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Biomedical subjects

L Bäckman

Publications and source records attributed to L Bäckman.

At least 19 recordsLinked to original sources
PubMed2007

Successful combined partial auxiliary liver and kidney transplantation in highly sensitized cross-match positive recipients.

Combined liver and renal transplantations can be performed against a positive cross-match, indicating that the liver protects the kidney from the harmful HLA antibodies. This led us to the hypothesis that a partial auxiliary liver graft may have a similar protective effect when performed together with the kidney in highly sensitized patients. Seven patients, with broadly reacting HLA antibodies and positive crossmatches, were transplanted with a partial liver and a kidney from the same donor. In one of the cases a living donor was used. We performed lymphocytotoxic and flow cross-matches before and after the transplantation. Cross-matches turned negative after grafting in five of seven cases. The kidney function was excellent, without rejections, during the follow-up (24-60 months) in these patients. In two cases the cross-match remained positive after transplantation, one with a never-functioning renal graft and the other with an early graft failure, probably due to humoral rejection. A simultaneous transplantation of a partial auxiliary liver graft from the same donor, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, can be performed successfully despite a positive cross-match and may thus be a new option of treatment for highly sensitized patients waiting for a kidney transplant.

Adult↗
PubMed2006

Contrasting cognitive trajectories of impending death and preclinical dementia in the very old.

BACKGROUND: Both impending death and preclinical dementia are associated with cognitive impairment in old age, although their effects on cognitive functioning have rarely been examined within the same study. METHODS: Participants (n = 1,200, aged 75+ years) from a community-based study completed a measure of global cognitive performance (the Mini-Mental State Examination [MMSE]) at 3-year intervals over an 11-year period. Level and change of MMSE performance were compared for three groups: persons in close proximity to death, persons in a preclinical phase of dementia, and persons who remained alive and nondemented throughout the study. RESULTS: There were significant group differences in MMSE performance 3 years before each outcome (death, dementia, or end of study). Those with preclinical dementia performed the poorest and declined twice as fast on the MMSE relative to the other groups. Although persons in close proximity to death declined faster in general, no accelerated decline was observed for the impending death group after persons with dementia or preclinical dementia had been excluded. Group differences were attenuated for the oldest-old (81+ years) compared to the old-old (75 to 80 years). CONCLUSIONS: The lack of accelerated decline in proximity to death after excluding persons with dementia or preclinical dementia suggests that part of the terminal decline effect demonstrated in previous investigations may reflect preclinical dementia deficits. Further, accelerated cognitive decline might be a more reliable indicator of preclinical dementia than a low cognitive score due to confounds associated with cross-sectional cognitive performance.

Age Factors↗
PubMed2006

Successful ABO-incompatible liver transplantation using A2 donors.

INTRODUCTION: The longer waiting time for a liver graft among patients with blood group O makes it necessary to expand the donor pool for these patients. We herein have reported our experience with ABO-incompatible liver transplantation using A(2) donors to blood group O recipients. PATIENTS AND METHODS: Between 1996 to 2005, 10 adult blood group O recipients received 10 A(2) cadaveric grafts. Mean recipient age was 52 +/- 7.7 years (mean +/- SD). The initial immunosuppression was induction with antithymocyte globulin (n = 2), interleukin-2-receptor antagonists (n = 3), or anti-CD20 antibody (rituximab, n = 1), followed by a tacrolimus-based protocol. No preoperative plasmapheresis, immunoadsorption, or splenectomies were performed. RESULTS: Patient and graft survival was 10/10 and 8/10, respectively, at 8.5 months median follow-up (range 10 days to 109 months). Two patients were retransplanted because of bacterial arteritis (n = 1) and portal vein thrombosis (n = 1). The six acute rejections, which occurred in four patients, were all reversed by steroids or increased tacrolimus dosages. The pretransplant anti-A titers against A(1) red blood cells were 1:128 (NaCl technique) and 1:8 to 1024 (IAT technique). The maximum postoperative titers were 1:64 to 4000 (NaCl) and 1:256 to 32000 (IAT). CONCLUSION: The favorable outcome of A(2) to O grafting, with a patient survival of 10/10 and graft survival of 8/10, makes it possible to consider this blood group combination also in nonurgent situations. There was no hyperacute rejection or increased rate of rejections. Anti-A/B titer changes seem to not play a significant role in the monitoring of A(2) to O liver transplantation.

ABO Blood-Group System↗
PubMed2006

Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial.

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.

Adult↗
PubMed2006

Pseudoaneurysm of the hepatic artery following liver transplantation.

We report 12 cases of pseudoaneurysm hepatic artery (PA) among 825 liver transplantations (OLT) performed between January 1985 and December 2005. In the early period (1985 to 1995), the incidence was 2.6% and in the later period (1996 to 2005), 0.9%. Median time to onset was 39.5 days post-OLT (range 14 days to 5 years). Six patients presented with rupture into the peritoneum (n = 4) or gastrointestinal tract (n = 2), while five patients presented with gastrointestinal bleed due arteriobiliary fistulation with hemobilia. The twelfth PA was found incidentally during retransplantation. PAs were detected with radiological imaging (n = 4), exploratory laparotomy (n = 6), at autopsy (n = 1) or at retransplantation (n = 1). We performed immediate revascularization, after surgical excision was performed in three and endovascular embolization in one patient. In six patients hepatic artery ligation without revascularization was inevitable with subsequent successful retransplantation in four patients. No PA-specific treatment was attempted in two cases due to the poor prognosis or diagnostic ambiguity. In 10 cases microbial pathogens were cultured in the blood, subhepatic abscesses, or from the wall of the hepatic artery. A hepaticojejunostomy was performed for biliary reconstruction in six patients and two had a hepaticojejunostomy conversion due to biliary leak. Survival in the early period (1985 to 1995) was 14%, whereas during the later period (1996 to 2005), the survival increased to 100% with a 4.2-year median follow-up (range 7.4 months to 6.9 years). Infrequently PA complicates OLT, becoming evident primarily after rupture with hemoperitoneum or a gastrointestinal bleed. Early recognition with angiography is important but acute hemorrhage often requires immediate exploration with ligation of the PA, although surgical or endovascular exclusion of the PA followed by revascularization provides a feasible treatment option.

Anastomosis, Surgical↗
PubMed2006

The cadaveric organ donor program at Sahlgrenska University Hospital, 1977 to 2005.

The transplantation program with cadaveric organs has been ongoing at our institution for more than 40 years, since 1965. The purpose of this report was to analyze changes in the donor population and causes of death over the years. This retrospective analysis of donor records between 1977 and 2005, included 1331 donors. Since 1977, the number of donors has remained unchanged, but their profile has changed. The median donor age today has almost doubled, from 30 to nearly 60 years. Early on the most common cause of death was head trauma and the majority of donors were men. Since the mid-1980s, the main cause of death was intracerebral hemorrhage or cerebral thrombosis and the gender distribution became equal. The number of procured and transplanted organs from each donor has increased, despite an increased donor age. The multi-organ donor rate exceeded 80% in the beginning of this decade; we retrieved 3.9 organs per donor. These results may be explained by improved organ donor care and organization, and by increased awareness of potential donors among elderly patients.

Adolescent↗
PubMed2006

Outcome of renal transplantation subsequent to liver, heart, or lung transplantation.

Renal dysfunction is a growing problem after liver, heart, or lung transplantation with the subsequent need for dialysis or renal transplantation. The aim of this study was to analyze the outcome after a subsequent kidney transplantation (secondary kidney transplantation) in liver, heart, or lung transplantation recipients. All secondary kidney transplantation patients from 1985 to 2006 were identified for the cause of kidney failure, time after initial transplantation, and current kidney function. One thousand two hundred three patient charts were reviewed including 22 (1.8%) secondary kidney transplantations: eight after lung, eight after heart, and six after liver transplantation. Renal failure was the result of perioperative renal failure (n = 3), toxic effects of cyclosporine (n = 16), a combination of cyclosporine nephrotoxicity and vascular ischemia (n = 3), or chronic renal failure due to polycystic kidney disease (n = 1). The median time after the initial organ transplantation was 114 months (range 30 to 241 months). The most recent median creatinine value was 103 micromol/L (82 to 704 micromol/L). Renal transplant rejection was noted in five patients: four in the lung transplant group, and one after heart transplantation. Three patients were deceased, one from secondary renal failure. One renal allograft was removed after renal artery thrombosis. In conclusion, there is sometimes a need for subsequent kidney transplantation after liver, heart, or lung transplantation. The outcome of renal transplantation subsequent to liver, heart, or lung transplantation is good with satisfactory renal function in this study population.

Heart Transplantation↗
PubMed2005

Preemptive therapy with pegylated interferon alpha-2b and ribavirin after liver transplantation for hepatitis C cirrhosis.

UNLABELLED: We present our results of preemptive treatment with pegylated interferon and ribavirin after liver transplantation for hepatitis C cirrhosis. PATIENTS: Between September 2001 and August 2002, four patients were started on combination therapy with pegylated interferon-alpha-2b (1microg/kg weekly) and ribavirin (400-1000 mg/d) 3 to 4 weeks' posttransplant. Treatment was continued for 6 (genotype 3a, 2 patients) or 12 (genotype 1b, 2 patients) months. Virologic and biochemical responses as well as side effects were evaluated. RESULTS: Two patients (genotype 3a) became HCV (hepatitis C virus)-RNA negative after 3 months of therapy and are persistently negative 20 and 14 months after end of therapy. One patient (genotype 1b) became HCV-RNA negative 6 months after start of treatment, but therapy had to be withdrawn after 9 months owing to fatigue and suspicion of angina pectoris. One patient who was later retransplanted because of hepatic artery thrombosis discontinued therapy after 2.5 months owing to anemia, leukopenia, and no signs of HCV-RNA reduction. Interestingly, two of the responders were nonresponders prior to liver transplant. Median ALT levels at start of therapy were 98 U/L (r = 60-126) and 12 months later 40 U/L (r = 24-58) (n = 4). No rejection episode was detected. CONCLUSION: In patients liver-transplanted due to HCV-cirrhosis, combination therapy with pegylated interferon and ribavirin can be effective and safe in the early posttransplant period, thus preventing recurrent hepatitis C.

Antiviral Agents↗
PubMed2004

APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging.

OBJECTIVE: To investigate whether presence of the APOE epsilon4 allele is related to the pathologic progression of preclinical Alzheimer disease (AD), as reflected by change in Mini-Mental State Examination (MMSE) scores among persons in the preclinical phase of AD, and cognitively intact adults confirmed as dementia-free during the 6-year assessment period. METHOD: In a population-based sample, participants were stratified according to APOE genotype (epsilon4 or non-epsilon4) and whether they received a diagnosis of AD at the end of either a 3- or 6-year assessment period. Participants were aged 75 years and older, and were nondemented at baseline. At the end of the 3-year period, 17.2% of non-epsilon4 and 26.7% of epsilon4 carriers became demented. For the 6-year period those percentages were 11.2% for non-epsilon4 carriers and 16.9% for epsilon4-carriers. RESULTS: Individuals in the preclinical phase of AD showed greater decline on the MMSE as compared to nondemented adults. However, the decline was most marked in the 3 years prior to clinical diagnosis. Further, APOE-epsilon4 genotype did not modify the rate of decline among to-be-demented participants, as well as individuals who would remain free of AD. CONCLUSIONS: Although possession of the APOE epsilon4 allele is a risk factor for AD in old age, it does not modify the progression of the disease during the preclinical period. Further, in the absence of preclinical dementia, APOE did not influence global cognitive change in nondemented persons.

Aged↗
PubMed2004

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Aged↗
PubMed2004

Multiple cognitive deficits during the transition to Alzheimer's disease.

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at-risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain-based) in order to increase prediction accuracy.

Aged↗
PubMed2003

Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.

In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA.

Adrenal Cortex Hormones↗
PubMed2003

Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries.

BACKGROUND: Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post-transplant survival. METHODS: Data from two groups of patients receiving liver allografts during 1982-2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival. RESULTS: A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of re-transplantation in PSC patients were an episode of early rejection and vascular thrombosis. CONCLUSION: In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re-transplantation compared to the comparison group.

Adolescent↗
PubMed2002

Sirolimus steady-state trough concentrations are not affected by bolus methylprednisolone therapy in renal allograft recipients.

AIMS: To determine whether bolus doses of methylprednisolone affect the steady-state trough concentrations of sirolimus. METHODS: Fourteen renal transplant recipients received concentration-controlled sirolimus therapy in combination with azathioprine and steroids (n=8) or mycophenolate mofetil and steroids (n=6). Bolus doses of methylprednisolone (mean total dose over 1-5 days, 1694 mg; range, 500-3000 mg) were given for the treatment of acute rejection. For each patient, the sirolimus dose (mean, 24.1 mg; range, 3.3-52.5 mg) was the same before and during methylprednisolone therapy. RESULTS: Mean sirolimus whole blood trough concentrations before and after treatment with methylprednisolone were 28.8 ng ml-1 (range, 13.9-45.3 ng ml-1), and 28.5 ng ml-1 (range, 13.0-47.9 ng ml-1), respectively (P=0.85; 95% confidence interval on the difference -3.3, 4.0 ng ml-1). CONCLUSIONS: Bolus methylprednisolone treatment does not affect steady-state sirolimus trough concentrations.

Adult↗