Antiviral treatment and prophylaxis of influenza in primary care: German recommendations.

Antiviral drugs are a valuable supplementation to vaccines for the control and prevention of influenza. In Germany, for treating influenza amantadine, oseltamivir and zanamivir are approved. Amantadine and oseltamivir are also licensed for prophylactic use. On behalf of the Paul-Ehrlich-Society of Germany and the German Association for the Control of Virus Diseases, as two independent scientific societies, the first consensus Conference on the Antiviral Treatment and Prophylaxis of Influenza was held in June 2002. Based on the available data of clinical studies an expert group developed the following recommendations for the appropriate clinical use of the antiviral drugs: (1) since oseltamivir (orally administered) and zanamivir (administered by inhalation) have apparently similar clinical efficacy both drugs can be used alternatively for treatment. (2) Amantadine is not an alternative to the neuraminidase (NA) inhibitors because it is not effective against influenza B viruses, it frequently selects resistant virus mutants and it can cause adverse events. (3) When influenza is prevalent in the community patients with the clinical diagnosis of influenza should be treated with neuraminidase inhibitors if the symptoms are lasting not longer than 48 h. (4) Immunocompetent patients with a non-febrile illness and patients with a symptom history of more than 2 days should not be treated with antiviral drugs. (5) Although there are no data from clinical trials immunocompromised patients should also be treated when influenza has been diagnosed. (6) The prophylactic use of antiviral drugs can be recommended for persons with close contact to acutely ill persons and no recent vaccination against influenza. (7) The use of anti-influenza drugs have to be considered for prophylaxis in pandemics. A precondition for the adequate use of anti-influenza drugs in the primary medical care is the timely information on the local influenza situation delivered by surveillance systems.

[Non-enzymatic glycation and oxidative stress in chronic illnesses and diabetes mellitus]. / Nichtenzymatische Glykierung und oxidativer Stress bei chronischen Erkrankungen und Diabetes mellitus.

UNLABELLED: New approaches in biochemistry and molecular biology have increased the knowledge on the pathophysiology of chronic diseases as late diabetic complications, Alzheimer's disease, arteriosclerosis and vascular disease by defining the concept of "AGE-formation and oxidative stress." Nonenzymatic glycation, in which reducing sugars are covalently bound to free aminogroups of macromolecules, results in the formation of Advanced Glycation End products (AGEs) which accumulate during aging and at accelerated rate during the course of diabetes. Glycation accompanying oxidation processes support AGE-formation. AGE-formation changes the physicochemical properties of proteins, lipids and nucleic acids. In addition, binding of AGEs to specific surface receptors induces cellular signalling and cell activation. Interaction of AGEs with one of the receptors, RAGE, generates intracellular oxidative stress, which results in activation of the transcription factor NF-kappa B and subsequent gene expression, which might be relevant in late diabetic complications. CONCLUSION: Knowledge of the basis molecular mechanisms allows to understand the interplay of different inducers such as redicals, cytokines, AGE-proteins and amyloid-beta-peptids and to define oxidative stress as a "common endpoint" of cell dysfunction. With respect to therapeutic options it is now possible not only to optimize blood glycemic control, but also to design drugs such as AGE-inhibitors and AGE-"cross-link" breakers. In addition patients with chronic disease associated with increased oxidative stress ay benefit from an antioxidant rich (and AGE protein poor?) nutrition.

Immunogenicity of an inactivated hepatitis A vaccine administered according to two different schedules and the interference of other "travellers" vaccines with the immune response.

A total of 2036 persons consulting vaccination centers in Germany were vaccinated with an inactivated hepatitis A vaccine (containing 720 ELISA units of antigen) either according to the standard schedule (two vaccinations given 4 weeks apart) or to an abbreviated schedule (two vaccinations given 2 weeks apart) in a controlled clinical study. The abbreviated schedule induced a similar rate of seroconversion and geometric mean antibody titre as compared to the standard schedule. The incidence of reactions reported after vaccination was similar in both groups. When other "travellers" vaccines were given simultaneously neither the immunogenicity nor the reactogenicity of the hepatitis A vaccine were influenced. These findings have considerable practical importance in the prevention of hepatitis A in travellers.

Idiopathic hemochromatosis in a 45-year-old infertile man.

The clinical manifestations of primary or idiopathic hemochromatosis include mainly hepatomegaly, diabetes mellitus, and hypogonadism. Most investigators postulated that the hypogonadism is caused by pituitary dysfunction and that the deposition of iron in the testes is of little importance. We found not only pituitary failure in a 45-year-old man with idiopathic hemochromatosis (low LH and FSH levels, no response to GnRH) but could also detect by light microscopy deposition of iron in capillary endothelial cells and in the perivascular space of the testicular tissue. Electron microscopic study of tissue from the testes showed intracytoplasmic hemosiderin deposits in capillary endothelial cells. Abundant lipofuscin granules were present in Sertoli cells and Leydig cells. The serum testosterone levels were also lowered. In our opinion, the androgenic deficiency in idiopathic hemochromatosis is not only caused by pituitary failure but also by testicular dysfunction due to deposits of hemosiderin and lipofuscin in the testes.

The patient in shock--clinical picture and pathophysiology.

The diagnosis of hemorrhagic shock can be made on the basis of a good knowledge of the clinical picture of the bleeding patient. The necessary lab tests must be carried out over a period of time to establish their evolution and thus the degree of shock. At present, attention is being focused on the microcirculation. In shock, tissue is starved of oxygen and nutrients, resulting in the liberation by degenerating cell structures of numerous substances that have an effect on vascular tone. Decompensation is accompanied by consumption coagulopathy, which also has an influence on the microcirculation. The inhibitor potential is very important here. The patient must be out of shock before endoscopy can be considered.

The treatment of consumption coagulopathy.

There has been a transformation in our views of consumption coagulopathy in recent years owing to the advances throughout intensive care. The findings about the importance of inhibitors in the coagulation system have resulted in new biochemical understanding. The aim nowadays is to diagnose the early phase of consumption coagulopathy-so-called hypercoagulability. It is possible in this phase to restore the balance by replacement of the inhibitor antithrombin III. This report deals with clinical observations.

[New observations in a case of Cronkhite-Canada syndrome]. / Neue Beobachtungen bei einem Fall von Cronkhite-Canada-Syndrom.

We report about a 76 years old patient with Cronkhite-Canada syndrome. The diagnosis has been found with the following clinical symptoms: diarrhea, anorexia, alopecia, and onychotrophia. Laboratory values: severe hypoproteinemia (total serum protein 4.3 g/dl, albumin 2.4 g/dl); endoscopical and radiological findings: a generalized polyposis which involved the whole intestine except the oesophagus. As far as we saw in our literature-overview of 55 patients with Cronkhite-Canada syndrome, this patient had for the first time a carcinoma of the urinary bladder and a Bricker operation 17 years before the onset of his disease. Further we remarked a lack in the resorption of the enterally administered thyroidal hormones. The progress was fatal despite a parenteral hyperalimentation and a treatment with antibiotics and glucocorticoids.

Improving x-ray report turnaround.

Transcription inadequacies within the radiology department can provoke much criticism and can adversely affect a radiology department's relationship with referring physicians. New governmental regulations give added impetus to finding ways to speed x-ray report delivery and improve accuracy. Astute managers are well advised to identify and correct stenographic deficiencies.

X-ray report turnaround studies.

In the attempt to meet the diagnostic requirements of patients, satisfy referring physicians, respond to the mandates of hospital administration and conform to the cost-efficiency commandments of the federal government, most radiology managers realize that expediting the x-ray reporting process is fundamental. Turnaround, or time measurement, surveys are the mechanism by which a radiology manager documents the department's efficiency in producing the typewritten x-ray report. Such surveys measure the time lapse between when a radiographic examination is performed and when the typewritten report is received by physician or nursing station. Turnaround studies reveal the reasons for poor reporting, whether originating from personnel inadequacies or organizational pitfalls. Equal in importance to the gathering of time flow statistics are the problem-solving methods which follow.

Quantification of extracorporeal fibrin deposits in haemodialysis with minimal and conventional heparinization.

The effects of minimal intermittent heparinization and of conventional heparinization on endogen fibrinogen concentration as well as on fibrin deposits were studied on 17 on patients hemodialysis. It was shown that the minimal intermittent heparinization did non reduce dialysis efficiency and that a total heparin dosage of 6,000 units is the lowest safe limit.

Early treatment with AT III in acute liver failure.

In acute liver failure there is often evidence of consumption coagulopathy in addition to interference with the synthesis of coagulation enzymes. Seven patients in hepatic coma (Grade IV-V) were treated by baboon liver perfusion bypass. Replacement therapy with antithrombin III (AT-III) proved useful in the management of the consumption coagulopathy. In the course of further work antithrombin III replacement therapy was given to 13 patients with acute liver failure at an early stage, before they could lapse into deep coma. Six patients with a Colombi index (the sum of Factors II, V and VII) below 75% - an unfavourable prognostic sign - survived the episode of acute liver failure. Early replacement with antithrombin III can be used to treat the coagulation abnormalities which occur during acute liver failure and should gain time for liver cell regeneration to take place.

The conflict between anticoagulation and hemostasis during hemodialysis.

Anticoagulation with comparatively small amounts of heparin has been carried out in more than 3,000 acute and chronic hemodialysis procedures without problems. In a selected high risk group of postoperative and polytrauma patients no patient hemorrhages have occurred, nor have there been any clotting problems in the dialyser circuit. Studies to elucidate the underlying mechanisms of coagulation and anticoagulation in the extracorporeal environment have been performed. Minimal intermittent heparin administration based on plastic anticoagulation monitoring with the APTT method, has proven to be particularly safe.

[Uremic tendencies for hemorrhage and hemodialysis]. / Urämische Blutungsneigung und Hämodialyse.

By means of a simple heparin test which reflects the actual processes in the contact of the blood with heterogeneous surfaces we can securely regulate the heparinisation in each phase of the dialysis, which, as I tried to explain, brings considerable consequences for the clinic.