Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes

Differentiation of the non-dividing trypomastigote form of Trypanosoma cruzi, the causative agent of Chagas disease, to the dividing amastigote form normally occurs in cytoplasm of infected cells. Here we show that calyculin A. a potent inhibitor of protein phosphatases 1 and 2A, induces at pH 7.5 extracellular transformation of long slender trypomastigotes to round amastigote-like forms which acquire characteristic features observed after the normal differentiation process: repositioning and structural changes of the kinetoplast, release of surface neuraminidase, and expression of amastigote-specific epitopes. Calyculin A inhibits parasite phosphatases and changes in the phosphorylation of specific proteins occur during the transformation process. As an exposure of trypomastigotes to calyculin A concentrations as low as 1 nM and for only 1-2 h is sufficient to induce transformation, the inhibition of calyculin A-sensitive phosphatase(s) appears to play a major role in initiating the trypomastigote differentiation.     

Perkutane Revaskulärisation von Nierenarterienstenosen Ballonangioplastie versus Stentimplantation

Renal artery stenosis (RAS) is the most common cause of secondary hypertension, with a prevalence of about 1% in the general population of people with hypertension. Severe arterial stenosis may also lead to impairment of excretory renal function. In experienced hands renal artery revascularization with or without stent implantation may be a safe and effective treatment in patients with sustained hypertension resistant to intensive antihypertensive treatment. Conventional balloon angioplasty of non-ostial RAS caused by fibromuscular dysplasia with a high technical and functional success rate may be the treatment of choice. However, there is continuous discussion concerning the utility of balloon angioplasty and renal stenting, respectively, in patients with atherosclerotic disease. At the time being, there are 3 randomized European trials ongoing to analyze the benefit of medical treatment versus percutaneous intervention. Several prospective studies dealing with renal artery stenting in ostial RAS found that the implantation of endoprostheses leads to much better morphologic longterm results as compared to those of balloon angioplasty alone and may be a safe and effective alternative to surgery. In addition, the functional results suggest that stent implantation in patients with mild or severe renal dysfunction may slow progression of renal failure and, thus delay the need for renal replacement therapy. It is to note that renal artery stenting does not impede any further surgical intervention. However, prior to any interventional treatment the indication of an eventual catheter procedure in patients with RAS should be discussed between experienced nephrologists and interventionalists based on clinical, functional and duplexsonographic data.     

Cerebral and renal embolization after lymphography in a patient with non-Hodgkin lymphoma: case report

An unusual case of lipid embolization to brain and kidney after lymphography in a patient with non-Hodgkin lymphoma of the upper anterior mediastinum is reported. Contrast material-enhanced echocardiography demonstrated a right-to-left shunt to the left atrium without evidence of a patent foramen ovale. Echo contrast particles were transiently present within the tumor surrounding the great vessels.     

Quantification of microglial late reaction to stereotactic irradiation of the rat brain using computer-aided image analysis

The role of microglial cells in the late delayed reaction following radiotherapy of brain tumors has not been elucidated. To investigate the late delayed response of microglial cells to radiation, we stereotactically irradiated spherical treatment volumes in the right frontal lobe of rat brains. Doses of 20, 30, 40, and 50 Gy were used in combination with two different collimators. The response of microglial cells at 10 and 19 months after irradiation was determined with Anti-CD 11 b/c (Ox 42) as an immunohistochemical marker. For evaluation of immunostaining, we developed a method using computer-aided image analysis in which the ratio of the area of stained cells to that of nonstained brain tissue is calculated. In addition, quantification of Ox-42+ cells per microscopic field was performed. Animals treated with 30 Gy or more had significantly increased total areas of staining at both time points studied. In contrast, the number of stained cells at 10 months increased significantly only in animals treated with 30 or 40 Gy. Likewise, at 19 months, this number increased significantly only in animals treated with 40 Gy or more. These results indicate that computer-aided determination of the area of stained cells is more sensitive than the counting of stained cells. We have demonstrated that microglial cells respond to stereotactic irradiation in a dose-dependent fashion. The image analysis we employed for this purpose is a systematic method to evaluate immunohistochemical staining.     

Economics and ethics in public health?

The topic suggests a conflict between ethics and economy in medical care. It is often argued that today's welfare state in affluent societies with their social insurance systems makes it easier for the doctor to translate ethical demands into reality without being hampered by economic restrictions. Both doctors and patients took advantage of this system of medical care by mingling social guarantees for health with the doctor's income. Hence, medical expenses expanded rapidly, additionally promoted by technical progress in medicine. This entailed a proportionate increase in medical expenses in relation to personal income, especially wage income. Budgets of state authorities were streamlined or deficits became larger. This state of affairs was promoted further by mechanisms of distribution of national income in accordance with the slogan "less state, more market". While national income continued to grow, although at a slower rate, the number of jobless persons grew continually and thus also the social expenses, this was not due, as is usually assumed and pretended, to an economic crisis. Society and economy are facing a crisis of distribution of national income under conditions of technical progress as a job killer, making economic production more productive and efficient. Not taking into account the new challenge of social market economy--the German innovation in market economy creating the economic miracle after World War II--reforms of the system of medical care took place and are still continuing along market principles, particularly the latest German reform law leading to individual contracts between patients and their doctors in respect of cost charging. However, marketing principles promote economy in medicine, but they do not promote medical ethics. Further German guidelines for medical care should take stock of past experiences. There will be more competition in the "growing market of medical care" (private and public) and this will need--as economic experience has shown and economists have affirmed--new organisational devices to ensure better outcomes for the individual patient as a consumer and the doctors as suppliers. More responsibility should be given to the different suppliers of collective security in medical care (private or social systems of insurance). No individual patient as a mere consumer has a genuine chance in handling contracts with doctors carefully who are considered to be "gods in white" according to a popular German saying. These consumers have only a slight chance when arguing in courts of justice for the performance of contracts. Diagnosis and therapy, the system of doctors who treat members of statutory social insurance schemes (National Health general practitioners in the U.K.) and doctors as "free entrepreneurs" in the growing market of medical care should be separated due to the different rules of charging costs and offering medical care. "Classless medical care" does not have a better chance by applying market principles. The same is true for ethics versus economy. Doctors as "free entrepreneurs" must learn that markets will not guarantee reimbursement of costs but react to supply and demand. Hence, regulation of medical care by economic instruments creates better chances even for ethics in medical care against economy.     

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomachin vitro

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO₂ and bicarbonate whereas, during normal acid, secretion cytoprotective CO₂/HCO₃- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in anin vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO₂ supply. Without acid inhibition there was no mucosal damage at any level of serosal CO₂/HCO₃- supply. Acid inhibition reduced metabolic CO₂ production by 29% (P<0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P<0.05). Although, 1% CO₂ supply completely replaced the reduction in metabolic CO₂, it did not protect against mucosal damage. Overreplacement by 5% serosal CO₂/HCO₃- was required to prevent damage. There was no correlation between luminal CO₂/HCO₃- output and mucosal damage. The protection by endogenous or exogenous CO₂/HCO₃- appears to act intracellularly rather than by intragastric or intercellular neutralization.This study was supported by Swiss National Foundation grants 32-26369.89 and 32-33626.92. The morphometry equipment was supported by a grant from the Osterreichische Nationalbank.     

DNA-protein crosslinks as a biomarker of cis-platinum activity in cancer patients

We have developed a new method to assess the amount of DNA-protein crosslinks (DNA-PC) in peripheral lymphocytes, based on the selective precipitation of the DNA crosslinked to proteins. We assessed the amount of DNA-PC in peripheral lymphocytes of 18 cancer patients who underwent chemotherapy with cis-platinum for the first time. Since the chemotherapy was administered over a two-day period, blood samples were drawn at baseline (before starting the therapy), 4 h after the infusion of the first dose of cis-platinum, the next day (24 h after the first dose, and immediately before the infusion of the second dose), and 2 days later (48 h after the first dose). The mean change of DNA-PC 4 h after therapy was 0.8+/-0.8% (p=0.006), 0.5+/-0.6% after 1 day (p=0.007), and 0.1+/-0.5% after two days (ns). The correlation between DNA-PC changes and cumulative dose of cis-platinum was -0.22 at 4 h, -0.19 after 1 day, and -0.68 at 2 days (p=0.005). The crosslinking effect of cis-platinum seems to vary among individuals and with dose; the DNA-PC may be used to define sub-populations of patients with various degree of sensitivity to the pharmacologic action of this chemotherapeutic agent, and thus to adjust the dosage on an individual basis.