Meclizine
By P. Surus. William Howard Taft University.
Studying the operationalization of chronotype in the population-based sample order 25mg meclizine fast delivery medications that cause dry mouth, it was observed that chronotype classes are characterized by differences in morning- and evening preference and also morning tiredness generic meclizine 25mg visa treatment improvement protocol. These Profiles were estimated to comprise of 45% and 47% of men and women, respectively. Epidemiological studies have previously observed physically active persons to report better sleep quality (Laugsand et al. Persons that report frequent insufficient sleep (Strine and Chapman, 2005) or insomnia-related symptoms (Haario et al. Long sleep did not strongly differentiate the Profiles in either men or women but self-reported sleep sufficiency did. It was observed that there was an equally high likelihood of self-reported insufficient sleep in Profile 3 and Profile 4 among women, but in men the clearly highest likelihood of insufficient sleep was observed in Profile 4. Even if many studies mention the clustering of behaviors, there is diversity in the used methods of clustering (McAloney et al. The use of actual clustering methods that model underlying associations between health-related behaviors is less common than studying the health behaviors in isolation or using approaches of co-occurrence or only selected combinations of behaviors (Conry et al. The observed or unobserved source of heterogeneity is an important aspect that separate different cluster analyses methodologically (Lubke and Muthen, 2005). Furthermore, a distinction between variable-oriented and person-oriented methods can be made. In variable-oriented methods the focus is on modelling associations between variables, whereas in person-oriented approaches the focus is on individuals and inter-individual variation (Bergman and Trost, 2006; Collins and Lanza, 2010; von Eye et al. Person-oriented modelling looks at the individual as a totality made up of inseparable components that form patterns of behavior or traits, whereas variable-oriented modelling sees the world as linear variables and the individual as a sum of variables (Bergman and Trost, 2006). In empirical research, theories are many times made up of complex interactions, mutual causality, and nonlinear relations that are not properly accounted for in variable-oriented modelling (Bergman and Trost, 2006). Only among the oldest participants (50-60 years) the two clusters differed in terms of sleep, but generally sleep was not an important discriminating factor in the clusters (de Bourdeaudhuij and van Oost, 1999). Of these two previous studies, the Spanish study is more alike to the substudy I in terms of the studied behaviors, whereas the Belgian study is more similar methodologically. These behavioral classes in adolescents are much like the Profiles identified in this adult sample. Interestingly though, a higher percentage of women than men most likely went with the class of poor behaviors, contrary to what was observed in adolescents. It is commonly thought that active athletes who live a disciplined and healthy life in many aspects, also have good and sufficient sleep. Findings however do not support these beliefs, as insufficient or poor sleep can be quite common in active athletes (Lastella et al. Many ways to operationalize chronotype exist, but the shortcomings of widely used questionnaire-based indexes and sum-scores include the choice of proper cut-off values and the impossibility to conclude on more specific characteristics behind the score (Adan et al. Using predefined classification scores, one also have to assume that the operationalization is valid for the sample studied, while it remains unknown what the best classification for the specific sample would be. Furthermore, the evening type has repeatedly been shown to associate with an increased risk of disease (Merikanto et al. The self-rated morning-evening preference, that also as a single item has been used to operationalize the chronotype, was as expected a clear differentiating item between the chronotypes. The findings support that also morning tiredness is an important dimension of the chronotype to recognize, in addition to morning and evening preference (Konttinen et al. The corrected midpoint of sleep is a measure of the timing of the sleep that considers both weekday and weekend sleep (Roenneberg et al. As evening types have been demonstrated to sleep longer during days off (Wittmann et al. The midpoint of sleep was indeed different between the four as well as the five latent chronotypes, with a later midpoint in each more evening oriented class and the latest midpoint of sleep in definitely evening types. For women, the likelihood of evening type was a feature of Profile 3 the “Occupationally active, unsatisfied evening type sleepers”, whereas in 73 Discussion men the evening type was as likely found in Profile 3 as in Profile 4.
Although they are impor- tant for generating the life force buy meclizine 25 mg with mastercard treatment centers for depression, they are also extraordinarily harmful cheap meclizine 25mg online medicine 5113 v. Over the course of evolution, different enzymatic and nonenzymatic antioxidative mecha- nisms were developed, such as various vitamins, ubiquinone, glutathione, and circulating proteins such as hemopexin. Hyaluronan may also be one such mecha- nism, acting also as a free radical scavenger (168). Sunlight (ultraviolet) is an additional generator of harmful oxygen-derived species such as hydroxyl radicals. Further complications have occurred in this assembly of metabolic attack and counterattack reactions that have been compiled in the selective forces of evolution. An unusually high level of antioxidants are present in skin, such as vitamins C and E, as well as ubiquinone and glutathione. To prevent this sun-induced cascade of oxidative injuries, topical prepara- tions containing antioxidants have been developed in the past several decades. Initially, such antioxidants were added as stabilizers to various dermatological and cosmetic preparations. However, following oxidation, vitamin E is degraded into particularly harmful pro-oxidative metabolites (176). Hyaluronan 341 In the past several years, increasing concentrations of antioxidants have been used in such skin preparations in an attempt to create complementary combi- nations, or to create constant recycling pairs that alternatingly oxidize and reduce each other (177). The alpha-hydroxy acids contained in fruit extracts, tartaric acid in grapes, citric acid in citrus fruits, malic acid in apples, mandelic acid in almond blossoms and apri- cots are thought to be active principles for skin rejuvenation. The cosmetic effects of these preparations of alpha- hydroxy acids, including lactic acid, involve increased skin smoothness with the disappearance of lines and fine wrinkles. Long-term use results in thickening of the skin, in both the epidermal and papillary dermal layers because of the mild fibrous reaction. These results derive from the mild fibrous reaction typical of diffuse wound healing, and may explain the increased thickness and firmness of both dermis and epidermis. The increased collagen deposition documented in skin after prolonged use is consistent with a wound-healing effect (186). Neutral or mildly acidic preparations of alpha-hydroxy acids, as would have been found in the fruit compresses of the ancients have yet to find current cosmetic equiva- lents, though such vehicles are actively being sought (187). Upon examining the structure, it is obvious that ascorbic acid is also an alpha-hydroxy acid. However, ascorbic acid is also present in fruit, and may underlie some of the effects attributed to fruit 342 Neudecker et al. Retinoic Acid and Its Derivatives Topical application of retinoic acid derivatives reduce the visible signs of aging and of photodamage (188) though there is little correlation between the histologi- cal changes and the clinical appearance of the skin. While vitamin D is considered the ‘‘sunshine vitamin,’’ vitamin A has been accepted as an apparent antidote for the adverse effects of sun exposure, and assumed to prevent and repair cutaneous photodamage (188). Application of vita- min A derivatives do reverse some of the sun damage to skin, the roughness, wrinkling, and irregular pigmentation (189,190). For the over-40 generation, brought up in an era of ‘‘suntan chic,’’ appropriate preparations to restore or to prevent further deterioration of skin are critically important. Down-regulation of nuclear receptors for vitamin A occurs (191), resulting in a functional deficiency of vitamin A. Application of vitamin A derivatives would appear to be an obvious treatment modality. A combination of vitamin A and such cytokines or growth factors may provide the requisite treatment to reverse effectively the effects of long-term sun expo- sure. The effect is achieved through both decreased synthesis as well as decreased rates of degradation (193). The high concentrations of cortisone also enhance terminal differentiation of keratinocytes and reduces rates of cell proliferation. This generates a material much lower in molecular weight that has the additional disadvantage of frequent contamination by residual bacte- rial pyrogens. Such solutions, applied to the skin form hydrated films that hold water for considerable periods, and confer the properties of a moisturizer. Another direction in such research is to combine it with other materials, such as chondroitin sulfate and 344 Neudecker et al.
Nonhuman primate studies are cheap meclizine 25 mg line symptoms quit drinking, however discount meclizine 25 mg without prescription symptoms walking pneumonia, orders of magnitude more expensive than rodent teratology studies, and few drugs are evaluated in primates. Unfortunately, the ultimate assessment of the safety of medication use in pregnancy must come from human studies (Schardein, 2000; Shepard, 2004). Human teratogens are discovered only after numerous children have been damaged, and an astute clinician recognizes a pat- tern (syndrome) of congenital anomalies, and makes the link to an exposure during pregnancy. For example, of approximately 2000 drugs and chemicals tested in animal models, 55 percent were found to have teratogenic effects (Shepard, 2004). A recurrent pattern of anomalies in babies who experienced similar well-defined exposures at similar points during embryogenesis are suggestive that the agent in question may be teratogenic. Case reports are important in raising causal hypotheses; however, most hypotheses are subsequently Human studies 7 proven incorrect. For example, a high incidence of environmental exposure to spermi- cides by pregnant women and congenital anomalies in offspring is a coincidental occur- rence, despite what the legal literature states. An example of a teratogen that was identified through epidemiologic studies, case reports, and animal studies is carabamazepine. For several decades, carabamazepine was assumed to be safer for the treatment of epilepsy during pregnancy than phenytoin or the other hydantoins. In 1993, a case report was published that reported a suicide attempt by a nonepileptic gravida during the period of spinal closure. Other epidemiologic studies throughout the 1990s were conducted, and in 2006 the association of neural tubes defects with carabamazepine exposure during early pregnancy is generally accepted as causal, and the risk is quantified at about 1 percent, compared to about 0. Quantitative estimates of risks for birth defects (strength and statistical significance of associations between agent exposures in pregnant women and abnormalities in their off- spring) are obtained only through epidemiological studies. Unfortunately, such studies are not informative until the agent has already damaged a number of children. There are two types of epidemiology studies: cohort studies and case–control studies. In cohort studies the frequencies of certain anomalies in the offspring of women who are exposed are compared to the frequencies in those who are unexposed to the agent in question. A higher frequency of anomalies among exposed pregnancies indicates that the drug or agent should be scrutinized as a teratogen. In case–control studies the frequency of pre- natal exposure to the agent is compared among children with and without a specific birth defect. If malformed children were more frequently exposed to a drug or agent than unaffected controls, then the drug or agent may be a teratogen. If an agent increases the risk of anomalies in the offspring only slightly, very large studies over a protracted period may be necessary to demonstrate that the increase is causal. Spurious associations often occur because many epidemiologists lack medical or biological training, and fail to scrutinize their ‘statistical associations’ for biological plausibility. Other confounders are sample size, investigations that involve small numbers of exposed or affected subjects, or situa- tions in which the maternal disease or situation that led to the exposure may be respon- sible for an observed association with a congenital anomaly, rather than the agent itself. Exposures that produce malformations in the embryo should do so only during organo- genesis or histogenesis. Affected structures should be susceptible to the teratogenic action of an agent only at specific gestational times. Systemic absorption of the agent by the mother and its presence at susceptible sites in the embryo or placenta should be demonstrable. Exposure to a greater quantity of the agent should be associated in a dose–response fashion with an increased frequency of abnormalities. Finally, a causal inference is supported if a reasonable pathogenic mechanism can be established for the observed effect. For example, lower birth weight is associated with maternal antihyper- tensive therapy, but maternal hypertension is itself strongly associated with decreased 8 Introduction to drugs in pregnancy birth weight. Is lower birth weight associated with the blood pressure medication, or the disease of hypertension, or some combination? In 1996, a new thalidomide embryopathy epi- demic was reported in Brazil and other South American countries (Castilla et al. The astute reader will note that some of the putative teratogens do not fit precisely the definition of teratogen (i. Exposure to drugs during pregnancy must be separated into these time periods because the conceptus responds dif- ferently in each of the three stages of development. Preimplantation No physiologic interface between the mother and the conceptus exists at conception (ovum penetration by the spermatid to form a single diploid cell).
Purge The Parasite order meclizine 25mg line treatment brachioradial pruritus, Cure The Cancer The good news is that when the fluke and all its stages have been killed cheap meclizine 25 mg without prescription medicine 9312, the ortho-phospho-tyrosine disappears. Why do the microscopic fluke stages choose the cervix or prostate or lung in which to settle for reproduction? Perhaps it is because this organ has developed “safety islands” for them, namely, precancerous tumors. A benign tumor has lost its im- mune power for you, so that it cannot catch and kill the tiny in- vaders. Fungus is even growing there and producing patulin, a carcinogenic myco- toxin (carcinogenic means cancer-causing; a mycotoxin is a toxin produced by a fungus). Is it just a coincidence that the parasite survives and reproduces itself best in your most un- healthy organs? Flush out the metals, common toxins, and bacteria from your body so you can get well. We have been taught to believe that every parasite is so unique that a different drug is required to kill each one. It would be best to kill them all together even though only the in- testinal fluke is causing cancer. It is not unusual for someone to have a dozen (or more) parasites out of the 120 parasites I have samples of (they are listed in The Tests). Our bodies are large enough to provide food and shelter for lots of these free loaders. If they were settled on the outside where we could see them, like lice or ticks, we would rid ourselves in a flash. Nothing is more distasteful to the imagination than hordes of biting, chewing, crawling, sucking creatures on our flesh. Herbal Parasite Remedies The Native American peoples knew that humans are parasi- tized. They had frequent purgings that included diarrhea or vomiting to rid themselves of their slimy invaders. I remember being forced to swallow a spoonful of sulfur and molasses and raw onion! Getting rid of all these parasites would be absolutely impos- sible using clinical medicines that can kill only one or two para- sites each. Flagyl is used for amoebas and Giardia; when the correct dos- age is used, it can cause extreme nausea and vomiting. Black walnut hull and wormwood kill adults and developmental stages of at least 8 100 parasites. If you kill only the adults, the tiny stages and eggs will soon grow into new adults. If you kill only the eggs, the million stages already loose in 8 This anti-cancer action of cloves was not discovered by me, but by a neighboring health practitioner, using a kinesiological technique she developed herself. It is the green hull surrounding the nut of the black walnut tree that has this miraculous parasiticide. Therefore, anyone wishing to make parasiticide must be careful not to let the critical time for harvesting pass. I encourage eve- ryone to make their own parasiticides and to take back the re- sponsibility for keeping themselves and their families free of these tiny monsters. The recipe for Black Walnut Hull Tincture Extra Strength is given in Recipes (page 587). Note that it is a tincture (extracted using ethyl alcohol), not an ordinary extract (which uses water). The black walnut ex- tract that is available from herb companies is not potent as a parasiticide. It is black, not pale green, indicating that the criti- cal harvesting time had passed. Of course there is no time to make your own if you have fast growing or metastasizing can- cer. While you are waiting for it to arrive, get your other two herbs ready: wormwood and cloves. Wormwood capsules are available as a combination of Ar- temisia and other herbs (see Sources).
Too Sick To Cook cheap meclizine 25mg on line medications hypothyroidism, Too Tired To Eat Pick three meals from the sample menu that need no cook- ing and eat them every day meclizine 25mg low price medications 5 rights, rotating as much as possible. Even if you have dry skin, difficult hair or some other unique requirement, just pure borax will satisfy these needs. A part of every skin problem is due to the toxic elements found in the soaps themselves. It does this by impregnating the skin and attracting water, giving the illusion of moist skin. In fact you simply have moist aluminum stuck in your skin which your immune system must remove. Borax Liquid Soap An empty 1 gallon jug 1/8 cup borax powder Plastic funnel Funnel the borax into the jug, fill with hot tap water. When you have used it down to the undissolved granules, discard them and start over. It does not contain cobalt (the blue or green granules) which causes heart disease and poisons the bone marrow. It is the main ingredient of non- chlorine bleach and has excellent cleaning power without fad- ing colors. For bleaching (only do this occasionally) use original chlorine bleach (not “new improved” or “with special brighteners”, and so forth). For get- ting out stubborn dirt at collars, rub in homemade bar soap first; for stains, try grain alcohol, vinegar, baking soda (check old recipe books for stain removal tricks). Any dish soap that you use should be safe enough to eat because nothing rinses off clean. Start each day by sterilizing your sponge (it harbors Salmonella) or with a new one while the used one dries for three full days. It does not lather but feels slippery between your fingers (If it is not slip- pery, the concentration is too low. It goes right to work removing sweat and soil without stripping your color or natural oils. Hair gets squeaky clean so quickly (just a few squirts does it) that you might think nothing has happened! Only citric acid is strong enough to rinse the borax out, lemon juice and vinegar are not. All hair shampoo penetrates the eye lids and gets into the eyes although you do not feel it. A single squirt of homemade liquid soap (see Recipes) added to borax liquid makes it quite lathery if you need time to adjust to plain borax. Remarkably, a little lemon juice (not from a bottle) has some holding power and no odor! Pour 3 cups of very cold water (refrigerate water over- night first) into the 2-quart saucepan. Slowly and carefully add the lye, a little bit at a time, stir- ring it with a wooden or plastic utensil. In olden days, a sassafras branch was used to stir, im- parting a fragrance and insect deterrent for mosquitoes, lice, fleas, ticks. Meanwhile, the unwrapped lard should be warming up to room tempera- ture in the plastic dishpan. If you do not, this soap may be too harsh for your skin, while it is excellent for cleaning the sink. Only the large size Everclear bottle (750 ml or 1 liter) is free of isopropyl or wood alcohol contaminants. If using 76% grain alcohol, mark your bottle one tenth of the way up but only add water to the ¾ full mark. Use this for general sanitizing purposes: bathroom fixtures, knobs, handles, canes, walkers, and for personal cleanliness (but use chlorine bleach for the toilet bowl once a week). This is still not clean enough; use a final damp paper towel with skin sanitizer added. After washing hands, sanitize them too, pouring a bit on one palm and put finger tips of the other hand in it, scratch to get under nails, repeat on other hand. Do not use this recipe, nor keep any bottles of alcohol in the house of a recovering alcoholic.
Any generic meclizine 25 mg line medicine lux, or all purchase 25 mg meclizine with amex treatment yeast overgrowth, of these processes could contribute to the feedback inhibition of transmitter release. Similar processes could explain the effects of activation of other types of auto- or heteroceptors. Studies of a range of substituted amphetamines, using cultured serotonergic neurons, have confirmed that this release is not prevented by either N-type or L-type Ca2 channel blockers, or removal of Ca2 from the incubation medium, or depletion of the vesicular pool of transmitter. Such carrier-mediated release could explain the massive Ca2-independent release of noradrenaline during ischaemia which increases intracellular Na concentration and reduces intracellular K. Amino acids might also be released in this way (see Attwell, Barbour and Szatkowski 1993). Glutamate release during ischaemia is also thought to involve such carrier-mediated transport. A similar process might also explain a glutamate-induced increase in glycine release from astrocytes in the hippocampus. Unlike the carrier-mediated release described above, this form of release is thought to be Ca2-dependent and to involve vesicular exocytosis. However, the contribution of this process to the physiological control of neurotransmission has not yet been resolved. However, many details concerning the supply of vesicles that participate in this process, as well as the processes which regulate the docking and fusion of synaptic vesicles with the axolemma, remain uncertain. Activation of these receptors is coupled to the release process through their respective second messengers. It is also evident that vesicular exocytosis is not the only process which leads to release of transmitter from nerve terminals. Under certain conditions, axolemma-bound transporters can export transmitters from neurons or even evoke exocytosis. It seems that a range of processes contribute to release of neurotransmitters, all of which could have a vital role in the regulation of neurotransmission. Benfanati, F, Onofri, F and Giovedi, S (1999)Protein±protein interactions and protein modules in the control of transmitter release. Greengard, P, Benfenati, F and Valtorta, F (1994)Synapsin I, an active-binding protein regulating synaptic vesicle traffic in the nerve terminal. In Molecular and Cellular Mechanisms of Neurotransmitter Release (Eds Starjne, L, Greengard, P, Grillner, S, Hokfelt, T and Ottoson, D), Raven Press, New York, pp. Operational characteristics of the alpha2 autoreceptors in the bed nucleus of the stria terminalis, pars ventralis. Winkler, H (1993)The adrenal chromaffin granule: a model for larger dense core vesicles of endocrine and nervous tissue. It is the chemical structure which determines to which receptor a drug combines and how specific it is in its action. Ideally a drug should only bind to one receptor type 1 but in reality very few, if any, are that specific, especially at high concentrations. In fact the magnitude of the response, like that of a chemical reaction, is proportional to the product of the concentration of the reactants, in this case the drug and its receptors, and as such obeys the law of Mass Action. Thus the lower the concentration of drug required to achieve this occupancy, the greater its affinity. Unfortunately its affinity does not necessarily reflect its potency in producing an effect. This is hyperbolic but is transformed to a sigmoid shape, which is linear over a large dose range, when the dose is plotted on a log scale (Fig. Comparison of the con- centrations of two or more drugs required to produce the same response is a measure of their relative potency. Often the potency of a drug is defined as the dose or concentration of drug required to produce 50% of the maximal response, i. It obviously has agonist activity but since it cannot produce a maximal response it is known as a partial agonist. While such a property may seem unwanted the drug could still produce an adequate effect and avoid the danger of that becoming too great with increasing dose. When a drug is administered to either humans or animals we obviously know the dose but not the concentration at its site of action. In this instance the relationship between the amount of drug and its effect really is a dose±response curve.
The implications are that retinoids may be able to repair intrinsically aged skin as well as photoaged skin generic meclizine 25mg lb 95 medications, and that retinoids may modulate skin cell function in a manner that is age-related generic 25mg meclizine fast delivery medicine joji, not simply a response to photo- damage. Fetal malformations, spontaneous abortions, hyperlipidemia (particularly elevated triglycerides), bone abnormalities, skin and mucosal dryness, retinoid dermatitis, pruritus, hair loss, pseudotumor cerebri, arthralgias, myalgias, and abnormal liver function tests (increased liver transami- nases and alkaline phosphatase) are among the myriad potential adverse effects of retinoid therapy (29). Most of the above effects are reversible upon discontinu- ation of the retinoid, although some serious effects, such as fetal malformations and bone abnormalities, are not. We do not have sufficient case population data to be certain of cause and effect and no true double-blind studies exist. The details of this mechanism are beyond the scope of this chapter and the reader is directed toward a recent review for elucidation (30). Topical application has the benefit of a significantly better adverse effect profile. The most common sequelae are mucocutaneous effects, characterized by skin and mucosal dryness (xerosis, cheilitis, conjunctivitis), desquamation, erythema, and pruritus. These effects typically start after several days of therapy, peak within the first few weeks, then wane as tolerance develops (31). They are easily treatable—frequent application of emollients and other precautionary measures (such as avoidance of harsh soaps, astringents, abrasives, and excessive bathing) will ameliorate the situation. The mucocutaneous effects are dose depen- dent and reversible upon discontinuation of the retinoid. Teratogenicity, well documented as the most serious side effect of oral retinoids (32), is logically the potential concern with topical retinoids. With oral retinoids, most aromatic retinoids cross the placenta; in utero exposure results in limb and craniofacial deformities, as well as cardiovascular and central nervous system abnormalities. Systemic absorption of topical retinoids, however, is thought to be negligible (33). A large retrospective study of birth defects in off- spring born to mothers exposed to topical tretinoin (all-trans-retinoic acid) during pregnancy has demonstrated no significant risk (34). Even in light of this evidence, many clinicians feel strongly about avoiding topical retinoids in pregnancy (36). Reports of enhanced photocarcinogenicity in experimental mice exist (37), but no evidence exists of a comparable process with humans (38). Conversely, topical retinoids appear to have a protective effect against ultraviolet-induced premalignant and malignant lesions. However, skin treated with topical retinoids is more reactive to chemical and physical stresses (including ultraviolet light), because of the thinner horny layer and amplified vasculature. The successful trials of topical tretinoin have inspired the pursuit of other topical retinoids that could be effective in photoaging with fewer adverse effects. Undoubtedly, newer derivatives with safer adverse effect profiles will be forthcoming. Specifically, two new retinoids, adapalene and tazarotene, Topical Retinoids 119 licensed for the treatment of acne and psoriasis, respectively, will almost certainly be investigated for photodamage. Sus- tained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin. Topical treatment of multiple ac- tinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double blind, comparative study. Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins character- istic of retinoic acid, but without measurable retinoic acid levels or irritation. Extraction of human epider- mis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters. In vitro metabolism by human skin and fibroblasts of retinol, retinal and retinoic acid. Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal. Among such diseases, malignant tumors should be diagnosed and treated properly be- cause some of them are quick to develop, destructive, or fatal. Hyperpigmentation of the face of middle-aged women, is most common; however, it is benign, and, if diagnosed and treated early, it can be prevented in the future. Melasma is commonly observed among middle-aged women (average age of 43) (1) and is rare in men. It is a diffuse or well-circumscribed noninflamma- tory brown hyperpigmentation that frequently occurs around the eyes, mouth, cheeks, and forehead. An experienced old Japanese dermatologist in Kyoto City often told melasma patients, ‘‘You need not treat melasma.
