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Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 19 recordsLinked to original sources
PubMed1995

Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis.

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.

Administration, Intranasal↗
PubMed1995

O6-methylguanine-DNA methyltransferase activity in breast and brain tumors.

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a main determinant of resistance of tumor cells to the cytostatic activity of chemotherapeutic alkylating agents (methylating and chloroethylating nitrosoureas) and is effective in protecting normal cells against genotoxic and carcinogenic effects resulting from DNA alkylation. Therefore, the level of expression of MGMT is significance for the response of both the tumor and the non-target tissue following application of nitrosoureas in tumor therapy. To determine the expression of MGMT in tumor tissue, we have assayed MGMT activity in 68 breast carcinomas and 38 brain tumors. There was a wide variation of MGMT expression in breast carcinomas ranging from below the level of detection up to 863 fmol/mg protein. About 4% of breast tumors did not display detectable MGMT, 15% had activity lower than 100 fmol/mg protein, and 26% expressed more than 500 fmol/mg. The mean level of expression was 321 fmol/mg. In brain tumors (astrocytoma WHO grade I, II, and III, and glioblastoma WHO grade IV) the MGMT activity was generally lower than in breast tumors, ranging from below the level of detection up to 238 fmol/mg. The mean level of expression was 55 fmol/mg. Five percent of the brain tumors had no detectable MGMT activity. The MGMT repair activity correlated well with the amount of MGMT protein present in tumor samples, as shown by Western-blot analysis, indicating that loss of MGMT repair activity is due to inability of these tumor cells to synthesize the protein.

Adult↗
PubMed1995

CD44 variant exon epitopes in primary breast cancer and length of survival.

CD44 designates a group of closely related cell-surface proteins generated by alternative splicing. We have previously shown that splice variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines and that they confer metastatic behaviour on non-metastatic animal tumour cell lines. In this study we set out to assess the expression of CD44 epitopes specific for variant exon sequences in human breast cancer and their potential for determining prognosis. We used affinity-purified polyclonal sera and four monoclonal antibodies raised against the human homologues of CD44 variant exon sequences to investigate the presence of CD44 on 100 primary invasive breast tumours, 12 local recurrences, 18 lymph node metastases, and normal tissue controls. Whereas normal mammary ductal epithelial cells and cells derived from hyperplastic lesions do not express CD44 variant exons, expression of v3, v5, and v6 epitopes was found in most tumour samples. The DIII (exon v6) epitope was present in 84% of the primary tumours and in 100% of axillary lymph node metastases and local recurrences. The presence of these CD44 epitopes is correlated with poor overall survival. 15 patients with exon-v6-negative tumours had good survival compared with 76 patients with exon-v6-positive tumours (p = 0.005; log rank test). Multivariate analysis showed that the CD44 epitope encoded by exon v6 was a good marker for prognosis independent of progesterone receptor, lymph node status, tumour size, and grade.

Adult↗
PubMed1995

Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer.

In different human tumors, splice variants of the surface glycoprotein CD44 (CD44v) are correlated with advanced stages of tumor growth and metastatic potential. In breast cancer and colon cancer, expression of epitopes encoded by exon v6 on primary tumors is an independent prognostic factor for poor patient survival. Two different screening methods for the detection of CD44 variants in tumors have been applied: immunohistochemistry (IHC) and semi-quantitative reverse transcription PCR (RT-PCR). In this study, we have compared the predictive capacity and the applicability of both approaches, using 31 human breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression of CD44v on normal ductal epithelial cells but strong expression on myoepithelial cells. The majority of tumors express CD44 epitopes encoded by several variant exons. RT-PCR detects splice variants in normal epithelium, probably derived from RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a wide range of splice variants, including new ones that are not detected in normal breast tissue, e.g. ones that contain all variant exons. The conclusion of this comparison is that IHC is the better method for breast-tumor sample screening but that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive from CD44v-negative tumors in cases where only a few tumor cells express variants or where epitopes are masked.

Antigens, Neoplasm↗
PubMed1995

A randomised study to compare the effect of the luteinising hormone releasing hormone (LHRH) analogue goserelin with or without tamoxifen in pre- and perimenopausal patients with advanced breast cancer.

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.

Adult↗
PubMed1995

[Initial experiences with laparoscopic intraoperative ultrasound].

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)

Equipment Design↗
PubMed1995

[Endoscopic colposuspension ("retziusscopy" versus laparoscopy). An effective extension of the surgical spectrum of stress incontinence?].

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.

Fasciotomy↗
PubMed1995

Effects of ketamine on cerebral blood flow velocity in humans. Influence of pretreatment with midazolam or esmolol.

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.

Adrenergic beta-Antagonists↗
PubMed1995

Nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane. A transcranial Doppler study.

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.

Adult↗
PubMed1995

[Congenital cystic duplication of the stomach--a rare surgical disease].

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.

Adult↗
PubMed1994

Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine cervical cancer and normal cervical epithelium.

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.

Adenocarcinoma↗
PubMed1992

The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1.

To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.

Antigens, Viral↗
PubMed1992

Goserelin depot in the treatment of premenopausal advanced breast cancer.

333 pre- and peri-menopausal patients with breast cancer entered a programme of open studies on the effect of goserelin. Of the 333 patients, 265 patients were entered into assessable efficacy studies. Efficacy data were analysed from 228 eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous injection of a depot formulation once every 28 days. Mean serum luteinising hormone (LH) and oestradiol concentrations were suppressed by day 22 after the first injection. Subjective response occurred in 68.3% of patients assessed. Objective response (UICC criteria) occurred in 36.4% of patients and the lifetable median duration of response was 44 weeks. Responses were observed in all histological grades of tumour, and regardless of oestrogen receptor status. Treatment was well tolerated with no withdrawals due to possible adverse reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly encountered. Goserelin provides an effective well tolerated medical alternative to ovarian ablation in the management of advanced breast cancer.

Adult↗
PubMed1992

[Three-dimensional ultrasound imaging of benign and malignant breast tumors--initial clinical experiences].

Previous experimental and clinical studies showed, that three-dimensional (3-D), i.e. dynamic spatial reconstruction of 2-D ultrasound images is feasible. A rotating acoustic plane helps to visualise the cross-sections serially and in a coordinated manner. When reconstructing the 2-D ultrasound images, surface reconstruction from planar contours of each cross-section is performed (so that the organ limits are defined) and the cross-sectional pictures are reconstructed into 3-D organ images. This approach had been described by the authors on a previous occasion. Another step forward is "transparent" spatial imaging eliminates the source of error involved in contouring. It is important to emphasise, that the 3-D system now described by the authors, yields a spatial image of the organ in question, and does not just present 3 planes of the organ (some authors have been claiming, that such an imaging method is also three-dimensional). Our system enables the imaging of several cross-sectional planes cut through the spatially calculated organ. This results in cross-sections, which cannot be performed by conventional sonography, thus disclosing new perspectives and possibilities. In the present article, the authors describe a clinical pilot study in the diagnosis of carcinomas of the breast. In our opinion, 3-D imaging of the tumours enables the physician to diagnose the status of the tumours; this is demonstrated by the examples of 35 malignant and benign tumours of the breast. In 95% of the cases of malignant tumours and 80% of the benign tumours, the diagnosis proved correct. This paper describes the fundamental possibilities and limitations of the new method.

Breast Neoplasms↗
PubMed1992

[B-streptococci in obstetrics--risks and consequences of maternal colonization and neonatal contamination].

2,373 mothers and their newborn were studied during two years with respect to B streptococci colonisation or contamination. Bacteriological, vaginal and anal smears were taken from mothers at the beginning of parturition, as well as the amnion and the aspirated stomach contents of the newborn, employing, in each case, conventional culture methods and a latex agglutination test as a rapid testing method. Smears from the ears were also taken from the newborn for bacteriological examination. The vertical transmission and its possible influencing variables were examined in 1,328 mother/child pairs of the first observation year. Surface contamination of the newborn was confirmed in 10% in at least one smear. In the group of mothers with B streptococci colonisation, the amnion showed the highest rate of contamination (43%), followed by the aspirated stomach contents (26%) and the ear smears (taken from each side separately) with 28% and 30% respectively. Vertical transmission was decisively influenced by vaginal maternal colonisation (50% of the cases resulting in contamination of newborn), whereas anal colonisation, if it was the only site of colonisation, resulted in contamination of newborn in only 32% of the cases. The rate of contamination of newborn dropped significantly from 50% to 20% after intrapartal antibiotic prophylaxis, the latter appearing to be meaningful only after at least 6 hours of exposure. In this group, the surface contamination could be reduced from 61% to 8%. A group of newborn suffering from early onset of sepsis (0.4%), was compared with a group of 13 newborn at risk of infection (0.9%) with established surface contamination and clinical or laboratory chemistry confirmation of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1992

[Ultrasound diagnosis of blood flow in benign and malignant breast tumors].

Malignant tumours can be differentiated from the benign ones by their vascular blood supply. We employed three methods to analyse the blood flow: the angiodynograph, the duplex system, and the continuous-wave Doppler method, and measured the blood flow in 151 patients on the preoperative day. Histology revealed a malignoma in 92 cases and a benign tumour in 59 cases. It was found, that in more than 90% of the malignomas, a high blood flow was identified in or around the tumour by means of the colour method (angiodynography), which could be quantified by the pulsed-wave Doppler. A significantly lower blood flow was evident in the benign tumours with a markedly increased resistance index (by 80%) established by means of the pulsed-wave Doppler. Continuous-wave (CW) Doppler showed a significantly higher blood flow with almost all malignomas in the entire breast, than was the case with benign changes. Our studies showed, that the enhanced blood flow in and around malignant tumours can be visualised by means of update technology, angiodynography being particularly suitable for demonstrating the flow by the B-mode. Quantification, however, is, at present, only possible by employing the duplex method with pulsed-wave Doppler. CW Doppler is suitable only for blood flow diagnosis of the entire organ, but it requires great precision of working method and is time consuming; tumour blood flow cannot be visualised on-target by this method.

Blood Flow Velocity↗