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Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 73 records · Page 4Linked to original sources
PubMed1999

Utilization of cardiovascular drugs (blood pressure lowering drugs, lipid lowering drugs and nitrates) and mortality from ischaemic heart disease and stroke. An ecological analysis based on Sweden's municipalities.

OBJECTIVE: To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between sales of nitrates and mortality from stroke and IHD. METHODS: Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other than the tested drug group and location of the municipality. RESULTS: Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure, geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering drugs persisted. CONCLUSION: Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of nitrates needs more investigation at the individual level.

Antihypertensive Agents↗
PubMed1999

Use of oral contraceptives and endometrial cancer risk (Sweden).

OBJECTIVES: To estimate the magnitude and persistence of the protective effect of use of combined oral contraceptives (COCs) and endometrial cancer risk. METHODS: We performed a nation-wide, population-based case-control study among postmenopausal women aged 50-74 years in Sweden, which included 709 subjects with incident, histopathologically verified endometrial cancer, and 3,368 controls with an intact uterus. We used unconditional logistic regression to calculate odds ratios as estimates of relative risks. RESULTS: Use of any sort of oral contraceptive decreased risk for endometrial cancer by 30%, while progestin-only pills reduced risk more markedly. For COCs the reduction in risk was noticeable following 3 or more years of use (OR 0.5, 95% CI 0.3-0.7), and increased with duration of intake, reaching 80% lower risk after 10 years of use. The protective effect of COC use was similar for all degrees of tumor differentiation and invasiveness, and remained for at least 20 years after cessation of use. Subsequent use of hormone replacement did not modify these protective effects. CONCLUSIONS: We conclude that COC use confers a long-lasting protection against endometrial cancer risk which is particularly marked for long-term users.

Age Distribution↗
PubMed1999

Holotranscobalamin - a sensitive marker of cobalamin malabsorption.

BACKGROUND: No simple and reliable method of identifying patients with cobalamin malabsorption is available at present. The measurement of plasma holotranscobalamin, i.e. the metabolically active cobalamins bound to the transport protein transcobalamin, has been suggested as a means of fulfilling such criteria. DESIGN: We describe a method that directly quantifies cobalamins attached to transcobalamin. The method is evaluated in patients referred for gastrointestinal examination because of suspected cobalamin malabsorption. RESULTS: Of the 101 patients referred, all 48 with gastrointestinal conditions compatible with cobalamin malabsorption had plasma holotranscobalamin below 35 pmol L-1 (interval of 35-160pmol L-1). None of the patients with plasma holotranscobalamin above the lower reference limit had conditions compatible with cobalamin malabsorption. CONCLUSION: The values obtained for plasma holotranscobalamin showed a better correlation with possible malabsorption than the values obtained for plasma cobalamins. The specificity of the test, however, needs to be elucidated further.

Adolescent↗
PubMed1999

10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial.

PURPOSE: To study the long-term effectiveness of postoperative radiotherapy after sector resection for breast cancer in a randomized trial in which mammography is a major pathway to diagnosis. PATIENTS AND METHODS: Three hundred eighty-one women with a unifocal breast cancer < or = 20 mm in diameter on the preoperative mammogram and without histopathologic signs of axillary metastases were treated by sector resection plus axillary dissection. Of these patients, 184 women were randomized to receive postoperative radiotherapy to the breast (XRT group), and 197 women received no further treatment (non-XRT group). RESULTS: The local recurrence rate was 8.5% (95% confidence interval [CI], 3.9% to 13.1%) in the XRT group and 24.0% (95% CI, 17.6% to 30.4%) in the non-XRT group (P =.0001). Survival free from regional and distant recurrence was 83. 3% in the XRT group (95% CI, 77.5% to 89.1%) and 80.0% in the non-XRT group (95% CI, 73.9% to 86.1%) (P =.23). Overall survival was 77.5% in the XRT group (95% CI, 70.9% to 84.1%) and 78% in the non-XRT group (95% CI, 71.7% to 84.3%) (P =.99). A subgroup analysis suggested that women older than 55 years of age without comedo or lobular carcinomas had a low risk of local recurrence of 6.1% (95% CI, 0.1% to 9.1%) in the XRT-group and 11.0% (4.0% to 18.0%) in the non-XRT group (P =.16). CONCLUSION: Sector resection plus radiotherapy resulted in an absolute reduction in local recurrence of 16% at 10 years compared with surgery alone. Women older than 55 years of age without comedo or lobular carcinomas may have a low risk of local recurrence. Postoperative radiotherapy was not shown to reduce distant recurrences or improve overall survival.

Breast Neoplasms↗
PubMed1999

Radiological diagnosis of acute stroke. Comparison of conventional MR imaging, echo-planar diffusion-weighted imaging, and spin-echo diffusion-weighted imaging.

PURPOSE: To compare conventional MR imaging, echo-planar diffusion-weighted imaging (EP-DWI) and spin-echo diffusion-weighted imaging (SE)-DWI at radiological diagnosis of acute stroke. MATERIAL AND METHODS: Twenty-seven patients (30-85 years old) were examined. Clinical examination was performed before MR imaging. All MR examinations were assessed by an experienced neuroradiologist blinded to clinical findings. RESULTS: In EP-DWI, every patient had a lesion corresponding to the clinical findings. EP-DWI was used as the gold standard. In conventional PD+T2 imaging, 23/59 focal lesions were interpreted as acute, which was false in 11 lesions, and 36/59 lesions were considered to be old, 6 were in fact acute. Nine acute lesions were only detected retrospectively and 12 acute lesions were not detected at all on PD+T2. SE-DWI including the apparent diffusion coefficient correlated fairly well with EP-DWI but the procedure was impractical. CONCLUSION: EP-DWI is reliable for diagnosis of early ischemic stroke, while SE-DWI performs reasonably well. Conventional PD+T2 imaging is not reliable for diagnosis of early ischemia.

Acute Disease↗
PubMed1998

Bioelectrochemical monitoring of phenols and aromatic amines in flow injection using novel plant peroxidases.

An amperometric flow system combined with a glucose oxidase-mutarotase reactor was optimized and used to determine aromatic amines and phenols using peroxidase-modified graphite electrodes. An increase in currents upon injection of the analyzed substrate was shown to be approximated by a Michaelis-Menten type dependence. The detection limit was calculated as 3 times the noise, and the sensitivity was calculated as Imax/K(m)app. Commercially available horseradish peroxidase was compared with tobacco anionic and peanut cationic peroxidases for determination of aromatic amines and phenols. Detection limits of 10 nM for determination of o-aminophenol and o- and p-phenylenediamine achieved with a tobacco peroxidase-modified electrode give a promise for further improvements in sensitivities and detection limits of biosensors.

Aniline Compounds↗
PubMed1998

Optimisation of a heterogeneous non-competitive flow immunoassay comparing fluorescein, peroxidase and alkaline phosphatase as labels.

Off- and on-line strategies for a non-competitive heterogeneous flow immunoassay were developed comparing three different labels. The samples, containing the model compounds digoxin or digoxigenin, were either pre-incubated off-line or on-line in a mixing coil with excess of labelled anti-digoxigenin Fab-fragments. The excess of Fab-fragments was then separated from the digoxin bound Fab-fragments by passing the sample through a column with immobilised digoxin. The off-line immunochemical detection system is suitable for sensitive high through-put screening of the analytes, whereas the on-line system is more suitable for coupling as a post-column detection unit to liquid chromatography. The digoxin and digoxigenin content in the sample were quantified using fluorescein (F) and enzyme (peroxidase (POD), alkaline phosphatase (AP)) labelled Fab-fragments. The fluorescein label was directly measured with the fluorescence detector, whereas a fluorescent enzyme product was measured in the two enzyme based systems, using 3-(p-hydroxyphenyl)-propionic acid (HPPA) and hydrogen peroxide for POD and, and 4-methylumbelliferyl phosphate (4-MUP) for AP. The highest sensitivity and lowest limit of detection (LOD) was obtained with the Fab-POD system with LODs for digoxin and digoxigenin in the off- and on-line configurations of 0.025 and 0.01 nM, respectively. The sample through-put for the off- and on-line systems were 43 and 32 samples per hour, respectively.

Alkaline Phosphatase↗
PubMed1998

Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.

OBJECTIVES: Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency. DESIGN: Clinical study of consecutive patients. SETTING: The catchment area of Sahlgrenska University Hospital, Göteborg. SUBJECTS: A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery. INTERVENTIONS: Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin. MAIN OUTCOME MEASURES: Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin. RESULTS: About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests. CONCLUSIONS: Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.

Adult↗
PubMed1998

Role of echocardiography in systemic arterial embolism. A review with recommendations.

The ability of echocardiography to diagnose sources of embolism and the role of the examination in the prediction of thromboembolism are reviewed. In addition, the yield of transthoracic (TTE) and transoesophageal echocardiography (TEE) is analysed in patients with suspected embolism and guidelines are proposed for performing echocardiography in this setting. In general, echocardiography is reliable for diagnosing sources of embolism and this applies in particular to TEE in the case of atrial, valvular, and aortic abnormalities. However, the method is useful for predicting embolism in a few cases only. There is a substantial risk in the event of mobile or protruding thrombi, but screening for these and other markers of thromboembolism seems to be unproductive in most groups of risk patients. Yet, in the presence of atrial fibrillation, echocardiography may be helpful in defining patients with an otherwise normal heart and low risk of embolism--and in defining the relatively rare patient with a clinically low-risk profile but moderate-to-severe left ventricular systolic dysfunction and a high risk of embolism. TEE-guided conversion of atrial fibrillation without weeks of preceding anticoagulation may prove useful, after further investigation. The risk of embolism in relation to the size and mobility of valvular vegetations has remained controversial. In patients with suspected recent embolism, TTE results in less than 5% new therapeutic consequences. In those with a normal TTE, the yield of TEE seems to be equally low. We therefore recommend a selective strategy: TTE and TEE can be omitted when a cardiac source of embolism appears from the clinical setting and in most patients with an obvious predisposition to cerebrovascular disease. However, in the latter cases TTE should be performed if indicated by the clinical situation, e.g. in the presence of fever and murmur. TTE is also recommended when there are no obvious markers of primary vascular disease. To preclude very rare sources of embolism (e.g. atrial thrombi despite sinus rhythm), supplementary TEE is recommended in younger patients in whom primary vascular disease is very unlikely. The diagnosis by TEE of common conditions such as atrial septal aneurysms and patent foramen ovale cannot, however, be taken as proof of the mechanism of a systemic arterial occlusive event; thus it is difficult to change therapy on the basis of such diagnoses.

Algorithms↗
PubMed1998

Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.

OBJECTIVES: To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. DESIGN: Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. SETTING: The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: Ninety seven consecutively referred patients. MAIN OUTCOME MEASURES: Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. RESULTS: Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. CONCLUSION: Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.

Adult↗
PubMed1998

Sensorimotor stroke; clinical features, MRI findings, and cardiac and vascular concomitants in 32 patients.

BACKGROUND AND PURPOSE: Sensorimotor stroke (SMS) is often included among the lacunar syndromes, although the underlying cause of this stroke-subtype is less well documented. To this end we analysed 32 patients presenting with a sensorimotor syndrome. METHODS: The study protocol included vascular risk factors, echocardiography, Doppler sonography of carotid arteries, CT scan and MRI of the brain. RESULTS: There were 23 men and 9 women, mean age 65.7 years. Hypertension was present in 28% and diabetes in 19%. In all, 63% had sensorimotor deficit of faciobrachiocrural areas and 37% had faciobrachial or brachiocrural deficits. MRI disclosed a presumably relevant infarct in 26 patients (81%); 20 patients (62%) localized to the territory of small perforating arteries, 3 patients (9.5%) in the internal borderzone, and 3 patients (9.5%) in cortical territories. Eight of 20 deep infarcts were larger than 15 mm. No hemorrhage or non-vascular lesion was found. A potential cardioembolic source was present in 5 patients (16%), whereas 2 patients (6%) had an ipsilateral carotid stenosis >50%. CONCLUSIONS: Small vessel disease was the most likely cause in 69% of our patients with SMS, whereas 31% had a potential cardioembolic source, large artery disease or infarcts not compatible with perforating artery disease.

Adult↗
PubMed1998

Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers.

PURPOSE: To investigate the prognostic and predictive value of c-erbB-2 overexpression in breast cancer in relation to other prognostic markers. PATIENTS AND METHODS: Paraffin-embedded tumors from 315 consecutive primary breast cancer patients were screened for c-erbB-2 protein (p185) overexpression by immunohistochemistry using the monoclonal antibody CB11. RESULTS: c-erbB-2 protein overexpression was detected in 19% of tumors and was associated with shorter 5-year overall survival (OAS) rate compared with c-erbB-2-negative cases in the total patient material (58% and 77%, respectively; P = .004) and in the 96 node-positive patients (31% and 61%, respectively; P = .02), but not in node-negative patients. For 47 node-positive patients treated with adjuvant tamoxifen and radiotherapy, the 5-year OAS was 13% for c-erbB-2 overexpression and 75% for c-erbB-2-negative patients (P = .00004). The frequency of c-erbB-2 overexpression decreased with age at diagnosis. The prognostic value of c-erbB-2 on OAS was independent of age, node status, tumor size, histopathologic grade, hormone receptor status, S phase, p53 status, and adjuvant treatment. c-erbB-2 status added prognostic information to p53-negative and low S-phase cases, but not to p53-positive and high S-phase cases. Correspondingly, these only added information to c-erbB-2-negative cases. CONCLUSION: c-erbB-2 protein overexpression may have a predictive value with regard to adjuvant therapy in node-positive patients, for whom adjuvant tamoxifen with radiotherapy appears insufficient in the presence of c-erbB-2 overexpression. Combination of conventional and newer tumor markers may identify patients with a worse prognosis within groups with a generally favorable prognosis.

Adult↗
PubMed1998

Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes P450 2D6 and 3A in human liver microsomes.

Tolterodine, a new muscarinic receptor antagonist, is metabolized via two pathways: oxidation of the 5-methyl group and dealkylation of the nitrogen. In an attempt to identify the specific cytochrome P450 enzymes involved in the metabolic pathway, tolterodine was incubated with microsomes from 10 different human liver samples where various cytochrome P450 activities had been rank ordered. Strong correlation was found between the formation of the 5-hydroxymethyl metabolite of tolterodine (5-HM) and CYP2D6 activity (r2, 0.87), as well as between the formation of N-dealkylated tolterodine and CYP3A activity (r2, 0.97). When tolterodine was incubated with human liver microsomes in the presence of compounds known to interact with different P450 isoforms, quinidine was found to be the strongest inhibitor of the formation of 5-HM. Ketoconazole and troleandomycin were found to be the strongest inhibitors of the formation of N-dealkylated tolterodine. A weak inhibitory effect on the formation of N-dealkylated tolterodine was found with sulfaphenazole, whereas tranylcypromine did not inhibit the formation of this metabolite. Microsomes from cells overexpressing CYP2D6 formed 5-HM, whereas N-dealkylated tolterodine was formed by microsomes expressing CYP2C9, -2C19, and -3A4. The Km for formation of N-dealkylated tolterodine by CYP3A4 was similar to that obtained in human liver microsomes and higher for CYP2C9 and -2C19. We conclude from these studies that the formation of 5-HM is catalyzed by CYP2D6 and that the formation of N-dealkylated tolterodine is predominantly catalyzed by CYP3A isoenzymes in human liver microsomes.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Cancer of the nasal cavity and paranasal sinuses: a series of 115 patients.

A total of 115 patients with sinonasal cancer was assessed during the period 1978-1995. Ninety-one patients received treatment with curative intent. A combination of irradiation and operation was used. The 5-year crude survival for patients, who were treated with curative intent, was 41%; the disease-specific survival throughout the period was 48%. Primary irradiation followed by maxillectomy was widely used in the first half of the period. Treatment in the last part was changed to primary lateral rhinotomy with post-operative irradiation whenever possible. Twelve maxillectomies were performed during the first half of the period, and during the last part, only two. Disease-specific survival was equal in the first and the second halves of the period.

Adenocarcinoma↗
PubMed1998

Biotransformation of tolterodine, a new muscarinic receptor antagonist, in mice, rats, and dogs.

Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms associated with an overactive bladder. The in vivo metabolism of 14C-labeled tolterodine was investigated in rats, mice, and dogs by analysis of blood and urine samples, whereas in vitro metabolism studies were performed by incubation of [14C]tolterodine with mouse, rat, dog, and human liver microsomes in the presence of NADPH. Tolterodine was extensively metabolized in vivo. Mice and dogs showed similar metabolite patterns, which correlated well with that observed in humans. In these species, tolterodine was metabolized along two different pathways, with the more important being the stepwise oxidation of the 5-methyl group to yield the 5-hydroxymethyl metabolite of tolterodine and then, via the aldehyde, the 5-carboxylic acid metabolite. The other pathway involved dealkylation of the nitrogen. In the subsequent phase II metabolism, tolterodine and the metabolites were conjugated with glucuronic acid to various degrees. Rats exhibited more extensive metabolism and a markedly different metabolite pattern, with metabolites also being formed by hydroxylation of the unsubstituted benzene ring. In addition, a gender difference was observed, with male rats showing more extensive metabolism than females. Incubation of [14C]tolterodine with liver microsomes yielded a total of five metabolites with rat liver microsomes and three with mouse, dog, and human liver microsomes. The 5-hydroxymethyl metabolite of tolterodine and N-dealkylated tolterodine were major metabolites in all incubations, representing 83-99% of total metabolism. Although the extent of metabolism varied among species, the metabolic profiles were similar. However, rat liver microsomes also formed metabolites hydroxylated in the unsubstituted benzene ring. These results show that the metabolism of tolterodine in mice and dogs corresponds to that observed in humans, whereas rats exhibit a different metabolite pattern.

Animals↗
PubMed1997

Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: a clinical study based on gastrointestinal histopathological findings.

We compared the sensitivity and specificity of the two metabolite tests, methylmalonic acid (MMA) and total homocysteine (Hcy) in serum, and serum cobalamin (Cbl) in patients referred to our hospital because of suspected cobalamin deficiency and a serum cobalamin value at the referring unit <200 pmol/L. All 111 patients included were investigated using upper gastrointestinal endoscopy with biopsy specimens taken from the gastric and duodenal mucosa to find a morphological basis for cobalamin malabsorption as well as the Schilling test for the validation of the serum tests. All patients were treated with cobalamin and new blood samples were taken after 4 weeks. We found no difference in sensitivity and specificity between serum MMA, Hcy, and Cbl in identifying patients with and without conditions compatible with cobalamin malabsorption. Elevated serum MMA and Hcy were also found in about 15% of the group of patients with normal Schilling tests and without a morphological basis for cobalamin malabsorption. Moreover, most patients in this group responded with decreased values of the metabolite tests following cobalamin treatment, suggesting that neither elevated metabolites nor a decrease in these values following cobalamin treatment are specific for cobalamin deficiency.

Adolescent↗