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P Jacobsen

Publications and source records attributed to P Jacobsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction. RESULTS: Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3-3.1)%, but it increased by 0.5 (-1.0-1.9)% in group 2, mean difference (95% CI), -2.1 (-4.0 to -0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0-25.0)% in group 1 but rose by 7.7 (-9.7-28.4)% in group 2, mean difference (95% CI), -19.6 (-35-0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.

Aged↗
PubMed1999

Progression of diabetic nephropathy in normotensive type 1 diabetic patients.

BACKGROUND: The first aim of our long-term study was to describe the natural history of diabetic nephropathy in 59 normotensive type 1 diabetic patients. Secondly, we evaluated genetic and nongenetic progression promoters. METHODS: The following progression promoters were determined: the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene, blood pressure, albuminuria, hemoglobin A1c, cholesterol, smoking, height, and gender. We studied the natural history by measuring 51Cr-EDTA plasma clearance at yearly intervals at least three times during [median (range)] 5.5 (2.2 to 18.3) years. RESULTS: At baseline the three groups (II, N = 11; ID, N = 25, and DD, N = 23) had comparable GFR (103 +/- 16; 99 +/- 19; 113 +/- 22 ml/min/1.73 m2, respectively; mean +/- SD), arterial blood pressure, albuminuria, and hemoglobin A1c. During the follow-up there was a median rate of decline in GFR in all 59 patients of 1.2 (range 12.9 to -4.4) ml/min/year. During the study period no significant differences were observed in: the rate of decline in glomerular filtration rate [median (range) 0.9 (10.6 to -1.9); 2.5 (12.9 to -4.4); 1.4 (10.8 to -1.9 ml/min/year)], arterial blood pressure, albuminuria, hemoglobin A1c or cholesterol between the three groups (II, ID and DD), respectively. At baseline, multiple linear regression analysis including the above-mentioned putative risk factors revealed that albuminuria, short stature, and male gender independently predict an enhanced decline in GFR [R2 (adjusted) = 0.33; P < 0.002]. During the follow-up period, only albuminuria acted as an independent progression promoter [R2 (adjusted) = 0.37; P < 0.0001]. CONCLUSIONS: Our study revealed a rather slow progression of kidney disease in normotensive type 1 diabetic patients with diabetic nephropathy. Albuminuria, short stature, and male gender act as progression promoters in such patients.

Adult↗
PubMed1998

ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma.

Stroke and head trauma are worldwide public health problems and leading causes of death and disability in humans, yet, no adequate neuroprotective treatment is available for therapy. Glutamate antagonists are considered major drug candidates for neuroprotection in stroke and trauma. However, N-methyl-D-aspartate antagonists failed clinical trials because of unacceptable side effects and short therapeutic time window. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists derived from the quinoxalinedione scaffold cannot be used in humans because of their insolubility and resulting renal toxicity. Therefore, achieving water solubility of quinoxalinediones without loss of selectivity and potency profiles becomes a major challenge for medicinal chemistry. One of the major tenets in the chemistry of glutamate antagonists is that the incorporation of phosphonate into the glutamate framework results in preferential N-methyl-D-aspartate antagonism. Therefore, synthesis of phosphonate derivatives of quinoxalinediones was not pursued because of a predicted loss of their selectivity toward AMPA. Here, we report that introduction of a methylphosphonate group into the quinoxalinedione skeleton leaves potency as AMPA antagonists and selectivity for the AMPA receptor unchanged and dramatically improves solubility. One such novel phosphonate quinoxalinedione derivative and competitive AMPA antagonist ZK200775 exhibited a surprisingly long therapeutic time window of >4 h after permanent occlusion of the middle cerebral artery in rats and was devoid of renal toxicity. Furthermore, delayed treatment with ZK200775 commencing 2 h after onset of reperfusion in transient middle cerebral artery occlusion resulted in a dramatic reduction of the infarct size. ZK200775 alleviated also both cortical and hippocampal damage induced by head trauma in the rat. These observations suggest that phosphonate quinoxalinedione-based AMPA antagonists may offer new prospects for treatment of stroke and trauma in humans.

Animals↗
PubMed1998

[The significance of deletion polymorphism in the ACE gene for progression of diabetic nephropathies treated with ACE inhibitors].

The aim of the study was to evaluate the effect of an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene on progression of diabetic nephropathy. We performed an observational follow-up study of 35 patients with insulin-dependent diabetes and diabetic nephropathy. Patients were investigated during captopril treatment for a median of seven (range three to nine) years. Eleven patients were homozygous for the deletion allele (DD) and 24 were hetero- or homozygous for the insertion allele (ID + II). The two groups had comparable glomerular filtration rate, albuminuria and blood pressure at baseline and captopril induced nearly the same mean reduction in blood pressure--to 103 (SD 5) mm Hg in the DD-group and 102 (8) mm Hg in the ID + II-group. The rate of decline in glomerular filtration rate was significantly steeper in the DD group than in the other group (mean 5.7 (SD 3.7) versus 2.6 (2.8) ml/min/year, p = 0.01). In conclusion, the deletion polymorphism in the ACE gene reduces the long term beneficial effect of ACE inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.

Adult↗
PubMed1998

Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy.

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hypertensive IDDM patients suffering from diabetic nephropathy were investigated during three months before and for the initial six month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were measured three (1 to 6) times before and three (1 to 13) times during ACE inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/- SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenced the decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01). A significant association between changes in MABP and albuminuria was demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are particularly susceptible to commonly advocated renoprotective treatment.

Adult↗
PubMed1998

Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients.

Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion < 20 microg/min or < 30 mg/24 h). Arterial hypertension, defined as antihypertensive therapy or a 24-h ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mmHg, was present in 57% of parents of DN+ patients compared with 41% of parents of DN- patients (P = 0.034; difference 16% [95% CI 1.3-29.6%]). In addition, the cumulative incidence of hypertension was higher among parents of DN+ patients (log-rank test P < 0.001), with a shift toward younger age at onset of hypertension in this group. However, the difference in prevalence of parental hypertension was not evident using office blood pressure measurements (64 vs. 57%; NS; difference 7% [-5.8-20%). Furthermore, patients with DN+ and with antihypertensive therapy in both parents were themselves more frequently treated for hypertension than were patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to essential hypertension increases the risk of diabetic nephropathy and may also contribute to the development of systemic hypertension in patients with IDDM and diabetic nephropathy.

Adult↗
PubMed1998

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

OBJECTIVE: To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. RESEARCH DESIGN AND METHODS: All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). RESULTS: Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. CONCLUSIONS: The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Adult↗
PubMed1998

Progress toward guidelines for the management of fatigue.

Fatigue is a subjective state of overwhelming, sustained exhaustion and decreased capacity for physical and mental work that is not relieved by rest. Cancer-related fatigue has many causes. Included in the causes are the illness itself, the side effects of virtually every treatment, depression, and other biopsychosocial factors. As a result, fatigue is the most common symptom reported by cancer patients in most descriptive studies. In addition to arising from multiple etiologies, fatigue is also multidimensional in its manifestation and impact. Its effect on the quality of life of the patient is comparable to that of pain. Experienced by most patients as an extremely frustrating state of chronic energy depletion, it leads to loss of productivity which can reduce self-esteem. As a subtle and chronic symptom, it also places people at risk for being questioned about the veracity of their complaints, particularly during the post-treatment, disease-free survival period. Patients themselves are reluctant to complain of fatigue, perhaps because they believe little can be done about it, or they wish to avoid drawing attention away from treating their cancer.

Fatigue↗
PubMed1998

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California↗
PubMed1997

Microalbuminuria as an early indicator of osteopenia in male insulin-dependent diabetic patients.

Reduced bone mineral density (BMD), termed diabetic osteopenia, has been reported in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). To examine BMD in long-term IDDM patients with normal kidney function, but with different degrees of urinary albumin excretion rate (UAER), compared to that of patients with elevated plasma creatinine, 36 IDDM male patients (mean duration 27 years) were subdivided according to UAER (<30, 30-300, >300, >300 mg 24 h(-1) and plasma creatinine 0.120-0.350 mmol l(-1)) and 15 controls were recruited. BMD was measured by dual energy X-ray absorptiometry and UAER by enzyme linked immunosorbent assay. BMD was normal in IDDM patients with normal UAER and reduced in the femoral neck, the trochanter major, and the Wards triangle in patients with increased UAER (p < 0.01, p < 0.05, p < 0.02). BMD correlated to creatinine clearance in both cortical and cancellous bone sites (p < 0.001, p < 0.0001), and inversely to the levels of plasma PTH (p < 0.0005). We conclude that BMD is normal in long-term IDDM male patients with normal kidney function and normal UAER and reduced in patients with increased UAER. Diabetic osteopenia seems to be a progressive phenomenon related to diabetic nephropathy and associated with the decrease in creatinine clearance and with the resulting rise in plasma PTH.

Absorptiometry, Photon↗
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↗
PubMed1996

[Diabetic nephropathy. Unchanged occurrence in patients with insulin-dependent diabetes mellitus].

Recently, a dramatic decline in the cumulative incidence of diabetic nephropathy (less than 10% after 25 years of diabetes) has been reported in IDDM patients diagnosed between 1961 and 1980. In a clinic based study we assessed recent trends in the incidence of diabetic nephropathy. All 356 patients in whom IDDM was diagnosed before the age of 41 years between 1965 and 1979, identified in 1984 were followed to 1991 or to death. The cumulative incidence of diabetic nephropathy (urinary albumin excretion 300 mg/24 hours in two out of three consecutive samples) after 15 years of diabetes and in 1991 were (cumulative incidence (SE)): 18 (4)% and 35 (5)% (onset of diabetes 1965-69, n = 113), 20 (4)% and 35 (5)% (onset of diabetes 1970-74, n = 130), and 16 (5)% (onset of diabetes 1975-79, n = 113), respectively (ns). The mean (SE) haemoglobin A1c measured yearly beginning in 1984 was higher in patients with nephropathy (9.4 (0.1)%), and persistent microalbuminuria (8.9 (0.1)%) than in patients with normoalbuminuria (8.5 (0.1)%, (p < 0.001)). Our study revealed no decline in the cumulative incidence of diabetic nephropathy with increasing calendar year of diabetes onset. This may in part be explained by poor metabolic control and a high prevalence of smokers (58-71%).

Adolescent↗
PubMed1996

Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy during inhibition of angiotensin converting enzyme: observational follow up study.

OBJECTIVE: To evaluate the concept that an insertion/deletion polymorphism of the angiotensin converting enzyme gene predicts the therapeutic efficacy of inhibition of angiotensin converting enzyme on progression of diabetic nephropathy. DESIGN: Observational follow up study of patients with insulin dependent diabetes and nephropathy who had been treated with captopril for a median of 7 years (range 3-9 years). SETTING: Outpatient diabetic clinic in a tertiary referral centre. PATIENTS: 35 patients with insulin dependent diabetes and nephropathy were investigated during captopril treatment (median 75 mg/day (range 12.5 to 150 mg/day)) that was in many cases combined with a loop diuretic, 11 patients were homozygous for the deletion allele and 24 were heterozygous or homozygous for the insertion allele of the angiotensin converting enzyme gene. MAIN OUTCOME MEASURES: Albuminuria, arterial blood pressure, and glomerular filtration rate according to insertion/deletion polymorphism. RESULTS: The two groups had comparable glomerular filtration rate, albuminuria, blood pressure, and haemoglobin A1c concentration at baseline. Captopril induced nearly the same reduction in mean blood pressure in the two groups-to 103 (SD 5) mm Hg in the group with the deletion and 102 (8) mm Hg in the group with the insertion-and in geometric mean albumin excretion-573 (antilog SE 1.3) micrograms/min and 470 (1.2) micrograms/min, respectively. The rate of decline in glomerular filtration rate (linear regression of all glomerular filtration rate measurements during antihypertensive treatment) was significantly steeper in the group homozygous for the double deletion allele than in the other group (mean 5.7 (3.7) ml/min/year and 2.6 (2.8) ml/min/year, respectively; P = 0.01). Multiple linear regression analysis showed that haemoglobin A1c concentration, albuminuria, and the double deletion genotype independently influenced the sustained rate of decline in glomerular filtration rate (R1 (adjusted) = 0.51). CONCLUSION: The deletion polymorphism in the angiotensin converting enzyme gene reduces the long term beneficial effect of angiotensin converting enzyme inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.

Adult↗
PubMed1996

[Exposure of children to lead from contaminated soil].

To assess lead exposure in infants from contaminated soil a review of epidemiological studies was performed. Seventeen studies fulfilled criteria of individual exposure measures and a relevant confounder control. In 10 of these a clear association between blood lead and lead in soil was demonstrated after control of confounders. With some reservations three additional studies indicated an effect. No effect on blood lead from soil exposure was found in four studies. Quantitative estimates of the contributions to blood lead from soil varied within a wide range. In the best designed study-a controlled intervention against contaminated soil-blood lead values declined a little more than 1 microgram/100 ml per 1000 ppm. reduction of soil lead concentration. Oral exposure, probably by mouthing behaviour, was indicated by modification of the association between blood and soil lead from time spent outdoors, area with uncovered soil, age and mouthing behaviour in several studies. The conclusions from the review were that children's mouthing behaviour on lead contaminated soil may affect blood lead, but the contribution to overall lead exposure seems to be relatively small. Considering the limited margin of safety for lead exposure an intervention regimen for contaminated areas where infants have direct and continued contact with soil is suggested. Intervention in other places is unlikely to significantly reduce the lead burden of children. Simultaneously with intervention a programme for the evaluation of its effect is proposed.

Child, Preschool↗
PubMed1996

Benefits of long-term antihypertensive treatment on prognosis in diabetic nephropathy.

We assessed the prognosis of diabetic nephropathy during long-term antihypertensive treatment as compared to the prognosis during the natural history of this complication in a prospective study of all IDDM patients (N = 45) aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Diabetes Center, and were followed until death or for at least 16 years [median 16 (4 to 21) years]. Antihypertensive treatment was started 3 (0 to 13) years after onset of diabetic nephropathy. Mean arterial blood pressure at start of antihypertensive treatment was 148/96 (sd 12/10) mm Hg and 143/86 (16/6) mm Hg during the whole interval of antihypertensive treatment (P < 0.01). The cumulative death rate was 45% (95% C.I. 38 to 52) 16 years after onset of diabetic nephropathy, in contrast to previous reports 88% and 94% 12 and 16 years after onset of diabetic nephropathy, respectively. The median survival time in our study exceeded 16 years as compared to five and seven years in untreated patients in the past. Uremia was the main cause of death (12 patients; 55%). In 1994 serum creatinine was 116 (74 to 311) mumol/liter in the 23 surviving patients. The preservation of kidney function and the prognosis of diabetic nephropathy has improved during the past two decades mainly because of effective antihypertensive treatment.

Adult↗