Paula Maasilta

Cognitive function and treatment of obstructive sleep apnea syndrome

Among patients with obstructive sleep apnea syndrome (OSAS), impairment of cognitive function, i.e. deficits in memory, attention, and visuconstructive abilities are common. We applied different forms of treatment for patients with newly diagnosed OSAS in a randomized study with a one‐year follow‐up. Patients with BMI > 40 kg/m4 and the Bourdon‐Wiersma (r=0.36). Success in treatment of OSAS did not affect neuropsychological outcome. We concluded that the standard cognitive test battery is insufficiently sensitive to identify positive changes in patients with OSAS, especially among those with a high level of overall mental functioning.

Biodegradation of the copolymeric polylactide stent : Long-term follow-up in a rabbit aorta model

The behavior of biodegradable polylactide as a stent material has not yet been fully established in small vessels such as arteries with a diameter <3 mm. The aim of this study was to investigate the long-term effect of a copolymeric polylactide (PLA96) stent. Appropriately sized spiral PLA96 stents were implanted into the infrarenal aortas of 20 rabbits. Intraoperative systemic heparinization (150 IU/kg), perioperative subcutaneous enoxaheparin sodium (10 mg), ticlopidine (250 mg/day) for 1 month, and acetosalicylic acid (12.5 mg/day) were continuously administered. Animals were euthanized according to a fixed timetable for up to 34 months for histologic and scanning-electron-microscopic assessment. Endothelialization was complete within 1 month. In 2 of the 3 aortas sampled 3 months after implantation, a mild inflammatory reaction was visible, with no sign of granulomatous or foreign-body reaction in the vessel wall. Instead, in 1 sample examined at the same time point, neointimal chondroid metaplasia was detected. After 6 months, inflammatory reaction declined in the vessel wall. Hydrolyzation of the stent was histologically evident at 12 months, with mild foreign-body reaction detectable in 2 of 5 aortas sampled at this time point. The stent disintegrated without fragmentation by 24 months, as it was gradually replaced by fibrosis. The vessel lumen remained patent at all time points. We conclude that the PLA96 stent degraded with minimal tissue response within 24 months. PLA96 may thus be a promising stent core material for small vessels in the future, although further investigation is needed to establish its final biocompatibility.

Deterioration in lung function following hemithorax irradiation for pleural mesothelioma

Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy.

Tumor necrosis factor-?? in a porcine bronchial model of obliterative bronchiolitis1

Background. In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-&agr; is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-&agr; in the development of OB in our heterotopic porcine bronchial transplantation model. Methods. Three groups were formed: autografts, nontreated allografts, and allografts treated with preoperative anti–TNF-&agr; monoclonal antibody (infliximab) infusion. The implants were harvested on days 2, 4, 7, 11, 14, 21, and 28 for histologic and immunohistochemical analysis. Results. TNF-&agr; inhibition reduced inflammation, rate of epithelial loss, fibrosis, and obliteration early in the development of OB. In the epithelium, the numbers of TNF-&agr;–positive epithelial and inflammatory cells and macrophages were significantly lower in treated than in nontreated allografts on day 4; furthermore, in the epithelium and in the bronchial wall, invasion of CD8+ lymphocytes was significantly decreased during the first week. Conclusions. These results indicate that TNF-&agr; promotes the development of OB, and inhibition of TNF-&agr; may prove beneficial in a clinical setting.

Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.

Nasal obstruction and sleep-disordered breathing: the effect of supine body position on nasal measurements in snorers.

Objective --Nasal obstruction is considered to be a potential etiological factor in sleep-disordered breathing. However, a significant correlation between nasal measurements and obstructive sleep apnea has not been demonstrated so far. The aim of this study was to investigate the relationships between nasal resistance, nasal volumes and selected sleep parameters using nasal measurements performed in both seated and supine positions. We also investigated whether snoring patients in our clinical sample showed increased positional or decongestive nasal mucosal changes. Material and Methods --Forty-one snoring men on a waiting list for correction of nasal obstruction underwent polysomnography, anterior rhinomanometry and acoustic rhinometry. Nineteen non-snoring control subjects were also recruited. Nasal measurements were performed in a seated position, after lying down in a supine position and, after decongestion of nasal mucosa, in a seated position again. Results --In the overall patient group, nasal volume at a distance 2-4 cm from the nares in the supine position correlated inversely with apnea-hypopnea index (AHI) ( r = m 0.32, p <0.05) and oxygen desaturation index (ODI) ( r = m 0.49, p <0.05). In the non-obese patients, total nasal resistance measured in a supine position correlated with AHI ( r =0.50, p <0.05) and ODI ( r =0.58, p <0.05) and supine nasal volumes were also inversely correlated with ODI. No significant correlations were found between baseline nasal measurements performed in a seated position and sleep parameters. Postural or decongestive changes in nasal measurements were not increased in snoring patients compared with control subjects. Conclusion --The relationship found between nasal measurements and sleep parameters suggests that nasal obstruction does augment airway collapse.

Prevention of small airway obliteration in a swine heterotopic lung allograft model

BACKGROUND In our swine model of obliterative bronchiolitis preventing obliteration by the standard immunosuppression with cyclosporine, methylprednisolone, and azathioprine was not successful. The purpose of this study was to test the ability of a new immunosuppressive regimen to prevent alloimmune reaction and obliteration of the allografts. This regimen includes the novel macrolide SDZ RAD, i.e., 40-O-(2hydroxyethyl)-rapamycin. METHODS Donor lung allografts of 1 cm3 were implanted sub-cutaneously into 11 random-bred non-related domestic pigs receiving daily oral cyclosporine (10 mg/kg) and methylprednisolone (20 mg). In addition, the animals received either oral azathioprine (2 mg/kg) (Group 1) or oral SDZ RAD (1.5 mg/kg) (Group 2). Histologic alterations were graded from 0 to 3 based on repeatedly removed implants during a follow-up period of 3 months. RESULTS Total epithelial destruction and permanent luminal obliteration occurred within 37 days in Group 1. After an initial grade of 2.3+/-0.3 destruction, epithelial recovery was evident in Group 2 (P < 0.01), and the bronchi stayed patent. Cartilaginous destruction was milder in Group 2 (P < 0.05) than in Group 1, but chondrocytic proliferation was more intense (P < 0.05). Alveolar tissue and native structures of the bronchial wall were destroyed in Group 1, but preserved in Group 2 with total recovery after a mild-grade initial necrosis. CONCLUSIONS Unlike the standard triple therapy, SDZ RAD combined with cyclosporine and methylprednisolone preserves the pulmonary allografts and prevents epithelial destruction and subsequent luminal obliteration. This suggests that this regimen might efficiently suppress obliterative bronchiolitis and improve long-term results in lung transplant recipients.

Diagnosis and Prognostic Factors in Malignant Pleural Mesothelioma: A Retrospective Analysis of Sixty-Five Patients

This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma.

Mortality from amyotrophic lateral sclerosis in Finland, 1986-1995

Objective– To study the possible changes, between 1986 and 1995, in the mortality due to amyotrophic lateral sclerosis (ALS) among Finnish patients. Materials and methods– A total of 1000 deaths from ALS were extracted from the Finnish Death Certificate Register for the study years. General population data were obtained from the Statistical Yearbooks of Finland. Results– From a death rate of 1.54/100,000 in 1986 an increase to 2.27/100,000 in 1995 was observed. Since 1963 the number of ALS deaths has tripled. The documented increased life‐expectancy in Finland correlates with the ALS death rate, at least partly explaining the increase. Contrary to other countries, on the whole equal numbers of men and women died of ALS. Women tended to be older than men when they died of ALS. Conclusion– In accordance with other countries ALS mortality in Finland is steadily increasing.

Pulmonary toxicity after radiotherapy in primary breast cancer patients: Results from a randomized chemotherapy study

PURPOSE Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC x 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high-dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. METHODS AND MATERIALS Lung function tests (FVC, FEV1, and DL(CO)) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. RESULTS Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, -6.5%, p = 0.0005; CTCb: -2.0%, p = 0.21; tailored FEC vs. CTCb: -4.5%, p = 0.05). DL(CO) decreased significantly in both groups (tailored FEC: mean difference, -11.2%, p < 0.0001; CTCb: -5.6%, p = 0.02; tailored FEC vs. CTCb: -5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC (p < 0.0001) and by 2.5% in patients treated with CTCb (p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). CONCLUSIONS Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT).