[Sclerodermiform chronic graft-versus-host disease after allogenic peripheral blood stem-cell transplantation]. / Sklerodermiforme chronische Graft-versus-Host-Erkrankung nach allogener peripherer Blutstammzelltransplantation.

HISTORY AND CLINICAL FINDINGS: A 46-year-old man presented with suberythrodermia and an acral-accentuated sclerosis, which had been progressing over the past 6 months, with extensive, painful ulcers within the sclerotic areas of the calf. Due to acute myelotic leukemia (AML), an allogenic peripheral blood stem-cell transplantation with subsequent immunosupression with mycophenolatmofetil (MMF) and ciclosporin A had been performed 8 years previously. The patient had discontinued treatment on his own after about 2 years, having suffered a cerebroischemic insult in the meantime. INVESTIGATIONS: Histological examinations revealed sclerodermatous changes. Titres of antinuclear antibodies were unremarkable. Laser-Doppler-flowmetry also indicated an active inflammatory and sclerosing process. FACS analysis of the peripheral blood did not reveal signs of AML recurrence. DIAGNOSIS, THERAPY AND COURSE: The histological pattern in conjunction with the anamnesis indicated a cutaneous chronic graft-versus-host disease (GvHD). No further organ involvement was observed. The MMF therapy which the patient had discontinued was restarted. In addition, PUVA therapy was initiated. These measures and intensive physiotherapeutic exercises in parallel prevented further progression of the sclerosis and secondary mobility limitations. The ulcers healed completely with pentoxifylline and anti-infective treatment. CONCLUSION: After stem-cell transplantation, early diagnosis of GvHD is especially important due to possible irreversible sclerodermatous changes and other organ manifestations. Also for this reason, strict clinical follow-up is especially important with respect to compliance and efficacy of the immunosuppression.

Use of complementary and alternative medicine in patients suffering from primary headache disorders.

Complementary and alternative medicine (CAM) is increasingly common in the treatment of primary headache disorders despite lack of evidence for efficacy in most modalities. A systematic questionnaire-based survey of CAM therapy was conducted in 432 patients who attended seven tertiary headache out-patient clinics in Germany and Austria. Use of CAM was reported by the majority (81.7%) of patients. Most frequently used CAM treatments were acupuncture (58.3%), massage (46.1%) and relaxation techniques (42.4%). Use was motivated by 'to leave nothing undone' (63.7%) and 'to be active against the disease' (55.6%). Compared with non-users, CAM users were of higher age, showed a longer duration of disease, a higher percentage of chronification, less intensity of headache, were more satisfied with conventional prophylaxis and showed greater willingness to gather information about headaches. There were no differences with respect to gender, headache diagnoses, headache-specific disability, education, income, religious attitudes or satisfaction with conventional attack therapy. A higher number of headache days, longer duration of headache treatment, higher personal costs, and use of CAM for other diseases predicted a higher number of used CAM treatments. This study confirms that CAM is widely used among primary headache patients, mostly in combination with standard care.

Differential diagnostic use of interleukin patterns in patients being monitored after transplantation.

BACKGROUND AND AIM: We investigated how far the determination of selected interleukins in bodily fluids of patients who had received kidney allografts can help to confirm the diagnosis of complications after transplantations. MATERIALS AND METHODS: Levels of soluble interleukin-2-receptor, interleukin 6 and interleukin 8 were determined in serum and urine of 79 patients. According to the type of diagnosis obtained with histological, serological and microbiological methods and to the clinical course, the groups "stable graft function without complication", "allograft rejection", "cytomegalovirus infection", "systemic extrarenal bacterial infection", "urinary tract infection" and "pyelonephritis" were created. RESULTS AND CONCLUSIONS: The activation of the immune system in different ways depending on the trigger substance (alloantigen, virus, bacterium) and the possibility to differentiate systemic and local processes cause typical patterns of interleukin levels in serum and urine in conjunction with the above mentioned complications after kidney transplantation. Cytomegalovirus infections and systemic extrarenal bacterial infections differ from rejection by the unchanged urine interleukins IL 6 and IL 8, the local urinary tract infections differ from rejection by the unchanged serum interleukins. Acute pyelonephritis differs from rejection by the significantly higher serum IL 6 level. During our daily clinical work, the practical interleukin determinations were proven to be an important tool for early and differential diagnosis of complications after kidney transplantation.

Relationship between mycophenolate mofetil side effects and mycophenolic acid plasma trough levels in renal transplant patients

There has been limited experience with routine therapeutic monitoring of mycophenolic acid (MPA; CAS 24280-93-1), which is the active metabolite of the new immunosuppressive prodrug mycophenolate mofetil (MMF; CAS 115007-34-6). MMF was introduced with recommendation for fixed oral dosing (1 g twice daily) in combination with cyclosporin A (CSA) and a glucocorticoid for the prevention of renal allograft rejection. In the course of routine CSA monitoring a MPA monitoring was performed in adult renal transplant patients receiving MMF in combination with CSA and methylprednisolone (MEP). For 30 consecutive patients with 234 plasma samples the relationship of MMF doses used and MPA plasma through levels estimated at steady state (C88 min) to clinical outcome was evaluated retrospectively. The MPA concentrations were determined with the enzyme-multiplied immunoassay technique (EMIT mycophenolic acid assay) on a Cobas Mira Plus analyzer. The within-run (n = 10) and between-run (n = 10) coefficients of variation were 3.6%, 3.5%, 3.1% and 3.6%, 5.1%, 6.7% analysing three MPA level plasma controls (1.25 mg/l, 7.5 mg/l, 12.5 mg/l), respectively. The data analysis of the MPA plasma trough levels resulted in a high variability between patients (0.3 to 3.4 mg/l) received the recommended fixed MMF dose (2 g/day). There was a higher incidence of adverse reactions with increasing MPA plasma trough levels (2.13 +/- 1.35 mg/l in 13 patients with side effects versus 1.53 +/- 0.67 mg/l in 17 patients without side effects; p < 0.001), regardless of reduction of MMF dose (1.77 +/- 0.3 g/day versus 1.89 +/- 0.2 g/day; NS), respectively. No acute rejection episodes occured under MMF administration in combination with CSA and MEP. The study shows that the to date recommended MMF dose resulted in individual, quite different MPA plasma trough levels, which were associated with incidence of side effects rather than the MMF doses. Therefore, monitoring of plasma MPA trough levels and individual dose adjustment could be helpful to reduce the incidence of adverse reactions and to increase the safety of MMF therapy.

Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients.

The possible pharmacokinetic interaction between the new immunosuppressive mycophenolate mofetil (MMF) and tacrolimus (TAC), respectively, was assessed by comparing routinely estimated mycophenolic acid (MPA) plasma trough levels of 15 consecutive renal transplant patients receiving MMF in combination with methylprednisolone (MEP) and cyclosporin A (CSA, 10 patients) or in combination with MEP and tacrolimus (TAC, 5 patients). Coadministration of TAC instead of CSA resulted in a significant increase of mean MPA plasma trough levels [3.4 +/- 1.3 microg/mL (n = 22) versus 1.87 +/- 1.1 microg/mL (n = 57); p < 0.001], despite lower MMF doses [1.5 +/- 0.5 g/d versus 1.7 +/- 0.3 g/d (not statistically significant)]. This elevation in MPA levels is possibly caused by an interaction between MMF and TAC and could lead to a recommendation to monitor MPA plasma levels with appropriate dose adjustment.

Effects of PUVA therapy on kidney allografts: results of a randomized prospective double-blind study.

After successful experimental organ transplant studies on the efficacy of PUVA therapy combining donor pretreatment with the photosensitizer 8-methoxypsoralen (P) and the ex vivo irradiation of organs with long-wave ultraviolet light (UVA) prior to transplantation, we started in 1989 the first randomized, prospective, double-blind study to clarify the efficacy of PUVA therapy in human kidney transplantation. This study included 50 kidney donors, 25 of whom were PUVA-treated. A total of 75 kidneys were transplanted in Berlin, Halle and Rostock. The complete data of these 75 recipients were available for the final evaluation. The PUVA group (n = 36) and the non-PUVA group (n = 39) were not statistically significantly different as to donor and recipient data. Regarding the results, no differences were seen in initial hospitalization time, early graft function, rejection rate, number and time of rejection episodes. After a follow-up of 24 months, both graft survival (PUVA vs. non-PUVA: 75% vs. 71.8%) and patient survival (97.2% vs. 97.4%, respectively) were comparably high. PUVA therapy did not influence the development of vascular rejection. Interestingly, the rate of late graft loss after the 6th posttransplant month was lower, but not statistically significantly so, in the PUVA than in the non-PUVA-group (2 vs. 6 graft losses). Thus, PUVA-pretreated kidneys may be associated with a reduced development of chronic rejection.

[Experiences with plasmapheresis in the treatment of vascular rejection following kidney transplantation]. / Erfahrungen mit der Plasmapherese in der Behandlung der vaskulären Rejektion nach Nierentransplantation.

In the first 6 weeks after kidney transplantation 15 patients suffering from vascular rejection were treated by 46 plasmapheres. In transplants with additional interstitial rejection the plasmapheresis was introduced after failure of ATG therapy. In 1 patient no histological confirmation was done. In 4 patients the plasmapheresis was successful and in 6 patients suffering from combined vascular and interstitial rejection the ATG therapy was successful only after initial plasmapheresis. In 4 cases the therapy failed to reverse rejection. The early use of plasmapheresis is recommended to obtain the best results.

[The effect of different factors on the immediate transplant function. A retrospective study of 172 kidney transplants]. / Uber den Einfluss verscheidener Faktoren auf die Transplantatsofortfunktion. Eine retrospektive Untersuchung bei 172 Nierentransplantationen.

The influence of different factors on the immediate function of the transplant was investigated retrospectively in 172 patients. The immediate function of the transplanted kidney was influenced negatively by dehydration of the patient, by intraoperative decrease in blood pressure above 30 mmHg, by an prolonged cold ischemia time, and by the "handling time".

[The effect of early urologic complications on the prognosis of kidney transplantation]. / Der Einfluss urologischer Frühkomplikationen auf die Prognose der Nierentransplantation.

The early urological complications of 200 patients receiving a kidney allograft between 1985 and 1987 were analyzed retrospectively. In the first 4 weeks after transplantation urological, complications were found in 25 cases (12.5%), with a portion of 74.1% ureteral fistulas. The treatment was conservatively in 4 cases and operatively in 21 patients (84%), in 3 cases a recurrent operation was necessary. After an urological complication the graft prognosis was diminished markedly and the letality was higher in comparison with uncomplicated cases.

[The biorhythm of gingival temperature]. / Zum Biorhythmus der Gingivatemperatur.

In two studies with a total of 16 test persons, gingival temperature being a measure of blood flow was taken in the region of the front teeth, canines and molars in defined intervals. Gingival temperature has got--like other biological criteria--a circadian rhythmic that may be both of therapeutical and methodical value.

[Report of experiences on the use of cyclosporin A]. / Erfahrungsbericht über den Einsatz von Ciclosporin A.

In September 1985 in our kidney transplantation centre for the first time ciclosporin A was used. Up to now altogether 50 patients received this new form of immunosuppression. During the sand immune application no essential side effects occurred. The success of the change of the therapy was independent of the degree of the serum creatinine level at the time of conversion. In the period of observation we performed altogether 106 kidney transplantations. With 88% of grafts functioning normally at the discharge under application of ciclosporin A we achieved a clear improvement of the results of transplantation in comparison with the classical immunosuppression (53.6%) in the period of observation.