Biomedical subjects
Publications and source records attributed to M Virolainen.
A significant correlation (r = -0.48) was found between the logarithm of the S-phase fraction of the primary tumour (SPF) and the logarithm of the doubling time of lung metastases (T2). The estimated median cell loss factor was 88% (range 35-99%).
Mucormycotic infections caused by fungi of the families Rhizopus, Mucor or Absidia are rare and usually associated with diabetes or immunosuppression. We describe a patient with invasive necrotizing cutaneous mucormycosis caused by Absidia corymbifera shortly after allogeneic BMT. The infection was successfully treated with surgical debridement and liposomal amphotericin B for 6 weeks. Recognition of these rare infections requires a high index of suspicion. These patients should be evaluated with tissue biopsy and cultures and treated without delay.
A total of 23 patients with metastatic sarcomas were treated with continuous oral trofosfamide, an alkylating agent structurally related to cyclophosphamide and ifosfamide. In all, 12 of the patients were chemotherapy-naive. Doses were escalated every 3rd week until the development of leukopenia of WHO grade 2. The treatment was well tolerated and produced little subjective toxicity. Leukopenia was the dose-limiting toxicity. The daily dose that produced grade 2 leukopenia was 200-250 mg in 65% of the patients. Three patients responded, all of whom had been treated with trofosfamide as first-line treatment.
We report the results of cytogenetic analysis of malignant fibrous histiocytoma of soft tissue (MFH). Seven of 12 successfully cultured MFHs had complex clonal aberrations, including translocations, deletions, and unidentifiable marker chromosomes. Telomeric associations were observed in five and the double minute phenomenon in four of seven MFHs with abnormal karyotypes. In one case (a storiform-pleomorphic MFH, grade IV) with a complex polyploid karyotype, two clonal ring chromosomes were present, one interpreted as r(19)(p13q13), one unidentified. In two tumors, clonal structural rearrangements of chromosome 1 were seen: del(1)(q21) in a storiform-pleomorphic MFH, grade IV, and add (1)(q21 or q32), t(1;10)(p22;q22) in a myxoid MFH, grade I. The remaining five MFHs had normal karyotypes, but in two of them nonclonal, structural aberrations were found. The modal chromosome number in the studied MFHs varied widely, but the majority of tumors with abnormal karyotypes had polyploid chromosome complements (five of seven cases). Our results confirm many of the previous findings and indicate that double minutes (dmins) may be more frequent in MFH than previously reported.
The term "gastrointestinal stromal tumor" (GIST) has been applied to mesenchymal tumors that represent neither typical leiomyomas nor schwannomas. In this study we analyzed immunohistochemically 67 histologically benign [< 2 mitoses/10 high-power field (HPF)], six borderline (3-5 mitoses/10 HPF), and 23 malignant GIST (> 5 mitoses/10 HPF) and compared them with 10 typical leiomyomas and 5 schwannomas of the gastrointestinal tract. The benign GISTs with spindle cell pattern (67 cases) were typically negative for muscle cell markers (only 3% positive for desmin and 25% for alpha-smooth muscle actin) and S100 protein, but 70% of the cases were positive for CD34, the myeloid progenitor cell antigen also present in endothelial cells and some fibroblasts. However, none of the cases was positive for CD31 (PECAM-1), a more endothelial cell-specific antigen. The absence of CD31 in GIST separates it from Kaposi's sarcoma, a tumor known to be positive for both CD34 and CD31. Fourteen cases of benign GIST of epithelioid cell type showed an immunophenotypic profile similar to the spindle cell tumors. The small intestinal tumors were more commonly actin positive and less commonly CD34 positive than were the gastric tumors. The malignant spindle and epithelioid GIST showed features essentially similar to those in corresponding benign tumors. In contrast, all typical leiomyomas were positive for muscle cell markers and were negative for CD34 and S100 protein. Gastrointestinal schwannomas were S100-protein positive, and negative for muscle markers and CD34. Our results show that gastrointestinal mesenchymal tumors can be immunophenotypically divided in categories that correlate with light microscopically defined diagnostic entities, namely typical leiomyomas, schwannomas, and GIST, most cases of the latter representing tumors of primitive mesenchymal cells that are CD34 positive.
A chemotherapy regimen consisting of dacarbazine (DTIC), vincristine, bleomycin and lomustine (CCNU) was combined with natural leucocyte interferon (IFN) in the treatment of 37 patients with cutaneous and subcutaneous metastases of malignant melanoma. Twenty-five also had concomitant lymph node, visceral, bone or brain metastases. Fifteen patients (41%) experienced complete response (CR) and 10 (27%) partial response (PR) of the superficial lesions. In addition, three patients were rendered surgically tumour-free after PR or disease stabilization during drug therapy. The median overall duration of response was 10.2 months (range 1-53 months). In disseminated disease, the combined therapy produced favourable results, particularly with regard to superficial lesions. It is also possible that this therapy may retard the growth of aggressive subcutaneous metastases in patients who have previously had multiple surgical procedures in an attempt to stabilize their disease. In a small proportion of patients, the long-term complete remission with the drug therapy alone, or in combination with surgery, suggests that this regimen might have been curative.
Translocation t(9;22)(q22-31;q11-12) is associated with the myxoid variant of chondrosarcoma. We present here a report of a patient with a dedifferentiated grade IV chondrosarcoma, which originated from the iliac bone and contained areas of grade I chondrosarcoma. There was no evidence of myxoid differentiation. The tumor had the karyotype 46,X,-X,t(9;22)(q34;q11-12), + mar[5]/52-61,x?,2-3 min,inc[9]/46,XX[2]. It is possible that the different breakpoints in the t(9;22) may reflect different histopathologic subgroups of chondrosarcoma.
The volume doubling time (T2) of 52 lung metastases in 21 patients was calculated from measurements done on plain chest radiographs. Follow-up times ranged from 14 to 819 days. The measurements were fairly well reproducible in the majority of patients, although considerable discrepancies in T2 estimates made by two independent observers were found in a few patients. The median doubling time was 34.9 days (estimated 95% range 3.9 to 352 days). The variation of T2:s between patients was significantly (P = 0.0001) larger than that between T2: of multiple metastases in the same patients. The growth of the metastases seemed to be well described by a simple exponential function in all patients with more than two measurements, without evidence of Gompertzian growth. There seemed to be a linear correlation between the logarithm of T2 and log-survival time from diagnosis of metastatic disease, even if only one third of the variation of survival times between patients could be explained by differences in T2. T2 was not a significant factor for survival in Cox-analysis (P = 0.10).
Eighteen patients with a biliopancreatic carcinoma in 15 different cancer family syndrome (CFS) families were studied. Only families with three or more first-degree relatives with colorectal carcinoma were included, and other characteristics of CFS were required in at least two cases. In 14 patients, the histologic specimen was available for reevaluation. In 11 (79%), the tumor was confirmed as a carcinoma of the biliary tract or papilla of Vater. In three (21%), carcinoma of the pancreas was the most probably alternative. In all four patients without histologic reevaluation, the diagnosis had been carcinoma of the biliary tract. This study suggests that carcinoma of the biliary tract or papilla of Vater is associated more commonly with CFS than with carcinoma of the pancreas. In this respect, CFS resembles familial adenomatosis coli, in which this association previously has been established.
A total of 37 adult patients with locally advanced or metastatic soft-tissue sarcoma (STS) entered a pilot study of combination chemotherapy based on the CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine) regimen, in which cyclophosphamide was replaced by ifosfamide and mesna (1 g/m2 ifosfamide given daily on days 1-5 as 2-h infusions, 1.5 mg/m2 vincristine given on day 1 as a bolus injection, 50 mg/m2 doxorubicin given on day 1 as a 5-min infusion, and 250 mg/m2 dacarbazine given daily on days 1-5 as 30-min infusions). The overall response rate in 24 patients who were evaluable for response was 46% [95% confidence interval (CI), 25%-67%] and that in subjects who had not undergone prior chemotherapy was 50% (CI, 27%-73%). In all, 4 patients achieved a complete response (17%; CI, 5%-37%) and 2 remain in remission; 3 additional subjects were surgically rendered disease-free after they had shown a partial response. Overall, 31 patients were evaluable for toxicity. Toxicity was mainly hematological; in 3 patients the nadir WBC was less than 0.5 x 10(9)/l, and in 2 cases the nadir platelet count was less than 50 x 10(9)/l. During neutropenia, infections requiring intravenous antibiotics occurred in 8 patients (26%) and in 14 of 190 cycles (7.5%); 1 of these was fatal. We conclude that this new regimen offers promise for the treatment of advanced STS, producing acceptable toxicity.
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We report the acquisition of skin test sensitivity to Candida albicans antigen and the ability to produce leukocyte migration inhibition factor (MIF) by a Candida-negative patient with chronic granulomatous mucocutaneous candidiasis after treatment with dialyzable transfer factor (TFd). The TFd was acquired from Candida-positive healthy donors. Three of seven attempts to transfer Candida skin test sensitivity were successful, and the acquired skin reactivity lasted for 12 to 21 days. The acquisition of cellular immunity to Candida was demonstrated in vitro by production of leukocyte MIF. No Candida-induced lymphocyte transformation was observed before or after TFd injection. The TFd did not cause Candida-induced blast transformation when added directly to cultures of lymphocytes from the patient. Pain, tenderness, redness, and edema were observed around the Candida granulomas on each occasion when the skin test to Candida became positive. Two weeks after TDd injection, the proliferative response of peripheral blood lymphocytes increased, as measured by incorporation of tritiated thymidine into lymphocytes within the first hour of in vitro incubation.
The purpose of this investigation was to compare the prevalence of soft tissue disorders in the neck, arms and hands between packers doing repetitive work and shop assistants with variable tasks. One hundred and fifty-two female assembly-line packers in a food production factory and 133 female shop assistants were interviewed about their symptoms and given a clinical examination of the neck and upper extremities. The number of cases of tension neck, cervical syndrome, scalenus syndrome, and humeral epicondylitis did not differ significantly between the two groups. The prevalence of tenosynovitis and humeral tendinitis was significantly higher for the assembly-line packers. The packing work consisted of static muscle work by the arms, grasping and maximal extensions of the fingers, and lateral deviations of the wrists. The movements numbered up to 25,000/workday. A relationship between some work load factors and some disorders of the upper extremities is probable.
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This report describes the clinical improvement and acquisition of tuberculin skin-test sensitivity by a tuberculin-negative, drug-resistant patient with lupus vulgaris after a single injection of dialyzable transfer factor (TFd) from a tuberculin-positive healthy donor. The patient's lymphocytes showed a slight response to tuberculin in the leukocyte migration inhibition test and in the lymphocyte transformation test before TFd injection. The acquisition of cellular immunity to tuberculin was demonstrated in vitro by enhanced tuberculin-induced blast transformation. A good correlation between skin test and in vitro tuberculin sensitivity and clinical improvement was seen during the three years that the patient was observed.
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