Blood pressure, antihypertensive treatment, and graft survival in kidney transplant patients

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (≤130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment ( P  < 0.05). Graft survival was longer in CTR than in non-CTR ( P  < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB ( P  < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria.     

Clinical outcome and quality of life after computer-assisted total knee arthroplasty: results from a prospective,single-surgeon study and review of the literature

Despite excellent results, there is a lack of prospective studies analysing functional outcome and quality of life after computer-navigated total knee arthroplasty. Fifty-two patients were investigated before and 6 months after surgery with the OrthoPilot navigation system (Aesculap, Germany). We used the SF-36 Health Survey, the visual analog scale (VAS), the Lequesne score and the Knee Society Score (KSS) for assessment. The operation was carried out by one single surgeon. At follow-up, the study population achieved a significant pain reduction on the VAS from 71 to 21 points, an average decline of the Lequesne score from 16 to 7 points coming along with a significant ascent of the KSS from 84 to 157 points. Concerning the SF-36 Health Survey, most of the patients re-achieved age- and gender-matched scores. Poor results were obtained in patients with multiple comorbidities and a severe flexion contracture preoperative.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Validation of the EORTC QLQ-C30 and EORTC QLQ-H&N35 in patients with laryngeal cancer after surgery

Background.

The aim of this study was to test the validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ‐C30) and Head and Neck Module (QLQ‐H&N35) for patients who have undergone surgery due to laryngeal cancer.

Methods.

A total of 323 patients from 6 different centers in Germany who had been operated on completed the QLQ‐C30 and the QLQ‐H&N35 in addition to being surveyed in a personal interview.

Results.

Multitrait scaling analysis confirmed the proposed scale structure of both questionnaires. Cronbach's alpha of the QLQ‐C30 scales ranged from 0.64 (Cognitive Functioning) to 0.94 (Global Health Status); the alpha of the QLQ‐H&N35 ranged from 0.55 (Speech) to 0.90 (Sexuality). Known‐groups comparisons showed multiple differences in sociodemographic and clinical variables.

Conclusion.

It can be concluded that the QLQ‐H&N35, in conjunction with the QLQ‐C30, is a reliable instrument that is able to differentiate between diverse groups of patients with laryngeal cancer after surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2009     

Estimation of the time since death—reconsidering the re-establishment of rigor mortis

In forensic medicine, there is an undefined data background for the phenomenon of re-establishment of rigor mortis after mechanical loosening, a method used in establishing time since death in forensic casework that is thought to occur up to 8 h post-mortem. Nevertheless, the method is widely described in textbooks on forensic medicine. We examined 314 joints (elbow and knee) of 79 deceased at defined time points up to 21 h post-mortem (hpm). Data were analysed using a random intercept model. Here, we show that re-establishment occurred in 38.5% of joints at 7.5 to 19 hpm. Therefore, the maximum time span for the re-establishment of rigor mortis appears to be 2.5-fold longer than thought so far. These findings have major impact on the estimation of time since death in forensic casework.     

Does calf muscle spasticity contribute to postural imbalance? A study in persons with pure hereditary spastic paraparesis

ObjectivesThe contribution of spasticity to postural imbalance in patients with upper motor neuron syndrome is still unclear. This study aimed to evaluate the responses to support-surface perturbations in patients with hereditary spastic paraparesis (HSP). These patients typically suffer from bilateral spasticity with relatively preserved muscle strength of the lower limbs. Particularly toes-up rotations were expected to be destabilizing due to insufficient suppression of calf muscle stretch reflexes.MethodsParticipants were seventeen symptomatic community-dwelling patients with autosomal dominant pure HSP and seventeen healthy controls. All patients had increased muscle tone of the triceps surae (TS) but no muscle contractures. Perturbations were applied by rotating or translating a platform with increasing intensity in four sagittal-plane directions. The primary outcome was maximum intensity (‘limit of stability’) sustained without stepping or grabbing in each type of perturbation. Leg muscle tone and strength were assessed with the Modified Ashworth Scale and Medical Research Council (MRC) scale, respectively.ResultsFor toes-up perturbations, limits of stability in patients were substantially lower than in controls, which were related to TS muscle tone but not to tibialis anterior (TA) strength. Toes-down rotations were indiscriminative. For backward perturbations, patients also had lower limits of stability, unrelated to TA strength or TS muscle tone. In forward perturbations, patients with TS strength MRC 4 were less stable than patients with normal TS strength and controls.ConclusionCalf muscle spasticity and weakness differently contribute to postural imbalance in patients with HSP. This notion could have implications for the clinical management of spasticity.     

Prophylaxis of Heterotopic Ossification in Patients Sedated after Polytrauma

BACKGROUND AND PURPOSE: Heterotopic ossification (HO) often follows acetabular fractures after multitrauma. Irradiation is a mean for prophylaxis. We established a standard procedure in our hospital for patients under sedation, when obtaining informed consent for HO prophylaxis is impossible. PATIENTS AND METHODS: We reviewed current scientific evidence, calculated the risks of radiation and presented the ethical and legal framework. The subject was scrutinised by an interdisciplinary panel. RESULTS: Irradiation is the most effective means for prophylaxis and has few adverse effects in adult patients with fractures of the acetabulum. The lifetime risk of radiation-induced cancer or infertility are insignificant. CONCLUSIONS: Informed consent for irradiation should be obtained before operation whenever possible. When this cannot be done prophylaxis can be postponed for a maximum of 3 days in order to obtain consent. If the patient is not able to communicate within this period, prophylactic irradiation should be given after consulting the relatives. The patient must be informed as soon as possible.     

Intestinal graft versus native liver cytokine expression in a rat model of intestinal transplantation with and without donor-specific cell augmentation

BACKGROUND: Immunomodulatory strategies such as donor-specific bone marrow or blood transfusions have been used to promote engraftment after intestinal transplants. We previously showed that delivery of donor antigen via the portal vein can effectively reduce the rate of intestinal graft rejection. The purpose of our current study was to investigate the impact of donor-specific cell augmentation (blood versus bone marrow) via the portal vein on cytokine expression in intestinal grafts versus native livers. MATERIAL AND METHODS: We performed heterotopic small intestinal transplants between male Brown-Norway (donor) and female Lewis (recipient) rats. We studied 10 groups according to the type of donor-specific cell augmentation and the use and dose of immunosuppressive therapy. For cell augmentation, donor-specific blood or bone marrow was transfused via the donor portal vein immediately before graft implantation. For immunosuppression, tacrolimus was used post-transplant at a high or low dose. Control rats received neither immunosuppression nor cell augmentation. Tissue samples for histological assessment were obtained at designated time points. RNA was extracted from intestinal graft and native liver biopsies for cytokine measurements (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, and TNF-beta). Chimerism levels were determined using Q-PCR analysis. RESULTS: Without concurrent immunosuppression, neither portal donor-specific blood nor bone marrow transfusion reduced the rate of rejection. With immunosuppression, outcome was significantly better after portal donor-specific blood (versus bone marrow) transfusion. Irrespective of the type of donor-specific cell augmentation, severe rejection caused strong cytokine expression in the grafts of IL-1 alpha, IL-1 beta, IFN-gamma, and TNF-alpha; in the native livers, mainly of TNF-alpha (with IFN-gamma showing hardly any increase). In general, rejection caused stronger cytokine expression in the grafts than in the native livers. Mild rejection correlated well with strong intragraft expression of IL-6, TNF-alpha, and TNF-beta (early rejection markers); severe rejection with IL-1 alpha, IL-1 beta, IFN-gamma, and TNF-alpha (late rejection markers).In addition to cell augmentation per se, the type of cell augmentation also had an impact on cytokine expression in both grafts and native livers. Cell-augmented (versus tacrolimus-treated) rats showed hardly any differences in intragraft cytokine expression, but the expression of almost all cytokines was significantly stronger in the native livers. With immunosuppression, bone marrow infusion increased intragraft cytokine expression of IL-1 alpha, IL-1 beta, IFN-gamma, and TNF alpha, as well as liver cytokine expression of IL-1 beta, compared to blood transfusion. This finding reflected the more advanced rejection stages in the bone marrow infused group; different types of donor-specific cell augmentation had similar effects on liver cytokine expression. In the absence of myoablative therapy, chimerism levels were low, in both cell-augmented and non-cell-augmented groups. CONCLUSIONS: Rejection and donor-specific cell augmentation independently causes differences in intragraft versus native liver cytokine expression after intestinal transplants. Portal donor-specific blood transfusion, as compared with donor-specific bone marrow infusion, lowered the incidence of rejection and diminished intragraft cytokine up-regulation.     

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.