Epidemiological surveillance of the general population and control of nature in the prevention of diseases and environmental impairment caused by pesticides.
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Environmental Pollution↗
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Evidence for the aetiological role of blood-borne virus infections in causing reduced lectin-induced T-cell proliferation in haemophilic boys.
T-lymphocyte function, as expressed by polyclonal proliferation to lectin mitogens phytohaemagglutinin and concanavalin A, has been studied in a normal control population and three groups of haemophilic boys: group 1, HIV and HCV seronegative and treated only with a single heat-treated factor VIII (FVIII) concentrate; group 2, HIV seronegative but HCV seropositive; group 3, all HIV and HCV seropositive. Groups 2 and 3 have been previously treated with unheated and heated FVIII concentrate. Group 1 boys (HIV/HCV uninfected) showed no significant reduction in lymphocyte proliferation when compared with a control population. Group 2 and 3 boys showed an impaired response to these mitogens compared to group 1 boys and the control group. There was no relationship between FVIII concentrate received and proliferative response. The absence of immune modulation in haemophilic boys who have not acquired HIV and HCV infection implicates chronic blood-borne virus infections as the major contributory factors to impaired lymphocyte proliferative responses seen in haemophiliacs treated with large-pool concentrates. The presence of virus infections, such as HCV, may account for similar lymphocyte function abnormalities observed in previously described cohorts.
Adolescent↗
Lipid abnormalities in Greek patients with coronary artery disease.
Lipid abnormalities are major risk factors for premature coronary artery disease (CAD). However, the type and prevalence of dyslipidemia in these patients have not been well characterised, especially in some ethnic groups. The purpose of the present work was to determine the lipid disorders in patients of Northwestern Greece with premature CAD. The study population comprised of 132 men and 38 women who underwent elective diagnostic arteriography in our University Hospital. Subjects with > or = 1 lesion that narrowed the lumen of any of the 15 coronary artery segments by > or = 70% were considered to be CAD cases (n=108), whereas those with narrowing < 70% were excluded (n=54). Asymptomatic subjects (n=104) matched for age and sex were taken as controls. Compared with the controls, patients with premature CAD had increased serum levels of total cholesterol, LDL cholesterol, triglycerides, Apo B, and Lp(a), and decreased serum levels of HDL cholesterol and Apo A1. A lipoprotein or apolipoprotein abnormality was identified in 89 CAD patients (82.4%). The increased serum Apo B level (> 130 mg/dl) was the most common lipid abnormality observed in 72 patients. However, the most prevalent dyslipidemic phenotypes in our patients were type IIA followed by hypoalpha and hyperApoB. Compared to the control population, CAD patients had increased incidence of IIA and hypoalpha phenotypes. On the contrary, a normal lipoprotein phenotype was more common in the control population compared to CAD patients (56.7% vs. 17.6%, P<0.001). We conclude that the majority of Greek patients with premature CAD exhibit lipid and lipoprotein abnormalities, which to a large extent can be defined by determining the traditional lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides). However, in some cases the value of the quantification of other lipid parameters such as apolipoproteins and Lp(a) should be taken into account.
Aged↗
Incidence of and mortality from cancer in hypertensive patients.
OBJECTIVES: To assess incidence of and mortality from cancer in hypertensive patients taking atenolol, comparing the findings with two control populations and with hypertensive patients taking other drugs. DESIGN: Retrospective analysis of patients first seen in the Glasgow Blood Pressure Clinic between 1972 and 1990. Patients' records were linked with the registrar general's data for information on mortality and with the West of Scotland Cancer Registry for information on incident and fatal cancers. Cancers were compared in patients and controls and in patients taking atenolol, beta blockers other than atenolol, and hypotensive drugs other than beta blockers. SUBJECTS: 6528 male and female patients providing 54,355 years of follow up. SETTING: Hypertension clinic in Glasgow. MAIN OUTCOME MEASURES: Observed numbers of cancers in clinic patients were compared with expected numbers derived from cancer rates in two control populations adjusted for age, sex, and time period of data collection. RESULTS: Cancer mortality was not significantly different in clinic patients as a whole and controls. Incident and fatal cancers were not significantly increased in male or female patients taking atenolol. Cancer incidence did not rise in the clinic after a large increase in prescriptions for atenolol after 1976. CONCLUSION: This analysis does not suggest a link between atenolol and cancer.
Age Factors↗
Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy.
OBJECTIVE: A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohn's disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammatory mediators, it seems likely that a genetically determined abnormal immune response may lead to a loss of barrier function. METHODS: In a geographic area in Southern Italy with high incidence of CD we investigated IP (lactulose/mannitol testing) together with the three main mutations of the NOD2/CARD15 and the D299G polymorphism of the toll-like receptor (TLR)-4 gene in 23 families of CD patients (patients and first-degree relatives). RESULTS: Forty-eight percent of CD patients and 40% of their healthy relatives were found to have an abnormal IP compared to 5% of an appropriate control population (p < 0.0001). IP, however, was not associated with the L1007finsC mutation of the NOD2/CARD15 or the D299G variant of the TLR-4 gene. Allele frequency of the only L1007finsC mutation of CARD15 was significantly increased in patients (8.7%, p < 0.003) and in relatives (8.3%, p < 0.024) compared with controls (2.4%), whereas the D299G variant of the TLR-4 gene was found to be increased only in relatives (8.3%, p < 0.022), but not in patients (4.3%) compared with the control population (1.7%). CONCLUSIONS: There was no association between IP and genetic markers. Our findings showed a very high proportion of healthy first-degree relatives to bare alterations suggested to constitute determinants of CD. Mutations of NOD2/CARD15 or TLR-4, however, do not lead to permeability defects emphasizing the importance of additional environmental and/or genetic factors for pathogenesis.
Adult↗
Direct causes of death in Japanese patients with hypopituitarism as analyzed from a nation-wide autopsy database.
OBJECTIVES: The direct causes of death in Japanese patients with hypopituitarism remain unclear. In this study, the direct causes of death were investigated and compared between Japanese patients with hypopituitarism from a nation-wide autopsy database and an age- and gender-matched control population from national reports. SUBJECTS: Three hundred and ninety-one subjects with hypopituitarism who had died were selected from a nation-wide autopsy database (1984-1993). The ratios of each cause of death among the age- and gender-matched control population were derived from national reports. RESULTS: In subjects with hypopituitarism, an increased relative frequency of death from cerebrovascular diseases (male; 2.02 (95% confidence interval (CI) 1.45-2.82), female; 1.73 (95% CI 1.18-2.52)) was found. In particular, the relative frequency of death from cerebral hemorrhage was 4.60 (95% CI 2.95-7.17) in male and 4.80 (95% CI 2.90-7.94) in female subjects with hypopituitarism. Unexpectedly, a decreased relative frequency of death from all heart diseases (male; 0.439 (95% CI 0.277-0.696), female; 0.267 (95% CI 0.149-0.478)) was found in subjects with hypopituitarism, although there was no difference between subjects with hypopituitarism and controls in the frequency of death from ischemic heart disease. CONCLUSIONS: These results provide useful information for the long-term care of Japanese patients with hypopituitarism.
Adolescent↗
Resistance and some enzyme activities in Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae) in relation to carbon dioxide enriched atmospheres.
Two populations (S-1 and S-2) of the psocid, Liposcelis bostrychophila Badonnel were exposed to carbon dioxide enriched atmospheres. Carbon dioxide resistance developed at steady rates in these two populations during this study period. Selection with 35 and 55% CO(2) resulted in resistance development as expressed by LT(50). Resistance increased steadily under continuous selection to 4.6- and 5.3-fold by generation F(30) for S-1 and S-2, respectively. Throughout the selection process, the slopes of regression lines were always lower than that of the control. The results of biochemical assays showed that the activities of carboxyl esterase (CarE) and superoxide dismutase (SOD) in vitro increased in the selection process. Exposure to higher CO(2) content (HCC) resulted in a gradual decrease in CarE activity in both selected and control populations. Although the induction effect of CO(2) on SOD was brief, the induction times for the S-1 and S-2 were greater than those of the control. The elevated catalase (CAT) activity in association with resistance development was also evident, but no statistical correlation was found between CAT activity and HCC resistance. No significant differences were found in acid phosphatase and alkaline phosphatase activities in both selected and control populations during this study. This study demonstrated that high CarE and SOD activities were positively correlated to CO(2) resistance.
Journal Article↗
Antibody immunity to prostate cancer associated antigens can be detected in the serum of patients with prostate cancer.
PURPOSE: Several immune based therapies targeting prostate cancer associated proteins are currently undergoing clinical investigation. In general, however, little is known about the immunogenicity of prostate cancer or which prostate cancer associated proteins elicit immune responses. We determine whether patients with prostate cancer have antibody immunity to known prostate cancer associated proteins, what the prevalence of this immunity is and whether immunity to individual proteins is associated with the stage of disease. MATERIALS AND METHODS: We evaluated the inherent humoral immune response against prostate specific antigen (PSA), prostatic acid phosphatase, p53 and HER-2/neu, all known prostate cancer associated proteins, in 200 patients with various stages of disease and male controls. RESULTS: Antibody immunity to PSA was significantly different between the patient (11%, 22 of 200) and control populations (1.5%, 3 of 100, p = 0.02), and titers 1:100 or greater were particularly prevalent in the subgroup of patients with androgen independent disease (11%, 6 of 56). Antibody immunity to prostatic acid phosphatase and p53 was detected (5.5%, 11 of 200 and 6%, 12 of 200), and was not different from the control population (4%, 4 of 100, p = 0.57 and 7%, 7 of 100, p = 0.74). Antibody immunity to HER-2/neu was significantly higher in patients with prostate cancer (15.5%, 31 of 200) compared to controls (2%, 2 of 100, p = 0.0004), and titers 1:100 or greater were most prevalent in the subgroup of patients with androgen independent disease (16%, 9 of 56). CONCLUSIONS: These findings suggest that prostate cancer is an immunogenic tumor. Moreover, for PSA and HER-2/neu the prevalence of antibody immunity was higher in patients with androgen independent disease, indicating that even patients with advanced stage prostate cancer can have an immune response to their tumor.
Acid Phosphatase↗
Gastroesophageal reflux and asthma: insight into the association.
Gastroesophageal reflux (GER) is a potential trigger of asthma. GER symptoms are more prevalent in asthma patients compared with control populations, with a prevalence of approximately 75%. GER symptoms are associated with respiratory symptoms and inhaler use. GER may also occur without esophageal symptoms. Abnormal esophageal acid contact times are also more prevalent in patients with asthma compared with control populations, with a prevalence of 80%. Pathophysiologic mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid may increase minute ventilation without evidence of bronchoconstriction. Esophageal acid is associated with the release of substance P in the bronchial mucosa, resulting in airway edema. Medical antireflux therapy with proton pump inhibitors results in asthma symptom improvement in approximately 70% of patients, similar to surgical results. Predictors of asthma response include the presence of regurgitation, proximal acid reflux, esophagitis healing with therapy, reflux-associated respiratory symptoms, or nocturnal asthma. Management of GER in adult patients with asthma should include a 3-month trial of high-dose proton pump inhibitor while monitoring asthma outcome. GER should be considered as a potential asthma trigger in all patients.
Asthma↗
Polymorphism of GSTM1 gene in patients with colorectal cancer and colonic polyps.
The frequency of the GSTM1 gene in patients with nonpolyposis colorectal cancer (CRC) (n = 70) and in subjects with colonic polyps (n = 27) was evaluated and compared with healthy individuals (n = 145). Patients with CRC were divided into the three groups: patients coming from the families with hereditary nonpolyposis colorectal cancer (HNPCC) (n = 17); patients with a high risk of HNPCC who were referred to as suspected of HNPCC (n = 25); patients with sporadic colorectal cancer without clinical features of hereditary tumours (n = 28). A simple polymerase chain reaction (PCR) - based assay to identify GSTM1 nulled and positive (non-nulled) genotype was used. No significant differences in frequency of nulled individuals were observed in both patients with HNPCC and patients suspected of HNPCC as well as in subjects with colonic polyps. The most interesting observation was made in the group of patients with sporadic CRC. Twenty individuals (71.4 %) of the group were GSTM 1 deficient which was significantly different from the control population (p < 0.04). The above data indicate that the absence of the GSTM1 gene is associated with a greater risk of sporadic colorectal cancer. There is an increase in the overall risk of approximately 2.5 as compared with the control population.
Adolescent↗
Genome-wide association study of long COVID.
Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.
Humans↗
Vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).
To follow-up our previous observation that vaginal agenesis might be associated with decreased activity of galactose-1-phosphate uridyl transferase (GALT), we studied activity and genotype of GALT in 13 daughters with vaginal agenesis and their mothers. For comparison, GALT measurements were available from 113 pre-menopausal women with no known Müllerian anomalies selected from the general population. Red cell GALT activity was significantly lower in both the daughters and their mothers in comparison with general population controls. Six out of thirteen (46%) daughters and two mothers of the remaining seven daughters (29%) were carriers for the N314D mutation of GALT associated with the Duarte variant of galactosaemia as compared to 16 out of 113 general population controls (14%) who possessed at least one N314D allele. Pigmentary skin changes and scoliosis were associated phenotypic findings in daughters with vaginal agenesis. We conclude that fetal or maternal GALT mutations that decrease GALT activity may be associated with vaginal agenesis and have, as their possible biological basis, increased intrauterine exposure to galactose which has been demonstrated in rodents to cause decreased oocyte survival and delayed vaginal opening in offspring.
Female↗
Frequency of p53 codon 72 genotypes in human papillomavirus associated squamous intraepithelial lesions and cervical cancer.
BACKGROUND: A recent study suggested that the p53Arg (at residue 72) homozygous genotype could be a potential genetic risk factor for cervical cancer among white women. To confirm this result we examined the proportion of p53 genotypes in a larger number of patients with cervical cancer and in patients with squamous intraepithelial lesions (SIL) compared to a control population. MATERIALS AND METHODS: We used allele-specific primers to amplify the p53Arg and p53Pro sequences and we examined the proportion of genotypes in the study populations using chi 2-test. RESULTS: The distributions of p53Arg homozygous, heterozygous and p53Pro homozygous genotypes were 63%, 27% and 10% in cervical cancer patients, 53%, 36% and 8% in individuals with SIL, and 60%, 36% and 4% in control population. Using chi-square test, no significant difference was found between genotype frequencies in the study groups. CONCLUSION: Thus, the p53Arg homozygous genotype does not seem to increase the risk of cervical cancer in Hungarian women.
Arginine↗
Insulin and gall stones: a population case control study in southern Italy.
BACKGROUND: Hyperinsulinaemia has been associated with many common diseases in developed countries, such as ischaemic heart disease and colon cancer. Gall stones are also very prevalent in these countries but little is known about the association between insulin and gall stones. AIMS: To study the relationships between insulin and the incidence of gall stones in a sample of the general population. SUBJECTS AND METHODS: Between May 1985 and June 1986, systematic sampling from the electoral register of Castellana, a small town in southern Italy, yielded 2472 subjects who had their gall bladder checked for gall stones by ultrasonography. Between May 1992 and June 1993, 1962 of the 2235 subjects without gall stones at the first examination agreed to a further ultrasound examination. A total of 101 subjects with newly diagnosed gall stones and 303 randomly chosen controls entered the study. Serum insulin was determined by radioimmunoassay, and concentrations of cholesterol, cholesterol high density lipoprotein (HDL), glucose, and triglycerides by standard enzymatic colorimetric methods. Unconditional multiple logistic regression was used to study the association between insulin and gall stones, controlling for the most common confounding factors. RESULTS: In individuals with no clinical diagnosis of diabetes and serum glucose <7 mmol/l, insulin was associated with gall stones. This association persisted even after controlling for sex, age, body mass index, and serum glucose. The risk of gall stones in the highest quintile of serum insulin was 2.66 (95% confidence interval 1.04-6.72; chi(2) test for trend, p=0.03). The association of insulin with gall stones persisted when total and HDL cholesterol were entered in the logistic regression models, and only slightly decreased when serum triglycerides were included in the model. CONCLUSIONS: The results of the study indicate that hyperinsulinaemia may play an important role in the aetiology of gall stones even in individuals without diabetes and with normal serum glucose levels.
Adult↗
Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia.
The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.
Alleles↗
Flow cytometric study of differentiating cultures of Bacillus subtilis.
We report on 1) the development of a flow cytometry-based technique for detecting beta-galactosidase in differentiating cultures of Bacillus subtilis and 2) the application of this technique in the study of early developmental gene expression. The problems associated with generating detectable signals (despite the small size of B. subtilis cells) have been overcome using the fluorogenic substrate 5-octanolyaminofluorescein di-beta-D-galactopyranoside (C8-FDG). Additionally, to control for background fluorescence during the staining process, we included a control population in the C8-FDG staining mixture that consists of cells devoid of the lacZ gene prestained with another dye, PKH26. The distinct emission spectra of C8-fluorescein and PKH26 allow nonspecific C8-FDG staining in this control population to be monitored using two-color analysis. This technique has been applied in the study of developmental gene expression in sporulating cultures of B. subtilis, and it has been found that such cultures are heterogeneous, comprising two cell populations. One population is induced for expression of early sporulation genes, which is determined using lacZ fusions, whereas the other remains uninduced. These results have allowed us to understand better the patterns of gene expression exhibited by wild-type and mutant cultures early during the development process of spore formation.
Bacillus subtilis↗
Simple method to observe the adaptive response of Listeria monocytogenes in food.
A simple, novel method for determining stress-adaptive response of Listeria monocytogenes in food systems is presented. The method involves plating samples on Listeria-selective agar (LSA) acidified to pH 5.25 with incubation at 36 degrees C for 60 h to detect acid adaptation and plating on LSA with 70 gl-1 NaCl and incubation at 7 degrees C for 7 d to detect cold-osmotic adaptation. Adapted cells produced larger colonies (> 1 mm) under these conditions than unadapted cells. Scot A (97%) and Brie-1 (100%) cells incubated in milk at pH 5 for 3 h manifested the acid-adapted colony type compared with 6% and 21% of viable cells in the unstressed control population. After a 5-d adaptation period at 4 degrees C in milk with 80 gl-1 salt, 29% of Scot A and 91% of Brie-1 viable cells exhibited the adapted colony type compared with < 1% of the unstressed control population. Stress-adapted L. monocytogenes were isolated from soft cheese held for 42 d at 10 C.
Adaptation, Physiological↗
Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients.
OBJECTIVE: To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations. DESIGN: Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir. RESULTS: Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS: Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.
Adult↗