Steroid withdrawal after long-term medication for immunosuppressive therapy in renal transplant patients: adrenal response and clinical implications

Background. Withdrawal of steroids should be attempted after organ transplantation because of their adverse cardiovascular and metabolic effects. However, immunological, haemodynamic and symptomatic complications may occur due to the suppression of endogenous corticoid hormone synthesis under exogenous steroid intake. We have examined the effect of chronic steroid medication on adrenocortical function, and of steroid withdrawal, in immunologically stable renal transplant patients. Methods. Sixty-three patients under long-term prednisone therapy (mean±SD 36±47 months) were assessed regarding basal fasting cortisol concentration and adrenocortical stimulation by the low-dose Synacten test both prior to and after stepwise prednisone withdrawal. Renal graft function (determined as the calculated glomerular filtration rate according to the Cockroft-Gault formula), mean arterial blood pressure and clinical status were evaluated concomitantly. Results. Basal fasting cortisol concentration was clearly suppressed in 14% of patients under long-term steroid medication, and adrenocortical stimulation by the low-dose Synacten test was impaired in 31% after steroid withdrawal. About a third of all patients were symptomatic with fatigue (60%), arthralgias (60%), muscular weakness (20%), loss of appetite (20%), hypotension (15%) or headaches (5%). The incidence of symptoms was much higher in patients with low basal fasting cortisol concentration prior to steroid withdrawal, and after >2 years of steroid medication. Renal graft function, determined as glomerular filtration rate, decreased only slightly overall by ∼5%, and was more pronounced in symptomatic vs asymptomatic patients (−7 vs −2 ml/min, respectively), as was the fall in mean arterial pressure (−10 vs −4.2 mmHg, respectively). Conclusions. Adrenal function is impaired in renal transplant patients receiving long-term steroid medication as part of their immunosuppressive regimen. This may lead to mainly symptomatic complications when steroids are withdrawn. The slight decrease in glomerular filtration rate probably can be ascribed mostly to the effect of steroids on systemic renal haemodynamics. It is recommended to consider cessation of steroid medication within 48 months of therapy, and after determination of basal cortisol to identify patients with potential complication

Silencing of Vlaro2 for chorismate synthase revealed that the phytopathogen Verticillium longisporum induces the cross-pathway control in the xylem

The first leaky auxotrophic mutant for aromatic amino acids of the near-diploid fungal plant pathogen Verticillium longisporum (VL) has been generated. VL enters its host Brassica napus through the roots and colonizes the xylem vessels. The xylem contains little nutrients including low concentrations of amino acids. We isolated the gene Vlaro2 encoding chorismate synthase by complementation of the corresponding yeast mutant strain. Chorismate synthase produces the first branch point intermediate of aromatic amino acid biosynthesis. A novel RNA-mediated gene silencing method reduced gene expression of both isogenes by 80% and resulted in a bradytrophic mutant, which is a leaky auxotroph due to impaired expression of chorismate synthase. In contrast to the wild type, silencing resulted in increased expression of the cross-pathway regulatory gene VlcpcA (similar to cpcA/GCN4) during saprotrophic life. The mutant fungus is still able to infect the host plant B. napus and the model Arabidopsis thaliana with reduced efficiency. VlcpcA expression is increased in planta in the mutant and the wild-type fungus. We assume that xylem colonization requires induction of the cross-pathway control, presumably because the fungus has to overcome imbalanced amino acid supply in the xylem

Steroids in kidney transplant patients

Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment

Asystolie in überraschendem Zusammenhang

Asystole in a surprising context: A previously healthy 37-year-old patient was admitted to our hospital for evaluation of syncope. Continuous ECG monitoring revealed repeated asystoles with a duration of up to 25 seconds. In the absence of echocardiographic abnormalities or evidence of a reversible cause of sinus node dysfunction, a dual-chamber pacemaker was implanted. In the following few days the patient developed fever, low grade headache, emesis and marked disorientation. Viral encephalitis was diagnosed by demonstration of lymphocytic pleiocytosis and herpes simplex virus type1 by PCR in the cerebrospinal fluid. An association between herpes simplex encephalitis and bradyarrhythmias has been described previously. We review the literature supporting a possible pathogenetic link. The arrhythmias are known to be of a transient nature and permanent pacing is not usually necessary

Steroid withdrawal after long-term medication for immunosuppressive therapy in renal transplant patients: adrenal response and clinical implications

Background. Withdrawal of steroids should be attempted after organ transplantation because of their adverse cardiovascular and metabolic effects. However, immunological, haemodynamic and symptomatic complications may occur due to the suppression of endogenous corticoid hormone synthesis under exogenous steroid intake. We have examined the effect of chronic steroid medication on adrenocortical function, and of steroid withdrawal, in immunologically stable renal transplant patients. Methods. Sixty-three patients under long-term prednisone therapy (mean±SD 36±47 months) were assessed regarding basal fasting cortisol concentration and adrenocortical stimulation by the low-dose Synacten test both prior to and after stepwise prednisone withdrawal. Renal graft function (determined as the calculated glomerular filtration rate according to the Cockroft-Gault formula), mean arterial blood pressure and clinical status were evaluated concomitantly. Results. Basal fasting cortisol concentration was clearly suppressed in 14% of patients under long-term steroid medication, and adrenocortical stimulation by the low-dose Synacten test was impaired in 31% after steroid withdrawal. About a third of all patients were symptomatic with fatigue (60%), arthralgias (60%), muscular weakness (20%), loss of appetite (20%), hypotension (15%) or headaches (5%). The incidence of symptoms was much higher in patients with low basal fasting cortisol concentration prior to steroid withdrawal, and after >2 years of steroid medication. Renal graft function, determined as glomerular filtration rate, decreased only slightly overall by ∼5%, and was more pronounced in symptomatic vs asymptomatic patients (−7 vs −2 ml/min, respectively), as was the fall in mean arterial pressure (−10 vs −4.2 mmHg, respectively). Conclusions. Adrenal function is impaired in renal transplant patients receiving long-term steroid medication as part of their immunosuppressive regimen. This may lead to mainly symptomatic complications when steroids are withdrawn. The slight decrease in glomerular filtration rate probably can be ascribed mostly to the effect of steroids on systemic renal haemodynamics. It is recommended to consider cessation of steroid medication within 48 months of therapy, and after determination of basal cortisol to identify patients with potential complication

The German Hip Outcome Score: validation in patients undergoing surgical treatment for femoroacetabular impingement.

To cross-culturally adapt and validate the Hip Outcome Score (HOS) for use in German-speaking patients undergoing surgical treatment for femoroacetabular impingement.After cross-cultural adaptation (German-language version of the HOS [HOS-D]), the following metric properties of the questionnaire were assessed in 85 consecutive patients (mean age, 33.4 years; 36 women) undergoing hip arthroscopy or surgical hip dislocation: feasibility, reliability, internal consistency, and construct validity (correlation with Western Ontario and McMaster Universities Arthritis Index, Oxford Hip Score, Short Form 12, and University of California, Los Angeles activity scale). We calculated floor and ceiling effects taking the minimal detectable change into account.The activities of daily living subscale of the HOS-D could be scored in all cases and the sport subscale in all but one. The HOS-D scores were highly reproducible with intraclass correlation coefficients of 0.94 for the activities of daily living subscale and 0.89 for the sport subscale. Internal consistency was confirmed by Cronbach \u3b1 values >0.90 for both subscales. Correlation coefficients with the other measures ranged from -0.08 (Mental Component Scale of Short Form 12) to -0.90 (Western Ontario and McMaster Universities Arthritis Index function subscale).The HOS-D is a reliable and valid self-assessment tool for patients undergoing surgical femoroacetabular impingement treatment. By use of the HOS, comparisons between studies and treatment regimens involving either German- or English-speaking patients are now possible.Level I, testing of previously developed diagnostic criteria in a series of consecutive patients with universally applied gold standard

Late repair of abductor avulsion after the transgluteal approach for hip arthroplasty

The abductor release sometimes does not heal after a transgluteal approach for hip arthroplasty. Factors influencing the success of subsequent repair are unclear. We used magnetic resonance imaging (MRI) to compare the condition of the gluteus medius with clinical outcome after late repair of abductor dehiscence in 12 total hip patients. Evaluation included a pain rating, gait evaluation, Trendelenburg test, strength grading, and Harris Hip Score. Most had both prerepair and postrepair MRI studies to assess the repair and to grade abductor muscle fatty degeneration. Two repairs without MRI were explored surgically. Although average pain, limp, and strength scores improved significantly, rerupture occurred in 4 subjects and fatty degeneration in the gluteus medius did not improve, even with intact repair. Nine patients were satisfied; 7 of these had an intact repair. Magnetic resonance imaging and operative observations suggest that chronic degeneration in the abductor mechanism is the major impediment to successful repair

No regeneration of the human acetabular labrum after excision to bone

Treatment options for a symptomatic, torn, irreparable, or completely ossified acetabular labrum are limited to either excision and/or reconstruction with grafts. In a previous animal model, regeneration of the acetabular labrum after excision to the bony rim has been shown. In humans, less is known about the potential of regeneration of the labrum. Recent studies seem to confirm labral regrowth, but it is still unclear if wide excision might be a surgical option in cases where repair is not possible

The Hip Sports Activity Scale (HSAS) for patients with femoroacetabular impingement

To develop and validate a sports activity scale for patients with a diagnosis of femoroacetabular impingement (FAI)