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Biomedical subjects

M Markiewicz

Publications and source records attributed to M Markiewicz.

At least 19 recordsLinked to original sources
PubMed2006

Vascular complications after pediatric liver transplantation from the living donors.

Early arterial or portal vein thrombosis is a complications that can lead to graft loss and patient death or need of immediate retransplantation. The aim of the study was to assess the incidence, causes, treatment, and outcome of vascular thrombosis after living related donor liver transplantation (LRdLTx). Between 1999 and 2004 71 LRdLTx were performed in children aged from 6 months to 10 years. Vascular thrombosis was found in 12 recipients. Hepatic artery thrombosis (HAT) occurred in 4 (5.6%), portal vein thrombosis (PVT) in 8 (11.2%) cases. HAT occurred 5 to 8 days, PVT 1 to 22 days after LTx. Diagnosis of vascular thrombosis was confirmed by routine Doppler ultrasound examination. Thrombectomy was successful in one patient with HAT and in three patients with PVT. Venous conduit was performed in one patient with PVT after second thrombosis. Two children developed biliary strictures as a late complication of HAT and required additional surgical interventions. Two children with PVT developed portal hypertension with esophageal bleeding, which required surgical intervention; one another underwent endoscopic variceal ligation for grade III varices. Follow-up ranged from 7 to 60 months. One patient died as a result of HAT after retransplantation due to multiple intrahepatic abscesses 2 months after first transplant. Any risk factors of vascular thrombosis that can be controlled should be avoided after transplantation. Routine posttransplant Doppler examination should be performed at least twice a day within 7 to 14 posttransplant days. Immediate thrombectomy should be always carried out to avoid late complications and even mortality.

Child↗
PubMed2005

Peripheral survival of naïve CD8+ T cells.

Maintenance of a sufficient population of naive CD8+ T cells in the peripheral lymphoid compartment is critical for immunocompetence. Peripheral T cell number is a function of T cell generation, survival, and death. Homeostasis, a critical balance between survival and death, must exist to prevent either lymphopenia or lymphocytosis. In the current review, we discuss known requirements for the survival of naive peripheral CD8+ T cells as well as mechanisms of death when survival signals are lost. We also discuss associations between survival and homeostasis-driven proliferation, and highlight the gaps in our knowledge of these critical processes.

Animals↗
PubMed2004

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients.

We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.

Antigens, CD↗
PubMed2004

Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient.

We describe the case of successful delivery in a 21-year-old woman who became pregnant 3 years after liver transplantation and who received sirolimus during the first 6 weeks of gestation. Sirolimus was discontinued when ultrasonography revealed a pregnancy, she was switched to tacrolimus and prednisone was continued. The course of pregnancy was uneventful; there were no signs or symptoms of graft rejection. Due to fetal intrauterine threatening asphyxia the pregnancy was concluded by cesarean section in the 39th gestational week, delivering a healthy, 2950 g, Apgar 10, female infant.

Adult↗
PubMed2004

Depletion of normal B cells with rituximab as an adjunct to IL-2 therapy for renal cell carcinoma and melanoma.

BACKGROUND: We postulated that in patients with metastatic renal cell carcinoma (RCC) or melanoma, depletion of normal B cells using the anti-CD20 mAb rituximab before treatment with low-dose interleukin (IL)-2 would improve clinical outcome. PATIENTS AND METHODS: Rituximab (375 mg/m(2)) weekly for 4 weeks. IL-2 [11 (million units) daily] s.c., 4 days a week for weeks 5-8, followed by a 2-week rest (weeks 9 and 10). Patients without disease progression continued on IL-2. Disease re-evaluation was performed after rituximab and after every course of IL-2. RESULTS: Fifteen patients with RCC and six with melanoma were enrolled. One patient had a partial response and seven patients had stable disease. Toxicities were similar to those expected with IL-2 alone, and there were no grade 4 events. Circulating B cells were depleted in all patients. The subsequent low-dose IL-2 increased absolute numbers of natural killer cells, activated CD4(+) and activated CD8(+) T cells. Expanded T cells produced interferon-gamma, but not IL-4. Proliferation of peripheral blood lymphocytes to phytohemagglutinin was diminished following rituximab treatment, suggesting that B cells participate in this response in vitro. CONCLUSIONS: Our results suggest that depletion of circulating B cells with rituximab does not increase the response rate, alter the toxicity profile or change the biological activity in response to low-dose IL-2 in patients with RCC or melanoma.

Adult↗
PubMed2003

Switching cyclosporine blood concentration monitoring from C0 to C2 in children late after liver transplantation.

BACKGROUND: Measurement of cyclospoprine (CsA) blood levels at 2 hours after oral administration (C(2)) has been proposed as a better measurement of trough level (C(0)) due to reduced intrapatient variability, acute rejection rate and renal toxicity. The aim of the present study was to assess whether there was any advantage to conversion from C(0) to C(2) CsA blood level monitoring in children late after liver transplantation. We reviewed the data from 44 children more than 1 year after liver transplantation. We measured the daily dose of CsA and the C(0) level before switching versus the daily dose and C(2) level at 6 months after conversion, in addition to the alanine aminotransferase (ALT) activity, creatinine blood concentration, and episodes of acute rejection. RESULTS: Conversion from C(0) to C(2) monitoring was not associated with a significant change in mean daily dose of CsA, mean concentration of creatinine, ALT activity or occurrence of rejection episodes. CONCLUSION: Switching from C(0) to C(2) monitoring did not seem to proffer any benefits for children late after liver transplantation.

Administration, Oral↗
PubMed2003

Acute coagulopathy after reperfusion of the liver graft in children correction with recombinant activated factor VII.

BACKGROUND: Several studies have proven that massive blood loss increases postoperative morbidity and mortality in liver graft recipients. Since we have successfully corrected coagulopathy preoperatively using an intravenous (IV) bolus of recombinant activated factor VII (rFVIIa) in 2 patients with fulminant liver failure, we observed that there was rapid reversal of preexisting advanced coagulopathy in another 40 patients with high risk for intraoperative bleeding by this treatment immediately before transplantation. Recently to control hemostasis we have administered rFVIIa also to patients presenting with acute coagulopathy and nonsurgical bleeding after graft reperfusion as described herein. MATERIALS AND METHODS: We have used rFVIIa in 7 children presenting with severe coagulopathy and nonsurgical bleeding after liver graft reperfusion. The dosage of rFVIIa ranged between 37 and 148 mcg/kg. An antifibrinolytic agent (aprotinin, tranexamic acid) was administered simultaneously. RESULTS: APTT before rFVIIa was 86.10 to 183 seconds, (mean, 132.1 +/- 39.88), after the bolus of rFVIIa 49.4 to 206.1 (mean, 112.7 +/- 58.53), and at the end of surgery 71.70 to 180 (mean, 110.3 +/- 40.98). INR after reperfusion was 1.82 to 3.91 (mean, 2.56 +/- 0.67), 1.03 to 1.92 (mean, 1.54 +/- 0.35) after rFVIIa, and 1.74 to 5.58 (mean, 2.64 +/- 1.35) at the end of surgery. Before rFVIIa administration intraoperative blood transfusions after graft reperfusion were 900 to 4200 mL of red blood cells (RBC) (0.82-5.4 total blood volume) and after reperfusion 0 to 1800 mL of RBC (0-2.5 TBV). No postoperative vascular complications were observed. CONCLUSIONS: A single dose of rFVIIa effectively reverses the severe coagulopathy developing after graft reperfusion, establishing effective hemostasis in liver transplant recipients without an increased risk of thrombotic complications.

Blood Coagulation Disorders↗
PubMed2003

Rapamycin in children after liver transplantation.

Experience with sirolimus (SRL) in pediatric liver transplantation (LTx) is limited. The aim of the study was to present our experience with SRL in this setting. During the last 2 years we administered SRL to 9 LTx: children in 3 due to chronic rejection and 6 due to impaired renal function. SRL was started at 2 months to 2.5 years after LTx. Target trough levels for tacrolimus for patients with chronic rejection was 8 to 10 ng/mL and SRL 10 to 12 ng/mL; for patients with impaired renal function, 4 to 6 ng/mL and 8 to 10 ng/mL respectively. For patients on only SRL and steroids the target level was 12 to 20 ng/mL. Our observation on SRL varied from 3 to 21 months, including liver function, renal function, and side effects. All patients are alive. In 3 patients with chronic rejection (ChR), follow-up biopsies showed no signs of ChR; they all normalized liver biochemistry. Independent of indication all improved their renal function. Follow-up GFR in 5 patients showed significant improvement in all. All patients showed elevated serum cholesterol values. SRL was discontinued in 3 patients due to elevation of liver enzymes in 1, persistently high serum cholesterol in 1, and repeated bouts of opportunistic infection in 1. Addition of SRL with reduced doses of tacrolimus or switching to SRL alone significantly improves renal function.

Acute Disease↗
PubMed2003

Liver retransplantation in children in Poland.

An average of 15% of patients require retransplantation due to irreversible liver graft failure due to primary graft nonfunction, chronic rejection, vascular and biliary complications, or infections. The survival of patients and grafts after retransplantation is inferior to that after primary transplantation. The purpose of the present study was to examine the incidence, indications, and outcome of retransplantation in children. In our center 169 liver transplantations had been performed in 154 patients, and 14 patients (9%) required 15 retransplantations: nine in the early postoperative period, five late after primary transplantation, and one late after the second transplantation. One-year patient survival after primary transplantation was 82%, but after early retransplantation it was 55%.

Child↗
PubMed2003

Surgical treatment of progressive familial intrahepatic cholestasis: comparison of partial external biliary diversion and ileal bypass.

AIMS: Progressive familial intrahepatic cholestasis (PFIC, Byler's disease) is an autosomal recessive disorder resulting in liver fibrosis/cirrhosis and liver insufficiency. Before the 1990s, liver transplantation was the only effective therapy for these children. During the last 12 years, two alternative methods of surgical treatment have been proposed: partial external biliary diversion (PEBD) and ileal bypass procedure (IB), which allow for effective elimination of bile acids accumulated in the body. In this study, we compare the efficacy of these surgical techniques for PFIC. METHODS: During the last 20 years, we have treated 52 children with PFIC. PEBD was done in 21 patients (since 1995), and IB in 5 patients (since 1998), transplantation was performed in 9 patients (since 1990). The efficacy of non-transplantation surgical treatment was assessed by patients' clinical outcome, liver biochemistry, and survival without transplantation during a follow-up period of 12 to 48 months. RESULTS: In 15 out of 21 patients clinical symptoms improved after PEBD and liver function tests normalised (blood bile acids), 1 patient had to be converted to IB due to too high output biliary fistula, 2 patients were transplanted and 3 are considered for transplantation. Out of the 5 children after IB, 4 improved clinically and biochemically, but, after 12 months, symptoms recurred in 3 patients, one patient was converted successfully to PEBD. No significant influence on growth was observed, irrespective of the type of treatment in this group of patients. CONCLUSIONS: PEBD is more effective than IB for the permanent improvement of symptoms of PFIC. Ileal bypass procedure, although initially effective, does not ensure good long-term results in more than 50 % of patients, probably due to intestinal re-absorption of bile acids increasing over time.

Adolescent↗
PubMed2000

Synthetic oligonucleotide combinatorial libraries and their applications.

The application of synthetic oligonucleotide combinatorial libraries is described in the studies of triplex DNA. A new method of selection of dispersed (beaded) oligonucleotide combinatorial libraries based on the use of streptavidin magnetic beads is presented. A combinatorial chemistry approach is also proposed for studies of polyaminooligonucleotides.

Carbohydrate Sequence↗
PubMed1999

Treatment of progressive familial intrahepatic cholestasis: liver transplantation or partial external biliary diversion.

Progressive intrahepatic familial cholestasis (PFIC), previously called Byler's disease, is a syndrome in which children develop severe cholestasis progressing to biliary cirrhosis and chronic liver failure, usually during the first decade of life. Clinical features include jaundice, hepatomegaly, splenomegaly, growth retardation and severe pruritus. Laboratory tests demonstrate elevated bilirubin and bile acids, without an increase in serum gamma-glutamyl-transpeptidase or cholesterol. This study was performed to evaluate our experience with medical therapy as well as two types of surgical treatment used in children with PFIC, particularly partial external biliary diversion (PEBD) as an alternative method of therapy to liver transplantation (OLTx). Between 1979 and 1998 we have treated 46 children with PFIC (27 boys and 19 girls), aged 10 months to 19 yr (at the time of this study). Medical treatment with ursodeoxycholic (UDCA) was used in 39 patients for the period between 6 and 82 months. PEBD (cholecysto-jejuno-cutaneostomy) was performed in 16 patients, OLTx in eight children (including one after unsuccessful PEBD). Retrospective analysis of the clinical course and selected laboratory tests (bilirubin, ASPAT, ALAT, bile acids), and histopathological examinations were performed. Results of treatment were assessed by means of influence of the type of treatment on clinical symptoms, laboratory tests, progress of liver cirrhosis and hepatic failure, as well as physical development and survival. Medical therapy was effective in the long term in four (10%) of the patients resulting in clinical and biochemical normalization. Both surgical methods of therapy of PFIC, PEBD and OLTx, resulted in an 80% success rate and therefore should be used as complementary therapies. In patients before established liver cirrhosis, PEBD should be the first choice of treatment. Patients presenting with cirrhosis or after ineffective PEBD should qualify for OLTx. With this strategy most children with PIFC can be cured.

Adolescent↗