[Dialogue between oncology and molecular biology].
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Biomedical subjects
Publications and source records attributed to M Kaufmann.
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The use of goserelin with or without tamoxifen was investigated in a randomised multicentre study involving 318 pre- and perimenopausal advanced breast cancer patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients had objective responses (UICC criteria) compared with 38% of goserelin plus tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of combination therapy in time to progression (P = 0.03) but not in survival (P = 0.25). Median follow-up for survival was 117.5 weeks. Median times for disease progression and survival were 23 and 127 weeks in the goserelin alone group and 28 and 140 weeks in the combination group, respectively. In 115 patients with skeletal metastases only, significant differences in favour of combination therapy were seen in response rate, time to progression and survival. Both treatments were well tolerated and no additional safety issues were associated with combination therapy.
Porcine 17 beta-estradiol dehydrogenase (EDH) was recently purified and cloned. It catalyzes the NAD(+)-dependent oxidation of estradiol to estrone 360-fold more efficiently than the back reaction with NADPH. The 32 kDa EDH is cut from an 80 kDa primary translation product with a multidomain structure unknown for other hydroxysteroid dehydrogenases. The highest EDH activities and strongest immunoreactions are found in liver (hepatocytes) and kidney (proximal tubuli) followed by uterus (luminal and glandular epithelium), lung (bronchial epithelium). Progesterone treatment of ovariectomized gilts stimulates oxidative EDH activity in uterus, anterior pituitary, skeletal muscle (diaphragm) and kidney. Constitutive levels of EDH activity were seen in the adrenals, the lung and the liver.
Preoperative ultrasound as well as intraoperative laparoscopic diagnosis have both their limits, a fact that might be significant for laparoscopic surgical management. In particular, since in this surgical domain, where almost everything has become technically feasible, the operator must decide what is to the benefit of the patient. A possible solution could be laparoscopic ultrasound, i.e. ultrasound diagnosis per laparoscopy at the very site of the lesion. The advantages are evident. Due to the closeness to the organ to be examined, the frequency of the scan head can be extremely high, resulting in better resolution. Also, structures could be visualized by ultrasound which e.g., due to adhesions cannot be seen with the laparoscope. Moreover, ultrasound offers a view into the structures which can be seen only from the exterior with the laparoscope. To perform these examinations we used a specially designed scanhead (Toshiba): Instead of the optical system a crystal array was inserted into a conventional gastroscope. The result was a high resolution 7.5 MHz linear array at the distal end of a freely movable gastroscope. Colour doppler sonography is feasible with this scanhead. We examined 19 patients, 16 of them with ovarian tumours, and attempted visualization of the uterine myometrium/endometrium as well as of the liver. In six cases of ovarian tumours in which only cystic structures were found by preoperative transvaginal sonography, laparoscopic ultrasound additionally revealed solid inner structures. In 5 cases direct laparoscopic view of the ovarian lesions was impossible due to severe adhesions. They were, however, easily detected by intraoperative ultrasound.(ABSTRACT TRUNCATED AT 250 WORDS)
Within the framework of "minimal access surgery" a prospective randomised study was initiated at the Dept. of Obstetrics and Gynaecology of Heidelberg University to examine the feasibility of endoscopical abdominal Burch colposuspension for stress incontinence (II-III), at laparoscopy and "retziusscopy". Further, also prospectively randomised, two suspension techniques: needle suspension and suspension by means of alloplastic material with stapler fixation, were compared, irrespective of the endoscopic approach chosen, especially because long-term results of our study population on colposuspension with fibrin glue which are now available, are below expectations, worse than those obtained with conventional techniques. Except for a bladder lesion (during laparoscopic dissection of the space of Retzius) no intra- or postoperative complications occurred in the pilot study group of 20 patients. Both types of endoscopic access proved technically feasible, and presented the typical advantages of minimal access surgery such as short hospitalization and rapid recovery. Short-term follow-up (2-12 months) showed subjective and objective results (continence in 18/20 patients), comparable to conventional abdominal procedures at laparotomy. Detailed evaluation of subgroups is not yet possible, since the number of patients it still too small and follow-up too short.
This was a retrospective study of acoustic stimulation response and perinatal outcome of 688 fetuses undergoing nonstress testing. Acoustic stimulation was performed within 7 days of delivery, and responses were classified based on the presence of an acceleration, deceleration, or both. Responses were correlated with perinatal outcome. Abnormal outcome was defined as: cesarean section for nonreassuring fetal heart rate patterns with an acidotic umbilical artery cord gas; delivery at less than 32 weeks for nonreassuring antenatal fetal testing; meconium aspiration syndrome or mechanical ventilation at 36 weeks or greater; neonatal seizures; 5-minute Apgar score less than 7; and stillbirth. Fetuses who demonstrated deceleration responses were significantly more likely to have abnormal perinatal outcomes when compared with those with acceleration responses (p < 0.001). Although combination acceleration-deceleration responses were more often associated with abnormal perinatal outcome when compared with pure acceleration responses, differences were not significant. A deceleration response following acoustic stimulation is associated with increased risk for adverse perinatal outcome and may merit further evaluation.
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During normoventilation and 'light', haemodynamically stable, steady-state anaesthesia with isoflurane 0.3%, the effect of ketamine intravenously was investigated in 24 patients randomly assigned to one of the following groups: group 1 (control group) no ketamine, group 2 (ketamine group) ketamine 2 mg.kg-1, group 3 (ketamine/midazolam group) ketamine 2 mg.kg-1 after pretreatment with midazolam and group 4 (ketamine/esmolol group) ketamine 2 mg.kg-1 while maintaining mean arterial blood pressure at a preketamine level with esmolol. Ketamine-induced cerebrovascular changes were measured by means of transcranial Doppler ultrasonography. Control readings in patients without ketamine challenge demonstrated stable cardiovascular and cerebrovascular baseline conditions. Cerebral blood flow velocity and mean arterial blood pressure, however, significantly increased after administration of ketamine without pretreatment. The increase in cerebral blood flow velocity could not be blocked by maintaining mean arterial blood pressure at baseline value with esmolol. In contrast, the effects of ketamine on cerebral blood flow velocity and mean arterial blood pressure were prevented by prior administration of midazolam. The results suggest that ketamine may significantly influence intracerebral haemodynamics via a direct drug effect rather than via a secondary effect due to changes in arterial carbon dioxide and/or mean arterial blood pressure.
Nitrous oxide during neurosurgical procedures is almost always given in combination with either volatile or intravenous anesthetics. The modifying influence of such interventions has been studied clinically and in experimental settings; the reported findings, however, are inconsistent. The present study compares the cerebrovascular effects of MAC equivalent concentrations of isoflurane alone and isoflurane plus nitrous oxide. Twenty lumbar laminectomy patients randomized either to receive isoflurane or isoflurane plus nitrous oxide were investigated over a dose range from 0.5 to 1.5 MAC. A transcranial Doppler (TCD) ultrasonography device was used to measure cerebral blood flow velocity (CBFV) in the right middle cerebral artery (MCA) as an index of anesthetic-induced alterations in cerebral blood flow (CBF). A small but marginally significant decrease in CBFV at 1 MAC and no change at 1.5 MAC occurred in the isoflurane anesthetized patients. In contrast, a small but significant increase in CBFV at 1 MAC and a very significant increase at 1.5 MAC occurred in the isoflurane plus nitrous oxide anesthetized patients. Nitrous oxide added to an isoflurane anesthetic regimen is concluded to be a potent vasodilator. In addition, the vasodilating effects of nitrous oxide were not uniform; they progressively increased with an increasing isoflurane concentration.
Duplication of the stomach is a rare congenital disease of the childhood. We report the exceptional manifestation in two adults. The clinical presentation and developmental theory is discussed by reviewing the literature. Today the therapy of choice is resection of the duplication with removal of the adjacent wall of the stomach.
A hysteroscopic endometrial ablation (HEA) under maximal anesthesiologic surveillance was performed on 34 high-risk patients (group I: chronic anticoagulant therapy n = 26; group II: endogenous coagulopathy n = 8) with therapy resistant meno-metrorrhagia to avoid a hysterectomy (HE). Total amenorrhea, or a least hypomenorrhea respectively cyclic spotting could be attained primarily in 22 patients (group I: 19; group II: 3), after a repeat procedure in further 6 patients (4 in group I, 2 in group II). Subjective evaluation of surgical results (overall 22 patients primarily satisfied, 6 secondarily) also differed between the two subgroups (group I: p < 0.01 primarily satisfied; p < 0.05 secondarily satisfied vs. p < 0.05 and p < 0.01 in group II). A HE had to be performed on two patients due to extensive adenomyosis uteri interna (group II). The significantly better results in the anticoagulation group were probably due to the basic illness. Larger groups will, however, be necessary before any conclusions from this difference can be drawn. No surgical or anesthesiological complications occurred. There also were no major postoperative complications (1 endomyometritis, 2 cervical stenoses). Endometrial ablation was found to be a valuable treatment alternative for this specific group of patients with severe coagulopathy, thrombo-embolic or thrombotic disease.
Congenital genetic disturbances in the genes BRCA1 and BRCA2 could lead to the forming of mamacarcinoma and ovarian carcinomas. The probability of illness is by an existing gene defect very high, and mostly young women are already affected. A direct anamnestic identification of high risk person with a following proof of gene mutations could help the patient. The way of the clinical-consultation which is recommending the BRCA1-BRCA2-test in reasons for an early recognition diagnosis is at the moment subject in clinical and scientific research.
BACKGROUND: In a prospective study, the differential diagnostic potential of pelvic examination, ultrasound, and serum CA 125 assay in postmenopausal patients presenting with a pelvic mass was assessed. METHODS: A total of 228 patients were evaluated preoperatively in an international, multicenter, prospective study using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 125 determination with a cut-off level of 35 U/ml. RESULTS: Ninety-five malignant (41.7%) and 127 benign (55.7%) pelvic tumors were found in addition to 6 borderline ovarian tumors (2.6%) in the 228 patients. Seventy-two patients had ovarian carcinoma, 49 of whom were International Federation of Gynecology and Obstetrics Stage III or IV. Borderline tumors were excluded from the statistical calculations. The individual accuracy of pelvic examination, ultrasound, and serum CA 125 in discriminating between benign and malignant pelvic masses was approximately the same (76, 74, and 77%, respectively). Using logistic regression analysis, the power of pelvic examination appeared to be the most relevant factor (adjusted odds ratio, 9.2), followed by serum CA 125 (odds ratio, 5.6), and ultrasound (odds ratio, 4.9). Age appeared to be nonpredictive. No cancer was found in any patient in whom all three methods scored negative (n = 53; positive predictive value for malignancy = 0 and 95%; confidence interval, 0-7). CONCLUSIONS: The combined use of pelvic examination, ultrasound, and serum CA 125 leads to improved discrimination between malignant and benign pelvic masses, because malignancy can be excluded when all three examination methods are negative. A change to a more patient-tailored surgical approach could be considered in those cases.
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Variant CD44 has recently been shown to serve as a metastasis marker in human breast cancer. Certain variant epitopes on primary tumors predict poor survival probabilities for the patients. In this study, immunohistochemical analysis of 16 uterine cervical carcinomas showed strong expression of several CD44 variant epitopes in all samples. In normal cervical epithelia from 5 patients, expression of these epitopes was restricted to particular cell layers, with expression being strong in basal and spinal cells but absent in superficial cells. Fifteen of 16 cancer samples were stained strongly with an antibody which recognizes one particular CD44 epitope that is encoded by both variant exons v7 and v8. This epitope was not detectable in normal cervical epithelium. CD44-mRNA splicing analysis showed qualitative and quantitative differences between malignant and normal tissues with a much more complex splice pattern and high expression of a large CD44 isoform containing variant exons v3 to v10 (including the v7/v8 transition epitope) in about one-half of the cancer samples. Interestingly, patients with lymph node metastases were in this group only. These differences in CD44 epitope expression and mRNA splicing in cervical carcinoma reveal dynamic changes in CD44 expression during carcinogenesis. Such changes could provide metastatic cells with a selective advantage during the carcinogenic process. Furthermore, the v7/v8 epitope may be suitable for screening early stages of cervical cancer.
The beta 2-subunit of tryptophan synthase from Escherichia coli was proteolyzed between Glu-296 and Ser-297 (Glu-nicked beta 2), using staphylococcal protease V-8. Recombining Glu-nicked beta 2 with native alpha-subunits yields an enzymatically active and stable complex (alpha 2.Glu-nicked beta 2) with Kd = 3 microM. Comparing the properties of alpha 2.Glu-nicked beta 2 with those of isolated native beta 2-subunits revealed that the corresponding beta-chains are almost identical with respect to enzymatic specificities as well as to some spectral characteristics. The ratio of beta-replacement to beta-elimination activity is approximately 0.6 for both species. In the presence of L-serine, alpha 2.Glu-nicked beta 2 as well as native beta 2 exhibits "aqua" fluorescence emission at 500 nm, and no "amber" absorption at 468 nm can be detected with both species. However, when ammonium ions are added, the alpha 2.Glu-nicked beta 2 complex dramatically alters its properties. Similar to the native alpha 2 beta 2 enzyme, the ratio of beta-replacement/beta-elimination activity increases by a factor of about 10, the aqua fluorescence disappears, and the amber complex becomes detectable. We conclude that the continuity of the hinge region in the tryptophan synthase beta 2-subunit plays a crucial role in the alpha-mediated structural alteration creating beta-replacement specificity. The addition of NH4+ ions to the alpha 2.Glu-nicked beta 2 complex partially restores the structure-function relationships as described for native alpha 2 beta 2 tryptophan synthase.
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