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Biomedical subjects

R Hautmann

Publications and source records attributed to R Hautmann.

At least 109 records · Page 6Linked to original sources

Resolution of proteins in the kidney stone matrix using high-performance liquid chromatography.

The organic matrix accounts for 2-3% of the total stone weight and has been considered to play a role in stone formation and growth. Thus far, fractionation of the matrix proteins has been insufficient due to low resolution and reproducibility. In this report the matrix proteins of 22 stones were resolved by means of high-performance liquid chromatography. Following pulverization, the organic matrix was obtained by dialysis against EDTA. The average content of nondialyzable extractable proteins was 1.6% of the total stone weight. Analysis of the matrix proteins with high-performance gel permeation liquid chromatography and high-performance ion-exchange liquid chromatography has indicated that the protein composition of the stone matrix is identical regardless of the mineral composition. The major component of the matrix proteins was identified as glycoprotein and/or proteoglycan from their absorption to a concanavalin A Sepharose column. Higher molecular weight matrix proteins seem to be polymers or condensation products, since they have been degraded into lower molecular weight subfractions by sodium dodecyl sulfate treatment.

Chromatography, High Pressure Liquid↗

[Prevention of calculus recurrence in impaired kidney function].

The pathophysiologic consequences of renal function impairment and chronic renal failure among others result from the loss of excretory and regulatory functions of the kidneys. The role of the exchange of cellular hydrogen ions of tubular fluid in the reabsorption of bicarbonate and in the urinary excretion of titratable acid and ammonia (acid-base regulation) is outlined. The effects of decreased glomerular filtration rate on calcium and phosphorus homeostasis are discussed. De novo urolithiasis in these patients is uncommon. However, it is well recognized that they may form matrix stones with calcium oxalate inclusions. Of greater significance is the prophylaxis in those patients, in whom urolithiasis has been the cause of chronic renal failure. In these patients it is of importance to modify the drug dosage or to abandon the prophylaxis when it interferes with the metabolic changes of renal function impairment. Some agents require no modification, others minor or major modifications. Some are even contraindicated. Hazards of stone prophylaxis in chronic renal failure: Acidification - cave metabolic acidosis! Cave RTA! Antibiotic agents - special rules to prevent accumulation. Thiazides - contraindicated! Hypokalemia; hyperuricemia; cave HPT! Triamterene - contraindicated! Acetazolamide (cystinuria) - contraindicated. Spironolactone - contraindicated. Sodium-cellulose-phosphate - Hyperoxaluria, hypomagnesiuria , hyperphosphatemia, cave HPT. Orthophosphate - cave urinary infection, cave poor renal function, cave obstruction. Allopurinol - dose reduction advisable. Brenzbromaron - contraindicated.

Acid-Base Equilibrium↗

Concentration profiles of calcium and oxalate in urine, tubular fluid and renal tissue--some theoretical considerations.

This paper analyzes some aspects of the pathophysiology of urolithiasis. It is emphasized that a better understanding of factors contributing to stone formation can only be gained when the primary nucleation site is identified. Three compartments are considered in which supersaturation as a precondition for stone formation could be present: urine in the urinary tract, tubular fluid from the glomerulus down to the duct of Bellini, and the interstitium of the medulla. From calculations based on micropuncture data it becomes apparent that the oxalate concentration in the tubular fluid at the bend of Henle's loop is 1 or 2 orders of magnitude lower than in the duct of Bellini and that the oxalate concentration maximum invariably must be located in the final urine. The calculation of a tubular concentration profile of oxalate shows, that the probability of intra luminal crystal formation is even less likely for plasma oxalate values of 2-3 microM as compared to 1.2 microM, which therefore should be the correct value. The time necessary for the growth of crystals up to a critical size which can obstruct tubules or ureter is not available in the urinary tract nor in the tubules. However, in the medullary interstitium, where solute concentration is highest, nearly unlimited time for crystal growth is available due to the fact, that in this compartment convective flow is very low. It is concluded that the interstitium of the inner medulla has the best chances to function as the primary nucleation site where particles can be formed of a size which subsequently can obstruct the urinary tract.

Calcium↗

Cefotetan in complicated urinary tract infections--clinical experience.

Cefotetan was evaluated to determine the efficacy and safety of a 1 g dose administered intravenously twice daily in the treatment of complicated urinary tract infections (UTI). Sixty patients entered and 58 patients completed the study. Duration of treatment ranged from 7 to 16 days with a mean of 10.1 days. A satisfactory clinical response was observed in 85%. Eradication of the infecting organisms was prompt and complete in 45 patients. Relapse, reinfection or superinfection occurred in seven patients and in six patients the infecting organisms did not respond to treatment. Cefotetan was well tolerated but two patients had treatment withdrawn because of macular rash. It is concluded that cefotetan is highly effective in treating complicated UTIs.

Adolescent↗

Clinical experience in the treatment of complicated urinary tract infection with different doses of moxalactam (lamoxactam).

Moxalactam disodium underwent phase II evaluation to determine its efficacy, safety, and tolerance in the treatment of complicated urinary tract infections (UTI). Bacteriologic cultures of a clean midstream urine specimen were made and antibiotic sensitivities determined by FDA standard disk testing. Urinalysis and cultures were performed on specimens obtained within 24 h of starting therapy, on the 3rd or 4th day, and the last day of treatment, and again 5-9 days later. Whenever possible a urine sample was obtained 4-6 weeks after therapy in an attempt to measure recurrence of infection. Duration of treatment ranged from 8 to 21 days. Patients were assigned to one of the three treatment groups in chronological order at entry: group I = 2 g single daily dose i.v.; group II = divided dose of 1.0 g i. m.; and group III = single daily dose of 1 g i. m. A total of 122 patients with 129 pathogens entered the study; all completed the protocol. Of 129 pathogens 85 were eliminated. The success rate of about 70% in the three different treatment groups showed no significant difference. In 12 cases the pathogen disappeared while the patient was on treatment but recurred during the post-therapy period. In 28 patients reinfection with a new pathogen, mainly Enterococcus, occurred. There were four therapeutic failures in which the pathogen was not eliminated during any time of treatment. The organisms were either persistent or resistant. In conclusion, moxalactam is highly effective in treating complicated UTIs even at a relatively low dose. We observed no significant difference between the three different treatment protocols used. The only major problem encountered was that Enterococcus is typically resistant to moxalactam, a problem of clinical relevance, particularly in cases of reinfections.

Adult↗

Calcium and oxalate concentrations in human renal tissue: the key to the pathogenesis of stone formation?

On the basis of what we know about urinary supersaturation and particle growth inhibitors stone formation is unlikely to start from free crystalluric particles in the renal tubule. Therefore, the object of this study is to report data on the intrarenal distribution of calcium and oxalate in man and to examine a possible relationship between calcium and oxalate concentrations in the renal tissue and stone formation. Fresh human renal tissue was obtained at operation from 7 subjects. The calcium concentrations in the papilla, medulla and cortex were measured by atomic absorption spectrophotometry. A radioenzymatic procedure was used to determine the corresponding oxalate concentrations. Significantly higher concentrations of calcium and oxalate were observed in the papilla compared to the medulla. The medulla, in turn, contained higher concentrations than the cortex. Calcium and oxalate concentrations were 6 and 25 times higher in the normal papilla than in the urine, respectively. The ion product of calcium oxalate concentrations in the human renal tissue have not been investigated, although the frequent finding of calcification in the renal papilla suggests that they may exist. The observed intrarenal calcium and oxalate concentration gradients seem to be a significant mechanism in the pathogenesis of papillary calcification and a strong indication for renal stone formation to start from fixed crystalluric particles in the papilla.

Calcium↗

Intrarenal distribution of oxalic acid, calcium, sodium, and potassium in man.

The renal papilla in man has been shown to contain a high concentration of oxalate (5 . 5 +/- 0 . 8 mmole/kg wet weight, mean +/- SEM, n = 7 kidneys), and that there is a significant concentration gradient between oxalate in the papilla and that of the medulla (0 . 4 +/- 0 . 08, P < 0 . 05) and the cortex (0 . 3 +/- 0 . 06, P < 0 . 05). Significant calcium and sodium gradients between renal papilla and medulla and cortex were confirmed and parallel that of oxalate. Potassium showed a significant decrease in the papilla (33 . 1 +/- 0 . 9) as compared to the medulla (42 . 1 +/- 1 . 9 P < 0 . 05). The concentrations of oxalate and calcium in the papilla were respectively 25-fold and 6-fold higher than the urinary concentration of oxalate and calcium. It is concluded that these high concentrations of oxalate and calcium in the renal papilla are related to the formation of Randall's plaques and may be an essential factor in the pathogenesis of renal stones which is still far from clear.

Calcium↗

[Belt-Fuqua technique: a useful alternative in hypospadias repair (author's transl)].

This Belt-Fuqua method is of particular help when the entire foreskin lies on the ventral surface of the penis. Such a situation results from an exaggerated buttonhole technique at the time the chordee is corrected as the initial procedure either by chance or intentionally. A portion of the transposed foreskin is used to fashion a tube of appropriate length and diameter to reach the end of the penis. This new urethra is then drawn through a tunnel on the ventrum of the penis. This operation has several advantages over the available alternative procedures: 1. The Belt-Fuqua technique uses the entire foreskin on the ventral surface of the penis for the extension of the uretha. 2. The abundance of foreskin allows easily to fashion a complete tube of appropriate length and diameter. 3. The new urethra is completely covered by intact subcutaneous tissue and the remainder of the foreskin and is crossed by no sutureline. 4. The procedure is relatively simple to perform, is less likely to result in fistula formation than the alternative procedure used and has not been accompanied by the complications of stricture or meatal stenosis in our hands.

Humans↗

Renal elimination kinetics and plasma half-life of oxalate in man.

The renal handling of oxalate was studied by the injection of 14C-oxalate together with inulin as a glomerular marker into the renal artery in 6 patients. From the recovered amounts of the injected substances in the urine, time-concentration curves were constructed. Oxalate was excreted into urine 2.31 +/- 0.05 (SE) fold when compared to inulin. The maximal concentration of oxalate occurred at the same time as inulin, and there was no urinary precession of oxalate in comparison to inulin. From this part of the study we conclude that oxalate in addition to its filtered amount can probably enter the early part of nephron. In a second type of study, plasma levels of oxalate and inulin were observed over a period of 180 min, following intravenous injections in 7 volunteers. The decline of oxalate plasma concentrations followed first-order kinetics. Calculation of the rate constants of elimination assuming the 'one compartment open' model resulted in an oxalate to inulin ratio of 1.21 +/- 0.05. The oxalate half-life of elimination was 92 +/- 8 min, whereas that of inulin amounted to 112 +/- 9 min. The higher value of the calculated volume of distribution of oxalate compared to that of inulin indicates that oxalate enters a larger space than the extracellular fluid volume. The urinary recovery of intravenously injected oxalate was 97.2 +/- 1.4%, indicating that oxalate is excreted exclusively by the kidney. The observed differences of oxalate excretion, obtained with these two methods, could be attributed to the higher amount of ionized oxalate in the disequilibrium technique (rapid injections), entering the urine in a higher rate. Such a mechanism could explain the hyperoxaluria in calcium oxalate stone-forming patients.

Half-Life↗

Pharmacokinetic studies of oxalate in man.

The observation of the plasma concentrations after rapid intravenous administration of inulin and 14C-oxalate to six normal and one hyperoxaluric subjects allowed estimations of the half-life of elimination of oxalate (mean 91.7 min), volume of distribution of oxalate (mean = 32.5 liters), calculation of the miscible oxalate pool (mean 3.7 mg), of the plasma oxalate concentration (mean = 11.1 microgram per 100 ml), of the oxalate clearance (252 ml per min), and the determination of the oxalate turnover rate (0.027 mg per min). The 14C-oxalate/inulin clearance ratio was 2.44 implying an additional excretion mechanism apart from glomerular filtration. Inasmuch as 97.2 per cent of the administered tracer were recovered unchanged in urine, nonrenal loss of oxalate is not an appreciable factor. The data of one hyperoxaluric patient are compared with those of the healthy subjects.

Amino Acid Metabolism, Inborn Errors↗

Long-term treatment of hypercalciuria with thiazides, sodium or potassium cellulose phosphate, separately or in combination.

Urinary supersaturation in respect to brushite or calcium oxalate represents the main pathogenic factor in stone formation. Of the patients with calcium oxalate stones 30 to 40% present with hypercalciuria. Herein we determine and compare the effects and side effects in the treatment of hypercalciuria with sodium cellulose phosphate or Campanyl, a potassium versus calcium ion exchanger, and thiazides alone or in combination with an ion exchanger.

Benzothiadiazines↗

Renal handling of oxalate. A micropuncture study in the rat.

Clearance and micropuncture experiments were performed in rats to study the renal handling of oxalate. The 14C-oxalate to 3H-inulin clearance ratio (Cox/Cin) was 1.36 +/- 0.04 and was lowered by probenecid (200 mg/kg) to 1.11 +/- 0.03 (+/- S.E., n = 6, P less than 0.005). An attempt was made to localize the assumed secretion of oxalate in three different micropuncture protocols. In free flow micropuncture experiments single nephron clearance of oxalate was not different when obtained from proximal or distal tubular puncture sites. The fractional delivery of oxalate averaged 0.84 +/- 0.03 regardless of the puncture site from mid-proximal to late distal. This finding indicates a net outflux of oxalate in an early proximal loop since oxalate is freely ultrafilterable. In microperfusion experiments the mean recovery of oxalate ranged from 79--90%. The outflux of oxalate correlated linearly with the tubular load (r = 0.95). The results suggest that no net secretion occurs in superficial nephron segments accessible for micropuncture. Since whole kidney clearances of oxalate always exceeded glomerular filtration rate, it is concluded that net addition of oxalate into the tubular fluid can occur at sites beyond the superficial late distal tubules or is due to higher delivery of oxalate by deep cortical nephrons.

Animals↗

Calcium oxalate stone disease: effects and side effects of cellulose phosphate and succinate in long-term treatment of absorptive hypercalciuria or hyperoxaluria.

Absorptive hypercalciuria was treated in 27 patients with cellulose phosphate. In all patients urinary calcium decreased and stone formation virtually ceased. The most striking side effect was an excessive hyperoxaluria, necessitating withdrawal of the drug in 8 patients. Succinate decreased the hyperoxaluria in 14 of 19 patients. All patients had mild hypercalciuria and hypermagnesiuria. This study was done to determine the therapeutic value and the side effects in the treatment of absorptive hypercalciuria with sodium cellulose phosphate and of hyperoxaluria with succinate.

Adult↗

Ureteral calculus: experience with 521 stone extractions.

Few urologic problems require the consideration of so many factors as does an obstructing calculus in the ureter. The questions that arise in each case are whether an operation should be done for immediate relief of the obstruction or whether manipulation should be done, possibly subjecting the patient to a period of disability, painful attacks of colic and febrile reactions.

Catheterization↗

Mercaptopropionylglycine: a progress in cystine stone therapy.

During a 4-year period 9 cases of severe recurrent cystine stones and cystinuria were treated with mercaptopropionylglycine. The oral long-term administration revealed the high effectiveness of the drug and resulted in no further stone formation. Mercaptopropionylglycine is free of side effects and more effective than D-penicillamine.

Adult↗