Biomedical subjects
Publications and source records attributed to W Heidenreich.
In order to prevent symptoms of drug withdrawal during pregnancy, we treated a woman with clonidine, an alpha-2 adrenergic agonist with central and peripheral actions. We saw a good response of the withdrawal symptoms without any period of severe hypotension or bradycardia. Two healthy babies were subsequently delivered by cesarean section.
Only 28 of 51 patients with the Mayer-Rokitansky-Küster (MRK) syndrome had the typical findings of vaginal aplasia and bipartite solid uterine buds. Among the other 23 patients 15 had additional malformations of the kidneys and urinary tract. Eight patients had more or less marked skeletal malformations, especially of the cervical vertebrae. The term "MRK syndrome" should no longer be used for such cases with extragenital malformations.
17 patients with the Mayer-Rokitansky-Küster-Syndrome who had been operated 1972-1978 using the Grossmann vaginoplasty are reviewed. 14 patients were examined 9-13 years after the operation. The results were rather similar: the vaginal opening seemed to be normal, but the vagina was only 6-7 cm long. 13 patients were completely satisfied and refused the proposal of lengthening the vagina.--Grossmanns vaginoplasty is a safe, rather simple method. Satisfying long-term-results can be obtained by this operation.
In 329 breast tissues (120 benign lesions and 209 invasive breast carcinomas) the growth fraction was determined using the monoclonal antibody Ki-67. The percentage of Ki-67 positive cells or the Ki-67 growth fraction was determined on histologic and cytologic specimens after immunoperoxidase staining. In benign breast lesions, the Ki-67 growth fraction never exceeded 11%, whereas in breast cancer 14.4 +/- 9.9% of cells were Ki-67 positive ranging from 1 to 48%. Breast carcinomas were classified according to the histologic grading system of Bloom and Richardson (G1-G3). Poorly differentiated carcinomas. (G3) had significantly higher Ki-67 growth fractions than well differentiated tumors (G1). Ki-67 was also correlated with axillary lymph node status. Growth fractions of N+ carcinomas were significantly higher than those of N0 tumors (16.4 +/- 10.4% versus 12.4 +/- 9.4%; p = 0.006). Thus, this new method yields similar results to those obtained by other researchers through the use of flow cytometry and thymidine labelling. As determination of Ki-67 growth fractions is an easy and rapid technique, it is ideal for routine clinical use. Ki-67 may be useful in prognosis and in the selection of patients for various treatment modalities such as adjuvant therapy. A wide-spread use of Ki-67 would be helpful to gain further experience.
Using monoclonal antibodies the total number of T-lymphocytes, as well as of helper and suppressor T-cells, was measured in peripheral venous blood of 78 women with carcinoma of the breast and 68 women without malignant disease (control group). There was no significant difference between the two groups as regards pre-operative values. The same was true with regard to different carcinoma stages. Serial tests on 15 patients who had received adjuvant chemotherapy revealed a reduction in the absolute number of all lymphoid cells except monocytes. Helper T-cells were more strongly affected than suppressor T-cells. By determining lymphocyte subpopulations in women with leukopenia caused by cytostatics one will probably be able to identify those patients particularly susceptible to infection. Determining T-cells may also make it possible to deduce a special recurrence risk.
The monoclonal antibody Ki-67 reacts with a human nuclear associated with cell proliferation that is expressed only in the G1, S, G2, and M phases of continuously cycling cells. This offers a simple opportunity to determine the growth fraction of tumors by immunostaining of fresh tissue. One hundred fifty-four invasive carcinomas of the breast were used in this study. The average number of Ki-67 positive cells was 15.3 +/- 10.1% (range, 1%-48%), whereas in 41 benign lesions of the breast only 4.4 +/- 2.6% (range, 1%-10%) of cells were positive. A correlation was found between growth fractions and histologic grading. On average, N+ tumors with less than four positive lymph nodes had a significantly higher growth fraction (20.4 +/- 14.2%) than N0 tumors (13.0 +/- 9.2%), whereas N+ tumors with more than three lymph node metastases had only 17.3 +/- 3.6% Ki-67 positive cells. This method yielded similar results to those obtained by other researchers through the use of flow cytometry and thymidine labeling. Determination of growth fractions by Ki-67 is suitable for routine use and may be useful in prognosis and in the selection of patients for various treatment modalities.
Certain types of benign breast disease (BBD) carry an increased risk of malignancy. Several morphological criteria such as an atypia score are used to define this group, and the use of a kinetic parameter may provide additional information. Therefore, the growth fractions of 120 benign breast lesions were determined using the monoclonal antibody Ki-67. The values obtained range from 0.3% to 10.8% (average 3.1% +/- 2.2%) compared to breast carcinomas with an average of 15.3% +/- 10.1%, range 0.8% to 47.8%. All specimens were classified using the terminology of Azzopardi. The prevailing histological entities were cystic disease, fibroadenoma, and blunt duct adenosis. Between these groups no differences in growth fractions were observed. Postmenopausal patients had slightly lower values than premenopausal women. Further prospective studies are needed to evaluate whether those cases of BBD with a high number of Ki-67 positive cells have an increased risk of breast cancer, independently from conventional histological classifications.
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1003 women with invasive breast carcinoma were treated in the Department of Obstetrics and Gynecology, Medical School Hannover, between 1970 and 1978. In 787 patients modified radical mastectomy was combined with postoperative radiation therapy. In 797 patients, who were observed for at least 5 years, the 5 year survival rate was 63.0%, depending on tumor stage. In spite of intensive loco-regional treatment, local recurrence occurred in 18.0%. For us, that was one among other reasons to discontinue routine postoperative radiation therapy.
From 1951 to 1976 234 patients with invasive carcinoma of the vulva were treated at the Department of Obstetrics and Gynaecology, Medical School Hannover. 53.3% of these patients underwent simple vulvectomy. Radical vulvectomy and lymphadenectomy was performed in 17.9%. 45.7% received postoperative radiotherapy. -213 patients were followed up 5 years or more. After surgery alone the 5-year-survival rate was 56.9%, after operation and radiotherapy 43.4%, after exclusive radiation 14.2%. The 5-year-survival rate of all patients was 42.7%.
Following a vaginal hysterectomy without complications, intraperitoneal after bleeding from an adnexal stump occurred, making a laparotomy necessary. On the following day a second laparotomy had to be performed because of a recurrence of hemorrhage in the abdominal cavity. The source of the bleeding could not be found. A third laparotomy the next day revealed a splenic rupture, which had evidently occurred spontaneously. Spontaneous ruptures of a normal spleen are considered rare. In cases of intraperitoneal hemorrhage where the source of bleeding cannot be found, the possibility of splenic rupture should be considered, even if there is no history of trauma.
The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.
Lymphoid subsets in the venous blood of 109 patients with various gynecologic malignancies were determined by monoclonal antibodies and compared with the results of 92 women without malignant disease. The patients were followed up for one year to study the influence of therapy on lymphoid cells. The results before treatment showed little difference between the two groups. In stage III and IV, total lymphocyte counts and OKT3+, OKT4+, OKT8+ and OKM1+ subsets were significantly lower compared with stage I and II. Radiation therapy caused a significant and long-lasting decrease of nearly all lymphoid cells. Patients who relapsed or died during the observation period had significantly diminished levels of OKT3- and OKT8-positive cells before treatment.
Lymphocyte subsets from peripheral venous blood of 11 patients with preeclampsia were enumerated by monoclonal antibodies and compared to the values of 10 normal term pregnant women. All women were in their last trimester of pregnancy. The number of B and T cells was similar in both groups. In the preeclampsia group, more helper T cells could be shown, whereas the number of suppressor T cells was reduced. Thus, the helper/suppressor ratio was increased from 2.01 in normal pregnancies to 3.97 in preeclamptic patients. In two patients with a true-positive angiotensin stress test similar changes as in preeclampsia could be seen. In only one out of five patients with preeclampsia the helper/suppressor ratio returned to normal values four to five weeks after delivery.
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Hysterectomies, as well as conservative surgery of the uterus (where indication might have been in favour of hysterectomy), were analysed according to case records during two periods, from 1960 to 1963 and from 1978 to 1980, at the Department of Obstetrics and Gynaecology at Hannover University. In the second period the average number of hysterectomies pro year doubled, whereas the conservative uterine surgery showed a definite decline. Descensus was diagnosed in 48.5% of the hysterectomies performed during the second period compared to 13.6% during first period. Prolapse frequency was about the same in both groups. In the second period, 97.7% of the descensus operations were combined with hysterectomy, whereas this applied in the first period to only 24.3%. The results show a definite tendency towards extending the indication for hysterectomy. In the second period, sterilisation and carcinoma prophylaxis were additionally considered as indications for surgery.
The following blood cells were examined in 100 patients with invasive carcinoma of the breast and 100 control patients without malignant disease: leukocytes, lymphocytes, monocytes and different sub-populations of lymphoid cells. Lymphoid cells were characterized by E-, EA- and EAC-rosetting technique, alphanaphtyl acetate esterase activity and by the ability of latex phagocytosis. Both groups showed no significant differences. In 81 patients undergoing postoperative radiation therapy lymphocytes and lymphoid cells were reduced considerably. These changes were still evident after 12 months (6 months after completion of radiotherapy). Mainly the T lymphocytes were effected by this decrease. A negative effect of the radiation induced reduction of immune competent cells must be discussed and examined further by clinical trials.