[Conventional epiphyseal chondrosarcoma of childhood and adolescence: a case report]. / Konventionelles epiphysäres Chondrosarkom des Kindes- und Jugendalters: ein Fallbericht.

INTRODUCTION: Conventional chondrosarcoma is the second most common primary malignant bone tumor and usually occurs at older adult ages. It is rare in childhood and adolescence. CASE HISTORY: This case report presents the treatment course of a 13-year-old boy with a symptomatic chondrogenic tumor of the right distal femur. Histopathologically, an epiphyseal intermediate-grade chondrosarcoma (G2) was diagnosed. DISCUSSION: Based on the following case, potential radiological and histopathological differential diagnoses, such as chondroblastoma or chondroblastic osteosarcoma, are discussed against the background of current standards in orthopedic oncology.

[Treatment concepts for complications after resection and defect reconstruction of pelvic tumours]. / Behandlungskonzepte von Komplikationen nach Resektion und Defektrekonstruktion pelviner Tumoren.

BACKGROUND: Partial pelvic resection, internal hemipelvectomy or sacrectomy as a result of bone sarcoma is still challenging. No matter what kind of reconstruction is used, there is still a much higher rate of complications in pelvic surgery compared to sarcoma surgery of the long bones. OBJECTIVES: We describe the most common complications in pelvic sarcoma surgery and specific complications related to the reconstruction method. Handling strategies for these complications are specified. METHODS: We performed a literature search and report our own experiences in the troubleshooting of pelvic surgery-related complications to gain an up-to-date overview of the state-of-the-art in management strategies. RESULTS: Prospective randomized trials or meta-analyses on this topic are lacking. The literature search depicted that, besides local recurrence, deep infection after reconstruction is the most serious complication. An early revision with radical debridement has to be performed in order to save the reconstruction. In the case of a deep infection, the removal of all implants with a total loss of the reconstruction is often unavoidable. Therefore, an individualized risk-benefit analysis prior to surgery with respect to the type of reconstruction, or no reconstruction at all (hip transposition), together with the patient is advisable. CONCLUSIONS: Complications-especially infections-after hemipelvectomy or sacrectomy are common. In the case of infection, in some cases, an early revision is the only chance to prevent a reconstruction from explantation.

[Complication management following resection and reconstruction of the upper limbs and shoulder girdle]. / Komplikationsmanagement nach Tumorresektion und Defektrekonstruktion an der oberen Extremität und am Schultergürtel.

BACKGROUND: Sarcomas of the upper limbs commonly affect the proximal humerus or scapula. Complications after tumor resection and reconstruction are rare but cannot be neglected, particularly after tumor endoprosthetic reconstructions. MATERIALS AND METHODS: The most common complications after resection of sarcomas of the upper limbs and shoulder girdle are described, and current knowledge regarding complication management is presented. Additionally, a selective literature search was performed, incorporating personal experiences. RESULTS: Wound healing disorders and infections after tumor resection without specific reconstruction (clavicle resection, scapulectomy) usually respond well to conservative or surgical treatment. However, periprosthetic infections after reconstruction using a megaendoprosthesis constitute a severe and frequent complication, with an incidence of 5-10%. Two-stage implant replacement still represents the gold standard, although in selected cases, one-stage revision with retention of the prosthetic stem appears warranted. Secondary amputation as a result of periprosthetic infection is rare compared to the situation with infections of the lower limb. Mechanical complications necessitating surgical revision are mostly limited to joint dislocation after inverse total shoulder replacement (TSR). (Sub)luxation in anatomic TSR can be tolerated provided there is no tendency toward perforation of the skin in a asymptomatic patient. Biological reconstructions are most often indicated for reconstruction of intercalary defects of the humerus, and revision is necessitated most frequently by mechanical complications. Despite multiple surgical revisions, stable reconstructions and limb salvage can usually be achieved in the upper limb.

[Hemipelvectomy for pelvic sarcomas]. / Hemipelvektomie bei Sarkomen des Beckens.

BACKGROUND: Hemipelvectomy is an important technique for the treatment of pelvic sarcomas. OBJECTIVES: Presentation of the technical overview, as well as surgical and oncological outcomes of sarcoma patients treated with pelvic tumor resections and treatment recommendations. METHODS: Retrospective analysis of 160 patients treated by pelvic tumor resection for chondrosarcoma between 1977 and 2014. RESULTS: Chondrosarcoma was the most common diagnosis leading to pelvic tumor resection in this collective (38%). The mean patient age at operation was 49 years. 44 patients were treated for G1, 83 patients for G2 and 33 patients for G3 or dedifferentiated chondrosarcoma. The mean tumor diameter was ≥10 cm in 76.1% of cases. Limb salvaging operations were possible in 82.5% of patients. The most common reconstruction technique was hip transposition (38.7%). Clear resection margins were achieved in 86.9% (R0). Local recurrence was observed in 22.5%. Distant pulmonal metastasis was diagnosed in 25% of patients. Grading-specific survival was 81.8% for G1, 59% for G2 and 24.2% for G3 or dedifferentiated chondrosarcoma with a mean survival of 84.4, 89 and 69.4 months respectively. CONCLUSIONS: Pelvic tumor resection with clear margins is the most important known positive predictive local factor affecting overall outcomes, in addition to uncontrollable factors such as grading and tumor size. Defect reconstruction depends on multiple factors such as patient age and adjuvant therapy. The stage of the disease has the greatest impact on overall survival rates and should be considered when contemplating pelvic tumor resections in sarcoma patients.

[Current results of tumour endoprosthetics in adolescents and adults]. / Aktuelle Ergebnisse der Tumorendoprothetik bei Jugendlichen und Erwachsenen.

BACKGROUND: The majority of osteoarticular defects after tumor resection in adolescent and adult patients are reconstructed using megaendoprosthetic implants. However, even infant and pre-teen children undergo reconstruction of defects using so-called growing prostheses with an increasing frequency. OBJECTIVES: Presentation of current techniques, outcomes and the most common complications of megaendoprosthetic reconstruction following tumour resection. METHODS: Selective literature review and discussion of current concepts and knowledge in megaendoprosthetic reconstruction against personal experience and treatment strategies. RESULTS: Megaendoprosthetic reconstructions achieve good functional results and long-term limb salvage (ca. 90% of cases) in adolescent and adult patients. Still, periprosthetic infection and mechanical failure of joint components are among the most common complications observed. In infant and pre-teen children treated by reconstruction using a growing prosthesis, mandatory maintenance operations-in the process of elongating the implant-must also be considered when assessing complication risks. CONCLUSIONS: Megaendoprosthetic reconstructions of osteoarticular defects are a standard procedure in adolescent and adult patients. Despite a substantial complication rate, limb salvage is achieved in a majority of patients. When using growing prostheses in younger children, one needs to be aware of additional servicing procedures that occur independently of those arising from complications.

[Endoprostheses for stump formation after hip disarticulation]. / Endoprothesen zur Stumpfbildung nach Hüftexartikulation.

BACKGROUND: Hip disarticulation is a psychologically and physically demanding procedure. However, it remains a therapeutical option whenever limb salvage proves impossible due to sarcoma, severe implant-associated infections or trauma. The stump lengthening procedure (SLP) is a surgical technique that allows partial salvage of the thigh through endoprosthetic proximal femur replacement after hip disarticulation, depending on the amount of viable soft tissue coverage. This leads to a more appealing visual appearance, facilitates prosthetic fitting and significantly improves limb function. OBJECTIVES: Description of indications for SLP, surgical technique, presentation of clinical and functional outcomes. METHODS: Review of applying literature and presentation of outcomes of our own SLP collective. RESULTS: The risk of local recurrence does not increase after SLP compared to hip disarticulation. While the majority of patients can be fitted with an exoprosthesis, a walking aid is usually necessary for ambulation. Exoprostheses are usually worn throughout the entire day, and patients manage distances of a mean of 2000 metres, even if reconstruction lengths are less than 10 cm. Patients aged 50 years or older tend to wear their exoprosthesis for shorter periods of daywear and achieve significantly poorer functional scores. Postoperative complications are common at a rate of 52%. Periprosthetic infection (21%) and soft tissue perforation of the implant with subsequent implant-associated infection (14%) were the most severe complications observed. CONCLUSIONS: The stump lengthening procedure poses a feasible alternative to classic hip disarticulation in patients with multiple prior operations and/or advanced stages of disease. It leads to satisfactory cosmetic and functional results without jeopardizing local tumor control. Stump perforation presents as the most common complication. Apart from improving the ability to sit down comfortably, both patients treated with a curative and palliative intent manage to ambulate using exoprostheses. With increasing age at the time of operation, walking aids are necessary for ambulation.

Ultra-short stem anchorage in the proximal tibial epiphysis after intercalary tumor resections: analysis of reconstruction survival in four patients at a mean follow-up of 56 months.

INTRODUCTION: Tumors localized in the proximal tibial meta-diaphysis often lead to osteoarticular resections. MATERIALS AND METHODS: In this study, we retrospectively reviewed four patients who underwent intercalary tumor resection and reconstruction using an ultra-short stem in the proximal tibial epiphysis, a procedure that to our knowledge has not been reported in literature so far. RESULTS: At the time of operation, the mean patient age was 26.2 years. Three patients were male and one was female. Patients were diagnosed with osteosarcoma in two cases, Ewing's sarcoma and malignant fibrous histiocytoma of bone in one case each. In all cases, wide tumor resections were achieved (osteotomy 3-3.5 cm below the tibia plateau joint surface, mean resection length of tibial bone 18 cm) at a mean time of operation of 198.8 min. Two superficial wound-healing disorders occurred, leading to one surgical revision in each case. One local tumor recurrence occurred 12 months after operation in a patient who discontinued his adjuvant chemotherapy. This patient died of disease, 31 months after operation. Three patients are alive with no evidence of disease at a mean follow-up of 56 months. Walking is not impaired and light sports activities have been reported in all cases. The mean MSTS score is 28/30. CONCLUSIONS: Therefore, we report this reconstruction technique to be considered for special indications where the functional outcome can be improved by preservation of the knee joint in tumors of the proximal meta-diaphyseal tibial region.

Stimulation of renal gluconeogenesis by angiotensin II.

Renal gluconeogenesis was studied in suspended tubule fragments isolated by collagenase treatment of rat kidney cortices. Angiotensin II increased glucose formation from pyruvate, lactate, and to a lesser extent from oxoglutarate and glutamine, but not from other substrates such as malate, succinate, dihydroxyacetone or fructose. Stimulation was significant with peptide concentration exceeding 1 . 10(-8) M and was also shown with an 8-Sar derivative. Other peptides such as 4-Ala-8-Ile-angiotensin II, hexapeptide and bradykinin had no effect. The stimulatory action of angiotensin II was additive to that of L-lysine, and 3',5'-adenosine cyclic monophosphate, suggesting a different mechanism of action. In the presence of maximally stimulatory concentrations of oleate, phenylephrine and 3',5'-guanosine cyclic monophosphate, however, the stimulatory effect of angiotensin II was absent. Cyclic GMP levels, however, did not increase in tubules after angiotensin II and phenylephrine addition, making a messenger function of this nucleotide unlikely. Omission of Ca2+ from the medium markedly reduced basal gluconeogenesis but did not result in a complete loss of angiotensin II effect. Reduction of medium potassium to 2 mM, however, increased basal gluconeogenesis and blunted the peptide effect. 1 mM ouabain was also able to inhibit the stimulatory effect of angiotensin II. Therefore changes in intracellular potassium levels are discussed as a possible mechanism of angiontensin action, whereas calcium seems not to be specifically linked to this metabolic action of angiotensin on the proximal tubule.

Phosphatidylcholine biosynthesis in rabbit kidney tubule suspensions. Effect of metabolic substrates on precursor incorporation.

To gain insight in the mechanisms that regulate phosphatidylcholine (PC) biosynthesis we studied the incorporation of [14C]choline and 14C-labelled fatty acids into PC of tubule suspensions of rabbit kidney cortex and outer medulla, in vitro. Moreover, the influence of renal substrates on these incorporation rates were examined. When incubated with saturating concentration of 1 mM [14C]choline tubules incorporated 4.40 +/- 0.36 mumol choline per g protein per h. Addition of fatty acids such as palmitate and oleate led to a significant increase in [14C]choline incorporation into PC. Further addition of renal substrates such as glucose, propionate, proline, glutamine and glutamate further enhanced this stimulated incorporation significantly. Maximal rates of [14C]choline incorporation were found to be 9.94 mumol per g protein per h in presence of choline, oleate and glucose. In tubules of the outer medulla only glucose showed a stimulatory effect. On the other hand, 14C-labelled fatty acids were incorporated into tubular PC to a similar extent as was found for [14C]choline incorporation (4.54 +/- 0.62 and 5.52 +/- 0.77 mumol/g protein per h for oleate and palmitate, respectively). Addition of choline or renal substrates increased fatty acid incorporation in an additive manner. Maximal rates of 14C-labelled fatty acid incorporation were found to be 17.7 mumol per g protein per h in presence of oleate, choline and propionate. In contrast to isotope studies, net PC content decreased rather than increased under all experimental conditions, indicating that results may represent membrane lipid turnover. The observed rates are sufficient to replace total renal membrane PC in 1 day.

Phospholipid metabolism in rat kidney cortical tubules. II. Effects of hormones on 32P incorporation.

To evaluate the effect of hormones on renal phospholipid metabolism and turnover, we studied the changes in 32P-labeling of phospholipids in rat cortical tubule suspension. Angiotensin II, phenylephrine and parathyroid hormone (PTH) stimulate 32P incorporation into PC by 25, 29 and 26% and into PI by 189, 328 and 33% above control rates, respectively, whereas phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate labeling was not affected. However, when phospholipids were prelabeled with [32P]Pi, addition of angiotensin II led to a significant decrease in phosphatidylinositol 4,5-bisphosphate labeling in the first 2 min with no effect on the other phospholipid fractions. The phenylephrine effect on phospholipid labeling was blocked by prazosin but not by yohimbine, indicating an alpha 1-mediated action. In contrast, the effect of angiotensin II was not inhibited by either antagonist. The stimulating effect of substrates on 32P incorporation reported in the preceding paper was additive to that of hormones. Our results confirm previous studies on renal gluconeogenesis that catecholamines act by an alpha 1-type receptor on proximal tubules, and indicate that phenylephrine and angiotensin II act by different receptor sites exerting the same metabolic effect. The additivity of hormone effects with that of renal substrates indicates that the former are not secondary to release of precursors for phospholipid biosynthesis. The rapid decrease in phosphatidylinositol 4,5-bisphosphate labeling after angiotensin II suggests that the polyphosphoinositide is degraded after hormone binding to the receptor and that PI labeling is a secondary event.

Phospholipid metabolism in rat kidney cortical tubules. I. Effect of renal substrates.

Renal phospholipid metabolism was studied in rat cortical tubule suspensions by combining net measurements with precursor incorporation studies in order to be able to calculate the turnover of the different phospholipid species. Net amounts of tubular phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) were 96.7 +/- 3.9, 29.2 +/- 2.9 and 74.1 +/- 6.0, mumol per g protein, respectively. Incubation of tubules in the absence or presence of renal substrates did not change net phospholipid contents. The predominant fatty acids were palmitate (47%) in PC and stearate in PI (56%) and PE (41%). Highest [14C]palmitate and [14C]glycerol incorporation rates were found in PC. In contrast, 32P-labeling was highest in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate exceeding PI-labeling by a factor of 2.4 and 5.2, respectively. In contrast, [3H]inositol incorporation into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate was only 20% compared to that into PI. Addition of renal substrates like lactate, glutamine, glycerol and fatty acids increased precursor incorporation. The stimulating effects of gluconeogenic precursors and fatty acids were more than additive. Comparison of rates of [14C]glycerol, [32P]- and [3H]inositol incorporation suggests that de novo phospholipid biosynthesis is represented by these measurements, while the fatty acid fraction in addition turns over by exchange processes. According to our conclusions PE, PC, PI and phosphoinositides turn over with a half-life of 139, 16, 15 and 0.7 h, respectively, under optimal in vitro conditions.

Compartmentation of ATP within renal proximal tubular cells.

Studies on the relations between active solute transport and cell metabolism require not only knowledge of the total cellular ATP, but also of the separate mitochondrial and cytosolic ATP levels. For this purpose, mitochondrial and cytosolic fractions were separated from isolated proximal tubular suspensions by the digitonin technique and the amount of ATP analyzed separately for each compartment. In a parallel series of experiments, the absolute volumes of mitochondrial and extramitochondrial spaces were determined in rat renal cortical tubular suspension utilizing electron microscopic morphometry. When referring ATP measurements to the morphometrically determined absolute volumes, the ATP concentrations were calculated to be 4.33 mmol/l for the cytosolic and 2.62 mmol/l for the mitochondrial space. The cytosolic and mitochondrial ATP, thus, represent 70 and 30% of the total cellular ATP, respectively.

[Osteosarcoma and chondrosarcoma of the pelvis and lower extremities]. / Osteo- und Chondrosarkome des Beckens und der unteren Extremitäten.

A wide tumor resection is essential in the therapy of primary malignant bone tumors to minimize the risk of local recurrence and ensure long-term survival. While chondrosarcoma is mainly treated surgically, osteosarcoma therapy consists of both chemotherapy and surgical resection of the tumor. While endoprosthetic replacement after hemipelvectomy tends to be associated with high infection rates and has been superseded by hip transposition and composite osteosynthetic replacements, the use of megaendoprosthetic tumor prostheses is the most common reconstruction technique when the extremities are affected. Biological reconstruction or ablative procedures are reserved for special indications. Overall, the reconstruction techniques presented in this article manage to ensure limb salvage in most patients. Functional outcome, however, greatly depends on the tumor size and site as well as postoperative residual soft tissue coverage.

Association of CSF apolipoprotein E, Abeta42 and cognition in Alzheimer's disease.

A significant association between CSF Abeta42 and cognition in patients with Alzheimer's disease (AD) homozygous for the epsilon3 allele of the apolipoprotein E (apoE) has been described. In this study we extended our observations on apoE, as another plaque component, and investigated the association between CSF apoE concentrations and cognitive performance after stratification for the apoE genotype in 62 patients with AD, 19 other forms of dementia and 18 controls. CSF Abeta42 and apoE concentrations were significantly and positively associated with Mini Mental State Examination (MMSE) score in AD (Abeta42: r = 0.332; P = 0.026; apoE: r = 0.386; P = 0.006). For Abeta42 this association was exclusively present in epsilon3 homozygotes (r = 0.44; P = 0.014), whereas apoE was correlated with MMSE in epsilon4 hetero- or homozygotes subjects (epsilon4/epsilonX: r = 0.638; P = 0.004: epsilon4/epsilon4; r = 0.812; P = 0.05). No association was observed between CSF concentrations of Abeta42 and apoE. The significant relationship between MMSE and CSF Abeta42 in epsilon3 homozygotes and apoE in epsilon4 hetero- and homozygotes respectively may suggest that both proteins may be associated independently from each other with cognitive decline.

Diagnostic strategies in urinalysis.

The traditional methods in urinalysis (visual microscopy, qualitative test strip screening) were compared with automated microscopy (UA-1000, TOA-medicals, Japan) and quantitative single protein analysis in 562 fresh morning urine samples. Albumin served as "glomerular" and alpha 1-microglobulin as "tubular" markers measured by turbidimetry. The test strip delivered at least one positive result in 60% of the urine for blood (21%), leukocytes (27%), or protein (34%). In only 4% casts or renal cells were found by traditional microscopy, whereas automated microscopy was positive for these findings in 28% of the urine. Quantitative urine protein analysis alone exhibited results outside the reference interval in 52% of the urine. Combination of the test strip procedure for blood and leukocytes with urine protein analysis increased the number of positives to 73%. Thirteen percent of these additional findings were classified as glomerular (64%) and tubular (72%) proteinurias. In 7% of the urine a false positive protein test strip result was confirmed by quantitative albumin determination. Of 157 urine samples, positive in mechanized video recorded screening, 60 (38%) were normal in single protein analysis. The results allow for the conclusion that the advanced techniques are superior to traditional screening procedures in detecting abnormal urine composition. It is suggested that traditional urinalysis should be supported or replaced by quantitative determination of albumin and alpha 1-microglobulin. This recommended strategy is able to exclude or detect tubulo-interstitial nephropathies or microalbuminuria in earlier phases of renal complications, such as in diabetes mellitus, hypertension or in nephrotoxic injury. A fully mechanized version is suggested to meet appropriate quality criteria and economic needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Differentiation of proteinuria and haematuria by single protein analysis in urine.

Single proteins and tubular enzymes have been proposed as markers to detect and differentiate prerenal, glomerular, tubular, and postrenal forms of proteinuria and haematuria. By quantitation of total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin, and N-acetyl-beta, D-glucosaminidase (beta-NAG) activity it has become possible to clearly separate these forms by analysis of a single sample of second morning urine. When this program was applied to screening of hospital patients, albumin, total protein, and NAG proved to be sufficient to exclude clinically relevant disturbances. alpha 1-Microglobulin was useful to separate primary glomerulopathies from tubulo-interstitial diseases. Glomerular and postrenal haematuria could be clearly separated by their different excretion rates of alpha 2-macroglobulin, when urine albumin concentration exceeds 100 mg/L. The results imply that wider application of these techniques can help to detect renal abnormalities at an earlier stage and differentiate the various forms by less invasive techniques.

Cerebrospinal protein tau is elevated in early Alzheimer's disease.

Protein tau concentration was determined by an enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) of 22 patients with clinically diagnosed Alzheimer's disease (AD), in three patients with dementia caused by other neurological disorders (OND) and in 19 cognitively healthy controls. A significantly elevated protein tau concentration was found in AD patients as compared with controls, even in 11 patients with very mild dementia. There was no correlation between protein tau and the severity of cognitive impairment as assessed with the Mini Mental State Examination (MMSE). Tau concentrations were not or only slightly elevated in OND. We conclude that protein tau in CSF might be helpful as a biological marker for the early diagnosis of AD.

Cerebrospinal beta-amyloid ((1-42)) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline.

The concentration of beta-Amyloid ((1-42)) protein (Abeta42) in cerebrospinal fluid (CSF) was determined in 75 Alzheimer's disease (AD) patients, 35 patients with other causes of dementia and 30 cognitively healthy age-matched controls. A significant decrease of Abeta42 concentration was found in AD patients, even in 25 subjects with very mild dementia as compared to patients with other causes of dementia and controls. Within AD patients we observed a significant decline of Abeta42 from very mild to mild and moderate dementia. In addition, Abeta42 levels were negatively correlated with the severity of cognitive impairment and with the number of varepsilon4 alleles inherited. We conclude that measurement of Abeta42 in CSF might be helpful for identifying AD at an early stage and also for tracking the clinical course.

The use of knowledge-based systems to improve medical knowledge about urine analysis.

Urine protein diagnostics has developed into a routine method for screening and monitoring kidney diseases. It is based on the quantitative measurement of total protein, albumin, alpha(1)-microglobulin, immunoglobulin G and alpha(2)-macroglobulin (all related to urine creatinine), as well as a dipstick screening. The excretion pattern of the marker proteins allows differentiation of haematuria, leukocyturia and proteinuria and to assign them to prerenal, renal and postrenal causes. In order to provide the clinical partner not only with pure analytical results, but to support clinical decision making by an interpretative report, a urine protein expert system (UPES) has been developed. Based on a database containing more than 500 excretion patterns of patients with known diagnoses, a knowledge base was extracted. In its modules plausibility control, glomerular filtration rate, hematuria, leukocyturia and proteinuria, IF-THEN-rules interpret the given patterns and select matching text elements. The knowledge base has been integrated in the modern expert system shell WILAS, and the resulting interpretation system has been thoroughly verified and validated. An internal acceptance study revealed that urine protein differentiation is widely accepted as a diagnostic option and that its interpretation, provided with the help of UPES, is appreciated as a service. In an external study, the usability of UPES in routine and its knowledge representation was evaluated in 11 centres consisting of laboratories and nephrological partners. Over seven months, more than 500 cases were interpreted using UPES and documented by questionnaires. The discussion of the results at a user conference revealed that the problem of analytical standardisation as well as the common definition of diagnostic terms by laboratory staff and clinicians play a crucial role for the use of knowledge-based systems in laboratory medicine. Whereas the user interface of UPES was judged very heterogeneously, the correctness of the proposed interpretations was unanimously rated as "good". As a result of the evaluation, the user interface has been modernised. The knowledge base has been extended to address paediatric issues as well, and to take clinical information and previous findings into consideration.

Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases.

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An enzyme preparation with specific activity of 102 Ug(-1) protein was obtained. The urinary activities of neutral endopeptidase and alanine aminopeptidase were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14.1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increases in the rate of excretion of these enzymes (2.5- and 3.5-fold), respectively, were observed in patients suffering from acute tubular insufficiency and even lower increases, 2- and 1.5-fold, respectively, were observed in patients with chronic renal diseases. In diabetics and kidney transplant patients the enzyme excretion rates were within the reference range. Assay of both transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could be employed as differentiation markers between acute and chronic tubular insufficiency.