Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health.

The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.

TOPS: an internet-based system to prevent healthy subjects from over-volunteering for clinical trials.

AIM: Our aim was to set up a system to help UK clinical research units to prevent healthy volunteers from participating in more than one non-therapeutic trial simultaneously, or from starting a second trial too soon after the first. METHODS: TOPS (The Over-volunteering Prevention System) is internet-based, simple and quick to use, free to users and a charity run by a Board of Trustees. Users enter only two or three pieces of information: (1) 'National Insurance number' (NINO) of UK citizens, or 'passport number' and country of origin of non-UK citizens, as their identifier, (2) 'date of last dose' of trial medicine or (3) 'never dosed'. Subjects must consent, but TOPS collects only non-personal data, so it does not require Ethics Committee approval and is not covered by the Data Protection Act. RESULTS: A total of 55 research units (29 clinical research organisations, 5 pharmaceutical companies, 13 universities and 8 hospitals) throughout the UK have registered to use TOPS, and have entered 124,906 volunteers since we launched it. All commercial and many non-commercial units now use TOPS. In our unit, no subject has to the best of our knowledge participated in two trials simultaneously. TOPS has reduced to <1% the incidence of subjects attempting to volunteer within 3 months of completing another trial elsewhere, and very few have to our knowledge succeeded. CONCLUSION: TOPS is widely used and effective, and helps research units to comply with UK clinical trial regulations.

Evaluation of microperfusion disturbances in the transplanted liver after Kupffer cell destruction using GdCl3: an experimental porcine study.

BACKGROUND: Organ function after liver transplantation is determined by ischemia-reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3) has been shown to have a possible preventive effect on the extent of this injury, which can be extrapolated by analyzing the distribution of hepatic microperfusion. The aim of this study was to evaluate the protective effect of GdCl3 on disturbances of microperfusion in the transplanted liver. METHODS: Landrace pigs were randomly divided into three groups. In the control group (CG; n=6) a mapping of the native liver was conducted. For mapping, the four hepatic liver lobes were named from right to left with A to D and every lobe was divided into three vertical segments (cranial, medial, and caudal). In each of these 12 areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100 g/min]). The other two groups were considered as transplanted treated group (TTG; n=10) and transplanted nontreated group (TnTG; n=10). The TTG received an infusion of 20 mg/kg GdCl3 intravenously 24 hours before organ harvesting. Then standardized orthotopic liver transplantation was performed. In TnTG, standardized orthotopic liver transplantation was carried out without prior GdCl3 injection. In the recipients, the microperfusion of transplanted livers were mapped in both TnTG and TTG, in two different time points (1 hour [n=5] and 24 hours (n=5]) after reperfusion. RESULTS: A significant reduction of macrophages in the TTG livers in comparison to the CG and TnTG livers was observed (P<.05). However, the number of macrophages in CG and TnTG livers showed no significant difference (P>.05). Regarding liver microperfusion, in TnTG, a marked heterogeneity was detected in the livers after reperfusion. Significant differences between liver lobes (horizontal planes; P=.032) and vertical layers of intralobar liver parenchyma (P=.029) were observed. The same pattern was seen in TTG livers after reperfusion and a significant difference between horizontal (P=.024) and vertical layers (P=.018) of liver tissue were observed. Comparing intralobar regional flow data between vertical planes 24 hours after reperfusion still showed a prominent variation of hepatic tissue perfusion in TnTG livers (P=.028). Within the same horizontal layers, no significant differences between lobes were measured anymore (P=.16). Contrary to TnTG, in TTG, a homogenous pattern of regional liver tissue perfusion was recorded 24 hours after reperfusion. Comparison of TD data on the liver regions showed no significant microperfusion differences in either horizontal (P=.888) or vertical (P=.841) layers. CONCLUSIONS: Application of GdCl3 resulted in a significant reduction of Kupffer cells. Twenty four hours after transplantation microperfusion showed a homogeneous pattern, which constituted an earlier and better recovery of the transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia-reperfusion injury and seemed to be responsible for the early recovery of microperfusion disturbances and thus for an improvement of graft function.

[Characterization of intraurethral relations of urine flow in childhood using the Doppler ultrasound technic]. / Charakterisierung der intraurethralen Harnflussverhältnisse im Kindesalter mittels Ultraschalldopplertechnik.

In a number of diseases in childhood (vesico-ureteral reflux, myelodysplasia, recurrent urinary tract infection, enuresis) it is important to evaluate the functional patterns of the micturition phase. The therapeutic regimen is influenced especially by changes of the urethral flow resistance. The value of urodynamic methods which are available for the characterization of the micturition phase is limited because of the small anatomic conditions in childhood. The presented method of measurement of the intraurethral urinary flow using an ultrasound doppler technique is recommended as an alternative technique because of its superior diagnostic safety and unrestricted application in childhood.

[Surgical management of double kidney in children]. / Die chirurgische Behandlung der Doppelniere im Kindesalter.

In 48 patients a heminephrectomy was carried out on account of a chronic relapsing pyelonephritis when a double kidney was present which for the largest part was combined with vesico-ureteral reflux, pyelectasia and hypertension. The partly severe histologic changes found in more than 80% in the resection preparation confirmed the supposition that in the majority of the cases the chronic relapsing inflammation issues from the hypoplastic renal pole with a decreased function. Also the courses observed in more than 3/4 which had no recidivation after operation show the possibility of the causal-surgical therapy in chronic relapsing pyelonephritis with double kidney, when the indication is correct.

[Surgical treatment of nephroptosis in children]. / Did operative Behandlung der Nephroptose im Kindesalter.

By a nephroptosis already in childhood an obstruction of the urine flow with reduction of the drainage effect and thus the appearance of a pyelonephritis may develop. Changes at the vascular pedicle are also possible on account of the abnormal mobility of the kidneys so that without treatment from there may result parenchymatous and functional lesions which, as a rule, become manifest only at adult age. On the basis of own experiences which support themselves on the results of 29 children with nephroptosis we recommend the nephropexy in childhood. The operation is an active prophylaxis of the pyelonephritis caused by nephroptosis with its deleterious sequelae.