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Biomedical subjects

S Franzén

Publications and source records attributed to S Franzén.

At least 19 recordsLinked to original sources

Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours.

BACKGROUND: Midgut carcinoid tumours often present with widespread disease making curative surgery impossible. Medical treatment therefore plays a major role in the treatment of these patients. METHODS: In this prospective randomized study, the effect of interferon (IFN) alpha on survival and risk of tumour progression was evaluated in 68 patients with midgut carcinoid tumours metastatic to the liver. All patients had undergone primary surgical treatment and hepatic arterial embolization of liver metastases before randomization. Patients were randomized to treatment with either octreotide alone (n = 35) or octreotide in combination with IFN-alpha (n = 33). RESULTS: Forty-one of the 68 patients died during a follow-up period of 33-120 months, equivalent to a 5-year survival rate of 46.5 per cent. There was no significant difference in survival between patients treated with octreotide alone (5-year survival rate 36.6 per cent) and those given octreotide in combination with IFN-alpha (56.8 per cent). However, patients treated with IFN-alpha had a significantly reduced risk of tumour progression during follow-up (P = 0.008). CONCLUSION: Addition of IFN-alpha to octreotide may retard tumour growth in patients with midgut carcinoid tumours.

Adult↗

HPV 16 infection in a patient with two primary squamous cell carcinomas: of the uterine cervix and the anal mucosa.

A 43-year-old woman presented with metrorrhagia and a polypoid anal tumor. Cervical dilatation and endocervical curettage and resection of the anal tumor revealed two primary squamous cell carcinomas: of the uterine cervix and the anal mucosa. HPV 16 was identified in both tumors using an in situ hybridization technique with probes against HPV 6, 11, 16, 18, 31 and 33. The cervical carcinoma was weakly positive for p53 protein, whereas the anal tumor was p53 protein negative. Five years later a recurrence of the cervical carcinoma was diagnosed and a hysterectomy was performed. Of 3,013 patients with squamous cell carcinoma of either the cervix or the anus registered in our files, only one had a primary carcinoma in both locations. It was concluded hat HPV-16-induced squamous cell carcinoma may occur simultaneously in the cervix and the anus, and carcinoma in either of the two locations has to be ruled out when dealing with HPV infection in the anogenital tract.

Adult↗

Assessment of frequency dependency of the class III effects of almokalant: a study using programmed stimulation and recording of monophasic action potentials and ventricular paced QT intervals.

The aim of the present study was to assess the frequency dependency of the effects of almokalant, a selective class III antiarrhythmic drug, on ventricular repolarization using recordings of monophasic action potentials and measurements of ventricular paced QT intervals. Twenty male volunteers were studied during almokalant infusion aiming at plasma concentrations (Cpl) of 20, 50, 100, and 150 nmol/l. The duration of monophasic action potential at 90% repolarization (MAPD) was measured during incremental and premature ventricular extrastimulation. The ventricular paced QT interval was measured during incremental stimulation from the apical region (RV APEX) and the outflow tract (RVOT) of the right ventricle, and the frequency dependence was analyzed using a linear regression model. At an almokalant dose of Cpl > or = 50, there was a significant prolongation of the MAPD of 10-15%. The prolongation was of equal magnitude at all paced cycle lengths (CL). The MAPD of ventricular extrasystole increased in parallel over the range of coupling intervals studied and was significantly prolonged at Cpl 100 and 150. The ratio between the MAPD of the extrasystoles and preceding beats was unaltered after almokalant infusion. The ventricular paced QT intervals increased during almokalant infusion in a similar manner as that of the MAPD. During RV APEX stimulation, the prolongation was more pronounced at low heart rates, an effect that was not seen during RV OT stimulation. Almokalant significantly prolonged the MAPD at dose levels Cpl > or = 50. There was no evidence of a frequency dependence of this effect. The ventricular paced QT intervals were prolonged in a similar manner as that of the MAPD, and this effect exhibited a small reverse frequency dependence during RV APEX stimulation.

Action Potentials↗

Radiologic appearance of nonpalpable intramammary lymph nodes.

Sixty-four well circumscribed nonpalpable lesions, mammographically evaluated as benign and cytomorphologically verified as lymph nodes, were studied concerning mammographic appearance, size and location within the breast. The great majority, 72%, were situated within the upper-outer quadrant, but lymph nodes were also diagnosed in other areas of the breast. Of the verified lymph nodes 50 (78%) had a lower density at the center than at the periphery. These were the only well circumscribed nodules with a low density center observed in a total of 3,623 nonpalpable lesions stereotaxically needled during the same period. Three of the lymph nodes were verified histopathologically. Till now, none of the other 61 lesions has turned out to be a malignant tumor during a follow-up time from 9 to 15 years. Thus a lesion presenting roentgenologically as a well circumscribed nodule with a central area of decreased density compared to the peripheral part can be confidentially diagnosed as a lymph node by the mammograms alone and no further investigation is indicated.

Adult↗

Late side effects of chemotherapy in ovarian carcinoma: a cytogenetic, hematologic, and statistical study.

Late side effects of chemotherapy were studied in 51 women who had received at least 300 mg of melphalan for ovarian cancer and had survived for at least three years. Hematologic, statistical, and cytogenetic methods were employed. Six cases of iatrogenic leukemia were found. They appeared to represent a hematologic entity that is fairly difficult to recognize. The risk of iatrogenic leukemia in women who survived for three years or more after melphalan treatment was calculated to be 950 times greater than the leukemia risk in the total female population. The cytogenetic changes were studied with three methods focused on sister chromatid exchange, chromosome aberrations, and DNA damage. The sister chromatid exchange frequency showed a marked increase, but it was corrected within a few months. Chromosome aberrations expressed by chromosome rearrangements were increased in the peripheral lymphocytes and may persist for several years. The frequency of DNA stand breaks was decreased indicating the presence of DNA cross-links. Any of these types of genetic alteration could be the initiating event in carcinogenesis.

Acute Disease↗

Transrectal aspiration biopsy of the prostate. A re-evaluation of the method in the diagnosis of prostatic carcinoma.

Cytologic results with transrectal aspiration biopsy of the prostate were analyzed after 20 years of experience, in order to re-evaluate the accuracy of the method in the diagnosis of prostatic carcinoma. Carcinoma was cytologically diagnosed with increasing frequency with increased age of the patient and increased grade of clinical suspicion. For instance carcinoma was diagnosed in only 10% of cases under 50 years of age and in more than 50% of cases over 80. At first biopsy carcinoma was diagnosed in only one out of 175 patients without clinical suspicion of malignancy and in 98% of the cases with strong suspicion of malignancy at rectal palpation. By repeating aspiration biopsy in clinically suspected cases the danger of false negative report is minimized. A good correlation was found between cytologic findings and histologic control in 350 patients. Prostatic carcinoma was detected cytologically in about 96% of the cases. A false positive diagnosis is not to be feared when the diagnostic work is performed by a trained staff.

Adult↗

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report.

Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Acute Disease↗

Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia.

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

Adult↗

Specific chromosomal aberrations in polycythemia vera.

The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received no treatment with cytotoxic drugs, while three had received 32P only and the other three, in addition, had received busulfan or busulfan and procarbazine. One 73-yr-old male patient treated with venesection only for 4 yr lacked the Y chromosome and had a deletion of the long arm of chromosome 20 (20q-) in all cells investigated. One of the other three patients who had received no drugs had a chromosome abnormality, but only in 1 of 19 identifiable metaphases. However, the abnormality was the same (+9) as the most common one in treated patients. In the group of treated patients, an extra chromosome 9 (+9) was found in three patients, an extra chromosome 8 (+8) in one, and a deletion of the long arm of one chromosome 20 (20q-) in one patient. Multiple aberrations in addition to the extra chromosome 9 were found in one patient in whom the disease had transformed into acute myeloblastic leukemia. The finding of identical chromosomal aberrations (20q- and +9, respectively) in two patients who had received no drugs and in four patients who had received 32P and busulfan or procarbazine favors the view that these aberrations are specifically associated with the disease and not induced by the drugs. With the exception of the patient with acute myeloblastic leukemia, all other patients are alive 1-11 mo after chromosome analyses and 1-229 mo after diagnosis.

Aged↗

L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia.

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.

Adolescent↗