown that two strains from a patient suffering from pneumonia as well as three environmental strains isolated from the shower in the hotel where the patient stayed 5 days before his illness were identical. Six strains of the same serogroup isolated from other sources were clearly separated. Thus, DNA fingerprints by pulsed-field gel electrophoresis are excellent epidemiological markers for the rarely occurring serogroup 2 of Legionella pneumophila.
Diabetes mellitus is one of the most frequent metabolic distortions predisposing for infectious diseases. Characteristic features of patients with diabetes mellitus are dysfunctions of professional phagocytes, in particular of polymorphonuclear leucocytes. Infections of skin and soft tissue in particular of the lower extremities, rhinocerebral mucormycosis, invasive external otitis and urinary tract infections are typically associated with diabetes mellitus. Frequently, a rapidly progressive infection requires urgent surgical intervention and parenteral antimicrobial therapy. Short-interval metabolic controls, improvement of metabolic functions, extended vaccination and strict hygiene measures are supportive to prevent infections or to reduce a complicated outcome of infections.
Free radicals and reactive oxygen species can damage cells and tissues of biological organisms. Due to the fact that these compounds are generated continuously in living cells defense mechanisms must exist. This so-called antioxidative system ensures that the formation of free radicals during different physiological processes does not result in cellular damage. Free radicals (oxidants) are produced form the immune system. The purpose of this immune cell products is to destroy invading organisms and damaged tissue. Oxidants enhance IL-1, IL-8 and TNF production in response to inflammatory stimuli. Sophisticated antioxidant defense systems like enzymes or vitamins protect directly and indirectly the host against the damaging influence of oxidants. While endogenous systems can hardly be influenced, exogenous antioxidants, delivered by the diet, can be upregulated in the body. By this way the pro-/antioxidative capacity can be balanced or even unbalanced.
Immunoadsorption is an improvement of extracorporeal therapy which differs from plasmapheresis. After plasma perfusion on a special adsorption filter the patient's plasma is reinfused. Meanwhile more than 270 immunoadsorptions have been performed. 7 patients with SLE and glomerulonephritis as well as 3 patients suffering from Wegener's vasculitis and glomerulonephritis had been treated with combined immunoadsorption and IVIG therapy. After three sessions of immunoadsorption (2-3 1 plasma filtrate) the patients received 10 g 7S-immunoglobulin infusions on three consecutive days. Patients with SLE and end-stage kidney involvement (2 patients) did not show any benefit by the above mentioned treatment regimen. Patients with Wegener's vasculitis and glomerulonephritis showed no significant improvement, except in one of three patients who showed a remarkable decrease in proteinuria. On the other hand, patients with SLE and "moderate" kidney involvement (short course of disease, no fixed structural changes) showed improvement on combined immunoadsorption and IVIG therapy.
Increasing resistance of pneumococci against antimicrobial agents in several parts of the world is reported. We observed a probably nosocomial transmission of a pneumococcal strain with reduced susceptibility to penicillin (capsular type 6A). Recommendations for diagnostic procedures in the laboratory and therapy are given.
Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.
Immunological complications of insulin therapy are extremely rare, since highly purified insulins, especially human semi- or biosynthetic insulin preparations became available for treatment of diabetes mellitus. Insulin antibodies of the immunoglobulin G or immunoglobulin E class can develop in 10-60%, however, in low titers in patients treated exclusively with human insulin. In rare cases these antibodies assume clinical significance, if the antigenic potential of the insulin used is high enough and if genetic predisposition exists. Two case reports presented here confirm this concept.
In experimental exposure studies with ozone or nitrogen dioxide a change in lung function and unspecific airway sensitivity was observed. These effects were paralleled by an induction of cellular and biochemical changes. The exposure of isolated cells in vitro led to a decrease in vitality, an increase in permeability and the secretion of mediators very similar to the composition found in bronchoalveolar lavage after in vivo exposure. The cell culture model, therefore, allows the study of the mechanism of these oxidative air pollutants and allows further the understanding of the influence of different cell types on the observed effects in vivo.
Vaccination against poliomyelitis remains an absolutely mandatory measure to prevent resurgence of this dreadful viral infection. Today, however, when the chance to get infected is extremely low, one has to reconsider much more the inherent risk of such a living vaccine which is principally able to induce neurologic disease especially in immunocompromised host the number of which is increasing in our population. Since these attenuated vaccine strains multiply largely in the orointestinal tract of a vaccine, those viruses are shed and easily spread into surroundings so that other persons which are not aware of this event are exposed. But also in normal hosts the vaccine strains are able to produce disease because the genetic mutation leading to reduced virulence is not absolutely stable. Back mutations with increased virulence develop during multiplication in the vaccinee and may threaten the vaccinee as well as contact persons. For the sake of security these consequences should be respected much more. Since a dead vaccine of polioviruses is available, one should much more often profit from this choice.
The aim of the study was to investigate the frequency and clinical significance of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE).32 of 100 patients with SLE had positive anticardiolipin antibodies. Increased aCL were associated with thrombosis, thrombocytopenia, miscarriage, vasculitic skin changes and neurological symptoms. The incidence of thrombosis, thrombocytopenia, and neurological symptoms was significantly increased in the aCL-positive group as compared to the aCL-negative group.These findings confirm the results of former investigations and underline the role of aCL in systemic lupus erythematosus.
Hyperacute graft rejection triggered by the activation of the recipient's complement system represents the major obstacle to a successful xenotransplantation. Inhibition of complement activation is, therefore, considered as a prerequisite for xenograft survival. Support of the physiological regulation of the complement system appears to be the most promising strategy as indicated by first results from animal xenograft experiments. The transfer of human membrane-bound complement regulatory proteins offers new chances to protect the xenograft against the cytolytic complement attack. Another approach aims at interfering with receptor/ligand interaction of the adhesion molecules CR3 and CR4 (CD11b,c/CD18). All strategies of complement intervention have to consider the important function of complement within the imunological defense.
Although the involvement of complement in hyperacute renal allograft rejection is well established, its possible implication in acute reversible and chronic graft rejection remains uncertain. In recent clinical studies with a total of 83 patients undergoing renal transplantation, plasma levels of complement activation products were elevated 4-7 days before clinical diagnosis of graft rejection. Immunohistochemical analysis of biopsies revealed local complement activation with glomerular deposition of the terminal C5b-9 complex within 1 h after organ reperfusion. Increasing levels of complement activation products, preceding the clinical manifestation of renal graft rejections may be of diagnostic value in recognizing patients at risk.
In clinical medicine mere colonization with yeasts is often hardly to be discriminated from true infection. Thus, a clear-cut separation of preventive from therapeutic use of antimycotics is not possible in practical medicine. The problem is that on the one hand one has no exact diagnosis of yeast infection, but on the other hand best therapeutic results are obtained when the drugs are given as early as possible.In comparison to the huge number of antibacterial compounds, the members of antimicrobials are limited. For prophylaxis, one can use the polyenes, such as amphotericin B and nystatin, or the azoles, such as fluconazole or itraconazole. Thereby the azoles act not only locally at the site of application but are absorbed and thus are distributed to remote sites, where the non-resorbable polyenes never arrive. Among the azoles, fluconazole has the advantage that resorption is independent from an acid pH in the stomach, whereas itraconazole resorption is variable in severely ill persons with neutralized gastric fluid.For therapeutic use systemically applied amphotericin B has certain disadvantages. Because of toxic reactions an optimal dose cannot be given; furthermore in some sites insufficient concentrations are achieved, particularly in the kidney and also in the CSF. In contrast, the azoles possess better pharmacologic and toxicologic properties. Resistance to antimycotics is principally possible but still rare, so that in practice a routine testing is not necessary. Candida glabrata as well as Candida krusei are primarily resistant to fluconazole.
For survival of plants, animals as well as main in a nature full of aggressive microbes, endogenous antibiotics play an essential role, which is not yet fully appreciated in medicine and science. For example in the granules of polymorphonuclear granulocytes and macrophages or even of specialized epithelial cells such as Paneth cells in the crypts of the intestinal mucosa, oligopeptides are produced with a wide range of antimicrobial activity. According to their chemical structures and modes of action they can be grouped into various different families. The physiological role of these agents on the surface of skin and mucosa or within host tissue is only incompletely understood.
Consistently high tuberculosis rates in many developing nations, the surprising increase in tuberculosis cases in numerous industrialized countries, together with the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis have reshapened public interest in this ancient scourge. Improved tuberculosis control could best be achieved by an efficacious vaccine. The available attenuated vaccine strain, Mycobacterium bovis BCG, has only limited efficiency. This vaccine is capable of protecting against disseminated miliary tuberculosis in the newborn, but it is unable to prevent stable infection and to cause sterile pathogen eradication. Hence, adult tuberculosis, representing the majority of all tuberculosis cases, is not preventable by BCG vaccination. Due to the extraordinarily high rate of asymptomatic M. tuberculosis infection (1/3 of the total world population) any novel vaccination strategy has to fulfil two major tasks: first, prevention of stable infection, second, eradication of already established infection. T lymphocytes represent the major target for any vaccine strategy, because they serve as central mediators of acquired immunity. They segregate into distinct populations, characterized by different activation conditions and biological functions. These T cell populations do not act independently from, but rather interact with, each Ether mostly through cytokines. Although CD4 T lymphocytes of T helper 1 type are essential for protection, CD8 T cells expressing cytolytic functions are required, in addition. Perhaps other T cell populations, such as gamma/delta T cells and double negative alpha/beta T cells, also participate. An effective vaccine has to stimulate the precise combination of T cells and cytokines required for the different tasks. It remains to be clarified in how far this can be achieved by a single vaccine.
Meanwhile more than 270 immunoadsorptions have been performed. 7 patients with SLE and glomerulonephritis as well as 3 patients suffering from Wegener's vasculitis and glomerulonephritis had been treated with combined immunoadsorption and IVIG therapy. After three sessions of immunoadsorption (2-3 1 plasma filtrate) the patients received 10 g 7S-immunoglobulin infusions on three consecutive days.Patients with SLE and end-stage kidney involvement (2 patients) did not show any benefit by the above mentioned treatment regimen. Patients with Wegener's vasculitis and glomerulonephritis showed no significant improvement, except in one of three patients who showed a remarkable decrease in proteinuria. On the other hand, patients with SLE and >>moderate<< kidney involvement (short course of disease, no fixed structural changes) showed improvement on combined immunoadsorption and IVIG therapy.
There is increasing evidence that reactive oxygen substances are involved in the pathogenesis and/or progression of different diseases. A short introduction to the biochemistry of reactive oxygen substances will be given in this review. Subsequently, the role of reactive oxygen substances will be discussed exemplarily on pathophysiological aspects of neutrophil granulocytes and of neurodegenerative diseases.
