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Iodine rapidly penetrates into microorganisms has been described as an effective antiseptic (248) prehypertension numbers buy coreg 25 mg visa. Hypochlorous acid they may also destabilize membrane fatty acids by reacting with has long been considered the active moiety responsible for unsaturated carbon bonds (486) blood pressure guidelines by age purchase coreg 25 mg. H2O2 is con- silver protein pulse pressure and map buy coreg once a day, all of which have antimicrobial properties blood pressure tester purchase coreg master card, are sidered environmentally friendly arrhythmia uptodate discount coreg 6.25 mg without a prescription, because it can rapidly de- listed in Martindale, the Extra Pharmacopoeia (312). Although years, silver compounds have been used to prevent the infec- pure solutions are generally stable, most contain stabilizers tion of burns and some eye infections and to destroy warts. The mechanism of the antimicrobial action of efficacy against viruses, bacteria, yeasts, and bacterial spores silver ions is closely related to their interaction with thiol (sul- (38). Liau et al (287) demon- or other peroxidases in these organisms can increase tolerance strated that amino acids such as cysteine and other compounds in the presence of lower concentrations. Higher concentrations such as sodium thioglycolate containing thiol groups neutral- of H2O2(10 to 30%) and longer contact times are required for ized the activity of silver nitrate against P. It has sulfite, and sodium thiosulfate were all unable to neutralize been proposed that exposed sulfhydryl groups and double Ag1activity. These and other findings imply that interaction of bonds are particularly targeted (38). Hydrogen bonding, the effects of sporicidal, bactericidal, virucidal, and fungicidal at low concen- hydrogen bond-breaking agents, and the specificity of Ag1for trations (,0. Its main application is as a low-temperature liquid ster- metals such as copper act by binding to key functional groups ilant for medical devices, flexible scopes, and hemodialyzers, of fungal enzymes. Ag1 causes the release of K1 ions from but it is also used as an environmental surface sterilant (100, microorganisms; the microbial plasma or cytoplasmic mem- 308). Silver nitrate causes marked inhi- bition of growth of Cryptococcus neoformans and is deposit- Phenols ed in the vacuole and cell wall as granules (60). Ag1 inhibits cell division and damages the cell envelope and contents of Phenolic-type antimicrobial agents have long been used for P. Bacterial cells increase in size, and the their antiseptic, disinfectant, or preservative properties, de- cytoplasmic membrane, cytoplasmic contents, and outer cell pending on the compound. It has been known for many years layers all exhibit structural abnormalities, although without any (215) that, although they have often been referred to as “gen- blebs (protuberances) (398). Srivastava and Thompson (487, brane blebs in susceptible (but not resistant) bacteria (96). Peroxygens Coagulation of cytoplasmic constituents at higher phenol con- centrations, which causes irreversible cellular damage, has been Hydrogen peroxide. Because of its phenolic na- phage band proteins unless treatments of 20 min or longer are ture, it would be expected to have an effect on microbial mem- used (303, 304). Bis-Phenols Quaternary Ammonium Compounds the bis-phenols are hydroxy-halogenated derivatives of two Surface-active agents (surfactants) have two regions in their phenolic groups connected by various bridges (191, 446). In molecular structures, one a hydrocarbon, water-repellent (hy- general, they exhibit broad-spectrum efficacy but have little drophobic) group and the other a water-attracting (hydrophilic activity against P. Triclosan and hexachlorophane are the sence of ionization of the hydrophilic group, surfactants are most widely used biocides in this group, especially in antiseptic classified into cationic, anionic, nonionic, and ampholytic (am- soaps and hand rinses. Of these, the cationic agents, as exem- have cumulative and persistent effects on the skin (313). Triclosan (2,4,49-trichloro-29-hydroxydiphenyl most useful antiseptics and disinfectants (160). In addition to having antimi- caused increased permeability of the outer membrane (282). The specific mode of action of triclosan is unknown, but active agents (221) (Table 2). Salton (460) proposed the hibitory concentrations inhibited the uptake of essential nutri- following sequence of events with microorganisms exposed to ents, while higher, bactericidal concentrations resulted in the cationic agents: (i) adsorption and penetration of the agent rapid release of cellular components and cell death (393). Specifically, a prominent 14:1 fatty organization and integrity of the cytoplasmic membrane in acid was absent in the resistant strain, and there were minor bacteria, together with other damaging effects to the bacterial differences in other fatty acid species. Minor changes in can be obtained by studying the effects of biocides on proto- fatty acid profiles were recently found in both E. The cationic agents react with phos- phenols, that the cumulative effects on multiple targets con- pholipid components in the cytoplasmic membrane (69), there- tribute to the bactericidal activity (318, 319). The threshold con- roplasts suspended in various solutes because they effect gen- centration for the bactericidal activity of hexachlorphene is 10 eralized, rather than specific, membrane damage. Unlike chlorhexidine, however, no biphasic effect on protoplast lysis was observed. The can be effectively sterilized by liquid sterilants (in particular asterisk indicates that the conclusions are not yet universally agreed upon. The most widely used active agents in these “cold systems are ethylene oxide, form- differences; with recent work, this classification can be further aldehyde and, more recently developed, hydrogen peroxide extended (Fig. Ethylene oxide and formaldehyde are both broad- differently, it is convenient to consider bacteria, fungi, viruses, spectrum alkylating agents. As alkylating agents, they Bacterial Resistance to Antiseptics and Disinfectants attack proteins, nucleic acids, and other organic compounds; In recent years, considerable progress has been made in both are particularly reactive with sulfhydryl and other en- understanding more fully the responses of different types of zyme-reactive groups. Ethylene oxide gas has the disadvan- bacteria (mycobacteria, nonsporulating bacteria, and bacterial tages of being mutagenic and explosive but is not generally spores) to antibacterial agents (43, 84, 414, 415, 419, 422, 496). Intrinsic resistance is demonstrated by gram- more active (as oxidants) at lower concentrations than in the negative bacteria, bacterial spores, mycobacteria, and, under liquid form (334). Both active agents are used in combination certain conditions, staphylococci (Table 5). Acquired, plasmid- with gas plasma in low-temperature sterilization systems (314). In recent years, acquired low toxicity, rapid action, and activity at lower temperature; the resistance to certain other types of biocides has been observed, disadvantages include limited penetrability and applications. The nature and As stated above, different types of microorganisms vary in composition of these layers depend on the organism type and their response to antiseptics and disinfectants. This is hardly may act as a permeability barrier, in which there may be a surprising in view of their different cellular structure, compo- reduced uptake (422, 428). Traditionally, microbial susceptibility to constitutively synthesized enzymes may bring about degrada- antiseptics and disinfectants has been classified based on these tion of a compound (43, 214, 358). Gram-negative bacteria tend to be more helped provide a considerable amount of useful information. Clostridium species are significant pathogens; for sporulation and may be an early, intermediate, or (very) late example, C. Many biocides are bactericidal or the development of resistance are toluene (resistance to which bacteristatic at low concentrations for nonsporulating bacteria, is an early event), heat (intermediate), and lysozyme (late) including the vegetative cells of Bacillus and Clostridium spe- (236, 237). In brief, (marker), sodium dichloroisocyanurate, sodium hypochlorite, the germ cell (protoplast or core) and germ cell wall are sur- lysozyme (marker), and glutaraldehyde. The association of the rounded by the cortex, outside which are the inner and outer onset of resistance to a particular antiseptic or disinfectant spore coats. A thin exosporium may be present in the spores of with a particular stage(s) in spore development is thereby dem- some species but may surround just one spore coat. The cortex gram-positive and gram-negative bacteriaa consists largely of peptidoglycan, including a spore-specific muramic lactam. These aspects, especially the roles of the coat(s) Cetrimide 4 16 64–128 Chlorhexidine 0. Phenol 2,000 2,000 2,000 Several techniques are available for studying mechanisms of o-Phenylphenol 100 500 1,000 spore resistance (428). They include removing the spore coat Propamine isethionate 2 64 256 and cortex by using a “step-down technique to achieve a high- Dibromopropamidine isethionate 1 4 32 ly synchronous sporulation (so that cellular changes can be Triclosan 0. In aqueous solution, formaldehyde forms a glycol in equilibrium (512, 524); thus, formaldehyde could well be acting poorly as an alcohol-type disinfectant rather than as an aldehyde (327). Resistance to formaldehyde may be linked to cortex maturation, and resistance to glutar- aldehyde may be linked to coat formation (262). Arabic numbers indicate the and hypochlorite but may not be the only factors involved, time (hours) following the onset of sporulation and the approximate times at since the coats and cortex also play a role (428). However, Bloomfield and the revival of disinfectant-treated spores has not been ex- Arthur (44, 45) and Bloomfield (43) showed that this treatment tensively studied. Spicher and Peters (483, 484) demonstrated also removes a certain amount of cortex and that the amount that formaldehyde-exposed spores of B. A the initial development and maturity of the cortex are im- small proportion of glutaraldehyde-treated spores of various plicated in the development of resistance to phenolics. Experiments designed to distinguish between resistance is enhanced in developing spores by the initiation of germination and outgrowth in the revival process have dem- spore coat synthesis (262). The effect of various concentrations onstrated that sodium hydroxide-induced revival increases the of chlorhexidine, sublethal to vegetative bacteria, on the de- potential for germination. Mycobacteria are well creased, spore index values (the percentage of cells forming known to possess a resistance to antiseptics and disinfectants spores) decreased and sensitivity to both heat and toluene that is roughly intermediate between those of other nonsporu- increased. By contrast, the control (untreated) culture was lating bacteria and bacterial spores (Fig. The peptidoglycan is covalently proaches, these procedures provide further evidence of the in- linked to the polysaccharide copolymer (arabinogalactan) made volvement of the cortex and coats in chlorhexidine resistance. Similar cell wall appears to be at odds with the extremely late development of structures exist in all the mycobacterial species examined to resistance to the dialdehyde, glutaraldehyde. The cell wall composition of a particular species hyde and the monoaldehyde, formaldehyde, contain an alde- may be influenced by its environmental niche (27). Pathogenic hyde group(s) and are alkylating agents, it would be plausible bacteria such as Mycobacterium tuberculosis exist in a relatively to assume that they would have a similar mode of sporicidal nutrient-rich environment, whereas saprophytic mycobacteria action, even though the dialdehyde is a more powerful alkyl- living in soil or water are exposed to natural antibiotics and ating agent. If this were true, it could also be assumed that tend to be more intrinsically resistant to these drugs. However, the activity of these can be have also observed an above-average resistance of M. The reasons for this high glutaraldehyde resistance are For example, a newer formulation (Sactimed-I-Sinald) con- unknown. There is no evidence to date that some doubt whether the antibacterial agents had been prop- uptake of glutaraldehyde by M. In support of this molecular-weight substances can readily traverse the cell wall contention, Mycobacterium phlei, which has a low total cell of staphylococci and vegetative Bacillus spp. Growth rate and any growth- highly hydrophobic nature of the cell wall, hydrophilic biocides limiting nutrient will affect the physiological state of the cells. How- linking of peptidoglycan are likely to be modified and hence ever, low concentrations of antiseptics and disinfectants such the cellular sensitivity to antiseptics and disinfectants will be as chlorhexidine must presumably traverse this permeability altered. The component(s) of the mycobac- However, lysozyme-induced protoplasts of these cells remained terial cell wall responsible for the high biocide resistance are sensitive to, and were lysed by, these membrane-active agents. Therefore, the cell wall in whole cells is responsible for their Inhibitors of cell wall synthesis increase the susceptibility of modified response. Eth- phenols or chlorinated phenols (263); removal of slime by ambutol, an inhibitor of arabinogalactan (391, 501) and phos- washing rendered the cells sensitive. Therefore, the slime pholipid (461, 462) synthesis, also disorganizes these layers. In plays a protective role, either as a physical barrier to disinfec- addition, ethambutol induces the formation of ghosts without tant penetration or as a loose layer interacting with or absorb- the dissolution of peptidoglycan (391). From these data, it may be against gram-positive and -negative organisms are provided in inferred that arabinogalactan is one cell wall component that Table 6.

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At the same time blood pressure too high purchase genuine coreg online, potassium ions (K+) diffuse out through other pores (see Figure 4-1) arteria occipitalis buy discount coreg online. The local anesthetic effect lasts as long as the agent maintains a certain critical concentration in the nerve membrane heart attack krokus album buy coreg 12.5mg otc. There is a potential problem: the local concentration needed to prevent conduction of the nerve impulse is much greater than the tolerable blood level arteria obturatoria best order for coreg. Vasoconstrictors (like epinephrine) are sometimes used in conjunction with local anesthetics blood pressure xl cuff buy coreg australia. Furthermore, the vasoconstrictor delays the absorption of the local anesthetic by reducing the blood flow to the affected area. Vasoconstrictors are of no value in delaying the absorption of the local anesthetic from mucous membranes (that is, topical blocks). This is because a very low pH is required to stabilize the epinephrine in these mixtures. In general, the content of one part epinephrine to 200,000 parts of the local anesthetic agent (is optimum) will minimize the side effects inherent with epinephrine. It should be noted that the standard solution of epinephrine supplied is a 1:1000 (1 to 1000) concentration in each glass ampule. This means that 1 milliliter of the 1:1000 epinephrine solution contains 1 milligram of epinephrine. In preparing a 1:200,000 dilution, epinephrine should be added to a local anesthetic solution on a ratio of 0. This does not apply to subarachnoid injections, in which a higher concentration of epinephrine is required. Hyaluronidase is an enzyme that breaks down the material that binds cells together. Thus, when hyaluronidase is combined with local anesthetic, greater infiltration (movement) of the local anesthetic in the tissues is made possible. Precautions should be taken against the danger of confusing the various agents with one another or mistaking different concentrations of the same drug. In order to avoid intravascular (into the veins) injection, aspiration in several planes with the plunger of the syringe should always be done before injecting the anesthetic solution into the tissues. The instillation of local anesthetic agents into the trachea and bronchi leads to immediate absorption, which soon reach blood levels comparable to those reached by straight intravenous injection. A previously punctured vial of local anesthetic solution should never be re- autoclaved. Therefore, to avoid a systemic toxic reaction to a local anesthetic, the smallest amount of the most dilute solution that effectively blocks pain should be administered. Although such allergies are very rare, a careful patient history should be taken in an attempt to identify the presence of an allergy. There are two basic types of local anesthetics (the amide type and the ester type). A patient who is allergic to one type may or may not be allergic to the other type. Local anesthetics if absorbed systematically in excessive amounts can cause depression of the cardiovascular system. Hypotension and a certain type of abnormal heartbeat (atrioventricular block) characterize such depression. The discussion does not cover every fact known about the use of a particular drug. Therefore, you are encouraged to read references or to ask knowledgeable personnel your specific questions concerning points not presented in this subcourse. Lidocaine is used as a local anesthetic for infiltrations, nerve blocks, spinal anesthesia, topical anesthesia, and for caudal and epidural anesthesia. Lidocaine is available in injection form (various percentage concentrations), jelly form, and in cream form. This drug is less toxic than lidocaine because it is metabolized and excreted faster than lidocaine. Dibucaine is available in cream, spray, suppository, ointment, and injection forms. Chloroprocaine is used for infiltration, nerve block, caudal, and epidural anesthesia. Tetracaine is used for topical, nerve block, infiltration, spinal, and caudal anesthesia. It has a rapid onset of action (20 seconds) and its duration of action is approximately 15 minutes. It is used in many over-the-counter spray preparations for the treatment of sunburn and itching. Cocaine is applied to produce local anesthesia with intensive vasoconstriction on mucous membranes. It is applied to procedure anesthesia in the nose, throat, ear, and in bronchoscopy (a procedure in which an instrument is used to inspect the bronchi). Dichlorotetrafluorethane is a nonflammable and non- explosive agent for topical anesthesia of the skin. This agent should not be sprayed on the skin for a period that exceeds 45 seconds. After you have completed all of these exercises, turn to "Solutions to Exercises" at the end of the lesson and check your answers. For each exercise answered incorrectly, reread the material referenced with the solution. A type of anesthesia achieved by applying the anesthetic agent to the surface of mucous membranes to block nerve transmissions. A type of anesthesia achieved when the nerve endings in the skin and subcutaneous tissues are blocked by direct contact with a local anesthetic that is injected into the tissue. A type of anesthesia accomplished by injecting a nerve that leads to the operative site. A type of anesthesia accomplished by injecting a local anesthetic into the peridural space. Which of the following statements best describes the mechanism of action of local anesthetics? Local anesthetics destroy the nerve tissue so that electrical impulses cannot be carried. Local anesthetics greatly increase the number of electrical impulses being transmitted so that pain cannot be felt in that particular area. Local anesthetics block depolarization of the nerve membrane so that the conduction of the nerve impulse is impossible. Local anesthetics remove both potassium and sodium ions from the nerve tissue so that polarity in the nerve cannot be accomplished; therefore, the impulses are not allowed to move past a certain point in the tissue. Hyaluronidase concentrates the local anesthetic in a particular area in order that its effects might be prolonged. Hyaluronidase neutralizes the local anesthetic so that undesired adverse effects are greatly reduced. Hyaluronidase is an enzyme that acts to tenderize the tissue and make the nerves more sensitive to the effects of the local anesthetic. Select the caution(s) and warning(s) associated with the use of local anesthetics. When a local anesthetic is to be injected, the plunger should be aspirated in several planes to ensure the drug is not being injected into a vein. Large amounts of systemically absorbed local anesthetics can cause depression of the cardiovascular system. Local anesthetics, even when given in small amounts, cause tremors, shivering, and convulsions. Used to produce both anesthesia and vasoconstriction when applied to certain tissues. Used to produce anesthesia in a localized area when applied topically (that is, bronchoscopy). Select the caution and warning associated with the use of procaine ® (Novocaine ). From a list of functions, select the function(s) for which nervous tissues are specialized. Given one of the following terms: neuron, dendrite, or axon, and a group of definitions, select the definition of that term. Given the shape, diameter, or function of a type of neuron and a list of types of neurons, select the type of neuron described. Given a group of statements, select the statement that best describes the neuromuscular junction. Given a group of statements, select the statement that best describes the function of a neurotransmitter. From a list of chemical substances, select the substance(s) which is/are neurotransmitter(s). Given a list of names, select the names of the three major divisions of the human nervous system. Given a list of names, select the names of the two major subdivisions of the central nervous system. Given the name of one of the major subdivisions of the human brain and a list of functions, select the function(s) of that part. Given a list of functions, select the function of the meninges surrounding the brain and spinal cord. There are several different types of glia, but their general function is support (physical, nutritive, and so forth. Cells receiving stimuli are said to be "irritable" (as are all living cells somewhat). An axon is a neuron branch that transmits information from the cell body to the next unit. Some neuron processes have a covering that is a series of Schwann cells, interrupted by nodes (thin spots). In order of decreasing thickness, they are rated A (thickest), B, and C (thinnest). In motor neurons, impulses are transmitted from the central nervous system to muscles and glands (effector organs). There are other, more specialized types of neurons found in the body (for example, central nervous system). There is just enough space to prevent the electrical transmission from crossing from the first neuron to the next. Information is transferred across the synaptic cleft by chemicals called neurotransmitters. Synaptic vesicles (bundles of neurotransmitters) are located within each terminal knob.

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Twenty samples were selected from women in each group (mean age of cases arrhythmia icd 9 code coreg 6.25mg on-line, 63 blood pressure medication zestril generic coreg 12.5mg with visa, range 36–86 years; mean age of controls arterial occlusion order coreg 6.25 mg fast delivery, 59 pulse pressure young buy coreg 25mg on line, range arteria gastroepiploica dextra order coreg 6.25mg overnight delivery, 45–76 years) for analysis of several pesticides, including three metabolites of chlordane (heptachlor epoxide, oxychlordane and trans-nonachlor). The mean value (wet weight basis ± standard deviation) of the sum of heptachlor epoxide and oxy- chlordane was 116 ± 50 ng/g for women with breast carcinoma and 97 ± 49 ng/g for those with benign disease (t test, p = 0. For trans-nonachlor, the corresponding figures were 87 ± 37 ng/g and 96 ± 80 ng/g (p = 0. Between November 1991 and May 1992, adipose tissue was collected from 41 women aged 40–69 who had undergone a biopsy in a hospital in Québec City (Canada), and the organochlorine content was determined (Dewailly et al. The mean oxychlordane concentration was 31 ± 12 ng/g in breast adipose tissue from the 17 subjects with benign disease, 27 ± 7 ng/g (Student t test, p = 0. For trans- nonachlor, the mean concentrations in the three groups were 42 ± 18, 35 ± 8 (p = 0. According to the Danish Cancer Registry, 268 of the women developed breast cancer between 1976 and 1993. For each case, two women free of breast cancer and matched for age, date of examination and vital status at the time of diagnosis were randomly selected as controls. Heptachlor, heptachlor epoxide, α- and γ-chlordane, oxychlordane and trans-nonachlor were among the com- pounds measured. Conditional logistic regression was used to estimate odds ratios for categories of pesticide concentrations. The authors did not report the concentrations of chlordane metabolites but indicated that no association was found. Although active postal follow-up continued until 1989, 70% of the cohort was last contacted in 1982–83. A histologically confirmed breast cancer was diagnosed in 105 of the 6426 women for whom at least 4 mL of serum remained in the bank and who had had no history of cancer at the time of blood collection. Two controls were selected for each case, who were alive and free of cancer and matched to the cases by age, date of blood sample collection and history of benign breast disease at enrolment. Since the serum samples of two controls could not be analysed, 208 controls were included in the analysis. Among the compounds measured by gas chromatography were heptachlor, heptachlor epoxide, cis- and trans-chlordane, oxychlordane and trans-nonachlor. None of the samples contained cis- or trans-chlordane or heptachlor epoxide at concentrations above the limit of detection. Of 824 women who were under the age of 80, were scheduled for biopsy in two hospitals in Toronto and Kingston (Canada) between July 1995 and June 1997, had no history of cancer, had not participated in tamoxifen trials, had not had a breast implant and were not too ill to participate, 735 (89%) agreed to participate in a case–control study and 663 (81%) completed a questionnaire by telephone or mail (Aronson et al. Organochlorine compounds were determined in benign tissue taken during biopsy from 217 women with in-situ or invasive breast cancer and in 213 women matched for age and study site whose biopsy samples showed no malignancy but most of whom had a diagnosis of some form of benign breast disease. For other compounds, the women were divided into four categories according to the tissue concentration. For cis- nonachlor, the odds ratios estimated by logistic regression and adjusted for several potential confounders were 0. When analyses were conducted separately for pre- and postmenopausal women, the results were similar in the two groups. A study conducted in Québec, Canada, between 1994 and 1997 included 315 women aged 30–70 years and residing in the Québec City area with histologically confirmed breast cancer, 219 controls recruited in four hospitals of the study area and free of gynaecological diseases and 307 controls selected from the general population (Demers et al. Blood samples were obtained before therapy, and cis- and trans-chlordane, cis-nonachlor, trans-nonachlor and oxychlordane were measured. As cis- and trans-chlordane and cis-nonachlor were detected in less than 70% of the blood samples, they were excluded from further analysis. In comparison with the first quintile of oxychlordane serum concentration, the adjusted odds ratios for women with concen- trations in subsequent quintiles were 1. The concentrations of oxychlordane and trans-nonachlor in blood were associated with the extent of disease. Of the 490 women enrolled, 304 had histologically confirmed breast cancer and 186 had histologically confirmed benign breast disease (excluding atypical hyperplasia). The age- and lipid-adjusted geometric mean adipose tissue concentrations of oxychlordane and trans-nonachlor were similar for cases and controls. In comparison with the lowest quartile of concentration, the odds ratios adjusted for several covariates were 0. A case–control study of endometrial cancer was conducted between 1996 and 1997 in 12 Swedish counties, which included 288 (73%) of the 396 cases of histologically confirmed endometrial cancer identified through a network of personnel at the departments of gynaecology and gynaecological oncology in the study area (Weiderpass et al. An additional 134 women were excluded since they had used hormone replacement therapy, thus leaving 154 cases. Of the 742 women selected as controls from population registers and frequency matched to cases by 5-year age group, 205 were included in the study; the others were excluded because they had undergone hysterectomy, had used hormone replacement therapy or refused to participate. Serum samples were taken from all participants and analysed for organochlorine compounds. The odds ratios were obtained by logistic regression and adjusted for age and body mass index. In comparison with women in the first quartile of serum concentrations of chlordane metabolites, the odds ratios were 1. Only 113 of 611 potential cases were included in the study (108 cases included in the analysis), the most common cause of exclusion being death of the patient (55%). Age- and sex-matched controls were selected by random-digit dialling (age, < 65) or from the Health Care Financing Administration lists (age ≥ 65). Eighty-two of the selected controls agreed to provide a blood sample, giving a participation rate of 78% for people < 65 and 65% for those ≥ 65. Cases had significantly higher median concentrations of trans-nonachlor than controls. The adjusted odds ratios relative to individuals with concentrations below the detection limit were 0. Two groups of controls were selected: the first consisted of friends of the children with brain cancer or of children with acute lymphocytic leukaemia (85 children; participation rate, 94%), and the second consisted of 108 children with cancer (mostly of the lymphohaematopoietic system; 71 children; participation rate, 78%). The adjusted odds ratio associated with living in a home that had been treated for termites within 1 year before residence or during residence from pregnancy to diagnosis was 2. Of the 21 patients who reported any termite control treatment, only seven reported specific use of chlordane, giving an odds ratio of 1. When 10 animals from each group that were killed for interim study at 6 months were excluded, the mortality rate at 18 months was 27–49%, with the exception of males and females receiving 50 mg/kg of diet, in which the rates were 86 and 76%, respectively. A review of the histopathology of liver samples from this study by a panel of the National Academy of Sciences (1977) indicated a significant increase in the incidence of hepatocellular carcinomas in males at the intermediate dietary concentration and in females at the two higher concentrations (Table 7). Males received an initial concentration of 20 or 40 mg/kg of diet and females received 40 or 80 mg/kg of diet; the time-weighted average dietary concentrations were 30 and 56 mg/kg for males and 30 and 64 mg/kg for females. The survival rates in all groups was relatively high, being > 60% of treated males, > 80% of treated females and > 90% of male and female controls (National Cancer Institute, 1977b). A review of the histo- pathology of liver samples from this study by the panel of the National Academy of Sciences (1977) indicated a significant increase in the incidence of hepatocellular carcinomas by linear trend analysis in males and females and a significant increase in the combined incidence of hepatocellular carcinomas and nodular changes in males and females at the higher concentration (Table 8). Groups of 210 male B6C3F1 and 160 male B6D2F1 mice, 9 weeks of age, were fed diets containing 55 mg/kg technical-grade chlordane. A stop group of 75 B6C3F1 mice was returned to normal diet when they were 70 weeks (491 days) of age. Groups of 100 male B6C3F1 and 50 male B6D2F1 mice were used as untreated controls. When the treated mice were about 8 months of age, the concentration in the diet was increased to 60 mg/kg. From 408 days of age, groups of 5–33 mice were killed for pathological examination. In B6C3F1 mice, the prevalence of hepatocellular adenomas in conti- nuously treated animals exceeded 99% by 530 days, and the prevalence of hepato- cellular carcinomas was 89% at terminal killing at 568 days. In B6D2F1 mice, the pre- valence of hepatocellular adenomas reached 91% and that of hepatocellular carcinomas 86% at the terminal killing, although there was a lag of more than 100 days for tumour development in this strain. The prevalence of hepatocellular tumours in controls was less than 22% in B6C3F1 males and 9% in B6D2F1 males throughout the study. In the stop group, the prevalence of adenomas decreased from 100% to 93% between 548 and 568 days and that of carcinomas from 80% to 54% between 526 and 568 days (Malarkey et al. Three groups of 100 male and 100 female C3H mice [age unspecified] were fed diets containing 0 (control) or 10 mg/kg heptachlor or 10 mg/kg heptachlor epoxide [purity unspecified] for 24 months. Tumour incidence in B6C3F1 mice treated with analytical-grade chlordane or technical-grade heptachlor Treatment Males Females Hepatocellular Hepatocellular Hepatocellular Hepatocellular carcinomas carcinomas carcinomas carcinomas and nodules and nodules Controls 2/20 5/20 1/19 1/19 Chlordane 5/45 16/45 0/46 2/46 (low dose) Chlordane 12/46 30/46 7/47 20/47 (high dose) (p = 0. Tumour incidence in C3H mice treated with heptachlor or heptachlor epoxide Treatment Males Females Hepatocellular Hepatocellular Hepatocellular Hepatocellular carcinomas carcinomas carcinomas carcinomas and nodules and nodules Control 29/77 48/77 5/53 11/53 Heptachlor 35/85 72/85 18/80 61/80 (10 mg/kg of diet) (p = 0. After exclusion of 10 animals from each group that were killed for interim study at 6 months, the mortality rate at 18 months was 34–49%, with the exception of males and females receiving the 10 mg/kg concentration, for which the rate was approximately 70%. In addition, comparatively large numbers of animals from all groups were lost because of autolysis. A review of the histopathology of liver samples from this study by the panel of the National Academy of Sciences (1977) indicated a significant increase in the combined incidence of hepatocellular carcinomas and nodules in the groups at the high concentration (Table 10). Males received an initial dietary concentration of 10 or 20 mg/kg and time-weighted average concentrations of 6 and 14 mg/kg; females received an initial concentration of 20 or 40 mg/kg of diet and time-weighted average concentrations of 9 and 18 mg/kg of diet. The survival rates in all groups were relatively high, with > 70% of treated and control males and 60% of treated and control females still alive at 90 weeks. The survival of treated female mice showed a significant decreasing trend in comparison with controls (National Cancer Institute, 1977a). A review of the histopathology of liver samples from this study by the panel of the National Academy of Sciences (1977) indicated a significant increase in the com- bined incidence of hepatocellular carcinomas and nodular changes (p < 0. Rat: Groups of 50 male and 50 female Osborne-Mendel rats, 5 weeks of age, were fed diets containing analytical-grade chlordane (71. These concentrations were reduced during the experiment because of adverse toxic effects, and the time-weighted average dietary concentrations were 204 and 407 mg/kg for males and 121 and 242 mg/kg for females. There were 10 male and 10 female matched controls and 60 male and 60 female pooled controls from similar bioassays of other compounds. The survivors were killed at 109 weeks, at which time approximately 50% of treated and control males, 60% of treated females and 90% of control females were still alive. Treated females showed a marginal increase in the incidence of thyroid follicular-cell neoplasms: 6/32 at the higher dietary concentration (four adenomas, two carcinomas; p < 0. There was also a marginal increase in the incidence of malignant fibrous histiocytomas [site unspecified] in treated males: 7/44 at the higher concentration (p < 0. Eight males and nine females in each group were killed for evaluation at 26 and 52 weeks. Combined evaluations by the original pathologist and a panel of seven other pathologists indicated incidences of hepatocellular adenomas in males of 2/64 in controls, 4/64 at the low concentration, 2/64 at 5 mg/kg of diet and 7/64 at 25 mg/kg (p = 0. Epstein (1976) reported on a study conducted by the Kettering Laboratories in 1959, but not published by that organization. A review of the histopathology of liver samples from this study by the panel of the National Academy of Sciences (1977) found no increase in the incidence of liver tumours in treated animals.

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It must heart attack enrique generic coreg 25 mg free shipping, how- there is a significant increase in the cell wall thickness hypertension 4011 order genuine coreg on line, with ever arrhythmia word parts buy coreg paypal, be added that destruction of the viral capsid may result in values of 0 blood pressure medication grapefruit buy genuine coreg on line. The mannoprotein consists of two fractions blood pressure norms chart cheap 6.25mg coreg with mastercard, sodium do- tor species for assessing the virucidal activity of disinfectants decyl sulfate-soluble mannoproteins and sodium dodecyl sul- (108) and could thus play an increasing important role in this fate-insoluble, glucanase-soluble ones: the latter limit cell wall context; for example, repeated exposure of E. Thus, glucan (and possibly mannoproteins) chlorine was claimed to increase its resistance to disinfection plays a key role in determining the uptake and hence the ac- (542). Lethal concentrations of antiseptics and disinfectants inferred that a more fluid membrane enhances ethanol resis- toward some yeasts and moldsa tance (6). There is no evidence to date of antiseptic efflux (although Lethal concn (mg/ml) toward: benzoic acid in energized cells is believed to be eliminated by b Molds Antimicrobial agent Yeast flowing down the electrochemical gradient [529]) and no evi- (Candida dence of acquired resistance by mutation (except to some Penicillium Aspergillus albicans) chrysogenum niger preservatives [436]) or by plasmid-mediated mechanisms (426, 436). Molds are generally more resistant than Chlorhexidine 20–40 400 200 yeasts (Table 14) and considerably more resistant than non- aDerived in part from data in reference 525. Kinetic approach: D-values at 20°C of phenol and benzalkonium chloride against fungi and bacteriaa D-value (h)b against: Antimicrobial agent pH Concn (%, wt/vol) Aspergillus niger Candida albicans Escherichia coli Pseudomonas Staphylococcus aeruginosa aureus Phenol 5. Acanthamoebae are capable of forming biofilms on sur- vation while overcoming the possibility of multiplicity reacti- faces such as contact lenses (186). Although protozoal biofilms vation (first put forward by Luria [293]) to explain an initial have yet to be studied extensively in terms of their response to reduction and then an increase in the titer of disinfectant- disinfectants, it is apparent that they could play a significant treated bacteriophage. Multiplicity reactivation as a mecha- role in modulating the effects of chemical agents. Another resistance mechanism also involves viral aggrega- normal host protein is implicated in the pathological process. A typical biphasic survival curve of enterovirus are often studied means that extraneous materials could, at and rotavirus exposed to peracetic acid is also indicative of the least to some extent, mask the true efficacy of these agents (503). According to Taylor (503), there is currently no known decon- Finally, there remains the possibility of viral adaptation to tamination procedure that will guarantee the complete ab- new environmental conditions. Clearly, much remains to be synergistic effect with autoclaving plus sodium hydroxide treat- learned about the mechanism of viral inactivation by and viral ment is observed. With the information presently available, it is difficult to Intestinal protozoa, such as Cryptosporidium parvum, Enta- explain the extremely high resistance of prions, save to com- moeba histolytica, and Giardia intestinalis, are all potentially ment that the protease-resistant protein is abnormally stable to pathogenic to humans and have a resistant, transmissible cyst degradative processes. It is clear that microorganisms can adapt to a variety of en- Cyst forms are invariably the most resistant to chemical disin- vironmental physical and chemical conditions, and it is there- fectants (Fig. The reasons for this are unknown, but it fore not surprising that resistance to extensively used antisep- would be reasonable to assume that cysts, similar to spores, tics and disinfectants has been reported. Of the mechanisms take up fewer disinfectant molecules from solution than do that have been studied, the most significant are clearly intrin- vegetative forms. In these cases, and trophozoites of Acanthamoeba castellanii to disinfectants “resistance may be incorrectly used and “tolerance, defined used in contact lens solutions and monitored the development as developmental or protective effects that permit microorgan- of resistance during encystation and the loss of resistance dur- isms to survive in the presence of an active agent, may be more ing excystation (251–255). Many of these reports of resistance have often pa- and of a polymeric biguanide were time and concentration de- ralleled issues including inadequate cleaning, incorrect prod- pendent, and mature cysts were more resistant than preencyst- uct use, or ineffective infection control practices, which cannot ment trophozoites or preexcystment cysts. Viral classification and response to some disinfectantsa a mutant of Pseudomonas aeruginosa. Transmission of a highly drug-resistant strain (strain W1) of philic spectrum Mycobacterium tuberculosis. Relationship be- B 2 Non-lipid picornaviruses (poliovirus, R S tween ethanol tolerance, lipid composition and plasma membrane fluidity Coxsackie virus, echovirus) in Saccharomyces cerevisiae and Kloeckera apiculata. In-hospital evaluation of orthophthal- (adenovirus, reovirus) aldehyde as a high level disinfectant for flexible endoscopes. Iodophor antiseptics: intrinsic microbial contamina- tion with resistant bacteria. However, few reports have further investigated tibility of vancomycin-resistant enterococci to environmental disinfectants. Efflux mechanisms are known to be important in tamination in commercially manufactured povidone-iodine. The effects of iodine on the biological activities of microorganisms at residual levels of antiseptics and disinfec- myxoviruses. Chemical disinfection that clinical isolates should be under continual surveillance and in hospitals, 2nd ed. A rapid method of evaluating permeabilizing activity against Pseudomonas aeruginosa. Chlorhexidine dition, a particular antiseptic or disinfectant product may be sensitivity of Enterococcus faecium resistant to vancomycin, high levels of better selected (as part of infection control practices) based on gentamicin, or both. Activity of glutaraldehyde at low concen- trations (,2%) against poliovirus and its relevance to gastrointestinal en- gram-positive than gram-negative bacteria, and C. Laboratory and In conclusion, a great deal remains to be learned about the in-vitro testing of skin antiseptics: a prediction for in-vitro activity. The membrane desta- nificant progress has been made with bacterial investigations, a bilizing action of the antibacterial agent chlorhexidine. Triclosan protects the skin against der- matitis caused by sodium lauryl sulphate exposure. Drug sensitivity and environmental adaptation of mycobacterial cell wall components. Resistance of Pseudomonas poliovirus having increased resistance to chlorine inactivation. The effects of silver nitrate on the antiseptiques et la pre´sence du ge`ne qacA chez Staphylococcus aureus. Role of glutaraldehyde and other liquid chemical ster- erichia coli katE gene product. Pig skin as a test substrate Disinfection, sterilization, and preservation, 4th ed. The effect of the phenolic antibacterial agent Fen- nidine monoacetate) in Pseudomonas syringae. Action of chlorhexidine on budding teraldehyde at low concentrations against capsid proteins of poliovirus type Candida albicans: scanning and transmission electron microscopic study. Antimy- cidal and growth inhibitory activities of the bisbiguanides alexidine and cobacterial activity of biocides. Interaction of the bisbiguanides tiation of the effects of chlorhexidine diacetate and cetylpyridinium chloride chlorhexidine and alexidine with phospholipid vesicles: evidence for sepa- on mycobacteria by ethambutol. Microbial resistance to veterinary disinfectants and anti- ions on Pseudomonas aeruginosa. Blackwell Scientific rate on susceptibility to antimicrobial agents: modification of the cell en- Publications Ltd. Inhibition of Providen- Pseudomonas aeruginosa grown under conditions of Mg limitation. Blackwell cell wall porosity in Saccharomyces cerevisiae after treatment with dithio- Scientific Publications Ltd. In Proceedings of the assay of relative cell porosity in Saccharomyces cerevisiae, Kluyveromyces 7th International Symposium on Staphylococci and Staphlococcal Infec- lactis and Schizosaccharomyces pombe. Biocide-induced damage to the Antimicrobial actions of hexachlorophane: lysis and fixation of bacterial cytoplasmic membrane. Peracetic acid sterilization: a timely development for a busy Febiger, Philadelphia, Pa. Interaction of chlorhexidine with the outer wall architecture caused by the inhibition of mycoside C biosyn- yeast cells. Action of biguanides, phenol and deter- trations of glutaraldehyde on Micrococcus lysodeikticus membranes. Comparative analysis of scrapie agent tion, preservation and sterilization, 3rd ed. Development of resistance to modern fungicides and rate and the resistance of Gram-negative biofilms to cetrimide. The reaction of hexidine diacetate to Escherichia coli and Pseudomonas aeruginosa and its nucleotides with aqueous hypochlorous acid. Mechanism of ation of associated with resistance to ethylenediamine tetraacetate resulting from chlorhexidine diacetate and phenoxyethanol singly and in combination growth in a Mg21-deficient medium. Economic micro- tance of Escherichia coli and Staphylococcus aureus to chlorhexidine. Topical therapy and the development of silver sulfa- development of resistance to antimicrobial chemicals and heat in spores of diazine. Antimicrobial actions Campylobacter jejuni and generation of a catalase-deficient mutant of of hexachlorophane: inhibition of respiration in Bacillus megaterium. Acan- structure and function of the bacterial membrane: effects of ethanol on the thamoeba, bacterial and fungal contamination of contact lens storage cases. Derivatives of 4-amino-quinaldinium and 8-hydroxyquino- dehyde-resistant Mycobacterium chelonae from endoscope washer disinfec- line, p. A staphylococcal multidrug resistance gene product is a member of a inhibition of fermentation in yeast by nickel ions. Nature and development of phenotypic resistance to resistance in Pseudomonas stutzeri isolated from a silver mine. Evidence for plasmid-mediated resistance Adaptation and growth of Serratia mascescens in contact lens disinfectant of Pseudomonas putida to hexahydro-1,3,5-triethyl-s-triazine. Multidrug resistance in enteric and other Gram-neg- susceptibility of hospital isolates of Gram-negative bacteria to antiseptics ative bacteria. Inactivation of enteroviruses, rotaviruses, bacteriophages membranes and isolated membrane fragments. Isolation and characterization of rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy a hydrogen peroxide resistant mutant of Bacillus subtilis. Compounds active against cell walls of medically im- the Gram-negative cell envelope towards high molecular weight polyhexa- portant fungi. Envi- chlorhexidine diacetate and cetylpyridinium chloride on whole cells and ron. In vitro susceptibility of analysis chlorhexidine-treated cells of Saccharomyces cerevisiae. Germination and resistance defects in spores of a role of yeast cell walls in modifying cellular response to chlorhexidine Bacillus subtilis mutant lacking a coat polypeptide. Phenotypic and genetic diversity of chlorine-resistant of late events in Bacillus subtilis sporulation from expression of genes that Methylobacterium strains isolated from various environments. A novel approach to mode of the phenolic antibacterial agent Fentichlor against Staphylococcus aureus action of cationic biocides: morphological effect on antibacterial activity. The determination of antimicrobial the phenolic antibacterial agent Fentichlor against Staphylococcus aureus characteristics of phenol. Plasmid-mediated formal- Staphylococcus aureus upon its resistance to antimicrobial agents. A dehyde resistance in Serratia marcescens and Escherichia coli: alterations in comparison of the response of normal and lipid depleted cells of S. The effect of chlorhexidine on the Effects of biocides on Acanthamoeba castellanii as measured by flow cytom- electrophoretic mobility, cytoplasmic content, dehydrogenase activity and etry and plaque assay. Blackwell Sci- mechanisms of action of biguanides on cysts and trophozoites of Acan- ence, Oxford, England.

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