[A clinical approach in neuromuscular diseases in childhood]. / Neuromuskuläre Erkrankungen im Kindesalter: Klinisches Vorgehen.

The group of neuromuscular disorders includes disorders of the motor neurons in the medulla oblongata and myelon, the peripheral nerves, the neuromuscular junction, and of the muscle. Clinical manifestation varies from pre-/perinatal to adulthood. The prevalence of all neuromuscular disorders is about 1:1500. In the last years, knowledge of genetic defects in neuromuscular disorders has dramatically increased. This is due to an increase in knowledge of the underlying genetic defects. Hence the classification of the neuromuscular disorders is still changing. In clinical practice the history and the clinical examination of patients with suspected NMDs is very important in the correct selection of the necessary investigations. Many investigations are possible, but should be chosen according to the patient's symptoms. Careful interpretation of the results most often defines diagnosis. The aim of this article is to establish a work-up according to the patient's symptoms and problems in childhood.

Continuous glucose monitoring reveals associations of glucose levels with QT interval length.

BACKGROUND: QTc interval lengthening during hypoglycemia is discussed as a mechanism linked to sudden death in diabetes patients and the so-called "dead in bed syndrome." Previous research reported a high interindividual variability in the glucose-QTc association. The present study aimed at deriving parameters for direction and strength of the glucose-QTc association on the patient level using combined Holter electrocardiogram (ECG) and continuous glucose monitoring. METHODS: Twenty type 1 diabetes patients were studied: mean (SD, range) age, 43.6 (10.8, 22-65) years; gender male (n [%]), 10 (50.0%); mean (SD) hemoglobin A1C, 8.5% (1.0%); and impaired hypoglycemia awareness (n [%]), six (30.0%). Continuous interstitial glucose monitoring and Holter ECG monitoring were performed for 48 h. Hierarchical (mixed) regression modeling was used to account for the structure of the data. RESULTS: Glucose levels during nighttime were negatively associated with QTc interval length if the data structure was accounted for (b [SE] = -0.76 [0.17], P = 0.000). Exploratory regression analysis revealed hypoglycemia awareness as the only predictor of the individual strength of the glucose-QTc association, with the impaired awareness group showing less evidence for an association of low glucose with QTc lengthening. CONCLUSIONS: Mixed regression allows for deriving parameters for the glucose-QTc association on the patient level. Consistent with previous studies, we found a large interindividual variability in the glucose-QTc association. The finding on impaired hypoglycemia awareness patients has to be interpreted with caution but provides some support for the role of sympathetic activation for the QTc-glucose link.

Combination of TMS and fMRI reveals a specific pattern of reorganization in M1 in patients after complete spinal cord injury.

PURPOSE: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood. METHODS: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1. RESULTS: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area. CONCLUSIONS: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.

A syringe exchange programme in prison as prevention strategy against HIV infection and hepatitis B and C in Berlin, Germany.

In two prisons in Berlin, Germany, provision of sterile injection equipment for injecting drug users (IDUs) started in 1998. To assess the programme's impact, the frequency of injecting drug use and syringe sharing, and the incidence of HIV, HBV, and HCV infection were determined in a follow-up study. Of all IDUs (n=174), 75% continued to inject. After the project start the level of syringe sharing declined from 71% during a 4-month period of previous imprisonment to 11% during the first 4 months of follow-up, and to virtually zero thereafter. Baseline seroprevalences for HIV, HBV, and HCV were 18, 53, and 82%. HIV and HCV seroprevalence at baseline was significantly associated with drug injection in prison prior to the project start. No HIV and HBV seroconversions, but four HCV seroconversions occurred. The provision of syringes for IDUs in appropriate prison settings may contribute to a substantial reduction of syringe sharing. However, the prevention of HCV infection requires additional strategies.

Biotransformation of glucose to 5-keto-D-gluconic acid by recombinant Gluconobacter oxydans DSM 2343.

For the conversion of glucose to 5-keto-D-gluconate (5-KGA), a precursor of the industrially important L-(+)-tartaric acid, Gluconobacter strains were genetically engineered. In order to increase 5-KGA formation, a plasmid-encoded copy of the gene encoding the gluconate:NADP-5 oxidoreductase (gno) was overexpressed in G. oxydans strain DSM 2434. This enzyme is involved in the nonphosphorylative ketogenic oxidation of glucose and oxidizes gluconate to 5-KGA. As the 5-KGA reductase activity depends on the cofactor NADP+, the sthA gene (encoding Escherichia coli transhydrogenase) was cloned and overexpressed in the GNO-overproducing G. oxydans strain. Growth of the sthA-carrying strains was indistinguishable from the G. oxydans wild-type strain and therefore they were chosen for the coupled overexpression of sthA and gno. G. oxydans strain DSM 2343/pRS201-gno-sthA overproducing both enzymes showed an enhanced accumulation of 5-KGA.

Urinary iodine concentration during pregnancy in an area of unstable dietary iodine intake in Switzerland.

We prospectively investigated urinary iodine concentration (UIC) in pregnant women and in female, non-pregnant controls in the canton of Berne, Switzerland, in 1992. Mean UIC of pregnant women [205 +/- 151 microg iodine/g creatinine (microg l/g Cr); no. = 153] steadily decreased from the first (236 +/- 180 microg l/g Cr; no. = 31) to the third trimester (183 +/- 111 microg l/g Cr, p < 0.0001; no. = 66) and differed significantly from that of the control group (91 +/- 37 microg l/g Cr, p < 0.0001; no. = 119). UIC increased 2.6-fold from levels indicating mild iodine deficiency in controls to the first trimester, demonstrating that high UIC during early gestation does not necessarily reflect a sufficient iodine supply to the overall population. Pregnancy is accompanied by important alterations in the regulation of thyroid function and iodine metabolism. Increased renal iodine clearance during pregnancy may explain increased UIC during early gestation, whereas increased thyroidal iodine clearance as well as the iodine shift from the maternal circulation to the growing fetal-placental unit, which both tend to lower the circulating serum levels of inorganic iodide, probably are the causes of the continuous decrease of UIC over the course of pregnancy. Mean UIC in our control group, as well as in one parallel and several consecutive investigations in the same region in the 1990s, was found to be below the actually recommended threshold, indicating a new tendency towards mild to moderate iodine deficiency. As salt is the main source of dietary iodine in Switzerland, its iodine concentration was therefore increased nationwide in 1998 for the fourth time, following increases in 1922, 1965 and 1980.

[Laboratory diagnosis of hyperkinetic movement disorders in adulthood]. / Labordiagnestik hyperkinetischer Bewegungsstörungen des Erwachsenenalters.

Hyperkinetic movement disorders such as dystonia, chorea, ballism, myoclonus, tics, and tremor may be idiopathic or symptomatic in origin. Symptomatic movement disorders need further diagnostic testing in order to identify their etiology. In addition to clinical findings, imaging techniques, and electrophysiological testing, laboratory studies are required. Here, we review the prevalence of diseases presenting with symptomatic hyperkinetic movement disorders and discuss the diagnostic relevance of laboratory studies.

Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types.

OBJECTIVES: To evaluate the stimulation effectiveness of different magnetic stimulator devices with respect to pulse waveform and current direction in the motor cortex. METHODS: In 8 normal subjects we determined motor thresholds of transcranial magnetic stimulation in a small hand muscle. We used focal figure-of-eight coils of 3 common stimulators (Dantec Magpro, Magstim 200 and Magstim Rapid) and systematically varied current direction (postero-anterior versus antero-posterior, perpendicular to the central sulcus) as well as pulse waveform (monophasic versus biphasic). The coil position was kept constant with a stereotactic positioning device. RESULTS: Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability. By normalizing the values with respect to the square root of the energy of the capacitors in the different stimulators, we found a homogeneous pattern of threshold variations. The normalized Magstim threshold values were consistently higher than the normalized Dantec thresholds by a factor of 1.3. For both stimulator types the monophasic pulse was more effective if the current passed the motor cortex in a postero-anterior direction rather than antero-posterior. In contrast, the biphasic pulse was weaker with the first upstroke in the postero-anterior direction. We calculated mean factors for transforming the intensity values of a particular configuration into that of another configuration by normalizing the different threshold values of each individual subject to his lowest threshold value. CONCLUSIONS: Our transformation factors allow us to compare stimulation intensities from studies using different devices and pulse forms. The effectiveness of stimulation as a function of waveform and current direction follows the same pattern as in a peripheral nerve preparation (J Physiol (Lond) 513 (1998) 571).

Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans--does it have an abettor role in oxalate, and calcium oxalate crystallization?

The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known.

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors.

AIM: To examine possible relation between diabetic maculopathy and various risk factors for diabetic complications in patients with diabetes mellitus type 1 and type 2. METHODS: Cross sectional study of two cohorts of diabetic patients, comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years, mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy were assessed by fluorescence angiography and fundus photography and binocular biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted electrocardiography and by thermal and vibratory sensory examination. Patients were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200 microg/min) according to their albumin excretion rates measured in urine collected overnight. Using univariate analyses, the effects of selected patient characteristics on the presence of maculopathy were evaluated. Multiple logistic regression analyses were performed to determine independent effects of risk variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was found to be present in 28% of type 1 diabetic patients and in 38% of type 2 diabetic patients. The prevalence of maculopathy in these patients was remarkably high (42% in type 1 and 53% in type 2 diabetic patients). Patients with maculopathy had significantly impaired visual acuity. Multiple logistic correlation analysis revealed that in both types of diabetes maculopathy exhibited independent associations with duration of diabetes and with neuropathy (p <0. 01); in type 1 diabetic patients there were significant associations with age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05); in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05). CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long standing diabetes have a high risk for the development of diabetic maculopathy. Diabetic maculopathy is closely associated with diabetic nephropathy and neuropathy and with several atherosclerotic risk factors which suggests that these factors might have an important role in the pathogenesis of maculopathy. However, prospective trials are necessary to evaluate the predictive value of such factors. The findings of the present cross sectional study reinforce the arguments of previous studies by others for tight control of hypertension and hyperglycaemia.

Motor reorganization after spinal cord injury: evidence of adaptive changes in remote muscles.

Purpose: Given that SCI leads to substantial changes in biomechanical properties of the body and to widespread postlesional reorganization of the motor system as determined by functional imaging studies, we sought to identify neurophysiological correlations and time course of reorganization affecting muscles more distant to a SCI. Methods: Two arm muscles distant to a SCI (T2-L3), M.biceps brachii (BIC), M.abductor pollicis brevis (APB), were studied in 13 SCI-patients and 15 controls. Motor thresholds at rest (MT), facilitatory effects on MEP-amplitudes (FE) with voluntary activation, MEP-amplitudes with maximal stimulation (MA) and recruitment curves (RC) were measured and correlated with level, age and severity of the lesion. Follow-up studies (t2) were performed in five patients with clinical recovery. Results: Patients exhibited smaller MA from activated BIC, a tendency towards smaller FE and smaller RC-slopes at t1. With clinical recovery, activated BIC-FE, MA and RC-slopes tended to normalize. Conclusions: Our data support the hypothesis that postlesional reorganization of the motor system also involves remote muscles. Considering pattern and time course of reorganization, we speculate that they appear as sequelae of the trauma, possibly representing an adaptation of the motor system to an altered biomechanical status after SCI.

Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis.

The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted.

Acute effects of calcium sodium citrate supplementation of a test meal on mineral homeostasis, oxalate, and calcium oxalate crystallization in the urine of healthy humans--preliminary results in patients with idiopathic calcium urolithiasis.

Calcium, in the form of regular food supplementation, can improve bone metabolism, but it can also increase the risk for renal calcium stones, and may aggravate pre-existing calcium urolithiasis. To study the first of these two aspects, ten healthy volunteers were given a conventional test meal (breakfast; calcium content 28 mg) with or without two dosages of calcium (as calcium-sodium citrate, CSC 1, 680 mg; CSC 2 1,360 mg), taken after an overnight 12 h fast. To study the latter aspect, patients with idiopathic recurrent calcium urolithiasis (ICU) received a balanced test meal of fixed composition, containing 1,000 mg calcium either as CSC (Meal + CSC3; n = 6) or as calcium gluconate (Mcal; n = 8). In normals, CSC induced a dose-dependent increasing intestinal absorption of calcium, and a decrease in oxalate absorption; in serum, CSC increased calcitonin and suppressed parathyroid hormone, but left unchanged the markers of bone turnover, serum osteocalcin and bone alkaline phosphatase. In urine, CSC decreased bone resorption markers (collagen crosslinks) and phosphaturia increased citrate, created signs of metabolic alkalosis, and inhibited several parameters of CaOx crystallization. In ICU, the CSC3 load failed to promote the crystallization of CaOx and calcium phosphate. It was concluded that CSC supplementation of a meal: (1) is well tolerated by healthy subjects and ICU patients, renders calcium highly available to bone, and prevents post-prandial oxaluria from rising; and, (2) is followed by the inhibition of crystallization of renal stone forming calcium-containing substances. Long-term studies aimed at evaluating the usefulness of CSC in preserving healthy bone, and in the metaphylaxis of renal stones would appear justified.

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study.

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.

Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study.

Activation maps in the primary motor cortex (M1) were investigated in three patients with complete spinal cord injury (SCI) at level TH3, TH7 and TH9 and in one patient with an incomplete spinal cord injury at level L1 during right elbow (4 patients), right thumb (4 patients), bilateral lip (2 patients) and right foot (3 patients during imagined, 1 patient during executed) movements using functional Magnetic Resonance Imaging (fMRI). Compared to controls fMRI activation maps of patients with complete paraplegia showed a cranial displacement of the activation maxima in the contralateral primary motor cortex during elbow movement of 13.3mm, whereas the maxima of thumb and lip movements were not altered. The patient with an incomplete spinal cord injury revealed no displacement of elbow activation maxima. The reorganization is likely to occur on the cortical and not on the spinal level.

Directional tuning of single motor units.

The directional activity of whole muscles has been shown to be broadly and often multimodally tuned, raising the question of how this tuning is subserved at the level of single motor units (SMUs). Previously defined rules of SMU activation would predict that units of the same muscle (or at least of the same neuromuscular compartment) are activated homogeneously with activity peaks in the same "best" direction(s). In the present study, the best directions of SMUs in human biceps (both heads) and deltoid (anterior, medial, and posterior portions) were determined by measuring the firing rate and threshold force of units for recruitment during isometric force ramps in many different directions. For all muscles studied, neighboring motor units could have significantly different best directions, suggesting that each muscle receives multiple directional commands. Furthermore, 17% of the units sampled clearly had a second-best direction, consistent with a convergence of different directional commands onto the same motoneuron. The best directions of the units changed gradually with location in the muscle. Best directions did not cluster into separate groups, thus, not supporting the existence of clearly distinguished neuromuscular compartments. Instead, the results reveal a more gradually distributed activation of the biceps and deltoid motoneuron pools. A model is proposed in which the central control mechanism optimizes the fulfillment of the continuously changing directional force requirements of a movement by gradually recruiting and derecruiting those units ideally suited for the production of the required force vector at any given time.

Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine.

The currently preferred calcium preparations for supplementation of food vary widely with respect to calcium availability, effects on systemic mineral metabolism, acid-base status, and the calciuria-induced risk of urinary tract stone formation. In eight healthy males we studied the response to an acute load with alkali(sodium)-containing soluble calcium citrate (CSC) (molar ratio calcium/sodium/citrate approx. = 1/1/1), when taken in three different doses (10, 20, 30 mmol calcium) together with a continental breakfast. Intestinal calcium absorption, serum calcium, calcitonin, parathyroid hormone (PTH) other markers of bone metabolism, net acid excretion and calcium oxalate crystallization in urine were evaluated. CSC evoked a dose-dependent increase in calcium absorption, calcium in serum and urine, but no overt hypercalcemia, and calciuria was low relative to the excess calcium ingested; PTH fell and calcitonin rose (p < 0.05 vs. breakfast alone), but the diet-independent markers of bone resorption declined only insignificantly, while the markers of bone formation and turnover remained unchanged. There was a significant "once-daily" effect (= cumulative 24 h postload response) of CSC: a decrease in urinary cyclic AMP, phosphorus, and ammonium, and an increase in urinary bicarbonate. Soon after CSC intake, urinary calcium oxalate and hydroxyapatite supersaturation increased dose-dependently, the calcium oxalate crystal diameter was increased, but crystal aggregation time, which is crucial for stone formation, remained statistically unchanged. Thus, CSC provides calcium in a bioavailable form, creates mild systemic alkalinisation and inhibition of bone resorption, but leaves the risk of developing urinary stones unchanged. Comparative long-term studies on bone growth and the maintenance of bone health, using alkali-containing versus alkali-free calcium citrate, appear worthwhile.

Structure and function of a second gene cluster encoding the formate dehydrogenase of Wolinella succinogenes.

Wolinella succinogenes contains a single formate dehydrogenase, but two gene loci (fdhI and fdhII) code for the subunits of the enzyme. The nucleotide sequence of fdhII is almost identical with that of fdhI in the region comprising fdhEABCD. The sequences of fdhI and fdhII differ in the promotor regions upstream of fdhE. Deletion mutants lacking either fdhI or fdhII synthesize functional formate dehydrogenases, as shown by growth with formate as electron donor and either fumarate or polysulfide as acceptor substrates, and by the presence of the FdhA subunit and of enzyme activity. In the wild-type strain, the fdhI genes appear to be expressed preferentially during growth with formate and fumarate. The six-times greater amount of the enzyme present upon growth with formate and polysulfide is due to the expression of both fdhI and fdhII. The transcription start sites were located 196-bp and 129-bp upstream of the fdhE start codons of fdhI and fdhII, respectively. An apparently single transcript (5.6 kbp) was detected in polysulfide-grown W. succinogenes by Northern-blot analysis, suggesting that the five open reading frames form operons.

Simultaneous occurrence of urothelial bladder carcinoma and primary retroperitoneal leiomyosarcoma.

A case of primary carcinoma of the urinary bladder associated with a primary retroperitoneal leiomyosarcoma is presented. Due to the lack of early symptoms, diagnosis of the retroperitoneal leiomyosarcoma was late and therefore the prognosis was poor. Twelve months after diagnosis the patient died not of the bladder tumor, but of the recurrent leiomyosarcoma.

Postprandial hyperinsulinaemia, insulin resistance and inappropriately high phosphaturia are features of younger males with idiopathic calcium urolithiasis: attenuation by ascorbic acid supplementation of a test meal.

In idiopathic recurrent calcium urolithiasis (RCU) the state of insulin and carbohydrate metabolism, and relationships to minerals such as phosphate, are insufficiently understood. Therefore, in two groups of males with RCU (n = 30) and healthy controls (n = 8) the response to an oral carbohydrate- and calcium-rich test meal was studied with respect to glucose, insulin, and C-peptide in peripheral venous blood (taken before and up to 180 min post-load), and phosphate and glucose in fasting and post-load urine. In one RCU group (n = 16) the meal was supplemented with ascorbic acid (ASC; 5 mg/kg body weight). The mean age (RCU 29, RCU + ASC 30, controls 27 years) and mean body mass index [RCU 24.4, RCU + ASC 25.0, controls 24.0 kg/m2] were similar. Insulin resistance (synonymous sensitivity of peripheral organs to insulin) was calculated from insulin serum concentration, as was also integrated insulin, C-peptide, and glucose. Untreated stone patients (RCU) developed hyperinsulinaemia between 60 and 120 min post-load, increased integrated insulin, and insulin resistance (P < or = 0.05 vs controls), whereas the rise of C-peptide and glycaemia (absolute and integrated values) was only of borderline significance. Fasting phosphaturia was low in both RCU subgroups vs controls; however, phosphaturia in untreated RCU rose in response to the meal, contrasting sharply with a decrease in controls. ASC supplementation of the meal (in the RCU + ASC subgroup) normalized insulin, failed to normalize post-load phosphaturia, but reduced post-load glucosuria and urinary pH significantly (mean pH values 5.55 vs 5.93 in untreated RCU, controls 5.50). Postprandial urinary oxalate, calcium, protein, and supersaturation products were not changed. The postprandial changes in phosphaturia and insulin sensitivity were inversely correlated (n = 38, r = -0.44, P = 0.007). It was concluded that in younger RCU males: (1) postprandial hyperinsulinaemia, the failure to reduce phosphaturia and - within limits - glucosuria, appropriately, as well as poor urine acidification are important features of the metabolism; (2) these phenomena are probably caused by insulin resistance of organs, the kidney included; and (3) the addition of a supraphysiological dose of ASC to a meal, the subsequent abolition of hyperinsulinaemia, and the restoration of normal urine acidification suggest that this antioxidant is capable of counteracting some pre-existing basic abnormality of cell metabolism in RCU.