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Biomedical subjects

J Michalski

Publications and source records attributed to J Michalski.

At least 19 recordsLinked to original sources

Molecular structure, IR and Raman spectra as well as DFT chemical calculations for alkylaminoacetylureas: vibrational characteristics of dicarbonylimide bridge.

The present work reports room temperature IR and Raman study of R-NH-CH2-CO-NH-CO-NH2 alkylaminoacetylureas (R=C3H7, C4H9, C5H11, C6H13, C7H15, C8H17, C9H19, C10H21, C12H25, C14H29, C16H33 and C18H37). The experimental energy levels have been compared to those obtained from DFT chemical quantum calculations performed with the use of B3LYP/6-31G (d,p) basis for the R=C3H7 derivative. Energies of 66 vibrational states have been calculated for this molecule. Its molecular symmetry was taken as C1 and was optimized in the both quantum models applied. The role of the hydrogen bond in the stabilization of the structure has been analyzed.

Copper↗

Second-generation recombination-based in vivo expression technology for large-scale screening for Vibrio cholerae genes induced during infection of the mouse small intestine.

We have constructed an improved recombination-based in vivo expression technology (RIVET) and used it as a screening method to identify Vibrio cholerae genes that are transcriptionally induced during infection of infant mice. The improvements include the introduction of modified substrate cassettes for resolvase that can be positively and negatively selected for, allowing selection of resolved strains from intestinal homogenates, and three different tnpR alleles that cover a range of translation initiation efficiencies, allowing identification of infection-induced genes that have low-to-moderate basal levels of transcription during growth in vitro. A transcriptional fusion library of 8,734 isolates of a V. cholerae El Tor strain that remain unresolved when the vibrios are grown in vitro was passed through infant mice, and 40 infection-induced genes were identified. Nine of these genes were inactivated by in-frame deletions, and their roles in growth in vitro and fitness during infection were measured by competition assays. Four mutant strains were attenuated >10-fold in vivo compared with the parental strain, demonstrating that infection-induced genes are enriched in genes essential for virulence.

Animals↗

Cloning, expression and characterization of the CHO cell elongating factor (Cef) from Vibrio cholerae O1.

CHO cell-elongating factor (Cef) is a recently identified putative virulence factor of Vibrio cholerae. Our previous studies show that this 85 kDa protein elongates CHO cells, causes fluid accumulation in suckling mice and has esterase activity. In this study, the cef gene was cloned in Escherichia coli using a yeast vector and subsequently expressed in the yeast Pichia pastoris. The cef genes from V. cholerae candidate vaccine strains JBK 70 and CVD 103-HgR were sequenced and found to be nearly identical (100 and 99.9% respectively) with an open reading frame (ORF) from the published sequence of V. cholerae N16961. Cloned toxin was purified to homogeneity in 3 steps using anion exchange, hydrophobic interaction and gel filtration chromatography. The size of cloned Cef on SDS-PAGE gels was 114 kDa. The increased size was probably due to glycosylation by the yeast since cloned protein reacted strongly with a glycoprotein stain. The cloned protein could not be directly sequenced, but when treated with trypsin, yielded a protein fragment with an amino acid sequence that matched the sequence predicted for the Cef protein. The purified cloned protein had esterase and CHO cell activity, but no suckling mouse activity.

Animals↗

The efficacy and safety of once-daily Kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy.

This multicenter, randomized, double-blind study compared the efficacy and safety of once-daily oral granisetron 2 mg (n = 134) and placebo (n = 126) as prophylaxis for nausea and emesis in patients receiving upper abdominal fractionated radiotherapy. Patients were scheduled to receive 10-30 fractions of radiotherapy; granisetron (two 1-mg tablets) or placebo was administered 1 hr before radiotherapy on each scheduled treatment day. Treatment comparisons were made at 24 hr and at 10 and 20 fractions. Patients treated with granisetron experienced greater emetic control than those treated with placebo as evidenced by median times to first emesis (35 vs. 9 days, p < 0.001) and first nausea (11 vs. 1 day, p < 0.001). Overall endpoint analysis showed that proportionally more granisetron than placebo patients were emesis free (57.5% vs. 42.1%, p = 0.0047) and nausea free (30.6% vs. 16.7%, p = 0.0042). Furthermore, 25% more granisetron-treated than placebo-treated patients were emesis free and 20% more were nausea free on at least 80% of study treatment days. The most commonly reported adverse experiences in granisetron-treated patients were diarrhea, asthenia, and constipation. These findings demonstrate that a once-daily, 2-mg dose of oral granisetron is well tolerated and significantly more effective than placebo in preventing nausea and emesis induced by fractionated radiotherapy to the upper abdomen.

Abdomen↗

The effect of nitric oxide donors and L-arginine on the gastric electrolyte barrier.

The potential difference across the stomach wall (PD) is determined by the gastric mucosal barrier. The decrease in the PD evoked by "the barrier breakers", e.g. aspirin, ethanol or bile acids is believed as a sensitive index of the mucosal damage. The effect of glyceryl trinitrate (GTN), isosorbide dinitrate (IDN) and molsidomine (MOL)--all exogenous donors of nitric oxide (NO), as well as L-arginine (L-ARG), which is a substrate for NO-synthase and Nomega-nitro-L-arginine (L-NNA), a non-selective NO synthase inhibitor on the gastric electrolyte barrier were studied against the gastric damage induced by ethanol. All NO donors given intragastrically alone caused only moderate, not significant changes in the PD and failed to affect the mucosal barrier, while L-NNA slightly decreased the PD. The NO donors and L-arginine applied as pretreatment prior to ethanol resulted in diminishing of its damaging action that was similar for all these drugs, while L-NNA intensified both the injury and the drop in the PD values caused by ethanol. In summary, our results showed the protective effect of endogenous nitric oxide from L-ARG and that originating from GTN, MOL and IDN on the gastric electrolyte barrier, supporting involvement of nitric oxide in the mechanism of gastric protection in the stomach.

Animals↗

[Lateral lumbar disk herniation].

The authors present the clinical evaluation of 41 patients with extreme lateral disc herniation in the lumbar spine. This group of patients represented 3.1% of all patients operated to to discopathy of the lumbar spine at the Department of Neurosurgery of the Medical Academy of Białystock in the years 1988-1997. Males constituted 95.1% of the study series, with an age range 41-60 years. In 92.7% of the patients extreme lateral herniation was diagnosed either at L4-L5 level or L5-S1 level. In 78.1% of the cases different types of motoric disturbances were observed, while in 65.8% radicular type disorders in superficial sensibility were noted.

Adult↗

[Early results of surgical treatment of herniated nucleus pulposus in the lumbar spine in adults patients].

Between 1978 and 1997, 2250 patients underwent surgery due to nucleus pulposus herniation in the lumbar spine at the Department of Neurosurgery of the Medical Academy in Białystok. Surgery was performed on 718 women (31.9% of the cases) and 1532 men (68.1% of the cases) age ranging from 19 to 71 years. In 90.1% of cases herniation was found at levels L4-L5 and L5-S1. In most cases the herniated disc was removed following a fenestration (58.7% of the cases) or following hemilaminectomy of the vertebral arch (28.5% of the cases). Basing on a questionnaire sent out 12 months post-surgery 78.3% of the female patients and 68.3% of the male patients evaluated the results of the above treatment as very good. Within the 12 months observation follow-up period, 9.9% of the analyzed group underwent repeated surgery.

Adult↗

Late posttraumatic epilepsy in patients with an alcoholic problem treated surgically for posttraumatic chronic subdural hematomas.

The frequency and time of late posttraumatic epilepsy in 34 patients (6 women and 28 men) was evaluated on the basis of a three-year observation and performed examinations (CT of the head and EEG). These patients were treated surgically in the years 1989-1994 in the Department of Neurosurgery of the Medical Academy of Białystok due to chronic posttraumatic subdural hematoma. On the basis of environmental and family interviews it was concluded that 41.1% of the patients operated systematically abuses alcohol. Within 14-30 minutes following the surgery, seizures of late posttraumatic epilepsy took place in 20.6% of patients. They took place over eight times more frequently in the case of patients with alcohol problems that in the ones without such problems.

Adult↗

[Anamnestic and anthropometric assessment of patients with herniated lumbar intervertebral disc].

The paper presents results of anamnestic and anthropometric assessment of patients with herniated lumbar intervertebral disc operated in the Department in the years 1978-1987 (983 patients) and in the decade 1988-1997 (1308 patients). Recent decade brought 33.1% increase in disectomies. Typically, discopathy patient is tall individual, with relatively high BMI and aged between 19 and 48 years. The number of female patients increased by 8.2% in recent decade and traumatic origin of the disc herniation was noted in 8.8% more than previously. Special attention should be paid to the twofold increase of female smokers among patients operated due to discopathy.

Adult↗

The Vibrio cholerae genome contains two unique circular chromosomes.

Vibrio cholerae, the etiologic agent of the diarrheal disease cholera, is a Gram-negative bacterium that belongs to the gamma subdivision of the family Proteobacteriaceae. The physical map of the genome has been reported, and the genome has been described as a single 3.2-Mb chromosome [Majumder, R., et al. (1996) J. Bacteriol. 178, 1105-1112]. By using pulsed-field gel electrophoresis of genomic DNA immobilized in agarose plugs and digested with the restriction enzymes I-CeuI, SfiI, and NotI, we have also constructed the physical map of V. cholerae. Our analysis estimates the size of the genome at 4.0 Mb, 25% larger than the physical map reported by others. Our most notable finding is, however, that the V. cholerae chromosome appears to be not the single chromosome reported but two unique and separate circular megareplicons.

Chromosome Mapping↗

Prostate-specific antigen levels are higher in African-American than in white patients in a multicenter registration study: results of RTOG 94-12.

PURPOSE: To compare serum prostate-specific antigen (PSA) levels in a national sample of African-American and white men with prostate cancer, and to attempt to explain any differences by using self-reported individual-level socioeconomic status adjustments. METHODS AND MATERIALS: During 4 1/2 months in 1994-95, 709 patients with nonmetastatic prostate cancer were enrolled in this prospective study; 17.5% were African-American and 82.5% were white. Information about clinical stage, tumor grade, pretreatment PSA, type of insurance, and educational and income status was obtained. Serum PSA levels were measured and racial differences were found; how the differences were influenced by other patient- or tumor-related factors and if the differences could be explained by socioeconomic status disparities were determined. In univariate analyses, factors associated with the mean PSA levels were studied; log-converted values were used to yield a normal distribution. Multivariate analyses were done on log-linear models for description of association patterns among various categorical variables; a perfectly fitted model should have a correlation value (CV) of 1.0. RESULTS: The mean PSA level was higher in African-Americans (14.68 ng/ml) than in whites (9.82 ng/ml) (p = 0.001). Clinical stage (p = 0.001), Gleason sum tumor grade (p = 0.0001), educational level (p = 0.001), and household income (p = 0.03) were also associated with mean PSA levels; age, type of biopsy, and insurance status were not. Disease stage (p = 0.0001), grade (p = 0.0001), education (p = 0.07), and income (p = 0.02) were all associated with PSA levels for whites, but none of these factors were important for African-Americans (all p values > 0.1). The best fitted log-linear model (CV = 0.99) contained PSA (< 10, 10-20, and > 20), Gleason sum grade (2-5, 6-7, and 8-10), race, and two interactions: PSA by race (p = 0.0012) and PSA by Gleason sum (p = 0.0001). Models replacing race for either income (CV = 0.82) or education (CV = 0.82) or both (CV = 0.78) did not fit as well. CONCLUSIONS: African-Americans with nonmetastatic prostate cancer have higher serum PSA levels at diagnosis than whites, implying a higher tumor cell burden. Individual-level household income, education, or insurance status alone or in combination account for racial differences, but only partially.

Analysis of Variance↗

[Long-term results of surgical treatment of lumbar discopathy in children and adolescents].

Long-term results of surgical treatment of lumbar discopathy in 29 patients with 5 years follow-up (14 girls, 15 boys) operated at the age of 13-18 years in Neurosurgery Department, Medical University in Białystok between 1970 and 1993. Ten years follow-up was available in 26 patients (14 girls, 12 boys) operated between 1970 and 1988. Over period of 10 years 64.3% girls and 16.7% boys preserved recommended diet, 92.8% and 8.3% boys continued muscle strengthening exercises. Cigarette smoking abandoned 100% girls and none of the boys. Ten years after surgical treatment for lumbar discopathy excellent results were found in 85.7% females and 50% males.

Adolescent↗

[Immediate and short-term results of surgical treatment for lumbar disc protrusion in children and adolescents].

Twenty-nine patients aged 13-18 (14 girls and 15 boys) were treated surgically for lumbar intervertebral disc herniation at Department of Neurosurgery, Medical University in Białystok between 1970 and 1993. Clinical and radiological assessment of these patients and results of surgical treatment are presented. The condition was of traumatic origin in 30% of the cases. Neurological deficit has been found in 16.6% of children below 15 years of age and in 50% of patients up to 18 years of age. The results were rated good in 100% of the children up to 15 and in 87% adolescents below 18 years of age at one month follow-up and, respectively, 100% and 78.3% at one year follow-up.

Adolescent↗

Initial experience with quality assurance of multi-institutional 3D radiotherapy clinical trials. A brief report.

In 1992, a 3D Quality Assurance (3D QA) Center was established at the Mallinckrodt Institute of Radiology under the auspices of the Radiation Therapy Oncology Group (RTOG). The role of the 3D QA Center is to provide quality assurance reviews of external beam treatment planning and verification (TPV) information for patients enrolled in multi-institutional 3D radiotherapy treatment protocols. Computer hardware and software components have been implemented which allow participating institutions to submit (via either the Internet or magnetic tape) common format 3D TPV data for QA review including: volumetric CT image data, normal structure, tumor and target volume contours, digitally reconstructed radiographs or simulator (prescription) and portal radiographs, beam geometry, dose distributions, fractionation information, and dose-volume histograms. Prior to enrolling patients on a 3D radiotherapy treatment protocol, each participating institution is required to complete a 3D Facility Questionnaire documenting their 3D treatment planning capability. In addition, the successful completion of a protocol "dry run" test is required to demonstrate the participating institution's ability to submit a protocol complaint digital data set to the 3D QA Center prior to placing patients on the 3D CRT study. Two site specific (prostate and lung) phase I/II 3D dose escalation trials are currently accruing patients. The QA center reviews at a minimum the first 5 cases from each participating institution and spot checks subsequent submissions. For each case review the following parameters are evaluated: 1. data exchange compliance, 2. CT data quality, 3. target volume contours, 4. normal structure contours, 5. field placement, 6. field shape, 7. dose prescription, 8. dose uniformity, and 9. dose conformity. By April 1997, over 300 protocol patient TPV data sets have been submitted and reviewed by the 3D QA Center.

Clinical Protocols↗

Cost benefit of emerging technology in localized carcinoma of the prostate.

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.

Adenocarcinoma↗