Biomedical subjects

L Brudin

Publications and source records attributed to L Brudin.

At least 19 recordsLinked to original sources

PubMed2007

Increased plasma levels of asymmetric dimethylarginine in patients with carotid stenosis: no evidence for the role of the common FABP2 A54T gene polymorphism.

OBJECTIVE: Both asymmetric dimethylarginine (ADMA), which is an inhibitor of endothelial nitric oxide synthase and the fatty acid-binding protein 2 (FABP2) A54T gene polymorphism have been associated with cerebrovascular disease. The objective of the present study was to investigate the role of ADMA and the FABP2 A54T polymorphism in carotid atherosclerosis. MATERIAL AND METHODS: 54 patients with severe carotid stenosis and 54 matched controls without significant carotid stenosis were compared. ADMA was analysed with an ELISA method. The FABP2 A54T polymorphism was determined with a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Patients with carotid stenosis had higher ADMA levels (0.76 +/- 0.16 micromol/l) than the controls (0.70 +/- 0.14 micromol/l, P < 0,01). Allele and genotype frequencies of the FABP2 polymorphism did not differ between patients and controls. CONCLUSIONS: ADMA levels in subjects with carotid stenosis are increased which emphasize the role of ADMA as a novel risk factor for atherosclerosis and future cardiovascular risk. The FABP2 A54T polymorphism is not associated with severe carotid stenosis.

Aged↗

PubMed2005

Asymmetric dimethylarginine (ADMA) as a risk marker for stroke and TIA in a Swedish population.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been shown to be involved in the pathogenesis of atherosclerosis. The present study was initiated to investigate the role of ADMA as a risk marker of acute cerebrovascular disease (CVD). We examined 363 CVD patients and 48 controls. The ADMA concentration (mean+/-S.D., mumol/L) in controls was 0.50 +/- 0.06. Compared to controls, increased concentrations of ADMA were observed in cardio-embolic infarction (0.55 +/- 0.08; p < 0.001; n = 71), and TIA (0.54 +/-0 .05; p < 0.001; n = 31), but not in non-cardio-embolic infarction (0.51 +/- 0.07; p = 0.56; n = 239) and haemorrhagic stroke (0.51 +/- 0.11; p = 0.77; n = 22). In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group (odds ratio for highest versus lowest quartile 13.1; 95% CI: 2.9-58.6; p trend 0.001) A decreased arginine/ADMA ratio was significantly associated with CVD in the entire study population (p < 0.01). Our results indicate that ADMA is a weak independent marker for acute stroke and a strong marker for TIA and that relative arginine deficiency, measured as the l-arginine/ADMA ratio, is present in acute CVD.

Acute Disease↗

PubMed2004

Stability of faecal hepatocyte growth factor determination.

In order to evaluate the accuracy and reproducibility of determination of hepatocyte growth factor (HGF) levels in faeces, the stability of HGF in samples processed in different ways was investigated. An ELISA method was used for determination of HGF concentrations. Faeces samples from healthy controls and patients with infectious diarrhoea were studied. It was found that faeces HGF concentration remained stable irrespective of whether samples were freeze-thawed several times, kept for 6, 12 or 24 h at room temperature or refrigerated for 6, 12, 24 or 36 h; the levels of HGF did not change significantly when samples were freeze-dried. Adding protease inhibitor to the faeces samples did not affect the HGF levels. There were no significant differences between HGF levels using phosphate buffered saline (PBS) (pH 7.4) or NaCL as buffer, but it was observed that levels of HGF were significantly lower in the samples that were diluted in distilled water. Although both HGF and albumin through various mechanisms may increase in faeces during infectious diarrhoea, there was no significant correlation between faeces HGF levels and albumin levels, which might indicate local production of HGF in the bowel in response to infection. It is concluded that determination of faeces HGF levels is feasible with a high degree of stability. Increased HGF levels in faeces might represent a local production of HGF during bowel injury and might be of use as a diagnostic and monitoring assay.

Adolescent↗

PubMed2004

A comparison of bispectral index and rapidly extracted auditory evoked potentials index responses to noxious stimulation during sevoflurane anesthesia.

In 21 patients given sevoflurane anesthesia, we simultaneously compared the abilities of Bispectral Index (BIS) and rapidly extracted auditory evoked potentials index (AAI) to display the effect of an increasing cerebral concentration of sevoflurane, with and without noxious stimulation. In addition to BIS/AAI, hemodynamic variables were monitored. After titrating sevoflurane to BIS = 50-55 during 15 min, the end-tidal concentration of sevoflurane (1.46% +/- 0.20%) was doubled followed by a noxious stimulus, laryngoscopy, applied at random time points within the following 15 min. After the end-tidal concentration of sevoflurane was doubled, a substantial reduction in BIS was observed, whereas only a slight reduction in AAI was seen (P < 0.0001). BIS/AAI responses to laryngoscopy were not attenuated with increasing wash-in of sevoflurane. After noxious stimulation, AAI exceeded the highest recommended value, 25, in 3 cases, whereas BIS did not exceed the recommended threshold, 60, in any of the patients. Response times for BIS and AAI were 44.5 +/- 26 and 47 +/- 31 s, respectively. These results suggest that, at a hypnotic level associated with surgical sevoflurane anesthesia, BIS better displays drug-related alterations in the level of hypnosis than AAI or hemodynamic variables but there is no difference between BIS and AAI in the time to response to a noxious stimulus.

Adult↗

PubMed2003

Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading.

BACKGROUND: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. METHODS: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). RESULTS: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 micromol/L, mean +/- SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 micromol/L, both p<0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 +/- 5.9 and 0.66 +/- 0.10 micromol/L, both p<0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 micromol/L, both p<0.001). However, the corresponding ADMA levels did not increase (0.73 +/- 0.17 and 0.76 +/- 0.22 vs. 0.70 +/- 0.10 micromol/L, both not significant). CONCLUSIONS: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions.

Administration, Oral↗

PubMed2002

Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia.

Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF-concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4-7 days while HGF values in breath condensate remained elevated even after 4-6 weeks. These results might imply local product on of HGF in the lungs and a long repair and healing process after pneumonia.

Adult↗

PubMed2002

Incidence and prognosis in early onset breast cancer.

The aim of this study was to assess the incidence and prognosis in early onset breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women diagnosed with breast cancer under the age of 40 between 1960 and 1996 was studied using data from the Swedish Cancer Registry and Swedish Death Cause Registry. A total of 107 consecutive young patients with invasive breast cancer undergoing surgery during 1980-1993 in the Southeast Swedish health care region were retrospectively followed up and their cancers reviewed and graded blindly. The median follow-up time was 11.2 years. The applicability of the Nottingham Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node status, tumour size, S-phase fraction and steroid receptor content were related to survival univariately and multivariately in a Cox proportional hazard analysis. The incidence of early onset breast cancer has increased moderately and the survival rate has not improved during the last 35 years. When young women are diagnosed with breast cancer their tumours are larger, their lymph nodes more often involved, and the median grade higher than in older with 64% having grade 3 tumours. Lymph node status was the strongest sole prognostic indicator but the use of NPI gave more accurate prognostic information than node status alone.

Journal Article↗

PubMed2002

High serum hepatocyte growth factor levels in the acute stage of community-acquired infectious diseases.

Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p < 0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly (r=0.65, p < 10(-7)). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.

Acute Disease↗

PubMed2002

Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study.

BACKGROUND: Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years. OBJECTIVE: To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers. METHODS: HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented. RESULTS: It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated (r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies. CONCLUSION: This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

Aged↗

PubMed2001

The mode of left ventricular pumping: is there an outer contour change in addition to the atrioventricular plane displacement?

The outer contour of the heart has in some studies been shown to be constant during the heart cycle and the epicardial apex almost stationary whilst the base of the ventricles moves towards apex during systole. The base of the left ventricle has been regarded as a cylinder with constant cross-sectional area with changes in height during the heart cycle, the latter corresponding to the amplitude of mitral annulus motion (MAM). In this echocardiographic study, including 20 healthy adults, the stroke volume calculated by the cylinder model was significantly lower than by a reference method (modified Simpson's rule). MAM explained 82% of the stroke volume and 18% must, therefore, be explained by an inward motion of the outer left ventricular wall. A mean outer diameter shortening of about 3% (about 2 mm) was calculated.

Adolescent↗

PubMed2000

Hepatocyte growth factor levels in cerebrospinal fluid: a comparison between acute bacterial and nonbacterial meningitis.

The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P<.001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

Acute Disease↗

PubMed2000

A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer.

Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2-11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.

Adult↗

PubMed2000

Indicators of loco-regional recurrence in breast cancer. The South East Swedish Breast Cancer Group.

AIM: The aim of the investigation was to contribute to the identification of patients who have increased or decreased risk of loco-regional recurrence. METHODS: Six hundred and twenty-nine consecutive patients with primary breast cancer diagnosed between 1988 and 1990 were studied. Two-thirds of the patients underwent mastectomy. Radiotherapy was administered if patients were node positive or breast conserved. The Nottingham histological grading protocol was used and presence of lymphovascular invasion was assessed. Investigated parameters were: age, size, grade, steroid receptor content, surgical radicality, vascular invasion and nodal status. Statistically significant risk factors for loco-regional recurrence using univariate or Cox proportional hazard analysis were grade and lymphovascular invasion. RESULTS: Women with grade 1-2, node-negative tumours without vascular invasion had a very low loco-regional recurrence rate-3.1%. Seventeen percent of patients with grade 3 tumours and vessel invasion had loco-regional recurrence. CONCLUSIONS: Our findings, and those of others, indicate that the use of adjuvant radiotherapy should be influenced to a greater extent by grade and lymphovascular invasion.

Adult↗

PubMed1999

Applying the Nottingham Prognostic Index to a Swedish breast cancer population. South East Swedish Breast Cancer Study Group.

The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988-91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1-5 and 32% of those with an index sum 5.1-6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.

Adult↗

PubMed1998

Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis.

BACKGROUND: The results of retrospective and prospective case-control studies have clearly established that mild elevations of the plasma homocysteine level are associated with increased risk of coronary, cerebral, and peripheral vascular disease. Recently, a mutation (677C-->T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene that results in reduced folate-dependent enzyme activity and reduced remethylation of homocysteine to methionine. Mutant homozygotes (TT genotype) constitute approximately 12% of the white population and frequently have mildly elevated circulating homocysteine. Therefore, it seems likely that they would also be at increased risk of vascular disease. A number of studies have investigated this during the past 3 years, and the present article evaluates the results in a meta-analysis. METHODS AND RESULTS: We identified 13 studies in which there were measurements of plasma homocysteine in relation to the 3 genotypes (TT, CT, and CC) and 23 case-control studies comprising 5869 genotyped cardiovascular disease patients (mostly coronary artery disease) and 6644 genotyped control subjects. Those bearing the TT genotype had plasma homocysteine concentrations 2.6 micromol/L (25%) higher than those with the CC genotype. However, there was no difference between patients and control subjects either in the frequency of mutant alleles (T) (34.3% versus 33.8%) or the TT genotype (11.9% versus 11.7%). In the analysis of the 23 studies, the relative risk (OR) of vascular disease associated with the TT genotype was 1.12 (95% CI, 0.92 to 1.37). CONCLUSIONS: We conclude that although the C677T/MTHFR mutation is a major cause of mild hyperhomocysteinemia, the mutation does not increase cardiovascular risk. Our findings suggest that the mild hyperhomocysteinemia found frequently in vascular disease patients is not causally related to the pathogenesis of the vascular disease.

Cardiovascular Diseases↗

PubMed1998

A common methylenetetrahydrofolate reductase gene mutation and longevity.

Homozygotes (TT genotype) for the C677T mutation in the gene of methylenetetrahydrofolate reductase (C677T/MTHFR mutation) constitute about 12% of the Caucasian population. They have mild hyperhomocysteinemia which is an established risk factor for cardiovascular disease. If the mutation is associated with premature death its prevalence is expected to be lower in the elderly than in the young. To test this we determined the C677T/MTHFR genotypes in 220 newborn and 222 elderly 80-108-year-old Swedes. In the newborn and elderly, the allele frequency, of the C677T/MTHFR mutation was 29.1 and 27.0% and the mutant homozygote frequency was 10.0 and 9.5%, respectively. In a meta analysis of the present and three previous studies including a total of 1388 elderly and 1415 younger subjects, the odds ratio (OR) representing the likelihood of the TT genotype to attain old age relative to the CC genotype was 0.87 (95% confidence interval (CI), 0.69-1.11) and relative to both the CC and CT genotypes was 0.83 (95% CI, 0.66-1.04). This finding does not suggest that the C677T/MTHFR mutation is a strong risk factor for diseases frequently leading to premature death.

Aged↗

PubMed1998

Hepatocyte growth factor (HGF) in patients with pneumonia: a comparison between survivors and non-survivors.

Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n = 14), Group 2 was survivors with abnormal liver function (n = 31) and Group 3 was non-survivors (n = 10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

Aged↗

PubMed1998

Intraprostatic temperature monitoring during transurethral microwave thermotherapy for the treatment of benign prostatic hyperplasia.

PURPOSE: We evaluated whether the results of transurethral microwave thermotherapy improve using high intraprostatic temperatures of 55C or greater. MATERIALS AND METHODS: We accrued 30 men 58 to 85 years old (mean age 69) from the waiting list for transurethral prostatic resection in whom maximum urinary flow was less than 13 ml. per second and Madsen score was greater than 8. According to the Abrams-Griffith nomogram all but 1 patient had obstruction. Before treatment 3 thin temperature probes, each containing 5 sensors in a row, were introduced into the prostate from the perineum and positioned using transurethral ultrasound guidance. The microwave power of the transurethral microwave thermotherapy equipment was set based on the actual temperature in the prostatic tissue. A temperature of at least 55C and often more than 60C was reached at the hottest spot. Treatment duration was 1 hour. Postoperatively an indwelling catheter remained in place for 2 weeks. Patients were followed for 6 months with the first followup after 3 months. RESULTS: At the 3-month followup mean maximum urinary flow had increased from 7.4 to 12.5 ml. per second and the mean Madsen score had decreased from 12.6 to 2.9. At the 6-month followup mean maximum urinary flow was 12.2 ml. per second and the mean Madsen score was 3.4. Using pressure-flow data we divided the patients into responders and nonresponders. In the 18 responders maximum urinary flow had increased from 7.2 to 14.6 ml. per second (103%), the Madsen score had decreased from 12.5 to 1.4 (89%) and detrusor pressure had decreased from 9.2 to 6 kPa. (35%). CONCLUSIONS: High energy transurethral microwave thermotherapy relieved bladder outlet obstruction in 60% of the patients and had a good effect on symptoms. Compared with a previous multicenter study with 40% responders, using the same criteria there were 60% responders in our series. Our results indicate that better control of intraprostatic temperature provides better results, approaching those after transurethral prostatic resection.

Aged↗