Improved survival in patients with type 1 diabetes mellitus after renal transplantation compared with hemodialysis: a case-control study

BACKGROUND: Diabetes mellitus is the leading cause of renal failure worldwide. The question of which treatment modality-hemodialysis versus renal transplantation-is associated with the lowest risk of cardiovascular morbidity and mortality in the diabetic end-stage renal disease (ESRD) population has not yet been investigated in a controlled trial. METHODS: We therefore conducted a case-control study of patients with ESRD caused by type 1 diabetes mellitus. The case patients were diabetics who received a renal graft between 1978 and 1997, whereas the controls were registered for renal transplantation but stayed on maintenance hemodialysis without ever undergoing transplantation. The groups were matched for age, sex, duration of diabetes, length of hemodialysis (up to the registration), and date of registration for renal transplantation. RESULTS: Kaplan-Meier life table analysis, based on 46 case patients and 46 controls, demonstrated a highly significant (P=0.0001) poorer survival in the control group compared with the case group. Logistic regression showed that hemodialysis was a significant risk factor for death (P=0.0002) and cardiovascular morbidity (P=0.0023). Patients with cardiovascular complications such as coronary artery and peripheral vascular events were significantly more frequent in the control group. Additionally tested risk factors for cardiovascular complications (serum cholesterol, arterial blood pressure, number of antihypertensive drugs, serum calcium, serum phosphate, and glucose control [hemoglobin A(1c)]) showed no significant correlation to survival or morbidity in either group by logistic regression. CONCLUSIONS: Renal transplantation is associated with a significantly improved survival compared with hemodialysis in patients with ESRD caused by type 1 diabetes mellitus. This seems to be a result of a reduced incidence of cardiovascular complications after renal transplantation.     

Robotic coronary artery bypass grafting (CABG)--the Leipzig experience

Technical and anatomical limitations as well as human factors complicate endoscopic coronary bypass surgery. Computer-enhanced telemanipulation systems overcome some of these shortcomings by restoring the dexterity and precision of a distant operator (surgeon) within a confined space. Endoscopic coronary artery bypass grafting (CABG) has evolved from a merely experimental approach to a clinical concept. Although CABG was initially exclusively performed on the arrested heart, adjunct technologies such as endoscopic vacuum-assisted stabilizers now allow a closed-chest, beating-heart procedure. The development of anastomotic devices, and further refinements in telemanipulator technology, optical systems, and image-guided augmented-reality scenarios will greatly facilitate endoscopic bypass grafting in the future.     

Metachromatic leukodystrophy: recent research developments

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A, causing the storage of the sphingolipid sulfatide. The disease is characterized by a progressive demyelination, which results in severe, finally lethal, neurologic symptoms. Genetically, the disease is heterogeneous, most mutant alleles are private, and only three have a frequency worth mentioning. An arylsulfatase A-deficient knockout mouse displays some of the disease features seen in patients but does not show the widespread demyelination characteristic of the disease. Nevertheless, this animal model was used to investigate the therapeutic potential of bone marrow stem cell-based gene therapy. Although treated animals show considerable arylsulfatase A activity in many tissues, including the brain, the effect on sulfatide storage was disappointing. Only in the kidney and liver of animals with very high enzyme levels was lipid storage positively affected. In particular, no effect was seen in the brain. These results suggest that bone marrow stem cell-based gene therapy could be of limited value in the treatment of this disease. The pathogenesis of the disease is poorly understood. It is not yet known how sulfatide storage negatively affects the metabolism of the oligodendrocyte. The amount and distribution of various proteins in the myelin of arylsulfatase A-deficient mice were investigated. It was shown that the myelin protein, myelin and lymphocyte protein (MAL), is reduced in deficient animals and that the myelin protein proteolipid displays an altered distribution within the myelin membranes. Possibly, these alterations contribute to the development of demyelination in this disease.     

Post-traumatic osteomyelitis: analysis of inflammatory cells recruited into the site of infection

Device-associated infections after implants or endoprostheses inflict local inflammation and ultimately osteolysis, a clinical entity referred to as posttraumatic osteomyelitis. The underlying molecular mechanisms are not yet known; formation of bacterial biofilms on the implant is presumed, conferring resistance to antibiotics and to host defense mechanisms as well. To gain insight into the pathogenesis of post-traumatic osteomyelitis, the infected site was analyzed for the presence of immunocompetent cells. In 18 patients, the infected site was rinsed intraoperatively. This so-called lavage contained 1-2 x 107 leukocytes, predominantly highly activated polymorphonuclear neutrophils (PMNs), as characterized by low expression of CD62L (selectin), and high expression of the adhesion protein CD18, of the high-affinity immunoglobulin (IgG) receptor CD64, and of the LPS-receptor CD14. CD16, the low-affinity IgG receptor, was affected in some patients only. Because the majority of infections were caused by staphylococci species, the effect of bacteria-derived lipoteichoic acid on PMN of healthy donors was tested in vitro. A similar activation pattern was found: rapid down-regulation of CD62L, a slower loss of CD16, and upregulation of CD18, CD64, and CD14. Lipoteichoic acid signaling required p38 mitogen-activated protein kinase and resulted in induction of CD14-specific mRNA and de novo protein synthesis. We conclude that PMNs infiltrate the infected site, but despite local activation they are unable to clear the bacteria, presumably because of biofilm formation. Our data are consistent with the hypothesis that during the ineffective "frustrated" attempt to phagocytose, PMNs release cytotoxic and proteolytic entities that in turn contribute to the progression of tissue injury and ultimately to osteolysis.     

Brain Glioma and Human Leukocyte Antigens (HLA) – is There an Association

Expression of human leukocyte antigens (HLA) is important for the immune response against infectious agents and malignant cells. Association of single HLA antigens or HLA haplotypes with disease has been investigated previously, and positive correlations between HLA and some cancers, such as cervical or nasopharyngeal carcinomas have been reported. In the present study, HLA antigen frequencies of 65 adult Caucasian patients with low-grade, anaplastic, or malignant astrocytic glioma (WHO grades II–IV) were compared with 157 racially similar, asymptomatic control individuals. Both standard serologic and PCR techniques for HLA typing were employed for all patients and controls.Our results suggest a positive association between single HLA antigens and presence of symptomatic cerebral glioma. Compared with the control population, patients positive for HLA-A*25 had a 3.0-fold increased risk of glioma (p = 0.04), patients positive for HLA-B*27, a 2.7-fold risk (p = 0.03), and patients positive for HLA-DRB1*15, a 2.2-fold risk (p = 0.03), whereas HLA-DRB1*07 was associated with a 0.4-fold decreased risk of glioma (p = 0.02). Occurrence rate of some HLA antigen combinations and estimated haplotypes was also different in glioma patients. Thus, HLA-DRB1*15:DRB5*(51) occurrence in combination with HLA-DRB1*11 was associated with a 13.4-fold increased risk of glioma (p = 0.001), and the incidence of HLA-Cw*6:DRB1*07 with a 0.2-fold decreased risk of glioma (p = 0.03).In conclusion, single HLA antigens and their combinations and estimated haplotypes are possibly significantly more or less frequent in persons developing symptomatic cerebral glioma during their adult life, compared with asymptomatic individuals.     

Language regression in childhood

Language regression is observed both in autistic regression and as part of acquired epileptic aphasia (Landau-Kleffner Syndrome). We prospectively identified 177 children with language regression at four major medical centers, and their clinical characteristics were recorded. Their mean age at regression was 22.8 months. The mean time-to-specialist referral was 38 months of age. Most children (88%) met criteria for autism or manifested autistic features. Males (P = 0.02) and children less than 3 years of age who regressed (P = 0.016) had a higher probability of developing autistic behaviors. Seizures were more common in children who regressed after they reached 3 years of age (P < 0.001), and children with seizures were less likely to have associated autistic regression (P < 0.001). Electroencephalogram abnormalities were reported in 37% of patients and were more common in children with seizures (P < 0.001). At last follow-up, language function was impaired in 88% of the children, although some improvement was noted in 57%. We conclude that the loss of previously acquired language at any age, even if that language only includes a few words or communicative gestures, is often associated with a more global regression in cognition and/or behavior and has serious implications for future function. Early identification and referral of these children is necessary to allow for diagnosis and intervention.     

Morphological alterations in the inner ear of the arylsulfatase A-deficient mouse

Metachromatic leukodystrophy of humans is an inherited sulfatide lipidosis due to deficiency of arylsulfatase A (ASA). As an animal model, ASA(-/-) mice have been generated. A previous study showed that the mice lose most of their spiral (acoustic) ganglion cells and develop deafness by the end of the first year of life. The present report describes the sulfatide histochemistry and ultrastructure of the inner ears of ASA(-/-) mice at 0.5-26 months of age. Lysosomal accumulation of sulfatides was observed in various cell types such as Schwann cells that maintain the myelin sheaths around the spiral and vestibular ganglion cells, periaxonal Schwann cells, macrophages, and spiral and vestibular ganglion cell perikarya. In the spiral ganglion, the only surviving neurons were those which are primarily non-myelinated (type 2 cells). However, the myelinated spiral neurons and their processes were rarely encountered within the process of dying, suggesting that this was a rather rapid process. Since the myelin sheaths around dying perikarya and axons appeared structurally normal, the primary cause of the neuronal cell death seems to reside in the neuron. In contrast to the spiral ganglion, the vestibular ganglion as a whole survived throughout the period of observation. The organ of Corti and the vestibular apparatus appeared preserved at the light microscopic level, despite massive sulfatide storage in the vestibular hair cells.     

Primary stability of unicompartmental knee arthroplasty under dynamic compression-shear loading in human tibiae

BackgroundThe objective of our study was to evaluate the impact of a single- (“implant only”) versus a double-layer (“implant & bone”) cementing technique on the primary stability of unicompartmental tibial plateaus under dynamic compression-shear loading conditions in human tibiae.MethodsTwelve fresh-frozen human knees of a mean donor age of 72.3 years were used to perform medial UKA under a less invasive parapatellar surgical approach. The tibiae were divided into two groups of matched pairs based on comparable trabecular bone mineral density. To assess the primary stability, a new method based on a combination of dynamic compression-shear testing, kinematic analysis of the tibial plateau migration relative to the bone and evaluation of the cement layer by CT-scans and fragments cut through the implant–cement–bone interface in the frontal plane was introduced.FindingsFor the “implant only” cementation technique the mean load to failure was 2600 (SD 675) N and for “implant & bone” it was 2820 (SD 915) N. Between the final load level at failure and the bone mineral density a significant correlation was found for the groups “implant only” (r_s = 0.875) and “implant & bone” (r_s = 0.907).InterpretationFrom our observations, we conclude that there is no significant difference between a single- (“implant only”) and double-layer (“implant & bone”) cementing technique in the effect on the primary stability of unicompartmental tibia plateaus, in terms of failure load, correlation between final load at failure and bone mineral density, migration characteristics, cement layer thickness and penetration depth.