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Biomedical subjects

S Braun

Publications and source records attributed to S Braun.

At least 127 records · Page 7Linked to original sources
PubMed1999

Monoclonal antibody therapy with edrecolomab in breast cancer patients: monitoring of elimination of disseminated cytokeratin-positive tumor cells in bone marrow.

Despite current advances in antibody-based immunotherapy of breast and colorectal cancer, we have recently shown that the actual target cells (e.g., tumor cells disseminated to bone marrow) may express a heterogeneous pattern of the potential target antigens. Tumor antigen heterogeneity may therefore represent an important limitation of the efficacy of monospecific antibody therapy. To measure the efficacy of such a monospecific approach, we analyzed the elimination of tumor cells coexpressing the epithelial cell adhesion molecule (EpCAM) under therapy with murine monoclonal antibody 17-1A (Edrecolomab) directed against EpCAM. In bone marrow aspirates from 10 breast cancer patients with metastatic (n = 8) and locoregional recurrence (n = 2), tumor cells were identified with the antibody A45-B/B3 directed against the epithelial differentiation marker cytokeratin (CK) and simultaneously typed for EpCAM expression using the antibody 17-1A. Patients were treated with a single dose of 500 mg of Edrecolomab and monitored by bone marrow analyses before and at days 5-7 after antibody treatment. In all 10 patients, we assessed a marked reduction in the mean numbers of both CK+ cells (73 versus 15; P = 0.003, t test) and EpCAM+/CK+ cells (17 versus 1; P = 0.003, t test) per 10(6) bone marrow cells. Complete elimination of EpCAM+ cells was possible in four patients. We conclude that Edrecolomab can be used in breast cancer patients to target isolated EpCAM+/CK+ cancer cells. Using CK-based immunoassays, we reliably detected residual tumor cells in bone marrow and typed EpCAM expression. This allowed us to monitor the cytotoxic elimination of such cells after Edrecolomab application. Selection of EpCAM-/ CK+ tumor clones showed that further antibodies directed against tumor-associated antigens are warranted to improve the efficacy of monospecific approaches.

Antibodies, Monoclonal↗
PubMed1999

[Long-term results of reconstructive surgery for mitral insufficiency].

BACKGROUND: Surgical repair is the procedure of choice for mitral insufficiency since it preserves better left ventricular structure and function. AIM: To assess the long term clinical and echocardiographic results of mitral valve reconstructive surgery. MATERIAL AND METHODS: A review of clinical and echocardiographic data of 68 patients (34 male, age range 17 to 82 years), subjected to surgical mitral valve repair between December 1991 and March 1998. Preoperative functional capacity of these patients was 2.96 +/- 0.7. Surgical repair was assessed using transesophagic echocardiography in all subjects. RESULTS: The etiology of mitral insufficiency was degenerative in 43 patients, rheumatic in 10, infectious in 6, ischemic in 5 and miscellaneous in 4. The most frequent pathological findings were dilatation of the mitral ring in 42% of patients, chordae tendinae rupture in 32% and enlargement in 24%. A mitral anuloplasty was done in 90% of patients, a cuadrilateral resection of posterior leaflet in 52% and chordae tendinae transference in 12%. An additional surgical procedure was done in 34% of subjects. Three patients died during hospitalization (4.4%). During the follow up of 36.5 +/- 22.3 months, five patients died and one required a mitral valve replacement. The actuarial survival probability was 95.3 +/- 2.6% at one year and 83.5 +/- 6.5% at five years. The reoperation free survival was 100% at one year and 97.4 +/- 2.5% at five years. At the end of follow up the functional capacity improved to 1.25 +/- 0.4. Echocardiography showed absence of mitral insufficiency in 48.4% of patients, minimal, mild and moderate insufficiency in 35.5, 14.5 and 1.6% of patients respectively. CONCLUSIONS: Surgical valve reconstruction in mitral insufficiency has satisfactory long term results and should be the procedure of choice for eligible patients.

Adolescent↗
PubMed1999

[Heart disease, pregnancy and anticoagulant therapy].

Pregnancy is a hypercoagulable state. Some women with cardiac disease and mechanical valve prosthesis are at increased risk of arterial thromboembolic phenomena. These women are maintained on oral anticoagulants and require effective permanent prophylaxis during pregnancy. The use of oral anticoagulants during pregnancy is controversial because of the risks of embriopathy (Chondrodysplasia punctata) in fetuses who are exposed to coumarin between the 6th and 9th week of gestation, the risk of neurological disorders all through pregnancy, and a higher incidence of abortion and stillbirths. The exact incidence of these complications is unknown. Most of this information comes from North American reports, when much higher mean daily doses of coumarin were administered, and they were probably overemphasised. Reports from Europe, Asia and our own, show that both embriopathy and central nervous system malformations are probably dose-related and that the risks of abnormality to the fetus are small. The ACC Antithrombotic Consensus (1998) recommends the use of subcutaneous heparin all through pregnancy or until the 13th week of gestation. Heparin does not cross the placenta, however there is a higher risk of maternal bleeding, abortion and stillbirths. With the use of small dose of heparin and of therapeutic heparin doses there is a risk of prosthesis thrombosis. Anticoagulant treatment of patients with prosthetic heart valves during pregnancy remains controversial. Subcutaneous heparin prophylaxis is feasible but the use of well controlled oral anticoagulants appear to offer lower risks of maternal and fetal complications.

Abnormalities, Drug-Induced↗
PubMed1998

Muscle could be the therapeutic target in SMA treatment.

A nerve-muscle coculture model (human muscle cells innervated by embryonic rat spinal cord) was used to explore the pathogenesis of spinal muscular atrophy (SMA). Previous studies showed that myofibers from donors with SMA type I or SMA type II (but not SMA type III) undergo a characteristic degeneration 1-3 weeks after innervation (Braun et al. [1995] Lancet 345:694-695). To determine which cells are involved in degeneration, we cloned satellite cells and fibroblasts derived from muscle biopsies of normal (healthy) donors and donors with SMA. We show that fibroblasts are required for successful innervation, that fibroblasts from normal and SMA donors contribute equally well to the establishment of cocultures, and that only SMA satellite cells are responsible for the degeneration of innervated cocultures. We succeeded in preventing the degeneration of cloned satellite cells from SMA donors by adding 50% cloned satellite cells from normal donors to the culture to make heteromyotubes. In mixed cocultures, after innervation, we did not observe degeneration. This result suggests that survival of the cocultures depends on a message derived from the muscle cells. Consequently, we propose that therapeutic approaches for SMA that could repair (or compensate for) the genetic defect in muscle cells (which are otherwise much more accessible for gene therapy than neurons) might prevent motoneuron degeneration. The role of muscle cells in the establishment and the degeneration of neuromuscular junctions deserves further attention and investigation.

Animals↗
PubMed1998

Characterization of a newly established endometrial stromal sarcoma cell line.

We describe a newly established human sarcoma cell line derived from an endometrial stromal sarcoma (ESS). The cell line has been maintained in long-term cell culture for more than 2 years. It has been repeatedly analyzed in terms of morphology, immunocytochemical features, ultrastructure and karyotypic characteristics. In contrast to uniform endometrial stromal differentiation in vivo, the tumor cells were shown to display distinct phenotypical heterogeneity in vitro. In addition to the predominant cell type, which retained sarcomatous differentiation, foci of epithelial-like cells were observed in the cell culture. Immunocytochemical and ultrastructural analysis demonstrated a mainly mesenchymal phenotype with signs of epithelial characteristics, such as expression of cytokeratins, and the presence of desmosomes and kinetocilia, respectively. Cytogenetic analyses in early and late passages revealed unbalanced translocations between chromosomes 3 and 6 and an additional i(19)(q10), as common karyotypic changes in all tumor cells, indicating a monoclonal origin. Our new cell line can be used as an in vitro model to study the mechanisms of heterogeneous differentiation patterns in ESS.

Aged↗
PubMed1998

Calcium channel blocking agents and risk of cancer in patients with coronary heart disease. Benzafibrate Infarction Prevention (BIP) Study Research Group.

OBJECTIVES: This analysis sought to estimate the risk ratio for cancer incidence and cancer-related mortality associated with the use of calcium channel blocking agents (CCBs) in a large group of patients with chronic coronary heart disease (CHD). BACKGROUND: Recent publications contend that the use of short-acting CCBs may double the risk of cancer incidence and possibly increase mortality in hypertensive patients. METHODS: Cancer incidence data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention (BIP) study, one-half of whom were treated at the time of screening with CCBs, over a mean follow-up period of 2.8 years. Cause-specific mortality was available through September 1996 (mean follow-up 5.2 years). The statistical power of detecting an odds ratio > or = 1.5 (given the cancer incidence rate of 2.1 in the nonusers of CCBs) was 0.91. The power declined to 0.77, 0.54 and 0.41, with declining odds ratios of 1.4, 1.3 and 1.25, respectively. RESULTS: Of 246 incident cancer cases, 129 occurred among the users (2.3%) and 117 among nonusers of CCBs (2.1%). After adjustment for age, gender and smoking, the odds ratio estimates for all cancers combined was 1.07 (95% confidence interval [CI] 0.83 to 1.37) for CCB users relative to nonusers. The adjusted risk ratio for all-cause mortality for age, gender and smoking and pertinent prognostic clinical characteristics was estimated at 0.94 (95% CI 0.85 to 1.04). The adjusted risk ratio for cancer-related mortality was 1.03 (95% CI 0.75 to 1.41). CONCLUSIONS: Patients with CHD treated with CCBs exhibited a similar risk of cancer incidence and total and cancer-related mortality compared with nonusers of CCBs. This analysis provides a certain assurance that CCB use in middle-aged and elderly patients with CHD is not associated with a meaningful difference in cancer incidence and related mortality.

Aged↗
PubMed1998

[Perforation into the heart--a rare complication of stomach ulcer in hiatal hernia].

Perforation into the heart is a rare ulcer complication in a hiatal hernia. Because of the massive bleeding, medical help is often in vain. The case of a 73-year-old patient reported by our department confirms this. Endoscopic treatment was not possible because of the extraordinary amount of blood in the stomach, and the high intraoperative blood loss was lethal. If gastric ulcers occur in upper regions of the stomach, the possibility of the presence of an paraesophageal hernia and elective surgical treatment must be considered.

Aged↗
PubMed1998

Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly.

We carried out cytogenetic analysis on 11 renal oncotytomas by using G-banding and DAPI-banding techniques. Four of our tumors exhibited structural rearrangements affecting chromosome 11 at band q13. Together with another case previously described by us, our tumors constitute the largest series of renal oncocytomas displaying translocations involving 11q13. A review of the literature disclosed only 6 similar oncocytomas, 1 tumor with a t(9;11)(p23;q12), 2 tumors with a nearly identical t(9;11)(p23;q13), and 3 tumors with a t(5;11)(q35;q13). Therefore, our findings provide further cytogenetic evidence that genes located on 11q12-13 may be involved in the tumorigenesis of renal oncocytomas.

Adenoma, Oxyphilic↗
PubMed1998

Prognostic significance of micrometastatic bone marrow involvement.

The present review focuses on the methodology and clinical significance of new diagnostic approaches to identify micrometastatic breast cancer cells present in bone marrow (BM), as a frequent site of overt metastases. Using monoclonal antibodies (mAbs) to epithelial cytokeratins (CK) or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic BM preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of these immunostained cells is prognostically relevant with regard to relapse-free and overall survival. The current interest in autologous bone marrow transplantation in patients with solid tumors further underlines the need for screening methods that allow the detection of minute numbers of residual tumor cells in the transplant. Although the development of new molecular detection methods based on the amplification of a marker mRNA species by the polymerase chain reaction technique is a very exciting area of research, the clinical significance of this approach needs to be demonstrated in prospective studies. The immunocytochemical assays may be, therefore, used to improve tumor staging with potential consequences for adjuvant therapy. Another promising clinical application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The extremely low frequency of BM tumor cells greatly hampers approaches to obtain more specific information on their biological properties. The available data indicate that these cells represent a selected population of cancer cells which, however, still express a considerable degree of heterogeneity with regard to the expression of MHC class I antigens, adhesion molecules (EpCAM), growth factor receptors (EGF receptor, erb-B2, transferrin receptor), or proliferation-associated markers (Ki-67, p120). Regardless of the detection technique applied, there is an urgent demand for large multicentre trials, in which standardized methods are related to specified clinical outcomes.

Bone Marrow↗
PubMed1998

The form of the human dental arch.

The human dental arch form is shown to be accurately represented mathematically by the beta function. The average correlation coefficient between measured arch-shape data and the mathematical arch shape, expressed by the beta function, is 0.98 with a standard deviation of 0.02. Forty sets of casts--15 Class I, 16 Class II, and 9 Class III--were examined. A precision machine tool device was used to record the X-, Y-, and Z-coordinates of selected dental landmarks on all casts to 0.001 mm accuracy. The coordinates were processed through a computer curve-fitting program. The Class III mandibular arches had smaller arch depth and greater arch width (beginning in the premolar area) than the Class I arches. The Class II mandibular arches exhibited generalized reduced arch width and depth compared with the Class I arches. Maxillary arch depths were similar in all three groups. However, the Class III maxillary arch widths were greater from the lateral incisor-canine area distally compared with the Class I maxillary arch, and the Class II maxillary arch form was narrower than the Class I arch form from the lateral incisor-canine area distally. The beta function more accurately described the dental arch form than representations previously reported.

Dental Arch↗
PubMed1998

Encoding and recall of parsed stories in hypnosis.

To define the relationship between aspects of memory concerning encoding and recall of short texts and hypnosis, standardized stories were narrated to 12 subjects, both during ordinary state of consciousness and after hypnotic induction by means of the Stanford Hypnotic Susceptibility Scale (Form C). The narrative material used as a stimulus was based on several stories taken from popular oral tradition, previously analyzed according to the classic criteria proposed by Rumelhart in 1975 and Mandler and Johnson in 1977. The subjects' memory performance during both experimental conditions was tape-recorded and compared with the analysis of the original stories (Terminal Nodes) as well as with the higher linguistic structures of the scheme (Basic Nodes), according to Rumelhart's typology. During hypnosis, the subjects recalled significantly fewer narrative elements at both levels of analysis (Terminal Nodes and Basic Nodes). We conclude that hypnosis does not enhance recent memory.

Adult↗
PubMed1998

[Coronary surgery. 20 years of follow-up].

BACKGROUND: Since the first surgical coronary revascularization done in Chile in 1971, 5000 such procedures have been performed. AIM: To assess the long term results of coronary revascularization surgery in our institution and to identify prognostic factors. PATIENTS AND METHODS: Five groups of 100 patients each, composed by the first consecutive patients subjected exclusively to coronary bypass surgery in the years 1975, 1980, 1985, 1990 and 1995 were retrospectively studied. RESULTS: Mean age of patients increased from a median of 52 years old in 1975 to 62 years old in 1995. No changes in the frequency of diabetes, hypertension, high serum cholesterol or previous myocardial infarction were observed. There was an increase in the proportion of patients with a recent (< 30 days) infarction that were operated along time. Seventy percent of patients had triple vessel disease or LMT and this proportion did not change. The number of grafts per patients increased form 1.9 to 3.4 and the use of arterial conduits from 0.18 to 0.81. Perioperative mortality remained constant and was 1.6%. Follow up information was obtained for 93% of 492 survivors. Actuarial survival at 5, 10, 15 and 20 years was 93 +/- 1, 82 +/- 2, 62 +/- 3 and 41 +/- 4% respectively. Ninety eight +/- 0.7, 89 +/- 2, 73 +/- 4 and 65 +/- 5% of patients remained free of a new myocardial infarction in the same lapses, respectively. Ninety seven +/- 1, 94 +/- 2, 76 +/- 4 and 47 +/- 7% of patients remained free of a new operation. Stepwise logistical regression analysis identified as bad prognostic factors, in decreasing order: cardiac failure, diabetes, smoking, hypercholesterolemia and age at the moment of operation. CONCLUSIONS: Coronary artery bypass surgery provides good and long lasting clinical improvement. The prognosis of patients is influenced by the presence of cardiac failure, some well known coronary risk factors and age at the moment of operation.

Aged↗
PubMed1998

[Cardiac rhythm and systemic embolism in long-term follow up of patients with non-valvular paroxysmal atrial fibrillation].

BACKGROUND: Paroxysmal atrial fibrillation may predispose to systemic embolism. There is little information about the evolution of cardiac rhythm and the occurrence of new embolic events in these patients. AIM: To report the results of a long term follow up of patients with paroxysmal atrial fibrillation. PATIENTS AND METHODS: Patients consulting for non valvular paroxysmal atrial fibrillation were followed for a mean period of 5 years. An EKG, 2D echocardiogram and brain CT scans were performed on admission and at the end of the follow up period to all patients. RESULTS: Sixty eight patients aged 65 +/- 1.5 years were studied. Thirty two had an idiopathic atrial fibrillation, 28 had a history of mild hypertension and 8 had a history of coronary artery disease. Evidence of systemic emboli was found in 17 patients at entry (to the brain in 14 patients). During the follow up 87% of patients required antiarrhythmics, 27% were anticoagulated and 28% received aspirin. Five patients had new embolic episodes. Of these, four had a history of prior embolism. Forty one percent of patients continued in sinus rhythm and remained asymptomatic, 32% had at least one recurrence of paroxysmal atrial fibrillation and nine patients evolved to chronic atrial fibrillation. Five patients required a permanent pacemaker due to symptomatic bradycardia. CONCLUSIONS: Most patients with non valvular paroxysmal atrial fibrillation remain in sinus rhythm but one third have recurrences of the arrhythmia. A main risk factor for embolism is the history of previous embolic episodes.

Aged↗
PubMed1997

Transfection of myoblasts in primary culture with isomeric cationic cholesterol derivatives.

Transfection of satellite cells from dog muscle (myoblasts) in primary culture has been optimized with respect to the position of the cholesteryl moiety along the polyamine chain of spermidine or spermine. Spermidine or spermine were derivatized with cholesterylchloroformate giving rise to three isomers in the case of spermidine and two isomers for spermine that were separated by reversed-phase high-performance liquid chromatography (rp-HPLC). The position of the cholesteryl moiety was assigned by 13C-NMR and coelution with synthetic isomers of defined structure. The isomeric cationic lipids were evaluated for their transfection activity in myoblasts from dog muscle and a human lung epithelial cell line (A549) using plasmid DNA expressing the luciferase reporter gene. The results showed that the position of the cholesteryl moiety is of critical importance for efficient transfection of myoblasts in primary culture with isomers having a derivatized secondary amine being significantly more effective than those with a derivatized primary amine. On the contrary, differences in the A549 cell line were less pronounced and did not follow the same pattern. The results show that slight structural differences between cationic lipids lead to significantly different transfection efficiencies for myoblasts in primary culture. This may also represent an advantage in view of cell or organ targeting.

Animals↗
PubMed1997

Incorporation of 1-deoxy-D-xylulose into isoprene and phytol by higher plants and algae.

In further substantiating the novel mevalonate-independent pathway for isoprenoid biosynthesis, which generates isopentenyl diphosphate (IPP) via 1-deoxy-D-xylulose-5-phosphate, labeling experiments with 1-[2H(1)]deoxy-D-xylulose were performed with various higher plants and algae: efficient incorporation was observed into isoprene emitted by Populus, Chelidonium, and Salix, into the phytol moiety of chlorophylls in a red alga (Cyanidium), in two green algae (Scenedesmus, Chlamydomonas), and a higher plant (Lemna). By contrast, 13C-mevalonate applied was incorporated into isoprene and phytol to a much lower extent or not at all. This demonstrates that this '1-deoxy-D-xylulose-5-phosphate pathway' for biosynthesis of plastidic isoprenoids is widely distributed in photosynthetic organisms.

Butadienes↗
PubMed1997

Antianginal and anti-ischemic effects of mibefradil in the treatment of patients with chronic stable angina pectoris.

Five placebo-controlled, double-blind, multicenter, parallel-design studies were performed to evaluate the antianginal and anti-ischemic characteristics of the novel T-channel-selective calcium antagonist, mibefradil, in the treatment of patients with chronic stable angina pectoris. Of the 5 studies, 2 were monotherapy dose-finding trials and 3 were conducted in patients receiving background antianginal therapy: either beta blockers (2 studies) or long-acting nitrates (1 study). A total of 865 patients were randomized to 1 of 4 mibefradil dose groups (25, 50, 100, and 150 mg; n = 565) and placebo (n = 300). The antianginal and anti-ischemic effects of mibefradil were assessed across all 5 studies by evaluating exercise tolerance test variables, weekly number of anginal attacks and short-acting nitroglycerin consumption, and in both dose-finding studies, the number and total duration of silent ischemic episodes (48-hour Holter monitoring). A statistically significant increase in exercise duration was achieved in 3 of 5 studies with the 50-mg dose of mibefradil and in 3 of 3 studies with the 100-mg dose of the compound over the effects observed in the placebo groups. A significant delay in time to onset of ischemia during exercise was induced in all studies with the 50- and 100-mg doses of mibefradil. The 25-mg dose of mibefradil was not significantly better than placebo, and the effects of the 150-mg dose of the compound were similar to those observed with the 100-mg dose. Across all studies, a dose-related decrease was observed in the number of weekly anginal attacks and in weekly nitroglycerin consumption. Similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed during Holter monitoring for 48 hours in the 2 dose-finding studies. The antianginal and anti-ischemic effects were associated with a dose-related decrease in heart rate and double product both at rest and at exercise termination. Treatment with the 50- and 100-mg doses of mibefradil was found to be well tolerated and safe compared with placebo, a finding that held true for patients on chronic beta-blocker or long-acting nitrate therapy. Taken together, these studies indicate that mibefradil is an effective and well-tolerated once-daily treatment for chronic stable angina pectoris at doses of 50 and 100 mg, which are the lowest and highest effective doses of the compound, respectively.

Aged↗