Antibiotic management of acute pharyngitis in primary care.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.

Problems with cigarette smoking and attitudes towards the ban of smoking in Shantou, China.

OBJECTIVES: To investigate the extent of cigarette smoking, knowledge of health hazards and attitudes towards the ban of smoking in Shantou, China, as causes for failure to control smoking. STUDY DESIGN: Environmental monitoring and population survey. METHODS: Particulate matter (PM2.5) measurements were conducted in randomly selected public places (restaurants, non-alcoholic drink shops and internet bars) and exposure-related health hazards were evaluated. University students and adult citizens were randomly selected to determine their extent of cigarette smoking, knowledge of health hazards and attitude towards the ban of smoking in public places. The collected data were used to evaluate possible causes and solutions to the smoking problem. RESULTS: From PM2.5 measurements, the average indoor to outdoor concentrations in non-smoking restaurants were 33.4 vs. 30.6 µg/m(3), P > 0.05; average indoor of smoking restaurants was 350.0% higher, P < 0.05; internet bars was 395.7% higher, P < 0.05; and non-alcoholic drink shops was 650.2% higher, P > 0.001. From our survey of 1100 university students: 1) 17.5% and 7.5% were active male and female smokers, respectively; and 2) 57.5% of students would accept a smoke-ban policy. From 502 adult citizens: 1) 27.5% were active male smokers; 2) Approximately 40 and 60% had inadequate knowledge of health hazards from smoking and second-hand smoke exposure; and 3) >90% of them would accept a smoke-ban policy. CONCLUSIONS: Our data indicate that failure to ban smoking was not caused by resistance from smokers but inadequate (national and local) government effort to educate the public and to enforce existing policy. The data suggest that development of a citizen-based approach, in collaboration with willing officials, may be highly successful in the control of cigarette smoking in China.

Environmental and DNA repair risk factors for breast cancer in South China.

PURPOSE: The incidence of breast cancer (BC) in China has been rapidly increasing. We hypothesize that China-specific risk factors, both life-style and inherent ones, contribute to the problem. METHOD: We have conducted an epidemiology and functional DNA repair investigation to identify risk factors for the development of BC in Shantou, China. RESULTS: Our survey of 372 patients and 419 matched normal controls confirmed the significant risk from many universal factors: high BMI, low education level, low fruit intake and sedate lifestyle. Significant risk factors can be organized into endogenous ones (low education and cooking with lard instead of vegetable oil) and externally-introduced ones (sedate life-style and cigarette smoking). We also found highly significant risk from passive exposure to cigarette smoke. Using the Challenge-Comet assay and blood samples from 57 patients who did not inherit the tumor suppressor BRCA gene mutations and 62 matched normal controls; we showed that reduced functional DNA repair capacity was a significant risk factor. In addition, the reduced repair capacity was associated with lymph node metastasis, and with tumors that had negative ER receptor and over-expression of Her-2. CONCLUSION: Our study indicates that combined externally-introduced and endogenous life-style factors were involved with the increased incidence of BC in China. We also showed, for the first time, that inherent deficiency in DNA repair function was a significant risk factor for BC. The inherent deficiency can interact with other risk factors to significantly increase risk for BC. In addition, the reduced repair capacity was associated with certain clinical features that are indicative of poor prognosis. In this context, it is possible to integrate DNA repair capacity knowledge in promoting prevention of BC and in enhancing personalized therapeutic protocols.

Development of esophageal cancer in Chaoshan region, China: association with environmental, genetic and cultural factors.

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer by incidence worldwide. Although the cancer is located at a readily recognizable and accessible site in the body, it is the sixth most common cause of cancer death. The 1- and 5-year survival rates in China are 50% and 15%, respectively. Furthermore, the cancer has distinct geographic and etiological risk factors in different locations around the world. Since ESCC is highly prevalent in the Chaoshan (Southeastern) region of China, this report will focus on a review of risk factors for the cancer in this area. From the review, it is clear that some important and traditional factors are involved, e.g. environmental mutagens, genetic predisposition. However, unique factors, e.g. the drinking of very hot tea, may play an important role. This review highlights the role of complex risk factors (environmental, genetic and cultural) which contribute to the multistage development of cancer: localized injury, inflammation, mitogenesis, mutagenesis, carcinogenesis and eventually mortality. The latter is contributed by unnecessary delay in seeking medical care which may be culturally related. The review emphasizes the need to identify causal mechanisms for the complex carcinogenic process which can provide opportunity for prevention and treatment of this potentially curable cancer.

A re-evaluation of auditory filter shape in delphinid odontocetes: evidence of constant-bandwidth filters.

The auditory filter shape of delphinid odontocetes was previously considered to be typically mammalian constant-quality in which filter bandwidths increase proportionally with frequency. Recent studies with porpoises demonstrate constant-bandwidth portions of the auditory filter. The critical ratios for a bottlenose dolphin were measured between 40 and 120 kHz by behaviorally determining the subject's ability to detect pure tones in the presence of white noise. Critical ratios as a function of frequency were constant, indicating the auditory filter acts as a constant-bandwidth system in this frequency range. Re-analysis of past studies supports these findings, and suggests the delphinid auditory system is best characterized as a constant-Q system below 40 kHz and a constant-bandwidth-like system between 40 kHz and 120 kHz before returning to a constant Q pattern at the highest frequencies.

Genetic polymorphisms and expression of minisatellite mutations in a 3-generation population around the Semipalatinsk nuclear explosion test-site, Kazakhstan.

We have reported previously that a population near the Semipalatinsk nuclear explosion test site had significantly increased minisatellite mutations (MM), suggesting increased germ-line mutation rates from the exposure in 3 generations. We hypothesize that the MM can be used as a surrogate biomarker for functional genetic alterations, e.g. gene mutations and chromosome aberrations. Therefore, we have investigated the influence of polymorphisms in genes on the expression of MM in the same two populations (247 and 172 individuals, for exposed and control, respectively, in 3 generations), and their relationships with radiation exposure. We have chosen the analyses of three polymorphic DNA - repair genes (XRCC1, XRCC1 and XRCC3) and two xenobiotic detoxification genes (GSTT1 and GSTM1). Among the exposed and in comparison with the wild-type gene, the functionally active XRCC1 Arg194Trp was significantly associated with low MM and over-represented in the exposed compared with the control populations. In a similar analysis, the functionally deficient XRCC1 Arg399Glu and XRCC3 Trp241Met were associated with increased and significantly reduced MM, respectively, but these variant genes were under-represented in the exposed population. Both GSTT1 and GSTM1 nulls were significantly associated with increased MM. The former was under-represented but the latter was significantly over-represented in the exposed compared with the control populations. In summary, the data indicate that the expected enzymatic functions of the polymorphic genes are consistent with the MM expression, except the XRCC1 Arg399Glu variant gene. In addition, the variant genes were retained in the three generations in association with their useful function, except for the GSTM1 null. However, the MM frequencies in the exposed were not consistently and significantly higher than those in the control populations, radiation exposure may therefore not have been the only cause for the high MM frequency among the exposed individuals. Since we studied three generations of citizens, the over- and under-representations of variant genes in the exposed population indicate their persistence and elimination, respectively, from the exposed individuals, suggesting their functional influence on survivability. The latter observation also indicates the complexity of gene and environmental interactions, e.g. the GSTM1 null was significantly over-represented in the exposed population.

Occupational exposure to mercury vapour on genotoxicity and DNA repair.

We have conducted a population study to investigate whether current occupational exposure to mercury can cause genotoxicity and can affect DNA repair efficiency. Blood samples from 25 exposed workers and 50 matched controls were investigated for the expression of genotoxicity. The data indicate that mercury exposure did not cause any significant differences between the workers and controls in the baseline levels of DNA strand breaks (as measured by the alkaline version of the single cell gel electrophoresis [SCGE] assay) or sister chromatid exchanges (SCE). However, the exposure produced elevated average DNA tails length in the SCGE assay and frequency of chromosome aberrations. In the studies, isolated lymphocytes were exposed to 6J/m2 UV-C light or 2 Gy dose of X-rays in a challenge assay and repair of the induced DNA damage was evaluated using the SCGE assay. Results from the UV-light challenge assay showed no difference between the workers and controls in the expression of DNA strand breaks after exposure followed by incubation in the absence or presence of the cellular mitogen (phytohemagglutinin, PHA). No difference in DNA strand breaks between the workers and controls was seen immediately after the X-ray challenge, either. However, significant differences were observed in cells that were incubated for 2h with and without phytohemagglutinin. Data from the X-rays challenge assay were further used to calculate indices that indicate DNA repair efficiency. Results show that the repair efficiencies for the workers (69.7% and 83.9% in un-stimulated and stimulated lymphocytes, respectively) were significantly lower than that of matched controls (85.7% and 90.4%, respectively). In addition, the repair efficiency showed a consistent and significant decrease with the duration of occupational exposure to mercury (from 75.7% for <10 years employment, to 65.1% for 11-20 years and to 64.1% for 21-35 years) associated with increase of cytogenetic damage. Our study suggests that the occupational exposure to mercury did not cause a direct genotoxicity but caused significant deficiency in DNA repair. Our observations are consistent with previous studies using the standard chromosome aberration assay to show that exposure to hazardous environmental agents can cause deficiency in DNA repair. Therefore, these affected individuals may have exposure-related increase of health risk from continued exposure and in combination with exposure to other genotoxic agents.

Risk contribution of sexual behavior and cigarette smoking to cervical neoplasia.

Infection with high-risk human papillomavirus (HPV) is considered a "necessary cause" for cervical cancer (CC); however, only some HPV-infected women develop CC. We report on the differential risk contribution of sexual behavior and cigarette smoking to cervical neoplasia in the US and Venezuela. A total of 142 patients and 158 matched-controls were recruited from both countries using the same recruitment protocol, the same pathologists for case verification, and the same experimental procedures for analysis. HPV infection was significantly associated with CC for both populations as expected, but the Venezuelan controls were twice as likely to be infected with HPV as the US controls. Having >2 lifetime sexual partners (OR = 4.7, 95% CI = 1.7-13.1) and initiation of sexual activities before the age of 18 (OR = 4.7, 95% CI = 1.6-13.7) were significant risk factors in a multivariate model for CC in Venezuela. In contrast, current cigarette smoking was a significant risk factor only in the US (OR = 3.6, 95% CI = 1.7-7.7). The observed differences in risk factors support the need for additional studies in different geographic regions and the information can be used to develop country-specific CC prevention programs.

Life style factors and acquired susceptibility to environmental disease.

Multifactorial risk factors are responsible for many diseases. They can be broadly categorized as environmental, genetic and life style factors. Much attention has been focused on the first two categories, e.g. the identification of environmental toxicants/carcinogens and the elucidation of genetic susceptibility to disease. Life style risk factors such as aging, poor nutrition, infection and exposure to toxicants can also increase susceptibility to illnesses. These life style factors can therefore be considered to cause acquired susceptibility for increased risk for environmental disease. Among Egyptians, infection with the parasite, Schistosoma, is the primary risk factor for bladder cancer and the risk is enhanced by exposure to mutagenic chemicals. We have shown that inheritance of susceptible metabolizing genes that can increase body burden of mutagenic chemicals enhances the risk. We have also hypothesized that chronic exposure to mutagenic chemicals causes cellular abnormalities that can reduce the capacity of cells to repair DNA damage and thus increase the risk for environmental disease. We have used a challenge assay to show that cells from cigarette smokers and from populations exposed to uranium, butadiene and pesticides have abnormal DNA repair responses compared to matched controls. On the other hand, the response is normal in workers exposed to very low concentrations of butadiene and benzene, and in mothers who had children with birth defects. This suggests that exposure to high enough concentrations of certain mutagens can cause acquired susceptibility in human populations. The acquired susceptibility is expected to interact with environmental factors and with genetic susceptibility to increase risk for environmental disease.

Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.

Flavonoids are polyphenolic compounds that are present in plants. They have been shown to possess a variety of biological activities at non-toxic concentrations in organisms. Galangin, a member of the flavonol class of flavonoid, is present in high concentrations in medicinal plants (e.g. Alpinia officinarum) and propolis, a natural beehive product. Results from in vitro and in vivo studies indicate that galangin with anti-oxidative and free radical scavenging activities is capable of modulating enzyme activities and suppressing the genotoxicity of chemicals. These activities will be discussed in this review. Based on our review, galangin may be a promising candidate for cancer chemoprevention.

Biomarker monitoring for health risk based on sensitivity to environmental mutagens.

Ongoing human and environmental genome programs have generated a tremendous amount of information regarding the genetic basis for human disease. The information can be used to enhance existing bioassays, as well as to develop new bioassays for improving human monitoring with the goal of disease prevention. In this review, some biomarkers that can be used for the purpose are presented, with an emphasis on using biomarkers to monitor human sensitivity to environmental mutagens. The application of biomarkers in clarifying the role of inherited and acquired susceptibility for developing environmental disease will be discussed. We emphasize the use of biomarkers that can detect mutagen sensitivity and DNA repair deficiency in the humans as an indication of susceptibility to disease. Such sensitivity can be either genetically determined or acquired from the exposure to environmental mutagens.

Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk.

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association between inheritance of polymorphic chemical metabolizing genes and development of environmental cancer (e.g., lung cancer among cigarette smokers). The early reports of such associations have been very encouraging. However, some reported positive associations were not substantiated in subsequent studies using larger sample sizes and different ethnic populations. In this review, some confounding factors that contribute to the discrepancies are presented (e.g., ethnic-dependent distribution of variant gene alleles, differential expression of metabolizing genes, and inadequate study design). It is possible that the precision of the association can be improved if the mentioned investigations are complemented with concurrent studies of biological activities/effects. The usefulness of integrating metabolic susceptibility with biomarker measurement for understanding the development of lung cancers is presented. The importance of using adequate sample size and experimental design is emphasized. Development of a reliable approach for prediction of environmental disease not only will provide fundamental information regarding the genetic basis of human disease but will be useful for reducing disease burden in the population and for advancing patient care. Environ. Mol. Mutagen. 37:215-225, 2001. © 2001 Wiley-Liss, Inc.

Cytogenetic assays for monitoring populations exposed to environmental mutagens.

A variety of cytogenetic assays have been used successfully for monitoring populations exposed to environmental mutagens. The traditional chromosome aberration (CA) assay is one of the most useful, and it also predicts cancer outcome on a population basis. However, the sensitivity of this assay requires improvement, and researchers need to understand other factors that influence the expression of CA and health outcome, especially on an individual basis. The sensitivity and specificity of the CA assay are improved with the use of the fluorescence in situ hybridization (FISH) procedure, which employs a variety of chromosome-specific and chromosome region-specific fluorescence probes to elucidate CA. Factors that influence the expression of CA in a population study include inadequate study design, genetic variations in metabolism of chemicals (genetic susceptibility), and lifestyle differences in response to exposure to environmental mutagens (acquired susceptibility). The latter may involve previous or concurrent exposure to environmental mutagens, e.g., cigarette smoking habits.

Genetic and environmental interactions on oral cancer in Southern Thailand.

Many countries are interested in understanding the relationship between genetic susceptibility and their prevalent environmental cancers for disease prevention. In Thailand we conducted a population-based case-control study of 53 matched pairs to assess the risk of oral cancer in relation to genetic polymorphism of the glutathione-S-transferase genes (GSTM1 and GSTT1) in cigarette smokers, alcohol drinkers, and betel quid chewers. Interaction of the genes with other potential risk factors such as local bean consumption were also elucidated. Homozygous deletion of GSTM1 has a frequency of 56.6% (n = 30 over 53) among the patients and 30.2% (16/53) among the controls. This gene is associated with a 2.6-fold higher risk for development of oral cancer (95% CI 1.04-6.5). Among the null GSTM1 individuals, those who smoke, consume alcohol, and/or chew betel quid have a significantly increased risk for oral cancer with an odd ratio (OR) = 4.0 (95% CI = 1.2-13.7), OR = 7.2 (95% CI = 1.5-33.8), and OR = 4.4 (95% CI = 1.1-17.8), respectively. Interactions between any two of the lifestyle habits for oral cancer risk, however, are not found. The frequency of the GSTT1 null genotype is 34.0% (18/53) among the patients and 47.2% (25/53) among our controls. There is no association between the GSTT1 null allele and oral cancer risk. In conclusion, our study provides data to indicate that individuals who have homozygous deletion of the GSTM1 gene have increased risk for oral cancer. The risk increases further when these individuals are exposed to environmental toxicants such as chemicals in cigarette smoke, alcohol, and betel quid. These baseline data can be applied to a larger population-based study, both to verify the observation and to conduct mechanistic investigations.

Variant metabolizing gene alleles determine the genotoxicity of benzo[a]pyrene.

Understanding the mechanisms involved with genetic susceptibility to environmental disease is of major interest to the scientific community. We have conducted an in vitro study to elucidate the involvement of polymorphic metabolizing genes on the genotoxicity of benzo[a]pyrene (BP). Blood samples from 38 donors were treated with BP and the induction of sister chromatid exchanges (SCE) and chromosome aberrations (CA) were evaluated. The latter is based on the tandem-probe fluorescence in situ hybridization (FISH) assay. The data indicate that the induction of genotoxicity was clearly determined by the inherited variant genotypes for glutathione-S-transferase (GSTM1) and microsomal epoxide hydrolase (EH). In a comparison of the two biomarkers, the CA biomarker shows a more definite association with the genotypes than does SCE. For example, the presence of the GSTM1 null genotype (GSTM1 0/0) is responsible for the highest level and significant induction of CA, irrespective of the presence of other genotypes in the different donors. This effect is further enhanced significantly by the presence of the excessive activation EH gene allele (EH4*) and decreased by the reduced activation EH gene allele (EH3*). Overall, the modulation of genotoxicity by the susceptibility genotypes provides support of their potential involvement in environmental cancer. Furthermore, the data indicate that the variant enzymes function independently by contributing their metabolic capability toward the expression of biologic activities. Therefore, studies like this one can be used to resolve the complexity of genetic susceptibility to environmental disease in human.

One-hydrophone method of estimating distance and depth of phonating dolphins in shallow water.

Previous attempts at localizing cetaceans have generally used multiple hydrophone arrays and multichannel recording systems. In this paper, a low-budget localization technique using only one hydrophone is described. The time delays of the signals traveling via the surface and bottom reflection paths to the hydrophone, relative to the direct signal, are used to calculate the distance and the depth of a phonating animal. Only two additional measures, the depth of the bottom and hydrophone, have to be taken. The method requires relatively shallow waters and a flat bottom surface. Echolocating and burst pulsing Hawaiian spinner dolphins (Stenella longirostris) at the Waianae coast of Oahu, Hawaii, were localized over different bottom substrates. A tracking range of up to 100 m was achieved. The accuracy of the method is estimated by the total error differential technique. The relative distance estimation error is below 35% and the absolute depth error below 0.7 m, so that the location method is sufficiently precise for examining source levels in our study area. Because of its simplicity, the method ideally complements sound recordings and visual sightings of marine mammals and could lead to a better understanding of the nature and use of click trains by dolphins.

Classification of electronically generated phantom targets by an Atlantic bottlenose dolphin (Tursiops truncatus).

Animal behavior experiments require not only stimulus control of the animal's behavior, but also precise control of the stimulus itself. In discrimination experiments with real target presentation, the complex interdependence between the physical dimensions and the backscattering process of an object make it difficult to extract and control relevant echo parameters separately. In other phantom-echo experiments, the echoes were relatively simple and could only simulate certain properties of targets. The echo-simulation method utilized in this paper can be used to transform any animal echolocation sound into phantom echoes of high fidelity and complexity. The developed phantom-echo system is implemented on a digital signal-processing board and gives an experimenter fully programmable control over the echo-generating process and the echo structure itself. In this experiment, the capability of a dolphin to discriminate between acoustically simulated phantom replicas of targets and their real equivalents was tested. Phantom replicas were presented in a probe technique during a materials discrimination experiment. The animal accepted the phantom echoes and classified them in the same manner as it classified real targets.

Role of polymorphic CYP2E1 and CYP2D6 genes in NNK-induced chromosome aberrations in cultured human lymphocytes.

Polymorphisms in genes of xenobiotic-metabolizing enzymes are largely responsible for interindividual differences in ability to activate and detoxify genotoxic agents and therefore may influence individual susceptibility to environmental cancer. The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), requires metabolic activation by cytochrome P450 (CYP) enzymes to generate DNA-reactive intermediates that induce mutations and cancer. In the current study, we investigated the role of the polymorphic CYP2E1 and CYP2D6 genes in the genotoxicity of NNK using the tandem-probe fluorescence in-situ hybridization (FISH) chromosome aberration assay as a marker. Our results, using whole blood cultures from 39 volunteers, indicated that NNK (0.12, 0.24 or 0.72 mM) induced a concentration-dependent increase in the frequency of chromosome aberration. The potential role of CYP2E1 and CYP2D6 in NNK-induced genetic damage in cultured human lymphocytes was characterized using specific CYP inhibitors. Treatment of blood cultures with 25 microM diethyldithiocarbamate (DDC), a specific CYP2E1 inhibitor, or 0.5 microM quinidine, a specific CYP2D6 inhibitor, simultaneously with NNK, significantly decreased NNK-induced chromosome aberration. We also studied the role of CYP2E1 and CYP2D6 allelic variants on NNK-induced chromosome aberration. Our results indicate that NNK induced a significantly higher level of chromosome aberration in cells with the CYP2E1 WT/*5B genotype compared to cells with the CYP2E1 WT/WT. In contrast, no difference in NNK-induced chromosome aberration was observed between cells with the CYP2D6 extensive metabolizers compared to cells with the CYP2D6 poor metabolizer genotypes. These results underscore the important role of polymorphic metabolizing genes in influencing the genotoxic responses to environmental mutagens and provide support to the reported findings linking CYP2E1 polymorphism to smoking-related lung cancer.

Acoustic interaction of humpback whales and whale-watching boats.

The underwater acoustic noise of five representative whale-watching boats used in the waters of west Maui was measured in order to study the effects of boat noise on humpback whales. The first set of measurements were performed on 9 and 10 March, close to the peak of the whale season. The ambient noise was relatively high with the major contribution from many chorusing humpback whales. Measurements of boat sounds were contaminated by this high ambient background noise. A second set of measurements was performed on 28 and 29 April, towards the end of the humpback whale season. In both sets of measurements, two of the boats were inflatables with outboard engines, two were larger coastal boats with twin inboard diesel engines and the fifth was a small water plane area twin hull (SWATH) ship with inter-island cruise capabilities. The inflatable boats with outboard engines produced very complex sounds with many bands of tonal-like components. The boats with inboard engines produced less intense sounds with fewer tonal bands. One-third octave band measurements of ambient noise measured on 9 March indicated a maximum sound pressure level of about 123 dB re 1 microPa at 315 Hz. The maximum sound pressure level of 127 dB at 315 Hz was measured for the SWATH ship. One of the boats with outboard engines produced sounds between 2 and 4 kHz that were about 8-10 dB greater than the level of background humpback whale sounds at the peak of the whale season. We concluded that it is unlikely that the levels of sounds produced by the boats in our study would have any grave effects on the auditory system of humpback whales.