Biomedical subjects

A Borowski

Publications and source records attributed to A Borowski.

At least 19 recordsLinked to original sources

PubMed1998

Application of interphase fluorescence in situ Hybridization for the detection of the Burkitt translocation t(8;14)(q24;q32) in B-cell lymphomas.

The translocation t(8;14)(q24;q32) is the characteristic chromosomal aberration of Burkitt's-type lymphomas and leukemias (BLs). On the molecular level, the t(8;14) juxtaposes the c-myc gene in 8q24 next to the IgH locus in 14q32, resulting in overexpression of the transcription factor c-Myc. The detection of a t(8;14) is a major aim in the diagnostic process of all patients with high-grade B-cell lymphomas because treatment strategies differ between BL and other high-grade lymphomas. As chromosome analyses are sometimes hampered by the low yield or poor quality of metaphase spreads and as the application of molecular genetic techniques is limited by the distribution of the 8q24 breakpoints over a region of about some hundred kilobases, we set out to establish an interphase fluorescence in situ hybridization (FISH) assay for the detection of the t(8;14). A cosmid probe hybridizing to the IgH constant region in 14q32 was combined with a differently labeled probe of pooled cosmid clones spanning the c-myc locus in 8q24. Interphase nuclei lacking a t(8;14) show two separated signals corresponding to each probe, whereas interphase nuclei carrying a t(8;14) display a split of the c-myc probe and a colocalization of at least one of the splitted signals with the IgH probe. Based on the results of extensive control studies, the cutoff level for this stringent (type I) criteria was set at 2%. Additionally, colocalization of at least one c-myc signal with one IgH signal alone (without signal split for the c-myc probe) was used as a less stringent (type II) criteria with a cutoff limit of 11%. Nine BLs and one Burkitt-like lymphoma were investigated by this approach. Cytogenetically, all tumors contained a translocation t(8;14)(q24;q32) except for one BL, in which cytogenetic analysis had failed. In interphase FISH, all lymphomas and leukemias met the less stringent criteria for the diagnosis of the t(8;14). Additionally, in all tumors but the Burkitt-like lymphoma, a t(8;14) could be diagnosed according to the stringent criteria. The percentage of cells found to harbor the t(8;14) by FISH ranged from 4.3% to 100%. Comparison of cytogenetic and FISH results revealed a significantly lower percentage of t(8;14)+ interphase nuclei than metaphase cells (P = .004). In conclusion, the described FISH assay provides a feasible and sensitive tool for the routine detection of the translocation t(8;14) in interphase cells which might also offer new insights into the biology of high-grade B-cell lymphomas.

Adult↗

PubMed1997

Spiral CT angiography in an infant with severe hypoplasia of a long segment of the descending aorta.

CT angiography, or the spiral CT technique, is a promising minimally invasive method of visualising the arterial vascular system and can be applied in children in whom ultrasound, MRI and/or angiography or cardiac catheterisation cannot be performed, or where an exact diagnosis cannot be made. CT angiography should be considered in special cases as a diagnostic alternative to MRI, ultrasound and angiography. As an example of the possibilities of CT angiography, a case is described in which hypoplasia of the descending aorta was diagnosed and a postoperatively encountered perigraft reaction was demonstrated. Perforation of the blood vessel could be excluded by CT angiography.

Angiography↗

PubMed1997

Myocardial protection by pressure- and volume-controlled continuous hypothermic coronary perfusion (PVC-CONTHY-CAP) in combination with ultra-short beta-blockade and nitroglycerine.

The aim of the study was to validate clinically a new technique of myocardial protection developed for intra- and extra-cardiac surgery on the beating heart. The concept combines the principle of continuous pressure- and volume-controlled coronary artery perfusion (PVC-CONTHY-CAP) with the specific myocardioprotective effects of hypothermia and nitrates and, on the other hand, with the beta-blocker-mediated reduction of chronotropy and inotropy necessary for convenient surgery. Under standard ECC conditions after cross-clamping the aorta coronary perfusion with oxygenated blood enriched with nitroglycerine (10 micrograms/kg/h) and esmolol (0.05 mg/ml flow/min) is started via an additional perfusion cannula placed in the aortic root. The temperature of the perfusate is maintained at 32 degrees C, the intraaortic pressure at 40-70 mmHg and the perfusion flow in the range 0.8-1.0 ml/g heart muscle/min. In CABG procedures an additional perfusion catheter is used for perfusion of distal coronary artery segments. Using this technique 100 consecutive patients, adults and children, were operated on between 2/96 and 8/96. In 84 adult patients (age: 45-82 yrs), 78 CABG procedures (54 elective, 13 urgent, 11 acute) with a mean bypass count of 3.7 (range 1-7), 69 ITA grafts, 72 grafts to CX, and 3 MVRec/MVRpl, and 6 pure MVRec/MVRpl procedures (1 urgent, 1 emergency) were performed. The mean coronary perfusion time was 48 min (range 21-88 min). In 5 patients perioperative infarction (CABG; 1 emergency after PTCA, 4 elective) with significant increase of CK-MB values (57-98 U/L) occurred. In the 4 elective patients (3 with diabetes mellitus) re-intervention was not possible due to small-vessel disease. In one patient with preoperative infarction IABP was necessary. No patient died. There were 16 children (age: 4weeks-16 yrs): VSD, n = 6, AV-C, n = 2, TOF, n = 1, MVRec, n = 1, DORV (Rastelli), n = 2, SV (TCPC), n = 3, and PV obstruction, n = 1. The mean coronary perfusion time was 97 min (range: 27-260 min). The mean ICU stay 3.9 d (range: 1-10 d). One child died (TCPC) on the 10th postoperative day due to multi-organ failure. In conclusion, PVC-CONTHY-CAP is designed especially for emergency and urgent procedures, i.e. patients with PTCA-related complications, patients with severely depressed LV function, and patients with complex congenital cyanotic heart defects. Using PVC-CONTHY-CAP, coronary artery bypass grafting as well as intracardiac procedures for congenital and acquired heart defects can be performed safely and conveniently, the system is easy to handle for both the cardiac surgeon and perfusionist. Due to its pharmacological properties continuous intracoronary application of nitrates in combination with hypothermia seems to be essential as a preventive treatment modality for the ischemic state.

Adolescent↗

PubMed1997

Open heart interventions in premature low- and very-low-birth-weight neonates: risk profile and ethical considerations.

In premature, very-low-birth-weight (VLBW) neonates, complex cardiac malformations can be successfully repaired under conditions of cardiopulmonary bypass. However, due to the immaturity of organ systems, these patients are exposed to a specific risk resulting from noxious effects of extracorporeal circulation, especially on the central nervous system. Two premature neonates with low and very low birth weight of 1160 g and 1650 g, were operated on using cardiopulmonary bypass for severe pulmonary artery stenosis and truncus arteriosus communis type II, respectively. The neonate with pulmonary valve stenosis survived, but at 2-year-follow-up examination motoricity retardation as a result of cerebral immaturity-related changes was evident. The other neonate died suddenly on the fifth postoperative day of a massive intracranial haemorrhage. Due to the fact that the natural history of VLBW children is a priori characterized by a high incidence of major neurological handicaps, open heart surgery may by improving survival chances contribute to an increased incidence of mentally handicapped children.

Brain Diseases↗

PubMed1997

Murine mucopolysaccharidosis type I: targeted disruption of the murine alpha-L-iduronidase gene.

Mucopolysaccharidosis type I (MPS I) is considered to represent the prototypical mucopolysaccharide storage disorder. Although a spectrum of severity is seen within the MPS I subgroup, Hurler syndrome represents the most severe and frequent manifestation of MPS I. We describe here the generation of a murine model for Hurler syndrome by targeted disruption of the murine Idua gene. Homozygous Idua -/- mice have no detectable alpha-L-iduronidase enzyme activity and show increased urinary glycosaminoglycan levels. Although normal appearing at birth, Idua -/- mice develop a flattened facial profile and thickening of the digits discernible by 3 weeks of age. No obvious growth deficiency nor mortality is seen within the first 20 weeks of life. Radiographs reveal anterior flaring of the ribs and thickening of the facial bones as early as 4 weeks of age with more extensive dysostosis detectable by 15 weeks of age. At 4 weeks of age, lysosomal storage is noted primarily within reticuloendothelial cells with abundant lysosomes noted in Kupffer cells, splenic sinusoidal lining cells, and glial cells. More widespread lysosomal storage is noted by 8 weeks of age in hepatocytes, chondrocytes, neurons, as well as renal tubular cells. Thus, targeted disruption of the murine Idua locus has produced a murine strain representative of the severe form of MPS I. This model should permit detailed evaluation of the pathophysiology of lysosomal storage disorders and provide a small animal model for the testing and development of enzyme replacement and gene therapy regimes.

Abnormalities, Multiple↗

PubMed1996

Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases.

We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.

Animals↗

PubMed1995

Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes.

Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5 mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia.

Animals↗

PubMed1995

[Mechanical circulatory support. 1: Intra-aortic balloon counterpulsation (IABP)].

In cardiac surgery mechanical circulatory support with intra-aortic balloon counterpulsation (IABP) is an established measure for the therapy of perioperative low-output-syndrome and refractory cardiogenic shock. The favourable influence on the myocardial oxygen supply and demand-relationship with an improvement of the energetic balance guarantees the functional and ultrastructural recovery of reversibly damaged ischemic myocardium. The efficacy of IABP is uncontradicted and verified by high survival rates even in patients with severe impairment of the ventricular function. The system is easy to applicate by standardized surgical techniques of im- and explantation, safely to handle due to improvements of the technical equipment and can be applied at a low risk.

Cardiac Output, Low↗

PubMed1995

[Mechanical circulatory support. 2: Ventricular assist systems].

In cardiac surgery, ventricular assist devices for mechanical circulatory support are implanted for short or mid-term use in patients with therapy refractory postoperative low-output-syndrome to overtake the function of the left, right or of both ventricles until recovery of myocardium can be achieved. In the long-term, these systems are in use as a bridge to transplantation. An increasing number of clinical reports clearly demonstrates that ventricular assist devices can guarantee in a relatively high percentage of patients with postoperative low-output-syndrome a sufficient regeneration of the cardiac function with satisfactory functional and hemodynamic long-term results. Furthermore, a high percentage of patients bridged to transplantation can be successfully transplanted with good clinical outcome and survival rates.

Cardiac Output, Low↗

PubMed1994

Mitral valve remodeling using autologous pericardium: an experimental study.

The aim of this study was to assess in vivo the efficacy of a new technique for remodeling the mitral valve. In 6 dogs during cardiopulmonary bypass and cardioplegic cardiac arrest, both mitral valve leaflets were totally separated from the mitral ring and resected subtotally, leaving intact their narrow margins with insertion sites of the chordae tendineae of the first and second order. To mimic pathologic conditions, the chordae tendineae were then altered by placing two shortening sutures for every chordal stem. Based on standardized geometric calculations and using autologous pericardium treated with 0.62% glutaraldehyde solution, the new leaflets were then remodeled intraoperatively and sutured in place, merging them with the subvalvular apparatus and the native mitral ring. After restoration of stable circulatory conditions, valve function was evaluated under rest and defined loading conditions using a 5.0-MHz ultrasound transducer, applied epicardially. We found that intraoperative remodeling of the mitral valve leaflets using autologous pericardium with preservation of the subvalvular apparatus is possible and reproducible, and can be performed even when the subvalvular apparatus is altered morphologically. Functionally, the remodeled valve proved to be satisfactory under conditions of rest and stress. The benefits conferred by autologous tissue, the reproducibility of the surgical technique, the good functionality of the remodeled valve, and the preservation of the subvalvular apparatus could make this technique a useful surgical alternative for extensive mitral valve reconstruction procedures in pediatric and adult patients.

Animals↗

PubMed1994

Efficacy of pulmonary artery banding in the prevention of pulmonary vascular obstructive disease.

In 57 nonconsecutive pediatric patients (mean age: 2.6 months) with shunt-related pulmonary hypertension, the efficacy of pulmonary artery banding (PAB) was analysed retrospectively with special reference to the development of pulmonary vascular obstructive disease (PVOD). The patients were grouped in accordance to morphology, hemodynamics and incidence of PVOD. Efficacy of PAB was assessed by pulmonary to systemic pressure, flow and resistance ratios obtained by heart catheterization performed pre- and postoperatively. PAB was very effective in 49 out of 57 patients (= 85.9%), in 8 cases a progression or possible progression of PVOD must be suggested. Only Down syndrome can be considered as a predisposing factor for the development of PVOD. Based on our results we conclude that PAB is a high effective procedure in the prevention of PVOD; however, despite the surgical effectiveness of PAB, PVOD can occur. Strict post-PAB examination of pulmonary flow and resistance parameters is recommended and the definite surgical repair should be performed as early as possible.

Female↗

PubMed1994

Cryopreservation of veins as an alternative to autografts in coronary by-pass grafting.

Cryopreserved venous segments could be used as allografts in coronary by-pass surgery in patients with limited availability of venous or arterial conduits for autologous grafting. After primarily disappointing clinical results it was the aim of these experiments to improve freezing procedure and incubation media in order to maintain most of the functional integrity of the biological material after cryopreservation, and thus to contribute to the essential prerequisites for a successful implantation. Freshly prepared segments of human saphenous vein were cryopreserved: 1) using various computer-assisted freezing programs with definite cooling rates and seeding temperatures; 2) after incubation in media consisting of RPMI 1640 and cryoprotective agents in different combinations and concentrations. The veins were stored at -196 degrees C, thawed quickly and analyzed in an in vitro perfusion system. The degree of vitality of the vein segments was assessed by measuring vasoconstriction after application of Norepinephrine and Serotonine and vasodilatation following release of endothelium-derived relaxing factor (EDRF) after perfusion with Acetylcholine. Our results show that the preservation of vascular smooth muscle can be maintained only by: 1) equilibrating the vein in RPMI 1640 with 2.2 M Glycerol and 1.6 M Ethylene-Glycol and 2) preventing an increase of temperature during the crystallization in the cooling process. The results clearly demonstrate the maintainance of vitality in vein segments after an appropriate freezing and equilibration process with specific cryoprotective agents. The data obtained in the study could serve as the basis for a better longterm prognosis of transplanted cryopreserved venous allografts.

Acetylcholine↗

PubMed1994

Left ventricular geometry and function before and after mitral valve replacement.

Left ventricular geometry and function were assessed in 20 patients with mitral stenosis (MS) and in another 20 patients with mitral insufficiency (MI) five days before and 12 days after mitral valve replacement by transthoracic (TTE) and transesophageal (TEE) echocardiography, as well as late postoperatively (mean: 194 days) by TTE. The continuity of the subvalvular apparatus could not be preserved in any of these patients. In mitral stenosis the area ejection fraction (AEF) in the short axis of the left ventricle (LV) did not change significantly early or late postoperatively. There was a significant lengthening of the left ventricular longitudinal axis in the apical four chamber view whereas the transverse axis remained unchanged. This was likely the result of the discontinuity between the mitral valve and the papillary muscles. AEF and ejection fraction (EF) determined in the four chamber view showed a slight tendency to decrease in the postoperative phase. Patients with mitral insufficiency likewise showed a significant increase of the LV longitudinal diameter postoperatively. In the short axis of the left ventricle and in the apical four chamber view a significant reduction of the AEF was observed. Furthermore, left ventricular EF dropped significantly postoperatively. This decrease was caused by the extension of the LV longitudinal axis accompanied by an enlargement of the transverse diameter as well as by an afterload increase, and a masked impairment of left ventricular function preoperatively. Wall motion analysis of the LV in both groups documented new postoperative hypokinesis especially in the septal segments. At late postoperative examination the hypokinesis disappeared in about 50% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Reduction of the left-ventricular outflow-tract obstruction by aortoventriculoplasty--long-term results of 96 patients.

The aortoventriculoplasty (AVP) is an established surgical procedure for enlargement of different types of congenital and acquired obstruction of the left-ventricular outflow tract (LVOTO), especially with narrowing of the aortic valvular and subvalvular segment. Between 1974 and 1992, 96 patients underwent AVP. There were 32 female and 64 male patients, aged 3 to 32 years (mean 11.2 +/- 2.7 years) at operation. Indications for the procedure were as follows: 1. narrowing of the aortic annulus (19 patients), 2. multi-level stenosis (26 patients), 3. "outgrown"-prosthesis (8 patients), 4. recurrent hypertrophic obstructive cardiomyopathy (HOCM) (5 patients), and 5. subaortic stenosis of different origins (38 patients; out of these 19 patients had a "tunnel-like" stenosis, 7 of them with a "Shone-complex"). Seventy-six patients had previous operations at different levels of the left-ventricular tract. The mean preoperative peak transvalvular gradient was 88 +/- 27 mmHg (range 50-160 mmHg) and could be reduced by AVP to 14 +/- 13 mmHg. The early mortality was 8.3% (8/96). Among the last 58 patients there were no deaths. Three patients underwent subsequent reoperations: one for ascending aortic aneurysm, one for right-ventricular outflow tract obstruction (RVOTO), and one for "outgrown" prosthesis. Three patients required pacemaker implantation for a permanent a-v block, 71 of 96 patients had sinus rhythm postoperatively. The long-term results are similar to those of standard aortic valve replacement in childhood and adolescents. The advantages and disadvantages of the AVP in comparison to the other alternative surgical methods for relief of LVOTO are discussed.

Actuarial Analysis↗

PubMed1992

[Peri-graft reaction. A complication after implantation of a prosthesis shunt in children with congenital cyanotic heart defects].

Two different clinical manifestations of perigraft-reactions complicating the implantation of prosthetic aortopulmonary shunts in children with cyanotic congenital heart disease are described and discussed. The incidence of this complication in the past 5 years in our own patients was 3%. The appearance of a localized mass on the chest film surrounding the prosthesis requires the exclusion of a hematoma, aneurysm or inflammation. In the case of a massive serous pleural effusion examination of the ingredients leads to diagnosis. Concerning our own patients the fluid is identical with serum; the leakage through the prosthesis can therefore be called plasmapheresis. The claimed pathogenetic causes are discussed intensively, including a chylothorax promoting this complication in the second case. Local variations in porosity and structure of the implanted prosthesis may play a critical role in the pathogenesis of perigraft-reaction, as indicated by both our reported cases. In the event of unsuccessful observation of a localized perigraft seroma or of unsuccessful chest drainage of a massive pleural serous effusion, graft replacement and placement of a different graft material are found to have the best results.

Blood Vessel Prosthesis↗

PubMed1991

[Surgical myocardial revascularization: indications, perioperative risk constellation and prognosis].

Since the inception of coronary artery bypass grafting, refinements in surgical technique, myocardial preservation, anesthesia and in pre- and postoperative care, reduced the perioperative mortality and improved the long-term results in patients with chronic coronary artery disease. Large-scale, multicentre randomized and a multitude of non-randomized clinical trials of surgical versus medical treatment have set therapeutic standards for quality and refined the indications for bypass surgery. In summary, these studies clearly indicate that surgery is superior to medical therapy in symptom relief, decreased antianginal drug use and improved exercise performance, but does not improve the likelihood of return to employment, non-fatal myocardial infarction prevalence or hospitalization rates. After surgery, survival is prolonged in those subsets of patients who are considered at high risk, i.e. patients with left main disease (greater than 70%), with two-vessel disease with severe left anterior descending artery stenosis or with three-vessel disease with signs of significant ischemia on exercise or left ventricular dysfunction present. Specific individual risk profiles during coronary artery surgery were evaluated by a multicentre retrospective analysis of 8363 patients (QuaDRA-study) documenting a significantly higher perioperative letality and incidence of postoperative complications (low output syndrome, infection, renal dysfunction, psychosyndrome) in the elderly (greater than 65 years).

Coronary Disease↗

PubMed1991

Primary closure of median sternotomy with interposition of hydroxyapatite blocks. A new approach in pediatric cardiac surgery.

Chest closure after correction of congenital heart disease with subsequent enlargement of the heart has been a problem encountered throughout departments performing pediatric cardiac surgery. Present techniques using Rehbein struts or an open chest with a Gore-Tex patch skin closure have not solved this issue satisfactorily. Between January 1989 and September 1990, median sternotomies could not be closed primarily due to hemodynamic consequences in nine patients age 3 months to 19 years operated upon in our department. In three children, a conduit exchange, in two a Mustard correction, in two a correction of Fallot's tetralogy, in one a prosthetic valve exchange and in one, a new implantation of a homograft was performed. Primary chest closure was achieved by interposing hydroxyapatite blocks (50 mm x 15 mm x 6 mm) without hemodynamic consequences. In a follow-up period of 10 +/- 8 months, all children are alive and well. There was no complication resulting from the implanted blocks. Due to the excellent functional and cosmetic results of this technique and the outstanding histomorphological characters of hydroxyapatite, we regard the implantation of hydroxyapatite blocks as a superb method for primary sternotomy closure especially in pediatric cardiac surgery.

Adolescent↗

PubMed1991

Endothelial function and contractility of human vena saphena magna prepared for aortocoronary bypass grafting.

The aim of this study was to examine whether contractility and endothelial function of the human saphenous vein prepared for aortocoronary bypass grafting are altered by the surgical technique, e.g. cannulation and gentle distension of the vessel. Two segments (2 cm length each) of native vena saphena magna and 2 segments (2 cm length each) of the same vessel prepared for coronary bypass grafting were taken for further experimentation. After ligation of all side branches the segments were cannulated and arranged in two systems (with two segments each) in a serial manner (system I: prepared vessel followed by a native segment; system II: native vessel followed by a prepared segment) and perfused with Tyrode's solution at a constant flow rate of 20 ml/min (PO2 = 45 mmHg). Pressure gradient was measured continuously over each segment as a function of the vessel's radius according to the Hagen-Poiseuille equation. Endothelial and smooth muscle function was checked by perfusion with increasing concentrations of acetylcholine (ACH) to provoke the release of endothelium-derived relaxing factor (EDRF) (ACH; 0.3, 1, 3, 10, 30 mumol/L) after precontraction of the vessels with 1 mumol/L norepinephrine (NE). This showed normal contractility and ACH-induced relaxation in the native vessels but a reduced contractile response and a total lack of ACH-EDRF-induced relaxation in the prepared vessels. Perfusion with 5-hydroxytrytamine (5-HT) (0.25, 0.5, 1, 10 mumol/L for 10 min each concentration) resulted in marked constriction of all vessels with preserved contractility which could be completely prevented by pretreatment with the 5-HT2-receptor antagonist ketanserine (20 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗