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PubMed1998

Regression equations in clinical neuropsychology: an evaluation of statistical methods for comparing predicted and obtained scores.

Regression equations are widely used in clinical neuropsychology, particularly as an alternative to conventional normative data. In neuropsychological applications the most common method of making inferences concerning the difference between an individual's test score and the score predicted by a regression equation is to multiply the standard error of estimate by an appropriate value of z to form confidence limits around the predicted score. The technically correct method is to calculate the standard error of a new individual Y and multiply it by the value of t corresponding to the desired limits (e.g., 90% or 95%). These two methods are compared in data sets generated to be broadly representative of data sets used in clinical neuropsychology. The former method produces confidence limits which are narrower than the true confidence limits and fail to reflect the fact that limits become wider as scores on the predictor deviate from the mean. However, for many of the example data sets studied, the differences between the two methods were trivial, thereby providing reassurance for those who use the former (technically incorrect) method. Despite this, it would be preferable to use the correct method particularly with equations derived from samples with modest Ns, and for individuals with extreme scores on the predictor variable(s). To facilitate use of the correct method a computer program is made available for clinical practice.

Algorithms↗
PubMed1996

Cancer risk after metal on metal and polyethylene on metal total hip arthroplasty.

The incidence of cancer after metal on metal total hip arthroplasty (McKee-Farrar) and polyethylene on metal total hip arthroplasty (Brunswik, Lubinus) was compared with that of the general population in Finland. The mean followup time for the patients who had metal on metal total hip arthroplasty was 15.7 (9092 person years) and for the patients who had polyethylene on metal total hip arthroplasty it was 12.5 years (19,846 person years). One hundred thirteen malignant cancers were observed in patients who had metal on metal total hip arthroplasty and 212 were observed in patients who had polyethylene on metal total hip arthroplasty. The standardized incidence ratio for all cancers of the metal on metal arthroplasty group was 0.95 (95% confidence limits 0.79-1.13) and that of the polyethylene on metal arthroplasty group was 0.76 (95% confidence limits 0.68-0.86). The risk of total cancer in the patients who had metal on metal total hip arthroplasty was 1.23-fold compared with that of the patients who had polyethylene on metal total hip arthroplasty. Both groups had significantly less lung cancer than the general population: the leukemia incidence in the patients who had metal on metal total hip arthroplasty was slightly increased (observed to experienced 7/3.03, standardized incidence ratio 0.61; 95% confidence limits 0.17-1.56). The leukemia rate of the patients who had metal on metal total hip arthroplasty was 3.77-fold compared with that of the patients who had polyethylene on metal total hip arthroplasty, but this difference was not statistically significant. No sarcomas were observed at the site of the prosthesis. The incidence of the other forms of cancers did not differ significantly from those in the general population. The observed variation in the incidence of different cancers among patients who had total hip arthroplasty compared with the general population suggests that factors other than total hip arthroplasty play a major role in the origin of cancer.

Aged↗
PubMed1995

[Pancreaticoduodenectomy (Whipple's operation) for periampullary cancer].

This study evaluated the indications for and effects of pancreaticoduodenectomy (102 patients) or total pancreatectomy (15 patients) with extensive lymph node dissection performed upon 117 patients with periampullary adenocarcinoma. Presenting symptoms and postoperative morbidity and mortality rates were recorded. Cumulative survival rates were evaluated in relation to origin, size, and staging of tumour. The postoperative mortality rate after Whipple's operation was 8% (eight patients). The median survival period was 1.1 year and the overall five year survival rate was 15% (confidence limits, 5 to 25%). The five year survival rate for patients without tumour extension beyond the pancreas was 25% (confidence limits, 5 to 50%), and in patients with adenocarcinoma of the ampulla af Vater, 34% (confidence limits, 3 to 65%). The median survival rate in patients with adenocarcinoma of the ampulla of Vater was 3.3 years, which was significantly longer than in the other patients. Fifty-nine patients with distant spread could be divided into 14 patients with para-aortic lymph node metastases who had a significantly shorter survival period than 45 patients without para-aortic lymph node metastases (p = 0.004). Resection of periampullary carcinoma provides a better palliation and survival rate than nonoperative biliary drainage or bypass operation. An improved preoperative verification of para-aortic metastases could restrict resection to patients with a prognostic five year survival rate of more than 25% and a postoperative mortality rate of less than 5%.

Adenocarcinoma↗
PubMed1992

Modification of the volumetric growth responses and steady-state hypoxic fractions of xenografted DLD-2 human colon carcinomas by administration of basic fibroblast growth factor or suramin.

We studied the growth characteristics and hypoxic fractions of DLD-2 human colon tumours xenografted into male nude mice either in the unperturbed state or after i.p. injection (q.i.d. x 7) of basic fibroblast growth factor (0.25 mg kg-1) or suramin (50 mg kg-1). Hypoxic fractions were measured by clonogenic excision assay 1 day after administration b FGF or suramin was stopped. As compared to controls, the growth of tumours in b FGF treated mice was increased by a factor of 1.5 as indicated by the relative volumes of tumours on the day of excision. Similarly, suramin decreased the growth of DLD-2 tumours by a factor of 1.6. The percentage of hypoxic cells in control neoplasms was 42.9% (95% confidence limits 34.2-52.1%). In mice that received basic fibroblast growth factor injections, hypoxic fractions decreased to 19.1% (95% confidence limits 13.5-26.9%). In contrast, in mice treated with suramin, the percentage of hypoxic cells increased to 74.0% (95% confidence limits 65.3-83.9%). These data indicate that the biology of solid tumours can be significantly modified by alteration of growth factor status.

Adenocarcinoma↗
PubMed1989

Maximal static respiratory pressures in the normal elderly.

To determine if a relationship exists between maximal static respiratory pressures measured at the mouth and age greater than 55 yr, and if so, whether regression equations can be derived that accurately reflect this, we measured maximal inspiratory (Plmax) and expiratory (PEmax) pressures in 64 normal women and 40 normal men older than 55 yr of age. We found no relationship between PImax and PEmax and age greater than 55 yr (all r squared values less than 0.14). We tested the reproducibility of our measurements of PImax and PEmax in 13 and 12 subjects, respectively, on three separate occasions. Repeated measures analysis showed no significant differences in these measurements. Using the measurements obtained in this large study, we calculated 95% confidence limits for PImax and PEmax values in men and women older than 55 yr of age. The 95% confidence limits for PImax in men were 55 to 161 cm H2O, and 26 to 124 cm H2O in women. The 95% confidence limits for PEmax in men were 90 to 256 cm H2O, and 46 to 184 cm H2O in women. We conclude that given the large interindividual variation, a cross-sectional study such as this or other previous studies may not be able to reveal age-dependent changes unless very large numbers are used, and even then potential for bias exists. However, with the small intraindividual coefficients of variation in repeated measurements of PImax and PEmax, a longitudinal study may provide more pertinent information.

Aged↗
PubMed1996

Celiac disease and pregnancy outcome.

OBJECTIVES: This study investigated the effect of gluten-free diet on pregnancy outcome and lactation in 125 women affected with celiac disease. METHODS: The study has been designed as a case-control study and a before-after study. RESULTS: In the case-control study, comparison of 94 untreated with 31 treated celiac women indicated that the relative risk of abortion was 8.90 times higher (95% confidence limits: 1.19/66.3), the relative risk of low birth weight baby was 5.84 times higher (90% confidence limits: 1.07/31.9), and duration of breast feeding was 2.54 times shorter (p < 0.001) in untreated mothers. Abortion, low birth weight of baby, and duration of breast feeding did not significantly relate to the severity of celiac disease among untreated women. In the before-after study, 12 pregnant celiac women in either treated or untreated condition were compared. Results indicated that the gluten-free diet reduced the relative risk of abortion by 9.18 times (95% confidence limits: 1.05/79.9), reduced the number of low birth weight babies from 29.4% down to zero (p < 0.05), and increased duration of breast feeding 2.38 times (p < 0.10). Both case-control and before-after studies indicated that threatened abortion and premature delivery did not significantly relate to treatment of celiac disease. CONCLUSIONS: The high incidence of abortion, of low birth weight babies, and of short breast-feeding periods is effectively corrected by gluten-free diet in women with celiac disease.

Abortion, Spontaneous↗
PubMed1997

Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo.

1. First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine the effects of tranilast on angiogenesis in vitro and in vivo and discuss the application of tranilast for angiogenic diseases. 2. Tranilast inhibited significantly the proliferation (IC50: 136 microM, 95% confidence limits: 134-137 microM) and vascular endothelium growth factor (VEGF)-induced chemotaxis (IC50: 135 microM, 95% confidence limits: 124-147 microM) of human dermal microvascular endothelial cells (HDMECs) at concentrations greater than 25 micrograms ml-1. No toxicity to HDMECs measuring by LDH release and no inhibitory effects on metalloproteinase (MMP)-2 and MMP-9 activity were observed even at 100 micrograms ml-1 (306 microM). 3. Tube formation of HDMECs cultured on the matrigel as an in vitro angiogenesis model was inhibited by tranilast in a concentration-dependent manner. The IC50 value and 95% confidence limits were 175 microM and 151-204 microM, respectively. 4. In vivo angiogenesis was induced in mice by the subcutaneous injection of matrigel containing 30 ng ml-1 VEGF and 64 micrograms ml-1 heparin. Tranilast was administered orally twice a day for 3 days. Tranilast dose-dependently suppressed angiogenesis in the matrigel and a significant change was observed at a dose of 300 mg kg-1. 5. These results indicate that tranilast is an angiogenesis inhibitor which may be beneficial for the improvement of angiogenic diseases such as proliferative diabetic retinopathy, age-related macular degeneration, tumour invasion and rheumatoid arthritis.

Animals↗
PubMed1995

Primary corneal graft failure. A national reporting system. Medical Advisory Board of the Eye Bank Association of America.

OBJECTIVES: To describe a national eye banking registry and to assess the effects of donor age, cause of donor death, time from death to procurement, storage time, and distance between the points of recovery and transplantation on the reported occurrence of primary corneal graft failure. DESIGN: We performed a retrospective case-control study to estimate the odds ratios of five donor factors for cases of primary graft failure voluntarily reported to a national registry using controls from selected eye banks. We also performed a nested case-control cohort study to compare cases of primary graft failure that occurred in both corneas from the same donor with those of nonmated corneas in which primary graft failure was reported to assess odds ratios for the same donor factors. PATIENTS: One hundred forty-seven patients developed primary graft failure in penetrating keratoplasty transplantations performed between January 1, 1991, and December 31, 1993. These cases were reported to the Adverse Reaction Registry of the Eye Bank Association of America, Washington, DC. Controls included 7240 donor corneas distributed by nine eye banks during 1992. RESULTS: Of the 147 donor corneas that developed primary graft failure, 17 (12%) were obtained from donors who were aged 70 years and older, 39 (27%) came from donors who died of trauma, 13 (9%) had a cadaver time longer than 12 hours, 10 (7%) had a storage time longer than 7 days, and 38 (26%) were distributed outside the eye bank's region. Compared with controls, these donor corneas were more likely to have a storage time longer than 7 days (odds ratio, 2.4; 95% confidence limits, 1.2 and 4.6) and to come from donors aged 70 years and older (odds ratio, 2.4; 95% confidence limits, 1.4 and 4.0). The 22 corneas (15%) in which primary graft failure occurred in both recipients from the same donor were 8.5 times (95% confidence limits, 1.1 and 51.5) more likely to be preserved beyond 1 week than were nonmated corneas with primary failure but were not from significantly older donors. Logistic regression analysis showed that the association between prolonged storage time and primary graft failure in mated corneas remained significant even when the analysis was controlled for other donor factors. CONCLUSIONS: No clearly defined donor or eye banking factor accounted for most cases of primary graft failure, although prolonged corneal storage and advanced donor age may increase its risk. Ophthalmologists are urged to report to their eye bank all cases of primary graft failure and other adverse events that might be attributable to donor eye tissue.

Adult↗
PubMed1995

The relationship between peak velocity in the fetal descending aorta and hematocrit in rhesus isoimmunization.

OBJECTIVE: To correlate the peak velocity in the fetal descending aorta, as measured by pulsed Doppler ultrasound, with fetal hematocrit values assessed by funipuncture in pregnancies complicated by rhesus isoimmunization. METHODS: One hundred twelve consecutive funipunctures were performed on 33 rhesus-negative gravidas of 21-36 weeks' gestation (median 30). Doppler flow, corrected for angle, was measured on the fetal descending aorta with pulsed Doppler equipment immediately before funipuncture. Differences between observed peak velocities and the calculated gestational age-dependent upper confidence limits (delta peak velocities) were compared with corresponding differences between observed hematocrits and the calculated lower confidence limits (delta hematocrits), and a regression analysis on the above paired difference values was performed. In addition, the correlation coefficient between delta peak velocities and delta hematocrits was calculated for the first procedure per pregnancy only. RESULTS: The mean peak aortic velocity of anemic fetuses was higher than that of unaffected fetuses (P < .001); delta peak aortic velocities correlated negatively with delta hematocrits (r = -0.66, P < .001). The correlation coefficient between delta peak aortic velocities and delta hematocrits for the first procedure peer pregnancy only was r = -0.72 (P < .001). Prediction of fetal anemia by Doppler using gestational age-dependent 95% confidence limits was possible with positive and negative predictive values of 73 and 66%, respectively. CONCLUSION: Peak aortic velocity, a noninvasive assessment of fetal anemia, may be used as an additional test for monitoring pregnancies complicated by rhesus isoimmunization. However, the limited predictive capacity hampers its clinical usefulness.

Anemia↗
PubMed1988

Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk.

Bronchogenic carcinoma is closely associated with cigarette smoking although additional environmental or individual factors might regulate a person's susceptibility to that disease. To further define such risk factors, the prevalence of the genetic debrisoquine 4-hydroxylation deficiency was determined before therapeutic intervention in 270 lung cancer patients. Nineteen homozygous carriers of this defect (poor metabolizers) were found (7.0%, 95% confidence limits 4.3%-10.8%), a number being lower than 30 out of 270 reference patients (11.1%, 95% confidence limits 7.6%-15.5%). The odds ratio of 0.61 was of marginal statistical significance (P = 0.067). Subdividing the collective according to histology revealed a trend towards underrepresentation of poor metabolizers especially among patients with adenocarcinoma (1 out of 37, P = 0.086) and among young patients not older than 50 years (none out of 32, P = 0.028). All poor metabolizers (PMs) in the cancer group were smokers. In 18 patients the phenotype assignment was confirmed by a second test several weeks after surgical or other treatment. In 220 of the lung cancer patients the N-acetyltransferase polymorphism was evaluated by means of the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine after ingestion of caffeine (coffee). There were 111 (50.5%) slow acetylators and 109 (49.5%) fast acetylators. A statistically significant clustering of either phenotype after stratification according to histology, or debrisoquine hydroxilator status was lacking. Moreover, there was no difference in the ratio of both phenotypes as compared to the reference collective of 245 patients (53.5% slow and 46.5% fast acetylators). As a third genetic host factor the AB0 blood group frequencies were evaluated in 263 lung cancer patients. The frequency ratio of A/O was significantly higher as compared to 41,423 blood donors (odds ratio 1.37, 95% confidence limits 1.02-1.84, P less than 0.05). A/O tended to be especially high in young patients not older than 50 years. The ratio B/O in bronchial cancer was significantly higher than expected. The results suggest that the debrisoquine hydroxilator status might have an impact on an individual's susceptibility to lung cancer. This association is either a weak one and/or is restricted to certain histological cancer types or to patients with certain characteristics. The acetylator phenotype could not be established as a risk factor, whereas AB0 blood groups seem to influence lung cancer susceptibility.

ABO Blood-Group System↗
PubMed1998

Importance of the sampling site for measurement of mixed venous oxygen saturation in shock.

OBJECTIVES: To determine if oxyhemoglobin saturation in blood samples taken from the superior vena cava or right atrium can be substituted for oxyhemoglobin saturation in blood taken from the proximal pulmonary artery (SVO2) in patients in shock. DESIGN: Prospective clinical investigation. SETTING: Mixed surgical/medical intensive care unit in a university hospital. PATIENTS: Thirty consecutive patients in severe circulatory shock who required insertion of a pulmonary artery flotation catheter (PAFC) immediately on intensive care unit admission. All patients fulfilled the criteria described below which were established in advance. MEASUREMENTS AND MAIN RESULTS: Oxyhemoglobin saturation in the superior vena cava, right atrium, and pulmonary artery (SVO2) was measured by cooximetry in consecutive blood samples from each site during initial insertion of the PAFC. The mean standard deviation of values from these sites was similar: 74 +/- 12.5%, 70.+/- 13%, and 71.3 +/- 12.7%, respectively. However, when superior vena cava and right atrial oxyhemoglobin saturations and SvO2 were compared, the ranges and 95% confidence limits were found to be clinically unacceptable. The ranges were -19.3 to 23.1% and -19.7 to 16.7%, respectively, and the 95% confidence limits were -18.4 to 24.2% and -18.6 to +17.3%, respectively. CONCLUSIONS: These wide range differences and confidence limits would lead to large errors if superior vena cava or right atrial oxyhemoglobin saturations were substituted for true mixed venous blood in oxygen transport or pulmonary venous admixture calculations, or if clinical decision making was based on individual results. In patients in shock in whom clinical decisions may be based on the value of mixed venous oxyhemoglobin, oxyhemoglobin saturation is only reliably measured in samples taken from the pulmonary artery.

Adult↗
PubMed1998

Relative bioavailability of rapidly dispersing, plain, and microencapsuled acetylsalicylic acid tablets after single dose administration.

UNLABELLED: Extent and rate of absorption of acetylsalicylic acid (ASA) from rapidly dispersing (Acesal Extra) and plain tablets (Acesal) relative to reference 1 (plain tablets, Aspirin) and from microcapsuled tablets (Micristin) relative to comparable listed tablets (reference 2, Colfarit) were assessed in 2 single-dose (0.5 g ASA), open, randomized, crossover studies with intervals of 14 days between 2 periods. Both studies were performed in 24 male and female healthy volunteers each (age 18-32 years, body weight 48-90 kg, body height 161-190 cm). ASA and its metabolite salicylic acid (SA) were measured with an HPLC method validated for ASA between 0.2 and 20 microg/ml and for SA between 0.4 and 40 microg/ml. The test tablets were considered bioequivalent with reference in extent of absorption if the 90% confidence limits of the AUC0 to infinity ratio were within the range of 0.80-1.25, and in rate of absorption if the confidence limits of the Cmax/AUC0 to infinity ratios were within 0.70-1.43. RESULTS: Geometric means and 90% confidence limits for the test/reference ratios of the comparisons Acesal vs reference 1, Acesal Extra vs reference 1 and Micristin vs reference 2 were 1.05 (0.97-1.13), 1.13 (1.05-1.22), 1.02 (0.92-1.14) for ASA AUC0 to infinity and 1.02 (0.96-1.07), 1.05 (0.99-1.11), 0.98 (0.91-1.04) for SA AUC0 to infinity, respectively. The results for Cmax/AUC of ASA were 1.16 (1.00-1.34), 1.72 (1.49-1.99), 0.83 (0.73-0.94) and of SA 1.02 (0.98-1.07), 1.07 (1.02-1.12), 0.93 (0.88-0.97). CONCLUSION: Acesal and Micristin were bioequivalent with the respective references in both extent and rate of absorption. Acesal Extra and reference 1 were bioequivalent with regard to extent only. Acesal Extra was absorbed faster.

Adult↗
PubMed1994

Pancreaticoduodenectomy for periampullary adenocarcinoma.

BACKGROUND: This study evaluates the indications for and effects of pancreaticoduodenectomy (102 patients) or total pancreatectomy (15 patients) with extensive lymph node dissection performed upon 117 patients for treatment of periampullary adenocarcinoma. STUDY DESIGN: Presenting symptoms and postoperative morbidity and mortality rates were recorded. Cumulative survival rates were evaluated in relation to origin, size, and staging of tumor. Postoperative follow-up of clinical symptoms was done after one year. RESULTS: The postoperative mortality rate after Whipple's operation was 8 percent (eight patients). The median survival period was 1.1 year and the overall five year survival rate was 15 percent (confidence limits, 5 to 25 percent). The five year survival rate for patients without tumor extension beyond the pancreas was 25 percent (confidence limits, 5 to 50 percent), and in patients with adenocarcinoma of the ampulla of Vater, 34 percent (confidence limits, 3 to 65 percent). The median survival rate in patients with adenocarcinoma of the ampulla of Vater was 3.3 years, which was significantly longer than in the other patients. Fifty-nine patients with distant spread could be divided into 14 patients with para-aortic lymph node metastases who had a significantly shorter survival period than 45 patients without para-aortic lymph node metastases (p = 0.004). Most patients surviving more than one year were doing well, although 60 percent needed exocrine pancreatic substitution therapy. CONCLUSIONS: Resection of periampullary carcinoma provides a better palliation and survival rate than nonoperative biliary drainage or bypass operation. An improved preoperative verification of para-aortic metastases could restrict resection to patients with a prognostic five year survival rate of more than 25 percent and a postoperative mortality rate of less than 5 percent.

Adenocarcinoma↗
PubMed2002

[Effect of sociocultural factors on maternal and perinatal morbidity with or without mortality among adolescents seen in 3 states of the Mexican Republic].

This study was aimed on comparing the degree of association between social-cultural factors and maternal or perinatal morbidity and/or mortality of the adolescent. A paired case-control study was designed with adolescent in puerperal immediate stage affiliated to the Mexican Institute of Social Security from Tabasco, Tlaxcala and Northern Veracruz, that were adjusted to the selection criteria of the sample, between June of 1998 and February of 1999. Two groups were integrated, cases, with adolescent in puerperal immediate stage affected (with maternal or perinatal morbidity and/or mortality) and controls, with adolescent not affected in puerperal immediate stage. Information concerned to biological and social-cultural risk factors from each subject was obtained applying a validated survey (EFRASEMA 1) and checking their clinical file, whose information was poured in a database (EFRASEMA 2). Interviewers did not know the outcome of the study, which in turn assured the blindness of the information. Once data was obtained, subjects were assigned to each group of study. Matching factors were age, nutritional status, intergenesic interval and previous pregnancy systemic pathology. Proportion of subjects, cases and controls; with or without social-cultural risk factors was determined. The risk of maternal or perinatal morbidity and/or mortality in the exposed subjects was estimated by odds ratio (OR) and the differences inferred through Mantel and Haenszel chi 2 and Fisher's exact tests (confidence intervals alpha = 0.05 and beta = 0.2). There was a sample of 486 subject, 44 were eliminated due to insufficient data. Studied population was integrated finally with 221 cases and 221 paired controls 1: 1. 71.950% of participants were married, 22.62% in free union, 4.98% single and 0.45% separate, average global age was 17.98 +/- 1.39 years. The inferential analysis showed an OR 0.64 (Cornfield 95% confidence limits: 0.40 < OR < 1.03, p = 0.0510600) concerning desired pregnancy in favor to controls. Appropriate reproductive information had an OR = 0.34 (Cornfield 95% confidence limits: 0.21 < OR < 0.54 p = 0.0000014). Ideal cumulated fertility offered an OR 0.62 (Cornfield 95% confidence limits: 0.39 < OR < 0.98, p = 0.0298500). These results show an association between the social-cultural factors and the presence of maternal or perinatal morbidity and/or mortality in the studied adolescents. Desired pregnancy, appropriate reproductive information and ideal cumulated fertility are protection factors to maternal or perinatal morbidity and/or mortality.

Adolescent↗
PubMed1994

Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3'-flanking region.

Genetic differences in the metabolism of carcinogens may codetermine individual predisposition to cancer. Cytochrome P-4501A1 (CYP1A1) metabolically activates precarcinogens in cigarette smoke, such as benzo(a)pyrene, which is also an inducer of CYP1A1. Two point mutations have been reported, m1 in the 3'-flanking region (6235T to C), and m2 within exon 7 (4889A to G), the latter leading to an isoleucine to valine exchange. In the Japanese population m1 and m2 are correlated with lung cancer, suggesting an increased susceptibility to cigarette smoking related lung cancer. We studied 142 lung cancer and 171 reference patients in an ethnically homogeneous German group for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively. No statistically significant difference was found in the distribution of m1 alleles between lung cancer and controls; the frequency was 8.5% and 7.3% of the alleles, respectively (odds ratio = 1.17). A trend to an overrepresentation of m1 alleles was observed among 52 squamous cell carcinoma patients (odds ratio = 1.65). In contrast, the frequency of m2 alleles in lung cancer patients was twofold higher (6.7%) than in the reference group (3.2%; odds ratio = 2.16; 95% confidence limits 0.96-5.11, P = 0.033); the odds ratio of m2 alleles in squamous cell carcinoma was 2.51 (95% confidence limits 0.85-7.05, P = 0.05). There was a close genetic linkage of m2 to m1 (10 of 11 reference patients), but a significantly higher number of cancer patients showed no linkage compared to the controls (odds ratio = 8.89, 95% confidence limits 0.83-433, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Detection and characterization of the heterozygote state for lipoprotein lipase deficiency.

Because there are no characteristic clinical or biochemical manifestations, the heterozygote state for lipoprotein lipase (LPL) deficiency has been difficult to detect. Measurements of postheparin plasma LPL activity and of LPL mass were performed in six families of probands with LPL deficiency to characterize the heterozygote state. LPL mass was measured in a sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody (5D2) that had been produced against bovine milk LPL. Thirteen obligate heterozygotes from these families had reduced LPL activity and mass below the 95th percent confidence limits of 34 normal controls, while one obligate heterozygote had LPL activity and mass between the 90th and 95th percent confidence limits. Potential heterozygotes in these families were identified as normal (n = 8) or heterozygotes (n = 6) by comparison to the 95th percent confidence limits of the controls. Some relatives in four of the six families exhibited mild hyperlipidemia, similar to the pattern seen in familial combined hyperlipidemia (FCHL). The hyperlipidemia segregated with the heterozygote state for LPL deficiency in these families (p less than 0.03). High density lipoprotein (HDL) cholesterol was significantly reduced in the heterozygotes for LPL deficiency (p less than 0.01). The measurement of LPL activity and mass allows identification of the heterozygote state for LPL deficiency, which is characterized by variable expressions of hyperlipidemia and reduced HDL cholesterol. These results suggest that the heterozygote state for LPL deficiency may form one subset of FCHL.

Adult↗
PubMed1996

A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility.

This study reports a C-->A transversion at position 4887 in exon 7 of cytochrome P4501A1 (CYP1A1), resulting in a threonine-asparagine exchange in codon 461. The polymorphism is located directly beside the known codon 462-Ile/Val mutation (m2) near the heme binding region. The C4887A mutation leads to the loss of a BsaI cleavage site, which allows analysis. No linkage of this mutation, termed m4, with other mutations such as m1 (MspI polymorphism in the 3'-flanking region) or m2 was observed on the same DNA strand. Systematic molecular genetic analyses of mutation linkages revealed that mutation m2 is in strict linkage disequilibrium with m1. To distinguish the different CYP1A1 alleles and genotypes, mutation linkages were considered. Frequency of the m4-containing allele, termed CYP1A1*4, among 880 unrelated Caucasian individuals was 2.95% (95% confidence limits, 2.21%, 3.86%). m1 was found in 7.73%, and m2 in 2.67% of alleles. No case of African black-specific mutation m3 was detected. The allele frequency of CYP1A1*4 among 157 lung cancer patients was 2.87% (95% confidence limits, 1.32%, 5.37%); it was 2.87% (95% confidence limits, 1.71%, 4.49%) in 314 controls matched by age and sex. Thus, the novel m4-mutation may not represent a susceptibility factor for lung cancer.

Aged↗
PubMed1985

Age at first primary as a determinant of the incidence of bilateral breast cancer. Cumulative and relative risks in a population-based case-control study.

This epidemiologic investigation comprised 1351 of 1423 women in a defined geographic area consecutively diagnosed as having a primary breast cancer. Simultaneous bilateral disease occurred in only 1 patient, whereas a history of previous cancer in the contralateral breast was reported by 65 patients. This prevalence was related to that of 23 previous cases in an age-matched control group of 1351 women from the same population. The relative risk of developing a second primary was 2.9 (95% confidence limit, 1.8-4.6) for the whole material and remained seemingly constant over several decades at a level predetermined by age at first diagnosis, namely 9.9 (95% confidence limit, 3.8-25.8) before the age of 50 and 1.9 (95% confidence limit, 1.1-3.2) after that age. The incidence ratio of bilateral to unilateral disease was used as an estimate of the lifetime risk of developing a second primary in this stable and well-defined population. This calculation revealed cumulative risk figures of 13.3% and 3.5% for women younger and older than 50 years, respectively, at first diagnosis. It was concluded that the occurrence of bilateral disease, which reflects a multicentric neoplastic transformation of the breast epithelium, is a characteristic of early-occurring (premenopausal) disease.

Adult↗