A novel modification of a flow cytometric assay of phosphorylated STAT1 in whole blood monocytes for immunomonitoring of patients on IFN alpha regimen.

We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)alpha regimen. CD14+ monocytes responded strongly to IFNalpha/gamma being sensitive indicators for recent immune activation. At 45 min after s.c. IFNalpha 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long-term deficient phosphorylated STAT1 response to IFNalphain vitro that in patients on standard IFNalpha regimen lasted for 48 h. In patients on pegylated IFNalpha the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.

Duodenal disaccharidase activities in the follow-up of villous atrophy in coeliac disease.

BACKGROUND: In active coeliac disease, mucosal atrophy is associated with a marked decrease in intestinal disaccharidase enzyme activities. We investigated the value of duodenal mucosal disaccharidases to predict the severity of mucosal villous atrophy and its recovery in 50 patients with coeliac disease. METHODS: Duodenal mucosal histology and disaccharidase activities were studied at least twice with a mean interval of 9 months. Histology of specimens from all patients was examined by the same pathologist blinded to the data on disaccharidase activities. Mucosal damage was scored into four groups as follows: Grade 0 = normal mucosa; grade I = slight villous atrophy, that is, cryptic component 30%-50%; grade 2 = moderate villous atrophy, that is, cryptic component 50%-90%; grade 3 = severe villous atrophy, that is, cryptic component >90%. The enzyme activities of the disaccharidases were determined as U/g protein. RESULTS: Duodenal mucosal disaccharidase activities were good predictors of the grade of mucosal villous atrophy. Positive predictive values for moderate or severe villous atrophy were 90% for maltase (maltase activity <150 U/g protein), 86% for sucrase (<40 U/g protein) and 71% for lactase (<20 U/g protein). Accordingly, negative predictive values, that is, none or only minimal villous atrophy (grades 0 or 1) with normal disaccharidase activities, were 71% for maltase, 70% for sucrase and 63% for lactase. CONCLUSIONS: The increase in duodenal disaccharidase activities correlated with recovery of the mucosa based on histology. Besides the histological examination, measurement of disaccharidase activities offers an additional tool to evaluate response to a gluten-free diet in patients with coeliac disease.

Sjögren's syndrome with chronic pancreatitis, sclerosing cholangitis, and pulmonary infiltrations.

We report a patient with Sjögren's syndrome and multiple gastrointestinal manifestations who successfully responded to therapy with ursodeoxycholic acid. Our patient had sialoadenitis with dry mouth, dry eyes, arthralgia, chronic pancreatitis, sclerosing cholangitis, and pulmonary infiltrations. The first signs of disease were the symptoms of chronic pancreatitis followed by icterus, caused by extrahepatic bile duct obstruction. Sclerosing cholangitis was diagnosed by liver biopsy and endoscopic retrograde cholangiography. Sialoadenitis, causing dry mouth, was verified by buccal biopsy. Pulmonary infiltrations were seen on standard chest x-ray, and also shown by high-resolution computed tomography examination. Obstructive icterus and even pulmonary infiltration responded successfully to treatment with ursodeoxycholic acid.

Acute thrombocytopenic purpura following measles, mumps and rubella vaccination. A report on 23 patients.

An acute thrombocytopenic purpura developed shortly after measles-mumps-rubella vaccination in 23 of approximately 700,000 children immunized over a period of seven years. The mean interval from inoculation to the onset of purpura was 19 days. Bone marrow aspirates obtained from 13 patients showed increased or normal amounts of megakaryocytes. Platelet survival time was markedly shortened in the two patients studied. Fifteen patients recovered (the platelet count exceeded 100 x 10(9)/l) in one month, five in two months and two in six months. Increase in platelet-associated immunoglobulin was detected in 10 of 15 patients. Circulating antiplatelet autoantibodies (AAb) against glycoprotein IIb/IIIa were detected in 5 of 15 patients. The findings are compatible with an autoimmune mechanism triggered by immune response to measles-mumps-rubella vaccination. As evaluated by the clinical course and the presence of AAb, post-vaccination thrombocytopenic purpura appears to be indistinguishable from childhood acute idiopathic thrombocytopenic purpura.

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.

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)

Clinical value of a direct platelet suspension immunofluorescence test in adult idiopathic thrombocytopenic purpura.

109 adult patients with ITP were tested with the direct platelet suspension immunofluorescence test (PSIFT) for platelet-associated immunoglobulins (PAIg). 88 patients (81%) had a positive direct PSIFT. The mean platelet level at the time of the test was 45.2 X 10(9)/l [corrected] (SD = 28.8) with no difference between PSIFT-positive and -negative groups. The results of direct PSIFT were of limited value in predicting patient outcome. The overall better prognosis of patients with a negative direct PSIFT compared to those with a positive result was statistically significant. The PSIFT negatives achieved complete remission more often than PSIFT positives; and they also showed a tendency for a better response to splenectomy and therapy with high-dose i.v.Ig. Moreover, all the 21 patients refractory to therapy with corticosteroids, splenectomy or i.v.Ig, were PAIg positives.

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.

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.

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.

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.

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.

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.

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.

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.