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Biomedical subjects

L Kapusta

Publications and source records attributed to L Kapusta.

At least 19 recordsLinked to original sources
PubMed2006

Potential additional indicators for pacemaker requirement in isolated congenital atrioventricular block.

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was -0.91 (n = 83) in the PM group and -0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was -0.94 (n = 61) in the PM group and -0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was -0.96 (n = 61) in the PM group and -0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.

Cardiac Pacing, Artificial↗
PubMed2005

CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.

BACKGROUND: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. METHODS: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. RESULTS: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. CONCLUSIONS: CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.

Abnormalities, Multiple↗
PubMed2005

New reference values for echocardiographic dimensions of healthy Dutch children.

AIM: To renew the echocardiographic reference values of heart dimensions in healthy children. METHODS AND RESULTS: Group 1 consisted of 587 children, of which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500 g, who visited the Pediatric Cardiology outclinic during the period January 2000 till March 2004. All included children were diagnosed as normal, or as having innocent heart murmur. The second group was taken from an earlier study and comprised 160 children (77 boys and 83 girls). The echocardiographic measures were taken from conventional M-mode recording of the left ventricle (LV) parasternal long axis view. End diastolic septal (IVS) and LV posterior wall thickness (LVPW) and end diastolic as well as end systolic LV intracavity dimensions were retrospectively analyzed. The regression lines from all measured sizes are significantly different from those collected in the early eighties. Especially the thickness of the IVS is smaller. The regression lines are independent of gender. CONCLUSIONS: New reference values have been found which should replace the presently used ones. There is no difference between boys and girls. Why the muscular wall thicknesses are thinner than found 20 years ago needs to be further explored.

Adolescent↗
PubMed2002

Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumours.

BACKGROUND: Diffuse proliferation of interstitial cells of Cajal (ICCs) in the myenteric plexus layer of the intestine has been described in patients with familial and multiple gastrointestinal stromal tumours (GISTs). However, it is not fully understood whether proliferation is polyclonal or monoclonal. AIMS: To evaluate the clonal nature of diffuse ICC proliferation in familial and multiple GIST cases, we carried out clonal analysis using inactivation at the human androgen receptor (HUMARA) locus. MATERIALS AND METHODS: Diffuse ICC proliferation tissues from three female patients were microdissected using a laser capture microdissection (LCM) system. Normal intestinal mucosal tissues were also microdissected for polyclonal controls and GIST tissues for monoclonal controls from the same patients, and genomic DNA was extracted. After digestion by restriction enzyme HhaI, the HUMARA locus was amplified by a fluorescent polymerase chain reaction (PCR) procedure and the PCR products were analysed. RESULTS: One case was uninformative because it was homozygous at the HUMARA locus. In the two other cases, PCR products from the diffuse ICC proliferation showed two alleles as well as those from normal intestinal mucosal tissues, indicating that ICC proliferation was polyclonal. In contrast, PCR products from associated GIST tissues showed only one allele, indicating that GISTs were monoclonal. CONCLUSION: The results suggested that diffuse ICC proliferation in familial and multiple GIST cases was non-neoplastic hyperplasia.

Cell Division↗
PubMed2001

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PURPOSE: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Adenocarcinoma↗
PubMed2001

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children.

OBJECTIVES: We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND: Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS: This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS: Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation. CONCLUSIONS: Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

Adolescent↗
PubMed2001

Discriminative ability of conventional echocardiography and tissue Doppler imaging techniques for the detection of subclinical cardiotoxic effects of treatment with anthracyclines.

This study investigated improvement of diagnosing myocardial damage caused by anthracyclines using tissue Doppler imaging (TDI). The optimal set of conventional echocardiographic and/or TDI parameters, needed for the discrimination of survivors from healthy controls, was retrospectively assessed. A total of 60 patients and 99 controls, age range 8.5 to 17.6 years, were studied. The survivors received 50 to 400 mg/m(2) cumulative dose of anthracyclines, with a mean follow-up of 7.3 (+/-2.3) years. The parameters used in the discriminant score (S-score) were selected from a large set of 51 echocardiographic parameters, using logistic regression analysis (stepwise selection). The correct classification probability (C-index) and the generalized distance (d) between the distributions of S-scores were used to measure the overall discriminative performance of each echocardiographic technique separately and in combination. The overall discriminative performance of the conventional echo-Doppler parameters (C = 77.3%, d = 1.04) was lower than that of the TDI (C = 84.2%, d = 1.37); the highest C-index was obtained using both techniques (C = 89.2%, d = 1.66). The set of parameters includes: LV fractional shortening and MV early diastolic flow velocity, two long-axis and five apical 4-CV TDI wall velocities (systolic and diastolic). In the patient group, the S-score was positively associated with cumulative dose of anthracyclines (p = 0.05) and duration of treatment (p = 0.01). The diagnostic index S-score, based on a limited number of variables from both techniques simultaneously, could retrospectively discriminate asymptomatic children with anthracycline-induced cardiomyopathy from healthy controls. The potentials of the S-score for serial and prospective studies are further investigated.

Adolescent↗
PubMed2000

Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer.

PURPOSE: Decreased levels of the cyclin-dependent kinase inhibitor p27(Kip1) in breast cancer are associated with a poor outcome. The prognostic significance of BRCA1/2 mutations is less clear, and the relationship between BRCA1/2 mutation status, p27(Kip1) protein levels, and outcome has not been studied. PATIENTS AND METHODS: Pathology blocks from 202 consecutive Ashkenazi Jewish women with primary invasive breast cancer were studied. Tumor DNA was tested for the three common BRCA1/2 founder mutations present in Ashkenazi Jews, and p27(Kip1) expression was evaluated by immunohistochemistry. The median follow-up was 6.4 years. RESULTS: Thirty-two tumors (16%) were positive for a BRCA1/2 mutation. Low p27(Kip1) expression was seen in 110 tumors (63%) and was significantly associated with BRCA1/2 mutations (odds ratio, 4.0; 95% confidence interval [CI], 1.4 to 11.1; P =.009). BRCA1/2 mutation carriers had a significantly worse 5-year distant disease-free survival (DDFS) compared with women without BRCA1/2 mutations (58% v 82%; P =.003). Similar results were seen for women whose tumors expressed low levels of p27(Kip1), compared with those with high levels (5-year DDFS, 68% v 93%; P<.0001). In a multivariate analysis, both BRCA1/2 mutation and low p27(Kip1) expression were associated with a shorter DDFS (relative risk [RR], 2.1; 95% CI, 1.0 to 4.3; P =.05; and RR, 3.9; 95% CI, 1.4 to 11.1; P =.01, respectively). CONCLUSION: In this study, we showed that BRCA1/2 mutations were associated with low levels of p27(Kip1) in breast cancer. Both BRCA1/2 and p27(Kip1) status were identified as independent prognostic factors.

Adult↗
PubMed2000

Sotalol in the treatment of fetal dysrhythmias.

BACKGROUND: Fetal tachycardia may cause hydrops fetalis and lead to fetal death. No unanimity of opinion exists regarding the optimum treatment. This study evaluates our experience with transplacental sotalol therapy to treat fetal tachycardias in terms of safety and efficacy. METHODS AND RESULTS: The charts of 21 patients who were treated with sotalol for fetal tachycardia were reviewed. Ten fetuses had atrial flutter (AF), 10 had supraventricular tachycardia (SVT), and 1 had VT. Hydrops fetalis was present in 9 fetuses. Drug treatment was successful in establishing sinus rhythm in 8 of 10 fetuses with AF and in 6 of 10 fetuses with SVT. The mortality rate in this study was 19% (4 of 21 fetuses; 3 had SVT and 1 had AF); 3 deaths occurred just days after the initiation of sotalol therapy, and 1 occurred after a dosage increase. At birth, tachycardia was present in 6 infants. Two patients who converted to sinus rhythm in utero suffered from neurologic pathology postnatally. CONCLUSIONS: Fetal tachycardia is a serious condition in which treatment should be initiated, especially in the presence of hydrops fetalis. The high success rate in fetuses with AF suggests that sotalol should be considered a drug of first choice to treat fetal AF. The low conversion rate and the fact that 3 of the 4 deaths in this study occurred in fetuses with SVT indicate that the risks of sotalol therapy outweigh the benefits in this group and that sotalol should, therefore, be limited in the treatment of fetal SVT.

Anti-Arrhythmia Agents↗
PubMed2000

Magnetic resonance thermometry for predicting thermal damage: an application of interstitial laser coagulation in an in vivo canine prostate model.

Magnetic resonance image-guidance for interstitial thermal therapy has proven to be a valuable tool in its traditional role in device localization and, more recently, in monitoring heat deposition within tissue. However, a quantitative understanding of how temperature-time exposure relates to thermal damage is crucial if the predictive value of real-time MR thermal-monitoring is to be fully realized. Results are presented on interstitial laser coagulation of two canine prostate models which are shown to provide an opportunity to evaluate three models of thermal damage based on a threshold maximum temperature, an Arrhenius damage integral, and a temperature-time product. These models were compared to the resultant lesion margin as derived from post-treatment T(1)- and T(2)-weighted MR images, as well as from direct histological evaluation of the excised canine prostate. Histological evaluation shows that the thermal-injury boundary can be predicted from a threshold-maximum temperature of approximately 51 degrees C or an equivalent Arrhenius t(43) period of 200 minutes, but it is not reliably predicted using the temperature-time product. The methods described in this study are expected to have implications for the treatment of benign prostatic hyperplasia and prostate cancer with interstitial laser coagulation, which will be the focus of future human studies.

Animals↗
PubMed2000

Tissue Doppler imaging in detection of myocardial dysfunction in survivors of childhood cancer treated with anthracyclines.

The applicability of tissue Doppler imaging (TDI) was investigated for estimating cardiac function in long-term survivors of childhood cancer treated with anthracyclines. A total of 63 children (age range 7.8-17.3 y) underwent standard echo Doppler cardiographic studies of blood flow velocities, left ventricular dimensions and fractional shortening, followed by measurements of peak myocardial velocities and direction using the noninvasive tissue Doppler imaging (TDI) technique. All 63 were late survivors (median 7.1 y, range 3.5-13.5 y after end of therapy) who had received mean (+/- SD) cumulative dose of 242 (+/- 141) mg/m(2) of anthracyclines. The control group consisted of 160 healthy subjects (age range 4 to 17.9 y). Standard echo-Doppler anatomical parameters that were found significantly (p < 0.01) different for the study group are: RV wall thickness (decreased); LV diameter (increased); and LV fractional shortening (decreased). Studied hemodynamic parameters were not found to be different between the two groups. Quantitative TDI parameters: peak late diastolic myocardial velocities, as well as transmyocardial systolic and diastolic velocity differences, were significantly lower in late survivors than in the healthy pediatric population (p < 0.01). Qualitative local functional impairment of the movement of the left ventricular walls was detected in 20% of the patients. TDI might become a useful noninvasive method for detecting subclinical myocardial damage in apparently healthy children who received moderate doses of anthracyclines for treatment of childhood malignancy. Prospective studies with TDI for the detection of regional myocardial abnormalities are recommended.

Adolescent↗
PubMed2000

Assessment of myocardial velocities in healthy children using tissue Doppler imaging.

The objective was to determine the normal range of tissue velocities in paediatric hearts as measured by tissue Doppler imaging. A prospective study was carried out involving 160 healthy children (mean age 10.8 y, range 4.0-17.9 y). Using tissue Doppler imaging (TDI) from parasternal long axis and apical views, peak velocities and peak myocardial velocity differences across the right ventricular anterior wall, interventricular septum and left ventricular posterior wall were assessed during systole, early and late diastole. The existence of transmyocardial velocity differences between the left and right side of the interventricular septum, as well as between the endocardium and epicardium of the left ventricular posterior wall was observed throughout the heart cycle. With range-gated TDI from apical four-chamber view, peak velocities were measured within the basal, mid and apical parts of the interventricular septum, and the left and right free ventricular walls. The highest peak systolic, early and late diastolic velocities were measured within the basal parts of all myocardial walls. The ranges of the calculated velocity ratios (early-to-late diastolic velocity and early diastolic-to-systolic velocity) for the various wall parts appeared to be overlapping. The correlations of peak myocardial tissue velocities and their ratios with age and weight were weak and practically irrelevant. These normal values of peak myocardial velocities, transmyocardial velocity differences and the ratios of peak wall velocities can be used as reference values in future investigations of ventricular dysfunction in this age group.

Adolescent↗
PubMed2000

p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder.

PURPOSE: Although the majority of patients with node positive transitional cell carcinoma of the bladder have disease progression, a definitive subset is cured by surgery only. Nuclear accumulation of p53 has been associated with disease progression in patients with superficial transitional cell carcinoma and decreased survival in those with muscle invasive disease. We determined whether p53 status would predict survival in a cohort with nodal metastasis. MATERIALS AND METHODS: We explored the comprehensive database of all 199 radical cystectomies performed at our institution between July 1988 and September 1999. The 59 patients in this database with node positive pathology comprise our study. We performed immunohistochemical analysis of specimens using the MAB1801 antibody with greater than 20% lymph node and primary tumor nucleus staining deemed positive. Additional covariates measured included patient age, sex, pathological disease stage, adjuvant chemotherapy and nodal stage. Disease-free survival curves were generated for the various covariates and compared using the log rank test. The Cox proportional hazards technique was used to determine covariate adjusted p53 survival. RESULTS: In the cohort overall median disease-free survival was only 21 months, although 18% of patients were disease-free at 5 years. There was evidence of p53 nuclear accumulation in 54% of cases and complete agreement of nodal with bladder p53 nuclear accumulation. No significant baseline differences were noted in the covariates with respect to p53 nuclear accumulation. For stratum specific disease-free survival univariate and multivariate analyses revealed that only pathological stages p0-p2b versus p3-p4 (hazards ratio 2.86, p = 0.03), and nodal stages N2 versus N1 and N3 versus N1 (hazards ratio 3.84, p = 0.01 and hazards ratio 13.3, p = 0.0002, respectively) were significantly associated with prolonged disease-free survival, while p53 nuclear accumulation was not. CONCLUSIONS: Despite credible evidence for p53 nuclear accumulation prognostication in patients with in situ and invasive transitional cell carcinoma, this marker is not predictive of disease-free survival in node positive disease.

Aged↗
PubMed2000

Female clear cell adenocarcinoma arising within a urethral diverticulum.

Clear cell adenocarcinomas arising from female urethral diverticulae are rare. The optimal management of this clinical entity is uncertain. Two cases managed by a combination of surgery and XRT (radiotherapy) are presented. The common histopathological findings and treatment options are highlighted. Individualized patient management in a multi-disciplinary setting is recommended.

Adenocarcinoma, Clear Cell↗
PubMed1999

Congenital heart defects and maternal derangement of homocysteine metabolism.

Methionine loading tests and folate, vitamin B(6), and vitamin B(12) analyses were performed in 27 mothers of children with congenital heart defects. Median fasting plasma homocysteine concentrations were significantly higher in the study group as compared with 56 control subjects (P =.0001). Maternal hyperhomocysteinemia may be a risk factor for congenital heart defects.

Adult↗
PubMed1999

Multiple familial gastrointestinal autonomic nerve tumors and small intestinal neuronal dysplasia.

Multiple small intestinal stromal tumors were removed from mother and natural daughter within 15 months of each other. Both had long histories of recurrent iron deficiency anemia and upper gastrointestinal bleeding. Light microscopy revealed that the tumors had arisen in conjunction with diffuse hyperplasia/ dysplasia of Auerbach's myenteric plexus. Immunohistochemistry generally did not show myogenic or paraganglionic phenotypes; CD34 was positive in most tumors. Electron microscopy confirmed the association with the abnormal Auerbach's plexus and showed the structure of gastrointestinal autonomic nerve tumors (GANTs). These findings provide information as to the origin and evolution of GANTs, and also have implications for the clinical management of these tumors which appear to occur more frequently than previously thought.

Aged↗