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PubMed1992

Evolving epidemiology of HIV infection among adults.

Whereas new, or changes in existing, routes of transmission of HIV have not been identified in the 11 years since AIDS was identified as a clinical syndrome, changes in the epidemiology of HIV infection in the US have been identified during that period. The role of injection drug use as a risk for both parenteral and sexual transmission of HIV has increased substantially during this period. Heterosexual transmission is becoming more prominent as the epidemic continues to "mature" in the US. The likelihood that heterosexual transmission will become progressively more important in the spread of HIV in the US in the next several years seems high. The ability of individuals in some populations at risk for infection to modify risk behaviors has led to a reduction in transmission of HIV in those populations. The addition of nucleoside analog antiretrovirals and effective chemoprophylaxis for Pneumocystis carinii pneumonia has led to increases in both the quality and duration of life for some populations of HIV-infected patients. Neither a chemotherapeutic cure nor a vaccine is on the immediate horizon; education and behavior modification remain the cornerstones of current prevention efforts. For a variety of complex reasons, inappropriate scrutiny has been focused on the remote risks of health-care provider-to-patient transmission of HIV. In the past 11 years medical science has made remarkable progress in understanding the etiology, biology, epidemiology, pathogenesis, and prevention of HIV infection. Despite this progress, a great deal of work remains to be done not only in the medical and basic science arenas but also in the behavioural and sociological sciences.

Adult↗
PubMed1992

Measuring ankle systolic blood pressure: validation of the Dinamap 1846 SX.

Clinical and epidemiologic situations requiring repeated measurements of blood pressure in the lower extremity are increasingly incorporating automated measurement devices; however, no device has been validated adequately for ankle blood pressure. This study evaluates the Dinamap 1846 SX against Doppler ultrasound in determining ankle systolic blood pressure (SBP) and compares a parallel with contour wrapping technique for applying the blood pressure cuff. Ankle SBP was measured on 71 adult volunteers by both devices simultaneously, for each cuff wrap. Averages of three readings were compared to evaluate Dinamap versus Doppler SBP estimates and to assess any cuff wrap effect. Multiple linear regression was used to assess potential effect modifiers. Instrument differences (Dinamap minus Doppler) for the parallel wrap (95% confidence intervals in parenthesis) were -1.5 mmHg (-3.1, 0.0) and -3.9 mmHg (-5.6, -2.2) for the contour wrap. Wrap effect differences (contour minus parallel) for the Doppler were -4.9 mmHg (-6.3, -3.5) and -7.2 mmHg (-8.7, -5.8) for the Dinamap. Degree of ankle taper was a strong modifier of cuff effect for the Dinamap but not for the Doppler: adjusted cuff effect with the Dinamap ranged from -3 to -10 mmHg. Measurement precision (within-person reproducibility, measured by within-person standard deviation [sigma 2] and reliability coefficient [R]) was higher for the Dinamap than the Doppler technique, lowest for the parallel wrap and Doppler configuration (sigma 2 = 5.4 mmHg, R = 0.88) and greatest for the contour wrap and Dinamap (sigma 2 = 4.0 mmHg, R = 0.94). In conclusion, cuff-wrapping technique can generate SBP differences of greater magnitude than instrument differences. Conditional on the use of the contour wrap, and by virtue of its high repeatability and ease of operation, the Dinamap is a useful tool for epidemiologic study and the clinical assessment of peripheral arterial disease.

Adult↗
PubMed2005

Carcinogenicity of the chlorination disinfection by-product MX.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, better known by its historical name 'mutagen X' or MX, is a chlorination disinfection byproduct that forms from the reaction of chlorine and humic acids in raw water. MX has been measured in drinking water samples in several countries at levels that ranged from non-detectable to 310 ng/L. Although the concentration of MX in drinking water is typically 100- to 1000-fold lower than other common chlorinated by-products of concern (e.g., trihalomethanes), some have hypothesized that MX might play a role in the increased cancer risks that have been associated with the consumption of chlorinated water. This hypothesis is based on observations that MX, in some test systems, is extremely potent relative to trihalomethanes in inducing DNA damage and altering pathways involved in cell growth, and that in some epidemiological studies increased cancer rates are associated with the bacterial mutagenicity of disinfected water of which MX contributes a significant portion. MX also appears to be more potent than other chlorination by-products in causing cancer in animals. This article reviews the available evidence on the carcinogenicity of MX. MX induced cancer at multiple sites in male and female rats, acted as a tumor initiator and promoter, enhanced tumor yields in genetically modified rodents, induced a myriad of genotoxic effects in numerous in vitro and in vivo test systems, and was a potent inhibitor of gap junction intercellular communication. Although the precise mechanism of MX-induced DNA damage is not known, MX is able to cause DNA damage through an unusual mechanism of ionizing DNA bases due to its extremely high reductive potential. MX may also cause mutations through DNA adduction. This article develops a mean cancer potency estimate for MX of 2.3 (mg/kg-d)(-1) and an upper 95% percentile estimate of 4.5 (mg/kg-d)(-1), and examines the potential health risks posed by this chlorination contaminant in drinking water. A discussion of additional data that would be desirable to better characterize the risks posed by MX and other halogenated hydroxyfuranones follows.

Animals↗
PubMed1989

An epidemiological model of rinderpest. I. Description of the model.

The development of an epidemiological model of rinderpest in cattle and wildlife populations is described. The model uses a state-transition structure, incorporating a stochastic element through the use of Monte-Carlo methods modified to allow large populations to be simulated. The potential applications include the estimation of "safe" host population immunity rates and the design of cost-effective rinderpest vaccination programmes.

Animals↗
PubMed1999

Helicobacter pylori infection on the risk of stomach cancer and chronic atrophic gastritis.

Helicobacter pylori infection is associated with gastric adenocarcinoma. However, the mechanisms of this interaction are still unclear. This study was conducted to explore the effects of H. pylori infection on early and late stage gastric carcinogenesis. This study included 134 patients with adenocarcinoma of the stomach (ACS), 67 patients with chronic atrophic gastritis (CAG), and 65 normal controls recruited at Memorial Sloan-Kettering Cancer Center (MSKCC) from November 1, 1992 to November 1, 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. H. pylori infection was diagnosed by pathological evaluation. Risk factors were analyzed using logistic regression. The odds ratio (OR) associated with H. pylori infection was 10.4 [95% confidence interval (CI): 2.6-41.6] for CAG and 11.2 (95% CI: 2.5-50.3) for gastric cancer in comparison with normal controls, with adjustment for pack-years of smoking, alcohol drinking, body mass index, total caloric intake, dietary fat and fiber intake, and Barrett's esophagus. But H. pylori infection was not associated with risk of stomach cancer when patients with stomach cancer were compared with patients with CAG (OR = 0.6, 95% CI: 0.3-1.3) after controlling for potential confounding variables. This association was persistent when only patients with both gastric cancer and chronic gastritis were considered as cases and patients with CAG were considered as controls (OR = 0.7, 95% CI: 0.3-2.0) in the multivariate analysis. Our results suggest that H. pylori infection may be involved in the early stage of development of CAG, but not in the development of stomach cancer from CAG, and indicate that strategies for prevention of stomach cancer should target the early stage to eliminate H. pylori infection in high-risk populations.

Adenocarcinoma↗
PubMed2002

Clinical and economic implications of antimicrobial resistance for the management of community-acquired respiratory tract infections.

Lower respiratory tract infections (RTIs), particularly community-acquired pneumonia (CAP), account for over 50 million deaths annually worldwide. They place an extensive clinical and financial burden on healthcare authorities. Upper RTIs, usually mild and non-life threatening, also incur significant healthcare costs. The rising prevalence of resistance of the major causative agents of CAP (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) to beta-lactam antimicrobials and newer macrolides has necessitated new strategies for appropriate antimicrobial usage. A successful clinical outcome will depend on the patient, choice of drug, and the epidemiology and resistance of the pathogen. Treatment failure will result in increased costs, particularly if hospitalization is required. Pharmacokinetic and pharmacodynamic parameters are being used increasingly to predict maximally effective therapy and optimal bacterial eradication, thus limiting the development of resistance. Antimicrobial susceptibility criteria by MIC should be dictated by the type and location of the infection. Modifying the current MIC breakpoints for penicillin so that more pneumococcal pneumonia isolates are reported appropriately as being susceptible may lead to a decrease in the use of broad-spectrum antimicrobial therapy and its associated increased costs, in favour of more narrow-spectrum therapy. Targeting the pathogen with the most effective antimicrobial in an appropriately selected patient should optimize clinical and microbiological success and, consequently, maximize response rates and economic outcomes. In addition, research efforts need to concentrate on developing new agents with low propensity to select for or induce resistance.

Community-Acquired Infections↗
PubMed1994

Etiology and pathogenesis of human neural tube defects: insights from mouse models.

Research into neural tube defects (NTDs) is now entering a rapid phase as advances in experimental embryology and genetics, together with new insights from clinical epidemiology, provide testable hypotheses of the etiology and pathogenesis of these defects. Especially important have been contributions from the study of mouse mutants. The embryologic mechanisms responsible for upper and lower NTDs appear to be distinct, correlating with genetic evidence that distinguishes these phenotypes. The complex genetic etiology of NTDs may result from the effects of several modifier genes acting on a Mendelian trait of major effect, although no candidates are readily apparent for either type of gene. Clues to etiology have come from the preventive effect of nutritional supplements, especially those involved in one-carbon metabolism. More generally, research on NTDs has yielded major insights into how genetic predisposition can interact with environmental influences to modulate the incidence and severity of congenital malformations.

Animals↗
PubMedDate not supplied

Epidemiologic evidence for cardiovascular disease initiatives in Israel and the United States.

There seems to be much epidemiologic evidence implicating a variety of modifiable risk factors in the occurrence of coronary artery disease. Although "common sense" would imply modification of each of these risk factors, on both an individual and a national basis, in order to prevent the occurrence of coronary artery disease in middle and later life, the direct evidence for a beneficial effect from such modifications is, at present, quite meager. Nevertheless, there seems to be a growing awareness and also a growing change in lifestyle and health behaviors that will tend to accomplish the "common sense" recommendations. It is important that monitoring systems be put in place to document the extent of these lifestyle changes and to evaluate their effect on the continuing trends in coronary artery disease incidence and mortality. Joint efforts in the United States, Israel, and other countries will go far to quantitate these effects in these naturally occurring experiments.

Adult↗
PubMed1996

Species-dependent post-translational modification and position 2 allelism: effects on streptococcal superantigen SSA structure and V beta specificity.

Epidemiologic and molecular population genetic analyses support a role for superantigens (SAg) in the pathogenesis of severe staphylococcal and streptococcal infections. To investigate how variations in SAg structure influence immunomodulatory activity, we examined the biochemical and functional properties of two allelic variants of streptococcal SAg SSA that differ at position 2. Mass spectrometry revealed both recombinant (Escherichia coli) and native (Streptococcus pyogenes) SSA allelic variants to have significantly larger molecular masses than predicted by primary sequence alone and provided evidence that the proteins were modified by the addition of biochemical moieties, a phenomenon that has not been described for related SAg. Furthermore, the molecular masses of native and recombinant SSA were not the same; SSA was differentially post-translationally modified by the two bacterial genera. The substitution of E. coli-dependent processing for that of S. pyogenes altered both protease digestion and V beta specificity, suggesting that recombinant SAg from E. coli may not accurately represent the native toxin. In addition, the observation that SSA allelic variants differed in V beta specificity supports a role for position 2 in SSA-TCR interactions. That SSA position 2 contributes to V beta specificity could not have been predicted from functional or crystallographic studies of other SAg and suggests that SSA may adopt unique interactions with TCR and/or MHC class II molecules. Determining the structural basis for these differences should offer additional clues to the manner in which SAg exert their effects on the immune system during infection and may allow the designing of SAg mutants with specific quantitative and qualitative immunomodulatory properties.

Alkylation↗
PubMed1999

Antibiotics in neonatal infections: a review.

The bacteria most commonly responsible for early-onset (materno-fetal) infections in neonates are group B streptococci, enterococci, Enterobacteriaceae and Listeria monocytogenes. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are the main pathogens in late-onset (nosocomial) infections, especially in high-risk patients such as those with very low birthweight, umbilical or central venous catheters or undergoing prolonged ventilation. The primary objective of the paediatrician is to identity all potential cases of bacterial disease quickly and begin antibacterial treatment immediately after the appropriate cultures have been obtained. Combination therapy is recommended for initial empirical treatment in the neonate. In early-onset infections, an effective first-line empirical therapy is ampicillin plus an aminoglycoside (duration of treatment 10 days). An alternative is ampicillin plus a third-generation cephalosporin such as cefotaxime, a combination particularly useful in neonatal meningitis (mean duration of treatment 14 to 21 days), in patients at risk of nephrotoxicity and/or when therapeutic monitoring of aminoglycosides is not possible. Another potential substitute for the aminoglycoside is aztreonam. Triple combination therapy (such as amoxicillin plus cefotaxime and an aminoglycoside) could also be used for the first 2 to 3 days of life, followed by dual therapy after the microbiological results. In late-onset infections the combination oxacillin plus an aminoglycoside is widely recommended. However, vancomycin plus ceftazidime (+/- an aminoglycoside for the first 2 to 3 days) may be a better choice. Teicoplanin may be a substitute for vancomycin. However, the initial approach should always be modified by knowledge of the local bacterial epidemiology. After the microbiological results, treatment should be switched to narrower spectrum agents if a specific organism has been identified, and should be discontinued if cultures are negative and the neonate is in good clinical condition. Penicillins and third-generation cephalosporins are generally well tolerated in neonates. There is controversy regarding whether therapeutic drug monitoring of aminoglycosides will decrease toxicity (particularly renal damage) in neonates, and on the efficacy and safety of a single daily dose versus multiple daily doses of these drugs. Toxic effects caused by vancomycin are uncommon, but debate still exists over the need for therapeutic drug monitoring of this agent. When antibacterials are used in neonates, accurate determination of dosage is required, particularly for compounds with a low therapeutic index and in patients with renal failure. Very low birthweight infants are also particularly prone to antibacterial-induced toxicity.

Anti-Bacterial Agents↗
PubMed2003

Effects of reduction mammaplasty on pulmonary function and symptoms of macromastia.

A number of studies have documented subjective improvement in somatic and psychological symptoms following breast reduction surgery. Objective data demonstrating improved postoperative function have been more difficult to assess, and particularly with respect to pulmonary function, the results have been contradictory. In this prospective study, patients completed a comprehensive preoperative questionnaire modified from the American Thoracic Society Division of Lung Diseases Epidemiology Standardization Project (1978). This questionnaire noted subjective pulmonary symptoms and pulmonary medical history. In addition, subjective symptoms related to breast size, including back and neck pain and shoulder pain and grooving, and a subjective evaluation of body image, were evaluated. All subjects received preoperative pulmonary function testing, including spirometry, lung volume measurements, and measurement of peak inspiratory and expiratory flow rates and pressures. Eight weeks after breast reduction, a repeat questionnaire and pulmonary function testing were administered. Preoperative and postoperative pulmonary function values were compared using Cochran-Mantel-Haenszel tests, and correlations were tested between changes in pulmonary function test values and subjective symptom improvement. Forty-four patients underwent an average of 2228-g bilateral reduction. All of these patients had their surgical procedures preauthorized as medically necessary by their insurance carriers. All subjective parameters examined were statistically significantly improved following breast reduction (p < 0.001). Of the 17 patients with preoperative complaints of shortness of breath, all noted significant improvement following breast reduction surgery (p < 0.001). Of the objective pulmonary criteria evaluated, inspiratory capacity, peak expiratory flow rate, and maximal voluntary ventilation showed a statistically significant improvement following surgery (p < 0.05). These changes correlated with body mass index; the greater the index, the greater the change in maximal voluntary ventilation and peak expiratory flow rate. Smokers in this group had the largest change in maximal voluntary ventilation (p < 0.008). No correlation could be found between preoperative pulmonary symptoms, a single subjective symptom, or grams of breast weight reduction and changes in pulmonary function tests. The results show that pulmonary parameters, related primarily to work of breathing (inspiratory capacity, maximal voluntary ventilation, peak expiratory flow rate), were statistically improved following breast reduction surgery, and these changes correlated with body mass index.

Adolescent↗
PubMed1988

Risk factors for breast cancer: pooled results from three Italian case-control studies.

The role of menstrual and reproductive factors, family history, and body weight in the epidemiology of breast cancer has been reassessed in a meta-analysis of three large case-control studies of breast cancer from several Italian regions, for a total data set of 4,072 cases and 4,099 controls. Multiple logistic regression equations were used to obtain relative risks adjusted for study, center, age, and various combinations of risk factors considered. Relative to women with menarche at age 15 or over, those with earlier menarche had a 20-30% higher breast cancer risk. However, there was no tendency for the risk to increase with lower age at menarche, and the association with menarche was stronger at younger age. The risk of breast cancer was directly related to age at menopause (relative risk (RR) = 0.7 for less than 45 years vs. greater than or equal to 50 years), age at first live birth (RR = 1.8 for greater than or equal to 28 years vs. less than 22 years), and family history of breast cancer in first-degree relatives (RR = 2.0). The effect of these factors was similar in various age strata. After allowance for age at first live birth, the risk of breast cancer did not differ among women with one to four live births, but it was significantly below unity (RR = 0.6) for those with five or more live births. Furthermore, there was a clear modifying effect of age at diagnosis on parity-related risk, since parous women had elevated breast cancer risk below age 35 and reduced risk above age 40.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Epidemiology and clinical features of sleep disorders in extrapyramidal disease.

Sleep disturbances are common in extrapyramidal diseases, including not only insomnia but excessive daytime sleepiness and parasomnias. In particular, complaints related to sleep are extremely common among patients affected by Parkinson's disease (PD). The underlying causes may include: patient age, associated illnesses, cognitive impairment, motor dysfunction caused by disease, neurochemical changes related to the disease, drugs, and secondary psychological responses to the disease. The exact prevalence of sleep disorders in PD is difficult to ascertain, due to the heterogeneity of patients as well as to the different criteria and methods used to diagnose and classify sleep disturbances. In this study, we will attempt to review the epidemiological data and to describe the various sleep disorders, which have been identified in extrapyramidal diseases, with particular reference to PD. There are no data available at present as to the role of gender in sleep disturbances. Finally, the benefit of sleep on extrapyramidal diseases will be addressed, taking into account that the above causes may modify the effects of sleep.

Aging↗
PubMed1999

Immunotoxicological effects of repeated combined exposure by cypermethrin and the heavy metals lead and cadmium in rats.

The immunotoxic effect of a 28 days oral exposure by 55.4, 22.2, and 11.1 mg/kg cypermethrin (CY) was investigated in 4 weeks old male Wistar rats. The applied test system involved the determination of general toxicological parameters (body weight gain, organ weight of thymus, heart, lung, liver, spleen, kidneys, adrenals and the popliteal lymph node), haematological parameters (white blood cell count, red blood cell count, haematocrit, mean cell volume of red blood cells, cellularity of the femoral bone marrow), as well as immune function assays (splenic plaque forming cell assay, delayed type hypersensitivity reaction). The highest dose resulted in a significant increase of the relative liver weight, and all three doses resulted in (although inconsistent) changes in the haematocrit and MCV values. The maximum of DTH reaction decreased at all three doses. On combination of the highest CY dose with non-effective doses of lead or cadmium the immunotoxic effects of the former were modified. When immunotoxic doses of Cd or Pb were combined with the lowest CY dose, further interactions were observed on the examined parameters. The alterations of the immunotoxic effects of CY by simultaneous exposure with Cd or Pb, as described here, can lead to unexpected health consequences and/or can lead to false positive or negative results in human epidemiological studies.

Animals↗
PubMed2006

Chemoprevention of second cancers.

BACKGROUND: "Second cancers" can be thought of in two general categories: (a) those occurring as a consequence of cancer treatment and (b) primary cancers that are thought to develop largely as a consequence of prior lifestyle habits (e.g., chronic smoking, drinking, sun exposures), genetic susceptibility, or interactions of the two. Because there has been limited work on chemoprevention of treatment-related secondary cancers, this minireview will focus on chemoprevention of second cancers with lifestyle/genetic origins. METHODS/RESULTS: Trials aimed at preventing second cancers in patients with tobacco-related cancers (head and neck, lung), skin cancers, breast cancer, and colorectal adenomatous polyps have been completed with some success. However, one finding that has emerged is that, across several cancer sites, subgroups are found with differential response to the chemopreventive agent. For example, smoking status, alcohol consumption, nutritional status, and host tumor characteristics seem to modify chemopreventive efficacy. Stratum-specific (subgroup) findings may occur by chance, requiring a need for supportive evidence from observational epidemiologic studies of the agent (where available), mechanistic studies, or results of other related trials. CONCLUSIONS: Although chemoprevention of second cancers has been realized, it has become increasingly apparent that not all benefit equally. The finding of subgroup effects in completed trials results in the need to consider such subgroup effects in the design of future trials, by either restricting enrollment to particular subgroups (e.g., never or former smokers), or by increasing sample size requirements to allow for variation in response in subgroups in a statistically powerful way.

Alcohol Drinking↗
PubMed2004

The pharmacological actions of nicotine on the gastrointestinal tract.

Increasing use of tobacco and its related health problems are a great concern in the world. Recent epidemiological findings have demonstrated the positive association between cigarette smoking and several gastrointestinal (GI) diseases, including peptic ulcer and cancers. Interestingly, smoking also modifies the disease course of ulcerative colitis (UC). Nicotine, a major component of cigarette smoke, seems to mediate some of the actions of cigarette smoking on the pathogenesis of GI disorders. Nicotine worsens the detrimental effects of aggressive factors and attenuates the protective actions of defensive factors in the processes of development and repair of gastric ulceration. Nicotine also takes part in the initiation and promotion of carcinogenesis in the GI tract. In this regard, nicotine and its metabolites are found to be mutagenic and have the ability to modulate cell proliferation, apoptosis, and angiogenesis during tumoriogenesis through specific receptors and signalling pathways. However, to elucidate this complex pathogenic mechanism, further study at the molecular level is warranted. In contrast, findings of clinical trials give promising results on the use of nicotine as an adjuvant therapy for UC. The beneficial effect of nicotine on UC seems to be mediated through multiple mechanisms. More clinical studies are needed to establish the therapeutic value of nicotine in this disease.

Animals↗
PubMed2006

Religious attendance and mortality: implications for the black-white mortality crossover.

This study investigates the relationships among religious attendance, mortality, and the black-white mortality crossover. We build on prior research by examining the link between attendance and mortality while testing whether religious involvement captures an important source of population heterogeneity that contributes to a crossover Using data from the Established Populations for Epidemiologic Studies of the Elderly, we find a strong negative association between attendance and mortality. Our results also show evidence of a racial crossover in mortality rates for both men and women. When religious attendance is modeled in terms of differential frailty, clear gender differences emerge. For women, the effect of attendance is race- and age-dependent, modifying the age at crossover by 10 years. For men, however; the effect of attendance is not related to race and does not alter the crossover pattern. When other health risks are modeled in terms of differential frailty, wefind neither race nor age-related effects. Overall, the results highlight the importance of considering religious attendance when examining racial and gender differences in age-specific mortality rates.

Black or African American↗
PubMed2000

[The role of statins in prevention of ischemic stroke].

Although associations between cholesterol and coronary heart disease (CHD) are well accepted, the association between cholesterol and stroke remains unclear. Epidemiological studies suggest lack of apparent correlation between cholesterol and cerebrovascular events, however meta-analyses of secondary prevention trials tested statins (HMG-CoA reductase inhibitors) efficacy in reducing cholesterol revealed a powerful statistically significant effect to reduce stroke as well as CHD (32%). Mechanism for stroke reduction can be connected with nonlipid mechanism of statins action: modifying endothelial function and inflammatory responses, plaque stabilisation and inhibition of plaque progression and thrombus formation in the intracranial and extracranial carotid arteries. Stroke events may be also reduced partially as a consequence of CHD reduction.

Coronary Disease↗