Labyrinthectomy after Cochlear Implantation: A Case of a Novel Approach for Vertigo Control.

Vertigo control in cases of Ménière disease and deafness can be achieved by labyrinthectomy before or as a single-stage procedure during cochlear implantation. The aim was to describe a case in which a labyrinthectomy was performed after cochlear implantation. The scar tissue was removed from the electrode cable, and the receiver was removed from the periostal pocket and placed out without electrode dislocation. Labyrinthectomy was performed after securing the electrode at the external canal. The patient disclaimed after three months no disabling vertigo. Intraoperatively, the electrode was not dislocated. A labyrinthectomy can be performed even after cochlear implantation to treat vertigo.

Limited value of positron emission tomography in treatment of pancreatic cancer: surgeon's view.

We aimed to assess, from a surgical point of view, the value of positron emission tomography (PET) in the routine preoperative diagnostic evaluation of a pancreatic mass. In particular, we were interested in PET's ability to distinguish a malignancy from a nonmalignant process and its impact on surgical decision making. We documented prospectively the results of preoperative ultrasonography, computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and PET in terms of a correct diagnosis of malignancy in 103 patients. All patients underwent surgery at our department and had a complete histologic workup. We then related the preoperative findings to the intraoperative and histologic findings and analyzed the advantages and limitations of PET in comparison with conventional diagnostic techniques. Both CT and PET showed high sensitivities (82% and 84%, respectively) but rather low specificities (61%). ERCP showed good specificity at 83% but weak sensitivity at 46%. The positive predictive value was higher than 80% for all methods, whereas the negative predictive value was around 60% at best. Both the CT and the PET diagnoses were wrong in 15% of the cases. In all cases with a false CT diagnosis, the results of the other conventional examinations provided sufficient evidence to indicate the need for surgical intervention. In all cases where PET gave misleading results, CT findings indicated the need for surgery. PET overlooked pT1 cancers in three of the patients. PET does not reliably prove or exclude malignancy in situations where conventional diagnostic procedures leave doubt as to the nature of a pancreatic mass. PET does introduce a new procedure-related spectrum of misinterpretations to the diagnostic process.

Interactive effects of cholecystokinin-8S and various serotonin receptor agonists on the firing activity of neostriatal neuronesin rats.

In rats anaesthetized with urethane single unit activity was extracellularly recorded in the neostriatum, and several drugs were microiontophoretically ejected. Separate administration of the sulfated octapeptide cholecystokinin (CCK-8S), serotonin (5-HT) or 8-OH-DPAT (a 5-HT(1A/7) receptor agonist) predominantly induced increases in the neuronal discharge rates (Wilcoxon test significant P<0.05), whereas the 5-HT(2A/2C) receptor agonist DOI affected only a few neurones and mainly reduced firing. After coadministration of CCK-8S and serotonin, activating effects also predominated (Wt P<0.05), but the neuronal responsiveness was significantly reduced (Chi2P<0.01). Similarly, concomitant application of CCK-8S and 8-OH-DPAT led to significant activation accompanied with a reduction of inhibitory effects. The block of serotonin- or 8-OH-DPAT-effects through specific 5-HT(1A) receptor antagonists implies the involvement of this receptor subtype within the striatum. In conclusion, concomitant action of CCK-8S and serotonin induces a mean level of neuronal activation that might promote normal function.

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Molecular epidemiology of Candida albicans isolates from AIDS and cancer patients using a novel standardized CARE-2 DNA fingerprinting technique.

A total of 277 Candida isolates from various body sites of 149 AIDS and cancer patients treated in four different university clinics in Würzburg, Germany were collected over a period of 27 months and phenotypically and genotypically characterized. The fingerprinting patterns of 194 Candida albicans isolates obtained with the moderately repetitive, C. albicans-specific DNA fragment CARE-2 were digitized and retrospectively compared with a highly accurate computer-assisted standardization method. A total of 168 different genotypic patterns (< 100% identity) could be differentiated using this technique. Although comparative analysis of C. albicans subsets revealed a pronounced tendency of C. albicans isolates from HIV patients to form clusters, the mean genetic variability in HIV and cancer patient isolates was virtually identical. Patients with a specific disease condition or in a certain age group were not found to harbour C. albicans isolates displaying a characteristic "signature genotype". Micro-evolutionary changes were detected by CARE-2 fingerprinting in temporal successive isolates of one patient, but nosocomial transmission of identical isolates between unrelated patients was never seen. Genotyping showed that patient isolates can replace one another; occasionally also species switches were observed. Secreted aspartic protease (SAP) production was not correlated with a specific C. albicans banding pattern; isolates obtained from HIV patients and from an internal control group secreted comparable amounts of SAP. Candida dubliniensis isolates in this study showed an elevated level of SAP production. When used under standardized conditions, CARE-2 fingerprinting is an efficient, reproducible and sensitive technique to characterize C. albicans isolates.

The visby lenses.

PURPOSE: In this study, 10 lens-shaped rock crystals, manufactured not later than the early Middle Ages, have been examined with respect to their image-forming qualities. METHODS: The spherical aberration of the lenses served as a scale for comparison. Measurements have been taken with a specially designed light section method. Some of the examined lenses have a silver mounting and have been used as pendants, whereas others are unmounted and show no signs of use as jewelry. RESULTS: The two largest unmounted lenses have very interesting surface curvatures, rendering a very small spherical aberration of the lens. The combination of top and bottom surfaces of the lens causes an imaging quality comparable to the modern aspheric lenses used, e.g., in today's projectors. CONCLUSION: According to the results of this study, the knowledge and comprehension of optical design was much further developed in the Middle Ages than we assume today.

Differences in endoscopic and clinicopathological features of primary and secondary gastric non-Hodgkin's lymphoma. German Gastrointestinal Lymphoma Study Group.

BACKGROUND: Lymphomatous neoplasia of the stomach is initially seen either as primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) or as nodal non-Hodgkin s lymphoma (NHL) secondarily involving the GI tract. One hundred seventy-six patients with primary gastric NHL (low grade, n = 65; high grade, n = 111) and 29 with secondary gastric NHL (low grade, n = 19; high grade, n = 10) were studied to evaluate whether differences in pathogenesis are associated with distinct clinical and endoscopic features. METHODS: Clinical features, tumor size, localization, and growth pattern were analyzed by means of esophagogastroduodenoscopy; grading was determined with histologic examination. RESULTS: The analysis of various clinical symptoms and endoscopic findings revealed a relationship between the occurrence of abdominal pain, vomiting, and unifocal growth pattern with an affiliation to the group with primary gastric NHL (p < 0.001), whereas tumor localization in the gastric fundus was predominantly found in secondary gastric NHL (p < 0.001). An equation has been generated that may help to predict affiliation to primary or secondary gastric NHL with an accuracy of 96%. CONCLUSIONS: Our results indicate that careful pretreatment analysis of clinical and endoscopic findings may be helpful in the diagnosis of primary or secondary gastric involvement by NHL, although reliable discrimination still requires histologic verification.

First-line therapy of advanced chronic lymphocytic leukemia.

There is general agreement that patients with advanced chronic lymphocytic leukemia (CLL) should be treated if they develop anemia or thrombocytopenia. The combination of chlorambucil (CLB) and prednisone is often used for first-line therapy of these patients, but compared to monotherapy with CLB, no difference in survival could be demonstrated. Steroids should be generally reserved, therefore, for the management of complications such as hemolytic anemia and thrombocytopenia or other autoimmune manifestations. CLB can still be considered standard therapy for advanced CLL, since polychemotherapy protocols as well as newer agents such as fludarabine have failed to show an improvement in survival compared to CLB. However, the results regarding response and survival of the CLB-treated patients seem to depend on dosage intensity and treatment duration. Biological response modifiers such as interferons, interleukins, and monoclonal antibodies have not improved responses or remission duration. Because experiences with CLL patients are limited, the indications and procedure of bone marrow transplantation are not yet clear. However, since results of current treatment protocols are unsatisfactory, regardless of age, patients should be involved in clinical studies that address the question whether high-dose CLB, fludarabine or the combination of fludarabine with other active agents can improve patients' outcome. In addition, autologous and allogeneic bone marrow transplantation as a consolidation therapy is under study and might be a step towards a potential cure of this disease.

Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates.

Staphylococcus epidermidis is a common cause of catheter-associated infections and septicemia in immunocompromised patients. To answer the question whether S. epidermidis skin isolates differ from isolates causing septicemic diseases, 51 strains obtained from blood cultures, 1 strain from shunt-associated meningitis, and 36 saprophytic isolates were characterized. The study demonstrates that most of the blood culture strains formed a multilayered biofilm on plastic material, whereas skin and mucosal isolates did not. Moreover, biofilm-producing strains were found to generate large bacterial autoaggregates in liquid culture. Autoaggregation and biofilm formation on polymer surfaces was associated with the presence of a DNA sequence encoding an intercellular adhesion gene cluster (ica) that mediates the production of a polysaccharide intercellular adhesin. The presence of the intercellular adhesion genes in blood culture isolates was also found to be correlated with the exhibition of black colonies on Congo red agar, whereas the adhesin-negative strains formed red colonies. Upon subcultivation on Congo red agar, the black colony forms of the blood culture strains exhibited red colony variants which were biofilm and autoaggregation negative and occurred at a frequency of 10(-5). The DNA analysis of these S. epidermidis variants by pulsed-field gel electrophoresis and Southern hybridization with an ica-specific gene probe revealed no detectable difference between the black and red colony types. Moreover, after repeated passage, the phenotype of the parent strain could be restored. Therefore, these colony forms were regarded as phase variants. This phenotypic change was observed exclusively in adhesin-positive clinical isolates and not in adhesin-negative saprophytic strains of S. epidermidis.

Topoisomerase II activities in AML and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.

We have developed a method to quantify topoisomerase (topo) II activities in partially purified nuclear extracts from human leukemia cells. By virtue of their different pH optima in the reaction buffer, two different topo II activities were found with activity optima at pH 7.9 and at pH 8.9 under high stringency conditions. The activities could be identified as topo II beta activity (pH 7.9) and topo II alpha activity (pH 8.9) by their different sensitivities to topo II alpha inhibitors, dephosphorylation experiments and immunoprecipitation with polyclonal antibodies. Seventy-two bone marrow or blood samples from patients with acute myeloid leukemias have been examined and their in vitro sensitivities to anthracyclines and epipodophyllotoxines correlated to the activities of topo II alpha and topo II beta. Although the topo II alpha activity could be directly inhibited by incubation of the cells with the mentioned drugs, no correlation between the topo II alpha activity and the sensitivity of the cells could be found. In contrast, the topo II beta activity which was not substantially inhibited by the drugs inversely correlated with the sensitivity of the cells. These findings were statistically significant for idarubicin (P= 0.017) and daunorubicin (P = 0.006). Vice versa, resistant cells (IC50 > median) had a higher topo II beta activity. Clinical relevance might be indicated by the finding that cells from patients that relapsed after initial treatment with anthracyclin-containing regiments had a significantly higher topo II alpha/beta activity ratio (P=0.0276). Obviously, the sensitivity of AML cells is substantially influenced by the activity of the resistant topo II (topo II beta) which gives evidence that the remaining topo II activity after treatment helps the cell to survive the DNA repair phase.

Topoisomerase II activities in AML blasts and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.

We have developed a method to quantify topoisomerase (topo) II activities in partially purified nuclear extracts from human leukemia cells. By virtue of their different pH optima in the reaction buffer, two different topo II activities were found with activity optima at pH 7.9 and at pH 8.9 under high stringency conditions. The activities could be identified as topo II beta activity (pH 7.9) and topo II alpha activity (pH 8.9) by their different sensitivities to topo II alpha inhibitors, dephosphorylation experiments and immunoprecipitation with polyclonal antibodies. Seventy-two bone marrow or blood samples from patients with acute myeloid leukemias have been examined and their in vitro sensitivities to anthracyclines and epipodophyllotoxines correlated to the activities of topo II alpha and topo II beta. Although the topo II alpha activity could be directly inhibited by incubation of the cells with the mentioned drugs, no correlation between the topo II alpha activity and the sensitivity of the cells could be found. In contrast, the topo II beta activity which was not substantially inhibited by the drugs inversely correlated with the sensitivity of the cells. These findings were statistically significant for idarubicin (P=0.017) and daunorubicin (P=0.006). Vice versa, resistant cells (IC90 > median) had a higher topo II beta activity. Clinical relevance might be indicated by the finding that cells from patients that relapsed after initial treatment with anthracyclin-containing regiments had a significantly higher topo II alpha/beta activity ratio (P=0.0276). Obviously, the sensitivity of AML cells is substantially influenced by the activity of the resistant topo II (topo II beta) which gives evidence that the remaining topo II activity after treatment helps the cell to survive the DNA repair phase.

Image analysis detects lineage-specific morphologic markers in leukemic blast cells.

This report outlines the morphologic classification of acute myeloid (AML: French-American-British FAB classification: M1) and lymphoid (ALL) leukemia by automatic image analysis and the correlation to immunologic and cytochemical classification. The investigation was carried out on Romanowsky-Giemsa stained bone marrow (n = 15) and blood smears (n = 10) from 25 patients with primary acute leukemia. The cases had been classified as of myeloid or lymphoid origin by three hematologic centers using immunochemistry or cytochemistry, but the specimens were submitted to the authors' laboratory without the diagnosis. The nuclear and cytoplasmic pattern of the blast cells were analyzed by a high resolution image analysis system and the measured and calculated cell features were sorted by means of a classifier program (CART). The image analysis classification was then compared with the immunophenotypical and cytochemical classification. Blood blast cells showed nuclear features that were significantly correlated to a myeloid or lymphoid immunophenotype. In contrast, bone marrow blast cells displayed overlapping and therefore nondiscriminating nuclear features. However, by generating a learning data set using the immunophenotypes the classifier program found specific cytoplasmic features that eventually permitted a differentiation into myeloid or lymphoid subtypes. In summary, the authors suggest that high resolution image analysis of leukemic blast cells detect nuclear and cytoplasmic features that are associated with the immunophenotype and therefore with the lineage determination of the cell. With this new objective and reproducible approach of morphologic cell analysis, it might not only be possible to classify blast cells with minimal cellular differentiation, but furthermore to discover prognostic features because the remarkable difference in classification quality between blood and bone marrow blast cells reported in this study, might be of biologic relevance and requires further investigation.

[Primary gastric lymphoma of the MALT type. The current knowledge on its etiology, therapy and prognosis]. / Primäre Magenlymphome vom MALT-Typ. Gegenwärtiger Wissensstand zu Atiologie, Therapie und Prognose.

Primary gastric lymphoma are nowadays considered as a distinct lymphoma entity. They are mostly classified as low or high grade malignant B-cell-lymphoma of the MALT (mucosa-associated lymphoid tissue). Within the gastrointestinal tract, the stomach is most frequently involved. In the pathogenesis of gastric lymphoma, Helicobacter pylori-associated gastritis plays an important conditioning role. Histological grading, stage and resectability of lymphoma are considered as major prognostic factors. Options in the therapy of gastric lymphoma are based on their histological grade and stage of the disease. They include surgical resection and/or radiotherapy for local tumor control as well as chemotherapy in the case of disseminated disease or high malignancy. Currently, special interest focuses on the effect of Helicobacter pylori eradication.

Malignant lymphomas of the upper gastrointestinal tract. Results of a prospective study in 103 patients.

BACKGROUND: There is a discrepancy between the incidence of gastrointestinal involvement by malignant lymphomas, as established in postmortem studies, and the rareness of the corresponding clinical diagnosis. METHODS: Therefore, the authors performed routine upper gastrointestinal endoscopic examination, within the framework of the usual staging examinations, in 103 consecutive patients with newly diagnosed Hodgkin disease (n = 21) and non-Hodgkin lymphoma (n = 82). RESULTS: One patient with Hodgkin disease (4.8%), 11 of 40 patients (27.5%) with non-Hodgkin lymphoma of low-grade malignancy, and 11 of 42 (26.2%) of those with highly malignant non-Hodgkin lymphoma showed involvement of the gastric and/or duodenal mucosa, as diagnosed with esophagogastroduodenoscopy. Of the 22 patients with non-Hodgkin lymphoma, 9 had involvement of other mucosa-associated lymphoid or epithelial tissue. In two patients with Stage III, two with Stage II, and two patients with presumptive Stage I disease, the disease was reclassified as Stage IV. Because of gastrointestinal involvement, treatment for two patients was changed from radiation therapy to chemotherapy and another two patients had gastric resections so that possible treatment-related complications could be avoided. CONCLUSIONS: In light of these results and the fact that a major basis for the therapeutic strategy for malignant lymphomas is tumor stage, routine esophagogastroduodenoscopic examination within the framework of the usual staging examinations is recommended. In individual cases, this procedure may be of decisive importance in the therapeutic approach to and prevention of complications.

Failure to detect any effect of amalgam restorations on peripheral blood lymphocyte populations.

Dental amalgam has been considered to have adverse side effects on the immune system. Reports have been contradictory, indicating both an increase and a decrease in peripheral blood lymphocyte counts associated with amalgam restorations. We investigated two groups of patients, one of which was treated with amalgam restorations for the first time. In the other group, all existing amalgam fillings were removed. Prior to and after treatment, we determined the absolute and relative numbers of granulocytes, lymphocytes, monocytes, T cells, B cells, cytotoxic T cells, helper T cells and natural killer cells. In addition, functional investigations of T cells were performed. We failed to find any effect of amalgam restorations on the immune system in terms of the parameters investigated.

Gamma/delta receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis.

Recently we described a cutaneous T-cell lymphoma expressing the gamma/delta T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating gamma/delta T-lymphoma cells we established T-cell clones bearing the gamma/delta T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these gamma/delta T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of alpha/beta T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-gamma, since it was detectable in high amounts in the SN of these gamma/delta T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN-gamma antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-gamma, which is secreted in high amounts from gamma/delta T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.