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Biomedical subjects

M Schemper

Publications and source records attributed to M Schemper.

At least 37 records · Page 2Linked to original sources

[Dilatation treatment of achalasia as initial therapy. Results of a prospective study].

From 1972 to 1991 primary dilatation therapy was investigated in a prospective study in 77 patients suffering from achalasia of the gastroesophageal sphincter. The patients were followed up continuously and the median follow-up period was ten years. 70% of patients were symptom-free after dilatation therapy at the time of the last follow-up examination, whereby 50% were cured of symptoms after a single dilatation. 27% required surgery after unsuccessful dilatation therapy. The probability of avoiding operation after dilatation therapy within 15 years of diagnosis of achalasia was 73%. The clinical symptomatology at diagnosis graded according to a scheme from I to IV, was significantly worse in patients requiring an operation (Wilcoxon test, p < 0.0005). The data of esophageal manometry were of no prognostic relevance.

Adult↗

EWS/FLI-1 antagonists induce growth inhibition of Ewing tumor cells in vitro.

Among primitive neuroectodermal tumors, Ewing tumors are characterized by a gene rearrangement recombining the 5'-EWS gene portion with one of two ETS-related proto-oncogenes, FLI-1 or ERG, in roughly 90 and 10% of cases, respectively. We attempted to antagonize EWS/FLI-1 function in Ewing tumor cell lines. As a control, a cell line derived from another small round cell tumor of neuroectodermal origin, neuroblastoma, was used. This cell line was found to express almost identical patterns of ETS proteins except for EWS/FLI-1 and a novel, ELF-related gene product. Stable expression of antisense EWS/FLI-1 cDNA resulted in decreased endogenous EWS/FLI-1 RNA levels and growth reduction of ET cells but not of neuroblastoma cells. DNA-binding FLI-1 derivatives localizing to the nucleus in which the 5'-EWS regulatory domain was replaced by bacterial beta-galactosidase dominantly modulated transcriptional transactivation from a degenerate ETS-binding motif. Transient transfection of these dominant-negative recombinants resulted in a significant decrease in the relative number of mitoses in four Ewing tumor cell lines tested but not in the neuroblastoma cell line. The presented evidence for modulation of tumor cell proliferation by EWS/FLI-1 antagonists suggests a causal role for EWS/FLI-1-mediated gene activation in the malignant transformation of the enigmatic Ewing tumor-precursor cell.

Blotting, Northern↗

Hemodynamic effects of prolonged abdominal insufflation for laparoscopic procedures.

Abdominal insufflation for laparoscopic procedures leads to numerous hemodynamic effects. We focused on blood flow distribution and arterial and venous pressure changes during CO2 insufflation at an intra-abdominal pressure of 12 mm Hg. Three segments of the vascular system were investigated (intrathoracic, cranial extrathoracic, caudal extrathoracic) in supine animals at insufflation, during a 90-minute period of pneumoperitoneum, and at desufflation. Except for instrumentation of the animals, no further surgery was performed. At insufflation (+5 minutes), cardiac output increased from 2.7 +/- 0.5 to 3.3 +/- 1.1 L/min while heart rate decreased from 138 +/- 26 to 128 +/- 17 beats per minute. Increases in jugular venous (from 6 +/- 1 to 11 +/- 4 mm Hg) and atrial (right, from 7 +/- 1 to 12 +/- 3; left, from 12 +/- 4 to 17 +/- 5 mm Hg) pressures occurred uniformly during inspiration. The great variance in atrial pressures during ventilation was not associated with changes in stroke volume, as the effective transmural filling pressures remained nearly constant. The increase in femoral venous pressure occurring during both inspiration and expiration (from 10 +/- 2 to 18 +/- 4 mm Hg) exceeded the increase in right atrial and jugular venous pressures during inspiration. Parallel increases were noted in arterial pressures (carotid, from 119 +/- 15 to 129 +/- 9; femoral, from 122 +/- 16 to 133 +/- 10 mm Hg), left ventricular pressure (from 133 +/- 17 to 143 +/- 10 mm Hg), and carotid and femoral flow (carotid, from 174 +/- 71 to 195 +/- 70; femoral, from 66 +/- 25 to 73 +/- 40 (NS) mL/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Resistance of nitrogen metabolism to growth hormone treatment in the early phase after injury of patients with multiple injuries.

OBJECTIVES AND DESIGN: Several studies have shown an anticatabolic effect of recombinant human growth hormone (rhGH) in surgical patients. We investigated, in a prospective, randomized, double blind, and placebo-controlled study, the effect of r-hGH on hormone and nitrogen metabolism in 14 patients with multiple injuries in the early phase of injury. MATERIALS AND METHODS: All patients were treated in the intensive care unit, had mechanical ventilation, and were highly catabolic, with a mean daily nitrogen loss of 13.2 +/- 1.8 g. r-hGH was given subcutaneously (once a day, at 8 PM) in a dosage of 0.2 IU/kg.d for seven days, starting on the second day after injury. RESULTS: Administration of r-hGH evoked a significant increase in plasma concentrations of GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding-protein-3 (IGFBP-3). No significant differences were found for either daily or cumulative nitrogen balances (-103.1 +/- 14 g for patients receiving r-hGH and -92.1 +/- 18.1 for those with placebo). r-hGH therapy did not affect skeletal muscle extracellular water, nor did it affect plasma or muscle concentrations of total free amino acids or glutamine. Plasma albumin, prealbumin, and retinol-binding protein concentrations were also unchanged by r-hGH therapy, as were the urinary excretion of potassium and urea. CONCLUSIONS: We conclude that elevated plasma levels of GH, insulin, and IGF-I are unable to effect a protein anabolic drive in patients with multiple injuries during the early postinjury phase and assume that this r-hGH resistance to nitrogen metabolism takes place at the level distal to IGF-I.

Adult↗

Comparison of high dose therapy of rhEPO, given two or three times a week in premature infants.

We investigated the question whether there is a difference in the response to high dose human recombinant erythropoietin (rhEPO) given twice or three times weekly in premature infants. 48 premature infants were randomly assigned to receive 300 U/kg rhEPO three times a week or 450 U/kg two times a week for at least 4 weeks and up to 6 weeks. Concomitant oral iron supplementation was compulsory, median daily dosage reached 6.6 mg/kg, doses exceeding 8 mg/kg/d were not tolerated. Our data showed no differences in the two groups in regard to hematocrit (HCT), reticulocytes and ferritin levels. A marked increase in reticulocyte counts could be observed in both groups. Serum ferritin decreased as expected. Premature infants starting with a baseline HCT lower than 32% showed a steady increase in HCT without any initial decline. No adverse effects could be observed in either group. Since there is no difference in the response to high dose rhEPO given two or three times weekly, we therefore conclude that the twice weekly regimen is compatible with outpatient treatment.

Anemia↗

Shouldice is superior to Bassini inguinal herniorrhaphy.

The original Bassini and Shouldice methods for inguinal herniorrhaphy were tested against each other and against their respective variants that avoid permanent suturing of the internal oblique muscle. Seven hundred fifty inguinal hernia repairs were prospectively allocated to 1 of 4 groups: group A: Bassini with absorbable sutures (polyglycolic acid); group B: Bassini with nonabsorbable sutures (polyester); group C: Shouldice with four rows of polypropylene sutures; and group D: Shouldice with two rows of polypropylene sutures. Outcome was correlated to prospectively defined types and risk factors such as direct hernia, repair for recurrent hernia, hernial sac diameter greater than 8 cm, age greater than 70 years, overweight, and chronic bronchitis. Actual (not actuarial) recurrence rates were determined through clinical examination by hospital staff surgeons (not through information by letter or phone) for 93.6% of surviving patients. Local complications exclusive of recurrence, but including the redoubtable and litigious sequelae of testicular atrophy and chronic ilioinguinal pain, were significantly reduced from 6.3% (group B and C) to 2.3% by omitting permanent muscle sutures (groups A and D; P < 0.05). However, the use of slowly absorbable suture material resulted in a disproportionately high recurrence rate of 12.8% in the modified Bassini group A. The original Bassini method, ie, division of the transversalis fascia and repair with nonabsorbable sutures, as was used in group B, had an actual 2-year recurrence rate of 8.7%, still a highly significant difference compared with 3.6% and 2.3% for Shouldice groups C and D, respectively (P = 0.012). For repair of recurrent hernia, the superiority of the Shouldice technique was not statistically significant: re-recurrence rate 7.6% versus 13.5% for the original Bassini group B. Repair of recurrent hernia was the only patient-related risk factor of equal significance as the method of repair. The Shouldice technique is superior to and more than merely a reinvention of Bassini's original method. The omission of muscle sutures is physiologically sound and recommended for the Shouldice operation.

Actuarial Analysis↗

[The value of the "vascular invasion" factor for prognosis of breast cancer].

The histological sections of 106 patients, who underwent a primary breast cancer operation in the years 1986 and 1987, were inspected for the presence of tumour vascular invasion. With immunohistochemical methods, tumour vessels were tomographed and the paraffin sections were stained with an antibody, which is sensitive to factor VIII-antigen. A tumour embolus was considered present, if a malignant cell was established within a positively stained lumen. The question of possible influence on the pathogenesis of breast cancer was examined in case of vascular invasion in the histological preparation. In 46 of the 106 patients (43.4%), tumour emboli were found. After an average observation period of 59 months, no tumour progression was seen in 60 patients, 46 patients developed a recurrence of the tumour at the check-up date. The presence of vascular invasion correlates with undifferentiated tumour grading. The probability of relapse- free survival after 5 years was 83.9% within the group without vascular invasion, compared with 47.9% (p = 0.0001) within the group with established vascular invasion. In the multivariate analysis of the factors lymphonodular status, grading and vascular invasion, it was found, that the presence of tumour vascular invasion with a relative risk of 3.68 (95% CI 1.93-7.03) was the strongest statistically significant prognostic factor for relapse-free survival (p = 0.0001).

Adult↗

Prolonged preoperative prismatic treatment in alternating convergent squint.

Our 10-year retrospective study includes 178 children below the age of 10 years, operated for alternating convergent squint. Inclusion criteria were: Absence of amblyopia and an angle of squint less than 45 pdpt so that alignment of the eyes in only one operation could be expected. One hundred children received preoperatively a prismatic correction of the distance deviation for a period of 6-15 months; 78 cases were treated with glasses and occlusion. In the prism-treated group a significantly better alignment (p = 0.0001) with a motorial gain of 7-8 pdpt was observed 6 months after surgery; also better sensorial results with significantly (p = 0.0001) more cases of stable NRC or harmonious ARC and improved binocularity were achieved. Unlike the type of esotropia, the preexisting retinal correspondence significantly influenced the motorial outcome (p < 0.05). Fewer reoperations were necessary in the prism-treated group (p = 0.001). Our results indicate that a prolonged prismatic correction is an effective preoperative treatment in patients with alternating convergent squint.

Child↗

The relative importance of prognostic factors in studies of survival.

The relative importance of prognostic factors in regression can be measured either by standardized regression coefficients or by percentages of explained variation in a dependent variable. One advantage of using explained variation is the direct comparability of qualitative prognostic factors with others, or of groups of prognostic factors. The description of relative importance can be accomplished within marginal or partial effects analyses. It is demonstrated that it is possible not only to provide a descriptive ranking of prognostic factors according to their statistically determined importance, but also to make inferences concerning their relative importance, employing bootstrap techniques and procedures for multiple comparisons. The methods presented, which are new in the context of Cox regression, are exemplified by analyses of studies of lung cancer and breast cancer.

Adult↗

Differences in anti-Fab antibodies in adult and late onset rheumatoid arthritis.

In the present study the ratio of antigen-bound anti-IgG-Fab antibodies (hidden aFab) to free aFab was found to be significantly increased in patients with adult onset rheumatoid arthritis (AORA) as compared to late onset rheumatoid arthritis (LORA). The overall amount of aFab was similar in both groups. The difference was only seen in seropositive patients. Within the seropositive AORA group, the aFab ratio was correlated with the duration and the stage of disease but not with the patients' age at investigation. This might reflect a higher affinity of anti-Fab antibodies and/or a greater diversity of the idiotypic repertoire in adult onset disease resulting in the formation of immune complexes, the stability of which might be enhanced further by the presence of rheumatoid factors. Although a pathophysiological involvement of aFab cannot be concluded from our observations, it is conceivable that different immunoregulatory mechanisms could be operative in RA with onset at different ages.

Adult↗

Statistical evaluation of epiluminescence microscopy criteria for melanocytic pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive technique by which the clinical diagnosis of pigmented skin lesions (PSL) can be improved. Many ELM criteria have been described, but their significance in the differential diagnosis of PSL has not yet been established. OBJECTIVE: The purpose of this study was to determine the value of ELM criteria in the differential diagnosis of PSL. METHODS: Two hundred one melanocytic PSL (61 common nevi, 60 dysplastic nevi, and 80 melanomas) were investigated with ELM for the presence of certain ELM criteria; their significance was determined by calculating the odds ratios. RESULTS: Individual ELM criteria have different weights of significance in the differential diagnosis of melanocytic PSL. Selected patterns of ELM criteria adjusted to the distinct types of PSL considerably improve the diagnostic accuracy of melanocytic PSL. CONCLUSION: The prevalence of certain distinct ELM criteria in a given melanocytic PSL has statistical value in differential diagnosis.

Confidence Intervals↗

Aneuploidy fraction but not DNA index is important for the prognosis of patients with stage I and II breast cancer--10-year results.

BACKGROUND: Individual assessment of the prognosis of patients with breast cancer is crucial for the selection of risk-adapted adjuvant therapy and in follow-up. Parameters from DNA flow-cytometry have been shown to provide significant prognostic information, but published results are in conflict and there are only a few investigations with long-term follow-up. The aim of this study is to clarify the impact of tumor DNA data on the clinical course of stage I and stage II breast cancer patients. PATIENTS AND METHODS: Several flow-cytometry DNA analyses were performed on tumor samples derived from 191 breast cancer patients entered in a controlled clinical trial after a median follow-up of more than 10 years. In addition to DNA index (DNI) and the percentage of cells in S phase (SPF), an index, designated aneuploidy fraction (AF), was determined. It ascertains the percentage of aneuploid cells out of all cells in the DNA flow-cytometry histogram, and its reproducibility has been tested by measurements of AF in two different samples of the same tumor. Univariate analyses and, in the 122 patients for whom complete information was available, a Cox model, were performed to investigate the individual prognostic impact of flow-cytometry parameters compared with established clinical factors. RESULTS: AF proved to be a very valuable prognostic indicator both in univariate and multivariate analyses, whereas DNI and SPF failed to provide independent prognostic information. The combination of AF and lymph node status clearly identifies different prognostic subgroups in operable breast cancer. CONCLUSIONS: Routine evaluation of patients with breast cancer should include tumor DNA flow-cytometry. Aneuploidy fraction is a valuable tool in assessing an individual patient's prognosis and thus can help in the choice of the appropriate adjuvant treatment strategy. Whether it, rather than DNI and SPF should be used, as we found, needs to be validated in a larger prospective investigation.

Aged↗

Blockade of endothelium-derived relaxing factor synthesis with NG-nitro-L-arginine methyl ester leads to enhanced venous reactivity in vivo.

This study was performed to examine whether endothelium-derived relaxing factor (EDRF) influences venous tone and reactivity in vivo. The inferior vena cava and abdominal aorta were studied simultaneously under continuous haemodynamic monitoring in anaesthetised rabbits. In addition, a 20-MHz intravascular ultrasound catheter was placed in the vena cava for on-line two-dimensional imaging of vessel cross-sectional area and calculation of wall stress (T(ension) = P(mean) * r(adius)/2). This approach enabled simultaneous visualisation of both venous (CA(ven)) and aortic (CA(art)) cross-sectional area with continuous recording of vessel dimensions. Measurements were made before and after administration of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg.kg i.v.), a specific inhibitor of EDRF biosynthesis. After L-NAME there was a significant increase in central venous pressure and a decrease in CA(ven). On the arterial side, L-NAME caused a significant increase in mean pressure and CA(art), resulting in a significantly augmented arterial wall stress. The venodilatation elicited by increasing doses of glyceryltrinitrate was markedly enhanced after L-NAME. Norepinephrine caused a parallel shift of the dose-response curve for CA(ven) in the presence of a lower baseline value. These results suggest that EDRF contributes substantially to the control of large capacitance veins in vivo and that L-NAME increases venous reactivity to both norepinephrine and glyceryltrinitrate.

Animals↗

Expression of p43 in breast cancer tissue, correlation with prognostic parameters.

Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H-9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product.

Breast Neoplasms↗

A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis.

To determine whether long-term oral anticoagulant treatment was effective in improving graft performance and preventing major amputation following vein bypass surgery for femoropopliteal atherosclerosis, a clinical trial was conducted in one single center and continued during 10 years. After 130 patients had electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group (treatment with phenprocoumon [n = 66]) or to a control group (n = 64) that remained without any anticoagulant treatment. Primary end points of the study were graft reocclusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. In addition, survival in the therapy group was longer. Following autologous vein bypass surgery in the treated group, the results were superior in terms of graft patency, limb salvage, and survival.

Administration, Oral↗

Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer.

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by 3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p = 0.0001), histologic grading (p = 0.0038), nuclear pleomorphism (p = 0.0019), rate of mitosis (p = 0.0002), and lymphocytic reaction (p = 0.0001), and significantly directly with the estrogen receptor status (p = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Our in vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.

Breast Neoplasms↗

Spontaneous growth in Turner syndrome: evidence for a minor pubertal growth spurt.

Spontaneous growth of 141 untreated girls with Turner syndrome was analysed. Of the patients 25% were born prematurely; their weight and height were normal when compared to prematurely born healthy infants. However, birth weight and height was significantly retarded in Turner patients born at term. A curve for height and growth velocity for the age range 0-16 years was constructed with a sensitive statistical method. By use of a mathematical model equations were created for calculating z-scores and the related percentiles for the height of individual patients at given age. Median height of 18 untreated patients at 18 years was 143.8 cm. Analysis of growth velocity revealed a minor but significant growth spurt at the age of 12.5 years. This growth spurt was also detectable in patients without signs of spontaneous puberty and occurred later in patients with 45,X0 karyotype. Bone age progression was linear up to the age of 7.5 years and decelerated thereafter.

Adolescent↗

Comparison of prognostic indices for burns and assessment of their accuracy.

Logistic regression was used to create four individual models of prognostic indices based on our patient population. The simplest index using only three factors, age, extent of full skin thickness burn and inhalation injury, proved to be best. These models were also compared with established indices, like Baux's, Bull's and Roi's. For a specificity below 80 per cent, Baux's rule fits as well as Roi's index does. Changes in treatment modalities and improvement in therapy will influence the accuracy of an index. Indices must be adapted to changing conditions to avoid increasing false prediction of death.

Adolescent↗