Biomedical subjects

Goran B Klintmalm

Publications and source records attributed to Goran B Klintmalm.

At least 19 recordsLinked to original sources

PubMed2007

Acute graft-versus-host disease after liver transplantation: role of withdrawal of immunosuppression in therapeutic management.

Graft-versus-host disease (GVHD) after liver transplantation is rare but associated with a very high mortality (over 85%). Most treatments focus on increasing immunosuppression, addition of antibody preparations such as OKT3 and antithymocyte globulin to eliminate the donor lymphocytes, and supporting myelopoiesis by use of cytokines. However, the results are very poor. We reasoned that a better therapeutic approach would be to reduce the immunosuppression and allow the patient's immune system an opportunity to reject the allograft donor T cells. We tested this novel therapeutic approach in 3 patients diagnosed with GVHD. Two patients had rapid loss of donor T cell chimerism and resolution of their symptoms. The other patient continued to progress to severe GVHD and died. The patients who responded to withdrawal of immunosuppression had a later onset of symptoms and a lower level of donor CD3+ T cells at the start of treatment. We conclude that larger studies are needed to further evaluate these results and to determine what factors may affect the likelihood that a patient may respond to this approach.

Adult↗

PubMed2006

Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.

BACKGROUND: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. METHODS: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. RESULTS: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). CONCLUSION: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Adult↗

PubMed2006

Graft-vs-host disease as a complication of lung transplantation.

We report a rare case of acute graft-vs-host disease (aGVHD) after a lung transplant. The patient presented with advanced disease manifested by skin rash, fever, diarrhea, liver dysfunction and severe pancytopenia. He went on to die of sepsis and multi-organ failure. aGVHD is a disease often confused with drug reactions or viral infection; therefore, it is important to have a high index of suspicion and to confirm the diagnosis early with tests for donor cell chimerism. Effective treatment is elusive but we are learning a great deal about the underlying mechanisms of this disease and hope to develop better treatment.

Chimerism↗

PubMed2006

Systemic and cerebrospinal fluid T-helper cytokine responses in organ transplant recipients with Cryptococcus neoformans infection.

BACKGROUND: The role of Th1 and Th2 mediated cytokine responses in the pathogenesis of Cryptococcus neoformans infection in organ transplant recipients has not been defined. METHODS: We assessed cytokine levels in the sera and CSF collected prospectively at the time of diagnosis of infection in 25 transplant recipients with cryptococcosis. Serum levels were compared with those in healthy individuals and transplant recipients without cryptococcosis. IFN-gamma or IL-12 (Th1)/IL-10 (Th2) ratio < 1.0 was considered a dominant Th2 response. RESULTS: Cases had lower ratios of IFN-gamma/IL-10 (p = 0.03) and IL-12/IL-10 (p = 0.03) compared to healthy individuals. Cytokine responses, however, did not differ significantly for cases vs. transplant controls. Cases with fungemia compared to those without fungemia tended to have higher serum IL-10 levels (p = 0.07) and lower IL-12/IL-10 ratios (p = 0.06). CSF ratios of IFN-gamma/IL-10 (p = 0.04) and IL-12/IL-10 (p = 0.04) were lower in cases with cryptococcal meningitis compared to those without meningitis; 80% (8/10) of the cases with cryptococcal meningitis vs. 0% (4/4) of those without meningitis had CSF IFN-gamma/IL-10 ratio of < 1.0 (p = 0.015). The levels of IL-10 (p = 0.04) and IFN-gamma (p = 0.04) in the CSF in cases with cryptococcal meningitis were significantly higher than those in their serum, respectively. CONCLUSIONS: High expression of Th2 phenotype in cryptococcal meningitis and in fungemia suggests that Th dysregulation may contribute to the pathogenesis of cryptococcosis in organ transplant recipients.

Cryptococcus neoformans↗

PubMed2006

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

BACKGROUND: : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. METHODS: : Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. RESULTS: : Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. CONCLUSIONS: : Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Adult↗

PubMed2006

Clinical outcomes from hepatic artery stenting in liver transplantation.

Hepatic artery stenosis after liver transplantation may affect liver function and result in hepatic artery thrombosis. Surgical reconstruction has been the first choice for treatment. Interventional radiologic technique can be used, but there is no report on long-term outcome. The aim of this paper is to assess current outcome and complications of hepatic artery stenting. Twenty-six adult patients were stented for hepatic artery stenosis between 1998 and 2003. Nine patients had previous surgical reconstruction for hepatic artery stenosis. Seventeen patients suffered newly developed hepatic artery stenosis. Three patients were retransplanted. After stenting, the patients were followed by Doppler ultrasound at day 1, 1 month, and 6 months. Angiography was scheduled in 6 months. Four patients died within 2 months. The other 22 patients were followed for mean 31 +/- 14 months (8-71 months). One of 22 patients died from renal failure 2 years later. Twelve patients' hepatic arteries looked normal after stenting. Restenosis was seen in 8 patients (36%). Other complications were artery thrombosis (n = 1) and long segment stricture (n = 1). In 2 patients (25%) restenosis resulted in thrombosis. Six of the 8 patients who developed recurrent stenosis were successfully treated interventionally: restent (n = 5) and balloon dilation (n = 3). However, 3 patients (38%) restenosed. Kaplan-Meier complication-free survival was 54% at 1 year after stenting. In conclusion, hepatic artery stenting is a viable treatment for hepatic artery stenosis with reasonable results. Stenting is useful as adjuvant treatment after surgical revision.

Adult↗

PubMed2006

An outcome comparison between primary liver transplantation and retransplantation based on the pretransplant MELD score.

Survival after liver retransplantation (RLTX) is worse than after primary liver transplantation (LTX). We studied retrospectively the 2-year outcome in 44 patients who received RLTX more than 30 days after the primary transplant and in 669 after LTX performed between December 1993 and October 1999, focusing on the relation between the model for end-stage liver disease (MELD) score immediately pretransplant and post-transplant survival. A 2-year survival for RLTX was inferior to LTX (65.9% vs. 82.9%, P < or = 0.01). This difference was greatest with MELD scores < 25; survival within 2 years remained 11.3-18.2% less for RLTX than for LTX (6 months, P = 0.002; 12 months, P = 0.029, 24 months, P = 0.123). Mortality was mainly related to early vascular complications and sepsis. Two-year survival after RLTX was 81.8% if RLTX occurred < 2 years after LTX and 50% if the interval between LTX and RLTX was > 2 years (P < 0.05). MELD scores were similar in 2-year survivors and nonsurvivors after late RLTX (P = 0.82). Late RLTX is marked by poor survival regardless of the pretransplant MELD score. The MELD-based allocation system may not benefit patients who undergo retransplantation.

Adolescent↗

PubMed2006

Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: the "hepatitis C 3" multi-institutional trial experience.

CONTEXT: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. OBJECTIVE: To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the "Hepatitis C 3" trial. DESIGN: The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin-stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs. RESULTS: Statistically significant agreement was found among all participating pathologists (P < .001). On kappa analysis, the degree of agreement was rated "moderate" for HCV grade and stage and ACR global grading (kappa = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (kappa = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (kappa = 0.76 "almost perfect" for HCV and 0.62 "substantial" for ACR). CONCLUSIONS: An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.

Acute Disease↗

PubMed2005

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.

BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed antifungal treatment practices for cryptococcosis in a cohort of prospectively followed organ transplant recipients. METHODS: The patients comprised 83 transplant recipients with cryptococcosis followed for a median of 2.1 and up to 5.2 years. RESULTS: Patients with central nervous system infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P = 0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive regimens containing amphotericin B than fluconazole as primary therapy. The use of fluconazole, on the other hand, was more likely for infection limited to the lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in patients whose CSF cultures at 2 weeks were positive compared to those whose CSF cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed in 68% (54/79) of the patients who survived >3 weeks. The median duration of maintenance therapy was 183 days; 55% received maintenance for > or = 6 months and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients. CONCLUSIONS: A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.

Adult↗

PubMed2005

Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome.

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Cryptococcosis↗

PubMed2005

Cadaveric orthotopic auxiliary split liver transplantation and kidney transplantation: an alternative for type 1 primary hyperoxaluria.

Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.

Cadaver↗

PubMed2005

An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.

BACKGROUND: We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. METHODS: The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. RESULTS: In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. CONCLUSIONS: This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

Adult↗

PubMed2005

Transmission of rabies virus from an organ donor to four transplant recipients.

BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

Antibodies, Viral↗

PubMed2005

Successful combined liver and kidney transplant for COACH syndrome and 5-yr follow-up.

The COACH syndrome is a very rare disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Nineteen cases with COACH diagnosis have been reported. Neurologic abnormalities are the first symptoms in most cases. Complications of the hepatopathy [portal hypertension, esophageal varices, and gastrointestinal (GI) bleeding] contribute extensively to the morbidity and lethality in the course of the disease. We describe a 28-yr-old female with COACH syndrome resulting in chronic renal and hepatic insufficiency. The patient was found to have significant mental retardation, truncal ataxia, motor abnormality and occulomotor abnormality. She began to develop GI bleeding and encephalopathy because of biopsy-confirmed cirrhosis. We performed combined liver and kidney transplant after challenging discussion. Her postoperative course was uneventful, and she was discharged on the ninth postoperative day (POD). She has not had any problems at 1, 3 and 5-yr follow-up with excellent liver and renal function. This is the first description of successful combined liver and kidney transplant with long-term follow-up. The decision for transplant is challenging because COACH syndrome is rare with only descriptive characterization and patients have non-progressive ataxia and mental retardation. However, our case shows that liver and kidney transplant can be medically successful, and the individuals achieve long-term success if they have a stable neurological condition and an excellent support system.

Abnormalities, Multiple↗

PubMed2004

Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation.

BACKGROUND: Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. METHODS: OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, n=637; group II: hemodialysis only post-OLTx, n=17; and group III: continuous RRT post-OLTx, n=70. Univariate and stepwise logistic multivariate analyses were performed. RESULTS: Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplant=(-2.4586+1.2726 [creatinine >1.9] + 0.9858 [blood urea nitrogen >27] + 0.4574 [Model for End-Stage Liver Disease score >21] + 1.1625 [intensive care unit days >3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. CONCLUSIONS: This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.

Adult↗

PubMed2004

Pseudohypocalcemia after magnetic resonance imaging with gadolinium in patients with cirrhosis.

Hypocalcemia in patients with cirrhosis may be due to a number of causes. We noted a relationship between injection with gadodiamide, a particular gadolinium chelate, during magnetic resonance imaging of the liver and the development of a falsely low serum total calcium level in a patient with cirrhosis. A cross-reference and retrospective chart review identified 10 additional patients in whom this phenomenon was noted. We describe the temporal relationship and clinical characteristics of these patients. Pseudohypocalcemia following magnetic resonance imaging with gadodiamide contrast should be considered in the differential diagnosis of hypocalcemia in patients with cirrhosis.

Adult↗

PubMed2004

Liver transplantation and health-related quality of life: scoring differences between men and women.

Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage liver disease of various etiologies. Its use, however, remains limited due to the scarcity of donor organs. Measures to assess health-related quality of life (HRQOL) are increasingly being implemented to examine the efficacy of medical therapies involving scarce resources. HRQOL was assessed and compared between 88 male and 61 female patients before and after liver transplantation. Data were gathered from subjects having completed a questionnaire pre-OLT, and again at 1 year and 2 years post-OLT. This questionnaire, developed specifically for OLT patients, contains at its core questions derived from several well-established instruments measuring health status and HRQOL. Male OLT recipients reported a higher degree of overall HRQOL than that reported by female OLT recipients, both before and after OLT. When controlling for disparity in education between the sexes, findings revealed that among the lesser educated (< or =12 years), men and women scored similarly, while among the more educated (>12 years), men scored higher than women. Employment findings revealed a higher percentage of men working before transplant and at 1-year post-OLT when compared with women. At 2 years post-OLT, men and women exhibited similar employment rates. Male OLT recipients report a higher level of overall HRQOL than that reported by female OLT recipients, both before and after liver transplantation. Education appears to significantly affect HRQOL and may account for, at least in part, differences in reported HRQOL between male and female OLT recipients.

Educational Status↗

PubMed2004

Estimation of glomerular filtration rates before and after orthotopic liver transplantation: evaluation of current equations.

The ability to estimate rather than measure the glomerular filtration rate (GFR) in patients before and after liver transplantation would be helpful in estimating risk, dosing drugs, and assessing long-term toxicity of calcineurin inhibitors. Currently available equations for estimating the GFR have not been validated in either the pre- or post-liver transplant population. We have evaluated the performance of currently used formulas for the estimation of the GFR in this setting. Data were collected prospectively on patients who underwent liver transplantation between 1984 and 2001. GFR per 1.73 m2 was measured by I125 iothalamate in patients at the pretransplant evaluation and at 3 months, 1 year, and yearly posttransplant thereafter. GFR estimated by the Cockcroft-Gault equation, the Nankivell equation, and the equations from the Modification of Diet in Renal Disease (MDRD) Study (6, 5, and 4 variables) was compared with the measured GFR. Pretransplant GFR was available in 1,447 patients. The mean GFR was 90.7 +/- 40.5 mL/min. Values for r and r2 were highest for the MDRD Study 6-variable equation (0.70 and 0.49, respectively). Only 66% of estimates were within 30% of the measured GFR. At 3 months, 1 year, and 5 years posttransplant, the mean GFR was 59.5 +/- 27.1 mL/min, 62.7 +/- 27.8 mL/min, and 55.3 +/- 26.1 mL/min, respectively. Values for r and r(2) for the MDRD Study 6-variable equations at 1 and 5 years posttransplant were 0.74 (0.55) and 0.76 (0.58), respectively. At these time points, however, only 67% and 64% of the estimated GFR were within 30% of the measured GFR. MDRD Study equations had greater precision than other equations, but the precision was lower than reported for MDRD estimation of GFR in other populations. Better methods for estimating the GFR are required for evaluation of renal function before and after liver transplantation.

Adolescent↗