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Biomedical subjects

U Nieminen

Publications and source records attributed to U Nieminen.

At least 19 recordsLinked to original sources

Quinidine-induced thrombocytopenic purpura: clinical presentation in relation to drug-dependent and drug-independent platelet antibodies.

We have studied the clinical course of quinidine-induced thrombocytopenia in relation to the presence of drug-dependent (dd-ab:s) and drug-independent antibodies in 14 patients. Thrombocytopenia was reversible in 9 d after discontinuation of quinidine treatment in 10 patients. In four it lasted more than 1 month. Drug-dependent antibodies of IgG class were detectable in seven patients: in six by an immunofluorescence test applying flow cytometry and in one patient by a monoclonal antibody-immobilized platelet protein assay (MAIPA) only. The dd-ab:s of this patient had glycoprotein (GP) IIb/IIIa specificity. Five of the six patients with dd-ab:s by immunofluorescence test had GPIb/IX-specific dd-ab:s by MAIPA. They recovered within 5 d after discontinuation of the drug. All four patients with prolonged thrombocytopenia had elevated platelet-associated IgG (PAIgG) in the acute phase as studied by a direct platelet immunofluorescence test. The remaining five patients displayed a relatively rapid clinical recovery but less uniform pattern of immunological findings. The results suggest that patients with GPIb/IX-specific dd-ab:s recover promptly despite an acute and profound thrombocytopenia. Another sub-group with prolonged thrombocytopenia had persistently elevated PAIgG during the convalescent phase.

Adult

Placebo-controlled study on the efficacy of the pyrimido-pyrimidine derivative RA 233 in ovarian cancer.

This prospective double-blind, multicenter study was aimed at evaluating the clinical efficacy of RA 233 (a derivative of dipyridamole) in ovarian cancer. Following primary surgery, 497 patients with ovarian cancer were treated with combination cytotoxic chemotherapy; those in clinical stage II were also treated with pelvic irradiation. The patients were randomly allocated to receive RA 233 (N = 251) or placebo (N = 246) for 2 years. The groups did not significantly differ from each other in any of the clinical, therapeutic, or histopathological variables evaluated. There were no significant differences between RA 233-treated patients and placebo-treated patients with respect to appearance of new metastases, progressive growth of malignancy, or survival of all patients, in any of the clinical stages of the disease, in radically operated patients or in nonradically operated patients, in different histopathological groups, or in different age groups. Hence, supplementation of carcinoma therapy with long-term administration of the antiplatelet drug RA 233 has no clinical benefit in this malignancy. Using Cox's multifactorial stepwise analysis, this study revealed that the clinical stage of the disease, the extent of surgery, and the histopathology of the tumor, but not the age of the patient or the use of RA 233, were significant and independent predictors of survival. With respect to the histopathology, the poor prognosis of serous and mesonephric carcinomas appeared to be independent of the other prognosis indicators.

Combined Modality Therapy

Comparison of mass spectrometry and radioimmunoassay to measure medroxyprogesterone acetate in patients with endometrial cancer.

Serum medroxyprogesterone acetate (MPA) was measured by radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS) in patients with endometrial cancer. Samples were obtained 3, 6 and 24 h after the oral administration of 100 or 200 mg MPA once a day. The levels obtained by GC-MS were lower (median 16-29%) than those obtained by RIA, which is probably attributable to the presence of metabolites interfering with the RIA. Two commercial MPA formulations gave different MPA serum levels by both RIA and GC-MS. The levels obtained by GC-MS were so low that frequently only partial saturation of the endometrial progesterone receptor may be achieved which may explain why high oral doses are needed to produce optimum therapeutic response.

Aged

Compartmental analysis of short-lived platelet dynamics.

111In-labelled platelets were used for analysing platelet dynamics in 43 patients with idiopathic thrombocytopenic purpura (ITP). The detected time-activity curves, recorded with a gamma camera, were analysed by three methods: two- and three-compartment models, and an open model in which only the splenic curve was analysed. In the two-compartment model the mean rate constant from blood to spleen was 0.328 +/- 0.028 min-1 (mean +/- SEM) and from spleen to blood 0.061 +/- 0.007 min-1, whereas in the three-compartment model the corresponding values were 0.236 +/- 0.020 and 0.044 +/- 0.007 min-1, respectively. The mean rate constant from blood to liver was 0.466 +/- 0.149 min-1 and from liver to blood 0.341 +/- 0.106 min-1 as derived from the three-compartment model. The rate constant from spleen to blood, as determined from the three-compartment model, was significantly higher in patients with a strongly positive result for platelet-associated auto-antibodies (platelet suspension immunofluorescence test (PSIFT] than in patients with a negative PSIFT. The mean hepatic net rate in patients with a high level of antibodies is into the liver, while in patients with little or no antibodies the net rate is into the blood pool. The mean half-life for the fast component of the inverted splenic curve was 2.5 +/- 0.2 min and for the slow component 16 +/- 2 min. In patients with a strongly positive PSIFT the half-life for the slow component was significantly longer than in patients with a negative PSIFT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Increase of cervical adenocarcinoma: a report of 520 cases of cervical carcinoma including 112 tumors with glandular elements.

A total of 520 new cases of cervical carcinoma were treated at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, in 1976 through 1980. Of these carcinomas, 95 (18.3%) were pure adenocarcinomas and 17 (3.3%) represented adenosquamous tumors. The mean age was 58.9 years (range 23-88 years). The age distribution was similar in patients with and without malignant glandular elements and the peak incidence was in the age group 60-69 years. In patients with adenocarcinoma, stage I was overrepresented (62.1%) whereas epidermoid carcinomas were more evenly distributed among various stages. The overall 5-year survival rate was 63.1%, with the corresponding corrected rate being 69.1%. The survival rate for patients with adenocarcinoma did not differ significantly from that for patients with squamous cell tumor. It is concluded that in our population the increasing frequency of cervical adenocarcinoma has not influenced the favorable results of the 5-year study. This disease, however, deserves more attention since its etiology, pathogenesis, and biology are still largely unresolved.

Adenocarcinoma

Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura.

Splenic dynamics of 111In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of 111In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 +/- 0.7 min vs. 3.6 +/- 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 +/- 5 min vs. 13.2 +/- 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

Adolescent

Platelet associated IgG, platelet mean life span and treatment with intravenous immunoglobulin in idiopathic thrombocytopenic purpura.

The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.

Adolescent

Cervical carcinoma complicated by malignant pericarditis.

Malignant pericarditis is a rare complication of cervical cancer. In the present case a metastatic pericardial disease developed in a patient who was initially treated by radiation therapy for stage IIb cervical carcinoma. Shortly after the first cycle of chemotherapy with cisplatin, VP-16 and hexamethylmelamine, a pericardial effusion was observed. After drainage of the pericardium and diagnosis of malignant metastatic disease the patient was successfully treated with the initial combination chemotherapy. The patient is still alive 12 months after pericardiotomy.

Adult

Endometrial adenocarcinoma: clinical outcome in 881 patients and analysis of 146 patients whose deaths were due to endometrial cancer.

Throughout 1970-1975, 881 patients were treated at Departments I and II of Obstetrics and Gynecology, Helsinki University Central Hospital. They were treated mainly by using surgery and/or radiotherapy combined with adjuvant progestin therapy. The over-all uncorrected 5-year survival rate was 72.2% and corrected rate was 82.1%. In 146 out of 245 cases death was due to endometrial cancer, and this group was analyzed separately.

Adenocarcinoma

Pervaginal cul-de-sac cytology and CT in the follow-up care of patients with advanced ovarian cancer.

Among 28 patients with advanced ovarian cancer (FIGO stage III) treated with cytotoxic chemotherapy there were 23 cases with residual malignant disease as revealed by "second-look" surgery. Preoperative studies including fine needle cul-de-sac washing samples (FD) for cytology and abdominopelvic computed tomography (CT) detected 13 tumors with residual disease. No false positive findings were encountered among preoperative studies. There were 2 cases in which both clinical examination and CT detected malignant growth. In 2 cases clinical examination revealed tumors not detected by CT. On the other hand in 3 cases CT found the residual disease. In 6 cases residual tumors were preoperatively detected only by FD cytology. Manually and radiologically undetectable tumors were greater than 1 cm in diameter in 7 cases, fine nodular involvements in 8 cases, and in 1 case the residual disease was only cytologically diagnosed.

Biopsy, Needle

Sarcomas of the uterus: a clinicopathologic study of 119 patients.

This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed müllerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed müllerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.

Adult

X chromatin, endomitoses, and mitotic abnormalities in human cervical cancer.

The incidence of X chromatin bodies and mitotic modifications and aberrations has been analyzed using Feulgen-squash preparations in 47 cervical cancers from Helsinki and 35 from Madison. Sixteen of the 82 tumors did not display any X chromatin bodies, and some others showed a lower than normal frequency, especially in the large nuclei. Different hypotheses to explain the absence of Barr bodies in female tumors have been reviewed. A new observation is that 44/82 tumors contained endomitoses. The metaphase/prophase ratio (M/P) was higher than 1.5 in all but three cases, reaching values as high as 23.0 (Madison) and 34.2 (Helsinki), and in one exceptional case, 51.8. The different types of cells, mitotic, endomitotic, and those with large to giant nuclei, form their own strands or layers. Cervical cancer is diagnosed earlier in Finland than in Madison due to a Pap mass screening program, and consequently, the survival of the patients after 5 years was 27/47 in Helsinki and 6/35 in Madison. No correlation could be established between the M/P (or other mitotic phenomena) or the stage and grade of the tumor, the age of the patient, or survival time.

Adult

Changing pattern of cervical carcinoma: a report of 709 cases of invasive carcinoma treated in 1970-1974.

Seven hundred and nine new cases of carcinoma of the uterine cervix were treated by surgery, radiotherapy, or both at Helsinki University Central Hospital between 1970 and 1974. Of these, 241 (34.0%) died of the disease during the 5-year follow-up period. Three hundred and eighty-three (53.9%) of the patients were operated on and in 112 (29.3%) of them the stage of the disease had been underestimated preoperatively. This was mainly due to the undetected lymph node involvement observed first at operation in 72 cases (18.8%). In 237 of the patients carcinoma was confined to the cervix according to findings at operation but in 24 (10.1%) of them a relapse or metastasis was observed within 5 years. Comparison of the results for 1970-1974 with those from the same hospital for 1926-1969 revealed a reversal in the steady improvement in the total 5-year survival rates. It is concluded that, even if the incidence of cervical carcinoma in Finland is to decrease, the prognosis for the disease may become poorer. This is mainly due to a shift in the peak incidence of cervical carcinoma to older age groups. Also a mass screening program is likely to decrease the relative number of slowly growing, less aggressive type of the disease.

Adenocarcinoma

A prospective, randomized, national trial for treatment of ovarian cancer: the role of chemotherapy and external irradiation.

A prospective, randomized, national trial for comparing the effects of cytotoxic agents and radiotherapy on survival in primary epithelial ovarian cancer stages I-IV was carried out in 363 patients. After laparotomy, the patients were staged according to disease spread and randomized into treatment groups within each stage. The single or combined cytotoxic agents used were: cyclophosphamide (C) and vincristine (V); 5-fluorouracil (F) and dactinomycin (D) and V; treosulfan (T); and CF. In stages I, II and III there was one treatment group receiving external irradiation; in stage IV only different cytostatics were used. It was found that, in stage I, surgery alone was superior to surgery +CV or surgery + irradiation. In stage II disease, no differences in survival between treatment groups receiving pelvic irradiation or FDV, and in stage III between whole abdomen + pelvic irradiation or CV or FDV were found. In stage IV, FDV, T and CF were of similar, poor efficacy. The authors conclude that in stage I pelvic irradiation or combined chemotherapy do not improve survival. In advanced disease, chemotherapy may be better tolerated and thus preferable to whole abdomen irradiation; the combination of more modern cancer drugs with the ones used in this study is probably likely to improve the treatment results.

Abdomen

Mitotic modifications and aberrations in human cervical cancer.

Mitotic modifications and aberrations characteristic of human malignant tumors have been analyzed and illustrated in cervical cancer. Most of them can be explained by assuming that the coordination of the centrosomal and chromosomal mechanisms, typical of normal mitosis, is disturbed. When the spindle mechanism is ahead of the chromosomes, the prophase is relatively shortened. This expresses itself in an increase of the ratio of metaphases to prophases (M/P), which in normal tissues is around 1. With M/P values of 4-6, the first tripolar metaphases are formed, and with higher ratios, divisions having more and more poles appear. The spindle and the chromosomes are out of step in the opposite direction in endocycles, in which the spindle is slowed down or absent. The most common of the endocycles is endoreduplication, followed by endomitosis, which is found in more than half of the cervical cancers. Mitotic abnormalities include lagging chromosomes in metaphase and anaphase and bridges in anaphase, which, when numerous, may lead to restitution. More sporadically occurring are C-mitosis and other abnormalities, including cell and nuclear fusions. There is a wide range of variation in the occurrence and frequency of chromocenters within a tumor, and an even greater variation between tumors. About one-fifth of cervical cancers lack X chromatin bodies. The abnormal chromosome constitutions in cancer are the result of various mitotic modifications and aberrations, as well as chromosome rearrangements. New chromosome combinations are constantly created and selection promotes the fastest dividing ones, which, in turn, become new stem lines of the tumor.

Chromatin

Clinical outcome in endometrial cancer.

Patients with endometrial carcinoma (N = 1113) were treated by conventional therapy, using surgery and radiotherapy, complemented by daily administration of 100 mg oral medroxyprogesterone acetate (MPA) for a 2-year period. Only 7.3% of the malignancies were at an advanced clinical stage (III or IV), whereas 75.9 and 16.8% of the carcinomas were detected at clinical stages I and II, respectively. The 5-year survival rate was 71.0% overall, and 77.8%, 61.0, 29.0, and 5.3 for clinical stages I, II, III, and IV, respectively. Patients with anaplastic carcinoma (grade 3) at all clinical stages had significantly lower survival rates than had patients with well-differentiated (grade 1) and moderately differentiated (grade 2) adenocarcinomas. Death of grade 1, grade 2 and grade 3 endometrial carcinoma during the first 2 years occurred in 4.7, 6.8, and 18.2% of cases, respectively, in stage II, indicating that adjuvant MPA cannot totally prevent the progression of endometrial malignancy. The incidence of anaplastic endometrial carcinoma increased with the spread of the disease. It often appeared in patients with low body weight or a second invasive malignancy, but seldom occurred in young patients or patients with diabetes, uterine myoma, or a history of previous estrogen use. The worsened prognosis associated with old age, low body weight, and presence of a second invasive malignancy thus seems at lest partly due to the increased incidence of anaplastic carcinoma, which, on the other hand, did not contribute to the decreased 5-year survival rate of patients with diabetes or severe hypertension.

Adenocarcinoma