Long-term kidney transplant graft survival—Making progress when most needed

Current short-term kidney post–transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000–2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014–2017 (1995–1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995–1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995–1999 to an estimated 19.2 years for transplants in 2014–2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.     

Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes

Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.     

Embryonic development of four different subsets of cholinergic neurons in rat cervical spinal cord

The developmental stage at which a neuron becomes committed to a neurotransmitter phenotype is an important time in its ontogenetic history. The present study examines when choline acetyltransferase (ChAT) is first detected within each of four different subsets of cholinergic neurons previously identified in the cervical enlargement of the spinal cord: namely, motor neurons, partition cells, central canal cluster cells, and dorsal horn neurons. By examining the temporal sequence of embryonic development of these cholinergic neurons, we can infer the relationships between ChAT expression and other important developmental events. ChAT was first detected reliably on embryonic day 13 (E13) by both biochemical and immunocytochemical methods, and it was localized predominantly within motor neurons. A second group of primitive-appearing ChAT-positive cells was detected adjacent to the ventricular zone on E14. These neurons seemed to disperse laterally into the intermediate zone by E15, and, on the basis of their location, were tentatively identified as partition cells. A third group of primitive ChAT-immunoreactive cells was detected on E16, both within and around the ventral half of the ventricular zone. By E17, some members of this "U"-shaped group appeared to have dispersed dorsally and laterally, probably giving rise to dorsal horn neurons as well as dorsal central canal cluster cells. Other members of this group remained near the ventral ventricular zone, most likely differentiating into ventral central canal cluster cells. Combined findings from the present study and a previous investigation of neurogenesis (Phelps et al.: J. Comp. Neurol. 273:459-472, '88), suggest that premitotic precursor cells have not yet acquired the cholinergic phenotype because ChAT is not detectable until after the onset of neuronal generation for each of the respective subsets of cholinergic neurons. However, ChAT is expressed in primitive bipolar neurons located within or adjacent to the germinal epithelium. Transitional stages of embryonic development suggest that these primitive ChAT-positive cells migrate to different locations within the intermediate zone to differentiate into the various subsets of mature cholinergic neurons. Therefore, it seems likely that spinal cholinergic neurons are committed to the cholinergic phenotype at pre- or early migratory stages of their development. Our results also hint that the subsets of cholinergic cells may follow different migration routes. For example, presumptive partition cells may use radial glial processes for guidance, whereas dorsal horn neurons may migrate along nerve fibers of the commissural pathway. Cell-cell interactions along such diverse migratory pathways could play a role in determining the different morphological, and presumably functional, phenotypes expressed by spinal cholinergic neurons.     

Soft lens lubricants and prelens tear film stability

Soft contact lens wearers complaining of "dry eye" are frequently prescribed rewetting drops, although the mode of action and efficacy of this treatment have not been established. Enhancement of prelens tear film (PLTF) stability could provide a basis for symptomatic relief with solution instillation. Thirty symptomatic hydroxyethyl methacrylate (HEMA) lens wearers participated in 4 separate trials of no solution (baseline), saline, and 2 soft lens lubricants. Solutions were applied for a 6-h adaptation period, and PLTF noninvasive break-up time (NIBUT) was monitored for 1 h after a final instillation. PLTF NIBUT was significantly elevated 1 min after instillation of all solutions (p less than 0.001, logrank test) but this effect persisted for less than 5 min. The transient enhancement of PLTF stability arising from the instillation of these rewetting solutions is unlikely to provide a basis for prolonged symptomatic relief.     

Clinical and genetic features of variegate porphyria in a Chinese patient

Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented.     

A pharmacoeconomic comparison of antithymocyte globulin and muromonab CD3 induction therapy in renal transplant recipients

Antithymocyte globulin (ATG) and muromonab CD3 (OKT3) are currently the only antilymphocyte preparations that are commercially available for induction immunosuppressive therapy for renal allograft transplantation in the US. ATG, in the usually prescribed doses, is more expensive than muromonab CD3, but muromonab CD3 is associated with more severe adverse effects that may affect clinical outcome and overall cost. We performed a retrospective study of all adult recipients of a first cadaveric renal allograft, who underwent transplantation between January 1991 and December 1994 who received either ATG (n = 92) or muromonab CD3 (n = 91) for induction therapy at our transplant centre. The average age of recipients was older (50 vs 44 yrs; p = 0.001) and extended donors were more commonly used in the ATG group (41 vs 13%; p = 0.0001) compared with the muromonab CD3 group. Nevertheless, at 1 year post-transplant, the incidence of rejection was lower (34 vs 47%) and graft survival was better (93 vs 85%; p = 0.03) in the ATG group. Patients who received ATG were discharged earlier (9.4 vs 13.3 days; p = 0.0001) and had similar serum creatinine levels on the day of discharge (2.4 +/- 1.5 vs 2.1 +/- 1.1 mg/dl; p = 0.25). Overall, the 1-year hospitalisation costs of transplantation and readmissions were similar [$US39,937 +/- 17,014 vs $US42,850 +/- 20,923 (currency year 1994); p = 0.22]. This is the first comparison of ATG and muromonab CD3 in renal transplant recipients to consider clinical as well as economic outcomes. For renal transplant patients in whom induction therapy is used at our centre, the initial expense of ATG can be justified by improved graft survival, fewer rejection episodes, and shorter hospital stays, which are associated with similar overall transplantation costs.     

Effects of altered left ventricular geometry on quantitative technetium 99m sestamibi defect size in humans: Perfusion imaging during coronary angioplasty

Background

Serial myocardial perfusion imaging is used to assess exercise-induced myocardial ischemia and myocardial risk area, salvage, and viability in patients with myocardial infarction. In an experimental animal model it has been shown that abnormal regional wall motion and altered left ventricular geometry can produce apparent perfusion defects independent of changes in blood flow. The effects of regional alteration in ventricular geometry on perfusion images in humans are not defined. The purpose of our investigation was to evaluate quantitatively the effect of altered left ventricular geometry on myocardial perfusion imaging with technetium 99m sestamibi during coronary angioplasty.

Methods and Results

Nine patients with normal baseline left ventricular function referred for angioplasty of the left anterior descending coronary artery were studied.^99mTc sestamibi was administered intravenously before angioplasty. Baseline planar electrocardiographic-gated imaging was performed. Imaging was repeated in the catheterization laboratory during angioplasty vessel occlusion when altered left ventricular geometry was produced and again later after angioplasty. Summed static, end-systolic, and end-diastolic images were generated from the electrocardiographic-gated acquisitions. Circumferential count profiles of images obtained during percutaneous transluminal coronary angioplasty (PTCA) were compared with those of a normal^99mTc sestamibi database and their own baseline images. Defect integral (the area below the reference profile) and nadir (maximum percent decrease in activity) were derived. Compared with a normal database, new quantitative defects appeared on PTCA-summed images in only two patients. The defects were small to moderate in size. However, compared with their own baseline profile, six patients had quantitative defects during PTCA (mean defect integral 3±2; mean defect nadir 12%±7%). Defect nadir was larger on end-diastolic images compared with summed images (22%±7% and 12%±7%, respectively;p<0.05).

Conclusions

Altered left ventricular geometry may create apparent, albeit small, planar myocardial perfusion defects in humans. Changes in defect size on serial images may be only partially caused by changes in regional wall motion or geometry.     

Assessing and planning home-based care for persons with AIDS

The HIV/AIDS pandemic continues to gather momentum in many developing countries, increasing the already heavy burden on health care facilities. As a result, donors, implementing partners and communities are beginning to create home-based care programmes to provide care for persons with HIV/AIDS. This paper recommends reorienting this home care provision as a service founded in, and coming from, the community rather than the health system. A methodology, in the form of an assessment matrix, is provided to facilitate the assessment of a community's capacity to provide care for people with AIDS. The focus is on rapid assessment methods using, where possible, readily available information to clearly and systematically define current circumstances. The matrix created for a specific community is then used in the development of an action plan with interventions prioritized and tailored to local needs. A case study from a hypothetical developing country, where HIV/AIDS is a significant problem, is used to illustrate the process.