Search PubMed⌕ Search

Biomedical subjects

H P Hansen

Publications and source records attributed to H P Hansen.

At least 19 recordsLinked to original sources
PubMed1999

Low-protein diet and kidney function in insulin-dependent diabetic patients with diabetic nephropathy.

BACKGROUND: Initiation of a low-protein diet (LPD) in patients with various nephropathies induces a faster initial and slower subsequent decline in the glomerular filtration rate (GFR). Whether this initial phenomenon is reversible or irreversible remains to be elucidated. METHODS: We performed an eight-week prospective, randomized, controlled study comparing the effect of an LPD with a normal-protein diet (NPD) in 29 insulin-dependent diabetic patients with diabetic nephropathy. At baseline, the patients were randomized to either an LPD (0.6 g.kg-1.24 hr-1, LPD group, N = 14) or their NPD (NPD group, N = 15) for four weeks (phase I). Between weeks 4 and 8, all patients received their NPD (phase II, recovery). Dietary protein intake (g.kg-1.24 hr-1), GFR (51Cr-EDTA, ml.min-1.1.73 m-2), albuminuria (enzyme-linked immunoadsorbent assay, mg.24 hr-1), and arterial blood pressure (Hawksley random zero sphygmomanometer, mm Hg) were measured at baseline and after four- and eight-weeks of follow-up. During the investigation, all patients in the LPD group (N = 12) and in the NPD group (N = 14) received their usual antihypertensive treatment. RESULTS: At baseline, the LPD group and the NPD group were comparable regarding dietary protein intake, GFR, albuminuria, and arterial blood pressure. During phase I, a significant decline in dietary protein intake, GFR, and albuminuria (mean, 95% CI) was observed in the LPD group [0.4 (0.3 to 0.5) g.kg-1.24 hr-1, 8.6 (3.2 to 13.9) ml.min-1.1.73 m-2, and 28.7 (14.0 to 40.9)%, respectively] compared with the NPD group [0.0 (-0.1 to 0.2) g.kg-1.24 hr-1 (P < 0.0001 between diets), 2.5 (-1.8 to 6.8) ml.min-1.1.73 m-2 (P = 0.07 between diets), and 0.0 (-20.1 to 23.5)% (P < 0.05 between diets), respectively]. Conversely, during phase II, a significant increase in dietary protein intake, GFR, and albuminuria [mean, 95% CI; 0.3 (0.2 to 0.5) g.kg-1.24 hr-1, 5.9 (0.8 to 11.1) ml.min-1.1.73 m-2, and 25.0 (4.5 to 49.6)%, respectively] took place in the LPD group compared with the NPD group [0.0 (-0.2 to 0.1) g.kg-1.24 hr-1 (P < 0.0001 between diets), -2.9 (-6.4 to 0.6) ml.min-1.1.73 m-2 (P < 0.01 between diets), and 2.9 (-18.3 to 29.7)% (P = 0.16 between diets), respectively]. Arterial blood pressure was comparable in the two groups of patients during phase I and II. CONCLUSIONS: Dietary protein restriction for four weeks induces a reversible decline in GFR and albuminuria in insulin-dependent diabetic patients with diabetic nephropathy, whereas systemic blood pressure remains unchanged.

Adult↗
PubMed1998

Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of 51Cr-EDTA.

Plasma clearance of 51Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total 51Cr-EDTA plasma clearance (C(T)). Simplified methods, using the final mono-exponential part of the plasma curve, have been suggested, e.g. four samples, taken 180 to 240 min after injection (C(IV)), or using one sample taken at 240 min (C(I)). Our aim was to evaluate the agreement between measurements of GFR and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq 51Cr-EDTA by determining the radioactivity in venous blood samples taken 5, 7, 10, 15, 30, 45, 60, 90, 120, 150, 180, 200, 220, and 240 min after the injection. Rate of decline in GFR was assessed using 12 (6-17) determinations of GFR over a period of time of 8 (4-10) years. Mean (SD) GFRT was 123 (21) ml x min(-1) compared to GFR(IV) 123 (21) ml x min(-1) (NS) and GFR(I) 115 (17) ml x min(-1) (p < 0.00001). The mean difference (95% limits of agreement) between GFR(T) and GFR(IV) was +0.6 (-16.6 to +17.7) ml x min(-1), and between GFR(T) and GFR(I) +8.0 (-6.0 to +22.2) ml x min(-1). The difference between GFR(T) and GFR(I) was significantly correlated with their mean value (r = 0.56, p < 0.00001), indicating increasing underestimation by GFR(I) with increasing GFR levels. The mean (SD) rate of decline in GFR(T) was 2.3 (3.9) ml x min(-1) x year(-1), compared to a mean rate of decline in GFR(IV) of 2.4 (3.6) ml x min(-1) x year(-1) (NS), and a mean rate of decline in GFR(I) of 2.2 (3.5) ml x min(-1) x year(-1) (NS). The mean difference (95% limits of agreement) between rate of decline in GFR(T) and rate of decline in GFR(IV) was +0.16 (-1.59 to +1.91) ml x min(-1) x year(-1), and between rate of decline in GFR(T) and rate of decline in GFR(I) -0.01 (-1.64 to +1.61) ml x min(-1) x year(-1), respectively. In conclusion, our cross-sectional study revealed a close agreement between GFR(T) and GFR(IV) with acceptable limits of agreement (precision), while GFR(I) lacked accuracy. However, a close agreement between rate of decline in GFR(T) and rate of decline in GFR(IV), and between rate of decline in GFR(T) and rate of decline in GFR(I), with acceptable limits of agreement (precision), suggests that both simplified methods are applicable for long-term follow-up.

Chromium Radioisotopes↗
PubMed1997

Impaired autoregulation of GFR in hypertensive non-insulin dependent diabetic patients.

We investigated the effect of acute lowering of blood pressure (BP) upon glomerular filtration rate (GFR) in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients, 14 with diabetic nephropathy and 12 with normoalbuminuria. The study was performed twice with the subjects receiving an intravenous injection of either clonidine (150 to 225 micrograms) or saline (0.154 mmol/liter). We assessed GFR, albuminuria, and BP. The two groups were well matched with respect to demographic data, baseline GFR and BP. Clonidine induced similar reductions in mean arterial blood pressure 19 (SE +/- 4) and 21 (SE +/- 3) mm Hg in patients with and without nephropathy, respectively. In the nephropathy group GFR diminished in average from 90 (SE +/- 6) to 81 (SE +/- 7) ml/min/1.73 m2 (P = 0.006), fractional clearance of albumin (x 10(-6)) declined from a geometric mean of 219 (antilog SE /divided by 1.3) to 186 (antilog SE /divided by 1.3) (P = 0.04), and four patients had a complete pressure-passive vasculature, defined as delta GFR% = delta MABP%. A significant correlation between relative reductions in MABP and GFR (r = 0.78, P < 0.001) was demonstrated in albuminuric patients. None of the normoalbuminuric patients had a complete pressure-passive vasculature and there were no significant differences in GFR between the two examinations, but five had abnormal autoregulation of GFR. Mean difference between changes in GFR (95% confidence interval) between the nephropathic and normoalbuminuric group was 5.5 (divided by 2.7 to 13.7) ml/min/1.73 m2 (P = 0.18). Our study suggests that hypertensive NIDDM patients, particularly patients with nephropathy, frequently suffer from impaired or abolished autoregulation of GFR.

Adult↗
PubMed1997

Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy.

Initiation of antihypertensive treatment in hypertensive non-insulin-dependent diabetic (NIDDM) patients with diabetic nephropathy induces a faster initial (0 to 6 months) and slower subsequent (6 months-end) decline in GFR [delta GFR (ml.min-1.1.73 m-2.month-1) approximately 1.5 vs. 0.4]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged antihypertensive treatment is not known. To elucidate these mechanisms we investigated 40 hypertensive NIDDM patients (age 61 +/- 7 years, mean +/- SD), known duration of diabetes 14 years (2 to 33 years) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P < 0.0001) and albuminuria [geometric mean (antilog SEM)] increased from 634 (1.3) to 1159 (1.2) (P < 0.0001), while GFR (mean +/- SD) remained unchanged (69 +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P < 0.01) was found. In conclusion, our results suggest that the faster initial decline in GFR after initiating antihypertensive treatment in hypertensive NIDDM patients with diabetic nephropathy is due to a irreversible effect, and should be accounted for when evaluating the beneficial effect of antihypertensive treatment on the progression of diabetic nephropathy in these patients.

Adolescent↗
PubMed1997

Characterization, mapping and partial cDNA sequence of the 57-kD intracellular Ki-1 antigen.

A novel antigen was identified by the cross-reactivity of the anti-CD30 antibody Ki-1. This 57-kD intracellular Ki-1 antigen (Ki-1/57) is induced upon activation of leukocytes and is transported to the nuclear compartment. We describe the partial cloning and sequencing of the Ki-1/57 cDNA from a lambda gt 11-cDNA library derived from the Hodgkin-analogous cell line L540. New monoclonal antibodies were produced against the recombinant Ki-1/57 protein fragment which were used to confirm that the Ki-1/57 antigen is associated with kinase activity and is expressed in a variety of tumor cell lines and in activated but not resting leukocytes. The Ki-1/57 gene was mapped to the bands 9q22.3-31 of human chromosome 9. This is an area which appears to be associated with secondary chromosomal aberrations in acute myeloid leukemias.

Amino Acid Sequence↗
PubMed1996

Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy.

The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood pressure, heart rate (HR) variation (autonomic nervous function) and extracellular fluid volume (ECV) were measured, and urine samples were collected three times during the corresponding day- and nighttimes in 47 insulin-dependent diabetic (IDDM) patients with DN. Mean arterial blood pressure (MABP) during the daytime [mm Hg, median (range)] was identical in group I [105 (96-137)], group II [109 (86-124)] and group III [dippers; average blood pressure reduction from day to night > 10%, 107 (93-132), P = NS], while the nighttime MABP differed [group I, 106 (95-144); group II, 100 (78-118); group III, 91 (76-118); P < 0.001]. No significant difference between the groups concerning the daytime or nighttime albuminuria [microgram/min; median (range)] was observed; [Day: group I, 1467 (235-3933); group II, 695 (170-6719); group III, 875 (228-3173). Night: group I, 1079 (279-4665); group II, 572 (113-3807); group III, 659 (81-2493)]. A significant correlation between MABP and albuminuria was demonstrated during day- (rho = 0.50, P < 0.0005) and nighttime (rho = 0.46, P < 0.005), while neither the absolute nor the relative changes in MABP from day to night correlated significantly with absolute or relative changes in albuminuria from day to night. The night/day ratio of HR was higher in group I [0.93 (0.76-1.09), median (range)] compared to group III [0.83 (0.74-1.02), P < 0.005] and a significant correlation between this ratio and the night/day ratio of MABP was found (rho = 0.54, P < 0.0005). ECV was about the same in the three groups. Our study indicated an association between blood pressure and albuminuria, but the mechanisms involved in the reduction of albuminuria from day to night was not unraveled. A relative lack of sympathetic withdrawal during sleep seems to be an important feature of nocturnal hypertension in diabetic nephropathy.

Adult↗
PubMed1996

The acute effect of smoking on systemic haemodynamics, kidney and endothelial functions in insulin-dependent diabetic patients with microalbuminuria.

The acute effect of smoking upon arterial blood pressure, urinary albumin excretion rate, glomerular filtration rate and transcapillary escape rate of albumin were investigated in nine normotensive insulin-dependent diabetic patients with microalbuminuria, who had been smoking for 19 (range 4-30) years. In a prospective, open randomized cross-over design, patients were investigated with and without smoking three cigarettes per hour during a 5.5-h period. A rise in systolic blood pressure and heart rate (Takeda TM2420, median (range)) was observed during the smoking day (10(-11 to 14) mmHg and 8 (-1 to 19) beats min-1), compared to the non-smoking day (1 mmHg (-7 to 13) (p = 0.05) and 0 beats min-1 (-2 to 4) (p < 0.01)). Urinary albumin excretion rate (ELISA), glomerular filtration rate (plasma clearance of 51Cr-EDTA) and transcapillary escape rate of albumin (125I-albumin) remained the same with or without smoking. Our study suggests that heavy smoking induces an abrupt rise in systolic blood pressure and heart rate, while vascular leakage of albumin and glomerular filtration rate remain unaltered in normotensive insulin-dependent diabetic patients with microalbuminuria who had been smoking for several years.

Adult↗
PubMed1995

A zinc metalloproteinase is responsible for the release of CD30 on human tumor cell lines.

The activation marker CD30 is expressed on the cell surface of the malignant cells in Hodgkin's disease and a few non-Hodgkin lymphomas. We have analyzed the regulation of membrane-bound CD30 and found that the binding of a variety of anti-CD30 antibodies induced down-regulation of CD30 on cell lines. In addition, such down-modulation was also observed after treatment of the cell surface proteins with the sulfhydryl reagent iodoacetamide or after stimulation of the second messenger pathway with phorbol ester or calcium ionophore. This modulation was abolished at 4 degrees C and strongly inhibited by chelators like EDTA or 1,10-phenanthroline, whereas EGTA, a selective inhibitor of Ca(2+)-dependent proteinases and other inhibitors of serine, thiol and acid proteinases, showed no effect. The down-modulation was strengthened by Zn2+ or Cd2+, but not by other divalent cations such as Fe2+, Mn2+, Mg2+, Ca2+ or Co2+, thus indicating the involvement of a zinc metalloproteinase in CD30 modulation which can be activated by protein kinase C and by alkylation of sulfhydryl groups. Pulse-chase experiments, analysis of the CD30 glycosylation and specific measurement of the 90-kDa soluble form of CD30 (sCD30) with a sandwich radioimmunoassay revealed that CD30 down-modulation results from enhanced release of 90-kDa sCD30 by the site-specific cleavage of CD30 accomplished by a zinc metalloproteinase. This release occurs at the cell membrane without prior endocytosis.

Antibodies, Monoclonal↗
PubMed1995

Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy.

Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0.35]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged AHT is not known. To elucidate these mechanisms we investigated 42 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured the last day on AHT and one month after withdrawal of AHT. The measured variables were all significantly elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P < 0.0001), BP [mean(SEM)] from 140/82 (2/1) to 151/89 (2/1) (P < 0.0005) and albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P < 0.0001). A correlation between relative rise in systolic blood pressure (delta Sys%) and relative change in GFR (delta GFR%) was found (r = 0.44, P < 0.005). Our results render some support of the hypothesis that the faster initial decline in GFR is due to a functional (hemodynamic) effect of AHT, which does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.

Adult↗
PubMed1993

Metformin ameliorates diabetes but does not normalize the decreased GLUT 4 content in skeletal muscle of obese (fa/fa) Zucker rats.

We studied the expression of the glucose transporter GLUT 4 in the soleus and red gastrocnemius muscles from obese, diabetic (fa/fa) Zucker rats compared to their lean littermates (Fa/-), with and without treatment with the antidiabetic drug metformin. In the untreated groups of rats, the GLUT 4 content in a crude membrane fraction of both the soleus and the red gastrocnemius muscles were significantly lower in the obese (fa/fa) rats (3.46 +/- 0.28 vs. 6.04 +/- 0.41, p < 0.001 and 6.0 +/- 0.24 vs. 9.1 +/- 0.48, p < 0.0001, respectively). Differences in GLUT 4 expression in soleus muscle from the same rats were confirmed by quantitative immunofluorescence microscopy, and the results were significantly correlated with the results obtained from quantitative immunoblotting (rho = 0.70, p < 0.0005). The decreased expression of GLUT 4 in fa/fa rats could contribute to the well-established insulin resistance in skeletal muscle of these animals. After 4 weeks of treatment with metformin, weight gain was not affected in either the diabetic (fa/fa) rats or the lean (Fa/-) rats. Improvement of glucose homeostasis by metformin was not associated with normalization of the GLUT 4 expression in the skeletal muscles studied, indicating (1) that the decreased GLUT 4 expression is not directly related to hyperinsulinaemia and diabetes mellitus and (2) that metformin does not normalize the expression of GLUT 4 in skeletal muscle of the diabetic (fa/fa) Zucker rats.

Animals↗
PubMed1989

[A dependent hierarchy--the relationship between qualitative and quantitative data from Anthony Wilden's "The Rules are no Game"].

This lecture is about the relationship between qualitative and quantitative data. The purpose is to show that quality and quantity are not opposites, the latter depends on the first. They are not of the same level of communication or reality. Quantity is a kind of quality, but quality is not a kind of quantity. To understand this dependent hierarchy it is necessary to withdraw the notion of context. Nature and culture also forms a dependent hierarchy, where complexity and diversity increase qualitatively from nature to culture. Context is most complex in culture, and for that reason it is often difficult to interpret the meaning of a statement. In life and society, meaning is a function of context.

Humans↗