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S Nielsen

Publications and source records attributed to S Nielsen.

At least 217 records · Page 12Linked to original sources
PubMed1996

Using a logistic model to identify women with first-trimester spontaneous abortion suitable for expectant management.

OBJECTIVE: To design a method to identify women with first trimester spontaneous abortion suitable for expectant management. DESIGN: A stepwise logistic regression analysis based on retrospective analysis of clinical and biochemical variables. SETTING: Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Gothenburg, Sweden. PARTICIPANTS: One hundred and three women with inevitable or incomplete spontaneous abortion at < 13 weeks of gestation were chosen for expectant management. Eighty-one women with complete spontaneous abortion (i.e. complete expulsion and/or resolution of pregnancy products within three days of expectant management) were compared with those (n = 22) who underwent surgical evacuation of the uterus, most commonly owing to retained products of conception after three days. RESULTS: Employing a stepwise logistic regression procedure, five diagnostic variables possessing prognostic power were identified: serum progesterone, daily serum hCG change, serum CA125, serum alpha fetoprotein and intrauterine diameter. The logistic regression analysis was also applied to three diagnostic variables chosen for routine clinical use: serum progesterone, serum hCG and intrauterine diameter. The probability of complete spontaneous abortion within three days of expectant management in each woman could be calculated. CONCLUSION: We have used a logistic model to calculate the probability of complete spontaneous abortion within three days in women with first trimester miscarriages. Such information may be of clinical use in caring for women, as well as for development of management guidelines for those with miscarriages.

Abortion, Spontaneous↗
PubMed1996

Mortality in anorexia nervosa in Denmark during the period 1970-1987.

In this nation-wide register linkage study of the mortality among psychiatric in-patients with anorexia nervosa who were admitted between 1970 and 1986 (n = 853), 50 deaths were recorded during a mean follow-up period of 7.8 years (6680 person-years of observation). Among male subjects, five of 63 probands died, and the mean age at death was 24.5 years (range 14.2-48.1 years). Among female subjects, 45 of 790 probands died, and the mean age at death was 36 years (range 18.1-64.7 years). The standardized mortality ratio (SMR) was 9.1 in both sexes. A significantly increased SMR was demonstrated in males up to 5 years after index admission, and for females up to 15 years. There was no mortality among childhood-onset female subjects, but among males one death was recorded in this age group. In male subjects the highest SMR was found among those with index admission in the second decade of life, and in females among those with index admission in the third decade of life. The SMR was maximal during the first year after index admission. Suicide was the dominant cause of death among subjects who died from unnatural causes (18 of 22 cases). Among those who died from natural causes (24 subjects), 13 individuals died from anorexia nervosa and 11 individuals died from other illnesses.

Adolescent↗
PubMed1996

Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study Group.

Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001) and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 x 10(9)l-1 had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP.

Adolescent↗
PubMed1996

In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats.

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.

Animals↗
PubMed1996

Bilateral ureteral obstruction downregulates expression of vasopressin-sensitive AQP-2 water channel in rat kidney.

Polyuria after release of bilateral ureteral obstruction (BUO) is frequently seen in patients with urological disorders. In this study, we examined the effect of BUO and release of BUO on the expression of the vasopressin-regulated water channel aquaporin-2 (AQP-2) in rat kidney. Ureters were obstructed for 24 h in all experiments, and BUO was either not released or released for 24 or 48 h or 7 days. Each group of experimental rats were matched with sham-operated controls. One kidney was used for membrane fractionation and immunoblotting, whereas the contralateral was fixed for immunocytochemistry. Immunoblotting demonstrated a significant reduction in AQP-2 expression in inner medullar during 24 h of BUO to 26 +/- 8% (P < 0.001). Release of BUO was associated with immediate onset of a predominant osmotic-dependent polyuria. Forty-eight hours after release of BUO, the reduction in AQP-2 expression persisted (19 +/- 8%, P < 0.001), concurrent with a marked nonosmotic postobstructive polyuria, as determined by a significant reduction in free-water clearance (-50 +/- 7 vs. -85 +/- 10 microliters.min-1.kg-1, P < 0.05). Immunofluorescence and immunoelectron microscopy confirmed the reduced levels of AQP-2 in collecting duct principal cells. Seven days after release, the renal excretion of water and electrolytes had almost normalized. However, the downregulation of AQP-2 was not partly reversed (49 +/- 14%, P < 0.001), and, consistent with this, the urinary concentrating capacity was significantly reduced 7 days after release to a 18-h period of thirst. This strongly suggests that the persistent downregulation of AQP-2 is the cause of the slow recovery in concentration capacity. In conclusion, BUO and release of BUO were associated with a marked reduction in expression of AQP-2, coincident with the development and maintenance of postobstructive polyuria. Thus reduced AQP-2 levels may represent an important factor in the slow recovery from postobstructive diuresis.

Animals↗
PubMed1996

Long-term regulation of four renal aquaporins in rats.

The aquaporins are molecular water channels expressed in the kidney and other organs. To investigate long-term regulation of renal expression of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AVP) infusion in Brattleboro rats caused significant increases in the expression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increases in aquaporin-2 and aquaporin-3 expression were seen in inner and outer medulla as well as cortex. Ablation of the corticomedullary interstitial osmotic gradient with an infusion of furosemide did not eliminate the upregulatory response to AVP infusion in Brattleboro rats. Furthermore, 5-day furosemide infusion to Sprague-Dawley rats did not decrease expression levels of the collecting duct aquaporins, but rather increased them. We conclude that the expression of aquaporin-2 and aquaporin-3, but not aquaporin-1 or aquaporin-4, is increased in response to elevated circulating AVP. Because regulation of aquaporin-2 and aquaporin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporin-3 expression.

Animals↗
PubMed1996

Development of urinary concentrating capacity: role of aquaporin-2.

The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP)-activated water channel aquaporin-2 (AQP-2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24-h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e., days 15-20. A similar developmental pattern was observed for AQP-2 mRNA levels in the renal medulla. AQP-2 protein levels also increased markedly from day 10 to 40. Immunohistochemistry revealed that AQP-2 was exclusively located in collecting duct principal cells both in infant and adult rats but that the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP-2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs. Twenty-four hours after treatment, there was an increase in urine osmolality, renal medullary AQP-2 mRNA, and AQP-2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 h significant increase of AQP-2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na(+)-K(+)-ATPase alpha-subunit, Na-K-2Cl cotransporter, and epithelial chloride channel also increased during the weaning period and were upregulated by glucocorticoids. We conclude that there is a well-synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP-2 is one of the limiting factors for low concentrating capacity in infants.

Aging↗
PubMed1996

Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1.

To investigate the role of the thick ascending limb (TAL) Na(+)-K(+)-2Cl- cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed "NKCC-2"). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na(+)-K(+)-2Cl- cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na(+)-K(+)-2Cl- transporter and demonstrate that the expression of this transporter is regulated.

Animals↗
PubMed1996

Autoantibodies to IL-1 alpha in sera from umbilical cords, children, and adults, and from patients with juvenile chronic arthritis.

Antibodies against interleukin-1 alpha (aAb-IL-1 alpha) have previously been demonstrated in sera of healthy adults and in patients with inflammatory diseases. In the present investigation the occurrence of aAb-IL-1 alpha was examined by second antibody precipitation technique in sera from umbilical cords (n = 11), children (n = 45), and adults (n = 20), as well as in 51 patients with juvenile chronic arthritis (JCA) of pauciarticular (n = 34), polyarticular (n = 8), or systemic onset type (n = 9). RESULTS. The frequency of positive sera was significantly lower in children than in cord blood and adults as were the levels of aAb-IL-1 alpha (p < 0.0001). In the non-neonatal group of individuals the levels of aAb-IL-1 alpha correlated positively with age (r = 0.394, p = 0.0015). The frequency of sera positive for aAb-IL-1 alpha was higher in the JCA patients, as were the levels (p < 0.005), and correlated positively with disease activity as evaluated by joint score and visual analogue score.

Adult↗
PubMed1996

The aquaporin family of water channels in kidney.

The longstanding puzzle of membrane water-permeability was advanced by discovery of a new class of proteins known as the "aquaporins" (AQPs). First identified in red blood cells, AQP1 was shown to function as a water channel when expressed in Xenopus oocytes or when pure AQP1 protein was reconstituted into synthetic membranes. Analysis of the primary sequence revealed that the two halves of the AQP1 polypeptide are tandem repeats; site directed mutagenesis studies indicate that the repeats may fold into an obversely symmetric structure which resembles an hourglass. Electron crystallography elucidated the tetrameric organization of AQP1, and functional studies suggest that each tetramer contains multiple functionally independent aqueous pores. AQP1 is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in multiple extra renal tissues. AQP2 is expressed only in the principal cells of renal collecting duct where it is the predominant vasopressin (ADH, antidiuretic hormone) regulated water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by ADH. Humans with mutations in genes encoding AQP1 and AQP2 exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of renal collecting duct principal cells providing an exit pathway for water; AQP4 is abundant in brain where it may function as the hypothalamic osmoreceptor responsible for secretion of ADH. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and disorders of water balance.

Animals↗
PubMed1996

Partitioning and purification of monoclonal antibodies in aqueous two-phase systems.

The partition behaviour of pure IgG in aqueous two-phase systems was examined in order to investigate the effects of changes in phase properties on the partition coefficient, K. Factors such as molecular weight (M.W.) of PEG, pH, and concentration of NaCl and other salts were all found to influence K. Due to the high level of interaction between the phase components, optimal conditions were found using a factorial design. Using this methodology it was possible to find conditions which gave extremely high values of K for the IgGs (> 100). Partition behaviour of some potential contaminants, BSA and transferrin, were also studied. All the components were characterized for hydrophobicity, pI and M.W. Conditions were chosen under which the partition coefficients of the contaminants was low (pH 6, 15% PEG 1450, 14% Phosphate and 12% NaCl). Precipitation of IgG was also minimized. These conditions were chosen for the extraction of IgG from the contaminants in a crude concentrated supernatant. The presence of culture media contaminants had a strong effect in the systems and hence on the partition of IgG which was lower than for pure IgG. The ratio of KIgG/Kcont was > 25. The conditions chosen for the first forward extraction into the PEG rich phase were 15% PEG 1450, 14% phosphate 12% NaCl and pH 5.5. Virtually all IgG partitioned to the top phase and the contaminants to the bottom phase. Optimal conditions for the back extraction of the IgGs into a bottom salt phase were also found (addition of 14% phosphate with no NaCl). An industrial serum free, crude, concentrated culture supernatant of hybridoma produced murine IgG, with a relatively low level of protein contaminants (14% IgG purity) was processed in this system. After the back extraction the contaminants were reduced 18 fold giving IgG with 80% purity. A 5.9 fold purification was obtained out of a 7.3 maximum possible (at 100% pure IgG). All of the IgG was recovered.

Antibodies, Monoclonal↗
PubMed1995

Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.

Water excretion by the kidney is regulated by the peptide hormone vasopressin. Vasopressin increases the water permeability of the renal collecting duct cells, allowing more water to be reabsorbed from collecting duct urine to blood. Despite long-standing interest in this process, the mechanism of the water permeability increase has remained undetermined. Recently, a molecular water channel (AQP-CD) has been cloned whose expression appears to be limited to the collecting duct. Previously, we immunolocalized this water channel to the apical plasma membrane (APM) and to intracellular vesicles (IVs) of collecting duct cells. Here, we test the hypothesis that vasopressin increases cellular water permeability by inducing exocytosis of AQP-CD-laden vesicles, transferring water channels from IVs to APM. Rat collecting ducts were perfused in vitro to determine water permeability and subcellular distribution of AQP-CD in the same tubules. The collecting ducts were fixed for immunoelectron microscopy before, during, and after exposure to vasopressin. Vasopressin exposure induced increases in water permeability and the absolute labeling density of AQP-CD in the APM. In parallel, the APM:IV labeling ratio increased. Furthermore, in response to vasopressin withdrawal, AQP-CD labeling density in the APM and the APM:IV labeling ratio decreased in parallel to a measured decrease in osmotic water permeability. We conclude that vasopressin increases the water permeability of collecting duct cells by inducing a reversible translocation of AQP-CD water channels from IVs to the APM.

Animals↗
PubMed1995

Expectant management of first-trimester spontaneous abortion.

Approximately 15% of registered pregnancies end in spontaneous abortion, and for 50 years or so dilatation and curettage (D&C) has been the usual management. In a prospective randomised trial we compared the clinical results after either expectant management or D&C, for miscarriages of less than 13 weeks' gestation in which transvaginal ultrasound examination showed intrauterine tissue and/or blood clots with a diameter 15-50 mm. 103 patients were randomised to expectant management and spontaneous resolution of pregnancy occurred within 3 days in 81 cases (79%). 52 patients were randomised to D&C. 3 infections were diagnosed among patients who underwent expectant management (3%); 5 infections and 1 case of postoperative anaemia were observed among patients randomised to D&C (11%). The duration of vaginal bleeding was a mean of 1.3 days longer in the expectant management group (p < 0.02). Convalescence time, time during which patients experienced pain, and packed-cell volume 3 and 14 days after inclusion did not differ significantly between the groups. This study shows that expectant management of selected cases of spontaneous abortion has a similar outcome to D&C.

Abortion, Spontaneous↗
PubMed1995

Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet.

Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean +/- SD: 145/78 +/- 25/10 vs 143/79 +/- 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 +/- 16/8 vs 143/79 +/- 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean x/divided by tolerance factor) 32.4 x/divided by 2.1 to 36.0 x/divided by 1.9 micrograms/min (NS) vs from 34.2 x/divided by 1.9 to 32.1 x/divided by 2.1 micrograms/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p < 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Aquaporin water channels: unanswered questions and unresolved controversies.

The long-standing biophysical question of how water crosses plasma membranes has been answered by the recent discovery of the aquaporins. Identification of this large family of membrane water-transport proteins has generated new questions about the physiological functions, tissue distributions, and regulatory mechanisms of individual aquaporins. The fast pace of developments in this field has also resulted in major discrepancies in published reports which warrant resolution.

Animals↗
PubMed1995

The aquaporin family of water channels in kidney.

The longstanding puzzle of membrane water permeability was advanced by the discovery of channel-forming integral protein (CHIP). This protein was shown to function as a water channel when expressed in Xenopus oocytes or when reconstituted into synthetic membranes. Site-directed mutagenesis and electron crystallography reveal tetrameric organization of CHIP, and the two halves of CHIP are tandem repeats folded into an obversely symmetric structure which resembles an hourglass. Each tetramer is comprised of functionally independent subunits. CHIP is the archetypal member of a newly-recognized family of membrane water transporters known as the "Aquaporins" (AQPs). AQP1 (CHIP) is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in a number of extra renal tissues. In the collecting duct, AQP2 is the predominant vasopressin-sensitive water channel. AQP2 is localized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by antidiuretic hormone. Humans are identified with mutations in AQP1 and AQP2 and exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of collecting duct principal cells providing an exit pathway for water, and AQP4 is abundant in brain, where it apparently functions as the hypothalamic osmoreceptor responsible for secretion of antidiuretic hormone. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and water balance disorders.

Animals↗
PubMed1995

Prorenin and renal function in NIDDM patients with normo- and microalbuminuria.

OBJECTIVES: To assess whether prorenin is elevated and perhaps a predictor of deteriorations in albuminuria and/or renal function in NIDDM patients with normo- and microalbuminuria. DESIGN: A cross-sectional and a longitudinal study. SETTING: Outpatient diabetic clinic. SUBJECTS: Twenty-eight NIDDM patients (16 with normoalbuminuria, 12 with microalbuminuric) and 16 healthy subjects, matched for sex, age and BMI. Fifteen patients were reinvestigated after (mean [range]) 3.1 (2.1-4.3) years. MAIN OUTCOME MEASURES: Serum prorenin and renin, urinary albumin excretion rate, and glomerular filtration rate. RESULTS: Serum prorenin was similar in both normoalbuminuric (116x/divided by) 1.9 microU ml-1 (geometric meanx/divided by antilog SD) and microalbuminuric (124x/divided by) 1.7 microU ml-1) as well as in healthy control subjects (90x/divided by) 1.7 microU ml-1). Prorenin did not correlate to either urinary albumin excretion rate or glomerular filtration rate. No difference between baseline and follow-up levels of albuminuria, glomerular filtration rate or prorenin were observed. The annual changes in albuminuria, glomerular filtration rate and prorenin were not correlated, and no correlation was found between baseline prorenin levels and annual changes in albuminuria or glomerular filtration rate. CONCLUSIONS: Serum prorenin levels are not elevated in either normoalbuminuric or microalbuminuric NIDDM patients, and serum prorenin is not a valid predictor of long-term changes in albuminuria in this patient group.

Aged↗