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P Jacobsen

Publications and source records attributed to P Jacobsen.

At least 19 recordsLinked to original sources
PubMed2006

Aldosterone synthase (CYP11B2) -344T/C polymorphism is not associated with the initiation and progression of diabetic nephropathy in Caucasian Type 1 diabetic patients.

AIMS: Aldosterone is one of the main effectors of the renin-angiotensin-aldosterone system regulating blood pressure. Previous studies have shown that the aldosterone synthase promoter polymorphism -344T/C influences aldosterone levels and is associated with hypertension, a risk factor for the initiation and progression of diabetic nephropathy. Therefore, we investigated whether the -344T/C polymorphism is associated with the development and progression of diabetic nephropathy in Type 1 diabetes mellitus. METHODS: The -344T/C polymorphism was determined using standard PCR techniques in 422 Type 1 diabetic patients with overt diabetic nephropathy [mean age 43 years (SD 11)], and in 479 patients with persistent normoalbuminuria and long-standing Type 1 diabetes [age 47 years (SD 12), duration of diabetes 27 years (SD 10)]. Furthermore, we genotyped 163 Type 1 diabetic patients with overt diabetic nephropathy treated with angiotensis-converting enzyme inhibitors (ACE-I). These patients were followed for a median of 6 years (range 3-14), with nine measurements (range 3-29) of glomerular filtration rate (GFR), and had a decline in GFR of 3.1 (-3.2; 23.7) ml/min per year. RESULTS: There was no significant difference between cases and controls in either genotype distributions (cases TT 0.33, TC 0.48, CC 0.19; controls TT 0.32, TC 0.48, CC 0.20) or allele frequencies (cases T/C 0.57/0.43; controls T/C 0.56/0.44). Furthermore, a genotype-phenotype interaction analysis in the normoalbuminuric patients revealed no differences in sex distribution, age, duration of diabetes, blood pressure, HbA(1c,) or urinary albumin excretion rate across genotypes. In the observational follow-up study, the rate of decline in GFR did not differ between groups of patients with different -344T/C genotype (P = 0.41). However, the T-allele made a statistically significant contribution to both systolic and diastolic pressure during follow-up (P = 0.006 and 0.032, respectively). CONCLUSIONS: The -344T/C polymorphism of the aldosterone synthase gene is not associated with initiation or progression of diabetic nephropathy in Caucasian Type 1 diabetic patients, but modulates blood pressure variation.

Adult↗
PubMed2005

Those who can, teach, but who teaches the learners to learn?

This article was stimulated by Mike Grace's editorial Can those who do--teach? I have been an undergraduate and postgraduate teacher for over 30 years and I agreed with everything that Mike said about the difficulties of combining doing and teaching. The best doers may not make the best teachers and conversely the best teachers are not always incapable of doing, whatever some colleagues may think to the contrary!

Education, Dental↗
PubMed2005

Dual blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy: the role of aldosterone.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with both ACE inhibitors and angiotensin II receptor-blockers has been shown to reduce both albuminuria and blood pressure compared to either monotherapy. The mechanisms behind these beneficial effects are not known, and we hypothesized that the effect of dual RAAS blockade may be due to a more complete suppression of circulating aldosterone. We performed a combined analysis on three randomized, double-masked, cross-over trials where 51 type 1 diabetic patients suffering from diabetic nephropathy received 8 weeks of dual RAAS blockade using an angiotensin II receptor blocker in combination with an ACE inhibitor and 8 weeks of monotherapy with the same ACE inhibitor. Albuminuria, 24 h blood pressure, GFR, and plasma aldosterone were determined at the end of each treatment period. Compared to ACE inhibition alone, dual RAAS blockade lowered blood pressure by 7/5 mm Hg from 137/76 mm Hg, decreased albuminuria by 37% from 558 mg/24 hour, and reduced plasma aldosterone by 28% from 59 pg/ml and caused a reversible decline in GFR of 4 ml/min/1.73 m2 (p < or = 0.01 for all comparisons). There was and a significant correlation between changes in 24-hour diastolic blood pressure and changes in albuminuria. Furthermore, the antialbuminuric response to dual blockade was influenced by the ACE/ID polymorphism, that is, patients carrying the D-allele had a significantly lower reduction of 31% compared to the 55% in patients with the II genotype (p = 0.021). Multiple linear regression analysis revealed that ACE/ID genotypes and reduction in plasma aldosterone, diastolic blood pressure and GFR is associated with changes in albuminuria on dual blockade treatment (R2 (adjusted) = 0.57, p < 0.001). Dual RAAS blockade is a new treatment concept that may offer additional cardiovascular and renal protection in type 1 diabetic patients with diabetic nephropathy. The beneficial response may be influenced by genetic factors and reductions in blood pressure and plasma aldosterone concentrations.

Adult↗
PubMed2003

Birth weight--a risk factor for progression in diabetic nephropathy?

OBJECTIVES: Intrauterine growth retardation, as seen in individuals with low weight at birth, may give rise to a reduction in nephron number. Oligonephropathy has been linked to hypertension and renal disease in adult life. We tested the concept that low weight at birth acts as a risk factor for progression of diabetic nephropathy. DESIGN AND SUBJECTS: We performed an observational follow-up study of 161 (97 men) type 1 diabetic patients with diabetic nephropathy [mean age (SD): 35 (11) years, mean duration of diabetes: 22 (8) years]. All patients had been followed for at least 3 years [median (range): 8 (3-20)] with at least three measurements [9 (3-31)] of glomerular filtration rate (GFR) (51Cr-EDTA). Information about birth size was obtained from midwife registrations. SETTINGS: Steno Diabetes Center, a tertiary referral centre. MAIN OUTCOME MEASURES: Loss of kidney function according to birth weight and weight/length ratio at birth. RESULTS: There was no correlation in univariate analysis between birth weight or weight/length ratio and rate of decline in GFR, neither in men nor in women. Furthermore, the 27 patients with birth weights below the 20th centile had a rate of decline in GFR [median (range)] similar to the 134 patients above: 2.6 (-4.7; 9.6) vs. 3.4 (-2.3; 19.3) mL min(-1) year(-1), respectively (NS). A multiple regression analysis revealed that albuminuria, arterial blood pressure, and haemoglobin A1C during follow-up showed a significant correlation with the decline in GFR [R2 (adjusted) = 0.34], whereas birth weight and birth weight/length ratio did not. CONCLUSIONS: Our study does not suggest that weight at birth is associated with progression of established diabetic nephropathy in type 1 diabetic patients, whilst several other potential modifiable risk factors were identified.

Adult↗
PubMed2003

Effect of short-term hyperglycaemia on haemodynamics in type 1 diabetic patients.

OBJECTIVES: Mechanisms underlying glucose-mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short-term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients. DESIGN AND METHODS: We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single-blinded cross-over trial using insulin-glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L(-1) (euglycaemia) and 15 mmol L(-1) (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period. RESULTS: Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P=0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P=0.02], angiotensin II [17 (8, 25)%, P<0.01] and adrenaline [20 (10, 29)%, P<0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL(-1) (P<0.01) from 43 (2) pg mL(-1). We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7-5.3)% and 5.0 (-4.7 to 8.6)%, respectively. CONCLUSIONS: In type 1 diabetic patients without signs of autonomic neuropathy short-term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin-angiotensin system, possibly caused by PV expansion because of fluid shift from intra- to extracellular compartment.

Acute Disease↗
PubMed2002

Pregnancy and progression of diabetic nephropathy.

AIMS/HYPOTHESIS: Pregnancy could damage kidney function in diabetic nephropathy. We investigated the long-term impact of pregnancy on the progression of diabetic nephropathy. METHODS: Our observational follow-up study included all women patients with Type I (insulin-dependent) diabetes mellitus who developed diabetic nephropathy between 1970 and 1989 at Steno Diabetes Center (n = 93). Follow-up lasted 16 years (range 3-28) from the onset of diabetic nephropathy until death or the year 2000. A total of 26 women became pregnant after the onset of diabetic nephropathy (group A). The remaining 67 served as control subjects (group B). All patients received aggressive antihypertensive treatment (blood pressure goal < 140/90 mmHg). RESULTS: The two groups were comparable at onset of diabetic nephropathy regarding blood pressure, albuminuria, s-cholesterol, smoking, retinopathy and s-creatinine (mean 79(SD 23) micromol/l). The slopes of 1/s-creatinine (1000.l.micromol(-1).year(-1)) during the whole observation period were -0.39(0.40) compared with -0.41(0.70) (group A vs B-NS). The slopes of 1/s-creatinine before and after pregnancy were similar. Decline in creatinine clearance (ml/min/yr) was 3.2 (3.4) compared with 3.2 (5.1) (group A vs B -NS). At the end of follow-up, 35 % (95 %-CI:17-53) of the pregnant women had died and 19 % (7-39) had reached end stage renal disease compared to 34 % (23-45) and 24 %(14-34) of the control subjects, respectively(NS). Group A and B had similar blood pressure levels during the whole observation period: 136(13)/83(7) vs 139 (14)/85(7) mmHg (NS). CONCLUSION/INTERPRETATION: Pregnancy has no adverse long-term impact on kidney function and survival in Type I diabetic patients with well-preserved kidney function (normal serum creatinine) suffering from diabetic nephropathy.

Adult↗
PubMed2002

Analysis of scenarios for sewerage, wastewater treatment and prioritised load on environment from the Greater City of Copenhagen.

The sewer system for the Greater Copenhagen area covers an area of 4460 ha contributing to the runoff. The total area serves in total 8 municipalities, however it is dominated by the areas in the City of Copenhagen proper. The catchments merge into interceptors, which feed two large treatment plants. The effluent from the two treatment plants discharges during dry weather to Oresund, the sound between Denmark and Sweden. This large system has been analysed for selected scenarios with respect to handling runoff in an optimal way in order to minimise the loads on the most sensitive receiving waters and optimising treatment plant performance.

Cities↗
PubMed2001

A key role for Pax7 transcripts in determination of muscle and nerve cells.

Embryonic teratocarcinoma mouse cells (P19) and embryonic NIH3T3 fibroblasts were induced chemically to differentiate along neurogenic or myogenic lineages. The expression profiles of Pax7 alternate transcripts were then assessed by RNA isolation and RT-PCR. Only two transcripts, Pax7b and Pax7d, were expressed in the neurogenic lineage. By contrast, in adult skeletal muscle, four transcripts, Pax7a-d, were expressed in the myogenic lineage. Moreover, P19 cells were shown to undergo neural cell differentiation when stably transfected with a single Pax7 transcript, PAX7b, generated from human skeletal muscle. Our results suggest a key role for Pax7 transcripts in lineage determination.

Animals↗
PubMed2001

[Gastrointestinal decontamination. Use in non-drug poisoning].

AIM: To assess whether Danish doctors use gastrointestinal decontamination (GID) in non-drug poisoning in accordance with recommendations for restricted application. METHOD: Doctors telephoning the Danish Poisons Information Centre about non-drug exposures were surveyed prospectively. The doctor's intention to treat, the age and sex of the patient, and information about poison, amount and time since exposure, were assessed. RESULTS: Of the 138 telephone calls, 64% concerned children below 5 years of age and 24% patients above 15 years of age. The risk was estimated as insignificant in 63%, minor in 30%, significant in 6% and severe in only 1%. The insignificant risk was found mainly in children and the severe risk solely in those above 15 years of age. GID was proposed in 33% with the highest frequency in children with minor or insignificant risks, and the time since exposure did not influence the frequency of GID. Charcoal was not proposed. CONCLUSION: It is clear from this small sample that Danish doctors tend to use GID more often than is recommended. Activated charcoal was apparently not used. GID was in most cases used in children with insignificant and minor risks, where it is likely to do more harm than good.

Adult↗
PubMed2001

Risk assessment by physicians and by the poison center: are nondrug exposures handled too actively?

BACKGROUND: The study was intended to evaluate the possible impact of poison center advice on physicians' treatment and referral of nondrug exposures. METHODS: Doctors seeking advice on nondrug poisoning were asked for their management plan before any recommendations were given. The proportions of cases in different treatment and referral categories were compared to the poison center recommendations. Rate ratios were used as effect measure. RESULTS: A total of 175 cases were included in the study. For 90% of these, the exposure was estimated by the poison center to be of no or minor risk. The inquiring physicians had intended to treat 43 more cases than the poison center recommended, rate ratios: 1.6 (95% CI: 1.3-2.0). The most marked difference wasfor treatment by gastrointestinal decontamination, rate ratios: 5.0 (95% CI: 2.5-9.8). For referral, 42 more cases would have been observed in a stationary hospital unit, rate ratios: 2.3 (95% CI: 1.6-3.3) and 28 excess cases would have been observed in an outpatientfacility, rate ratios: 2.0 (95% CI: 1.3-1.6). A more active attitudefor treatment and referral by the inquirers was independently associated with patients < or =14 years of age, lack of symptoms at presentation, and insignificant exposures. CONCLUSIONS: Doctors seeking advice on the management of nondrug poisoning intended to treat and refer to health care facilities more actively than recommended by the poison center. The tendency was most pronouncedfor children exposed to substances of minor toxicological significance and treatment with gastrointestinal decontamination.

Humans↗
PubMed2000

Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor.

1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine (NNC 45-0095) is a novel compound which represents the parent pharmacophore structure of a series of pyrrolo[2,1,5-cd]indolizine derivatives with mixed estrogen agonist/antagonist properties. NNC 45-0095 binds with high affinity to the estrogen receptor (IC50=9.5 nM) and exhibits full protection of bone loss in the ovariectomized mouse model for post-menopausal osteoporosis.

Animals↗
PubMed2000

Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy.

AIMS: Elevated urinary albumin excretion is associated with macrovascular atherosclerotic complications in Type 1 diabetes mellitus. Adhesion molecules mediate leucocyte adhesion to the endothelium early in the atherosclerotic process. The present study tests the hypothesis that microalbuminuria and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess cardiovascular disease in diabetic patients with renal complications. METHODS: Soluble adhesion molecule concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in healthy controls (n = 16) and in 59 Type 1 diabetic patients: group 1-patients with normoalbuminuria (n = 16); group 2-patients with microalbuminuria (n = 15); group 3-patients with macroalbuminuria and normal serum creatinine (n = 15), group 4-patients with macroalbuminuria and moderately elevated serum creatinine (n = 13). RESULTS: Plasma concentrations of sVCAM-1 and sICAM-1 were similar in healthy controls and normoalbuminuric Type 1 diabetic patients, but the concentrations were increased by the presence of microalbuminuria and overt nephropathy (P < 0.001 and P < 0.0001, ANOVA). Concentrations of sE-selectin did not differ between diabetic patients and controls. CONCLUSIONS: Plasma concentration of sICAM-1 is elevated in Type 1 diabetic patients with microalbuminuria and the concentrations of sICAM-1 as well as sVCAM-1 are elevated in patients with macroalbuminuria and normal s-creatinine. The elevated plasma concentrations of these soluble adhesion molecule concentrations in patients with renal complication can be of pathogenetic importance for the development of atherosclerosis and plasma soluble adhesion molecule concentrations may provide additional information on cardiovascular risk.

Adult↗
PubMed1999

[Lung damage after use of conditioner sprays for leather and textiles].

A series of poisoning cases have been caused by private spraying of leather and textiles with a conditioner. Symptoms and signs from the airways as well as general symptoms have not been explained by any of the ingredients. Spray impregnation should be carried out where efficient ventilation is available.

Aerosols↗
PubMed1999

Measurement of depressive symptoms in cancer patients: evaluation of the Center for Epidemiological Studies Depression Scale (CES-D).

The Center for Epidemiological Studies Depression Scale (CES-D) is commonly used to measure depressive symptomatology in cancer patients, yet there is little known about the psychometric properties of the measure when applied to a cancer population. The aim of this study was to examine the psychometric properties of the CES-D with cancer patients. For purposes of comparison, the psychometric properties of the CES-D were assessed both in women undergoing treatment for breast cancer and women with no history of cancer. The CES-D and other study measures were administered to women undergoing treatment for breast cancer on two occasions: prior to treatment and midway through treatment. The measures were also administered to a group of women similar in age to the cancer patients who had no history of any type of cancer. These healthy comparison subjects were also assessed on two separate occasions. The CES-D was found to have good internal consistency, with alpha coefficients > 0.85 for both groups, as well as adequate test-retest reliability in both groups. Construct validity was demonstrated in two ways, via comparisons between the groups and by comparing the CES-D with measures of fatigue, anxiety, and global mental health functioning. The CES-D was established as a valid and reliable measure of depressive symptomatology in this sample of breast cancer patients. This measure may be appropriate for use in clinical psychosocial research with cancer patients, yet further research is needed to evaluate its usefulness in other cancer populations. The importance of measuring psychological symptoms with standard measures that have been validated with cancer patients is highlighted.

Adolescent↗
PubMed1999

Breakthrough pain: characteristics and impact in patients with cancer pain.

Few surveys have been performed to define the characteristics and impact of breakthrough pain in the cancer population. In this cross-sectional survey of inpatients with cancer, patients responded to a structured interview (the Breakthrough Pain Questionnaire) designed to characterize breakthrough pain, and also completed measures of pain and mood (Memorial Pain Assessment Card (MPAC)), pain-related interference in function (Brief Pain Inventory (BPI)), depressed mood (Beck Depression Inventory (BDI)), and anxiety (Beck Anxiety Inventory (BAI)). Of 178 eligible patients, 164 (92.2%) met the criteria for controlled background pain. The median age was 50.6 years (range 26 to 77 years), 52% were men, and 80.6% were Caucasian. Tumor diagnoses were mixed, 75% had metastatic disease, 65% had pain caused directly by the neoplasm, and a majority had mixed nociceptive-neuropathic pain. The median Karnofsky Performance Status score was 60 (range 40 to 90). Eighty-four (51.2%) patients had experienced breakthrough pain during the previous day. The median number of episodes was six (range 1 to 60) and the median interval from onset to peak was 3 min (range 1 s to 30 min). Although almost two-thirds (61.7%) could identify precipitants (movement 20.4%; end-of-dose failure 13.2%), pain was unpredictable in a large majority (78.2%). Patients with breakthrough pain had more intense (P < 0.001) and more frequent (P < 0.01) background pain than patients without breakthrough pain. Breakthrough pain was also associated with greater pain-related functional impairment (difference in mean BPI. P < 0.001), worse mood (mood VAS, P < 0.05; BDI, P < 0.001), and more anxiety (BAI, P < 0.001). Multivariate analysis confirmed that breakthrough pain independently contributed to impaired functioning and psychological distress. These data confirm that cancer-related breakthrough pain is a prevalent and heterogeneous phenomenon. The presence of breakthrough pain is a marker of a generally more severe pain syndrome, and is associated with both pain-related functional impairment and psychological distress. The findings suggest the need for further studies of breakthrough pain and more effective therapeutic strategies.

Adult↗