Biomedical subjects

A Hesse

Publications and source records attributed to A Hesse.

At least 37 records · Page 2Linked to original sources

PubMed2002

Analysis of the genes SLC7A9 and SLC3A1 in unclassified cystinurics: mutation detection rates and association between variants in SLC7A9 and the disease.

Cystinuria is a common inherited disorder of defective renal reabsorption of cystine and dibasic amino acids. Recently, 2 responsible genes have been identified: mutations in the SLC3AI gene encoding the glycoprotein rBAT cause cystinuria type I, while variants in the SLC7A9 gene have been demonstrated in non-type I cystinuria; its gene product b(0)+AT is the light chain of the renal cystine transport system rBAT/b(0),+-AT. To estimate the role of both genes in the etiology of cystinuria, we searched for sequence alterations in SLC7A9 and SLC3AI: 30 unclassified cystinurics were investigated. In 50% of patients (15/30), point mutations in SLC3A1 were detected. Screening of the SLC7A9 gene revealed 10 mutations in 8 patients corresponding to a frequency of 27%. In addition to previously published mutations in the SLC7A9 gene, we detected 2 new mutations (F 140S, c747delG). An overall detection rate of 73% (22/30) in unclassified patients is delineated for mutations in both genes. In 33% (10/30), 2 mutations were detected, in 40% (12/30) 1 mutation. Furthermore, 5 new polymorphic sites were identified in SLC7A9. While the base pair variation in intron 9 is homogeneously distributed in patients and control individuals, the allelic and genotypic distributions of the polymorphisms in 3 exons of SLC7A9--exons 2, 5 and 6--and intron 3 differ significantly between both groups. Our results suggest that some haplotypes defined through the exons 2, 5 and 6 and intron 3 might be markers of a functional variant in the SLC7A9 gene. Evidently, since the mutation detection rates in the 2 so far known cystinuria genes never reach 100%, further genes and modulating factors should influence the phenotype in a subset of patients. However, the presented data show that testing for mutations in the 2 currently known cystinuria genes is already a meaningful approach to the molecular diagnostics of the disease.

Amino Acid Transport Systems, Basic↗

PubMed2001

The relation of urinary Tamm-Horsfall-protein on CaOx-crystallization under the scope of the Bonn-Risk-Index.

In previous papers we introduced the Bonn-Risk Index (BRI) as a new method of evaluating an individual's actual risk of forming calcium oxalate (CaOx). A comparison of our results with the calculated urinary relative supersaturations (RS) with respect to CaOx, showed that samples with similar values of RS can have different values of BRI. We suggested that this may reflect the individual influence of the urinary macromolecular constituents which are not taken into account at the calculation of RS. To estimate the role of macromolecules on the value of BRI, we examined 45 unprepared 24-h urine samples from 24 persons (16 healthy subjects, eight CaOx stone-formers) with respect to BRI, RS, and the concentration of urinary Tamm-Horsfall-protein ([THP]). The crystallization experiments were carried out by the use of a laser-probe. Based on the data of BRI and RS, the effect of THP may shift from a minor promoter in stone-formers and persons "at risk", to an inert urinary constituent in healthy subjects and persons "without risk". However, the observed effects are small and at least in the latter group close to zero.

Adult↗

PubMed2001

Urinary oxalate excretion in female calcium oxalate stone formers with and without a history of recurrent urinary tract infections.

Therapy with antibiotics in recurrent urinary tract infections may destroy colonies of Oxalobacter formigenes in the intestinal tract. A lack of oxalate degradation caused by the absence of this bacterium is suggested to contribute to the hyperabsorption of dietary oxalate and to the increase in urinary oxalate excretion. The present study was performed to evaluate the effect of recurrent urinary tract infections and subsequent changes induced in the urinary excretion profile in female calcium oxalate stone formers. Serum biochemical profiles, 24-h urinary parameters, and the personal characteristics of 57 female calcium oxalate stone patients with recurrent urinary tract infections (RUTI) were compared with 78 female calcium oxalate stone patients without a history of urinary tract infection. All subjects were recruited during the same period. In female patients with RUTI, urinary oxalate excretion was significantly higher (0.374 mmol/day) than in females without urinary tract infection (0.308 mmol/day) (P < 0.05). Moreover, the mean 24-h pH value and urinary sodium excretion were significantly higher in women with RUTI than in women without a history of urinary tract infection. The significantly higher urinary oxalate excretion in female calcium oxalate stone formers with recurrent urinary tract infections may be associated with the application of antibiotics and a subsequent temporary or permanent decolonization of Oxalobacter formigenes.

Adult↗

PubMed2001

Pediatric urolithiasis in Armenia: a study of 198 patients observed from 1991 to 1999.

To study prospectively the risk factors and etiology of urolithiasis in all stone patients aged <15 years admitted from 1991 to 1999 to the Arabkir hospital in Yerevan. Stones were obtained by surgery (64%), extracorporeal shockwave lithotripsy (ESWL) (7%) or cystoscopic extraction (4%); 25% passed spontaneously. All were examined by infrared spectroscopy, and spot urines were analyzed chemically. 198 patients, 180 (68% males) with renal stones and 18 (83% males) with primary bladder stones, were studied. Calcium oxalate (CaOx) was the predominant constituent in 62% of the kidney stones, followed by struvite (17%), calcium phosphate (7%), uric acid (7%), ammonium acid urate (5%), and cystine (2%). Bladder stones contained CaOx in 72%, uric acid in 22% and ammonium acid urate in 6% of patients. Etiology was obviously metabolic in 5% and possibly metabolic in 26%. Twenty percent of stones were infectious, and 19% were endemic (9% bladder and 10% kidney stones); 4% were secondary to urinary stasis with malformation but no infection. Etiology in 26% remained unknown. Stone composition and metabolic etiology are similar to that in central Europe and North America. In contrast, infectious calculi and particularly endemic stones are still common, although becoming less so now. Urolithiasis in Armenia thus reflects the transition from a rural to an urban society.

Adolescent↗

PubMed2001

Calcium-binding capacities of different brans under simulated gastrointestinal pH conditions. In vitro study with (45)Ca.

The present study was performed to investigate calcium-binding characteristics of different brans under simulated gastrointestinal pH conditions and to explore the significance of dietary fiber, oxalate, and phytate for calcium binding. Different brans (rice, rye, soy, fine wheat, coarse wheat, and oat) and CaCl(2) solution containing (45)Ca were incubated at 37 degrees C at gastric pH (2.2) followed by buffering steps of 1 degree from pH 3.0 to pH 8.0. Total calcium binding and calcium-binding capacity of the pH 2.2 soluble bran fraction were determined. Additionally, oxalate and phytate contents of brans and solubility profiles of phytic acid were investigated. Calcium-binding capacities of brans showed a clear pH dependence. At gastric pH calcium binding was low in all brans, ranging from 0.022 to 0.040 mmol of calcium/g of bran. Soy bran, nearly phytate-free, showed higher binding values up to pH 4.0 and lower values between pH 5.0 and 8.0. In all other brans, binding values increased strongly with increasing pH in the quantitative order rice bran > coarse wheat bran > fine wheat bran > rye bran > oat bran. The solubility profiles indicate that in the cases of rye, wheat, and rice bran phytate accounts for 70-82% of their total calcium-binding capacities. The results suggest that dietary fiber makes no important contribution to calcium binding, except for soy and oat brans. Oxalate plays only a minor role in calcium binding by brans.

Avena↗

PubMed2001

Chemolysis of struvite stones by acidification of artificial urine--an in vitro study.

OBJECTIVE: The aim of the study was to look for strategies that improve the clinical outcome of struvite stones. An in vitro experimental set up with artificial stones made of struvite (BON(N)-STONES) was chosen to perform standardized and reproducible analyses on various artificial urines with pH-values that may be reached by acidification with oral methionine treatment. MATERIALS AND METHODS: Artificial ball-shaped stones made of struvite (BON(N)-STONES) with a diameter of 0.8 cm were used. The investigations on chemolysis were performed using a dissolution device which simulates the physiological conditions in the upper urinary tract with computer-assisted on line measurement of data. For chemolysis of struvite BON(N)-STONES artificial urines according to Griffith at four different pH-values (pH 5.75, pH 6.0, pH 6.25, pH 6.5) were used. Furthermore natural and struvite BON(N)-STONES were treated with Suby G-solution (pH = 4.0). RESULTS: Comparing natural and artificial struvite stones after treatment with Suby G there was no significant difference regarding their dissolution rate. The dissolution rate of struvite stones in artificial urine rose with a decreasing pH-value. The diminution of the pH-value from 6.5 to 5.75 lead to an increase of the dissolution rate of more than 35%. This increase in the dissolution rate decreased with falling pH-value. CONCLUSIONS: The acidification of urine accelerated the dissolution rate of struvite stones in vitro. Considering in vivo conditions the intake of 1,500-3,000 mg L-methionine may lead to a sufficient acidification for a good dissolution of struvite stones.

Humans↗

PubMed2001

Hippuric acid as a modifier of calcium oxalate crystallisation.

Hippuric acid (HA) originating from the conjugation of benzoic acid with glycine is a physiological component of human urine. Findings suggest that HA inhibits calcium oxalate (CaOx) growth and considerably enhances the CaOx solubility in artificial urine. Thus, it is assumed that HA is a major modifier of CaOx formation. However, only a slight CaOx growth inhibition of 1-8% was also reported. These values were also derived from artificial urine. The key mechanism, which led HA to be of interest in urolithiasis research is the fact that in presence of Ca2+ ions HA can form a hippurate complex. By forming such a complex, Ca2+ concentration in urine decreases, and as a consequence, CaOx formation is inhibited. This study was performed in order to clarify the role of HA in native and artificial urine. Biochemical analyses to calculate the relative CaOx supersaturations and crystallisation experiments using an in-line laser probe were examined. BONN Risk Indices indicating the risk of CaOx crystallisation were calculated from the results of the crystallisation experiments. The results obtained from artificial as well as from native urines showed that HA has no significant effects on CaOx formation. We suggest that HA plays only a minor role as a crystallisation modifier in human urine.

Benzoic Acid↗

PubMed2001

Testing the predictability of the relative urinary supersaturation from the Bonn-Risk-Index for calcium oxalate stone formation.

When introducing a new parameter, it is necessary to compare the power of the new measure with already established ones. For a new method it is quite difficult to compete with established methods which have already ascertained sets of data over many years. A formal comparison of the new parameter with the actual "gold-standard" method can be a useful approach to reduce that problem. It cannot be expected that a new measure would reflect the "gold-standard" method in a simple proportionality. Therefore, it is important to find out the accuracy of the prediction of one parameter from the other, based on simple, e.g. linear, functions. A number of methods exist to determine the crystallization risk of calcium oxalate salts from urine. The most established method is the calculation of the relative urinary supersaturations with respect to these salts using the EQUIL-program, a program computing the equilibrium concentrations of complexes of primary cations and anions commonly found in urine. The Bonn-Risk-Index (BRI) is a new strategy for the evaluation of the risk of calcium oxalate formation, by performing crystallization experiments on native unprepared urine samples. Although the analytical and computational efforts of both approaches are quite different (relative supersaturation = high, BRI = low), the measurements revealed a considerable and significant linear relationship between the relative urinary calcium oxalate supersaturation, and BRI. We were, therefore, interested in predicting the relative supersaturation from the BRI and in the accuracy of this prediction.

Calcium Oxalate↗

PubMed2000

A new approach to calculate the risk of calcium oxalate crystallization from unprepared native urine.

This work focuses on the in vitro calcium-oxalate (CaOx) crystallization behaviour of native and synthetic urine samples in order to establish a CaOx crystallization risk index for unprepared native urine. Native 24-h urine samples from healthy persons and from stone-formers were examined. Within a [Ca2+] versus added oxalate (Ox2-) diagram, we observed fields which allow the discrimination of each urine sample in terms of more or less risk. The [Ca2+]/(Ox2-) ratio is calculated and termed the "Bonn-Risk Index" (BRI; per litre). We propose that BRIs > 1/l denote samples "at risk", whereas BRIs < or = 1/l denote those "without risk". Second. the effects of different concentrations of citrate and Mg2+ on BRI were investigated in artificial urine. The transferability of BRI between native and synthetic urine samples is proved. To evaluate the impact of the proposed BRI, it is compared with the more familiar relative urine saturation index calculated for CaOx and brushite. Urine sampled from stone-formers shows risk indexes between 0.278 and 23.0/l (mean 2.87/l), while urine from healthy persons varied between 0.060 and 4.890/l (mean 1.05/l). Comparing the results of healthy volunteers and patients, the significance of BRI and relative urine supersaturation (RS) with respect to CaOx is P < 0.0005 and P = 0.013, respectively. Fast and easy to perform, determination of the risk index is a suitable tool for estimating the actual CaOx formation "status"--"at risk" or "without risk"--from the native urine of any person.

Adult↗

PubMed2000

Improving cystine stone therapy: an in vitro study of dissolution.

OBJECTIVES: To perform an in vitro study analyzing the possibilities in therapeutic strategies for an effective treatment of cystine stones. METHODS: Artificial stones made of cystine [Bon(n)-Stones] with a ball-shaped size of 0.9 cm in diameter were used. Chemolysis of artificial cystine stones with different solvents (artificial urine, physiologic sodium chloride solution, acetylcysteine, tris-(hydroxymethylene)-aminomethane [THAM], and combinations of these) was investigated. An experimental arrangement with computer-assisted online measurement of data simulating the physiologic conditions in the upper urinary tract at varying pH values was used. RESULTS: All solutions showed a statistical improvement in the solubility of cystine stones compared with artificial urine and physiologic sodium chloride solution. The combination of THAM (pH 10) and 2% acetylcysteine was most effective (1 3.91 +/- 1.73 mg/hr) and demonstrated a 41 -fold higher ability to dissolve cystine calculi compared with artificial urine. CONCLUSIONS: Our data indicate that local chemolysis with special solutions is an effective treatment modality in cystine stone therapy.

Acetylcysteine↗

PubMed2000

Experience with the [13C2]oxalate absorption test.

Hyperoxaluria is the most important risk factor for a formation of calcium oxalate-urinary stones. Usually, the bulk of oxalate will be formed in the human body, but in many patients the oxalate from food plays the decisive role. Conventionally, in urine the endogenous oxalate can not be distinguished from food derived oxalate. We have developed a standardized oxalate-absorption test, applying a physiological dose (50 mg disodium salt of [13C2]oxalic acid) of labelled oxalate. The assay has been published. Now we report on the first extensive applications of this test in 86 volunteers and 135 patients from different groups with calcium oxalate stones or an increased risk of the formation of such stones. In one-third of the patients with calcium oxalate-urinary stones an oxalate hyperabsorption was diagnosed. For these patients, a dietetic stone prophylaxis and/or therapy is indicated.

Absorption↗

PubMed2000

Chemolysis of artificial cystine stones (BON(N)-STONES) in vitro using a new dissolution device: first results.

BACKGROUND AND PURPOSE: The treatment of cystine stones is a clinical problem. This in vitro study was performed to establish an experimental system that enables standardized and reproducible investigations on chemolysis of cystine stones to look for an improvement of dissolution strategies. MATERIALS AND METHODS: Artificial spherical stones made of cystine (BON(N)-STONES) with a diameter of 0.9 cm were used. A new dissolution device was developed simulating the physiological conditions in the upper urinary tract with computer-assisted online measurement of data. For chemolysis of artificial cystine stones, different solvents (artificial urine, physiologic sodium chloride solution, 2 % acetylcysteine, 8.4 % sodium bicarbonate solution, THAM, and combinations) were used. RESULTS: Chemolysis is an effective tool in the management of cystine stone disease. Statistical analysis showed significant differences (p < or = 0.05) for all solutions compared with artificial urine alone. A combination of THAM at pH 10 with acetylcysteine (2%) showed a 48-fold stronger ability to dissolve cystine calculi than did artificial urine. CONCLUSION: By performing standardized in vitro investigations, new basics to improve the dissolution of cystine stones have been developed. It is recommended to use artificial stones made of cystine and a dissolution device simulating physiological conditions for investigations on chemolysis in the future.

Acetylcysteine↗

PubMed2000

A new type of artificial urinary calculi: in vitro study by spiral CT.

RATIONALE AND OBJECTIVES: Artificial urinary calculi similar to natural stones have long been sought in urologic research. In an experimental study, the authors assessed the CT characteristics of a new type of artificially produced urinary calculus [BON(N)-STONE]. METHODS: Six different types of urinary calculi (uric acid, struvite, cystine, calcium oxalate, brushite, and apatite) were produced by a coating technique in which several layers of a suspension of pure substance were applied around a core and dried. A total of 60 stones (10 per group) were studied by spiral CT at two energy levels (100 and 120 kV, 250 mA) with 1-mm slice thickness. RESULTS: All calculi showed a small hyperdense core surrounded by a homogeneous matrix and a slightly hyperdense outer rim. From the least to the most dense, the stone types were uric acid, struvite, cystine, calcium oxalate, brushite, and apatite. Absolute CT values at 100 and 120 kV could differentiate between all groups of stones at a significance level of P < 0.001 or better. Attenuation values were in a comparable range to reported values for natural stones, with the exception of uric acid and struvite, which were notably lower. CONCLUSION: These artificially produced urinary calculi showed properties similar to those of natural stones. Thus, this seems to be a promising stone model for further investigations.

Humans↗

PubMed2000

Influence of alkaline solutions on chemolitholysis and lithotripsy of uric acid stones. An in vitro study.

OBJECTIVES: This study was performed to look for an improvement of therapeutic strategies with regard to the treatment of uric acid stones using artificial stones made of uric acid (BON(N)-STONES) which are comparable to their natural counterparts. MATERIALS AND METHODS: Using an experimental arrangement simulating the physiological conditions in the upper urinary tract the efficacy of different alkaline solutions and artificial urine in dissolving artificial uric acid stones (BON(N)-STONES) was investigated. The dissolution of natural uric acid stones was measured and investigations on shock wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. RESULTS: The efficacy of alkaline solutions, especially THAM at a pH of 10, in dissolving artificial uric acid stones was demonstrated. The investigations on SWL showed a significant improvement on stone comminution of artificial uric acid stones after initial chemolytic treatment with THAM. CONCLUSIONS: New basics to improve dissolution of uric acid stones have been developed by performing standardized in vitro investigations. The suggestion was confirmed that stone fragility and thus SWL can be improved by varying the physical properties of uric acid stones through initial treatment with THAM solution.

Lithotripsy↗

PubMed2000

Acoustic and mechanical properties of artificial stones in comparison to natural kidney stones.

PURPOSE: Standardized and reproducible artificial kidney stone models are important for performing comparative studies of different lithotripsy modalities. The acoustic and mechanical properties of renal calculi dictate the manner by which stones interact with the mechanical stresses produced by shock wave lithotripsy (SWL) or intracorporeal lithotripsy modalities. We have developed a novel artificial kidney stone model that is made of natural substances found in real kidney stones. These stone models appear to be much closer in physical properties to natural kidney stones than previously used stone models. MATERIALS AND METHODS: The acoustic and mechanical properties of six groups of artificial stone models were compared to corresponding natural stones of similar compositions. Moreover, three groups of artificial stone models made of plaster-of-Paris were compared to their natural counterparts. In terms of acoustic properties, stone density was measured using a pycnometer based on Archimedes' principle, whereas longitudinal and transverse (or shear) wave propagation speeds were measured using an ultrasound pulse transmission technique. These values were used to calculate wave impedance and dynamic mechanical properties (bulk modulus, Young's modulus, and shear modulus) of the stones. The microhardness of the stones was measured and the effect of composition on stone fragility was evaluated. RESULTS: Artificial stones, when compared to natural stones of similar composition, showed similar trends in longitudinal and transverse wave speeds, wave impedance, and dynamic elastic moduli. However, values for the artificial stones were uniformly low compared to those of natural stones, suggesting that these artificial stones may be more amenable to shock wave fragmentation. The results of SWL on stone fragmentation of artificial and natural stones also revealed similar trends with the exception of artificial cystine stones which were found to be the most resistant to shock wave fragmentation. CONCLUSIONS: The results indicate that the physical properties of artificial stones made of natural stone materials are comparable to renal calculi of the same chemical composition. The data suggests that these stone phantoms are suitable for performing standardized and reproducible in vitro investigations, especially with regards to fragility of kidney stones of different chemical compositions during SWL.

Acoustics↗

PubMed2000

Cross-over study of the influence of bicarbonate-rich mineral water on urinary composition in comparison with sodium potassium citrate in healthy male subjects.

Urine volume is the greatest risk factor for nephrolithiasis. High fluid intake is the first general advice given to stone-forming patients for the prevention of their recurrence. The aim of the present study was to evaluate the influence of bicarbonate-rich mineral water (1715 mg bicarbonate/l) on urinary-stone risk factors in comparison with sodium potassium citrate, a well-established treatment for urinary stones. The mineral water and sodium potassium citrate were administered in equimolar concentrations, with respect to the alkali load. All investigations were carried out in healthy male subjects aged 23-38 years. The study followed a cross-over design. All subjects received a standardized diet during the cross-over phase, which was formulated according to the dietary recommendations of the German Society of Nutrition (Deutsche Gesellschaft für Ernährung, 1996). On the loading day of the cross-over phase, fruit tea was substituted for either mineral water or sodium potassium citrate dissolved in fruit tea. The treatment offered during the second part of the cross-over phase was continued for a 4-week follow-up under normal dietary conditions. During the cross-over phase, there was a significant increase in urinary pH (p < 0.001). There was also a significant increase in the excretion of citric acid (P < 0.01), a decrease in the excretion of oxalic acid, and therefore a decrease in the relative supersaturations for calcium oxalate and uric acid. In the follow-up phase also, the relative supersaturations decreased and there were beneficial effects on the other urinary variables. The effect of the bicarbonate-rich mineral water was similar to that of the sodium potassium citrate, which suggests that it could be useful in the prevention of the recurrence of calcium oxalate and uric acid stones.

Adult↗

PubMed1999

Direct measurement of calcium oxalate nucleation with a laser probe.

To understand the genesis of urinary stones different crystallization models have been developed to simulate the crystallization processes that occur at the beginning of the stone formation. In this study a laser probe working on the principle of the measurement of back-scattered light was mounted on a batch crystallization model, in which calcium oxalate nucleation was induced by titration of an artificial urine with ammonium oxalate. With the laser probe the particle numbers and particle size distributions in the range from 1-250 microm can be measured in a single experiment. Measurement is performed directly at the place of crystal development and, therefore, falsification of the results (by dilution, mechanical transport or isolation, temperature gap, multiple measurements, mathematical calculations after indirect measurements, etc.) is prevented. In a basic urine, containing 7.5 mmol/l calcium (4.13 mmol/l free calcium), nucleation of calcium oxalate appears at a concentration of 0.58 mmol/l oxalate. At the start of nucleation the particle size rises to 7 microm. After addition of citrate and magnesium in concentrations up to 12 mmol/l the metastable limit is clearly shifted up to 1.50 mmol/l oxalate. Both findings are in good agreement with the literature. The laser crystallization model has proved to be useful for the testing of inhibitors and promoters of urinary stone formation.

Calcium Oxalate↗

PubMed1999

How to improve lithotripsy and chemolitholysis of brushite-stones: an in vitro study.

Because of their resistance to fragmentation, treatment of brushite stones is a big problem. This study was performed to look for an improvement in therapeutic strategies by using artificial stones made of brushite (Bon(n)-stones), which are comparable to their natural counterparts. Using an ultrasound transmission technique, longitudinal wave propagation speeds were measured at different time intervals during treatment with hemiacidrin. From these and density measurements, transverse wave speed, wave impedance and dynamic mechanical properties of the artificial stones were calculated. Moreover, the microhardness of artificial stones was measured and investigations on shock wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. The suggestion was confirmed that stone fragility and thus SWL can be improved by varying the physical properties of brushite stones through treatment with hemiacidrin. Additionally, we demonstrated the efficacy of Suby G in dissolving artificial brushite stones using an experimental arrangement simulating the physiological conditions in the upper urinary tract. Moreover, the efficacy of four different intracorporeal lithotripsy devices (electrohydraulic, pneumatic, laser and ultrasound) was tested and it was shown that electrohydraulic lithotripsy seems to be the best system for comminution of brushite stones.

Calcium Phosphates↗