Effect of footwear on the external knee adduction moment - A systematic review

ContextFootwear modifications have been investigated as conservative interventions to decrease peak external knee adduction moment (EKAM) and pain associated with knee osteoarthritis (OA).ObjectiveTo evaluate the literature on the effect of different footwear and orthotics on the peak EKAM during walking and/or running.MethodsA systematic search of databases resulted in 348 articles of which 33 studies were included.ResultsSeventeen studies included healthy individuals and 19 studies included subjects with medial knee OA. Quality assessment (modified Downs and Black quality index) showed an (average ± SD) of 73.1 ± 10.1%. The most commonly used orthotic was the lateral wedge, with three studies on the medial wedge. Lateral wedging was associated with decreased peak EKAM in healthy participants and participants with medial knee OA while there is evidence for increased peak EKAM with the use of medial wedges. Modern footwear (subjects' own shoe, “stability” and “mobility” shoes, clogs) were likely to increase the EKAM compared to barefoot walking in individuals with medial knee OA. Walking in innovative shoes (“variable stiffness”) decreased the EKAM compared to control shoes. Similarly, shoes with higher heels, sneakers and dress shoes increased EKAM in healthy individuals compared to barefoot walking.ConclusionsFurther development may be needed toward optimal footwear for patients with medial knee OA with the aim of obtaining similar knee moments to barefoot walking.     

Expression of mRNA of neurotrophic factors and their receptors are significantly altered after subchronic ketamine treatment

The neurotrophic factors play an important role in the maintenance of neurone viability and neuronal communication which are considered to be altered in schizophrenia. Subchronic application of ketamine (Ket) was found to be a useful model in schizophrenia research. To further validate this model the mRNA levels of neurotrophic factors NGF, NT-3, and BDNF and their receptors TrkA, TrkB, and TrkC, respectively, were measured in different brain areas in Ket-pretreated rats subchronically dosed with the atypical antipsychotic drug risperidone (Ris). With the exception of NGF in the frontal cortex, Ket pretreatment did change NGF, NT-3, and BDNF mRNA levels in the frontal cortex, the hippocampus, the striatum, the thalamus/hypothalamus region, and in the cerebellum. These changes correspond with changes at their tyrosine kinase receptors. Ris treatment normalised altered NT-3 levels in the hippocampus and balanced BDNF levels in the same structure. It was concluded that the Ket model might reflect distinct alterations in neurotrophic factor activity as found in schizophrenic patients and, moreover, that Ris treatment rebalances disturbed neurotrophic factor activity.     

Perigestational alcohol consumption induces altered early placentation and organogenic embryo growth restriction by disruption of trophoblast angiogenic factors

Research questionMaternal alcohol consumption produces fetal retardation and malformations, probably associated with placental defects. Does perigestational alcohol consumption up to organogenesis lead to abnormal placentation and embryo growth restriction by disrupting the vascular endothelial growth factor (VEGF) system in embryo–placental development?DesignFemale mice were treated with 10% ethanol in drinking water before and up to day 10 of gestation. Control mice received ethanol-free water. After treatment, the trophoblastic tissue, embryo growth and the angiogenic VEGF pathway were analysed.ResultsFemale mice who had received treatment had resorbed and delayed implantation sites with poor ectoplacental cone development. Reduced trophoblastic area tissue from female mice who had received treatment had abnormal junctional zone and diminished labyrinthine vascularization. After treatment, the labyrinth had increased chorionic trophoblast proliferation, hypoxia inducible factor-1α immunoexpression but reduced apoptosis. The embryo growth was reduced concomitantly with low VEGF immunostaining but high endothelial nitric oxide synthase (eNOS) expression. In junctional and labyrinth of treated female mice, gene and protein immunoexpression of VEGF was reduced and the protein expression of FLT-1 increased compared with controls. Increased activation of kinase insert domain receptor receptor (phosphorylated KDR) and expression of eNOS were observed in placenta of treated female mice. Immunoexpression of metalloproteinase-9, however, was reduced in junctional zone but increased in labyrinth, compared with controls.ConclusionsThese data reveal inadequate expression of VEGF/receptors and angiogenic eNOS and metalloproteinase factors related to abnormal early placentation after perigestational alcohol ingestion, providing insight into aetiological factors underlying early placentopathy associated with intrauterine growth restriction caused by maternal alcohol consumption.     

Murine polyomavirus-like particles induce maturation of bone marrow-derived dendritic cells and proliferation of T cells

We analysed the effects of murine polyomavirus-like particles (PLPs) on bone marrow-derived dendritic cells (BMDCs) and T cells in vitro. BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines. Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells. Our results suggest that PLPs may be used as vaccine adjuvants priming dendritic cells to induce potent T cell responses.     

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.

Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG. METHODS: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis. RESULTS: Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions. CONCLUSION: (18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.     

Steinfeld syndrome: Report of a second family and further delineation of a rare autosomal dominant disorder

We report on a fetus with alobar holoprosencephaly, microphthalmia, midline cleft lip and palate, absent nose, dysplastic ears, radial defects, pentalogy of Fallot, unilateral renal aplasia, absent gallbladder, vertebral anomalies, and absence of ribs. The father had a cleft palate, bilateral colobomas of the iris and retina, a bifid uvula, vertebral anomalies, and unilateral congential hearing loss. His sister had a cleft lip. On the basis of this family and the family reported by Steinfeld [1982], this malformation syndrome can be defined as a rare autosomal dominant syndrome whose main component manifestations are holoprosencephaly, predominantly radial limb deficiency, heart defects, kidney malformations, absence of gallbladder, and vertebral anomalies. © 1993 Wiley-Liss, Inc.     

Determination of human rotavirus VP4 using serotype-specific cDNA probes

Summary The VP4 genetic groups of 151 field strains of human rotaviruses obtained from infants and young children with diarrhea from four locations in Malaysia were analyzed. The strains were adapted to growth in tissue culture and studied further by molecular hybridization of northern blotted RNA to PCR-generated cDNA probes representing amino acids 84–180 of the KU strain VP4, 83–181 of the DS-1 strain VP4, and 83–180 of either the 1076 or K8 strain VP4, representing VP4 genetic groups 1–4 (P1A, P1B, P2, and P3), respectively. The majority (79% of the field strains hybridized with the KU VP4 genetic group 1 probe and were associated with G1, G3, G4, untypable, or mixed G serotypes. VP4 genetic group 1 (P1A) strains were the most common in all locations in Malaysia between 1978–1988. Three strains which exhibited G3 and subgroup I specificity hybridized with the K8 VP4 genetic group 4 probe. These three VP4 genetic group 4 (P3) strains were detected in two different years and locations, extending the initial detection of this VP4 genetic group (the K8 strain) in Japan to a larger geographical area of Asia.     

ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient-constellation A1B/B

BACKGROUND: Antigen-specific immunoadsorption combined with rituximab offers the possibility for ABO-incompatible kidney transplantation without splenectomy. PATIENT AND METHOD: An 8-year-old mentally retarded girl with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis due to mitochondriopathy poorly tolerated hemodialysis. Paternal blood group A1B was incompatible with blood group B of the child. Therefore, we decided to perform the first ABO-incompatible renal transplantation in a child in Germany using antigen-specific immunoadsorption. Rituximab (1 x 375 mg/m2) was administered 2 weeks before the first immunoadsorption (Glycosorb) ABO A-column). Triple-drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) was simultaneously started with immunoadsorption. Initial tacrolimus levels were targeted between 15 and 20 ng/ml. Before transplantation, six immunoadsorptions were applied on days -9, -7, -4, -3, -2 and -1. Intravenous immunoglobulin (0.5 g/kg) was administered preoperatively. After transplantation, three immunoadsorptions were performed on days +4, +6 and +8. RESULTS: Before transplantation, antibody (Ab) titers against paternal erythrocytes (20 degrees C) were reduced from 1 : 64 to 1 : 4 by six antigen-specific immunoadsorptions. After transplantation, we performed three more immunoadsorptions and the Ab titers were stable between 1 : 1 and 1 : 8. One, 2 and 8 months later we observed increases in the Ab titer up to 1 : 32 requiring no change in immunosuppressive therapy. No side effects of immunoadsorption were observed. The girl had excellent initial graft function with a serum creatinine of 55 to 70 micromol/l. Two weeks after transplantation, graft biopsy showed no signs of rejection; there was focal positivity for C4d only. Twelve months after transplantation, renal function was stable, with a serum creatinine of 117 micromol/l. Episodes of rejection or severe infections were absent. CONCLUSION: ABO-incompatible transplantation using antigen-specific immunoadsorption and rituximab may serve as a suitable alternative for children urgently needing renal transplantation and missing a blood group-compatible donor.     

Herpes Zoster in Breast Cancer Patients after Radiotherapy

Background: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative interent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. Conclusions: The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response. Hintergrund: Wir haben in einer retrospektiven Analyse die Häufigkeit eines Herpes zoster bei Patientinnen mit Mammakarzinom und postoperativer Radiotherapie untersucht. Patientinnen und Methode: Von Januar 1985 bis Dezember 1993 erhielten 1 155 Patientinnen an unserer Klinik eine postoperative Bestrahlung nach Mastektomie (n = 961) oder brusterhaltende Operation (n = 194) in kurativer Intention. Das Alter betrug 34 bis 79 Jahre. 443 (38%) waren prä- und 712 (62%) postmenopausal, 21% hatten T3- bis T4-Tumoren, und 55% wiesen einen axillären Lymphknotenbefall auf. Alle Patientinnen erhielten eine Bestrahlung der Restbrust bzw. Thoraxwand bis 50 Gy, bei mastektomierten Patientinnen wurden zusätzlich die regionären Lymphknoten mit 44 Gy bestrahlt. 65% der Patientinnen erhielten eine zusätzliche Systemtherapie. Die Nachbeobachtungszeit betrug drei Monate bis 12,5 Jahre (Median 3,1 Jahre). Ergebnisse: 41/1 155 Patientinnen (3,7%) entwickelten im Nachbeobachtungszeitraum einen Herpes zoster. Alle Infektionen waren lokalisiert, eine generalisierte Hautinfektion oder systemische Infektionen traten nicht auf. Alter, Menopausenstatus, Erkrankungsstadium oder Art der Therapie (Brusterhaltung vs. Mastektomie, zusätzliche Chemotherapie) hatten keinen Einfluss auf die Frequenz von Zoster. Patientinnen mit starker akuter Hautreaktion waren ebenfalls nicht signifikant stärker betroffen als Patientinnen mit geringer Hautreaktion im Bestrahlungsfeld (5% vs. 2%). Das Auftreten eines Zosters nach Therapie hatte keinen Einfluss auf die Prognose hinsichtlich lokaler Kontrolle oder Überleben. Schlussfolgerungen: Die beobachtete Häufigkeit von Herpes zoster (etwa 4% nach drei Jahren Follow-up) lässt vermuten, dass ein Herpes zoster im untersuchten Kollektiv etwa drei- bis fünffach häufiger auftritt als anhand der Inzidenzen in der Normalbevölkerung erwartet. Dies ist nicht mit einer schlechteren Prognose assoziiert. Ob die erhöhte Frequenz auf die Radiotherapie zurückzuführen ist oder in Zusammenhang mit der Krebserkrankung steht, kann nich beurteilt werden.     

Características y pronóstico de pacientes ingresados en un servicio de urgencias hospitalario por traumatismo craneoencefálico y con tratamiento anticoagulante o antiagregante

Background and objective

To determine mortality and complications of patients with traumatic brain injury (TBI) with antiplatelet or anticoagulant treatment in a hospital emergency department.