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J Dørup

Publications and source records attributed to J Dørup.

At least 19 recordsLinked to original sources

Epidemiology of juvenile chronic arthritis: risk dependent on sibship, parental income, and housing.

OBJECTIVE: We studied the socioeconomic background of children with juvenile chronic arthritis (JCA) diagnosed during the years 1988-91 in Denmark. The working hypothesis is that JCA may be triggered by one or several different infectious agents and that the amount of exposure to infectious agents in infancy and childhood affects the risk of JCA. METHODS: In this case-control study, we investigated socioeconomic variables prior to disease onset from national registers, primarily the Fertility Database of Statistics Denmark, in a national cohort of all 220 known cases of JCA fulfilling the EULAR criteria incident during the years 1988-91, identified from national and local diagnosis registers. There were 4 controls per case, matched for sex, age, and county of residence. Socioeconomic variables as risk factors were quantified by odds ratios, which are equivalent to relative risks of contracting JCA if exposed to a risk factor. RESULTS: Three socioeconomic variables were significantly and mutually independently associated with the risk of developing JCA during the following year. An only child had a risk of JCA 1.6 times that of a child with siblings. Children whose parents had a high income had a relative risk of 1.9. Children living in an urban flat had a risk 2.7 times that of children living on a farm. We found no space-time clustering of cases and no cyclical variations of incidence rates. CONCLUSION: The absence of clustering and of seasonal variation does not support a theory of triggering by infection. The hitherto unreported effects of the socioeconomic variables on the risk of JCA are of the same order of magnitude as reported for certain HLA alleles. Our findings do not lend full support to either of the 2 mechanisms, that growing up under either hygienic or unhygienic conditions increases the risk of JCA, and lack an obvious biological explanation.

Adolescent

11Beta-hydroxysteroid dehydrogenase, mineralocorticoid receptor, and thiazide-sensitive Na-Cl cotransporter expression by distal tubules.

Mineralocorticoid hormones regulate salt transport along the distal nephron by binding to intracellular receptors and activating gene transcription. Previous experiments showed that systemic aldosterone infusions stimulate thiazide-sensitive Na and Cl transport by distal convoluted tubule (DCT) cells; this effect could have been direct or secondary to systemic hormonal effects. Aldosterone target tissues express both mineralocorticoid receptors and the metabolic enzyme 11beta-hydroxysteroid dehydrogenase type 2. Mineralocorticoid receptors have been localized to the DCT in some experiments, but not in others. Expression of 11beta-hydroxysteroid dehydrogenase type 2 by DCT cells has not been investigated. The present experiments were designed to test the hypothesis that rat DCT cells are targets of aldosterone action. Patterns of mineralocorticoid receptor, 11beta-hydroxysteroid dehydrogenase, thiazide-sensitive Na-Cl cotransporter, and Na/Ca exchanger expression along the distal tubule were examined. A polyclonal antibody was generated to localize the thiazide-sensitive Na-Cl cotransporter. Thiazide-sensitive Na-Cl cotransporter and 11beta-hydroxysteroid dehydrogenase expression were examined using both in situ hybridization and immunocytochemistry; Na/Ca exchanger and mineralocorticoid receptor expression were examined by immunocytochemistry. The results indicate that 11beta-hydroxysteroid dehydrogenase is expressed by DCT cells, as well as connecting tubule cells and principal cells of the collecting duct; expression levels are low near the junction with the thick ascending limb and rise near the transition to the connecting tubule. Mineralocorticoid receptors are expressed by DCT cells, as well as along the thick ascending limb, connecting tubule, and collecting duct. The results indicate that components of the mineralocorticoid receptor system are expressed by DCT cells, suggesting that these cells are targets of aldosterone action.

11-beta-Hydroxysteroid Dehydrogenases

Quantitative morphology of the rat kidney during diabetes mellitus and insulin treatment.

A morphometric study was performed on moderately hyperglycaemic streptozotocin diabetic rats after 10 and 50 days of diabetes, and on groups of rats that, after initial hyperglycaemia for 50 days, were insulin treated for 2 h or for 5, 15 or 38 days. A group of hyperglycaemic diabetic animals were fasted for 18 h. Another group of rats had acute hyperglycaemia induced by intravenous glucose injection. After 10 and 50 days of diabetes, kidney weight was increased by 55 and 93%. Glomerular volume, tubule length, and tubular and interstitial volume increased in diabetic animals compared with controls. After 4 h insulin treatment, the kidney weight was 20% decreased; after 5 days it was 31% decreased. After 38 days the kidney weight was still 26% greater than in controls. In diabetic animals, 18 h fasting induced a 30% decrease in kidney weight. In normal animals, acute hyperglycaemia induced a 22% increase in kidney weight. Volume fractions of most kidney structures remained similar in all groups. However, the glomerular volume fraction was smaller during kidney enlargement, and the tubular volume fraction was larger after induced hyperglycaemia compared with controls. In conclusion, high blood glucose levels in diabetic and normal animals are associated with increased kidney weight. In hyperglycaemic diabetic animals, normalization of blood glucose after insulin treatment or fasting was followed by a decrease in kidney weight.

Animals

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest., 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27+/-3.4% of control levels (n=11, P<0.001) in inner medulla, and 34+/-15% of controls (n=5, P<0.05) in cortex. Urine production increased in parallel, from 11+/-1.4 to 30+/-4.4 ml/day (n=11, P<0.01). After return to a potassium-containing diet both urine output and AQP2 labels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4+/-1% of control levels in the inner medulla and 4+/-2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary,hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link.

Animals

Renal growth during pregnancy in insulin-dependent diabetic women. A prospective study of renal volume and clinical variables.

Kidney volume was measured during pregnancy in insulin-dependent diabetic women by an ultrasound technique and prognostic value of these measurements evaluated. A prospective study was performed on 87 pregnant women with insulin-dependent diabetes attending the maternity clinic of Aarhus Kommunehospital. Patients with proliferative retinopathy alone, hydronephrosis, or nephrotic syndrome were excluded. The patients were grouped according to onset and duration of diabetes and to vascular lesions; group I (n = 35, White class B+C), group II (n = 11, White class D0), group III (n = 26, White class D+), and group IV (n = 15, White class F+F/R). The patients visited the hospital every 2 weeks during pregnancy for general obstetric and glycaemic control and blood sampling. The volume of both kidneys was measured by a computerized nephrosonograph during the three terms of pregnancy, the puerperium and 4 months postpartum. The kidney volume increased significantly in all four groups from first to third trimester. In the third trimester the kidney volumes were 375 +/- 68 ml (I), 341 +/- 50 ml (II), 362 +/- 63 ml (III), and 343 +/- 54 ml (IV). The kidney volume in the third trimester was positively correlated with creatinine clearance (r = 0.33, P < 0.01) and inversely correlated with creatinine in serum (r = -0.27, P = < 0.02). Total kidney volume decrease (in percent) defined as the difference of maximal volume and value at 4 months postpartum was inversely correlated to albuminuria in the third trimester (r = -0.25, P < 0.05) and vascular lesions of the patients: (mean +/- SEM) 37 +/- 4% (I), 25 +/- 7% (II), 19 +/- 5% (III), and 11 +/- 7% (IV), P < 0.01. In the puerperium, kidney volume decreased significantly from third trimester in groups I, II, and III, whereas we observed no change in group IV. Six of 15 women in groups II and III with kidney volume < 300 ml and normoalbuminuria in the first trimester developed persistent microalbuminuria after pregnancy (P < 0.02). The renal volume in insulin-dependent diabetic women increases significantly during pregnancy and is inversely related to the vascular lesions of the patients. The decrease in renal volume after pregnancy is related to the albuminuria at the end of pregnancy. Women with longstanding diabetes, White class D (= groups II+III), and kidney volume < 300 ml in the first trimester have a high risk of developing permanent microalbuminuria after pregnancy.

Adult

Blood glucose and insulin responses to different meals in non-insulin-dependent diabetic subjects of both sexes.

The influence of sex on glucose and insulin responses in patients with non-insulin-dependent diabetes was studied in 12 men and 11 matched women. Two meals of either 100 g white bread or 60 g (raw weight) white rice were given. Blood glucose response areas to white bread (517 vs 509 mmol/L) and to rice (306 vs 353 mmol/L) over a 300-min observation period were similar in females and males, respectively. Insulin responses showed an identical pattern to that of glucose in females and males--35784 vs 28230 pmol/L after white bread and 28044 vs 19464 pmol/L min after rice (NS) over a 300-min observation period, respectively. Within the two study groups, blood glucose-response areas to white bread were significantly higher than those to rice (P less than 0.05), whereas there were no differences in insulin-response areas within or between the two groups. The glycemic index of rice for females (62 +/- 9; mean +/- SE) and males (66 +/- 5) was similar.

Blood Glucose

Day-to-day variation of blood glucose and insulin responses in NIDDM subjects after starch-rich meal.

OBJECTIVE: To study day-to-day variation of postprandial blood glucose and insulin increments in non-insulin-dependent diabetes mellitus (NIDDM) subjects and to analyze intra- and interperson variance of response. RESEARCH DESIGN AND METHODS: Ten NIDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied. The subjects ate three meals of 90 g of white bread, with 7 days between tests. RESULTS: Mean +/- SD areas under the blood glucose response curve (above basal) over a 3-h period were 557 +/- 60, 569 +/- 74, and 565 +/- 67 mM x 180 min (NS), and areas under the insulin-response curve were 3350 +/- 448, 2815 +/- 359 and 3551 +/- 679 mU/L x 180 min (NS) on each of the three occasions. The 95% confidence intervals of blood glucose and insulin areas for the test meal repeated three times were 564 +/- 120 mM x 180 min and 3240 +/- 1645 mU/L x 180 min, respectively. Intra- and interperson components of variance were 25 vs. 75% (glucose) and 78 vs. 22% (insulin) of the total variance. The intraperson components of variance included all sources of variation other than between-person variation. There was no significant correlation between blood glucose and insulin response areas. CONCLUSIONS: A valid estimate of the glycemic response in a single patient is obtained after a single meal. Because of the large between-person variation, paired data should preferably be used when comparing glycemic responses to different foods.

Blood Glucose

Tubule-tubule and tubule-arteriole contacts in rat kidney distal nephrons. A morphologic study based on computer-assisted three-dimensional reconstructions.

BACKGROUND: Functional investigations of the tubulo-glomerular feedback mechanism have indicated the existence of a contact between the distal nephron and the macula densa region. The structural justification of such a contact is investigated. EXPERIMENTAL DESIGN: Tubule-tubule and tubule-arteriole contacts were investigated in distal nephrons from normal rat kidneys. Computer-assisted three-dimensional reconstructions of distal nephrons were made from serial sections of renal cortical tissue and selected sections were examined by electron microscopy. RESULTS: In 14 of 15 reconstructed nephrons, the distal convoluted tubule or the connecting tubule approached the macula densa region. A wall-to-wall contact between two tubules corresponding to a three-dimensional distance below 28 microns between the axes of the two tubules was found in only five of the reconstructed tubules. The distal nephron contacts to afferent and efferent arterioles of the same nephron were also examined. The efferent arteriole revealed no consistent contacts but the afferent arteriole contacted the distal convoluted tubule/connecting tubules consistently in all 10 of the superficial nephrons and in 3 of 5 midcortical nephrons. Electron microscopy confirmed a close contact between the distal tubule and the afferent arteriole in superficial nephrons and small nerves were often found at or near the site of contact, but the morphology at the site of contact was not unique. The arteriole contacts were made with late distal convoluted tubules, connecting tubules, or cortical collecting ducts. CONCLUSIONS: In conclusion, the present study shows that tubule-tubule contacts are inconsistent between the macula densa region and the distal nephron but that the tubule-afferent arteriole contact is consistent and close in superficial nephrons. This morphology is compatible with the existence of a feedback mechanism between the superficial distal nephron and the afferent arteriole, apart from the one located at the juxtaglomerular apparatus.

Animals

Spinal analgesia with plain 0.5% bupivacaine administered at spinal interspace L2-3 or L4-5.

Forty patients (age range 60-79 yr) undergoing transurethral surgery were allocated randomly to receive 0.5% plain bupivacaine 4 ml at the L2-3 (n = 20) or L4-5 (n = 20) space. The solution was injected over 30 s with the patient in the sitting position. The patient was kept sitting for 2 min, then placed supine and, 5 min later, placed in the lithotomy position. No significant differences were found in onset time, extent and duration of analgesia or duration of motor block.

Aged

[Clinical aspects of spinal anesthesia administered using 0.5% isobar bupivacaine (Maracine) at the L2/L3 or L4/L5 level].

The effect of employing different interspaces for lumbar puncture during spinal anaesthesia was evaluated in 40 patients receiving 4 ml of 0.5% plain bupivacaine at level L2/L3 or L4/L5. No differences were observed in onset, spread or duration of analgesia. Furthermore, we found that only 80% of the patients, independently of the interspace used, had a cephalad spread to T8 and conclude that spinal anaesthesia using plain bupivacaine is not ideal for supraumbilical surgery.

Aged

Lithium-induced structural changes in the cortical distal nephron localized by computer-assisted three-dimensional reconstruction.

Lithium treatment is known to cause tubule dilation in distal nephron segments both in rat and in man. However, due to the heterogeneous cell composition of the distal nephron and the cellular changes following lithium treatment, it has been difficult to identify the structurally changed segments. In this study we have therefore applied computer-assisted reconstruction of cortical distal nephron segments. Tubule dilation was demonstrated in connecting and initial collecting tubules and in the first part of cortical collecting ducts (CCD) whereas it was absent from distal straight and distal convoluted tubules. Principal cells (P cells) in the CCD showed swelling of the cytoplasm, accumulation of actin-like microfilaments, and abnormal arrangements of basolateral membranes. Connecting tubule cells (CNT cells) showed similar but less pronounced changes. Intercalated cells (I cells) showed an accumulation of vesicles in the apical cytoplasm and a reduced luminal surface area. Lesions in P and CNT cells may, at least in part, explain the diabetes insipidus and sodium loss found during lithium treatment. Proton secretion in I cells is probably mediated by an ATPase present in the luminal membrane. The reduction in area of this membrane may explain why lithium-treated animals have a lowered ability to excrete an acid load.

Animals

Ultrastructure of three-dimensionally localized distal nephron segments in superficial cortex of the rat kidney.

The ultrastructure of superficial distal nephron segments was analyzed after precise localization of tubule cross sections using computer-assisted three-dimensional reconstructions. Five systems of tubules, each with three interconnected distal tubules, were reconstructed and the lengths of the post macula densa segment of the distal straight tubule (DST), the distal convoluted tubule (DCT), the connecting tubule (CNT), and the initial collecting tubule (ICT) were determined. Each cortical collecting duct (CCD) was in continuity with only one tubule in contact with the renal capsule. In three of the five reconstructions, the two nonsubcapsular tubules fused and had a common connection to the subcapsular tubule. The length, between the macula densa (MD) and the confluence, of subcapsular tubules (2.68 +/- 0.15 mm) significantly exceeded the length of tubules not in contact with the renal capsule (2.05 +/- 0.10 mm). This difference was mainly due to a longer ICT in subcapsular tubules. Subcapsular tubules always contacted the renal capsule in the early DCT and often again in the ICT. Cells in the early DCT showed more microvilli on the luminal surface and more infoldings of basolateral membranes than cells in the late DCT. The ultrastructure of intercalated cells (I cells) varied within a range of different manifestations and the ultrastructural variation of I cells was similar in all the analyzed tubule segments. Connecting tubule cells and principal cells were similar in ultrastructure in all tubule segments and cortical levels analyzed.

Animals

Erectile dysfunction in multiple sclerosis.

In a sample of 29 impotent men with multiple sclerosis and erectile problems, penile arterial inflow and venous outflow were within normal limits. In 26 patients, the pudendal evoked potential (PEP) was abnormal, and eight of these also had abnormal bulbocavernous reflex (BCR). Three patients had abnormal PEP and normal BCR, and of these, two had normal and one had abnormal nocturnal erectile activity. The validity of PEP/BCR testing was supported by normal findings in six patients with MS and without erectile problems. Nocturnal erectile activity was normal in 11 patients, of whom nine had abnormal PEP and/or BCR. A high disability score corresponded poorly with both reduced sexual function, insufficient nocturnal erectile activity, and abnormal PEP and/or BCR. Intracavernous injection of papaverine gave erection in 27 patients, the dose needed to create an erection being inversely related to the level of disablement. PEP and BCR testing may be more sensitive in defining neurogenic erectile dysfunction (ED) than nocturnal erectile activity. We considered 26 of the cases to have a neurogenic cause of ED and three to have mainly a psychogenic cause.

Adult

Electron microscope analysis of tissue components identified and located by computer-assisted 3-D reconstructions: ultrastructural segmentation of the developing human proximal tubule.

A method is described for ultrastructural analysis of renal tubules after precise identification of tubule segments by computerized 3-D reconstruction at the light microscope level. Semithin serial sections were cut of entire nephrons and 3-D coordinate information was obtained by digitization of tubule cross sections in the semithin sections. With the aid of the computer the tubule axis was traced from one section to the other. Precise lengths and positions of the tubules in three dimensions were calculated and stereoscopic images generated. The method was used to analyze the 3-D structure of developing human nephrons, and the ultrastructural development of the proximal tubule. Ultrastructural segmentation of the proximal tubule was demonstrated in the human fetal nephron in developmental stage IV.

Computers

Ultrastructure of distal nephron cells in rat renal cortex.

Distal nephron segments in the rat renal cortex contain distal convoluted tubule cells (DCT cells), connecting tubule cells (CNT cells), intercalated cells (I cells), and principal cells (P cells). The present study was carried out to expand present knowledge on the ultrastructure of these cells. The cells were sampled from superficial cortex and analyzed by electron microscopy. Several morphometric parameters were determined and statistical comparison between cell types was performed. Significant structural differences between the cell types were demonstrated. DCT cells showed the highest volume density of mitochondria whereas the amplification of basolateral membranes was higher in CNT cells than in I and P cells. The surface density of the membrane that bounds intermediate vesicles in the apical cytoplasm was twofold higher in I cells than in the other cell types. The morphological differentiation found in the present study adds to available evidence indicating a functional differentiation between the cell types and provides a reference for structure-function correlations in these cells.

Animals