[Cystic gastric tumor with calcifications]. / Zystischer Magentumor mit Verkalkungen.

In imaging techniques was seen a thickness of the gastric wall in a patient with pain for several months and loss of weight. Biopsies taken out of the tumor mass by gastroscopy and laparoscopy have not been ground-breaking. For this disease pattern is it not unusual that the diagnosis of heterotopic pancreatic tissue with pancreatitis is not confirmed until a resection of the stomach.

[The extracellular matrix structure in keratoconus]. / Die Struktur der Extrazellulärmatrix bei Keratokonus.

PURPOSE: Keratoconus is a non-inflammatory disease characterized by progressive thinning of the central cornea. There are indications for an autosomal dominant heredity. Our purpose was to find correlations between gene expression and structural changes in extracellular matrix components. METHODS: Stromal RNA (keratoconus and comparison) was isolated from corneas, transformed to cRNA and analysed using biochips (Affymetrix). Structural investigations were performed by laser scanning and transmission electron microscopy. RESULTS: In keratoconus corneas there was an upregulation of different extracellular matrix components (collagen XV, metalloproteases) and a down-regulation of collagen IV (alpha1, alpha3) and versican. The morphological changes correlated to genetic obtained data. The orthogonal arrangement of the collagen fibrills (anteriorly and central) was altered in the collagen matrix of keratoconus corneas. CONCLUSIONS: The changes point on deregulation of the matrix arrangement. The interest in the cause of the disease is focused on the interfibrillar arrangement, the interaction between collagen and proteoglucanes.

[Cystic lymphangioma with endosalpingiosis as a rare cause of gastrointestinal bleeding]. / Zystisches Dünndarmlymphangiom mit Endosalpingiose als seltene Ursache einer gastrointestinalen Blutung.

We report on a 31-year-old woman with an iron-deficiency anemia and positive Guaiac test, existing for more than 2 years. Despite an extensive gastrointestinal examination a bleeding source could not be found. Also angiography of the abdominal arteries with injection of heparin as provocative protocol was normal. Enteroclysis showed a remarkable finding which led to laparotomy. A cystic lymphangioma with endolymphatic endosalpingiosis as the bleeding source was identified and removed. Lymphangioma is a rare benign soft tissue tumor which usually appears during the first 2 years of life. Only in some cases the lymphangioma is intraabdominal and there can be different, no specific symptoms. Endosalpingiosis is also a rare benign disease, it consists of scattered epithelium of the Fallopian tube. It is the first case to our knowledge, in which the appearance of the endosalpingiosis in a lymphangioma is described.

Differentiation of intracardiac tumors and thrombi by echocardiographic tissue characterization: comparison of an artificial neural network and human observers.

The feasibility of classifying ultrasound images of intracardiac tumors and thrombi with a neural network-based algorithm was compared with the performance of experienced echocardiographers. The neural network used statistical descriptors of the apparent echocardiographic texture of the masses, and the blinded echocardiographers were given photographic prints of enlarged regions of interest without clinical data. The network classified 66% of the images correctly and the echocardiographers, 83%. The network and echocardiographers agreed in 88% of the images. Human observers usually base their classification of intracardiac masses on clinical data. The echocardiographic texture of tumors is quantitatively different from that of thrombi. This difference can be recognized by a neural network and potentially be useful in assisting with the diagnosis when clinical clues are insufficient.

[Economic aspects of using electron beam computerized tomography]. / Okonomische Aspekte bei der Anwendung der Elektronenstrahlcomputertomographie.

Electron beam computed tomography (EBCT) allows visualization and quantification of calcium in the coronary arteries. This has been demonstrated to correlate well with the overall plaque burden in the coronary arteries. EBCT is, therefore, well suited for the detection of early stages of coronary atherosclerosis. Especially in asymptomatic patients with several risk factors, staging coronary artery disease by coronary calcium, scanning may allow prognostic assessment and guide preventive and therapeutic interventions. To date, only scant data are available regarding the cost effectiveness and the economic impact of this imaging technique. In this manuscript we compare various methods for the diagnosis of coronary artery disease using a theoretical model and review the results of a prospective trial in our emergency room of coronary calcium scanning in patients with acute chest pain. Using Framingham data and prognostic data from long-term follow-up, we discuss the impact of coronary calcification scanning on primary preventive measures and its economical consequences. EBCT is a promising technique which has created a lot of attention due to its ease of application. It is currently undergoing critical appraisal in the medical literature. Further randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA II) to better define its value and limitations in the clinical arena.

Digoxin, hypercalcaemia, and cardiac conduction.

The cardiac effects of hypercalcaemia are usually manifest as a shortening of the QT-interval. Hypercalcaemia is infrequently associated with a clinically manifest arrhythmia. However, concomitant therapy with digoxin or underlying cardiac disease can potentiate the arrhythmogenic effects of hypercalcaemia, leading to a symptomatic rhythm disorder. We describe a symptomatic arrhythmia, which developed in a patient with hypercalcaemia secondary to squamous cell carcinoma of the bronchus. The patient was on digoxin therapy at the time. The arrhythmia did not recur after discontinuation of digoxin therapy and correction of the hypercalcaemia. Because of its effect on cardiac conduction, hypercalcaemia should be considered in the evaluation of any patient with an unexplained bradyarrhythmia. Conversely, patients with hypercalcaemia should discontinue digoxin therapy and be evaluated for the presence of rhythm disorders while receiving appropriate treatment for hypercalcaemia.

[Acute gonarthritis--application of current diagnostic study methods exemplified by a case report]. / Akute Gonarthritis--Einsatz neuer diagnostischer Untersuchungsmethoden anhand eines Fallbeispiels.

The evaluation of acute inflammatory knee arthritis deserves special emphasis, because immediate benefit may result from identification and treatment of the underlying disease. The diagnostic approach to and the differential diagnosis of an acute knee arthritis are presented. By means of a case report, the use of the needle arthroscopy and the polymerase chain reaction (PCR) method for analysis of synovial fluid and synovial tissue in the diagnosis and evaluation of treatment of Lyme disease is described. The significance of this approach in diagnostic and therapeutic procedures has yet to be defined.

Characterization of the RNA dependent DNA polymerase of bovine leukemia virus.

The reverse transcriptase-RNA dependent DNA polymerase of Bovine Leukemia Virus (BLV) was isolated and characterized. The enzyme has a molecular weight of about 80kd and the isoelectric point is 7.6. The enzyme prefers magnesium, as a divalent cation using synthetic homopolymeric template primer poly (C) oligo (dG). Monoclonal antibodies directed against reverse transcriptase of human immunodeficiency virus type I (HIV-I) did not crossreact with the isolated polymerase.

[Electron beam tomography in cost effective diagnosis of coronary heart disease]. / Die Elektronenstrahltomographie in der kosteneffizienten Diagnostik der koronaren Herzkrankheit.

BACKGROUND: Electron beam CT (EBCT) can acquire rapid, multiple thin-section tomograms of the beating heart in synchrony with the electrocardiogram and quantity coronary calcification without intravenous contrast. Coronary calcification is an active process exclusively associated with atherosclerotic plaque formation and regulated in a manner similar to the calcification of bone. Clinical studies have demonstrated that EBCT coronary calcification (1) follows a pattern similar to the epidemiology of coronary artery disease (CAD), (2) has a high sensitivity (90-95%) for coronary plaque and significant angiographic coronary stenoses, and (3) has the potential to assess the prognosis of patients with coronary atherosclerotic disease. Coronary calcium area or "score" correlates best with overall plaque burden within the coronary system. However, coronary calcium is of limited value in distinguishing coronary stenosis on a segment-by-segment basis. EBCT AND CAD: Due to spiraling health care costs, there is a need for cost-efficient strategies in the diagnosis and stratification of patients with known or suspected CAD. There are two major patient groups in which EBCT calcium scanning has a potential for cost-efficient application: (1) in asymptomatic, high-risk patients, identification of significant plaque burden may direct judicious use of long-term drug therapy or further investigation to those individuals most likely to benefit from an aggressive risk factor modification and medical program; (2) in patients with chest pain syndromes but no prior CAD, EBCT calcium scanning compares favorably with conventional diagnostic methods. In particular, using receiver operating characteristic analysis, the sensitivity and specificity of an EBCT calcium score of 80 in detecting obstructive CAD are both about 85%. Using a theoretical model, EBCT calcium scanning was found to be the most cost-effective approach to diagnosis in populations with a low-to-moderate likelihood of obstructive CAD when compared with treadmill exercise, stress thallium, and stress echocardiography. CONCLUSIONS: EBCT calcium scanning is not a substitute for coronary angiography, but it has clear advantages over other more traditional diagnostic methods for CAD. In particular, it can be performed conveniently and inexpensively in most patients. Additionally, the site and extent of calcification are intimately related to the atherosclerotic plaque burden. The analyses presented suggest that it may also provide a cost-effective clinical alternative in specific subsets of the population.

Dissection following balloon angioplasty of aortic coarctation: review of the literature.

Balloon angioplasty of the coarctation of the aorta can result in intimal or medial or even adventitial dissections as demonstrated by in vitro studies and animal experiments. As a typical sign of stretching of the aortic wall, patients complain of pain during the angioplasty procedure. In the literature, aortic wall rupture and ventricular fibrillation during the procedure are reported. Additional sudden deaths can occur within 40 hours after the procedure. Mortality ranges from 0.1% to 2.5%. By transesophageal echocardiography, monitoring of balloon angioplasty, control of the positioning of the balloon, and control of the results and detection of complications are possible. Intimal as well as medial dissections can be detected with observed healing for intimal but also medial dissections. In order to avoid the patient's discomfort, intraaortic ultrasound will be used in the future, when major methodological improvements are done. Computed tomography demonstrates medial dissections but is not able to visualize intimal dissections. Using computed tomography and magnetic resonance after angioplasty of the coarctation of the aorta, irregularities are described in up to 17% of the patients. For angiography, a low detection rate of medial dissections has to be expected, when not biplane angiographies of the whole thoracic aorta are performed. Medial dissections can be seen, but intimal dissections are missed. In conclusion, a review of the literature demonstrates a high incidence of intimal and medial dissections after angioplasty of the coarctation of the aorta with spontaneous healing in most patients. As is the way with coronary angioplasty, aortic wall ruptures are rare, but stand-by surgery is necessary.

[Experimental evaluation of the accuracy and safety of intraluminal ultrasound]. / Experimentelle Uberprüfung der Genauigkeit und Sicherheit des intraluminalen Ultraschalls.

In this in vitro investigation, we studied the feasibility and accuracy as well as the safety of intravascular ultrasound imaging. Plastic cylinders were used in order to validate measurements of luminal area, perimeter, diameter, and wall thickness. Fifty-nine segments of human arteries were also examined by intravascular ultrasound; then the results regarding the luminal area, perimeter, and wall thickness were compared with the corresponding histopathologic section. Close correlations were found in plastic cylinder studies (r = 0.999, 0.999, 0.998, and 0.994 for area, perimeter, diameter, and wall thickness, respectively). There was also an excellent correlation between intravascular ultrasound imaging and pathologic measurements (r = 0.993, 0.994, and 0.915 for luminal area, perimeter, and wall thickness). Five different cylinders, with a volume of 2, 5, 10, 20, and 50 mls, were employed to evaluate the effect of ultrasound on temperature. Ten blood samples anticoagulated with EDTA were used to detect the effects of ultrasound on blood elements. In the course of time, the ultrasound caused a slight increase of solution temperature (from 23.9 degrees C to 24.6 degrees C after 1-h examination in a 2-ml cylinder) and the temperature change became less obvious as the solution volume increased (the temperature raised 0.3 degrees C in the 2-ml cylinder, 0.1 degrees C in the 20-ml cylinder, but no change was detectable in the 50-ml cylinder after 10 min). No significant differences about WBC, RBC, and platelet counts were found between test and control group (p greater than 0.1) before and 5, 10, 15, 30, and 60 min after ultrasound examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel features of retroviruses associated with human diseases.

The last decade has witnessed a new chapter in the history of retrovirology. As of now, four human retroviruses have been identified and molecularly characterized. They are associated with a wide spectrum of human diseases including cancer, immunodeficiency and neurological disorders. By virtue of their clinical relevance, their novel genes and regulatory mechanisms these viruses have become the focal point of research in retrovirology. The study of these viruses is of fundamental importance in understanding the mechanisms leading to transformation of human cells and distortion of the immunological state.

A host-mediated in vivo/in vitro assay with peritoneal murine macrophages for the detection of carcinogenic chemicals.

We have developed a host-mediated assay system for the detection of the transforming action of chemical carcinogens on peritoneal macrophages. Directly as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and were cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells, for example, from alpha-naphthylamine or diphenylhydantoin-treated animals with those from control mice proved that the test is positive at least on a significance level of 5% using the t-test. Further substances revealing a cell-transformation potential were benzene, benz(a)pyrene, 2,3,7,8-tetrachlorodibenzodioxin, N-nitrosodimethylamine, ethidium bromide, aflatoxin B1,N-methyl-N-nitrosourea, 1-methyl-3-nitro-1-nitrosoguanidine, 2-naphthylamine, dieldrin, suramin and trichloroethylene. A weak transforming potential was found for chlorambucil as well as for tetrachloroethylene. With toluene or azidothymidine no cell transformation could be observed. Several immortal cell lines could be established form NMRI mice treated with alpha-naphthylamine or N-methyl-N-nitrosourea. Athymic nu/nu mice injected subcutaneously with these cells developed tumors, establishing the oncogenic potential of these cell lines.

Epitope mapping of the low-molecular-mass subunits of reverse transcriptase in human immunodeficiency virus type 1 by monoclonal antibodies.

With the aid of monoclonal antibodies to the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), low-molecular-mass subunits (p29, p32, and p40) were identified in HIV-1 RT purified from HIV (HTLV-IIIB) virions by isoelectric focusing. Epitope mapping with synthetic polypeptides from various regions of the pol gene suggests that the low-molecular-mass subunits result from N-terminal cleavage of the p51 subunit. The subunits could be separated only by SDS-polyacrylamide gel electrophoresis and detected by immunoblotting. They could not be separated on chromatographic columns, suggesting that the subunits are complexed or conformationally arranged in such a way that their separation on the basis of molecular mass is not possible. The molecular mass of the active enzyme eluted from a chromatographic column (Sephacryl S-300) loaded with a mixture of the subunits was estimated to be 100 kDa.

The care of diabetic patients by ophthalmologists in New York State.

All ophthalmologists in New York State whom the authors could identify through state sources and professional societies (n = 1655) were surveyed about eye care of diabetic patients. Over 90% recommended at least annual retinal examinations for the presented hypothetical patients. Ninety-four percent said they "usually" (31%) or "almost always" (63%) recommend laser treatment for proliferative retinopathy, while 6% said they "occasionally" or "almost never" recommend such treatment. Almost all the latter physicians were general ophthalmologists. The decision to treat macular edema was highly dependent on the quality of the patient's vision. The percentage who "usually" or "almost always" recommend laser treatment for macular edema was 24% when the patient's vision was excellent, 63% when vision was mildly compromised, but 73% when vision was significantly compromised. General ophthalmologists and retina specialists differed significantly in their recommendations for follow-up and treatment of diabetic retinopathy. Ophthalmology 96:739-745, 1989.

Serological relationship between reverse transcriptases from human T-cell lymphotropic viruses defined by monoclonal antibodies. Evidence for two forms of reverse transcriptases in the AIDS-associated virus, HTLV-III/LAV.

The immunological relationship between reverse transcriptases purified from human T-cell lymphotropic viruses (HTLV-I, HTLV-II, HTLV-III) was defined using monoclonal antibodies specific for HTLV-III reverse transcriptase, secreted by a mouse/mouse hybridoma clone (4F8) developed in our laboratory. The viral proteins from HTLV-I and HTLV-II do not bear any cross-reactive epitope to antibodies secreted by this clone. These antibodies specifically cross-react with HTLV-III reverse transcriptase. The antibodies failed to neutralize the catalytic activity of reverse transcriptase; however, after immunoprecipitation with a magnetic conjugate of goat anti-mouse IgG, the residual activity was completely inhibited. This shows that the antibodies are not directed towards the catalytic active center of the enzyme. Using an immunoblotting technique (Western blotting), we have found two cross-reactive proteins with HTLV-III lysate with molecular masses of 53 and 66 kDa. This suggests that HTLV-III possesses two reverse transcriptase activities with a common determinant recognized by the same epitope.

Biochemical heterogeneity of reverse transcriptase purified from the AIDS virus, HTLV-III.

The reverse transcriptase from AIDS virus, HTLV-III, was purified and characterized. The purified enzyme has a very high affinity for template primers (rC)n X (dG)12 and (rCm)n X (dG)12 compared to that for (rA)n X (dT)12. In addition, the HTLV-III reverse transcriptase was able to transcribe (rAm)n X (dT)12 very efficiently. The ionic requirements are unique in the sense that HTLV-III reverse transcriptase prefers Mg2+ as divalent ions to transcribe (rC)n X (dG)12 and (rA)n X (dT)12. The Mr of the enzyme is 95 000-98 000. Unlike the HTLV-I reverse transcriptase, the HTLV-III enzyme is highly stable and has a much higher activity in the presence of (rC)n X (dG)12; the Vmax for HTLV-III reverse transcriptase is several-fold higher than that for HTLV-I enzyme. The enzyme activity of the purified reverse transcriptase from HTLV-III was resolved into two peaks on a preparative isoelectric column, one at pH 5.75 and the other at pH 6.25. This leads us to conclude that the reverse transcriptase of HTLV-III is biochemically heterogeneous.

Inhibitors of retroviral DNA polymerase: their implication in the treatment of AIDS.

Compared to other T-lymphotropic human retroviruses, human T-cell leukemia (lymphotropic) virus I (HTLV-I) and HTLV-II, the acquired immunodeficiency syndrome (AIDS)-associated virus, HTLV-III, is a nontransforming cytopathic virus without immortalizing activity. Thus the virus replication is an important event in the manifestation of this disease, and the interruption of viral replication offers an important strategy for the control of AIDS. For this reason we have purified the reverse transcriptase (RT) from HTLV-III and from HTLV-III infected cells to study the structure-activity relationship of RT inhibitors developed in our laboratory. The cellular DNA polymerases from H9 cells were also purified to study the selectivity of RT inhibitors. Purified HTLV-III RT has several distinguishing features: (a) unlike the HTLV-I enzyme it is highly stable and can be kept for several weeks without any loss of activity; (b) using identical procedures of isolation the HTLV-III enzyme shows a much higher activity than does the enzyme from HTLV-I; (c) the Vmax for HTLV-III RT is by severalfold higher than that for the HTLV-I enzyme in the presence of (rC)n X (dG)12 and (rCm)n X (dG)12, and besides the usual template-primers used for RT assay this enzyme has a relatively high affinity for (rAm)n X (dT)12; and (d) the cationic requirements for the transcription of various template-primers are unusual. The purified enzyme has a molecular weight of 95,000-98,000, as judged by the gel filtration method. The purified HTLV-III RT was inhibited by a partially thiolated polycytidylic acid (5-mercaptopolycytidylic acid); the cellular DNA polymerase beta from H9 cells was not sensitive to 5-mercaptopolycytidylic acid. Germanin (synonym, suramin), an antiprotozoan drug, also inhibits HTLV-III RT activity, but the DNA polymerase alpha activity was also sensitive to Germanin. The nonspecific effect of Germanin is probably due to the high content of sulfonic acid residues. This paper describes new approaches for designing specific inhibitors of retroviral reverse transcriptases which may be useful in developing a potential drug against AIDS.

Accessory muscle activity and respiration.

The relationship between the accessory muscle activity (sternohyoid and sternothyroid) and respiration was studied in canines. These animals do not have an omohyoid muscle such as found in primates. Therefore, chair-trained monkeys that have all three accessory muscles were used in a portion of the study. Findings in canines supported those previously reported. The sternothyroid muscle fired spontaneously with the onset of inspiration, but there was no similar activity in the sternohyoid. The activity of both muscles was observed after sectioning the recurrent laryngeal nerves and inducing hypoxia and hypercarbia. The severely hypoxic animals produced some negligible activity in the sternohyoid muscle. The data obtained from the chair-trained monkeys showed no consistent accessory muscle activity during normal respiration with recordings taken immediately after electrode placement, at 24 hours, and one week later. Respiratory activity was consistent in the omohyoid and sternothyroid but not in the sternohyoid muscle when partial airway obstruction and hypoxia were induced.