The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506: Clinical significance and comparison with cyclosporine

The histopathological changes in 51 renal allograft biopsies from patients immunosuppressed with FK506 were compared with those seen in 30 needle biopsies obtained from patients on cyclosporine. The frequency and severity of rejection episodes were similar in both groups. Tubular vacuolation and myocyte vacuolation were found to be useful morphological markers to monitor short-term drug toxicity associated with both drugs. Long-term administration of FK506 led to striped interstitial fibrosis and arteriolar hyalinosis, similar to that previously documented for cyclosporine. One case each of hemolytic uremic syndrome and necrotizing arteriopathy was noted in patients receiving FK506. FK506 and cyclosporine are structurally unrelated compounds; hence the parallelism observed in their nephrotoxicity profile suggests that the interactions of these drugs with renal tissue involves the operation of two different initial signal-transducing mechanisms, ultimately activating the same final metabolic pathways

In-situ measurements of oxygen, carbon monoxide and greenhouse gases from Ochsenkopf tall tower in Germany

We present 2.5 years (from June 2006 to December 2008) of in-situ measurements of CO2, O2, CH4, CO, N2O and SF6 mixing ratios sampled from 23, 90 and 163m above ground on the Ochsenkopf tower in the Fichtelgebirge range, Germany (50?0104900 N, 11?4803000 E, 1022ma.s.l.). In addition to the in-situ measurements, flask samples are taken at Ochsenkopf at approximately weekly intervals and are subsequently analysed for the mixing ratios of the same species, as well as H2, and the stable isotopes, ?13C, ?18O in CO2. The in-situ measurements of CO2 and O2 from 23m show substantial diurnal variations that are modulated by biospheric fluxes, combustion of fossil fuels, and by diurnal changes in the planetary boundary layer height. Measurements from 163m exhibit only very weak diurnal variability, as this height (1185ma.s.l.) is generally above the nocturnal boundary layer. CH4, CO, N2O and SF6 show little diurnal variation even at 23m owing to the absence of any significant diurnal change in the fluxes and the absence of any strong local sources or sinks. From the in-situ record, the seasonal cycles of the gas species have been characterized and the multi-annual trends determined. Because the record is short, the calculation of the trend is sensitive to inter-annual variations in the amplitudes of the seasonal cycles. However, for CH4 a significant change in the growth-rate was detected for 2006.5–2008.5 as compared with the global mean from 1999 to 2006 and is consistent with other recent observations of a renewed increasing global growth rate in CH4 since the beginning of 2007

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation

What is the nature of peer interactions in children with language disorders? A qualitative study of parent and practitioner views

Background and aims: Children with Language Disorders (LDs) can exhibit increased levels of social withdrawal, aggression and problems managing social conflicts. The reasons underlying this pattern of social interaction profiles remain unclear. This qualitative study aimed to document the nature of social interactions between children with LDs and their peers, and to evaluate explanations for their social behaviour, as understood by parents and practitioners. Methods: This study focused on children with LDs who spend school hours with other children with LDs. Three parent focus groups (n ¼ 8) and three practitioner focus groups (n ¼ 10) were conducted with parents of children aged 4–12 attending specialist language schools and practitioners working at these schools. This was a mixed clinical sample. All children of participating parents had LD as their primary area of need, which was the reason they required specialist schooling. Focus groups were conducted across two specialist schools in the UK between March and June 2018. Results: An inductive reflective thematic analysis of the data identified three themes; social knowledge, coping strategies, and emotional competence. Parents and school staff reported that children with LDs experience difficulties managing peer interactions due to a combination of challenges including difficulties with understanding and regulating emotions, and difficulties understanding social situations. Some of the children with LDs were described as having developed strategies to cope with their challenges, for example imposing structure on their social interactions to manage uncertainty, which has implications for their social interactions with peers. Conclusions: Children with LDs have difficulties understanding emotions, difficulties understanding their peer’s intentions and difficulties resolving conflict situations independently according to their parents and practitioners working with these children. Participants proposed a novel explanation that social withdrawal may be used adaptively by children with LDs to process information. This study demonstrates the complexity of the relationship between Language Disorders and peer interaction profiles. Implications: Suggestions are offered regarding future research directions, such as investigating the specific contribution language skills make to children’s emotion understanding, to better understand the reasons for peer interaction difficulties in children with Language Disorders

A prospective randomized trial of FK506-based immunosuppression after renal transplantation

A group of 204 adult patients was entered into a prospective, randomized trial comparing FK506/pred-nisone with FK506/azathioprine/prednisone after renal transplantation between August 1, 1991 and October 11,1992. The purpose of the study was to see if the addition of azathioprine would reduce the incidence of rejection and improve graft survival. The recipient population was unselected, with 61 (30%) patients undergoing retransplantation, 37 (18%) having a panel-reactive antibody greater than 40%, and 33 (16%) over 60 years of age. The mean recipient age was 43.8±13.7 years (range 17.6-78). The mean donor age was 34.0±20.1 years (range 0.3-75); 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4±8.4 hr. Living donors were the source of 13% of the kidneys. The mean follow-up was 22±4 months (range 12-29). Overall one-year actual patient survival was 94%. Overall one-year actual graft survival was 87%. Patients starting on double therapy had a one-year actual patient survival of 96% and a one-year actual graft survival of 92%. Patients starting on triple therapy had a one-year actual patient survival of 91% (P=ns compared with double therapy), and a one-year actual graft survival of 82% (P<0.02, compared with double therapy). Overall results with first cadaver transplants included a one-year actual patient survival of 94% and one-year actual graft survival of 88%, with no differences between double and triple therapy. The overall incidence of rejection was 48%, with 54% in the double therapy group and 41% in the triple therapy group (P<.07). The incidence of steroid-resistant rejection requiring antilymphocyte therapy (OKT3 or ATGAM) was 13%, and was not different between the double and triple therapy groups. The mean serum creatinine was 1.8±0.8 mg/dl. The mean BUN was 33±21 mg/dl, with no significant difference between the therapy groups. The mean serum cholesterol was 192 ±49 mg/dl. A total of 56% of the patients are off prednisone, and 35% of the patients are not taking any antihypertensive medications. Other complications included cytomegalovirus—14%; new-onset diabetes—16% (half of which was reversible); and posttransplant lymphoproliferative disorder—1%. There was a high incidence of crossover between the two groups, 27% of the patients in the double therapy group requiring the addition of azathioprine, and 45% of the patients in the triple therapy group requiring its discontinuation (usually tempoгагу). These results show that FK506 is an excellent immunosuppressive agent after renal transplantation and that azathioprine is not routinely effective as a third agent. A high quality of life resulted from the ability to use no (56%) or low-dose maintenance steroids. © 1995 by Williams and Wilkins

Tacrolimus rescue therapy for renal allograft rejection - Five-year experience

Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft salvage with tacrolimus conversion in a total of 169 patients (median age 33 years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression after failure of high dose corticosteroids and/or antilymphocyte preparations to reverse rejection. The indications for conversion to tacrolimus were ongoing, biopsy confirmed rejection in all patients. The median interval to tacrolimus conversion was 2 months (range 2 days to 55 months; mean 4.3±2.6 months) after transplantation. All patients had failed high dose corticosteroid therapy and 144 (85%) of the 169 patients had received at least one course of an antilymphocyte preparation plus high dose corticosteroid therapy prior to conversion. Twenty-eight patients (17%) were dialysis-dependent at the time of conversion owing to the severity of rejection. With a mean follow-up of 30.0±2.4 months (median 36.5 months, range 12-62 months), 125 of 169 patients (74%) have been successfully rescued and still have functioning grafts with a mean serum creatinine (SCR) of 2.3±1.1 mg/dl. Of the 144 patients previously treated with antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have functioning grafts (mean SCR 2.15±0.37 mg/dl) at a mean follow-up of 37.3±16.7 months. In the 125 patients salvaged, prednisone doses have been lowered from 28.0±9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5±4.1 mg/d (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%) are currently receiving no steroids. This 5 year experience demonstrates that tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft rejection. Based on these data, we recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy in renal transplantation