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Biomedical subjects

J M Baumann

Publications and source records attributed to J M Baumann.

At least 19 recordsLinked to original sources

Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.

BACKGROUND: Exercise induced bronchoconstriction (EIB) is common in elite athletes. Eucapnic voluntary hyperventilation (EVH) is a laboratory test recommended for the identification of EIB in athletes, secondary to a field exercise challenge. Montelukast attenuates EIB, but its protective effect against airway narrowing from EVH has not been investigated. OBJECTIVE: To examine the effectiveness of montelukast after exercise and after EVH. METHODS: A randomised, placebo controlled, double blind, crossover study was performed with 11 physically active EIB positive subjects (eight men, three women; mean (SD) age 22.8 (6.8) years). Six hours before each of the following challenges 10 mg montelukast or placebo was ingested: (a) a six minute, cold air (-3 degrees C) maximal effort work accumulation cycle ergometer exercise; (b) EVH, breathing 5% CO(2) compressed air at 85% maximal voluntary ventilation for six minutes. Spirometry was performed before and 5, 10, and 15 minutes after the challenge. At least 48 hours was observed between challenges. RESULTS: No differences in forced expiratory volume in one second (FEV(1)) were found after the two challenges. Exercise and EVH resulted in falls in FEV(1) of 22.4 (18.0) and 25.6 (16.8) respectively. Falls in FEV(1) after montelukast were less than after placebo (10.6 (10.6) and 14.3 (11.3) after exercise and EVH respectively; p<0.05). Montelukast provided protection against bronchoconstriction (59% and 53%; p<0.05) for eight exercising subjects and 10 EVH subjects; no protection was afforded for three exercising and one EVH challenged subject. CONCLUSIONS: Both exercise and EVH were potent stimuli of airway narrowing. A single dose of montelukast provided reasonable protection in attenuating bronchoconstriction from either exercise or EVH. The similar protection by montelukast suggests that EVH is a suitable laboratory surrogate for EIB evaluation.

Acetates↗

Calcium oxalate aggregation in whole urine, new aspects of calcium stone formation and metaphylaxis.

OBJECTIVES: To assess the influence of pH, Ca(2+)-concentration, hydroxyapatite (HAP) and preformed calcium oxalate (CaOx) aggregates on the aggregation (AGN) of CaOx crystals directly produced in unpretreated whole urine (U) by oxalate loads (OL). METHODS: After OL at pH 5.0 and pH 6.5 minimal sedimentation time of precipitates (ST = minutes for 0.05 optical density [OD] decrease) was measured in 40 U of 5 healthy men by spectrophotometry. An ST(P) (< or =2.8) was taken as indicator for primary AGN and an ST(S) (< or =1.4) as one for secondary AGN. In 20 U Ca(2+) was determined initially, Ca(2+) at pH 6.5 was readjusted by adding CaCl(2) to the value measured at pH 5.0 and an OL of 1.5mM performed. OL of 0.25-0.75 mM were given to 20 U either with 0.05 mg/ml HAP or after a primary OL of 2mM. RESULTS: Alkalinization of U from pH 5.0 to 6.5 decreased Ca(2+) by 44+/-15% (mean+/-S.D.) and, in U with total Ca <3mM, below a crucial value of 1mM where no ST(P) was observed. At identical Ca(2+), pH had no influence on ST. With HAP, an ST(P) was found after an OL of 0.5mM in 10% and of 0.75 mM in 35%, predominantly at pH 5.0. An ST(S) was observed after a second OL of 0.5mM in 55% and of 0.7 5mM in 75% of experiments. CONCLUSIONS: Provided that AGN is important for stone formation, calcium nephrolithiasis might be initiated at high urinary Ox and low pH by HAP of kidney calcifications, prevented at moderate calciuria by alkali treatment and augmented during relative hyperoxaluria by secondary AGN.

Adult↗

Hydroxyapatite induction and secondary aggregation of calcium oxalate, two important processes in calcium stone formation.

Stone formation has often been ascribed to crystal aggregation and fixed particle growth on kidney calcifications. In this paper, the influence of hydroxyapatite (HAP) and of preformed calcium oxalate (CaOx) aggregates on CaOx crystallization was studied in freshly voided urine. Crystallization was induced by different oxalate loads and precipitates were analyzed by the spectrophotometric measurement of sedimentation time (ST), which decreases with increasing particle size. The fact that the ST of aggregates (STA) is significantly lower than the ST of other particles demonstrates that STA is a useful indicator for aggregation. At relatively low oxalate loads the addition of HAP to urine increased STA by a factor of 4.3 (P < 0.001). After a second oxalate load, STA decreased by 56% (P < 0.001), indicating secondary growth of the preexisting aggregates. HAP induced and primary CaOx aggregation occurred at low pH at which a high ionic calcium concentration (Ca2+) was measured. In urine, crystals are coated by macromolecules creating a negative surface potential with a consecutive accumulation of cations such as Ca2+. This Ca2+ accumulation could be responsible for the enhancement of aggregation by preexisting particles, which seems to be important for stone formation and which can otherwise hardly be explained in the presence of coated crystals.

Calcium↗

Nucleation and aggregation of calcium oxalate in whole urine; spectrophotometric sedimentation analysis: a new approach to study the aggregation of calcium oxalate dihydrate.

Spectrophotometric and scanning electron microscopic (SEM) studies of oxalate-induced crystallization have been performed in whole urine with and without continuous magnetic stirring and before and after millipore filtration of urine. With continuous stirring, preferential nucleation was observed and this followed second order kinetics. Important crystal aggregation only occurred after an oxalate load above 1 mmol/l and without stirring. Under these conditions and at an ionic calcium concentration of 2 mmol/l, single crystals and aggregates of calcium oxalate dihydrate and monohydrate of well defined sizes were produced. Single dehydrates, their aggregates and the other particles could be distinguished by their significantly different sedimentation rates. From sedimentation curves an aggregation ratio for calcium oxalate dihydrate (aggregated/total dihydrate particles) was extrapolated. Millipore filtration removing important urinary macromolecules increased this aggregation ratio as well as the size of the aggregates on SEM pictures.

Calcium Oxalate↗

Stone prevention: why so little progress?

Despite intensive research the knowledge of stone pathogenesis, which is the basis of every rational stone metaphylaxis, has remained rather scanty. Epidemiology shows that stone formation in most patients is only a sporadic event, probably resulting from a coincidence of different factors. The hypercalciuria, hypocitraturia, hyperuricosuria and hyperoxaluria frequently found in calcium stone formers can be influenced therapeutically and, in affluent societies, seem to be the result of protein over-consumption. These four factors favour crystallization processes in urine. However, urine is normally protected from nucleation, growth and aggregation of calcium minerals by crystallization inhibitors. In urine, crystallization of calcium oxalate can only be induced by an extreme supersaturation, a deficient inhibitor activity and promoters of crystallization. To form a stone, crystals have to be retained in the urinary collecting system. Two mechanisms of retention are discussed: large crystal aggregates trapped in collecting ducts of renal papillae, or a pre-existing calcification of the papilla (mainly calcium phosphate) that may be responsible for growth of an initially fixed particle to a concretion large enough to become symptomatic. An excessive oxalate intake combined with a low calcium consumption can produce marked hyperoxaluria. In the animal model, hyperoxaluria induces not only calcium oxalate crystallization but also papillary damage and incrustations. Hypercalciuria at a low pH favours the aggregation of calcium oxalate, and at a high pH the crystallization of calcium phosphate, a promoter of heterogeneous nucleation of calcium oxalate. All these factors and further complex phenomena mentioned in this paper have to be taken in account to perform rational stone metaphylaxis.

Calcium Oxalate↗

Measurement of metastability, growth and aggregation of calcium oxalate in native urine. A new approach for clinical and experimental stone research.

Nucleation, growth and aggregation are thought to be the most important crystallization processes in stone formation. Since crystallization properties change with urinary dilution, centrifugation and filtration, crystallization should always be studied in freshly voided and not pretreated urine. Recently we developed an automated method where calcium oxalate crystallization is induced in native urine by an exogenous oxalate load and nucleation and growth are monitored by an ion-selective calcium electrode. The method has now been supplemented with the spectrophotometric measurement of crystal aggregation. Repeated experiments in the same urine with different oxalate loads enable the determination of the critical oxalate additionable to induce crystallization (metastable limit) and the calculation of an oxalate load-independent growth rate constant. Preliminary results obtained in the native urine of healthy controls showed an extremely high limit of metastability and a complete absence of crystal aggregation. These findings may explain why, despite frequent urinary calcium oxalate supersaturation, healthy people do not form stones.

Calcium Oxalate↗

Automated and computer-controlled method for the measurement of the crystallization of calcium oxalate monohydrate in urine.

Monitoring of crystallization of calcium salts with ion-selective electrodes has turned out to be a very sensitive method. The difficulties of handling these electrodes in native whole urine and other biological fluids have been eliminated by new calcium analyzers, which clean and calibrate the electrodes after each measurement. To study crystallization kinetics, repeated calcium ion measurements have to be performed at regular intervals. For this purpose we have developed a special sampler and software. The sampler brings a thermostat-controlled crystallization chamber to the analyzer at preselected intervals. The computer directs and coordinates the sampler and the analyzer, stores the received results and prints out growth curves. Furthermore it calculates the half-time (h) and the maximum decrease of ionic calcium at infinite incubation time (delta Ca2+ infinity). Both values are shown to characterize the growth of calcium oxalate monohydrate in urine. Results are obtained within 40 min.

Calcium↗

Rapid method of measuring the inhibition of calcium-oxalate monohydrate growth in urine.

In order to have a rapid method of measuring the inhibition of calcium-oxalate monohydrate growth in freshly voided whole urine, a test system by Meyer and Smith that has originally been developed for diluted urine was modified. The crystallization processes were monitored by an ion-selective calcium electrode, which allowed determination of the half-life value of the decrease in calcium within 25 min. Even given the high inhibitory activity of whole urine, the test gave reliable results when a high seed concentration was used. Inhibition was expressed as the ratio between the half-lives of the calcium decrease obtained in the presence and in the absence of inhibitors. This approach allowed kinetic studies of individual inhibitors in model solutions. Furthermore, the measurements of inhibitors in urine could be performed before the chemical composition was determined.

Calcium Oxalate↗

The influence of hydroxyapatite and pyrophosphate on the formation product of calcium oxalate at different pHs.

The nucleating effect of hydroxyapatite (HAP) and the inhibitory effect of pyrophosphate (PPi) on calcium oxalate crystallization have been studied at different pH's in solution metastabely supersaturated with respect to calcium oxalate but saturated with respect to HAP. Crystallization was monitored by a decrease of calcium in the supernatant and formation products were calculated. At a pH above 6.0 already minimal HAP concentrations proved to be a suitable substrate for heterogeneous nucleation and growth of calcium oxalate. PPi showed a pronounced inhibitory effect on spontaneous as well as on HAP induced crystallization of calcium oxalate, this effect being highly pH dependent. HAP was found to neutralize the inhibitory effect of PPi in a molar ratio of 10:1.

Calcium Oxalate↗

Influence of calcium content in mineral water on chemistry and crystallization conditions in urine of calcium stone formers.

19 idiopathic recurrent calcium stone formers were examined on a constant diet supplemented with mineral water of high (386 mg/l) and low (10 mg/l) calcium content. The effects of calcium and oxalate loading were studied separately. Ingestion of mineral water with high calcium content lead to an increase of urinary calcium and a decrease of urinary oxalate compared to mineral water with low calcium content. On the calcium-rich mineral water, urinary saturation with Whewellite was lower and it hardly reached the critical level for calcium oxalate crystallization after oxalate loading, which was in contrast to the results on low calcium mineral water. Urinary Brushite saturation was generally low and showed no significant differences between the two mineral waters.

Adult↗

Chemical factors governing the state of saturation towards brushite and whewellite in urine of calcium stone formers.

Variations of urinary pH and concentrations of calcium, phosphate, oxalate, magnesium and citrate have been produced by 4 different diets given to 19 idiopathic calcium stone formers. The state of saturation towards whewellite and brushite was directly measured in the 76 urine samples by equilibration with the corresponding salts and was compared to chemical constituents by regression analyses. The state of saturation towards calcium oxalate monohydrate was significantly governed only by the urinary oxalate concentration, and a soluble oxalate fraction not contributing to calcium oxalate chelation was demonstrated. The state of saturation towards brushite was exclusively determined by urinary calcium and pH, the latter below 5.5 showing a high influence on brushite solubility.

Adolescent↗

Crystallization conditions in urine of patients with idiopathic recurrent calcium nephrolithiasis and with hyperparathyroidism.

The highest degree of urinary supersaturation with respect to calcium oxalate monohydrate (COM) and brushite at which secondary nucleation and growth of small amounts of COM and hydroxyapatite (HAP) are inhibited was determined by new and simple methods. There were 39 subjects who produced 24 h-urine collections (11 idiopathic stone formers (ISF), 12 patients suffering from primary hyperparathyroidism (HPT) and 16 healthy controls (HC). These subjects had a moderate calcium and low oxalate intake. The results obtained were compared with the state of urinary saturation and with urine chemistry. The measurements of crystallization conditions with respect to COM were repeated in 26 subjects (11 ISF, 5 HPT, 10 HC) after a dietary oxalate load. In 24 h-urines of HC diluted to 2.4 1/24 h the degree of supersaturation necessary to induce crystallization of COM and HAP was 2-5 times higher than the state of urinary saturation measured under the same test conditions. ISF showed a decreased pyrophosphate concentration and a decreased inhibitory activity to HAP crystallization in their 24 h-urine. The urinary inhibitory activity towards crystallization of HAP showed a positive correlation to urinary pyrophosphate concentration. In the 24 h-urine of HPT hypercalciuria and increased saturation with respect to brushite which reached values to induce HAP crystallization were found. After a dietary oxalate load urinary supersaturation with respect to COM reached values to induce COM crystallization in ISF and HPT but not in HC.

Adult↗