Biomedical subjects

A Michalski

Publications and source records attributed to A Michalski.

At least 19 recordsLinked to original sources

PubMed2006

Transmission electron microscopy studies of microstructure of Ti-Nb and Ti-Ta alloys after ball milling and hot consolidation.

Two Ti alloys with compositions Ti-10Ta and Ti-10Nb (at.%) were milled in a high-energy mill for a maximum of 80 h in an argon atmosphere. A nanocrystalline structure of alpha-Ti(X) (X = Ta or Nb) solid solution was formed in both investigated alloys after milling, as shown by X-ray diffraction. Transmission electron microscopy observations of powders milled for 80 h revealed chemical inhomogeneity of particles in nanometre-scale regions and an average crystallite size of about 10 nm. The pulse plasma sintering method was applied for hot consolidation of milled powders. The mean density of pulse plasma sintering compacts of Ti-Nb alloy was about 99.5% of the theoretical value, whereas the density of the Ti-10Ta sample was lower, close to 92% of the theoretical value. Transmission electron microscopy observation of compacted samples showed that the sintering process caused the formation of a two-phase alpha + beta structure in both investigated alloys, with a mean grain size of 220 nm. The chemical inhomogeneity and high degree of deformation in nanometre-scale regions of milled powders led to a martensitic transformation, resulting in formation of a 9R martensite structure.

Journal Article↗

PubMed2005

Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation.

AIM: To identify a gene linking microphthalmia with cyst with early onset medulloblastoma. METHODS: Mutation analysis of the PTCH gene. RESULTS: A mutation in exon 10 of the PTCH gene was identified, confirming a diagnosis of Gorlin syndrome. CONCLUSIONS: This is the first genetically identified mutation giving rise to microphthalmia with cyst and provides a valuable link in the eye developmental gene pathway.

Basal Cell Nevus Syndrome↗

PubMed2003

Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12.

Neuroblastoma immunotherapy using cytokine-modified tumour cells has been tested in clinical trials. However, because of the complex nature of antitumour immune responses, a number of therapies may be required for complete tumour eradication and generation of systemic immunity. We report here the improved antitumour effect of two cytokines, interleukin-2 (IL-2) and interleukin-12 (IL-12), when coexpressed by neuroblastoma cell lines. Initially, transfection of human and mouse neuroblastoma cell lines resulted in high expression levels of biologically active IL-2 and IL-12 in vitro. These cytokines when expressed by transfected Neuro-2A cells completely abolished their in vivo tumorigenicity in a syngeneic neuroblastoma model. Vaccination of established tumours with IL-12-producing cells exhibited a clear effect with reduced tumour growth in the presence of IL-2. In vivo depletion studies showed that CD4(+) and CD8(+) T cells mediate the response against cytokine-producing cells. These results suggest that IL-2 and IL-12, when cotransfected in tumour cells, are effective against established disease and provide a promising immunotherapeutic approach for the treatment of neuroblastoma.

Adjuvants, Immunologic↗

PubMed2003

Tolerance of nitrosurea-based multiagent chemotherapy regime for low-grade pediatric gliomas.

The aim of this study was to compare tolerance of a nitrosurea-based regime with 'standard' therapy of vincristine (VCR) and carboplatin for low-grade gliomas. Ten children with low-grade gliomas received second line therapy consisting of thioguanine, procarbazine, CCNU and vincristine (TPCV). Two groups were identified, i.e. patients who had either experienced significant toxicity with carboplatin (reaction group) or had re-growth of their tumor (re-growth group) following first line therapy. Patients were evaluated for toxicity. Data was available on nine patients. Patients in the reaction group completed a mean of 3 cycles of TPCV (range 2-4). One patient stopped after 2 cycles of TPCV due to tumor progression and died 3 months later and one remained on therapy at the time of analysis. Patients in the re-growth group received a mean of 5.5 cycles of TPCV (range 4-8). Treatment was discontinued in one patient after 4 cycles due to hematological toxicity, one experienced tumor progression after 4 cycles and one stopped after 6 cycles because of neurological toxicity. There was no difference in the incidence of grade 3/4 neutropenia or thrombocytopenia, transfusion requirements or delays in chemotherapy between TPCV and VCR/carboplatin in either group. There were no serious infections or toxic deaths. Seven of nine patients had stable disease at a mean of 13 months of follow up. TPCV therapy is a well-tolerated regime with comparable bone marrow toxicity to VCR/carboplatin. Significant disease stabilization was observed with TPCV and hence this regime may be used as second line therapy.

Adolescent↗

PubMed2001

Neuroblastoma in monozygotic twins--a case of probable twin-to-twin metastasis.

Concordance for neuroblastoma in monozygotic twins has been reported only rarely, and the cause of the shared pathology has not been established. We describe a case of infant monozygotic twins developing tumours that were morphologically, clinically and molecularly indistinguishable, but with a delay of 6 months between times of presentation. Both tumours were metastatic and had amplification of MYCN and deletion at 1p36. Twin 1, who developed neuroblastoma first, had constitutional karyotype abnormalities in at least 5% of peripheral blood mononuclear cells involving 1p and 3p, and a deletion of 1q44 in 21% of cells. Twin 2 had a normal constitutional karyotype and lacked rearrangement or deletion of these regions. We propose an acquired neuroblastoma predisposition specific for twin 1, and in utero metastatic spread of tumour cells to twin 2 via the shared placental circulation.

DNA, Neoplasm↗

PubMed2001

Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children.

BACKGROUND: Congenital alveolar rhabdomyosarcoma (RMS) is extremely rare and invariably fatal with current therapy. Its clinical presentation is unusual and is distinct from RMS in older children, with > 50% of patients presenting with multiple cutaneous metastases. To the authors' knowledge, the biology of this condition has not been studied to date. METHODS: The clinical and pathologic findings of four cases of congenital RMS are presented along with those of other cases found in the literature. Molecular analysis was undertaken to detect the characteristic chromosomal translocations of alveolar RMS in three cases with suitable material. RESULTS: To the authors' knowledge, there are no recorded survivors of congenital alveolar RMS. Clinical and histopathologic findings in four patients with congenital alveolar RMS are detailed along with treatment responses. It now is recognized that tumor specific translocations can be detected in the majority of cases of alveolar RMS using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. However, detailed molecular analysis using RT-PCR was unable to detect the presence of either the classic t(2;13) or variant t(1;13) translocation in three cases analyzed at the molecular level. CONCLUSIONS: To the authors' knowledge the optimal treatment for this rare tumor is not known. The longest survivor in the current series underwent myeloablative therapy with peripheral stem cell support, suggesting that more intensive treatment may be of value in this rare condition. None of the three tumors analyzed by RT-PCR harbored characteristic RMS translocations. The molecular biology of this highly malignant and aggressive congenital tumor appears to be different from alveolar RMS in older children and warrants further investigation.

Female↗

PubMed2001

Imaging of non-central nervous system primitive neuroectodermal tumours: diagnostic features and correlation with outcome.

AIM: To document the varied radiological features before, during, and after treatment of non-Central Nervous System Primitive Neuroectodermal Tumours (PNETs), which are rare tumours of childhood. MATERIALS AND METHODS: Thirty-three children with PNETs have been treated at our institution between 1990 and 1999. Full radiological and clinical follow-up was obtained in 29 (17 females, 12 males). Imaging was retrospectively reviewed, with particular attention to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). RESULTS: Age range at diagnosis was 0-16 years old (mean 4.4 years). There were five main sites of tumour: head and neck (n = 7), scapula/axilla (n = 2), chest (n = 11), abdomen (n = 3), and spinal/paraspinal (n = 6). Overall mortality was 62%. Tumours of the scapula or paraspinal region appear to show better survival than other sites. Of 23 patients who had Tc99m-methylene diphosphonate (MDP) bone scans at diagnosis, four patients showed widespread distant metastases, seven showed focal increased uptake in an adjacent bone only, and 12 had normal examinations. CT was performed in 25 patients and MRI in 20, both at diagnosis and follow-up. Average size of tumours at presentation was 4.5 cm in the paraspinal, head and neck and scapular regions and 7.5 cm in the chest and abdomen. Tumours were typically of soft tissue density on CT with the larger (>5 cm) masses tending to be more heterogeneous in character. The lesions were slightly higher signal than muscle on T1-weighted (T1W) MRI and all masses were heterogeneous on T2W sequences. Calcification was uncommon (n = 6) and generally sparse. Tumours tended to displace adjacent soft tissue structures such as vessels and bronchi rather than invade or encase them. Tumours rarely crossed the midline. Local or bony invasion was seen in 12 patients at diagnosis. Metastases were identified in the lung (n = 5), pleura (n = 2), brain (n = 4), bone (n = 4), lymph nodes (n = 2), liver (n = 2), subcutaneous tissues (n = 2), kidney (n = 1) and peritoneum (n = 1). CONCLUSIONS: Imaging characteristics of non-CNS PNETs are described. Tumours tend to displace rather than encase adjacent structures; local invasion occurred in 43%. Tumour calcification is uncommon. Poor prognostic features included the presence of distant metastases at diagnosis (all four patients with distant metastases at diagnosis died), but even patients without metastatic disease have a relatively poor prognosis.

Abdominal Neoplasms↗

PubMed2001

Interactions between P300 and passive probe responses differ in different visual cortical areas.

The regulation of firing thresholds of cortical neurons was suggested as one of the mechanisms underlying the generation of the P300 component in the human event-related potential. According to this hypothesis, the detection of an important stimulus produced the widespread inhibition of "irrelevant" networks, interrupting their ongoing activity and facilitating the analysis of selected information. In the present experiment, the responsiveness of visual cortex was evaluated during the P300 potential by using additional, probing stimuli. Large separation of the cortical visual fields permitted separate analysis of the input and more advanced stages of processing. Responses were recorded from Fz, Cz, Pz and Oz scalp sites. P300 waves were evoked by visual, mentally counted stimuli in a standard "odd-ball" procedure. Visual probes were delivered 200, 300, 400, 500, 700 and 1000 ms later. No responses to the probes were required. Significant suppression of responses to the probes delivered less than 400 ms after target stimuli was found in Oz and Pz but not in Cz or Fz. The suppression was not proportional to the voltage levels from which probe responses started. In Fz and Cz, latencies of probe responses were elongated if probes were delivered less than 400 ms after target stimuli. The results suggest that probe responses suppressed by the P300 potential in occipital and parietal cortex may be restored in frontal areas. In these areas the P300 potential could delay probe responses instead of suppressing them.

Adult↗

PubMed2001

[Plasminogen activators (t-PA and u-PA) and other fibrinolysis parameters in patients with atherosclerosis obliterans and diabetic macroangiopathy].

UNLABELLED: The aim of the study was to evaluate plasminogen activators in compare fibrinolysis parameters in patients with atherosclerosis obliterans (AO) and diabetic macroangiopathy (DM) of lover extremities. The study group consist of 40 patients with AO (mean age 59 years) and 40 with DM (mean age 61 years). All the patients were diagnosed as the II stage in Fontaine scale. Ischemia lover extremities were: aorta-hip, femoral-popliteal and peripheral dependent closure. The control group consist of 30 healthy volunteers (mean age 51 years). Concentration of: tissue plasminogen activator antigen (t-PA:Ag), urokinase plasminogen activator antigen (u-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) (ELISA), PAI-1 activity (PAI-1 act.), euglobulin lysis time (ELT) (Kowarzyk-Buluk method), fibrinogen, fibrin degradation products (FDP) (Merskey method) in blood plasma were evaluated. The results shows statistically higher concentrations of: t-PA:Ag, PAI-1:Ag, fibrinogen, and lower concentrations of u-PA:Ag and elongated ELT in blood plasma patients with AO and DM in compare with healthy volunteers. Comparing analysed parameters between patient groups shows higher concentration FDP in patients with AO than patients with DM. CONCLUSIONS: 1) Although elongated ELT in both groups it was shown evidence of the fibrinolysis activation in the shape of elevated FDP concentration. It was probably compensation for hypercoagulability. 2) Elevated t-PA:Ag concentration in patients with AO and DM is an evidence of the higher releasing of the endothelium in AO and DM.

Adult↗

PubMed2001

Do fibrinolytic proteins of human bile derive exclusively from gall bladder?

BACKGROUND: In this study we addressed the issue of whether fibrinolytic proteins are presented in gall bladder bile only or in choledochus bile as well. MATERIAL AND METHODS: Gall bladder bile was obtained from 20 patients (Group I) undergoing laparoscopic cholecystectomy. Bile from common bile duct was aspirated after insertion Kehr drainage from 9 patients (Group II). The concentrations of t-PA, u-PA, PAI-1 and PAI-2 were measured by ELISA. RESULTS: We have shown that in cholecystectomized patients fibrinolytic proteins can be detected in bile both from gall bladder and from choledochus. Mean concentrations of t-PA, u-PA, PAI-1 were lower in Group II (5.69 ng/ml vs 15.7; 0.46 ng/ml vs 0.7; 16.82 ng/ml vs 26.16 ng/ml) or nearly equal for PAI-2 (343.53 ng/ml vs 341.02). All differences were insignificant (p > 0.05). CONCLUSIONS: Based on these results we concluded that the entire biliary tree produces the fibrinolytic proteins thus this production is not restricted to the gall bladder as it was earlier reported [1].

Bile↗

PubMed2000

Expectation of an important event affects responses to irrelevant stimuli of different modalities.

Periodic alterations of event-related potentials (ERPs) were studied during "oddball" tasks. Sequences of randomly intermixed frequent (non-target) and rare (target) stimuli were presented. In visual experiments, these were flashes of light of two different colors. In auditory tests there were two tones of different frequencies. The instruction was to keep a mental count of each target stimulus. To study the alterations of the "state of the brain" produced by target detection, responses to non-targets immediately following targets were compared with responses to an eighth subsequent non-target stimulus. To evaluate the effect of such "brain states" on responses to stimuli of a different modality, additional visual stimuli (probes) were delivered after both auditory and visual "oddball" stimuli. It was found that responses to the eighth presentation of non-target stimulus were preceded by significant negative shift of recorded potential. This shift was smaller before the responses to non-targets immediately following the presentation of target stimuli. The difference was significant both in auditory and visual tests. Responses to "oddball" stimuli were little affected: only the reduction of P200 peaks in "after target" responses was significant in visual tests. Responses to probes showed stronger effects: when visual probes followed visual "oddball" stimuli, all three components measured (N100, P130 and P200) were shifted positively in responses to eighth presentations of non-targets. When visual probes were presented in auditory tests, only the amplitude of the N100 component was significantly affected.

Acoustic Stimulation↗

PubMed1999

The effect of accomplishment and failure on P300 potentials evoked by neutral stimuli.

The effects of emotional states of 'being successful' vs. 'being unsuccessful' were studied by measuring the P300 component of event-related potentials (ERPs). Nine subjects were instructed to reduce their P300 amplitude using feedback. Feedback was random but the relative probability of different signals created the situations of 'being successful' or 'being unsuccessful'. The probability of 'small' feedback was 0.7 in 'successful' and 0.15 in 'unsuccessful' trials. ERPs recorded without the feedback were used as a reference. Potentials, evoked by light stimuli in a standard 'odd-ball' procedure, were recorded from Fz, Cz and Pz scalp sites. The amplitudes of P300 components were reduced in 'unsuccessful' trials whereas in 'successful' trials they did not differ significantly from responses recorded without the feedback. There were no significant differences in peak latencies. These findings indicate that tonic emotional states affect the processing of neutral stimuli and that late components of ERPs can be useful indices in the analysis of these alterations. The results also indicate that the effects of positive and negative emotional states are not always reciprocal. Manipulated feedback is suggested as an useful model in the studies of emotions. Data can also facilitate the interpretation of the real feedback effects.

Adult↗

PubMed1999

Feedback processing as parallel task in P300 conditioning.

Previous reports on conditioning P300 amplitude indicated that downtraining produced a stronger effect than uptraining. This asymmetry can be due to the effect of drain on processing resources of the brain produced by the attempts to use feedback information (parallel task effect). Such a drain should reduce P300 amplitude regardless of the direction of training. The aim of the experiment was to demonstrate this effect. Event-related potentials (ERPs) evoked by light stimuli in a standard odd-ball procedure were recorded from Fz, Cz and Pz scalp sites. Subjects were instructed to enlarge or to reduce the P300 amplitude. The first 30 presentations of the target stimulus were analyzed during which the effect of learning should be negligible and processing of feedback information should be intensive. ERPs recorded during uptraining and downtraining were compared with the no-feedback recordings. As predicted, downtraining significantly reduced the P300 amplitude even in the first session of learning. Unexpectedly, uptraining recordings did not differ from no-feedback ERPs but differed significantly from downtraining waves. Such results support the prediction that feedback procedures involve a number of processes that alter the P300 amplitude even before the effects of learning can be expected. But if the hypothesis of the parallel task is to be accepted there must be another instantaneous process that compensates for P300 amplitude reduction during uptraining.

Adult↗

PubMed1999

[The influence of ozone therapy on endothelial damage markers in patients with atherosclerosis of lower extremities].

The aim of study was to evaluate the influence of the treatment with oxygen-ozone mixture on the blood plasma antigen concentration of tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) in patients suffering from atherosclerotic disease of lower extremities. The study was performed in the group of 28 (M/F 22/6) patients means aged 64.1 years with atherosclerotic diseases of lower extremities, in whom 2 weeks therapy with oxygen-ozone mixture was used. The control group consisted of 30 healthy volunteers in mean age 51.0 years. In the blood plasma obtained from the patients before and after treatment with oxygen-ozone mixture and from the control group determinations of t-PA and vWF antigen using ELISA were done. Both parameters were significantly increased in the patients before the treatment in comparison to the healthy controls. The treatment with oxygen-ozone therapy caused in patients slight statistically not significant raise of t-PA and vWF antigen showing the endothelial stimulation but not the destruction of vascular endothelium.

Adult↗

PubMed1998

Radiotherapy omitted in the treatment of selected children under 3 years of age with stage III favorable histology Wilms tumor.

BACKGROUND: Current treatment of stage III favorable histology (FH) Wilms tumor is surgery, radiotherapy to residual disease, and "triple" chemotherapy (vincristine, dactinomycin, and doxorubicin) for 12 months. This study tests the hypothesis that some stage III patients, especially very young children with minimal residual abdominal disease, might be successfully treated without radiotherapy, thereby avoiding the adverse late effects associated with radiotherapy. PROCEDURE: From 1984, radiotherapy was omitted from the treatment of 8 carefully selected children who were younger than 3 years of age at diagnosis with stage III Wilms tumor by virtue of microscopic residual disease after surgery and whose lymph nodes were not involved by tumors. They were followed with bimonthly abdominal ultrasound examinations to assess local control. RESULTS: Follow-up is now from 2 to 12 years (median 6 years) and 7 of the 8 children are alive and well with no abdominal recurrence. One child relapsed in the lungs and despite further treatment died of progressive disease. The disease-free survival (DFS) and overall survival (OS) are therefore both 87.5%. CONCLUSIONS: The DFS and OS in this admittedly small sample are consistent with the survival rates for stage III FH Wilms tumor in the first United Kingdom Children's Cancer Study Group (UKCCSG), North American (NWTS), and European (SIOP) Wilms Tumor studies, Larger numbers of patients are needed to determine whether or not this treatment approach is generally applicable, but we conclude that some children in this stage III "substage" may be treated successfully without radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Primitive neuroectodermal tumours: anatomic location, extent of surgery, and outcome.

BACKGROUND/PURPOSE: Primitive neuroectodermal tumours (PNET) are rare tumours sharing similar histology, immunohistochemistry, and cytogenetics to Ewing's sarcomas. The aim of the study was to document the effect of site of origin and the completeness of surgical excision on the outcome in infants and children with PNET. METHODS: All patients (n = 26) with PNET treated in our hospital during the last 6 years were included in the study. The diagnosis was based on the histopathologic findings and a positive MIC2 antibody test. The tumours were classified according to the Intergroup Rhabdomyosarcoma Study III, and were treated according to the UKEESG protocol for Ewing's Sarcoma. RESULTS: Complete remission (CR) was achieved in 52% of the patients completing their chemotherapy. Overall, survival was 42% (11 of 26). Tumours from the paraspinal and scapula areas responded relatively well (CR, 83%), whereas abdominal PNET did not respond to treatment. Tumours arising from the head, neck, or chest had an intermediate prognosis (37% survival). Three of the 10 patients who had a complete excision of the tumour died of progressive disease. CONCLUSIONS: Complete surgical excision reduced the risk of local recurrence but did not prevent metastatic spread. These data indicate that PNET have a worse prognosis and different favourable sites than other sarcomas. New treatment strategies are necessary for these rare tumours.

Abdominal Neoplasms↗

PubMed1998

Potential prognostic factors of relapse-free survival in childhood optic pathway glioma: a multivariate analysis.

There is still no consensus on the natural history and optimal management of optic pathway gliomas (OPG) in children. In order to tackle optimal management issues, we need to clearly understand the prognostic and confounding factors affecting relapse of OPG. We propose the use of the Cox proportional hazards (PH) model in a retrospective study of childhood OPG of 69 children seen from 1977 to 1994. We have developed a comprehensive model capable of multivariate analyses and handling time-dependencies. Our studies showed that relapse-free survival improves with increasing age, the presence of neurofibromatosis 1 (NF1), and chemotherapy and radiotherapy (p < 0.0005). Sex, tumor position and surgery do not significantly affect survival. Older children with NF1 have extremely good prognosis. We noted behavior that departs from the strictly proportional hazards model, but results were inconclusive.

Adolescent↗

PubMed1998

The effect of tonic pain on processing the non-painful stimuli indexed by late components of event-related potentials.

Event-related potentials (ERPs) evoked by light flashes and auditory tones in a standard odd-ball procedure were recorded from Fz, Cz and Pz scalp sites. Tonic pain was evoked by immersion of the hand in cold water (5 degrees C). Significant effects of pain were found in responses to target stimuli but not in responses to non-target stimuli. P300 wave was affected more than the earlier P200 component. The reduction of P300 amplitude was the strongest effect, both in auditory and visual tests. P300 latency was not significantly affected. Difference curves (target minus non-target ERPs) showed the additional effects: latency of P200 component was elongated and its amplitude enlarged but only in auditory experiments. In control experiments with warm water stimulation no significant alterations of P300 or P200 components were found. The results show that the effect of tonic pain is specific: it predominantly affects the processes that manifest themselves as amplitude changes of P300 components in responses to target stimuli.

Adult↗