Plasmodium falciparum malaria occurring four years after leaving an endemic area.

We present a case of a 52-year-old woman of Ghanaian origin who developed Plasmodium falciparum malaria 4 years after leaving Africa. She had not returned to an endemic area since. We hypothesize several possible scenarios to explain this infection, of which we believe recrudescence of P. falciparum is the most plausible. This occurred most likely as a consequence of waning immunity several years after leaving a high-transmission area. She recovered after a 3-day treatment with atovaquone/proguanil.

Tetanus: a diagnostic challenge in the Western world.

Tetanus is a very serious neuromuscular disease caused by a powerful exotoxin, tetanospasmin, from the Clostridium tetani bacillus. Its incidence in the developed world has diminished considerably since the introduction of primary vaccination. Tetanus is diagnosed clinically, through recognition of the characteristically inducible muscle spasms. Three clinical forms described in adults are generalised, localised and cephalic tetanus. Management of tetanus aims at removing the source of tetanospasmin, neutralising circulating toxin, and providing adequate supportive care for muscle spasms, respiration and autonomic instability. Tetanus is a forgotten disease in developed countries since many practicing primary care physicians have not seen a single case in their career. We present a case of tetanus and review briefly the pathogenesis, clinical features and therapy in order to educate the internist in recognising and adequately treating this disease.

Fluctuations of haemoglobinaemia in chronic haemodialysis patients.

In March 2008 and June 2009, an ad hoc working group of nephrologists discussed the status of anaemia therapy with erythropoiesis-stimulating agents [ESA] in patients on chronic haemodialysis, the phenomenon of fluctuations of haemoglobinaemia, and the need for individualisation of ESA treatment. The working group put together the following statements: (1) ESAs increase the haemoglobin concentration and adaptations of the ESA dose adjust the response according to a negative-feedback loop. The long lag time between an ESA dose change and its effect on erythropoiesis is cumbersome. The optimal haemoglobin target concentration is different for every haemodialysis patient; the lowest haemoglobin concentration upon which one could consistently demonstrate a positive subjective and objective clinical benefit in chronic dialysis is 11 g/dL, in contrast to the lowest haemoglobin concentration of 10 g/dL recommended in the current EMEA label for ESAs. (2) Intra-individual fluctuation of haemoglobinaemia over time is unavoidable, not only due to the ESA dose/haemoglobin response interaction, but also, and more importantly, due to the occurrence of acute illnesses and exacerbations of co-morbid conditions. Many different methodologies to characterise haemoglobin variability have been described but there is currently no universally applied definition of the phenomenon. (3) An impact of the haemoglobin level and the amplitude of the haemoglobin fluctuations on patient outcome has been observed. Without disclosing any causal relationship, worse outcomes were associated with haemoglobin fluctuations around the lower target level, but later on, more simply linked to the relative time spent below the haemoglobin concentration of 11 g/dL and to the administration of inappropriately high ESA doses in order to achieve the recommended haemoglobin target range. A plausible mechanism might be that acute illnesses blunt the patients' basal ESA sensitivity; this leads to subnormal and/or varying haemoglobin levels, currently initiating an ESA dose increase. The longer it takes the patient to recover from the acute illness, the more the prolongation of the clinically poor condition is to some extent maintained by the persistence of low haemoglobinaemia and/or by the administration of high ESA doses, and, as such, on their turn possibly contributing to an ultimate poor outcome. In the absence of clinical trials, recommendations should be offered how to proceed with the administration of ESAs as optimal as possible in periods of clinical instability.

Severe diarrhea in renal transplant patients: results of the DIDACT study.

Diarrhea is common in transplant recipients. While the majority of cases are mild and transient, some are severe and prolonged, which can threaten graft survival through dehydration. While it is known that some immunosuppressive agents can elicit diarrhea, there does not appear to be any consensus on the role that other nonimmunosuppressive causes can play in transplant patients. The aim of the present open, nonrandomized, multicenter study was to identify nonimmunosuppressive factors involved in severe diarrhea in renal transplant patients. Patients (n = 108) with severe diarrhea (>/=3 stools/day for >/=7 days) were enrolled from 16 Belgian transplant centers. Patients were diagnosed according to an agreed flowchart that consisted of identification of possible infections, followed by changes in empirical and immunosuppressive treatment. Approximately 50% of patients experienced resolution of severe diarrhea following treatment for infections, dietary problems or diarrhea-causing concomitant medications. In conclusion, a large proportion of the severe diarrhea observed in renal transplant recipients is not associated with immunosuppressive therapy and can be treated through anti-infectives, changes to concomitant medication and other empirical treatments. Correct diagnosis of the cause of severe diarrhea in such patients should help to protect graft survival in transplant recipients.

Repositioning and leaving in situ the central venous catheter during percutaneous treatment of associated superior vena cava syndrome: a report of eight cases.

PURPOSE: To describe a combined procedure of repositioning and leaving in situ a central venous catheter followed by immediate percutaneous treatment of associated superior vena cava syndrome (SVCS). METHODS: Eight patients are presented who have central venous catheter-associated SVCS (n = 6 Hickman catheters, n = 2 Port-a-cath) caused by central vein stenosis (n = 4) or concomitant thrombosis (n = 4). With the use of a vascular snare introduced via the transcubital or transjugular approach, the tip of the central venous catheter could be engaged, and repositioned after deployment of a stent in the innominate or superior vena cava. RESULTS: In all patients it was technically feasible to reposition the central venous catheter and treat the SVCS at the same time. In one patient flipping of the Hickman catheter in its original position provoked dislocation of the released Palmaz stent, which could be positioned in the right common iliac vein. CONCLUSION: Repositioning of a central venous catheter just before and after stent deployment in SVCS is technically feasible and a better alternative than preprocedural removal of the vascular access.

Five years of surgical experience with peritoneal dialysis.

In this study, we evaluate retrospectively five years experience with the Swann Neck Missouri DC catheters. Sixty three catheters are placed in 51 patients. The total observation period is 695.6 months and the average time is 13.6 months per patient. The last 21 catheters are coiled type. Infectious complications remain the most worrisome problem in peritoneal dialysis. Exit site infections are seen in 24%, tunnel infections in 8%, peritonitis in 38% and abdominal hernias in 16% of the patients. The results in our series (peritonitis every 29.0 patient-months) are in accordance with data from the literature. The combination of a good surgical technique and an efficient postoperative attendance have reduced this frequency. In the situation of a tunnel infection, surgical removal remains the treatment of choice. To prevent an exit site infection, the entry port must be well nursed and protected. A coexisting abdominal hernia can be repaired during the implantation procedure. Fourty six peritoneal dialysis catheters have been removed. Transplantation and death are the main reasons (59%).

High prevalence of hepatitis G virus infection compared with hepatitis C virus infection in patients undergoing chronic hemodialysis.

A recently discovered non-A-E hepatitis virus has been designated as hepatitis G virus (HGV) and identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood-borne hepatitis and usually in the presence of hepatitis C or hepatitis B virus (HBV) infection. In this study, the presence of HGV-RNA in serum or plasma and the prevalence of antibodies against an HGV envelope protein (E2) were investigated in patients undergoing chronic hemodialysis using a sensitive reverse-transcriptase polymerase chain reaction and an enzyme-linked immunosorbent assay, respectively. HGV-RNA was detected in 19 of 112 patients investigated (17%) and anti-E2 antibodies were detected in 15 of 106 patients studied (14.2%). With the exception of two patients, the appearance of anti-E2 is associated with the clearance of serum HGV-RNA. The total prevalence of current (HGV-RNA positivity) and/or past (anti-E2 positivity) HGV infection in this patient population is thus 28.6% (32 of 112 patients were positive for serum HGV-RNA and/or anti-E2 antibodies). In apparently healthy blood donors, serum HGV-RNA was detected in four of 358 individuals (1.12%) and anti-E2 was not detected in 50 individuals investigated. From the 19 patients with serum HGV-RNA positivity, nine were coinfected with other hepatitis viruses (seven with HBV; one with HBV, hepatitis C virus [HCV], and hepatitis D virus; and one with HBV and cytomegalovirus). Thirteen of 15 patients with anti-E2 positivity (10 were positive for only anti-E2 and three were also positive for anti-HBc) had no detectable HGV-RNA. In two patients, both HGV-RNA and anti-E2 antibodies were concomitantly present (both patients were coinfected with HCV or HBV). Of the HGV-infected patients, only three who were coinfected with HBV showed elevated serum alanine aminotransferase levels. The serum HCV-RNA and/or anti-HCV were detected in five (4.5%) of 112 patients. From these findings, we conclude that there is a high prevalence of HGV infection (28.6%) compared with HCV (4.5%) in patients undergoing hemodialysis in our hospital. However, approximately 50% of patients had spontaneously lost the viremia and developed anti-HGV-E2 antibodies. We confirm that HGV infection alone is not associated with elevated serum transaminases, and the appearance of anti-HGV-E2 is usually accompanied with clearance of serum HGV-RNA. In contrast to the results of our previous study, the majority of patients infected with HGV are not coinfected with HCV, indicating that HGV is capable of independent transmission. It is likely that there is a preferential HGV acquisition in the hemodialysis unit. The clinical significance of long-term infection with HGV remains to be established.

Inferior outcome of cadaveric kidneys preserved for more than 24 hr in histidine-tryptophan-ketoglutarate solution. Leuven Collaborative Group for Transplantation.

BACKGROUND: During recent years, an increasing number of transplant centers within the Eurotransplant organization have used histidine-tryptophan-ketoglutarate (HTK) solution instead of University of Wisconsin (UW) solution as their preferred cold storage solution for abdominal organ preservation. We report on our single-center experience on the outcome of imported kidneys preserved with either HTK or UW solution in relation to the duration of cold ischemia time (CIT). METHODS: Between July 1989 and July 1997, 323 cadaveric kidneys preserved with UW or HTK and imported as a result of an exchange within the Eurotransplant organization were transplanted at our institution. CIT was <24 hr in 216 kidneys (UW: n=174, HTK: n=42) and > or =24 hr in 107 kidneys (UW: n=67, HTK: n=40). Renal functional outcome was evaluated by comparing delayed graft function and initial non-function rates, daily urinary output, the evolution of serum creatinine, and creatinine clearance at 1, 3, 5, 7, and 14 days and at 1, 3, 6 and 12 months, and graft survival at 1 year after transplantation in relation to the type of cold storage solution and CIT < or > or =24 hr. RESULTS: Whereas the incidence of delayed graft function did not differ significantly between kidneys preserved for less than 24 hr in UW (18.6%) or HTK (26.2%), this rate increased to 50% in HTK kidneys compared to 23.9% in UW kidneys when CIT exceeded 24 hr (P=0.006). Mean serum creatinine and creatinine clearance values were better at 1 and 5 days postoperatively in kidneys preserved <24 hr with UW as compared to HTK (P<0.05). After 24 hr of CIT, HTK-preserved kidneys showed an impaired renal function, not only in the immediate postoperative phase but also at 1, 3, 6, and 12 months after transplantation (P<0.05). Graft survival at 1 year was 92.9% in UW vs. 87.5% in HTK kidneys preserved for <24 hr (NS), and 91% vs. 77.4% when CIT exceeded 24 hr (P=0.059). CONCLUSIONS: From these single-center findings, it can be concluded that UW is superior to HTK in kidney preservation, particularly when CIT exceeds 24 hr.

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure.

An ELISA specific for a wide spectrum of oxidized apo B-100 in OxLDL was developed and applied to blood samples from 27 control subjects, 20 mild chronic renal failure (MCRF) patients, 21 severe chronic renal failure patients on conservative treatment (SCRF) and 56 severe chronic renal failure patients on maintenance hemodialysis (HEMO). Mean levels of OxLDL were 0.59 mg/dl in controls (95% CI, 0.52-0.66 mg/dl), and were 2.7-fold (p < 0.01), 3.1-fold (p < 0.001) and 5.4-fold (p < 0.001) higher in MCRF, SCRF and HEMO patients, respectively. Levels of von Willebrand factor, a marker of endothelial injury, were 100 percent in controls (95% CI, 90-110 percent), and were 1.5-fold (p = NS), 1.6-fold (p < 0.01) and 2.1-fold (p < 0.001) higher in MCRF, SCRF and HEMO patients, respectively. Multiple regression analysis revealed that the extent of renal failure (F = 14; p = 0.0004) accounted for a significant fraction of the variation in OxLDL levels, also after exclusion of patients with evidence of ischemic atherosclerotic disease (F = 21; p = 0.0001). After adjustment for the extent of renal failure, hemodialysis (F = 5.6; p = 0.021) and LDL cholesterol levels (F = 7.1, p = 0.0095) contributed significantly to the variation in OxLDL levels. Whereas the extent of renal failure contributed only marginally to the individual variations in vWF levels (F = 4.1; p = 0.048), these levels correlated significantly with plasma levels of OxLDL (F = 26; p = 0.0001). In conclusion, OxLDL increase progressively during the development of renal failure suggesting that the oxidation of LDL may be associated with endothelial injury and atherogenesis in these patients.

A single-center multiple regression analysis of covariates associated with long-term cadaveric renal allograft survival: further improvement of long-term results with CsA.

This single center analysis shows further improvement in the already excellent long-term, cadaveric renal allograft survival with Aza since the introduction of CsA. In contrast to the findings from the UCLA/UNOS multicenter registries, these results support other observations that the type of maintenance immunosuppression does indeed influence the long-term attrition rate of cadaveric, renal allografts.