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PubMed1998

Molecular diagnosis of medium-chain acyl-CoA dehydrogenase deficiency by oligonucleotide ligation assay.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a recessively inherited defect in the mitochondrial beta-oxidation of fatty acids. A single nucleotide change, the A985 --> G transition, in the MCAD gene accounts for approximately 90% of all the disease-causing mutations in the patients. We have used PCR to amplify a segment of the human MCAD gene and typed the allelic sequence variation at base 985 by a colorimetric oligonucleotide ligation assay (OLA). PCR/OLA provides a technique that permits differentiation of the homozygotes, heterozygotes, and normals for the A985 --> G allele in the MCAD gene. Genotyping of 1908 random Finnish DNA samples by OLA identified 10 carriers of the mutant allele, but no homozygotes were found. The calculated carrier frequency for the A985 --> G mutation was 1:191 (95% confidence limits, 1:118-1:501), and the calculated frequency for the A985 --> G homozygotes was 1:147,000 (95% confidence limits, 1:56,000-1:1,004,000).

Acyl-CoA Dehydrogenase↗

PubMed1995

Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic fibroblast growth factor).

T cell infiltration is prevalent in wound healing, atherosclerosis, vascular lesions in chronic allograft rejection, and autoimmune diseases. Whether T cells play a role in the migration and proliferation of vascular smooth muscle cells and endothelial cells in these lesions is not known. We previously reported that some human T cells express FGF-1, a potent growth factor for vascular smooth muscle cells and endothelial cells. In this study, we extend this observation and examine the expression and function of FGF receptors on human T cells. Using reverse transcription-PCR, Northern analysis, and immunohistochemistry, we found that some human T cells also express high affinity FGF receptor 1 (FGFR-1) respond to FGF-1. In the presence of anti-CD3, exogenous FGF-1 functions as a costimulator for these T cells, while FGF-1 alone does not induce T cell proliferation. [3H]Thymidine incorporation is sevenfold higher in T cells costimulated with FGF-1 compared with stimulation with anti-CD3 alone. Using limiting dilution, we demonstrate that FGF-responsive T cells are present in normal peripheral blood at a mean frequency of 1:19780 (95% confidence limits, 1:15100-1:23000), and similar T cells are increased in the peripheral blood of heart transplant recipients (mean frequency, 1:4210; 95% confidence limits, 1:3420-1:6781). In addition, a subline of Jurkat, a human T cell tumor, expresses FGFR-1 receptor. The function of FGFR-1 receptor in Jurkat T cells is demonstrated by the production of IL-2 after stimulation with FGF-1 and anti-CD3. IL-2 levels are sevenfold higher in Jurkat T cells costimulated with FGF-1 compared with those stimulated with anti-CD3 alone. FGF-1 alone has no effect on Jurkat T cells. These findings thus provide evidence that a subset of human T cells expresses a receptor for vascular cell growth factors, and this receptor functions to increase IL-2 production consistent with costimulation. The potential role of FGF-responsive T cells in a variety of vascular and inflammatory lesions is discussed.

CD4-Positive T-Lymphocytes↗

PubMed1985

Brief report: evaluation of polymerized ragweed extracts by intradermal end point titration, RAST inhibition, and parallel line bioassay.

We have evaluated six polymerized ragweed extracts on the basis of RAST inhibition, parallel line bioassay, and intradermal end point titration. The results of the parallel line bioassay and intradermal end point titration are highly correlated (r = 0.995, df = 2, p less than 0.01). Both intradermal end point titration (r = 0.973, df = 4, p less than 0.01) and parallel line bioassay (r = 0.985, df = 2, p less than 0.05) are highly correlated with RAST inhibition. We have evaluated the utility of intradermal end point titration as a quantitative assay of relative allergenicity of polymerized extracts. The between assay reproducibility was derived by comparing a reference polymerized ragweed extract against itself. The 99% confidence limits of relative allergenicity were 53% to 188% when four assays were used. This compares favorably to the published 99% confidence limits of the parallel line bioassay 60% to 166% when three assays were used. Intradermal end point titration is highly reproducible, is highly correlated with RAST inhibition or parallel line bioassay, and thus is an appropriate bioassay of allergenic activity.

Allergens↗

PubMed2005

Comparative analysis of logistic regression and artificial neural network for computer-aided diagnosis of breast masses.

RATIONALE AND OBJECTIVE: To compare logistic regression and artificial neural network for computer-aided diagnosis on breast sonograms. MATERIALS AND METHODS: Ultrasound images of 24 malignant and 30 benign masses were analyzed quantitatively for margin sharpness, margin echogenicity, and angular variation in margin. These features and age of patients were used with two pattern classifiers, logistic regression, and an artificial neural network to differentiate between malignant and benign masses. The performance of two methods was compared by receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve Az (+/-SD) of the logistic regression analysis was 0.853 +/- 0.059 with 95% confidence limit (0.760-0.950). The area under the ROC curve of the artificial neural network analysis was 0.856 +/- 0.058 with 95% confidence limit (0.734-0.936). Although both the logistic regression and the artificial neural network had the same area under the ROC curve, the shapes of two curves were different. At 95% sensitivity, the artificial neural network had 76.5% specificity, whereas logistic regression had 64.7% specificity. CONCLUSION: There was no difference in performance between logistic regression and the artificial neural network as measured by the area under the ROC curve. However, at a fixed 95% sensitivity, the artificial neural network had higher (12%) specificity compared with logistic regression value.

Breast Neoplasms↗

PubMed2000

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Adolescent↗

PubMed1988

[Are filiform fibromas of the skin a marker for colonic neoplasia?].

750 consecutive out-patients undergoing diagnosis for possible disease of the colon but no history of colon neoplasia were examined for skin tags (achrocordons). They were found in 257 patients, in 30 as multiple (greater than five) lesions. Benign adenoma of the colon was found with similar frequency in patients with (27.6%) and without (22.1%) tags. However, colon carcinoma was twice as frequent in patients with skin tags (8.2%) than controls (4.1%). Patients with multiple tags had an even higher risk of colon carcinoma (odds ratio 7.8; 95% confidence limits 2.2-24.4; P less than 0.01) and a slightly increased risk of benign colon adenoma (odds ratio 2.4; 95% confidence limits 0.9-6.0; P less than 0.05). Whether this association is important in the diagnosis of colon tumours should be tested further by investigating healthy subjects with skin tags.

Aged↗

PubMed1989

The effect on serum cholesterol levels of coffee brewed by filtering or boiling.

Previous reports have indicated that coffee consumption may increase serum cholesterol levels. We studied the effects of coffee prepared by two common brewing methods (filtering and boiling) on serum lipid levels in a 12-week randomized trial involving 107 young adult subjects with normal serum cholesterol levels. After a three-week run-in period during which they all consumed filtered coffee, the participants were randomly assigned to one of three groups receiving four to six cups of boiled coffee a day, four to six cups of filtered coffee a day, or no coffee, for a period of nine weeks. As compared with the change from base line in the filtered-coffee group, the serum total cholesterol level increased after the consumption of boiled coffee by 0.48 mmol per liter (95 percent confidence limits, 0.13 and 0.83), and the low-density lipoprotein cholesterol level increased by 0.39 mmol per liter (95 percent confidence limits, -0.04 and 0.82). There was no significant difference in the change in serum total or low-density lipoprotein cholesterol levels between the filtered-coffee group and the group that drank no coffee. The levels of high-density lipoprotein cholesterol and apolipoproteins were not affected by boiled or filtered coffee. We conclude that drinking filtered coffee does not affect serum lipid levels. The consumption of boiled coffee, however, has an effect on serum cholesterol levels amounting to a mean net increase of 10 percent of the base-line level after nine weeks.

Adult↗

PubMed2000

Rapid tracheal intubation with large-dose rocuronium: a probability-based approach.

UNLABELLED: There are situations in anesthesia in which it may be desirable to achieve rapid tracheal intubation with perfect conditions, i.e., no coughing or straining. To determine the dose of rocuronium that gives a high probability of achieving perfect conditions for rapid (within 60 s) tracheal intubation, we administered a range of doses of rocuronium, some larger than used previously. Sixty adults, anesthetized with thiopental 4 mg/kg IV and alfentanil 10 microg/kg IV, received rocuronium 0.4 to 2.0 mg/kg IV. We used logistic regression to define the relationship of rocuronium dose to probability of achieving perfect intubation conditions. We estimated the doses giving 90% and 95% probability of achieving perfect intubation and used resampling to determine confidence limits for these estimates. Rocuronium 1.85 and 2.33 mg/kg gave, respectively, 90% and 95% probability of perfect intubation conditions. The confidence limits (5th and 95th percentile) for these estimates were 1.15 to 2.31 and 1.23 to 3.22 mg/kg, respectively. In conclusion, it is possible to achieve perfect intubation conditions with large doses of rocuronium, but the long duration of action and expense may limit the usefulness of the technique. IMPLICATIONS: We found that it is possible to have a 90% probability of achieving perfect conditions for rapid tracheal intubation with large (up to 2.0 mg/kg) doses of rocuronium. These large doses of rocuronium may be useful in, for instance, head trauma or open globe injuries if succinylcholine is contraindicated.

Adult↗

PubMed2007

Informed consent and subject motivation to participate in a large, population-based genomics study: the Marshfield Clinic Personalized Medicine Research Project.

BACKGROUND: The objective of this study was to measure subject perspective and reaction to participation in the Personalized Medicine Research Project (PMRP) and to identify factors predicting understanding of the study elements. METHOD: Self-administered questionnaires were mailed to 1,593 subjects (10% sample). The questionnaire had three sections: section A consisted of 21 factual questions; section B consisted of 14 questions to assess the level of understanding about the PMRP concepts, and section C asked about the purpose of the PMRP. RESULTS: The mean age of the 924 survey respondents was 52 years (SD = 16.9), with a range of 18-95 years. The majority of participants were female (n = 561, 61%). The percent of total correct responses for section A was significantly higher for females compared with males (males: 58.4% and females: 60.4%, t test = -2.18, p = 0.03) and age was significantly inversely related to percent of correct responses (beta coefficient = -0.122, p < 0.001). More than one third of the participants indicated that the USD 20 greatly influenced their decision to participate in the project. In a multiple logistic regression model, people living outside of Marshfield were significantly more likely to indicate that the USD 20 greatly influenced their decision to participate (odds ratio = 1.40, 95% confidence limit = 1.06, 1.86) and age was inversely related to the monetary influence on decision to participate (odds ratio = 0.98, 95% confidence limit = 0.97, 0.98). CONCLUSION: Future community consultation efforts should highlight areas of lower understanding. In addition, research coordinators may need to take more time informing males and older individuals about project details so that they are making truly informed decisions about study participation.

Female↗

PubMed1989

Transient ischemic attacks in the community: occurrence and clinical characteristics. A population survey in the area of Florence, Italy.

A simple self-administered questionnaire was mailed to a population sample of 8,626 (40-65 years old) to identify transient ischemic attacks (TIAs) that occurred in the previous 12 months. This study was conducted in a well-defined, medically controlled geographic area. 75.4% of the questionnaires were returned. The procedure identified 52 TIA cases (43 definite and 9 uncertain). The 12-month period prevalence for TIAs was 6.6 per 1,000 (95% confidence limits of 4.8-8.9) among the respondents. The annual incidence rate for first TIAs was 3.1 per 1,000 (95% confidence limits of 1.9-4.7). Our results differ from those reported in hospital series or in population surveys based on clinical records, with higher incidence and prevalence rates, female preponderance and higher frequency of vertebrobasilar attacks.

Adult↗

PubMedDate not supplied

Estimating the frequency of nonpaternity in Switzerland.

In linkage analysis and gene mapping in general, typing error and/or errors in specifying pedigree relationships between individuals typically lead to an upwards bias in recombination fraction estimates and to a loss of power for detecting linkage. [Ott J: Analysis of Human Genetic Linkage. Baltimore, Johns Hopkins University Press, 1991]. The presence of nonpaternity is the most common source of error of misspecification of pedigree relationships between individuals that can have a negative impact on pedigree analysis. We have developed estimates of underlying nonpaternity probabilities based on observed Mendelian inconsistencies. The methods were applied to a sample of 1,607 children and their parents. Genetic marker data were investigated to test for exclusions due to nonpaternity. Among the 1,607 children, 11 or 0.68% exclusions were found. When a constant nonpaternity rate was assumed for each child, its maximum likelihood estimate turned out to be 0.78% with asymptotic 95% confidence limits of 0.41% and 1.35%. When varying nonpaternity rates were assumed, its mean was estimated as 0.83% with asymptotic 95% confidence limits of 0.32% and 1.33%.

Child↗

PubMed1993

Lifestyle factors and risk of cerebrovascular disease in women. The Copenhagen City Heart Study.

BACKGROUND AND PURPOSE: The purpose of the present analysis was to determine how lifestyle influences the risk of cerebrovascular disease in women participating in the Copenhagen City Heart Study. METHODS: A random sample of a white, lower and middle-class, urban population selected in 1976 was invited to two cardiovascular examinations at 5-year intervals. The present analysis was based on 7060 women invited to an initial examination from 1976 through 1978, aged 35 years or more, and without previous stroke or transient ischemic attack. At the initial examination, potential risk factors were recorded. The 265 first cases of stroke and transient ischemic attack were ascertained at a second examination 5 years later and through hospital records and death certificates through 1988. The Cox regression model was used to estimate the influence of the factors recorded on the risk of cerebrovascular disease. RESULTS: The relative risks of cigarette smoking and lack of physical activity were 1.4 and 1.45; 95% confidence limits, 1.02 to 1.94 and 1.01 to 2.08, respectively). The relative risk of daily consumption of tranquilizers was 1.25 (95% confidence limits, 0.96 to 1.62). No significant influence was found for number of cigarettes, body mass index, or alcohol intake. In postmenopausal women, there was a statistically significant interaction (P < .041) between smoking and hormone replacement therapy. Smokers receiving this therapy had a 28% lower risk of cerebrovascular disease than smokers not receiving it. CONCLUSIONS: The statistically significant and equally potent effects on the risk of cerebrovascular disease were found for cigarette smoking and lack of physical activity. The risk associated with smoking seemed to be influenced by hormonal replacement therapy.

Adult↗

PubMedDate not supplied

Predictors of injury among 1638 riders in a recreational long-distance bicycle tour: Cycle Across Maryland.

To assess the incidence of and risk factors for injuries in a group of bicyclists with a well-defined exposure to bicycling, we conducted a prospective study of 1638 recreational bicyclists who rode in the 6-day 339-mile Cycle Across Maryland tour in 1994. The mean age of participants was 39 years (range, 7 to 79), and two-thirds were male. All riders wore helmets. During the tour there were 85 acute traumatic injuries (15.4 per 100,000 person-miles), 76 overuse injuries (13.7 per 100,000 person-miles), and 37 other medical problems (6.7 per 100,000 person-miles). Acute traumatic injuries were associated with a history of racing versus none (relative risk = 2.2, 95% confidence limits = 1.3, 3.7) and with inexperience, no previous Cycle Across Maryland tours versus one or more (relative risk = 1.7, 95% confidence limits = 1.04, 2.8), but not with sex, training, or prior injuries. Inexperience and lack of preride conditioning were risk factors for overuse injuries. The most common overuse injuries and medical problems were knee pain, hand or wrist numbness, foot blisters, insect stings and bites, and heat and dehydration. Study results provide exposure-based incidence rates of bicyclist injuries and suggest overuse injuries may be reduced by increased preride conditioning.

Adolescent↗

PubMed1975

Circannual and circadian rhythms in plasma testosterone in five healthy young Parisian males.

Every other month, during the course of 14 months, the circadian rhythm in plasma testosterone (among others variables) of 5 healthy males (26 to 32 years) was documented. Subjects' synchronization: light-on at 7 +/- 1 h; light-off at 23 +/- 1.5 h during the whole year. Blood sampling 4-hourly, at fixed times during 28 h, for radioimmunological testosterone determinations. The cosinor method was used for statistical analyses. An annual rhythm in the testosterone 24-h mean is detected (P less than 0.025) with a peak in October (from 16 July to 26 December, with 95% confidence limits). Annual mean (+/-1 se)= 759 (+/- 26) ng/100 ml. Peaktrough difference=197 ng/100 ml (from 106 to 290 with 95% confidence limits). The timing of the testosterone circadian peak, in the 24-h-scales also varies during the course of the year. The peak is found around 8 h in May and around 14 h in November, this phase-shift being statistically significant (P less than 0.05).

Adult↗

PubMed1985

Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis. A randomized trial.

Impedance plethysmography is an accurate noninvasive method to test for proximal vein thrombosis, but it is insensitive to calf-vein thrombi. We randomly assigned patients on referral with clinically suspected deep-vein thrombosis and normal impedance plethysmographic findings to either serial impedance plethysmography alone or combined impedance plethysmography and leg scanning (which has been shown to be essentially as sensitive as venography) and compared the long-term outcomes. During the initial surveillance, deep-vein thrombosis was detected in 6 of 311 patients (1.9%) tested by serial impedance plethysmography alone and in 30 of 323 patients (9.3%) (most with calf-vein thrombi) tested by the combined approach (p less than 0.001). During long-term follow-up, no patient died from pulmonary embolism; but 6 patients (1.9%; 95% confidence limits, 0.7% to 4.2%) tested by serial impedance plethysmography developed deep-vein thrombosis compared with 7 patients (2.2%; 95% confidence limits, 0.9% to 4.4%) tested by the combined approach. Serial impedance plethysmography used alone is an effective strategy to evaluate such symptomatic patients.

Adult↗

PubMed2002

Pretreatment with midazolam suppresses morphine withdrawal response in mice and rats.

AIM: To investigate the roles of pretreatment with midazolam on morphine withdrawal in mice and rats. METHODS: Acute and chronic morphine dependence and naloxone-precipitated withdrawal models were employed in the present study. Cyclic adenosine monophosphate (AMP) content and Fos protein expression were measured by radioimmunoassay and immunocytochemistry, respectively. RESULTS: Coadministration of midazolam (2 mg/kg, ip) and morphine prevented the development of both acute and chronic morphine dependence in mice. Compared to saline-morphine group (3.0, 95 % confidence limits: 1.9-4.3 mg/kg), ED50 of naloxone-precipitated withdrawal jumping increased significantly in midazolam-morphine group (10.4, 95 % confidence limits: 8.5-12.3 mg/kg) in acute morphine-dependent mice (P<0.01). Pretreatment with midazolam lowered the number and incidence of naloxone-precipitated withdrawal jumping and prevented loss in body weight in chronic morphine-dependent mice (P<0.01). Midazolam-pretreatment inhibited the increase of Fos protein expression, not cyclic AMP content, in rat spinal cord during morphine withdrawal. CONCLUSION: Midazolam suppresses morphine withdrawal response by inhibiting hypersensitization of the spinal cord neurons, and this effect may not be mediated by cAMP pathway.

Adenosine Monophosphate↗

PubMed1988

Antiphospholipid antibodies in early repeated abortions: a case-controlled study.

The relation among lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and repeated abortions was evaluated in a case-controlled study of 49 women with two or more unexplained spontaneous abortions (cases) compared with 141 control subjects, who had had one or more normal pregnancies and no previous spontaneous abortion. The women were admitted to the same hospital where the cases had been identified for acute conditions other than immunologic neoplastic, gynecologic or cardiovascular. LAC was detected in 7 out of 49 cases (14%, 95% confidence limits 8% to 26%) but in none of the 141 controls. Similarly, ACA were detected in four cases (8%, 95% confidence limits 0.3% to 30%) but no controls. These differences in frequency were statistically significant. These findings confirm that LAC and ACA are associated with a history of repeated abortions in clinically asymptomatic patients for immunologic conditions.

Abortion, Habitual↗

PubMed1995

Low blood pressure and mortality in the elderly: a 6-year follow-up of 18,022 Norwegian men and women age 65 years and older.

Several studies have shown that low blood pressure in individuals age 65 years and older is related to increased overall mortality. We hypothesize that this association is secondary to serious underlying illness, which has caused blood pressure reduction and, subsequently, has increased the risk of dying. Our study population was comprised of individuals age 20 years and older in the county of Nord Trøndelag in Norway, who were studied in a general health survey between 1984 and 1986. We had measurements of blood pressure, blood glucose, weight, height, and other information for 9,732 women and 8,290 men age 65 years or older. During approximately 6 years of follow-up, 2,122 women and 2,578 men died. For both genders, low systolic pressure was not associated with increased mortality, and the mortality curve did not display a J-shaped relation, after adjustment for age, marital status, body mass index, blood glucose, self-assessed health, use of antihypertensive medication, and history of diabetes and cardiovascular diseases. For diastolic pressure, however, women in the lowest category (< 75 mmHg) had an adjusted mortality rate ratio of 1.21 (95% confidence limits = 1.05, 1.39), compared with reference women (80-87 mmHg). Among men, the analogous mortality rate ratio was 1.16 (95% confidence limits = 1.02, 1.31). To reduce further the potential confounding between diastolic pressure and underlying illness, we excluded users of antihypertensive medication as well as the 2 first years of follow-up. After these procedures, the J-shaped mortality curve was not present among women, and it was substantially reduced among men. Thus, the results for both men and women indicated that the age-adjusted J-shaped relation between diastolic blood pressure and mortality was confounded with indicators of ill health, and that the often-found association between low diastolic blood pressure and increased mortality is indirect, possibly caused by serious underlying disease.

Aged↗