[Immunity of habitual abortion. Principles and current status of research].
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Biomedical subjects
Publications and source records attributed to H Schmid.
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Bone marrow transplantation improves the chances of survival in a variety of hematological malignancies. However, infectious complications during the post-transplant phase contribute significantly to morbidity and mortality. To reduce the duration of granulocytopenia, which is approximately 20 days after BMT, in this study patients with ALL, relapsed or high-grade NHL, relapsed or refractory HD, or Neuroblastoma stage III/IV, were given rh GM-CSF to assess the effects on hematological and immunological reconstitution after conditioning therapy and BMT. The results of 9 patients are presented. After autologous BMT and subsequent rh GM-CSF therapy, a peripheral blood neutrophil count of 500/microliters was reached within 8-12 days, i.e., between 7 and 10 days earlier than would have been expected without rh GM-CSF. Furthermore, it appeared that rh GM-CSF was useful in case of insufficient bone marrow regeneration post autologous transplant. The influence of rh GM-CSF after allogeneic BMT is not yet clear. Further studies will be necessary to evaluate the potential of this promising new drug after BMT.
From January, 1975 through June, 1986, 426 patients with mammary carcinomas were submitted to primary, breast-preserving therapy at the Gynecological Hospital of the University of Heidelberg. 212 women with a minimum observation time of twelve months fulfilled the criteria of a "typical" treatment: tumor size up to 3 cm, segment/quadrant resection and axillary lymphonodectomy with at least eight lymph nodes removed, radiotherapy of the residual breast with greater than or equal to 45 Gy, in case of histological lymph node manifestation adjuvant hormonal and/or chemotherapy. The average observation time was 38 months, the medium age 48 years. Patients with histological lymph node manifestations were compared with a matched control group of women treated treated by modified radical therapy. According to the error estimation of Kaplan and Meier (1958), no differences were found for local recurrence rate, disease-free survival, and overall survival. Patients treated by organ-preserving therapy with adjuvant chemotherapy were opposed to a matched control group of women treated only by surgical/radiological, organ-preserving therapy. In patients with chemotherapy, the incidence of cutaneous erythema (29% versus 24%), telangiectasia (34% versus 24%), hyperpigmentation (41% versus 34%) showed an upward tendency, but was not significantly increased. There was no difference in the incidence of clinically palpable fibroses (37% versus 42%) and fibroses shown by mammography (54% versus 51%). The frequency of pneumonitis/fibrosis of the retromammary lung area (22% versus 10%) after chemotherapy was two times higher than in the matched control group not treated by chemotherapy.
138 advanced ovarian serous carcinoma--all FIGO stages III/IV--were investigated by prognostic morphological factors like tumour grading and rate of psammomabody content--subdivided in to serous carcinoma with a high, a moderate and a low rate of psammomabodies and a group of serous carcinoma without psammomabodies. Additionally 91 of these tumours were examined by DNA-flow-cytometry--respectively DNA-ploidy and s-phase-fraction. All prognostic factors were correlated to the overall survival time. The psammomabody content factor is only important if histologically a high or moderate rate of psammomabodies is found in the tumour tissue. Tumours with a low rate of psammomabodies do not differ from serous tumours without psammomabodies. DNA-flow-cytometry is a qualified method to demonstrate a slow tumour growth tendency. The majority of carcinomas with a high rate of psammomabodies is DNA-diploid and has a low -phase-fraction. The overall survival rate for these tumours is much better. Tumour grading--a more subjective method--is also of high value, but there is a certain difficulty in reproducing the results in individual cases. By the combination of the two morphological methods--semiquantitative assessment of psammomabodies and DNA-flow-cytometry--we were able to discover a small group of patients with advanced ovarian cancers who have a favourable prognosis.
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Ia antigens (class II HLA molecules) have been detected on cells eluted from affected human cartilage in certain disease states, but not on normal cartilage cells. Because the presence of Ia antigens on chondrocytes may play an important role in rheumatic diseases, we investigated the induction of these molecules by gamma-interferon (gamma-IFN), a potent Ia-inducing lymphokine. Human articular chondrocytes were incubated with recombinant gamma-IFN, and the expression of Ia antigens was studied by cell sorter analysis, using a panel of reagents that detect monomorphic and polymorphic specificities of the DR and DQ Ia antigen families. While the induction of DR antigens, including polymorphic DR specificities, was readily obtained with gamma-IFN (50-95% positive cells), DQ antigens were negative or were displayed only on a lower percentage of chondrocytes (5-60%). In addition, incubation with gamma-IFN led to an increased expression of HLA class I antigens. The expression of various other surface markers either remained unchanged (as in 4F2 and BA-2) or showed tendencies toward decreased percentages (as in 83c2) or increased percentages (as in M phi R-17). No apparent change in cell morphology or growth pattern was observed.
Borderline tumors of the ovary are morphologically characterized by histologic and cellular criteria and by lack of evidence of invasion. During an observation period of 12 years at Heidelberg University Gynecological Clinic, 49 patients with borderline tumors underwent surgery and the clinical course was followed up. In 15 cases the tumor was at an advanced stage (FIGO III/IV); chemotherapy was instituted after surgery in 12 of these women. None of the patients with early-stage tumors (FIGO I/II) were lost due to the tumor during the period of observation; the death rate among patients with stage III/IV tumors (FIGO) was 40%. However, the death of three of these women was also due to their advanced age and high internal risks. As in the case of ovarian carcinomas, the survival rates improve if the postoperative residual tumor mass is smaller than 2 cm. Subsequent histologic work-up of archived, formalin-fixed tumor tissue and metastases thereof showed that two forms of the metastasizing borderline tumor exist: one with a favorable prognosis, a "pure" form with borderline changes in the ovary and metastases, and one with a less favorable prognosis, with borderline changes in the ovary and destructive-invasive portions of tumor in the metastazation areas. Impulse cytophotometric studies (ICP) showed that all primary tumors had the same degree of ploidy i.e., diploid. However, detection of an aneuploid distribution pattern in a metastasis correlated with subsequent histological confirmation of tumor invasion and rapid tumor death. The S-phase fraction was low, at 2.02% +/- 1.3.(ABSTRACT TRUNCATED AT 250 WORDS)
Apart from the stage of the tumour and the method of surgical approach, factors of special importance in prognosis are the histological type of tumour and the histological and cytological grading of malignant ovarian tumours. To supplement the prognostic factors, DNA flow cytometry has recently been introduced to determine parameters of cell kinetics such as ploidy (the status of the chromosome set in the karyotype) and the number of DNA-synthesized cells. In the present study 81 patients with a malignant tumour of the ovary--most of them classified according to FIGO stage III/IV--were followed up for 12 to 56 months (FIGO = Fédération Internationale de Gynécologie et d'Obstétrique). The survival times are correlated with clinical, morphological and cell kinetics data. The FIGO stage is the most important prognostic factor. None of the patients in stage I/II (FIGO) died during the study period, whereas of 63 women in stage III/IV (FIGO) 41 have already died. The histological tumour type is not so significant for prognosis. The survival curves show that of all the examined prognostic factors in stage III/IV (FIGO) the S-phase proportion (i.e. the proportion of DNA-synthesized cells) is the most important one. Statistically significant differences are also seen in ploidy and in grading. However, in histological grading of tumours the differences are noticeable only in grading G 1 and in grading G 3. G 2 carcinomas--which, by the way, account for one-third of all carcinomas-are a kind of collecting "pool" of tumours whose prognosis cannot be assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
Fourteen patients were examined one to four years after cricopharyngeal myotomy that had been carried out because of dysfunction of the pharyngo-esophageal sphincter. Twelve patients were examined radiologically. Eleven of the 14 patients were clinically improved or cured. In two patients who were not improved, the underlying condition was a polymyositis. The other patients suffered from an idiopathic dysfunction. Because of the small numbers involved, no detailed statistical analysis was carried out. Nevertheless, our results indicate that: Cricopharyngeus myotomy produces marked improvement or cure in patients with idiopathic dysfunction. Weak propulsive peristalsis of the pharyngeal constrictors is a prognostic factor indicating a poor clinical result of surgery. There is little chance of clinical improvement in patients with polymyositis.
Dysphagia due to upper esophageal sphincter dysfunction is usually diagnosed by cineradiography. If the treatment of an underlying disorder fails to improve swallowing or if the dysfunction is thought to be idiopathic, cricopharyngeal myotomy is considered the treatment of choice. In properly selected cases (i.e. significant dysphagia and radiological proof of pharyngo-esophageal dysfunction) cricopharyngeal myotomy offers complete or at least substantial relief of symptoms for three out of four patients. The use of an operating microscope is strongly advised.
We evaluated the diagnostic value of EEG tracings in cases of non-arteriosclerotic symmetrical calcification of the basal ganglia (Fahr's syndrome). The group of 41 tracings was composed of probands and patients of a family with hereditary occurrence of the syndrome and other patients where the characteristic calcifications were discovered by chance or in CT screening of persons who had undergone thyroidectomy. The comparison of our EEG results with those presented in the relevant literature yielded no discernable diagnostic value of the investigation. All kinds of alterations of central electrophysiological activity seem possible, at least in our collection, similar to previous findings, but no characteristic EEG pattern associated with Fahr's syndrome was seen. Only a vague correlation of alterations to the age of patient could be surmised, this being, of course, wholly unspecific. Thus psychopathology, neurological data and CT are the prime techniques for diagnosis of Fahr's syndrome, the EEG so far offering only marginal assistance.
In cases of ovarian carcinoma the trend today is toward postoperative cytostatic follow-up therapy which is as aggressive as possible, though of limited duration. The aim is to achieve full clinical remission and to verify it histologically by a second-look-operation. This paper presents the results obtained in 41 women who underwent second-look surgery, out of a total of 87 women with advanced epithelial ovarian carcinoma (FIGO stage III and IV) who had been given combination chemotherapy with cisplatin postoperatively. Taking various well-known prognostic factors into account (stage, age, histologic grading, primary postoperative residual tumor mass), the situation before and after a second-look laparotomy was analyzed. The survival data (life table analyses according to Kaplan-Meier) indicate the importance of these prognostic factors. Approximately one-third of the patients had full clinical remission after aggressive cisplatin combination chemotherapy; complete remission was verified microscopically in 18% of all cases, with a mean of 12 biopsies. The long-term prognosis for such women, who can be cured even if they have primary advanced ovarian carcinoma, is likely to be good. In addition, present-day indications and the standard surgical procedure for a second-look operation are described.
This prospective trial was designed to help in selecting therapy for patients with elevated and normal plasma prolactin. Ninety-two patients entered this trial, of whom 86 were evaluable for final analysis. Hyperprolactinemic patients (n = 31) were randomized to receive VAC/FMC chemotherapy with or without bromoergocryptine. Normoprolactinemic patients with 'low risk' metastatic disease (disease-free interval greater than 30 months, ER/PR positive or unknown) were treated with medroxyprogesterone acetate or VAC/FMC chemotherapy. Normoprolactinemic 'high risk' patients (n = 42) (disease-free interval less than 30 months, EP/PR negative) received VAC/FMC chemotherapy with or without medroxyprogesterone acetate (MAP). The results show that bromoergocryptine does not improve response rate, duration of response and survival. Median survival of patients with elevated basal plasma prolactin (greater than 15 ng/ml) is reduced to 9 months compared to patients with normal basal plasma prolactin (17 months, log-rank p = 0.005). Unexpectedly, TRH stimulation proved inappropriate to separate normo- and hyperprolactinemic patients in terms of survival. Normoprolactinemic 'low risks' (tamoxifen failures) were observed to qualify for further hormone therapy (median survival 21+ months). Normoprolactinemic 'high risks' showed median survival of about 12 months with no apparent benefit for those receiving MAP, additionally. The results suggest that basal hyperprolactinemia, disease free interval, ER/PR receptor status, and liver metastasis are important prognostic variables. Endocrine and cytotoxic chemotherapy should be selected according to these risk factors.
The catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase, constituents of luminal brush-border membranes and lysosomes of kidney tubular cells, were measured in human kidney allografts in the maintenance and recovery phases of acute renal failure and in acute rejection crisis. The enzyme activities were fluorometrically determined in single microdissected cortical nephron segments of biopsies from 4 kidney allografts taken intraoperatively and postoperatively at different periods, which exhibited either good function or dysfunction. For comparison, the unaffected part of a human kidney nephrectomized due to hypernephroma as well as a biopsy of a morphologically normal human kidney were examined. Both enzymes displayed highest activities in the proximal part of the human nephron. In some intraoperative and postoperative biopsies with acute renal failure, alkaline phosphatase activity was reduced in proximal tubules, predominantly in the straight portion. This reduction could not be correlated with function. In acute rejection, very low alkaline phosphatase activities were uniformly found in proximal convoluted and straight tubules. Furthermore, intraoperative biopsies and biopsies of the functioning allograft have only approximately 50% of normal N-acetyl-beta-D-glucosaminidase activity in proximal convoluted tubules, but generally normal values in the straight portion. However, in acute renal failure, this enzyme activity was several-fold enhanced along the whole nephron, when compared with intraoperative values. In acute rejection, N-acetyl-beta-D-glucosaminidase activity was slightly reduced in proximal convoluted tubules, when compared with biopsies showing good function. It is suggested that the decrease of proximal tubular enzyme activities is the consequence of increased enzymuria and inadequate enzyme regeneration. On the other hand, the overshoot of N-acetyl-beta-D-glucosaminidase activity in the maintenance phase of acute renal failure appears to indicate increased degradative capacity, associated with cellular regeneration along the whole nephron.
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1. Various aspects of carbohydrate metabolism were evaluated in rats exhibiting chronic uremia induced by the surgical removal of 5/6 of the kidneys (NX group). Operated rats developed moderate uremia and maintained a nutritional status similar to that of a sham-operated control group (C rats). 2. After a 12-h fast, the NX group showed a 32% decrease in plasma glucose vs 20% for the C group. 3. After intravenous glucose administration (75 mg/100 mg body weight), plasma glucose and insulin levels were similar in both NX and C rat groups. 4. The decrease in plasma glucose after insulin administration (0.025 U/100 g body weight) was larger in the NX group than in controls. 5. No significant difference was found between the hepatic glycogen levels of NX and C animals although diaphragm muscle glycogen levels in the NX group were nearly twice that of controls. 6. Carcass fatty acid levels in the NX group were 42% lower than in the C group, while total liver lipids were similar for both. 7. These findings suggest that nephrectomized rats exhibit increased sensitivity to exogenous insulin, are not intolerant to intravenous glucose and after a 12-h fast show hypoglycemia that could be related to higher glucose utilization by muscle tissue.