Realistic three-dimensional imaging of injuries in forensic medicine - Survey-based method comparison of CRT and VRT.

OBJECTIVE: A comparison between Cinematic Rendering Technique (CRT) and Volume Rendering Technique (VRT) in cases with postmortem CT-angiography (PMCTA) was carried out. METHODS: For different injuries seen in PMCTA, a VRT and a CRT image of exactly the same pathological section was generated. Two questionnaires were created, one with CRT and one with VRT reconstructions, with the same questions per 3D-image. The questionnaires were sent to forensic pathologists, lawyers and police officers. In total eleven different injuries had to be analyzed. RESULTS: In total 109 questionnaires were answered fully. Of these returnees, 36 stated that they were forensic pathologists. Seventy-three people were assigned to the group of medical laypersons, in the study this group consists mainly of police officers, judges and lawyers. Between the two software programs CRT and VRT that were compared, no significant difference could be identified in any of the participating groups with regard to the assessment of the life-threatening nature of the injury images shown. When asked about the comprehensibility of pathology, there was a significant difference in favour of CRT. This advantage was apparent to named medical laypersons and to forensic pathologists. CONCLUSIONS: The study showed a positive trend that CRT may be more understandable than VRT. Not only the medical laypersons, but also the forensic physicians found CRT to be beneficial.

Complex dynamics of a single neuron model.

We study a mathematical model of a single neuron with self-coupling. The model is based on the FitzHugh-Nagumo oscillator and an equation describing synaptic properties of the neuron. The analysis of the model is focused on its dynamics, depending on parameters characterizing synaptic time constants and external signals that affect the neuron. Applying Lyapunov exponents and bifurcation analysis, we point out the occurrence of parameter regions with different behavior such as bursting (chaotic or periodic), spiking, and multistable phenomena. Moreover, we can describe the dynamics of the model using an analytical approximation of the one-dimensional Poincaré map extracted from the numerical simulations.

Clopidogrel diminishes hemodialysis access graft thrombosis.

BACKGROUND: The most common complication of hemodialysis access graft is thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to prevent this serious complication. METHODS: Nineteen patients on chronic hemodialysis whose vascular accesses were grafts were divided into two groups: Group A (n=11, 58%) consisted of patients who did not receive anti-thrombotic therapy after graft placement; Group B (n=8, 42%) received clopidogrel 75 mg/day from two days after surgery onwards. Both groups were well matched with respect to age, gender, cause of renal failure, hematocrit, platelet count and Kt/V. All patients' thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed. Finally, the survival difference between both groups was determined. RESULTS: Ten thrombotic episodes were diagnosed in Group A while no events were reported in Group B (p<0.001). Graft access days of patency were significantly more in Group B than in Group A (350.8+/-166 vs 86.8+/-69, p<0.001). The time elapsed from dialysis initiation to graft placement was not different (Group A: 18+/-12 days; Group B: 20+/-10 days). Days in hemodialysis were different between both groups (Group A: 195.9+/-96; Group B: 545.5+/-291, p<0.001) and all patients of Group A (n=11, 57.9%) and two patients of Group B (25%) died (p=0.001). No major bleeding events were reported. CONCLUSIONS: Clopidogrel significantly decreased thrombotic graft episodes. Patients on clopidogrel had a prolonged vascular access patency, longer time on hemodialysis and longer survival.

Low initial vitamin B12 levels in Helicobacter pylori--positive patients on chronic hemodialysis.

BACKGROUND: Helicobacter pylori has been identified as a possible cause of vitamin B12 deficiency in the general population. We assessed any potential relationship between low cyanocobalamin serum levels and Helicobacter pylori status in hemodialysis patients and subsequently correlated these results with the existence of anemia (a common complication in hemodialysis patients), and macrocytosis. METHODS: In 29 chronic hemodialysis patients, active H. pylori infection was diagnosed using two different methods regardless of digestive symptoms: by searching for bacterial antigens in stools and by the detection of urea breakdown through breath testing. If these results were non-coincident, gastroscopy was performed and antral biopsies obtained. Patients were subsequently divided into group A (H. pylori-positive, n = 8, 28%) and group B (H. pylori-negative, n = 21, 72%). The corresponding initial values of erythrocytic folic acid, vitamin B12 and homocysteine prior to the first hemodialysis session of each patient were retrospectively collected. RESULTS: Vitamin B12 levels (normal 200- 900 pg/ml) were significantly lower in group A compared to group B (225.4 +/- 111.9 vs. 707.9 +/- 258.3 pg/ml, p < 0.011). In group A, 5 patients (63%) had vitamin B12 deficiency (154 +/- 24.6 pg/ml). Baseline hematocrits, erythrocyte folic acid and serum homocysteine levels were not different between the groups, but mean corpuscular volumes were significantly higher in group A compared to group B (109.7 +/-14.1 vs. 91.8 +/- 8.8 fl, p = 0.002). CONCLUSIONS: H. pylori-positive chronic hemodialysis patients may present with lower vitamin B12 blood levels and macrocytosis. H. pylori infection should be suspected in this population when low or low-normal vitamin B12 levels or macrocytosis exist.

Thrombotic events of arteriovenous fistulae in hemodialysis patients related to the C677T thermolabile variant of methylenetetrahydrofolate reductase.

BACKGROUND: Hyperhomocysteinemia is a risk factor for thrombosis, a frequent complication of vascular access (VA) in hemodialysis (HD). The enzyme methylenetetrahydrofolate reductase (MTHFR) is necessary for the remethylation of homocysteine (Hcy) to methionine. It has been postulated that patients homozygous and, to a lesser extent, heterozygous for the C677T thermolabile variant of this enzyme present a reduced catalytic activity, with secondary increases in plasmatic Hcy levels (normal: 10 +/- 5 micromol/L) and an elevated risk of vascular thromboses. METHODS: Sixty-two patients on chronic HD were divided into two groups: group A (n = 23, 37.1%) was normal for the enzyme (CC); group B (n = 39, 62.9%) was heterozygous (CT). Both groups were not different according to age, sex, time on HD, hematocrits (Hct), baseline levels of Hcy, folic acid and vitamin B12. After the 1st HD session patients were started on folic acid 10 mg/day and 500 microg/week of intravenous (i.v.) methylcobalamin. RESULTS: Two years later, thrombotic events were not different between the two groups. Group A = 5 (21.7%) vs. group B = 12 (30.7%), Hcy levels were significantly different between final and baseline measurements (group A 21.5 +/- 5.2 vs. 16.6 +/- 3.9 micromol/L, p = 0.02; group B 22.1 +/- 8.9 vs. 16.1 +/- 3.9 micromol/L, p = 0.008), folic acid (group A 22.1 vs. 346.9 ng/ml, range (r) =166-527, p < 0.001; group B 19.2 vs. 218.5 ng/ml, r = 138-298, p < 0.001) and vitamin B12 (group A 1489 vs. 3192.3 pg/ml, r = 1494-4890, p = 0.01; group B 1086 vs. 1513.8 pg/ml, r = 1092-1934, p = 0.02). CONCLUSIONS: HD patients heterozygous for the C677T variant of the enzyme MTHFR can present a similar risk of thrombotic events in arteriovenous fistulae (AVF) compared to patients normal for the enzyme at a 1-yr follow-up. These results could be explained by an adequate control of Hcy levels after folic acid and methylcobalamin replacement therapy.

Cyclosporine-associated thrombotic microangiopathy during daclizumab induction: a suggested therapeutic approach.

A woman on daclizumab developed thrombotic microangiopathy secondary to cyclosporine after a living-unrelated kidney transplant. Despite cyclosporine discontinuation, hemolysis persisted. The second dose of daclizumab was postponed 24 h, and after a maximum of two sessions of plasmapheresis (to avoid further modifications in daclizumab schedule) with plasma exchange, daclizumab was administered. Plasma infusions were prescribed until D-dimer and fibrinogen-degradation products normalized; thereafter, FK-506 was started without recurrence of the hemolytic picture and renal function restored. This observation suggests that in patients on daclizumab who develop thrombotic microangiopathy secondary to immunosuppressants, if discontinuation of the offending drug is unsuccessful, plasmapheresis with plasma exchange can be performed when the lowest levels of daclizumab exist, followed by daclizumab infusion. Plasma prescription must be continued thereafter until D-dimer and figrinogen-degradation products normalize. However, if hemolysis persists when daclizumab levels are high, plasma infusions are useful and plasmapheresis avoided. FK-506 administration did not result in recurrence of hemolysis during daclizumab induction.

Cytomegalovirus maculopapular eruption in a kidney transplant patient.

Cytomegalovirus (CMV) is the most important viral agent in kidney transplantation. Clinical manifestations of CMV disease in transplantation include hepatitis, pneumonitis, pancreatitis, kidney allograft dysfunction, colitis, and meningoencephalitis. However, skin involvement is rare. We describe a severely compromised cadaveric-kidney transplant recipient who developed renal failure, colonic ulcers, and a maculopapular rash accompanied by fever and malaise 4 months after transplantation. Only the skin biopsy was diagnostic and consistent with CMV disease. Intravenous ganciclovir administration resulted in clinical improvement of CMV-induced skin lesions; kidney function normalized and the patient became asymptomatic after 14 days of ganciclovir therapy. Nephrologists should consider the diagnosis of CMV disease in the febrile immunosuppressed patient with skin involvement. Skin biopsy must be considered as a useful and safe procedure in patients with a rash to obtain a prompt diagnosis and efficiently treat this immunocompromised population.

Late-onset cytomegalovirus-associated interstitial nephritis in a kidney transplant.

Cytomegalovirus is the most important viral infection in kidney transplants, but rarely affects the allograft after the sixth month posttransplantation. We present a patient who developed renal failure eighteen months posttransplant; a kidney biopsy showed cytomegalovirus inclusions, acute tubular necrosis and mild interstitial nephritis. After intravenous ganciclovir, renal function transiently improved. Cytomegalovirus pp65 antigen was weekly reported as negative. One month later another biopsy was performed due to renal failure. The findings were consistent with tubular atrophy and severe interstitial nephritis. No cytomegalovirus cellular inclusions were found on histology, including immunohistochemical and polymerase chain reaction studies; pp65 antigen studies were persistently negative. Despite an attempt to recover renal function with steroid therapy, the patient restarted hemodialysis 20 months posttransplantation. This report suggests that cytomegalovirus should be considered as a late cause of kidney failure even in the absence of infection-related symptoms. The irreversible allograft damage can be caused despite the successful eradication of the virus with intravenous ganciclovir.

La hiperhomocisteinemia como factor de riesgo vascular en hemodializados crónicos / Hyperhomocysteinemia as a vascular risk factor in chronic hemodialysis patients

La homocisteína es un factor de riesgo independiente de enfermedad cardiovascular en la población general, y juega un rol protagónico en el desarrollo de la aterogénesis y las trombosis vasculares, sobre todo en pacientes con insuficiencia renal. Así pues, los pacientes en hemodiálisis están bajo los efectos tóxicos de la hiperhomocisteinemia, presente en cerca del 90% de estos pacientes. En nuestra experiencia hemos encontrado que el ácido fólico es un tratamiento eficaz para disminuir los niveles de homocisteína, y el agregado de metilcobalamina intravenosa potencia este efecto; sin embargo, la metilcobalamina por sí sola fue insuficiente para normalizar la homocisteinemia. A lo largo del tiempo, un grupo de pacientes requirió dosis más elevadas de ácido fólico para corregir la hiperhomocisteinemia. Los pacientes homocigotas y, en menor medida hete-rocigotas para la variante termolábil C677T de la enzima metilentetrahidrofolato reductasa (MTHFR), presentaron una actividad catalítica reducida reflejada en la necesidad de una mayor dosis de ácido fólico para normalizar los niveles de homocisteína. Los efectos trombóticos vasculares fueron similares en todos los pacientes respecto a las variantes genéticas de la enzima metilentetrahidrofolato reductasa, sugiriendo que el tratamiento de la hiperhomocisteinemia es importante para disminuir el riesgo de trombosis. Sin embargo, también la hipoho-mocisteinemia, asociada generalmente a estados de desnutrición, se asocia a mayor mortalidad. Si bien se considera a la hiperhomocisteinemia como un factor de riesgo vascular en los pacientes con insuficiencia renal, aún no se determinó en esta población si su corrección se asocia a una disminución de la tasa de enfermedad vascular y de trombosis. No obstante...

Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.