[Support of spontaneous atrioventricular conduction in patients with DDR(R) pacemakers: effectiveness and safety]. / Unterstützung der spontanen atrioventrikulären Uberleitung bei Patienten mit DDD(R)-Schrittmachern. Effektivität und Sicherheit.

AIM: In a prospective and randomized multicenter study using a cross-over protocol we compared the efficacy and the safety of the ELA medical mode-switch algorithm (DDD/AMC = DDD to AAI) to conventional DDD stimulation in patients with spontaneous AV conduction. PATIENTS AND METHOD: Forty-eight patients with a mean age of 67 +/- 13 years were included. Underlying heart disease was present in 54%. Pacemaker indications were paroxysmal AV block (21%), sick-sinus syndrome (46%), paroxysmal AV block + sick-sinus syndrome (31%) and tachycardia-bradycardia syndrome (8%). Patients were excluded from the study in case of a permanent 1st to 3rd degree AV block, a right bundle-branch block with QRS > 120 ms, severe coronary heart disease or idiopathic cardiomyopathy. The programming of the pacemaker was randomized to either DDD/AMC or DDD and was crossed over after 1 month. The AV interval (AVI) which was programmed in conventional DDD pacing was calculated as AVI = PR (or AR) + 30 ms at rest or as AVI = PR (or AR) - 50 ms during exercise. When the DDD/AMC mode was programmed, the AV interval was calculated automatically. We analyzed the AV interval, the frequency of ventricular pacing, the number of pacemaker-induced tachycardias, the number of atrial tachyarrhythmias, and the final programming which was left to the physician's choice. RESULTS: The AV interval after conventional DDD stimulation was 201 +/- 38 ms vs 195 +/- 28 ms with DDD/AMC (p = ns). Ventricular stimulation was significantly less often in the DDD/AMC mode than in the DDD mode (15 +/- 17% vs 48 +/- 37%, p < 0.001). Thereby the DDD/AMC algorithm led to a 69% reduction of ventricular pacing which means an approximately 5.5 months prolongation of the battery lifetime. There was no significant difference in the incidence of pacemaker-induced tachycardias. At the end of the study 77% of the physicians programmed the DDD/AMC mode. CONCLUSION: The analyzed DDD/AMC mode-switch algorithm leads to a significant reduction of ventricular pacing in patients with spontaneous AV conduction or with only paroxysmal AV block. Thereby the battery lifetime is prolonged and the incidence of complications due to ventricular pacing can be reduced.

Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity.

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.

Antigenic phenotyping of lymphoid cells and B cell gene rearrangement in type B gastritis and in gastritis not associated with Helicobacter pylori colonization.

Marginal-zone B cells of the mucosa-associated lymphoid tissue (MALT) are the normal counterpart of the neoplastic cells in MALT lymphoma. In both cases these lymphocytes express surface immunoglobulins, but are negative when stained for B cell associated antigens like CD10 and CD23. Furthermore, the B cell gene rearrangement has been found in Helicobacter pylori associated chronic gastritis and in extranodal type of marginal-zone lymphoma. The aim of this study was to quantify the number of IgM-, CD10-, and CD23-positive lymphocytes in patients with type B gastritis and to compare the results with the antigen profile of mononuclear cells in patients with gastritis not associated with H. pylori. Additionally, the immunoglobulin heavy-chain (IgH) gene rearrangement in H. pylori positive and H. pylori negative gastritis was studied. From 23 patients with a positive urease test and/or histologically proven H. pylori infection and chronic gastritis and from 22 patients with H. pylori negative chronic gastritis mucosa biopsy specimens were taken. Single-cell suspensions were obtained following enzymatic digestion. For immunocytochemistry, an alkaline phosphatase-antialkaline phosphatase method was applied. IgH gene rearrangement in formalin-fixed, paraffin-embedded specimens was determined by polymerase chain reaction in 11 patients with chronic gastritis. An increase in mu-positive plasma cells and B lymphocytes was detected in patients with H. pylori positive gastritis as compared with patients with H. pylori negative gastritis (10.0 vs. 3.9%, p < 0.001, and 4.3 vs. 1.6%, p < 0.01, respectively). In both groups, the proportion of CD10- and CD23-positive lymphocytes was <1%. IgH gene rearrangement was not restricted to type B gastritis; single bands were also present in 3 of 7 patients with H. pylori negative chronic gastritis. Our finding of IgH gene rearrangement in some of the patients with H. pylori negative chronic gastritis indicates that additional factors may be critical for these genotypical changes and for the pathogenesis of gastric MALT lymphoma.

Eating-disordered behaviors and personality characteristics of high school athletes and nonathletes.

OBJECTIVE: To assess whether high school athletes are at risk for an eating disorder, whether personality characteristics differentiate athletes from nonathletes, and whether high levels of perfectionism put athletes at risk. METHOD: 318 high school athletes were randomly matched to 360 nonathletes. Comparisons were made by means of the Eating Disorders Inventory (EDI), Restraint Scale, Risk Symptom Checklist, Multidimensional Personality Questionnaire (MPQ), and body mass index (BMI). RESULTS: Athletes did not have higher levels of disordered eating behaviors and attitudes than their nonathletic counterparts. Athletes had less negative views of life than nonathletes. However, perfectionistic tendencies may put some athletes at risk. DISCUSSION: High school athletes are not at greater risk for the development of an eating disorder than other students. Athlete's positive outlook on life and high self-efficacy may serve as protective factors. Alternatively, athletes may not be at risk until they train for one particular sport in a highly competitive environment.

Assessment of satisfaction with the communication process during consultation of cancer patients with potentially curable disease, cancer patients on palliative care, and HIV-positive patients.

The aim of this study was to evaluate the attitudes of cancer patients towards the medical interview and to determine their psychosocial satisfaction subsequent to the dialogue. The answers given by patients with curable cancer were compared to those given by cancer patients whose treatment intent was palliative and to the replies of patients infected with the human immunodeficiency virus (HIV), a nonmalignant but also incurable state. The subject population comprised a total of 139 patients. Patients had to complete a questionnaire with a total of 34 items. The answers to the questions were rated on a 5-point scale with response options ranging from 1 to 5 or consisting of true-false statements. Cancer patients, palliative and curative, and HIV-positive patients considered their physicians to be honest (x = 4.34, x = 4.58, and x = 4.30, respectively; p = 0.104), and they emphasized that he/she took enough time answering their questions (x = 4.00, x = 4.30 and x = 4391, respectively; p = 0.12). Cancer patients treated with potentially curable disease were more frequently afraid of being informed about additional diagnostic examinations and about the disclosure of results as compared to cancer patients on palliative care (p < 0.05 for both questions). Patients with HIV-infection considered themselves less informed about the treatment they received as compared to curative cancer patients (x = 3.73 and x = 4.28, respectively; p < 0.046). Only 8.0% of the tumor patients on palliative care, but 63.6% of the HIV-positive patients realized that their medication was given with the objective to relieve symptoms (p < 0.001). When asked about additional goals of treatment, 48% of the palliative cancer patients and 15.1% of the HIV-positive patients checked "cure" (p < 0.002). In conclusion, particularly patients with curable cancer were afraid of information they might receive during the medical interview. Cancer patients considered themselves better informed compared to patients with HIV-infection. This is in significant contrast with the actual, measurable knowledge about their disease in the latter group. It is indeed surprising that only a small minority of incurable cancer patients realized that the goal of the medical care they received was relief of symptoms, the principle objective of palliation.

Spacing requirements between LexA operator half-sites can be relaxed by fusing the LexA DNA binding domain with some alternative dimerization domains.

The dimerization domain of the LexA repressor has been replaced by two heterologous dimerization motifs: the "leucine zipper" from the jun oncogene product and the carboxy-terminal oligomerization domain of Escherichia coli lac repressor. The corresponding hybrid proteins LexA1-87-Jun zipper and LexA1-87-lac repressor have been purified and their DNA binding properties have been studied using gel mobility shift assays. Both fusion proteins form stable specific complexes with a short DNA duplex harboring the CTGT(at)4ACAG consensus sequence of the LexA repressor. This conserved DNA binding capacity distinguishes these two fusion proteins from many others containing a LexA DNA binding domain fused to different heterologous transactivation and/or dimerization domains. However the fusion proteins LexA1-87-Jun zipper and LexA1-87-lac repressor behave differently from native LexA repressor in that these fusion proteins tolerate the insertion of additional base-pairs between the two invertedly repeated CTGT motifs. LexA1-87-Jun zipper requires two CTGT motifs and tolerates the insertion of at least two additional base-pairs between these motifs, whereas LexA1-87-lac repressor requires in fact only a single CTGT motif for the formation of a specific complex detectable in gel mobility shift assays. The inability of the normal LexA repressor to form well-defined complexes with operators containing additional base-pairs in the center suggests that the LexA "hinge region" between the amino-terminal DNA binding and the carboxy-terminal dimerization domain might not be entirely flexible. In an attempt to remove a hypothetical interaction between the LexA cleavage site (which is situated within the hinge region) and the catalytic cleavage center (situated within the carboxy-terminal domain) a LexA mutant repressor containing five simultaneous mutations in the hinge region has been constructed and purified. Surprisingly this mutant repressor failed to form stable complexes detectable by the gel mobility shift assay even with the normal consensus sequence, suggesting that the LexA hinge region is more than a simple connector between the two structural domains and that its chemical nature is important not only for LexA cleavage, but also for the formation of stable LexA-DNA complexes.

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.

Construction, purification, and characterization of a hybrid protein comprising the DNA binding domain of the LexA repressor and the Jun leucine zipper: a circular dichroism and mutagenesis study.

An increasing number of eukaryotic transcription factors interacting specifically with DNA comprise a dimerization motif called the "leucine zipper". These leucine zipper proteins form homodimers and/or heterodimers with another protein containing a leucine zipper motif. The leucine zipper of the oncoprotein Jun is particular in that Jun may form homodimers as well as heterodimers with the oncoprotein Fos, which are however more stable than the Jun-Jun homodimers. Leucine zipper dimerization is thought to occur through a coiled-coil arrangement of parallel alpha-helices, but the rules governing the specificity of homo- and/or heterodimerization are still largely unknown. To address this question in the case of the Jun leucine zipper, we constructed a fusion protein containing the amino-terminal DNA binding domain of the LexA repressor from Escherichia coli fused to the Jun leucine zipper. This hybrid protein (LexA-JunZip) is stable in E. coli and confers much tighter repression in vivo than the DNA binding domain of LexA alone. DNA binding competition experiments with synthetic Jun and Fos leucine zipper peptides in vitro showed that the leucine zipper mediated dimerization of LexA-JunZip is essential for DNA binding of the fusion protein. The purified LexA-JunZip protein dimerizes in vitro with a dimerization constant of 2 x 10(7) M-1 at 5 degrees C. Dimerization is very sensitive to temperature, since the dimerization constant drops at 20 degrees C to 2 x 10(6) M-1 and at 30 degrees C to only 3 x 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspergillus deflectus infection in four dogs.

Four cases of disseminated aspergillosis caused by Aspergillus deflectus in German Shepherds are presented. Three of the cases, which involved multiple organs, terminated in euthanasia. One case, with bony involvement of the limbs and skull, lived. The unique morphological characteristic of the conidial head resembling a briar pipe led to the identification of A. deflectus. To the authors' knowledge these are the first reported cases of infections caused by A. deflectus in man or animal.

Multiple myeloma in a horse.

Multiple myeloma was diagnosed in a 22-year-old Arabian mare with a history of chronic weight loss. Quantitative immunoglobulin analysis revealed monoclonal gammopathy (IgG(T), 9,800 mg/dl). Due to progressive weight loss, the horse was euthanatized. Microscopy of tissues revealed plasma cell infiltrates in bone marrow, spleen, pituitary gland, adrenal cortex, muscle of the tongue, and bronchial, renal, and mesenteric lymph nodes.

Protozoal myeloencephalitis in horses in California.

Three cases of equine protozoal myeloencephalitis were diagnosed over a 12-month period in horses that had never left the state of California. These cases suggest that the disease is enzootic in California.

Renal pelvic and ureteral dilatation in male rats ingesting trisodium nitrilotriacetate.

Renal pelvic and proximal ureteral dilatation has been observed in male Charles River (CD) and Fischer 344 rats ingesting comparable doses of Na3NTA X H2O. Ureteral dilatation is accompanied by epithelial surface ulceration and erosion. Taken together with previous work (Anderson, Alden & Merski, Fd Chem. Toxic. 1982, 20, 105), these findings demonstrate that the ingestion of high doses of NTA results in similar effects on the transitional epithelium throughout the urinary tract.