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Biomedical subjects

A Wozniak

Publications and source records attributed to A Wozniak.

At least 19 recordsLinked to original sources
PubMed2006

Minimally-invasive treatment of intra-articular fractures of the calcaneum.

We describe the results of 287 intra-articular fractures of the calcaneum in 247 patients treated by minimally-invasive reduction and K-wire fixation between 1994 and 2003. There were 210 men (85%) and 37 women (15%). The most common cause of injury was a fall from a height in 237 patients (96%). Fracture classification was based on the method described by Sanders and Essex-Lopresti. All patients were operated on within 21 days of injury and 89% (220) within 48 hours. The reduction was graded as nearly anatomical (less than 2 mm residual articular displacement and satisfactory overall alignment) in 212 (73.9%) fractures. There were 20 cases (7%) of superficial pin-track infection and five (1.7%) of deep infection. All healed at a mean of 6 weeks (3 to 19). Loss of reduction was observed in 13 fractures (4.5%) and a musculocutaneous flap was needed in three (1%). The results were evaluated in 176 patients (205 fractures) with a mean age of 44.3 years (13 to 67), available for follow-up at a mean of 43.4 months (25 to 87) using the Creighton-Nebraska Health Foundation Assessment score. The mean score was 83.9 points (63 to 100). There were 29 (16.5%) excellent, 98 (55.7%) good, 26 (14.8%) fair and 23 (13%) poor results. A total of 130 patients (73.9%) were able to return to their original occupation at a mean of 5.6 months (3.2 to 12.5) after the injury. Semi-open reduction and percutaneous fixation is an effective treatment for displaced intra-articular fractures of the calcaneum.

Adolescent↗
PubMed2005

Novel amino acid substitution in the Y-position of collagen type II causes spondyloepimetaphyseal dysplasia congenita.

We report on monozygotic twins with short stature and severe spondyloepimetaphyseal dysplasia congenita (SEMDC) from the Polish population. Phenotype of the twin girls resembles spondyloepiphyseal dysplasia congenita Spranger-Wiedemann (SEDC-SW), but shortening of the stature is more severe and the cranioface is normal. The distinctive radiographic features, in spite of similarity to SEDC-SW, indicate different spinal and, notably, severe metaphyseal involvement. Molecular analysis of the COL2A1 gene revealed an A to G transition at nucleotide +79 of exon 41 that converted the codon for arginine at amino acid 792 to a codon for glycine (Arg792Gly). The twins were heterozygous for the mutation and neither parent had this change. The Arg792Gly substitution is located at the Y-position of Gly-X-Y triplet, and it is likely that this substitution decreased the thermal stability of the triple helix and may affect fibril growth by replacement of an arginine residue, which is important for a conformation of the triple helix.

Amino Acid Substitution↗
PubMed2005

Kidney preserving solutions containing lidocaine may increase urological complication rate after renal transplantation: an in vitro study.

OBJECTIVE: The frequency of urological complications after renal transplantation is up to 12%. Some authors consider that lidocaine addition to preservation solutions produces a favorable influence on allograft function. However, lidocaine may influence urinary tract epithelial cells. The aim of this work was to establish the influence of lidocaine on cultured primary rabbit urothelial cells (PRUC) as a tool to understand mechanisms of urological complications after kidney transplantation. DESIGN AND METHODS: A PRUC culture was established from an 8-month-old male rabbit bladder. The cells were cultured alone and then with in various concentrations of lidocaine for 24 hours or 1 hour. After an additional 24 hours, cell viability was assessed by the trypan blue exclusion test. Student's t test was used for statistical analysis, with significance set at P < .05. RESULTS: The cytotoxic effects of lidocaine on PRUC were concentration dependent. One-hour exposure of PRUC culture to 0.5 or 1.0% lidocaine decreased cell viability. Both lidocaine concentrations decreased cell viability in PRUC culture after a 24-hour incubation; even 0.25% lidocaine caused changes in the PRUC culture morphology after a 1-hour incubation. Cells became rounded and detached from the growth surface. No cells were observed in the monolayer after 1-hour incubation with 1% of lidocaine. CONCLUSIONS: The toxic effects of lidocaine on PRUC may forecast problems with supplementation of kidney preservation solutions, leading to impaired epithelial layer healing with an increased risk of urological complications.

Animals↗
PubMed2005

Arbovirus circulation, temporal distribution, and abundance of mosquito species in two Carolina bay habitats.

Carolina bays, a type of geomorphic feature, may be important in the ecology of mosquito vectors in South Carolina. Their hydrology varies from wetland habitats with marked flooding/drying regimes to permanently flooded spring-fed lakes. Moreover, they possess characteristics that contribute to the support of a particularly abundant and diverse invertebrate fauna. Although it has been estimated that 2,700+ bays exist in South Carolina, approximately 97% have been altered; < or = 200 bays remain intact, and only 36 are protected by state-funded conservation projects. We conducted a study in two distinct Carolina bay habitats, Savage Bay Heritage Preserve (SBHP) and Woods Bay State Park (WBSP), from June 1997 to July 1998 to determine mosquito temporal distribution, species composition, and the occurrence of arbovirus activity. The largest mosquito collection was obtained at WBSP (n = 31,172) representing 25 species followed by SBHP (n = 3,940) with 24 species. Anopheles crucians complex were the most common species encountered in both bays. Two virus isolates were obtained from SBHP in 1997: Keystone (KEY) virus from Ochlerotatus atlanticus-tormentor and Cache Valley (CV) virus from Oc. canadensis canadensis. Twenty-nine (29) arbovirus-positive pools were obtained from WBSP: 28 in 1997 and one in 1998. KEY virus was isolated from three pools of Oc. atlanticus-tormentor and Tensaw (TEN) virus was isolated from two pools of An. crucians complex; 10 isolates could not be identified with the sera available. Additionally, 14 pools of An. crucians complex tested positive for Eastern equine encephalitis (EEE) virus antigen. These represent the first record of KEY and CV viruses in South Carolina. Our data indicate the presence of high mosquito density and diversity in both Carolina bay habitats, which may be influenced, in part, by seasonal changes in their hydroperiods. The study of mosquito and arbovirus ecology in Carolina Bay habitats could provide more information on the transmission dynamics of arboviruses and its impact on human and animal arboviral disease occurrence in South Carolina.

Aedes↗
PubMed2005

Second primary tumors (SPT) of head and neck: distinguishing of "true" SPT from micrometastasis by LOH analysis of selected chromosome regions.

The reason of treatment failures in head and neck tumors is often connected with the appearance of second primary tumors (SPT). Three mechanisms of SPT development of clonal or non clonal secondary tumors were described: 1. via micrometastases (clonal); 2. from a common carcinogenic field - Second Field Tumors (SFT - partially clonal); 3. via independent events (from different carcinogenic fields - "true" SPT - not clonal). Assessing the clonality of diagnosed tumors carries important clinical implications including chemoprevention, radiotherapy and general patient management. In this study a set of 12 microsatellite markers was used to find similarities and/or differences in allelic imbalance patterns between 22 pairs of tumors (the first tumor designate as index and SPT). The aim of the study was to identify a potential clonal origin and progression within given pairs of tumors. The results indicate that within the tumors diagnosed by clinical examination as SPT at least two mechanisms mentioned above should be taken into account as 6/23 (26%) were clonally unrelated ("true" SPT) and 3/23 (13%) carried clonal genetic changes (formation by micrometastasis or SFT). In 14/23 (61%) cases the results were insufficient or ambiguous to determine the clonality status. The final results indicate the complexity of carcinogenesis in these tumors and thus stress that clinical diagnosis of second primary tumors should be considered carefully.

Adult↗
PubMed2005

Activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma.

UNLABELLED: THE AIM of this study was to determine the activity of cathepsin D and alpha(1)-antitrypsin in the blood serum of patients with mammary carcinoma. PATIENTS AND METHODS: The study was conducted on 52 women operated for a unilateral breast tumor, divided into two groups, according to the number of metastases and tumor size. Cathepsin D activity was determined using the method of Anson, while alpha(1)-antitrypsin activity was determined according to the Eriksson method. RESULTS: Both groups of patients with mammary carcinoma were found to have higher activity of cathepsin D before the treatment compared to healthy females. After the surgery the enzyme activity increased significantly, whereas 6 months after the surgery it generally decreased. The activity of alpha(1)-antitrypsin was significantly lower in patients before the treatment than in the controls, while after 6 months an increase in alpha(1)-antitrypsin activity was observed. The correlation between activity of cathepsin D and alpha(1)-antitrypsin was revealed. High enzyme activity and low alpha(1)-antitrypsin activity may result from the stage of neoplastic transformation. CONCLUSION: The determination of cathepsin D activity together with alpha(1)-antitrypsin activity may serve as useful biochemical marker in monitoring of malignant changes in breast tumor.

Adult↗
PubMed2004

Charge translocation during cosubstrate binding in the Na+/proline transporter of E.coli.

Charge translocation associated with the activity of the Na(+)/proline cotransporter PutP of Escherichia coli was analyzed for the first time. Using a rapid solution exchange technique combined with a solid-supported membrane (SSM), it was demonstrated that Na(+)and/or proline individually or together induce a displacement of charge. This was assigned to an electrogenic Na(+)and/or proline binding process at the cytoplasmic face of the enzyme with a rate constant of k>50s(-1) which preceeds the rate-limiting step. Based on the kinetic analysis of our electrical signals, the following characteristics are proposed for substrate binding in PutP. (1) Substrate binding is electrogenic not only for Na(+), but also for the uncharged cosubstrate proline. The charge displacement associated with the binding of both substrates is of comparable size and independent of the presence of the respective cosubstrate. (2) Both substrates can bind individually to the transporter. Under physiological conditions, an ordered binding mechanism prevails, while at sufficiently high concentrations, each substrate can bind in the absence of the other. (3) Both substrate binding sites interact cooperatively with each other by increasing the affinity and/or the speed of binding of the respective cosubstrate. (4) Proline binding proceeds in a two-step process: low affinity (approximately 1mM) electroneutral substrate binding followed by a nearly irreversible electrogenic conformational transition.

4-Chloromercuribenzenesulfonate↗
PubMed2003

A phase I clinical trial of spicamycin derivative KRN5500 (NSC 650426) using a phase I accelerated titration "2B" design.

The spicamycin derivative KRN5500 was considered as a potential anti-cancer agent based on in vitro and preclinical studies. A Phase I study involving 24 cancer patients in whom tumors were refractory to all other conventional therapies was conducted to determine the dose limiting toxicity, maximum tolerated dose, effectiveness, and pharmacokinetic parameters of this drug administered by 1-h IV infusion daily for five consecutive days every 3 weeks. Using an accelerated dose titration strategy, 8.4 mg/m2/d x 5 days was the maximum administered dose. Severe gastrointestinal and hepatic toxicities were observed at doses at or above 4.3 mg/m2/d x 5. The recommended Phase II dose i s 4.3mg/m2/d x 5. The distribution of KRN5500 followed a two-compartment model, and clearance did not decrease significantly over the dose range 0.8-8.4 mg/m2/d x 5. No significant correlation was observed between plasma levels and toxicity. No tumor responses were observed among the 14 patients evaluable for response.

Adult↗
PubMed2001

Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18.

We report the results of detailed clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Classical cytogenetics and fluorescence in situ hybridization (FISH) analysis with the chromosome 18 painting probe identified five non-mosaic and two complex mosaic 46,XX,dup(18)(p11.2)/47,XX,dup(18)(p11.2),+r(18) and 46,XX,dup(18)(p11.32)/47,XX,dup(18)(p11.32),+r(18) cases. FISH analysis was performed for precise characterization of the chromosome 18 breakpoints using chromosome 18-specific short-arm paint, centromeric, subtelomeric, and a panel of fifteen Alu- and DOP-PCR YAC probes. The breakpoints were assessed with an average resolution of approximately 2.2 Mb. In all r(18) chromosomes, the 18q terminal deletions ranging from 18q21.2 to 18q22.3 ( approximately 35 and 9 Mb, respectively) were found, whereas only in four cases could the loss of 18p material be demonstrated. In two cases the dup(18) chromosomes were identified as inv dup(18)(qter-->p11.32::q21.3-->qter) and inv dup(18)(qter-->p11.32::p11.32-->p11.1: :q21.3-->qter)pat, with no evidence of an 18p deletion. A novel inter-intrachromatid mechanism of formation of duplications and ring chromosomes is proposed. Although the effect of "ring instability syndrome" cannot be excluded, the phenotypes of our patients with characteristic features of 18q- and 18p- syndromes are compared and correlated with the analyzed genotypes. It has been observed that a short neck with absence of cardiac anomalies may be related to the deletion of the 18p material from the r(18) chromosome.

Abnormalities, Multiple↗
PubMed2001

The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a molecular genetic study of eight cases.

Perineurial cell tumors (PNTs) are rare neoplasms derived from or showing differentiation toward specialized lining cells of the nerve sheath, the perineurial cells. In this study, we have evaluated neurofibromatosis type 2 (NF2) gene alterations in eight PNTs using archival formaldehyde-fixed, paraffin-embedded tissue. Two conventional soft-tissue PNTs from the upper back and chest wall, one retiform soft tissue variant from the scapular region, and five sclerosing PNTs from the fingers and palm were studied. All cases showed histological features of PNTs, and the neoplastic cells were positive for epithelial membrane antigen and negative for S100 protein. The coding sequences (exons 1 to 15) of the NF2 gene were polymerase chain reaction (PCR) amplified and evaluated for mutations by direct sequencing of the PCR products. Five NF2 point mutations, two in the 5'-untranslated region (UTR) and three in exons 3, 6, and 8, were identified in four of eight cases (50%) studied. Exon mutations resulted in changes of predicted amino acids sequences: Asp-->Asn at codon 83, Glu-->Asp at codon 182, and Leu-->Val at codon 241. In two cases (one with a missense mutation in codon 241), the same point mutation in the 5'-UTR at the nucleotide position 8958 was identified. A loss of heterozygosity (LOH) study was performed in three cases. LOH at the NF2 locus was found in one case with a mutation in the 5'-UTR. However, in another case with exon 8 and 5'-UTR mutations, deletion of one allele of the NF2 gene was previously documented by fluorescence in situ hybridization. The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism.

Adolescent↗
PubMed2001

Chronic oral administration of CI-994: a phase 1 study.

OBJECTIVES: CI-994 (N-acetyl dinaline, PD 123654) is a novel oral agent active in a broad variety of murine and human tumor xenografts. While cytotoxic in the Brown Norway (BN) rat leukemia model, growth inhibition in other murine and human tumor xenografts is predominantly cytostatic. Its specific mechanism of action remains unknown. Following CI-994 administration, inhibition of both histone deacetylation and cellular proliferation at the G1 to S transition phase of the cell cycle are observed. This Phase 1 study in patients with solid tumors was carried out to determine a maximum tolerated daily oral dose (MTD) for CI-994 administered on a chronic basis. METHODS: Fifty-three patients received CI-994 daily for treatment durations ranging from 2 to 10 weeks. Dosage escalation proceeded in 2 phases; an Acute Dosing Phase (n = 11) to define the MTD for CI-994 administered over 2 weeks and a Chronic Dosing Phase (n = 29) to define the MTD for daily administration for 8 weeks. Upon completion of the Chronic Dosing Phase, a third cohort of patients (n = 13) received CI-994 at the recommended Phase 2 dose and schedule with 2 additional single doses of drug administered separated by a 1-week washout to assess the effect of food on CI-994 pharmacokinetics. RESULTS: Thrombocytopenia was dose limiting at the MTD of 8 mg/m2/day for 8 weeks. Other toxicities included fatigue and gastrointestinal effects such as nausea, vomiting, diarrhea, constipation and mucositis. Pharmacokinetic studies revealed that peak plasma levels and AUC's generally increased with dose and that food intake did not affect the rate or extent of drug absorption. One patient with heavily pre-treated adenocarcinoma of the lung achieved a Partial Response (PR) lasting over 2 years and 3 additional patients achieved Stable Disease (SD), 1 each with non-small cell lung, colorectal, and renal cancer. CONCLUSIONS: The recommended Phase 2 starting dose is 8 mg/m2/day for 8 weeks repeated after a 2-week drug-free interval.

Administration, Oral↗
PubMed2001

Effect of altitude training on the peroxidation and antioxidant enzymes in sportsmen.

PURPOSE: The aim of this work was an evaluation of the influence of physical exercise in high-altitude conditions (about 2000 m above sea level) on thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) and catalase (CAT) activities in 10 kayakers and 10 rowers. METHODS: During their training, the sportsmen performed different kinds of static and dynamic efforts. The blood samples were taken from the cubital vein on the control day at low altitude and at high altitude, and on the 4th, 10th, and 18th days of the training camp before and after exercise. The TBARS and lactic acid concentrations in blood plasma and SOD and CAT activities in erythrocytes were measured. RESULTS: A statistically significant increase of SOD and CAT activities in erythrocytes after exercise on the 4th, 10th, and 18th days of training was found. The TBARS concentration in erythrocytes decreased in a statistically significant way after the end of the 10th day of exercise (P < 0.01), and on 18th day it more than doubled (P < 0.001) when preexercise values were compared with postexercise values of each day. A statistically significant increase of TBARS concentration in blood plasma was observed only after the end of exercise on the 10th day-using the same comparison as above. A statistically significant increased lactic acid concentration in blood plasma was noticed both on 4th or 18th days of training. CONCLUSIONS: The results obtained show the increasing generation of oxygen-derived free radicals and the compensatory intensification of SOD and CAT activities after training in altitude (high mountain) conditions.

Adult↗
PubMed2001

Arbovirus surveillance in South Carolina, 1996-98.

Arboviruses isolated and identified from mosquitoes in South Carolina (USA) are described, including new state records for eastern equine encephalitis virus (EEE), St. Louis encephalitis virus (SLE), Flanders virus, Tensaw virus (TEN), and a variant of Jamestown Canyon virus (JC). Mosquitoes were collected at 52 locations in 30 of 46 South Carolina counties beginning in June 1996, and ending in October 1998, and tested for arboviruses. Of 1,329 mosquito pools tested by virus isolation (85,806 mosquitoes representing 34 mosquito species or complexes), 15 pools were positive. Virus isolations included EEE from 1 pool each of Anopheles crucians complex and Culex erraticus; a variant of JC from 1 pool of An. crucians complex; a California serogroup virus from 1 pool of Aedes atlanticus/tormentor; TEN from 5 pools of An. crucians complex and 1 pool each of Culex salinarius and Psorophora ciliata; Flanders virus from 1 pool of Culiseta melanura; and Potosi virus from 1 pool each of Aedes vexans, Coquillettidia perturbans, and Psorophora columbiae. Of 300 mosquito pools tested by antigen-capture assay for EEE and SLE (14,303 mosquitoes representing 16 mosquito species or complexes), 21 were positive for EEE and I was positive for SLE. Positive EEE mosquito pools by antigen-capture assay included An. crucians complex (14 pools), Anopheles punctipennis (1 pool), Anopheles quadrimaculatus (1 pool), Cq. perturbans (4 pools), and Cs. melanura (1 pool). One pool of Cx. salinarius was positive for SLE by antigen-capture assay. Arbovirus-positive mosquito pools were identified from 12 South Carolina counties, all located in the Atlantic Coastal Plain, and from 4 of 8 Carolina bays surveyed.

Aedes↗
PubMed2001

[The significance of cathepsins B and D and their inhibitors in cancer disease].

Cathepsins play an important role in the pathogenesis of the great number of cancer diseases i.e. in breast, head and neck, liver, pancreas, colon and skin cancer. Estimation of cathepsins activity referring to different kinds of cancer diseases has a significance both in diagnostics and in monitoring of their running. An essential role in cancer disease development is also reported for cathepsins B and D inhibitors. Using drugs that are able to inhibit the harmful activity of cathepsins, would give a chance to supplement an anti-cancer therapy with the new agents. In future, it could increase the efficiency of cancer treatment in a significant way.

Antineoplastic Agents↗
PubMed2000

Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases.

Adult↗
PubMed2000

Phase I pharmacokinetic study of the novel antitumor agent SR233377.

SR233377 is a novel thioxanthenone analogue that demonstrated solid tumor selectivity in vitro with activity confirmed in vivo against several murine tumors including those of colon, pancreas, and mammary origin. Its primary preclinical dose-limiting toxicities included myelosuppression and neurological toxicity. The neurological toxicity was acute and could be ameliorated in mice when the drug was administered as a 1-h infusion instead of rapid i.v. injection. As a result of its preclinical efficacy profile, SR233377 entered Phase I clinical investigation. The compound was administered i.v. over 2 h on day 1 repeated every 28 days. The starting dose was 33 mg/m2 (one-tenth the mouse LD10). Escalations continued to 445 mg/m2 (six escalations), where dose-limiting toxicity was observed. At this dose, acute ventricular arrhythmias, including one patient with torsades de pointes and transient cardiac arrest, occurred. Because this toxicity might have been related to the plasma peak, the protocol was amended to a 24-h infusion beginning at 225 mg/m2. With this dose, prolongation of the corrected QT interval (QTc) over the pretreatment levels resulted. Because prolonged QTc is a known forerunner to acute ventricular arrhythmias, clinical development of SR233377 was stopped. However, preclinical antitumor and toxicity studies with analogues are underway with hopes of identifying a new clinical candidate with similar antitumor effects that is devoid of cardiac toxic effects.

Adult↗
PubMed2000

A case with 47,XXY,del(11)(q23) karotype-coexistence of Jacobsen and Klinefelter syndromes.

A case with 47,XXY, del(11)(q23) karyotype-coexistence of Jacobsen and Klinefelter syndromes: A two-year-old dysmorphic male child was found to have 47,XXY,del(11)(q23) karyotype. Domination of the clinical features of Jacobsen syndrome was observed: mild mental retardation, trigonocephaly, ptosis, downward slanting palpebral fissures, low set ears, carp-shape mouth and micrognathia. Transient thrombocytopenia and leukopenia were also present. Over the following five years gynecomastia and eunuchoid body proportions became evident as clinical features of Klinefelter syndrome. This is the first description of the coexistence of both syndromes.

Brain↗