Biomedical subjects
Publications and source records attributed to J Salo.
Recently the physics of ballistic phonon propagation in anisotropic crystals has been studied with new phonon-imaging methods. In this paper we consider nondiffracting waves that can propagate in anisotropic crystals and analyze their properties that emerge specifically due to the anisotropy. We further present a detailed generation and detection scheme for the experimental verification of the wave modes considered.
OBJECTIVES: There is little reliable quantitative information on preoperative quality of life of patients with brain tumours. The aim of this study was to clarify the effect of the volume, location, and histological grade of brain tumours on the preoperative quality of life of patients. METHODS: The study population consisted of 101 successive patients with brain tumour at Oulu Clinic for Neurosurgery studied with CT or MRI for preoperative determination of tumour location and size. The Nottingham health profile (NHP) and Sintonen's 15D scale were used at that time to measure quality of life. RESULTS: Tumour size did not correlate linearly with impairment of quality of life. Large tumours (>25 ml) were associated with poorer quality of life than small tumours (< or =25 ml). The patients with a tumour located on the right side or in the anterior region reported a poorer quality of life than those with a tumour on the left side or posteriorly. Quality of life assessments made by doctors using the Karnofsky performance scale showed no differences between the two hemispheres. Patients with the most malignant gliomas (grades III-IV) displayed the poorest quality of life. CONCLUSIONS: Large tumours apparently damage several parts of the brain and/or raise intracranial pressure to a level that exceeds the brain's compensatory capacity. Contrary to earlier understanding, tumours in the right hemisphere seemed to be related to poorer quality of life. This effect was especially clear in the patients' subjective evaluation of their quality of life. As the location of the brain tumour thus affects perceived quality of life, any measurements of the quality of life of patients with brain tumours should take into account the location and laterality of the tumour.
BACKGROUND AND AIMS: In this study the results of endovascular treatment of aortic aneurysms in Finland are presented and compared to the results of the Eurostar registry. MATERIAL AND METHODS: A total of 229 patients with aortic aneurysm were treated in five different Finnish centres during 1996-2000. The data of these patients were collected prospectively by surgeon or interventional radiologist involved. During the same period of time 2464 patients were registered in the Eurostar registry. RESULTS: The procedure was performed successfully in 97% of patients in Finland, and the 30-day mortality was 0,9%. A graft limb thrombosis was detected in 9% of the patients in Finland. A permanent primary endoleak at the first 30-day control was seen in 23 patients (10%). During the follow-up 17 secondary endoleaks (7%) were detected. A secondary intervention was necessary in 26% of the patients. Three patients (1.3%) had late rupture of the abdominal aortic aneurysm. CONCLUSIONS: According to the Finnish short-time results, endovascular treatment of aortic aneurysms is safe and associated with relatively low morbidity and mortality. The mid-term results are more disappointing with relatively many graft thromboses and endoleaks, and a frequent need of secondary interventions.
The nitrogen-containing bisphosphonate alendronate inhibits osteoclast-mediated bone resorption through inhibition of the mevalonate pathway. This results in impaired protein prenylation and may affect the function of small GTPases in osteoclasts. Since these proteins are important regulators of vesicle transport in cells, we investigated the possible interference of alendronate with these processes in isolated rat osteoclasts. We show here that alendronate-induced inhibition of bone resorption coincides with accumulation of tartrate-resistant acid phosphatase- and electron dense material-containing tubular vesicles in osteoclasts. Alendronate-induced changes in osteoclasts also included widening of the sealing zone areas and incomplete organization of tight attachments and ruffled borders. Osteoclasts also appeared partially detached from the bone surface, and organic matrix was typically dissolved only at the edges of the resorption pits on alendronate-coated bone slices. In contrast, resorption pits on the control and clodronate-coated bone slices were thoroughly resorbed. Inhibition of bone resorption by alendronate was not, however, related to a decrease in osteoclast number. In conclusion, our findings suggest that alendronate inactivates osteoclasts by mechanisms that impair their intracellular vesicle transport, apoptosis being only a secondary phenomenon to this.
The alpha subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor has several isoforms that result from alternative splicing events. Two forms, alpha-1 and alpha-2, have intracytoplasmic sequences that are identical within a membrane-proximal domain but differ completely distally. Variant and mutated GM-CSF receptor alpha subunits, along with the beta subunit (beta(c) protein) were expressed in M1 murine leukemia cells. and the ability of the receptors to signal for differentiation events and to activate Jak/Stat signaling pathways was examined. All cell lines expressing both alpha and beta(c) proteins exhibited high-affinity binding of radiolabeled human GM-CSF. Receptor alpha subunits with intact membrane-proximal intracellular domains could induce expression of the macrophage antigen F4/80 and down-regulate the expression of CD11b. Addition of recombinant human GM-CSF to cells expressing alpha-1 subunits induced the expression of CD86 and tyrosine phosphorylation of Jak-2 and its putative substrates SHPTP-2, Stat-5, and the GM-CSF receptor beta(c) subunit. Cells containing alpha subunits that lacked a distal domain (term-3) or had the alternatively spliced alpha-2 distal domain showed markedly decreased ability to support tyrosine phosphorylation of Jak-2 and its substrates or to up-regulate CD86. Ligand binding induced stable association of the alpha-1 subunit and beta(c) protein. In contrast, the alpha-2 subunit did not stably associate with the beta(c) subunit. These data identify potential molecular mechanisms for differential signaling of the alpha-1 and alpha-2 proteins. The association of unique signaling events with the 2 active GM-CSF alpha subunit isoforms offers a model for variable response phenotypes to the same ligand.
We screened 18 specimens of Barrett adenocarcinoma for genetic alterations using comparative genomic hybridization (CGH) to analyze DNA copy number changes. The most common gains were at 20q (56%) and 17q (39%). High-level amplifications were observed in the same chromosomes. The most common losses were in chromosomes 4 (22%) and 5 (22%). Other recurrent changes were gains of chromosomes 8, 10q, and 13. We compared the copy number changes in Barrett adenocarcinoma and those previously reported in the intestinal type of stomach carcinoma. The similarities we found suggest a common molecular pathogenesis, whereas dissimilarities seen between Barrett adenocarcinoma and esophageal squamous cell carcinoma are in keeping with a well-known different etiology.
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Normal bone remodeling and pathological bone destruction have been considered to be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid- and cathepsin K-driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.
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OBJECTIVES: To determine whether prostate-specific antigen (PSA) complexed to alpha(2)-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and total PSA (tPSA) for the diagnosis of prostate cancer (PCa). METHODS: In a series of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA, tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific immunoassays. The assay for PSA-A2M was based on the immunoadsorption of immunoreactive PSA in serum and the measurement of the PSA immunoreactivity released by denaturation of PSA-A2M at pH 11.4. RESULTS: The median proportion of PSA-A2M [ %PSA-A2M=PSA-A2M/(tPSA+PSA-A2M)] and that of fPSA ( %fPSA=fPSA/tPSA) were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively). The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH (P <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for PCa, 57% of patients with "falsely" elevated PSA concentrations (4 to 10 ng/mL) caused by BPH could be correctly identified without missing patients with PCa compared with 18% of the patients with BPH but not PCa using %fPSA alone. CONCLUSIONS: Measurement of the sum of %PSA-A2M and %fPSA in serum significantly improves the cancer specificity of the PSA test compared with the use of tPSA and %fPSA.
OBJECTIVES: This article reports a cost-effectiveness analysis of targeted screening for abdominal aortic aneurysm (AAA). A major emphasis was on the estimation of distributions of costs and effectiveness. METHODS: We performed a Monte Carlo simulation using C programming language in a PC environment. Data on survival and costs, and a majority of screening probabilities, were from our own empirical studies. Natural history data were based on the literature. RESULTS: Each screened male gained 0.07 life-years at an incremental cost of FIM 3,300. The expected values differed from zero very significantly. For females, expected gains were 0.02 life-years at an incremental cost of FIM 1,100, which was not statistically significant. Cost-effectiveness ratios and their 95% confidence intervals were FIM 48,000 (27,000-121,000) and 54,000 (22,000-infinity) for males and females, respectively. Sensitivity analysis revealed that the results for males were stable. Individual variation in life-year gains was high. CONCLUSIONS: Males seemed to benefit from targeted AAA screening, and the results were stable. As far as the cost-effectiveness ratio is considered acceptable, screening for males seemed to be justified. However, our assumptions about growth and rupture behavior of AAAs might be improved with further clinical and epidemiological studies. As a point estimate, females benefited in a similar manner, but the results were not statistically significant. The evidence of this study did not justify screening of females.
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A unified spectral and temporal representation is introduced for nondiffracting waves. We consider a set of elementary broadband X waves that spans the commonly considered nondiffracting wave solutions. These basis X waves have a simple spectral representation that leads to expressions in closed algebraic form or, alternatively, in terms of hypergeometric functions. The span of the X waves is also closed with respect to all spatial and temporal derivatives and, consequently, they can be used to compose different types of waves with complex spectral and spatial properties. The unified description of Bessel-based nondiffracting waves is further extended to include singular Neumann and Hankel waves, or Y waves. We also discuss connections between the different known nondiffracting wave solutions, and their relations to the present unified approach.
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Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks. Natural interferon (IFN)-alpha (3 MIU days 2-10) and recombinant IFN-gamma1b (50 microg m(-2) on days 2, 6 and 10) were injected subcutaneously after each MTX dose. At the end of MTX treatment the IFNs were continued as maintenance therapy until disease progression. Seven partial responses were observed among 24 patients evaluable for response (response rate 29%, 95% confidence interval 13-51%). Median duration of response was 10 months (range 3-24 months). Median survival was 17 months and 1-year and 2-year survival rates 62% and 31% respectively. The toxicity of the chemo-immunotherapy was acceptable. Treatment was stopped in one patient who developed grade IV neurological toxicity. MTX dose reductions were rare (two patients with grade 1-2 renal toxicity). The combination of high dose MTX and IFN-alpha and IFN-gamma is active against malignant pleural mesothelioma and well-tolerated. The survival rates are encouraging.
In order to assess the appropriateness of lung cancer surgery in the elderly and determine optimal subjects and resection procedure, 75 patients operated on in 1976-1996 at age > or =75 years (including 13 > or =80) were followed up. The operations included limited resection (8), lobectomy (47), bilobectomy (10) and pneumonectomy (10) and were judged to be radical in 59 cases (79%). Perioperative mortality was 9% and morbidity 29%, including 21% major complications. Cumulative 5-year survival was 32%, in stages IA-IIB 27-41%, and cancer-related survival 61-79%. Mortality did not differ significantly between resection types, but morbidity did. Nor did mortality, morbidity or survival differ between the age groups 75-79 and > or =80 years. In stage I cancer there was no significant difference in survival or cancer-related survival after lobectomy vs limited resection. We conclude that age, even >80 years, is not incompatible with curative resection. Lobectomy is the treatment of choice, but a less radical resection may be advisable if there is comorbidity. If more extensive resection is performed, the individual surgical risk must be weighed against the potential long-term benefit.
Mycoplasma hominis infections are easily missed because conventional methods for bacterial detection may fail. Here, 8 cases of septic mediastinitis due to M. hominis are reported and reviewed in the context of previously reported cases of mediastinitis, sternum wound infection, pleuritis, or pericarditis caused by M. hominis. All 8 patients had a predisposing initial condition related to poor cardiorespiratory function, aspiration, or complications related to coronary artery surgery or other thoracic surgeries. Mediastinitis was associated with purulent pleural effusion and acute septic symptoms requiring inotropic medication and ventilatory support. Later, the patients had a tendency for indolent chronic courses with pleuritis, pericarditis, or open sternal wounds that lasted for several months. M. hominis infections may also present as mild sternum wound infection or as chronic local pericarditis or pleuritis without septic mediastinitis. Treatment includes surgical drainage and debridement. Antibiotics effective against M. hominis should be considered when treating mediastinitis of unknown etiology.