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Biomedical subjects

A Wallgren

Publications and source records attributed to A Wallgren.

At least 37 records · Page 2Linked to original sources
PubMed1996

Soft tissue sarcoma after treatment for breast cancer.

In a register study all women in the West of Sweden Health Care Region with a breast cancer diagnosed between 1960 and 1980 (n = 13,490) were followed up in the Swedish Cancer Register to the end of 1988 for later occurrence of a soft tissue sarcoma (STS). Nineteen sarcomas were reported, whereas 8.7 were expected and the relative risk (RR) was 2.2 (CI 95% 1.3-3.4). The absolute risk was 1.7/10(4) person years (PY) in comparison with 0.8 expected. To obtain a more detailed analysis of the associations between arm lymphoedema, radiotherapy and STS development, and to control the quality of the register data, a case control study was also performed. Clinical records from the different hospitals in the region were collected for all the 19 cases as well as for three selected controls per case. The histopathology of the cases were reviewed, and one of the cases was reclassified as a malignant melanoma and excluded from further analysis. Thirteen of the cases were clustered around the treated breast area. To quantify the exposure to radiotherapy, the integral dose was estimated. The presence of lymphedema was included as a binary variable in the analysis. The exact conditional randomisation test indicated a significant correlation between the integral dose and the development of an STS (p = 0.008) and this association was still significant after stratification for arm oedema. A conditional logistic regression analysis with STS as the dependent variable and the integral dose as the explanatory variable gave an odds ratio (OR) of 5.2/100 J (CI 95% 1.3-21.2), and if this regression was restricted only to the STS developing in the radiation fields the OR was 3.2/100 J (CI 95% 0.8-12.9). Thus, the excess of STS in this breast cancer cohort was very low (0.9/10(4) PY). However the integral dose correlates well to the development of STS and can be useful in quantifying even small risks of secondary malignancies in the breast cancer population.

Arm↗
PubMed1995

Cancer incidence after radiotherapy for skin haemangioma during infancy.

An infant cohort treated for skin haemangioma with 226Ra between 1930 and 1965 (n = 11,807) was studied. The median age at treatment was 5-months and 88% were treated before 12 months of age. This cohort was followed up in the Swedish Cancer Registry during the years 1958 to 1989, giving 370,517 person-years at risk. A total number of 248 malignancies have been observed and the standardized incidence ratio (SIR) was 1.21 (confidence interval (CI) 95%, 1.06-1.37). Significantly increased numbers of cancers were found in the central nervous system, 34 cases (SIR = 1.85, CI 95% 1.28-2.59), the thyroid, 15 cases (SIR = 1.88, CI 95% 1.05-3.09) and other endocrine glands, 23 cases (SIR = 2.58, CI 95% 1.64-3.87). The absorbed dose in 11 specified risk organs has been estimated using a phantom of the size of a 5-6-month-old child. The mean absorbed dose in the thyroid was 0.12 Gy and the excess relative risk (ERR) for thyroid cancer was 7.5 per Gy (CI 95% 0.4-18.1). The mean dose in the central nervous system was 0.077 Gy and the ERR for brain tumours was 10.9 per Gy (CI 95% 3.7-20.5). This cohort gives a unique opportunity to analyse long-term effects of low-dose irradiation during infancy.

Adolescent↗
PubMed1994

Role of antibody synthesis and complement activation in concordant xenograft retransplantation.

A mouse-to-rat heart retransplantation model was used to study the effects of complement depletion and antibody production with regard to graft survival and anti-donor antibody specificity. Retransplantation was performed 3 weeks after the first transplantation in the presence of absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated animals rejected their first graft after 3 days and retransplantation resulted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endothelium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graft vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted with hamster antigens and a hyperacute rejection of a hamster heart graft occurred in a mouse-sensitized rat. Immunofluorescent staining revealed that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolonged the survival of the first graft by a median of 8 days. Continuous treatment until retransplantation resulted in a prolongation to 30 (20-127) min of the survival of the second graft and no increase in antibody titers against mouse antigens was observed. However, immunofluorescent staining revealed a weak binding of anti-mouse antibodies of the IgM subclass in the rejected mouse heart graft. Additional complement depletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but histology revealed massive mononuclear infiltration. In conclusion, xenograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatment is administered from the day of transplantation, this reduces the synthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.

Animals↗
PubMed1993

Efficient killing of chronic B-lymphocytic leukemia cells by superantigen-directed T cells.

In vitro studies have indicated that chronic lymphocytic leukemia of B-cell origin (B-CLL) is resistant to cytotoxic effector lymphocytes such as natural killer and lymphokine activated killer (LAK) cells. We show here that B-cell cells are sensitive to Staphylococcal enterotoxin (SE) A-directed T-cell killing. Activation of the target cells by phorbol ester (tetradecanoyl phorbol acetate, [TPA]) greatly enhances their sensitivity to lysis. In SE-dependent cellular cytotoxicity (SDCC), members of the SE superantigen family form a bridge between T cells and target cells expressing major histocompatability complex class II molecules. Binding of SEA to the T-cell-receptor V beta region induces a strong cytotoxic capacity and cytokine production. Cells from 9 B-CLL patients were cultured in the presence or absence of TPA and used as targets in a 4-hour SDCC assay using an allogeneic T-cell line as effector. At an effector:target cell ratio 30:1, 70% to 80% of TPA-induced B-CLL cells were killed. Even at the effector:target ratio of 3:1, 47% +/- 6% of TPA-activated B-cell cells were lysed compared with 13% +/- 2% of resting cells (P < .001). A T-cell line established from a B-CLL patient killed autologous tumor cells as efficiently as allogeneic effectors. SEA-directed T cells were far more lytic to B-CLL cells compared with LAK cells or lectin (phytohemagglutinin-directed T cells. Mechanisms of SDCC lysis were investigated. Effector plus target cell supernatants contained high levels of tumor necrosis factor (TNF)-alpha and interferon-gamma, but these supernatants were not directly toxic to B-CLL cells in short term culture. High concentrations of recombinant TNF-alpha or TNF-beta had no lytic effect. Addition of neutralizing anti-TNF-alpha and anti-TNF-beta antibodies into the SDCC assay did not inhibit SEA-directed T-cell killing. TPA-activated B-CLL cells showed a 1.2- to 13-fold increased expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen (LFA)-1, and LFA-3, whereas expression of HLA class II molecules increased up to 5 times. The expression of CD72, CD40, and BB-1/B7 increased 1.8 to 4.5 times. The role of these surface molecules in SDCC was analyzed in blocking experiments with monoclonal antibodies. Antibodies to ICAM-1, CD18, and HLA-DR abolished the cytotoxicity, and a substantial reduction was seen with antibody to CD72.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Neuropathologic findings after long-term intrathecal infusion of morphine and bupivacaine for pain treatment in cancer patients.

Epidural or intrathecal infusions of morphine and bupivacaine mixtures are presently used for the treatment of "refractory" cancer pain even though the neurotoxic potential of such mixtures is unknown. The pathologic findings of the spinal column, the meninges, the nerve roots, and the spinal cord, and the clinical neurologic deficits were recorded in 15 patients (5 men and 10 women), aged 26-83 (median 68) yr, treated for 4-274 (median 81) days with intrathecal infusions of morphine (with preservatives [sodium metabisulfite and sodium edetate]) and bupivacaine mixtures, given through open, subcutaneously tunneled nylon catheters. Six patients had been subjected to radiation therapy (20-96 Gy), applied over the spinal column, and four had been treated with antineoplastics believed to be neurotoxic. Ten patients had various neurologic deficits before the intrathecal treatment. The cumulative doses (ranges) given intrathecally were: morphine 33-11,900 mg, sodium metabisulfite 3.3-1,050 mg, sodium edetate 0.33-105 mg, and bupivacaine 10-41,400 mg; cumulative volumes were 16-9,400 ml. The concentrations of the drugs in the mixtures were: morphine 0.25-4.0 mg/ml, sodium metabisulfite 0.025-0.40 mg/ml, sodium edetate 0.0025-0.04 mg/ml, and bupivacaine 3.0-4.75 mg/ml. The osmolality of the mixtures in vitro ranged from 282 to 286 mOsm/kg and the pH from 4.1 to 4.6. The pathologic findings consisted of vertebral metastases (n = 6), epidural and/or intrathecal tumor masses (n = 8), focal subdural fibrosis (n = 6), infiltration of mononuclear cells in the subarachnoid space (n = 10), and discrete injuries (nerve fiber degeneration or fibrosis) to the anterior (five patients) and posterior (seven) nerve roots, and spinal cord (tumor compression [one], slight thickening of the leptomeninges [one], and thrombosis of a spinal artery and medullary infarction [one]). In none of the cases was any reaction against the nylon catheter within its subarachnoid course recorded. The neuropathologic findings were not related to the duration or cumulative doses of the intrathecal treatment. No new neurologic deficits that could be attributed to the intrathecal administration of the opiate-bupivacaine mixtures were recorded. The neuropathologic and clinical neurologic findings in cancer patients treated with intrathecal morphine-bupivacaine mixtures appeared similar to those in animals and humans reported with either intrathecal morphine or bupivacaine alone.

Adult↗
PubMed1992

Late effects of radiotherapy in the treatment of breast cancer.

Late effects after radiotherapy for breast cancer include radiation induced malignancy and changes in irradiated tissues leading to e.g. edema of the arm, decreased mobility of the shoulder joint, brachial plexus neuropathy, pulmonary fibrosis, telangiectasia or atrophic ulceration of the skin. While radiation-induced malignancy depends on the volume of tissue irradiated and the total dose, other late effects are also fractionation dependent. Several reports have shown increased rates of such late effects after changes of the fractionation schedule which should be isoeffective according to the mathematical models commonly used to predict early effects. Although knowledge of the relation between total dose, number of fractions and radiation effects in late responding tissues has increased, extrapolations from the models should be used cautiously. The dose-response curve seems to be steeper for late effects than for tumour control. The possibility of late effects should be included in the decision as to when and how to treat breast cancer with radiotherapy.

Brachial Plexus↗
PubMed1991

Uptake and retention of platinum in patients undergoing cisplatin therapy.

Results of in vivo measurements of the platinum concentration in kidneys and tumours of patients treated with cisplatin for testicular carcinoma, head and neck tumours and brain tumours are presented. The measurements were performed with an x-ray fluorescence technique. Our earlier studies have shown that maximum platinum levels in kidneys were reached 3-4 h after an intravenous injection of cisplatin. The present study showed that, at that time, the ratio between the concentration of platinum in kidney and in blood serum was 22 +/- 7 (+/- 1 S.D.). Between 24 and 72 h after administration this ratio was 10 +/- 3, as shown in another group of patients. Measurements of platinum concentration in brain tumours showed varying maximum uptake, between 14 and 40 micrograms/g, 5-15 h after administration. There was an indication that radiotherapy may increase the uptake of cisplatin in normal brain tissue. The technique described can be used for further studies of the platinum concentration in tumours and risk organs in connection with cisplatin therapy. Such studies are needed to find out how to improve the therapeutic effects and lower the toxic ones.

Adolescent↗
PubMed1991

Primary radiotherapy for glottic laryngeal carcinoma stage I and II. A retrospective study with special regard to failure patterns.

A retrospective study has been made of 302 patients with vocal cord carcinoma stage I and II treated between 1963 and 1983, emphasizing treatment failure patterns. The primary treatment modalities were radiotherapy for 266 patients and surgery for 36 patients. The minimum follow-up was 4 years. After primary radiotherapy there were 63 local recurrences and 7 neck lymph node recurrences, all appearing outside the target volume. The actuarial loco-regional recurrence-free rates at 5 years were 78% for T1, 76% for T2a (normal cord mobility) and 60% for T2b (impaired cord mobility) tumors. The actuarial regional lymph node recurrence-free rates at 5 years were 99, 100 and 93% for T1, T2a and T2b tumors respectively. The actuarial corrected survivals at 5 years were 95, 96 and 79% for T1, T2a and T2b tumors with primary radiotherapy and salvage surgery for recurrence. Salvage surgery was less successful in T2b compared to T1 and T2a tumors. In conclusion, after primary radiotherapy with salvage surgery the loco-regional control rate was high and very similar for glottic cancer T1 and T2a but less satisfactory for T2b tumors. Regional lymph node metastases were not a large problem in any of the subgroups. More effective radiotherapy with higher dose levels or an altered fractionation might increase the local control rate for T2 tumors with impaired cord mobility.

Adult↗
PubMed1990

Extracting knowledge from a large primary health care database using a knowledge-based statistical approach.

Clinical databases from automated medical records represent a growing resource for deriving new medical knowledge. In this study a large primary health care database was explored with respect to the association between hypertension and diabetes. Data collection was made with a query language, and data analysis performed with an interactive knowledge-based statistical tool, MAXITAB, employing a multivariate tabular analysis technique. In the study population of 6660 patients the prevalence of diabetes was almost three times higher for hypertensive patients than for those with no hypertension. Conversely, the prevalence of hypertension was 2.6 times higher for diabetic patients than for those with no diabetes. The results support the assumption of a relationship between hypertension and diabetes, although the question of causality between the two diagnoses remains unsolved. Knowledge-based statistical tools of this kind may be feasible for exploring large clinical databases and may result in new medical hypotheses, worthy of further investigation.

Aged↗
PubMed1990

Clinical trials in locally advanced breast cancer.

Survival after treatment of locally advanced breast cancer is poor and resembles that for untreated breast cancer. Although retrospective comparisons have suggested that the addition of systemic treatment might be beneficial, a literature survey of the controlled clinical trials failed to show consistent survival benefits of any treatment modality. The local control, or time to local progression, on the other hand seems to be improved by increasing the dose of radiotherapy, or by the addition of endocrine or cytostatic treatment. Further studies should be undertaken to find better means to subdivide patients in different treatment groups. Since the present treatment modalities are unlikely to improve survival more than marginally, clinical studies are necessary to search for the best palliative treatment, until experimental work provides us with better treatment tools.

Antineoplastic Combined Chemotherapy Protocols↗