Biomedical subjects

B Wikström

Publications and source records attributed to B Wikström.

At least 109 records · Page 6Linked to original sources

PubMed1985

Allopurinol treatment of renal calcium stone disease.

Thirty-one calcium stone patients were treated with 300 mg allopurinol daily during a mean follow-up period of 2 years. They were also given advice on diet and fluid intake. The effects on the recurrence rate of stones were compared with the effects on the recurrence rate in 43 calcium stone patients who were given similar advice on diet and fluid intake but were not treated with allopurinol. In both groups there was a reduction in the recurrence rate but no difference between patients treated with allopurinol and the control group. Some patients with only hyperuricosuria prior to treatment seemed to benefit from allopurinol treatment, whereas those with hypercalciuria continued to form stones with the same frequency. Allopurinol treatment in calcium stone disease appears less effective than treatment with thiazides, magnesium hydroxide or orthophosphate.

Adolescent↗

PubMed1985

The effect of strontium and manganese on freshly isolated chondrocytes.

The effect of Strontium (Sr) and Manganese (Mn) was studied on freshly isolated chondrocytes obtained from costal cartilage of young male rats. Cells isolated from rats rendered rachitic by oral exposure to Sr or Mn exhibited a decreased synthesis of glycosaminoglycans and collagen as judged by incorporation of 35SO4 and 3H proline. In vitro exposure of chondrocytes from untreated (control) animals to Sr or Mn at concentrations comparable to those found in cartilage from Sr and Mn rachitic rats, lowered the O2 consumption in both groups, but only Sr had any influence on the other parameters studied.

Animals↗

PubMed1985

Tubular proteinuria in renal calcium stone formers.

The incidence of tubular proteinuria measured as urinary excretion of beta 2-microglobulin was evaluated in 68 consecutive renal calcium stone formers, 14 of whom had impaired urinary acidification capacity. During normal conditions 13% of these stone formers had tubular proteinuria. There was no statistical difference in the incidence of tubular proteinuria between subgroups with proximal or distal acidification defects. During transient metabolic acidosis induced by an ammonium chloride load a pronounced increase in beta 2-microglobulin excretion was noticed in all patient groups but especially in those with urinary acidification defects. In stone formers with normal acidification capacity the degree of acidosis-induced beta 2-microglobulinuria was moderate but a small group of patients exhibited a large urine excretion of beta 2-microglobulin. This finding may reflect a latent tubular defect of importance for stone genesis.

Acidosis↗

PubMed1984

Congenital spondyloepiphyseal dysplasia. Morphological and biochemical examination of skeletal tissue in an unusual case of this disorder.

This report deals with an unusual case of spondyloepiphyseal dysplasia, where the diagnosis was suspected clinically and radiologically and where cartilage and osseocartilaginous specimens were taken for ultrastructural and biochemical analyses. Unlike cases described previously the electron microscopic studies of chondrocytes showed dilatation of the rough endoplasmic reticulum cisternae. The dilated cisternae contained an amorphous substance, and the picture is suggestive of a metabolic disturbance. The results of the biochemical analyses were within the normal range and did not indicate storage of glycosaminoglycans.

Bone and Bones↗

PubMed1984

Morphological studies of the epiphyseal growth zone in the brachymorphic (bm/bm) mouse.

Light microscopy, including immunohistochemical techniques, and electron microscopy were performed on epiphyseal growth cartilage from brachymorphic (bm/bm) mice and age-matched phenotypically normal siblings aged 5, 16 and 25 days. In the bm/bm mice light microscopy showed a disturbed columnar arrangement and numerous chondrocytes with pronounced regressive changes. The normal development of proliferative cells into hypertrophic cells was halted and thus only a rather small and ill-defined hypertrophic zone was seen. The calcifying zone was irregular and the normal lacunae were replaced by a densely staining matrix. Using immunofluorescence techniques, the presence of considerable amounts of both type II and type V collagen was demonstrated in the bm/bm mice, while the cartilage from controls contained only type II. Ultrastructurally the lacunar matrix contained bundles of fine fibrils without the typical collagen periodicity which might indicate synthesis of a defective procollagen. Our observations together with the previously demonstrated deficiency of 3'-phosphoadenosine 5'-phosphosulphate, illustrate the complexity of the growth cartilage disturbance in the bm/bm mouse. Most of our findings are at variance with those described in the literature and possible pathogenetic mechanisms for the observed alterations in the growth cartilage are discussed.

Animals↗

PubMed1984

Stereological analysis of the epiphyseal growth cartilage in the brachymorphic (bm/bm) mouse, with special reference to the distribution of matrix vesicles.

The brachymorphic (bm/bm) mutation in the mouse leads to disproportional dwarfism due to a disturbance of endochondral bone formation. The morphological characteristics of bm/bm epiphyseal growth cartilage are signs of cellular degeneration and disintegration and alteration of the composition of the extracellular matrix, with an abnormal mineralization pattern. The present stereological study of the bm/bm growth plate revealed a clearly altered distribution of matrix vesicles as compared with the controls. It was also demonstrated that the bm/bm matrix vesicles have an abnormal size distribution, with an increased mean caliper diameter. The biological significance of these findings is discussed in relation to the different hypotheses on the origin of matrix vesicles and their possible role in the mineralization process. The results support the opinion that extracellular matrix vesicles, at least partly, constitute cellular debris.

Animals↗

PubMed1984

Enalapril treatment in a patient with impaired renal function and intolerance to captopril.

In a 36-year-old woman with malignant hypertension and moderate renal insufficiency from nephrosclerosis normotension was not achieved by the combination of a beta-blocker, a vasodilator, and a loop-diuretic. The angiotensin-converting enzyme (ACE) inhibitor captopril was then added to the therapy. The blood pressure control was good. However, due to adverse reactions, captopril had to be withdrawn. Later on, the patient was successfully treated with enalapril, another ACE inhibitor, without the relapse of any adverse reactions.

Adult↗

PubMed1984

Structural and functional integrity of chondrocytes immediately following isolation.

Chondrocytes were isolated from costal cartilage in young rats after digestion with collagenase and hyaluronidase. The immediate survival of the cells was investigated with the use of different criteria for viability, namely structural integrity and metabolic activity. Structural integrity was studied by transmission and scanning electron microscopy, trypan blue exclusion and NADH oxidation. Metabolic activity was measured both as O2 consumption and as proline and sulphate incorporation, as indicators of collagen and proteoglycan synthesis. The cellular content of glutathione was also measured. The chondrocytes isolated were found to be structurally intact and metabolically active. Early after isolation the chondrocytes varied considerably in size similarly to the native tissue. A selective loss of the larger sized cells was observed during further incubation for 24 h.

Animals↗

PubMed1983

Ambulatory diagnostic evaluation of 389 recurrent renal stone formers. A proposal for clinical classification and investigation.

389 consecutive renal stone formers (275 males, 114 females) were investigated in an out-patient stone clinic. Renal tubular acidosis (RTA) was found in 83 patients (22%). Proximal RTA was twice as common as the distal tubular type. The acidification defects were exclusively of the incomplete form with normal basal blood acidbase status. Main diagnoses besides RTA were primary hyperparathyroidism (3.5%), medullary sponge kidney (3.5%), infection induced stones (3%), urate stones (2%), intestinal disorder (1.5%) and cystinuria (0.5%). The metabolic evaluation was mainly based on 24 h urine sampling on a free diet. In 248 patients (64%) no distinct abnormality was considered to be primarily responsible for stone formation. Clinical and biochemical analysis of these so-called idiopathic stone formers disclosed a male preponderance (80%) and, compared to a non-stone-forming control group, a higher urinary calcium excretion, yet with a considerable overlap between the two groups. Hyperuricosuria and hyperoxaluria were rare findings. The conclusion of the study is given as a proposal for clinical classification and ambulatory investigation of renal stone formers.

Adolescent↗

PubMed1983

Analysis of dentine glycosaminoglycans using high-performance liquid chromatography.

Puppy dentine was prepared using ultracentrifugation of tooth powder in organic density gradients. The glycosaminoglycans of the obtained tissue fraction were prepared after papain digestion and beta-elimination, using preparative chromatography on DEAE-cellulose and CPC-cellulose. These polysaccharide fractions were analyzed using highly sensitive HPLC procedures. One such HPLC procedure allowed hyaluronic acid to be determined in less than microgram amounts. The glycosaminoglycans thus prepared consisted only of chondroitin-4-sulfate, chondroitin-6-sulfate, and small amounts of highly hybridized dermatan sulfate, while the experiments failed to demonstrate even trace amounts of keratan sulfate, hyaluronic acid or heparan sulfate.

Animals↗

PubMed1983

Uricemia and urinary acidification in renal calcium stone disease.

Serum urate concentrations were determined in 487 consecutive patients with stone disease and in 89 controls. Male controls had higher concentrations than female controls but men and women with stones had lower concentrations than controls. Renal acidification defects, incomplete and complete forms, were found in 25 per cent of the patients with stones, with the highest frequency in patients with hyperuricemia. Patients with proximal renal acidification defects had a higher serum urate concentration than patients with normal acidification of the urine. The urinary excretion of urate was higher in hyperuricemic than in normouricemic patients but lower in patients with hyperuricemia and renal acidification defects than in those with hyperuricemia and normal acidification of the urine. This finding indicates that underexcretion rather than overproduction contributes to the higher serum urate concentration in patients with renal acidification defects. Stone patients with high serum urate levels, especially in combination with renal acidification defects, had more severe stone disease and underwent more operations than other patients with stones. Thus, hyperuricemia does not appear to be a common feature in patients with calcium stone disease, although it is associated with formation of large stones for unknown reasons.

Adult↗

PubMed1983

Dyggve-Melchior-Clausen dysplasia. Morphological and biochemical findings in cartilage growth zones.

The results of light and electron microscopic examination and of biochemical proteoglycan studies of costochondral and iliac crest biopsies from a recently diagnosed case of Dyggve-Melchior-Clausen dysplasia are reported. At light microscopy of resting cartilage large lacunae containing clusters of five or more chondrocytes were seen in some areas. In the hyaline cartilage there were scattered fibrous foci but no mineralized areas. Electron microscopy revealed chondrocytes containing widened cisternae of rough endoplasmic reticulum and vesicles coated with a smooth single-layered membrane. The content of the cisternae and of the vesicles was amorphous. Throughout the cartilage a considerable proportion of the chondrocytes displayed more or less pronounced necrobiotic changes. The biochemical analysis showed an increased amount of glucosaminoglycans in the cartilage and indicated that the ability of proteoglycan monomers to reaggregate to hyaluronic acid chains was decreased. Our findings support the suggestion that Dyggve-Melchior-Clausen dysplasia is due to a disturbance in proteoglycan metabolism.

Cartilage↗

PubMed1982

Urinary excretion of urate in renal calcium stone disease and in renal tubular acidification disturbances.

The 24-hour urinary excretion of urate was investigated in 467 consecutive stone formers - 350 males and 117 females - and 89 apparently healthy controls with no history of stone disease. Males had a higher urinary excretion of urate than females but there was no difference between stone formers and controls. Urinary urate decreased with advancing age. Patients with a proximal tubular acidification defect had a lower urate clearance than patients with a normal acidification of the urine. Patients with hyperuricosuria presented a higher frequency of stone operations but a lower stone episode rate than matched normouricosuric stone formers. Hyperuricosuria in combination with renal acidification defects was associated with the highest frequency of stone operations. Hyperuricosuric patients also had a higher excretion of calcium than normouricosuric patients. Hyperuricosuria is not a common feature of calcium stone disease but when present is associated with a more severe stone disease in terms of stone operations.

Acidosis, Renal Tubular↗

PubMed1982

Effects of bendroflumethiazide on urate metabolism during treatment of patients with renal stones.

Treatment with bendroflumethiazide (2.5 mg, twice daily with potassium supplements) in 63 patients with calcium-containing renal stones for a minimum period of 1 year (average duration of treatment 2.6 years) increased the serum urate values in all patients with an average of 90 mumol./l. (conversion factor: 1 mmol. urate = 183 mg.). Despite this the mean urinary urate excretion was unchanged. In the individual patient a systematic effect of therapy was evident since in patients with low pretreatment values the thiazide increased the urate output while in those with the highest levels before therapy it caused a reduction. In most patients there was a reduction of the urate clearance during therapy, which was most evident in those with the highest pretreatment clearance values. In patients with incomplete types of renal acidification defects the same effects were seen on urate metabolism during thiazide treatment as in the other, idiopathic, stone formers. Although the possible role of urate in calcium stone formation has not been definitely settled this study shows that thiazides do not cause hyperuricosuria and hence their beneficial effects on calcium excretion are not counteracted.

Adult↗

PubMed1982

Inhibitory activity of human urine on calcium oxalate crystal growth: effects of sodium urate and uric acid.

1. Freshly voided urine from healthy subjects was pooled and ultrafiltered (10,000 daltons). The ultrafiltrable and the macromolecular portions were preincubated with calcium oxalate, uric acid and sodium urate crystals and the effects on the inhibitory activity of calcium oxalate crystal growth assessed by monitoring the disappearance of [14C]oxalate from the solution. 2. The inhibitory activity of the ultrafiltrate was higher than that of the urinary macromolecular fraction. Both uninhibited and inhibited crystal growth processes followed second-order kinetics. 3. Calcium oxalate crystals adsorbed almost all the urinary macromolecular inhibitors whereas sodium urate or uric acid crystals adsorbed only 10-20%. 4. In the presence of a metastable solution of calcium oxalate, the incubation of the urinary macromolecular fraction with sodium urate crystals caused a pronounced reduction in the inhibitory activity. A similar effect was seen with uric acid crystals, but to a lesser degree. 5. We conclude that the effect of sodium urate or uric acid crystals alone on naturally occurring urinary macromolecular inhibitors of calcium oxalate crystal growth is weak, but that in the presence of metastable calcium oxalate this is greatly enhanced. A substantial adsorption of the inhibitors on to the crystals is suggested, possibly secondary to epitaxial growth of calcium oxalate on the surface of the urate crystals.

Calcium Oxalate↗

PubMed1982

Effects of magnesium hydroxide in renal stone disease.

Magnesium is a known inhibitor of the formation of calcium oxalate crystals in the urine and was proposed for prophylactic treatment in renal stone disease as early as the 17th and 18th centuries. We have treated 55 patients with recurrent renal calcium stone disease without signs of magnesium deficiency (normal serum magnesium, urinary magnesium, intracellular magnesium in muscle biopsies, gastrointestinal absorption of 28Mg, and magnesium loading test) from our outpatient stone clinic for up to four years with 500 mg Mg2+, in the form of Mg(OH)2, daily. The mean stone episode rate before therapy was 0.8 stones/year/patient. Forty-three recurrent renal calcium stone-formers without medical therapy served as controls. Serum magnesium increased initially but after one year returned to the pretreatment level. Urinary magnesium excretion increased promptly and remained elevated during the follow-up period. The urinary calcium excretion remained unchanged. The magnesium/calcium ratio in the urine increased and approached a value earlier found in healthy subjects without stone disease. Urinary citrate increased on therapy when analysed after three years of treatment. The mean stone episode rate decreased from 0.8 to 0.08 stones/year on treatment and 85% of the patients remained free of recurrence during follow-up, whereas 59% of the patients in the control group continued their stone formation. Side effects were few. Magnesium treatment in renal calcium stone disease is effective with few side effects. No clinical signs of magnesium excess were observed.

Adult↗

PubMed1982

Clinical studies on phosphate handling in hypercalcaemia.

Phosphate indices (serum phosphate, tubular reabsorption of phosphate, renal threshold phosphate concentration (TmP/GFR) and index of phosphate excretion) were studied in 88 hypercalcaemic subjects: 64 with primary hyperparathyroidism (HPT) and 24 with hypercalcaemia from other causes, predominantly malignant disease. HPT patients as a group could easily be separated from normal subjects (n = 16) and patients with functional hypoparathyroidism (n = 7) by use of the phosphate variables but these indices were of little discriminating value for the differential diagnosis between HPT and hypercalcaemia from other causes. There was no difference in the urinary cyclic adenosine monophosphate (cAMP) excretion between the two hypercalcaemic patient groups, but HPT patients had clearly elevated serum parathyroid hormone (PTH) levels compared with normal PTH concentrations in patients with other causes of hypercalcaemia. A positive correlation between cAMP and serum calcium and an inverse relationship between cAMP and TmP/GFR were found in patients with hypercalcaemic malignant disease. These findings suggest the existence of a humoral factor with PTH-like effects in malignant disease. Since PTH levels were low, the physiological actions were apparently not mediated by circulating PTH. No difference in the values for phosphate variables, PTH, cAMP or serum calcium was found between renal stone-forming and stone-free patients with HPT.

Adolescent↗

PubMed1982

Morphological and biochemical analysis of biopsy specimens in disorders of skeletal development.

A programme for combined morphological and biochemical analysis of cartilage-bone biopsy material is described. The structural analysis includes light and electron microscopy, and the biochemistry is focused on polysaccharides. A procedure for isolation and characterization of proteoglycans and glycosaminoglycans from dry cartilage in amounts down to 1 mg is described. The procedure is exemplified by analyses of material from patients with osteogenesis imperfecta, mucopolysaccharidosis IV-Morquio and metaphyseal chondrodysplasia type McKusick. In osteogenesis imperfecta characteristic morphological alterations were demonstrated. Apart from increased chondroitin sulphate molecular weights, the biochemical analyses showed values within the assumed normal range. In Morquio's disease extensive intracellular deposits in single membrane vacuoles were observed in both chondrocytes and osteocytes. There were indications that these deposits contained keratan sulphate, which also occurred in increased amounts in the total tissue preparation. Furthermore, the tendency to formation of proteoglycan aggregates was decreased. In the tissue from the patients with the McKusick syndrome insignificant ultrastructural changes, mainly affecting the mitochondria, were found. The biochemical results were within the assumed normal range. The significance of these findings and the possibilities of further methodological development are discussed.

Bone and Bones↗