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Extramammary Paget’s disease treated with topical and systemic photodynamic therapy symptoms urinary tract infection buy discount atomoxetine 10 mg on line. Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid medications 7 rights generic atomoxetine 40 mg. Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to medicine 5 rights buy generic atomoxetine on-line photodynamic therapy treatment ingrown toenail cheap 40 mg atomoxetine otc. Topical photodynamic with 5-aminolaevulinic acid does not induce hair regrowth inpatients with extensive alopecia areata. Simulations on the selectivity of 5-aminolevulinic acid-induced uorescence in vivo. Fluorescence contrast and threshold limit: impli cations for photodynamic diagnosis of basal cell carcinoma. B Tissue optics dictate how light gets to a particular structure and most often thermal effects dictate the clinical result. B Q-switched lasers are best at removing tattoos with minimal scarring but require many treatments and do not always clear tattoos. B Laser hair removal can also be used for noncosmetic indications such as dissecting cellultis. This chapter highlights some of the most important advances in the medical use of lasers by relating how these advances pertain to basic optical principles. Regardless of the device or dermatologic indication, speci c biophysical laws govern how all light affects the skin. This chapter will go on to cover the medical uses of laser while deferring most of the cosmetic uses for photodamage and ethnic skin to other chapter of this book. The key to developing and re ning any type of light-based therapy is understanding how to ef ciently and effectively deliver this energy to cutaneous structures in a highly targeted fashion so as to limit collateral light-induced trauma or to modify certain immune-based tissue responses. While the term “light” is sometimes restricted to electromagnetic radiation that is visible to the human eye. Treating the skin with light can be considered in two stages: (i) understanding how to selectively deliver photons to speci c structural targets in the skin, that is, tissue optics; and (ii) understanding the biological pro cesses that occur after a skin target absorbs light photons, that is, photobiological reactions. The interaction of radiation with tissue is governed by three basic processes that can occur when a photon of light reaches the skin: re ection, scattering, and absorption (Fig. Radiation that is re ected from the skin and perceived by the human visual system provides the means for diag nosing skin disease, but re ected radiation does not itself result in any direct therapeutic effect. In the absence of an absorption event (see below), the forward propagation of radiation deeper within the skin is in uenced by the degree to which its direction of travel has been scat tered by tissue structures. Tissue scattering of ultraviolet, visible, and near-infrared light is wave length-dependent, and in general longer wavelength radiation penetrates the skin more deeply because longer wavelengths tend to scatter less in the skin. Thus, targets that are deeper in the skin require the use of devices that can deliver longer wavelength radiation. Lasers and Intense-Pulsed Light in Dermatology 391 Absorption is an important biophysical event that involves the transfer of energy from radiation to tissue. Absorption is strictly de ned as when a molecule, which makes up the chromophore, absorbs electromagnetic energy with a characteristic ef ciency given by the molecules extinc tion coef cient in a wavelength-dependent manner (1). Without photon absorption, energy will not be taken up by the skin and no biological or therapeutic effect will occur. The absorption of photons by speci c molecules within the skin also in uences light penetration, since any photon that is absorbed is no longer capable of propagating through the skin, as that particular photon no longer exists (2). Like scattering, absorption is wavelength-dependent, but in a somewhat more complicated manner since it depends on the absorption pro le or “spectrum” of the chromophore. These chromophores absorb light over a broad spectrum of wavelengths as shown in Figures 2A and B (3,4). All phototherapeutic applications must, by de nition be mediated by chromophores present in the skin. Thus, in order for a given photon to have a clinical effect it must actually reach the target structure within the skin and then be absorbed by a speci c chromophore within that target. Whether or not these events occur and the degree to which they occur is dependent on the wavelength of light used, the structures of the skin which affect re ection/ scattering, and the concentration and location of chromophores. Once the photon is absorbed by the chromophore, the source’s radiation energy is trans ferred to the skin to either (i) generate heat, or (ii) drive photochemical reactions. In the case of ultraviolet therapy, it is now gen erally accepted that the therapeutically useful photochemical reactions culminate in cutaneous immunosuppression although the exact sequence of reactions is less clear. The energy of the excited chromophore is rst transferred to molecular oxygen to form singlet oxygen which then reacts with a diverse range of biomolecules (2). In clinical parlance, there is often an undue preoccupation with the technical speci ca tions for a given light device rather than a well grounded understanding of the desired under lying photobiological and phototherapeutic endpoints. The reality is that for any clinical indication a multiplicity of possible photonic devices are often available. This simply re ects the fact that from the point of view of the tissue and its chromophores, the exact source of the photons. As with any therapeutic modality, the ultimate arbiters for the bewildering array of competing light-based therapies and devices are well designed and rigorously executed controlled clinical studies which must be evaluated with photobiological principles in mind. Clinical trials information must be coupled to the operators comfort level with regards to the devices ease of use for the particular indication for which the patient seeks treatment. These variables are used to selectively thermally damage particular structures in the skin. The core technology is relatively simple and involves the use of polychromatic broadband Lasers and Intense-Pulsed Light in Dermatology 393 ashlamps equipped with optical lters that allow preselected visible to infrared wavebands (500–1200 nm) to reach the skin (7). Since multiple wavelengths are delivered, several different chromophores including hemoglobin, melanin, and perhaps, even water can be targeted with the same light exposure. These side effects include crusting, pigmentary changes, hair loss, and paradoxical increases in hair growth (8). The versatility and effective marketing of these devices is a driving force behind their popularity. In addition, there is a much lower acquisition and maintenance cost along with their multiple uses which have made them an often used technology (9). In addition, vas cular laser pulse durations have been extended from the sub-microsecond to millisecond domain for two reasons. A longer duration of exposure will heat a greater tissue volume, which is necessary for larger caliber vessels. Second, longer pulses will conduct heat more gradually within blood vessels resulting in a lesser tendency to immediate purpura which, although temporary, patients nd very dis guring. The depth of penetration of these wavelengths are enhanced using wider spot sizes which increase forward scattering which minimizes super cial thermal injury (10,11). Not unexpectedly, these lasers are often less effective for ner red telangiectasias presumably due to a mismatch between the vessel’s thermal relaxation time and the laser’s pulsewidth. The deeper penetration of the recently developed 595 nm, long pulse (up to 40 ms) dye laser allows the operator to obtain clearance for some port wine stains that is equivalent to the original 585 nm, 450 ms pulsed dye laser results with fewer side effects such as prolonged purpura and crusting (12). A more detailed explanation of vascular laser treatments can be found in the cosmetic laser chapter of this book (chap. The selectivity can be obtained by appropriate selection of the wave length, pulse duration, spot size, and recognition of biological endpoints. There are a variety of wavelengths in the visible range which are absorbed by melanin as indicated in Figures 2A and B, but the over-riding principle of this therapy is to target the melanin in the Lasers and Intense-Pulsed Light in Dermatology 395 pathological skin without destroying the normal skin. Selectivity is obtained by appropriate selection of wavelength, pulsed duration, spot size, and cooling the targeted areas. Nevus of Ota and tattoos are best treated with high-peak power devices with very short pulse durations. Q-switched lasers are the best options for these con ditions but lead to some crusting post-treatment with the potential side effects of hypopigmen tation. Q-switched lasers are effective devices but they do suffer from an inadequate response in some patients along with postin ammatory hyperpigmentation in Asians, in particular (9). The response of melasma to light treatment has been less than sat isfactory and this particular disorder of pigmentation must be approached differently. This is covered in more detail in the cosmetic sections and the section on treatment of ethnic skin diseases. Other wavelengths that were speci c to particular tattoo colors were added that resulted in scarring as well. However, in the 1990s, lasers were designed based on experimental data from the 1960s and 1980s, which suggested that shorter pulsed durations in the nano second domain of high-peak power could more speci cally target smaller structures with less collateral damage. Since that time, Q-switched lasers have become the preferred modality of tattoo removal (5,13) (Fig.
The proposed Phase 3 study will include treatment-naive treatment e coli purchase line atomoxetine, non-cirrhotic subjects and will evaluate whether or not the treatment duration in such subjects can be reduced from 12 weeks to medicine 911 purchase atomoxetine from india 8 weeks medications vascular dementia purchase genuine atomoxetine line, without compromising efficacy medicine cabinets recessed order atomoxetine in india, based on a non-inferiority margin of 12%. Similarly, substantial increases in exposure (and hence dose) would be required to improve on the efficacy prediction of 77% in the plateau of the exposure-response curve and to observe an appreciable increase in antiviral effect (see model prediction in Figure 1-1). For this reason, a 90 mg dose has been selected as for further clinical testing in Phase 3 studies. During the conduct of the study the Sponsor will perform ongoing safety data review. All subjects will complete a 4-week and 12-week Post-Treatment visit regardless of treatment duration. The assessments performed at each visit are described in Section 6 and shown in Appendix 2. Original Confirmation should be performed as soon as possible and must occur no later than 2 weeks after an initial observation indicating virologic failure during the on-treatment phase. Study drug(s) must be discontinued in the following instances: • Unacceptable toxicity, as defined in Section 7 of the protocol, or toxicity that, in the judgment of the investigator, compromises the ability to continue study-specific procedures or is considered to not be in the subject’s best interest • Pregnancy of female subject • Efficacy failure as defined in Section 3. Additionally, all subjects must complete the 4-week and 12-week Post-Treatment visits, based on their last dose date. All subjects should also complete a 4-Week and 12-Week Post Treatment visit, based on their last dose date. Number of Subjects and Subject Selection Approximately 600 subjects will be enrolled in this study with approximately 200 subjects randomized to one of three treatment groups. Original ii) Cirrhosis as defined as any one of the following: (1) Liver biopsy showing cirrhosis. Female subjects using a hormone-containing contraceptive prior to Screening may continue their contraceptive regimen in addition to the study specified methods of birth control. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to randomization or has not required medication in the last 12 months may be included. Each bottle contains 30 tablets and a silica gel desiccant canister or sachet and polyester packing material. All drug products should be stored in a securely locked area, accessible only to authorized site personnel. Consideration should be given to handling, preparation, and disposal through measures that minimize drug contact with the body. Each subject must be given instructions to maintain approximately the same daily dosing interval between study drug doses. For missed dose(s) of study drug, subjects should be instructed to take the missed dose(s) of study drug as soon as possible during the same day. To ensure the stability of the study drug and to ensure proper product identification, the drug product should not be stored in a container other than the container in which they are supplied. Subjects who are to receive total daily doses of 1000 mg, should be instructed to take 3 tablets in the morning and 2 tablets in the evening (or 2 tablets in the morning and 3 in the evening). Examples of representative medications which are prohibited from 21 days prior to Baseline/Day 1 through the end of treatment are listed below: Table 5-1. Disallowed and Concomitant Medications to be Used with Caution Drug Class Agents Disallowed Use with Caution Acid Reducing Proton Pump Inhibitors H2-Receptor Antagonists a Agents Antacids b Antiarrhythmics Quinidine c Anticonvulsants Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine c Antimycobacterials Rifabutin, Rifapentine, Rifampin b Cardiac Medications Digoxin Valsartan, Olmesartan, Telmisartan, Ranolazine, Bosentan Herbal/Natural St. Monitor for signs and symptoms of muscle weakness or myopathy, including rhabdomyolysis. All subjects will complete a 4-week and 12-week Post Treatment visit regardless of the treatment duration. The following procedures will be performed and documented: • Obtain signed informed consent — A separate informed consent will be required from subjects participating in the pharmacogenomic substudy • Determine inclusion eligibility (Reference Section 4. Unscheduled Visit A subject should attend an unscheduled visit if requested by the sponsor or investigator. Post Treatment Assessments All subjects must complete the Post Treatment Week 4 and Week 12 visits. All subjects, including early termination subjects, must return for Post Treatment Visit at Week 12. Blood pressure will be measured using the following standardized process: • Subject should sit for 5 minutes with feet flat on the floor and measurement arm supported so that the midpoint of the manometer cuff is at heart level; • Use a mercury sphygmomanometer or automatic blood pressure device with an appropriately sized cuff with the bladder centered over the brachial artery; • Measure and record the blood pressure to the nearest 2 mm Hg mark on the manometer or to the nearest whole number on an automatic device. Additionally, at any unscheduled visit initiated for the purpose of confirming virologic breakthrough, a viral sequence analysis plasma sample must be collected. Original drugs immediately (if applicable) and return to the clinic as soon as possible for a serum pregnancy test. The subject should read the questionnaire by himself/herself and write/mark answers directly onto the questionnaire. The specimens collected for optional future research will be used to increase our knowledge and understanding of the biology of the study disease and related diseases and to study the association of biomarkers with disease pathogenesis, progression and/or treatment outcomes, including efficacy, adverse events, and the processes of drug absorption and disposition. These specimens may be used also to develop non-genetic biomarker or diagnostic assays and establish the performance characteristics of these assays. Biomarker Sample for Optional Pharmacogenomic Research A separate, specific signature will be required to document a subject’s agreement to provide an additional sample for the optional pharmacogenomic research. The specimen collected for optional pharmacogenomic research will be used to identify or validate genetic markers that may increase our knowledge and understanding of the biology of the study disease and related diseases and to study the association of genetic markers with disease pathogenesis, progression and/or treatment outcomes, including efficacy, adverse events, and the processes of drug absorption and disposition. From subjects who agree to participate and provide their additional specific consent, one blood sample will be obtained. Due to a clinical or laboratory event, administration of all study drugs(s) may be discontinued. Post Treatment 4-Week and 12-Week visits must also be scheduled, 4 and 12 weeks from the last dose of study drug. Adverse events also include the following: • Pre or post-treatment complications that occur as a result of protocol mandated procedure. Transmission of such documents should occur with Personal Subject Details de-identified, without losing the traceability of a document to the Subject Identifiers. Original this is required by local regulatory authorities, and in accordance with the local institutional policy. A pregnancy report is used to report pregnancies occurring in subjects or their partners during the study whether or not maternal or paternal exposure to the product occurred. Study drug error is any unintentional error in the prescribing, dispensing, or administration of a medicinal product while the drug is in the control of a healthcare professional, patient or consumer. Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a patient accompanied by harmful, physical, and/or psychological effects. Misuse refers to situations where the medicinal product is intentionally and inappropriately used in a way that is not in accordance with the protocol instructions or the local prescribing information and may be accompanied by harmful physical and/or psychological effects. An overdose is defined as a dose taken (accidentally or intentionally) exceeding the dose as prescribed by the protocol or the maximal recommended daily dose as stated in the Product Labelling (as it applies to the daily dose for the subject/patient in question). In cases of a discrepancy in drug accountability, overdose will be established only when it is clear that the subject has taken the excess dose(s) or the investigator has reason to suspect that the subject has taken the additional dose(s). Product complaint is defined as any written or verbal report arising from potential deviations in the manufacture, packaging or distribution of the product. Subjects who become pregnant or who suspect that they are pregnant during the study must report the information to the Investigator and discontinue study drug immediately. Subjects whose partner has become pregnant or suspects she is pregnant during the study must report the information to the investigator. The subject should receive appropriate monitoring and care until the conclusion of the pregnancy. Details of the symptoms and signs, clinical management and outcome will be reported, when available. Safety the primary analysis set for safety analyses will include subjects who received at least one dose of study drug. Data Handling Conventions Missing data can have an impact upon the interpretation of the trial data. Other than the endpoints discussed below, values for missing data will not be imputed. For the analysis of post-baseline categorical efficacy endpoints, if a data point is missing and is preceded and followed in time by values that are deemed successes, then the missing data point will be termed a success; otherwise the data point will be termed a failure. Any subject with missing data due to premature discontinuation of the study drug will be considered a failure at the date of premature discontinuation and all timepoints subsequent to the date of premature discontinuation.
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Figure Table 4 Comparison of Pesticide Poisoning Data From 1998 to medicine 657 discount atomoxetine 10mg fast delivery 2002 Total Percentage fatalities Total Percentage Total of total reported fatalities of total poisonings Pesticide poisonings due to symptoms meaning atomoxetine 40mg fast delivery all due to treatment for strep throat buy cheap atomoxetine 25 mg on line fatalities Year reported poisonings reported poisons pesticides reported 1998 2 symptoms jaw pain and headache generic atomoxetine 18 mg otc,241,082 86,289 3. Available as dusts, granules, or liquids, organophosphorus insecticides are among the most popular and widely used insecticides throughout the world. They began to be synthesized first around 1820 with the esterification of alcohols to phosphoric acid. The earliest synthesis of an organophosphate, tetraethyl pyrophosphate, was reported by Phillipe de Clermont at a meeting of the French Academy of Sciences in 1854 (21). Many different organophosphorus com pounds were synthesized in the early 1900s, but their toxicity was first recognized 270 Aggrawal Fig. Five different categories of organophosphates depending on variations of different side chains. Lange stated that inhalation of the vapor of dimethyl or diethyl phosphofluoridate produced a choking sensation and dimness of vision. By 1940, Schrader in Ger many and Saunders in England and their study groups had synthesized a num ber of highly toxic organophosphates for possible use in warfare. Currently, about 50 organophosphorus compounds are in use as insec ticides worldwide. Tetraethyl pyrophosphate enjoys two distinctions among organophos phates: it was the first organophosphate to be synthesized in 1854 and is the Agrochemical Poisoning 271 most dangerous organophosphorus insecticide by either oral or dermal route of application. Rarely, there is chromolachryorrhoea (shedding of red or bloody tears) (22) because of a disturbance in porphyrin metabolism and its accumulation in lacrimal glands. Compounds that are extremely toxic are chlorfenvinphos, diazinon, and methyl parathion, whereas those that are slightly toxic are malathion, acephate, and trichlorphon (23). Most patients who have ingested a fatal dose will die within 24 hours of ingestion. Organophosphorus toxicity has recently been reviewed extensively by Rousseau and co-workers (24). External Findings Signs of asphyxia are commonly found in fatal intoxications with organophosphorus insecticides. There is congestion of the face and cyanosis of the lips, nose, fingers, and acral parts of the extremities. One of the most remarkable findings is the characteristic odor emanating from the corpse: it has been described as garlic or kerosene-like and is due to the fact that organophos phates are dissolved on a kerosene base. There is often frothy, bloody staining at the mouth and nostrils, and the pupils may be constricted. A coloring agent, indigocarmine, is added to parathion (E605) to prevent its accidental ingestion or criminal use as a poison. For instance, in India and several other Asian countries, this practice is not followed. An interesting sign to be observed (albeit only in somewhat less modern mortuaries) is the death of bluebottles and others insects and flies dying immediately after they alight on an opened cadaver at autopsy (25). Congested and hemorrhagic stomach mucosa in a case of fatal organophosphorus poisoning. Internal Findings the gastric mucosa is congested and may appear hemorrhagic (Fig. The mucosa of the respiratory tract is congested and the airway passages contain frothy hemor rhagic exudate. Histopathology Parathion (E605) has been studied most extensively for histopathological lesions and these are considered to be representative of other organophospho rus insecticides, too (26). In the kidneys, there is epithelial necrosis in the straight sections of the renal tubules. In the epithelia of the remaining renal cor tical sections, there is pronounced plasma granulation, nuclear wall hyperchro matosis, and clumping and reduction in the chromatin and marginal nucleoli. The liver is more resistant to the effects of organophosphates, partly because of its ability to manufacture serum cholinesterase on its own. Hepa Agrochemical Poisoning 273 tocytes show opaque swelling and glycogen depletion; there are destructive changes in the liver cell strands, detached hepatocytes, and perivascular edema. Myocardium, medulla oblongata, and vagal nuclei of the brain show fine, maculate perivascular hemorrhages. Limaye has described a type of toxic myocarditis that he had observed in 76 autopsy cases (27). Kiss and Fazekas described focal myocardial damage with pericapillary hemorrhage, micronecrosis, and patchy fibrosis in victims of organophophorus poisoning (28). Pimentel and da Costa (29) have described the following myocardial ultra structural changes in fatal poisonings with organophosphorus: 1. Mitochondria exhibiting decreased electron density, swollen forms and fragmen tation or lysis of cristae. Nuclei showing irregularity in shape and various degrees of disorganization of chromatin. The glomus caroticum shows an increase in the number of dark-cell nuclei, perhaps as a consequence of increased nuclear metabolism owing to augmented demand. The measurement of their levels can assist in the determination of the cause of death (30). The plasma cholinesterase (pseudocholinesterase) is more sensitive and levels fall more rapidly than those of the red blood-cell cholinesterase. Red blood-cell cholinesterase levels are more satisfactory for the diagnosis of organophosphorus poisoning because they represent the true cholinesterase levels. The recommended procedures for collection and storage of biological fluids are as follows: 1. The samples must be collected and stored in glass rather than plastic containers to avoid contamination by leachates from plastic. Samples must be immediately refrigerated because ChE catalytic activity is tem perature dependent. If enzyme activity is not deter mined immediately, samples can be stored for several days at 4°C. If tissues are intended to be stored for longer periods, the storage temperature should be –20°C or below. One of the most popular is the pH method by Michael (33), whereby a change in pH is measured when ChE acts on acetylcholine. The principle is that cholinesterase hydrolyzes acetylcholine, thus producing acetic acid, which in turn decreases the pH of the reaction mixture. A 25% or greater depression of the red blood-cell ChE level is a true indicator of poisoning. Toxicological Analysis Blood and urine should be preserved for toxicological analysis of ChE levels. It is excreted in urine and its presence in urine is characteristic of organophosphorus poisoning. Organophosphates and Putrefaction Organophosphates usually resist putrefaction and can be detected in the viscera for quite some time after death. Wehr (36) studied five exhumations where the decedents were suspected having been poisoned with parathion. He could detect the degradation products of parathion (aminoparathion and p-nitro phenol) up to 7 years after burial, but after 13 years, neither parathion nor any of its degradation products were detectable. Pohlmann and Schwerd found evi dence of parathion in a corpse exhumed after 21 months (37). More recently, Karger and co-workers (38) described a case where they detected paraoxon, the main conversion product of parathion, from the abdom inal cavity of a 9-month-old boy, 8 months after his death. His mother had poi soned him with parathion; her deed was detected when, several months later, her second child—a 3-year-old girl—also suffered the same fate and parathion was detected in her blood. The first recognized anti-ChE was in fact a carbamate, physostigmine (also called eserine), obtained in pure form in 1864 by Jobst and Hesse from the Calabar bean (39). Some common carbamates used as insecticides today are aldicarb, carbaryl, benzene hexa chloride, triallate, propoxur, methomyl, carbofuran, and carbendazim. This is a reversible type of binding, and therefore, their toxicity is less severe and of 276 Aggrawal Fig. Signs and symptoms are the same as those seen in poisoning with organophosphates/organophos phorus insecticides but they are milder in nature.
They quantity of gas bubbles formed in body tissues as divers cannot take into account the wide range of human body ascend symptoms your having a boy buy 10 mg atomoxetine with mastercard. Navy Dive Tables have a fairly which typically records bottom time as being from the good track record when it comes to medicine natural atomoxetine 18mg on-line helping divers avoid beginning of descent until the end of ascent medicine go down purchase 10mg atomoxetine fast delivery. Still medication 3 checks best buy atomoxetine, there are many steps experts believe can be taken to further reduce the risk of decompression sickness. For this reason, wise divers choose to remain well within Many dives, however, are what are known as multi dive table or dive computer limits. Several recreational level dives—in which participants will be at a variety of diver training organizations go so far as to publish dive depths throughout the dive. Dive computers automati tables with no-decompression limits that are more con cally account for multi-level diving, providing computer servative than those of the U. Dive tables, in Earlier in this section, examples were presented of how contrast, assume that the deepest depth reached during one would go about finding the minimum allowable Surface the dive was the actual depth for the entire dive. Wise divers avoid “pushing” dive table or dive com additional margin of safety that computer users do not puter limits unless absolutely necessary. The num For example, a dive is made to a depth of 65 fsw for bers on the chart represent bottom time in minutes. Normally decom row for the appropriate depth and move to the right along pression would be based on a 70 fsw/40 minutes sched the line until you find a bottom time that meets or exceeds ule. Now follow that column downward, exit the decompression is based on 70 fsw/45 minutes schedule. It makes sense to manage these risks intelligent of that nitrogen is the purpose of Chart 2, (see Table 4. It consists of blocks containing two numbers which represent the mini • Avoid factors such as cold, dehydration, and mum and maximum times for assignment to a particular fatigue. The times are expressed as hours and minutes protection both above and below the water. Then follow that row horizontally to the left, exit the • Maintain a high level of personal fitness. Chart 3 has 120 160 15 50 10 15 25 30 40 50 60 70 80 90 100 5 21 already done the work for you. Although equipment is a big factor in diver performance, equipment alone cannot make up for a diver’s lack of abili ty in the water. A good diver must have a high level of fit ness and must be comfortable in the water. A competent diver should be able to dive with most any type of equipment provided he has been trained to use it. Selecting the right dive gear for a scientific dive is a mat ter of defining the objectives of the dive and the location. For some work, snorkeling equipment may be all that is required, while for other jobs surface-supplied gear may be the best choice. A diver must become totally familiar with new equipment before entering a working situation. The more equipment the diver wears, the more drag and change of center of gravity will be created. Each piece of equipment should have a def inite purpose on a particular dive; and if it is not going to 5. Face masks for scuba diving are designed to cover the Given the durability of most diving gear, making the eyes and nose. The nose must be included inside the mask right selection at the time of purchase is critical, since it is to allow the diver to equalize the pressure inside the mask hard to justify equipment replacement if the equipment is by exhaling through his nostrils. By talking with diving officers and other sci that goggles that cover only the eyes are not acceptable for entific divers, the preferred models of gear for a particular diving. The program, which includes yearly main ing it normally, but without using the strap to hold the tenance and testing of all scuba regulators, pressure and mask in place. Divers with mustaches having dif Many snorkels today are available with top mounted ficulty achieving a mask seal may have to use some type of valves that help to keep water out of the snorkel while substance such as Vaseline on their mustaches to achieve surface swimming. These ture of a mask in that it provides a means for the diver to can be extremely effective and make surface swimming pinch his nostrils closed in order to aid in equalizing the much easier. Other features include Most modern snorkels use plastic rings or attachment purge valves and double feather edge seals. These one-way valve through which water can be expelled that rings allow the snorkel to be easily removed from the enters the mask. Water can also be removed from a mask mask, so that the mask can be stored in a protective box without a purge. A double feather edge is a type of sealing for transport to and from the dive site or during airline (double) edge on the material that fits against the face. Once it is determined that the mask fits properly, the In the United States, the snorkel is traditionally mount next most critical feature is visibility. Side windows in the ed on the left side of the diver’s head, since the regulator is masks can enhance peripheral vision (Egstrom 1982), but routed over the diver’s right shoulder. Fins for scuba diving are usually much more rugged For divers who require glasses, prescription lenses are and have larger blades than those used for snorkeling or available that will fit many popular dive masks. The fins provide propulsion for divers who are divers who have a common prescription and do not need heavily encumbered with equipment and make underwa bifocals, many dive stores stock lenses for their more pop ter swimming much easier. Divers who have an unusual prescrip efficient for underwater propulsion when properly tion will need to order specially prepared lenses for their equipped. When divers are fully geared up, it may not be possible the lenses of new masks need to be washed with a for them to use their hands for swimming purposes, since mild liquid detergent, such as dishwashing detergent, to straps and thermal protection suits inhibit normal arm help remove any chemicals that may remain from manu movement. In addition, scientific divers are usually carry facturing and may cause the mask to fog. The purpose of the snorkel is to are of different lengths in each individual, providing a differ allow the diver to swim more easily on the surface without ent mechanical advantage for each diver, there is no one fin consuming the compressed gas in his cylinder. A fin that works very Ideally, the snorkel should not exceed 14 inches in length and should have the minimum number of bends possible. If the snorkel has a corrugated hose, allowing it to bend easily, the inside bore of the hose must be smooth, not ribbed. Small diame ter snorkels, and those with corrugated hoses with internal ribs, produce high breathing resistance, add substantially to equipment dead air space (where no gas exchange takes place), and a corrugated hose also makes elimination of all water in the snorkel all but impossible. These suits are form fitting, have good stretch, and are generally referred to as “dive skins” or just “skins. There are also suits made from Lycra combined with additional materials such as polyolefin microfibers which provide good wind resistance. Dive skins may be worn in tropical waters when the diver’s activity level is relatively high. In some cases where buoy ancy is desirable, wet suits made from rubber are recom mended. The suits are designed to allow water to enter the area between the diver’s skin and the suit. Ideally, a wet suit should fit snugly, allowing only a minimum of water inside the suit. This thin layer of water is warmed up by the diver’s body and provides rea sonable comfort at moderate temperatures. Booties Wet suits come in a variety of thicknesses, one mil limeter up to seven millimeters. They also come in numer well for one diver may not work satisfactorily for another; ous designs, including shorty suits, one-piece suits, and therefore, divers may have to try several different types and multi-piece suits. As the water temperature drops, from either rubber or graphite and are available in different thicker suits and multiple layers of insulation become nec foot pocket sizes. For example, in Southern California, the preferred frequently used in the tropics, they are rarely used in colder wet suit is usually six or seven millimeters thick with a waters. One of the disadvantages to the full-foot fin is that “farmer john” set of bib overalls and a jacket of the same when the foot pocket wears out, the fin cannot be repaired. The open heel adjustable fin is normally worn with neo the use of zippers in wet suits is a personal preference prene booties (see Figure 5. While zippers make it easier to don a suit, type of fin is that if the heel strap breaks, it can be replaced. Some divers prefer a suit without a the water temperature, the diver’s work load, personal nylon lining and use a diluted solution of hair conditioner physiology, and any contaminants that may be present in or talcum powder to make the neoprene surface slippery the water.
Such a case came to treatment tracker generic atomoxetine 40 mg online notice in the late 1970s in Lakhmipur in Kheri district symptoms 2 days after ovulation purchase 25 mg atomoxetine, in the Indian state of Agrochemical Poisoning 309 Fig inoar hair treatment discount atomoxetine amex. Farmers in this state were found to treatment lichen sclerosis buy 25 mg atomoxetine visa be preserving food grains with benzene hexachloride. A severe convulsive epidemic broke out among several hundred people because of this ignorance and more than 250 people died. In 1997, improper use and application of benzene hexachloride in the town Sunser in the Indian state of Madhya Pradesh resulted in many people falling ill. In March 1999, a case of agricultural poisoning from India was reported where an entire family was poisoned owing to leakage of pesticides into cereal (sorghum/jowar) stored in the same room (185). Because these areas are close to local residential areas, deleterious effects occurring in humans have caused a major controversy in recent times (23). Pillay (40) suggests that accidental poisoning due to pesticides can occur in four different scenarios: (a) occupational exposure among agriculturists and those engaged in the task of pesticide spraying, (b) contamination of foodstuffs on account of negligence, (c) inadvertent ingestion by children, and (d) reusing 310 Aggrawal pesticide containers for storing food or drink (the latter is very common among third-world countries). Instances of fatalities among agricultural workers due to accidental expo sures have been reported from time to time (186). Accidental poisoning owing to some pesticides, such as paraquat, occurs in a number of scenarios. Book of Bloemfontein, South Africa, reported a unique case of accidental poisoning with paraquat: a young woman tried to “achieve a high” by spiking her Coca-Cola with paraquat. At the time of her admission she had told the doctor that her husband had maliciously put paraquat in her drink a few days before; how ever, only 2 days later she changed her version as just mentioned (188). It is noteworthy that in India it is very common for married women at the time of their death to shield their murderous husbands by making such statements. According to Harry (4), accidental pesticide intoxications are mainly caused by ingestions of diluted fertilizers, low-concentration antivitamin K rodenticides, ant-killing products, or granules of molluscicides containing 5% metaldehyde, whereas voluntary intoxications are mostly by chloralose, strych nine, organophosphorus or organochlorine insecticides, concentrated antivita min K products, and herbicides, such as paraquat, chlorophenoxy compounds, glyphosate, and chlorates. Suicidal Poisoning Suicidal poisoning with agrochemicals, especially organophosphates and AlP, is very common in countries like India. Many companies now add an emetic to dan gerous agrochemicals, such as paraquat and AlP. Addition of a “stenching” agent to paraquat has apparently not deterred suicidals from consuming this poison. Organophosphorus and Organochlorines Homicidal poisoning with organophosphorus compounds is possible and from time to time, one gets to hear or read about cases of a homicide commit Agrochemical Poisoning 311 ted with these substances. Svraka and colleagues have described four cases of homicide with organophosphorus compounds (189). However, homicidal poisonings with organophosphorus compounds are rare because of the unpleasant taste of most agrochemicals, especially of organochlorines, such as endrin, but they have been mixed with alcohol, espe cially Toddy (a strong liquor that is very popular in India), which masks its smell and has been used with organophosphorus compounds for homicidal pur poses in this way. Paraquat the commonly used herbicide paraquat is odorless and gives rise to symp toms mimicking viral pneumonitis. These two properties—classically hailed as the properties of an ideal homicidal poison—make it very attractive as a homi cidal poison. Paraquat is supposed to have a burning taste, but this can be masked in hot liquids or spicy foods (194). Teare and Teare and Brown (46,195) described five cases of paraquat poi soning, of which, two were homicidal in nature. The first is a well-documented case (Reg vs Kenyon and Roberts) in which a 22-year-old man, Keith William Kenyon, was killed by his wife Jennifer Kenyon and her friend, David Roberts, a consultant on the effects of agricultural chemicals. She purchased Gramoxone along with her friend Olive Hemming (who turned out to be the chief prosecution witness) from a farm shop, and most likely administered it to her husband in repeated small doses. During his illness, he displayed all the classical symp toms and signs of paraquat poisoning. Kenyon was convicted of murder, whereas David Roberts was acquitted because of lack of evidence against him (195). After Christmas 1973, on the Falkland Islands, four local agricultural workers had been having a Boxing Day party when some Gramoxone was slipped for some unknown reason into one of their beers. Criminal charges against the other three laborers were contemplated, but eventually it was decided to drop them. Paul (196) described the case of a 28-year-old woman who killed her hus band by mixing paraquat in his steak-and-kidney pie twice. When he developed 312 Aggrawal a sore throat and was prescribed medicine for treatment, she mixed paraquat in the medicine as well. The cause of death was attributed to cardiac arrest in combination with renal failure and bilateral pneumonia and it was only by a curious chain of circumstances that paraquat was detected in the young man’s tissues preserved in the mortuary in a bucket, 8 months after the man’s death. Of these, the first three murders were perpetrated by one man against members of his immediate family, and the fourth case was equivocal—it could either have been suicide or homicide. When the fourth wife threatened to divorce him, she found herself ill and died 24 days after the onset of her illness (19 days after hospitalization). Eight years later, when his fifth wife threatened divorce, she suffered the same fate, and a few months later, his 79-year-old mother also died. Although a suggestion of paraquat poison ing was made in all three cases, the concerned pathologist was reluctant to sign death certificates as paraquat poisoning. Toxicological analysis in the second and third cases revealed the presence of paraquat in the victims’ tissues and this resulted in conviction of the murderer. It was found that the defendant worked as a mechanic on a large agricultural ranch and had easy access to paraquat; his thumb print was found on one of the opened paraquat containers, although he had earlier denied having to do anything with those containers. The fourth case involved a 27-year-old man, a registered herbicide and pesticide user, who had marital difficulties with his aggressive, “shrew-like” wife who also stood to benefit from a large insurance policy upon his death. While in hospital, the vic tim denied suicidal ingestion; he died 21 days after the start of his illness. No testing of toxic effects from the compounds he worked with was ever per formed, nor was any consideration given to this possibility. Stephens and Moormeister concluded that the reason why such cases will often go unnoticed is because of the reluctance on the part of both clinicians and forensic pathologists to even think in the direction of paraquat poisoning when they see such a clear and typical picture of “viral pneumonia. The pathologist conducting the postmortem would do well to go through the clinical history, if available, in detail to rule out Agrochemical Poisoning 313 the possibility of paraquat poisoning. In all doubtful cases, a full toxicological analysis should be done and the tissues should be particularly analyzed for paraquat. Daisley and Simmons from the University of the West Indies in Trinidad reported two cases of homicide by paraquat poisoning (197). Both cases occurred in children and the common clinical presentations were gastrointesti nal ulceration and acute respiratory distress with pneumomediastinitis. The authors stress that pathologists should be aware of this finding because they feel that if this autopsy finding is seen combined with the typical clinical presentation mentioned in Sections 3. Sodium Chlorate Another weed killer that has been used commonly for homicidal purposes is sodium chlorate. In Reg vs Hargreaves, Hampshire (Winchester) Assizes, April 1962, a 54-year-old woman was charged with the murder of a 78-year-old man whom she had known for the last 50 years as an uncle. On January 10, 1961 the accused bought the weed killer sodium chlorate apparently for a friend who was a gardener. On January 19, 1961, the old man died and the postmortem examination showed signs of death from sodium chlorate poisoning. The vic tim had consumed beer and the remaining beer in the mug contained some 65 mg of sodium chlorate. The jury found the woman guilty of manslaughter and sentenced her to 18 months of imprisonment (199). Agent Orange One of the biggest and most well-known medicolegal controversies in connection with herbicides has been that of Agent Orange. Agent Orange is the name given to a mixture of herbicides that United States military forces sprayed in Vietnam from 1962 to 1971 during the Vietnam War for the dual purpose of destroying crops that might feed the enemy and defoliating forest areas that might conceal Viet Cong and North Vietnamese forces. The defoliant consisted of approximately equal amounts of the unpurified butyl esters of 2,4-D and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Agent Orange also contained small, variable proportions of 2,3,7,8-tetra chlorodibenzo-p-dioxin—commonly known as dioxin—which is a byproduct of the manufacture of 2,4,5-T and is toxic even in minute quantities; dioxin is considered one of the most toxic compounds synthesized by humans. About 50 million liters of Agent Orange were sprayed over Vietnam from low-flying aircrafts. Among the Vietnamese, it is considered to be the cause of an abnormally high incidence of miscarriages, skin diseases, cancers, birth defects, and congenital malformations (often extreme and grotesque).
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