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Moreover purchase ethambutol 800mg with amex infection you can get when pregnant, there is extensive evidence that anti-anxiety drugs prevent activation of the behavioural inhibition system by blunting monoaminergic transmission in the hippocampus generic ethambutol 600 mg otc bacteria jekyll island. Gray (1987) proposes that the central grey is normally inhibited by the (ventromedial) hypo- thalamus and that the influence of the hypothalamus is governed in opposing ways by the behavioural inhibition system and the amygdala discount ethambutol 400mg on line bacteria 365 days plague inc. Whereas the former augments hypothalamic inhibition of the flight/fight response, the latter inhibits it, thereby releasing the flight/fight response (Fig. In the former region, they are thought to augment active avoidance of aversive signals by exaggerating the amygdalar response to conditioned aversive stimuli (Deakin and Graeff 1991; Graeff et al. Inputs from the behavioural inhibition system also augment the activity of the (ventromedial) hypothalamus which suppresses the flight/ fight response generated in the periaquaductal grey. In contrast, the amygdala inhibits hypothalamic activity and releases the flight/fight response. Anti-anxiety drugs are thought to inhibit monoaminergic activation of the behavioural inhibition system cortex, which is thought to process the perception of sensory information, and the hippocampus, which processes contextual (environmental) cues. It is suggested that a reduction of serotonergic transmission in this area releases the flight/fight response. Under normal conditions, activity in this system is governed by higher centres in the forebrain (the cortex and hippocampus) so that, when interpretation of prevailing stimuli deems it appropriate, the flight/fight response is suppressed. It could also explain why patients often report that they are woken up during the night by their panic attacks. Activity within the defence system is governed by higher centres, such as the frontal cortex and hippocampus. Serotonergic neurons projecting from the dorsal Raphe nucleus are proposed to activate the amygdala (‡) thereby promoting the response to conditioned aversive stimuli (anxiety). A deficit in serotonergic transmission to this brain region is thought to underlie panic. In fact, this has been offered as an explanation for the panic attacks experienced by some patients given buspirone. It could also explain the increase in panic attacks in the early stages of treatment with antidepressants. Obviously, any explanation of anxiety must account for the actions of benzo- diazepines. According to this scheme, benzodiazepines might activate this latter system and generate spurious safety signals (see Handley 1995). The finding that noradrenergic neurons innervating the frontal cortex, but not those projecting to the hypothalamus, respond to conditioned environmental cues (McQuade and Stanford 1999) suggests that there could be a similar subdivision of function in this monoamine system as well. Clearly, any theory for anxiety must eventually take account of evidence that serotonergic and noradrenergic systems do not operate independently. The outcome of preclinical and clinical investigations (together with further references) are detailed in Jackson and Nutt (1996). So far, no compounds have emerged as clear candidates for the clinic, not least because pharmacokinetic considera- tions and adverse effects in the periphery are common confounding factors. Nevertheless, the results from clinical trials of this compound are not promising, mainly due to low bioavailability and unacceptable side-effects. Whether it is this action of caffeine (which has many molecular targets in the brain) that explains its anxiogenic actions is not at all certain and, so far, selective adenosine receptor agonists have not yielded promising results. Another is the need to develop better treatments for other manifestations of anxiety. Novel agents, targeting peptidergic systems, might provide solutions to both these problems. It is only through the combined efforts of all the approaches outlined in this chapter that we are likely to identify the cause(s) of anxiety and develop the ideal treatment. Chaouloff, F (1993) Physiopharmacological interactions between stress hormones and central serotonergic systems. In Anxiety, Neurobiology, Clinic and Therapeutic Perspectives (Eds Hamon, M, Oilat, H and Thiebot, M-H), John Libbey Eurotext Ltd, 232, pp. Nakajima, M, Unui, A, Asakawa, A, Momose, K, Ueno, N, Teranishi, A, Baba, S and Kasuga, M (1998) Neuropeptide Y produces anxiety via Y2-type receptors. Sieghart, W and Karobath, M (1980) Molecular heterogenity of benzodiazepine receptors. Tyrer, P (1989) The Psychopharmacology of Anxiety, Oxford Medical Publications, Oxford. Mania is expressed as heightened mood, exaggerated sense of self- worth, irritability, aggression, delusions and hallucinations. In starkcontrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20. A major difficulty in unravelling the neurobiological basis of depression is that it is not a simple, unitary disorder. Also, whereas about 33% of patients recover spontaneously, about the same proportion do not respond to any treatment and only about 60±70% of patients who do respond show any improvement with the first drug of choice. There is an urgent need to find a solution to these problems, though, because this is a debilitating disorder that affects about 1 in 10 women and 1 in 50 men at some stage in their life. In over half of these cases, the depression recurs and about 15% of depressives commit suicide. These statistics alone stress the urgency of finding more effective and safer treatments for depression but this requires a better understanding of its underlying neurobiology and the mechanism(s) of action of existing drug treatments. At that time, reserpine was used as an Neurotransmitters, Drugs and Brain Function. These behaviours, and consequently those in humans, were attributed to the depletion of neuronal vesicular stores of monoamines and the reduction in monoamine transmission caused by this drug. In fact, these patients, when given iproniazid, could become quite disruptive and this action was regarded as an undesirable side-effect! However, its beneficial effects in depression were soon recognised and it was regarded as the first effective antidepressant drug. Reserpine blocks vesicular uptake of monoamines which, as a consequence, leak from the storage vesicles into the cytosol. It is now known that, when the concentration of cytoplasmic monoamines is increased in this way, they are exported to the synapse on membrane-bound monoamine trans- porters. The ensuing increase in monoamine transmission, despite the depletion of the vesicular pool, presumably accounts for the effects of iproniazid on the behaviour of reserpine-pretreated rats. In 1958, another agent, imipramine, was discovered by chance to have beneficial effects in depression.

It is also used in severe infections—toxemia order 400mg ethambutol free shipping antibiotics left in hot car, vascular collapse in meningococcosis ethambutol 600 mg without prescription antibiotics and diabetes, septicemia discount 800mg ethambutol visa antimicrobial klebsiella, diphtheria, typhoid fever, and peritoni- tis. It is used in severe allergic conditions—asthmatic status, laryngeal edema, severe ana- phylactic reactions to medicinal drugs, and pyrogenic reactions. Betamethasone: Betamethasone is 9α-fluoro-16β-methyl-11 β,17,21-trihydroxypregna- 1,4-dien-3,20-dione, or simply 9α-fluoro-16β-methylprednisolone (27. As seen from the chemical name of the drug, betamethasone only differs from dexamethasone in the ori- entation of the methyl group at C16. The proposed method of synthesis differs from the other method in a number of details and successive reactions besides the first stage, in particular concerning the addition of the methyl group at C16 of the steroid ring. Betamethasone, like dexamethasone, is synthesized from 3α-acetoxy-16-pregnen-11,20-dione; however, the methyl group at C16 of the steroid ring is not reacted with methylbromide, but rather is reacted with diazomethane followed by hydrogenation of the double bond between carbon atoms C16–C17 of the steroid ring using a palladium on carbon catalyst, which results in the corresponding β-orientation of the introduced methyl group [29]. In the first stage, both carbonyl groups of this compound undergo ketalization by ethylene glycol. Acetylating the hydroxyl group once again with acetic anhydride gives a triene 27. The secondary hydroxyl group at C16 of this product undergoes acetylation by acetic anhydride in pyridine, which forms the diacetate 27. Treating the product with N-bromoacetamide in chloric acid gives a bromohydrin (27. Opening of the epoxide ring, using hydrofluoric acid, gives the corresponding 9-fluoro-11-hydroxy derivative 27. Upon microbiological dehydrogenation, the C1–C2 bond is oxidized to a double bond, forming triamcinolone acetate (27. Corticosteroids Triamcinolone is similar to dexamethasone in terms of pharmacological action, and it is better tolerated in some cases. The main endogenic mineralocorticoid is aldosterone, which is not used in clinical med- icine, however. Unlike glucocorticoids, mineralocorticoids have an insignificant effect on carbohydrate volume. They are used for chronic adrenal insufficiency, as well as for raising tonicity and work capacity of muscles. The correlation between chemical structure and action of mineralocorticoids is extremely complex; however, a number of partial conclusions can be synthesized. The necessity of either a simulta- neous presence of acidic functions at C11 and C18, or the necessity of simultaneous absence of acidic functions at C11 and C17 in the structure of the pregnane system is also apparent. Fluorination at C9α-position increases the mineralocorticoid activity of both C11-hydroxy (hydrocortisone) and C11-deoxy (deoxycorticosterone) compounds. Alkaline hydrolysis of the acetyl group of this compound leads to the desired aldosterone (27. Reacting this with isopropenylacetate in the presence of p-toluenesulfonic acid gives the enolacetate 27. Treating the resulting enolacetate with iodosuccinimide, which reacts exclusively with the enolacetate double bond, an iodoketone is formed, which is reacted with potassium acetate to form the acetate 27. The double bond at C16–C17 is reduced by hydrogen using a palladium on carbon catalyst, forming the product 27. Oxidizing this product with aluminum, isopropylate in the presence of cyclohexanone gives desoxycorticosterone acetate (27. Corticosteroids Desoxycorticosterone causes an increase in reabsorption of sodium ions and excretion of potassium ions from the renal tubules, which leads to increased tissue hydrophilicity. It is used for an insufficiency of function of the adre- nal cortex, myasthenia, asthenia, adynamia, and overall muscle weakness. In the first stage of synthesis, dehydration of the hydrocortisone molecules is accomplished using phosphorous chloride in pyridine, which forms a product with a double bond at C9–C11 27. The resulting double bond is synthesized into an epoxide by an initial transformation to a bro- mohydrine using N-bromoacetamide and subsequent dehydrobromination using sodium acetate, which forms 21-O-acetoxy-9d-11β-epoxy-17α-hydroxy-4-pregnen-3,20-dione (27. As described above, the epoxide ring is opened by hydrofluoric acid, which results in the formation of the 21-O-acetate of fludrocortisone 27. Hydrolysis of the acetyl group of this compound using potassium acetate gives fludrocortisone (27. Present in the body in insignificant amounts, they regulate sexual differentiation and reproduction as well as affect the performance of many other physiological systems. Despite the great similarity in chemical structure, they are very different in terms of phys- iological action. Together they carry out a very important function in the development of secondary female sex organs, controlling pregnancy, controlling ovulation and menstrual cycles, and modulating a large number of metabolic processes. One of the most important areas of synthetic estrogens and progestins are their use as oral contraceptives, for hormone replacement therapy, and as drugs for menstrual disorders. These drugs can be a fixed composition containing a constant amount of estrogen (for example, ethinyl estradiol) and progestin (for example, norethindrone), a composition that contains a constant amount of estrogen with varying doses of progestin, or pills that con- tain only progestin in constant doses. They also play an important role in the development of some tumors, estrogen in particular, and antiestrogens are also used to treat breast and 365 366 28. Estrogen is a general term used to describe compounds that possesses estrogenic activity. However, they in turn can be subdivided into two groups: estrogens, which are functionalized derivatives of a steroid structure, and compounds that do not contain a steroid ring. There are three natural human estrogens: 17β-estradiol, the most powerful estrogen that transforms into a weaker metabolite estron, and which in turn is metabolized to estriol. Its oxidized analog, estrone, is secreted to a significantly lesser degree by premenopausal ovaries. The hormonal effect of estrogens on target tissues is based on a complex mecha- nism that includes their reaction with specific estrogenic cytoplasmic receptors. After binding with these receptors, a conformational change occurs, which results in the estro- gen–receptor complex penetrating into the nucleus, where it disassociates and returns to its native condition. Estrogen replacement therapy is used in agonadal, menopausal, hypothalamic, and amenorrheal conditions (i. Estrogens are also recommended for other clinical endocrine diseases if hypoestrogenism has been established. Estrogens are most widely used in combination with progestins in a number of oral contraceptive drugs.

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This seems to be true for most substances of abuse ethambutol 600mg with visa infection home remedy, except alcohol and perhaps cocaine buy ethambutol 400 mg mastercard treatment for gbs uti in pregnancy. Methadone Methadone is a synthetic opiate narcotic structurally similar to propoxyphene generic 400mg ethambutol with amex infection resistant to antibiotics. The prin- cipal medical use of methadone is as a maintenance therapy for heroin addiction, but it is used illegally as a substitute for heroin. Published studies reported include only preg- nant women on regimented-dose maintenance therapy who took methadone of known pharmacological purity. Congenital anomalies were not increased in frequency compared to the background rate among infants born to heroin-addicted women treated with methadone during pregnancy (Fundaro et al. However, withdrawal symptoms occurred frequently (up to 80 percent) and birth weights were significantly lower (2600 g) among methadone-exposed infants (n = 278) (Connaughton et al. Neonatal complications occur at a high rate, and include asphyxia neonatorum, transient tachypnea, aspiration pneumonia, congenital syphilis, jaundice, meconium staining, and neonatal death. Adverse maternal effects include prolonged rupture of membranes, breech presentation, abruptio placentae, preeclampsia, and postpartum hemorrhage (Naeye et al. Of the 17 infants, 14 were born to mothers who were enrolled in a methadone treatment program, but who continued to use other drugs as well. Review of effects of methadone maintenance during pregnancy on neonatal out- come showed two consistent findings across studies: withdrawal symptoms (70–90 per- cent) and lowered gestational age and birth weight of infants in the drug-exposed group compared to a control group (Behnke and Eyler, 1993). Developmental outcomes of heroin- and/or methadone-exposed children Several researchers have been following, assessing, and reporting on the progress of chil- dren born to heroin- and methadone-using mothers. Overall, heroin- and methadone- exposed children obtained lower scores than comparison groups in the domains of motor coordination, attention and focus, activity level and behavior, emotional distur- bances, and behavioral problems (aggression, anxiety, and rejection) (Behnke and Eyler, 1993; Davis and Templer, 1988; de Cubas and Field, 1993; Deren, 1986; Kaltenbach and Finnegan, 1984; Wilson et al. Summary of opiates during pregnancy Chronic use/abuse of opiates during pregnancy does not significantly increase the risk of congenital anomalies. Adverse pregnancy outcomes are increased in frequency: abruptio 324 Substance abuse during pregnancy placentae, neonatal withdrawal, preterm birth, and fetal growth retardation. Some dif- ferences were found in cognitive abilities, motor development and behavior between opiate-exposed children and nondrug-exposed children, but the postnatal environment with a drug-abusing mother must be considered because it is an important factor. Maternal personality traits, degrees of life stress, the quality of the mother–child rela- tionship, and assessment of the environment must be considered. In Dallas, it was estimated that 1 per- cent of women used inhalants during pregnancy, including toluene, spray paint, gasoline, freon, and other substances (Madry et al. Women who use inhalants during preg- nancy are primarily Hispanic or American Indian, with an age range of 20–29 years (Goodwin, 1988; Wilkins-Haug and Gabow, 1991). In Dallas, the majority of women using inhalants during pregnancy are young, 15–20 years of age, and usually Hispanic. Fetal solvent syndrome A collection of dysmorphic features called the ‘fetal solvent syndrome’ was observed among infants born to women who ‘huffed’ or ‘sniffed’ toluene, gasoline, benzene, and other aromatic liquids during pregnancy. Importantly, women who use a substance of abuse, including inhalants, during pregnancy frequently use other substances, including alcohol. Nonetheless, data from case reports seem to support the notion that inhalants such as toluene or gasoline, independently of concurrent use of other substances of abuse, may be associated with congenital anomalies consistently described as the fetal solvent syndrome. Anecdotal evidence suggests that the fetal solvent syndrome is associated with significant mental retardation. It is important to note that usual occupational exposure to organic solvents cannot be compared to inhalant abuse. Animal studies The frequency of congenital anomalies was not increased among rats whose mothers were exposed to high levels of toluene, but growth retardation was observed (Gospe et al. Gasoline is sometimes ‘sniffed’ Inhalant (organic solvent) abuse during pregnancy 325 by inhalant abusers to produce a euphoric effect. Acute poisoning by gasoline is associ- ated with pneumonitis, shock, cardiac arrhythmias, convulsions, coma, and death. A case report was published of two infants with profound mental retardation, neuro- logical dysfunction, and minor dysmorphic features (‘fetal gasoline syndrome’) born to women who had abused gasoline by inhalation throughout pregnancy (Hunter et al. It has not been possible to assess a causal relationship based upon two children in a case report. It is a substance of abuse used by ‘huffing’ or ‘sniffing’ for its euphoric effect. It has caused organic brain syndrome in adults and is associated with cerebral atrophy (Allison and Jerrom, 1984; Cooper et al. Adult brain damage suggests the same damage may be caused by toluene exposure in utero. Among 35 infants with the toluene embryopathy phenotype, 42 percent were premature, 52 percent had low birth weight, and 32 percent were microcephalic. Postnatally, they were below the fifth percentile for all measures, including neurodevelopment and had dysmorphic facies (Arnold et al. Preterm delivery, perinatal death, and prenatal growth retardation are associated with toluene use during pregnancy (Wilkins-Haug and Gabow, 1991). Two cases of renal tubular dys- function and metabolic acidosis (including hyperchloremic acidosis and amnioaciduria) were recently reported in infants whose mothers chronically abused inhalants contain- ing toluene (Lindemann, 1991). Early childhood growth and development were also sig- nificantly delayed among toluene-exposed infants (Wilkins-Haug and Gabow, 1991). They had the typical syndrome stigma of the toluene embryopathy at follow up (Arnold et al. Four of five neonates born to women who abused toluene during preg- nancy had low birth weight (< 2500 g), but only one had a congenital anomaly (Goodwin, 1988). Summary of solvents during pregnancy Solvent abuse during pregnancy poses significant risks to the pregnancy, endangering both the mother and the fetus. A fetal solvent syndrome probably exists and consists of dysmorphic facial features and severe growth and developmental delay (below 5th per- centile). Distal renal tubular acidosis and hyperchloremic metabolic acidosis should be expected in solvent using pregnant women and it may precipitate labor. However, tobacco native to North America is not the tobacco used today because it was too bitter to be smoked or chewed alone, and was mixed with a variety of other substances for use, including willow bark, mushrooms, and wild lettuce. The tobacco, Nicotiana tabacum, is widely used by smoking, chewing, or dipping, and is a hybrid of South and North American species. Tobacco smoke comprises several-hundred different chemicals, including nicotine and carbon monoxide in greatest abundance.

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One or both of the testicles chronically swollen discount ethambutol 600mg amex antibiotic resistance epidemiology, or showing a knotty infection (Sarcocele) discount 400 mg ethambutol with mastercard antibiotic 625. The menses are slow in setting in after the fifteenth year and later cheap ethambutol 600 mg without a prescription treatment for uti keflex, or after appearing one or more times, they cease for several months and for years. The male and the female genital parts cannot then be excited to any agreeable or voluptuous sensation - the body of the male penis hangs down relaxed, is thinner than the glans penis, which feels cold and is of a bluish or white color; in the female parts the labia are not excitable, they are relaxed and small; the vagina almost numb and insensible, and usually dry ; sometimes there is a falling out of the hair of the pudenda, or entire bareness of the female genital parts. The menses flow for five, six, eight and more days, but only intermittently, a little flow every six, twelve, twenty-four hours, and then they cease for half or whole days, before more is discharged. Menses accompanied with many ailments, swoons or (mostly stitching) headaches, or contractive, spasmodic, cutting pains in the abdomen and in the small of the back; she is obliged to lie down, vomit, etc. Leucorrhoea from the vagina, one or several days before, or soon after, the monthly flow of blood, or during the whole time from the one menstrual discharge to the other, with a diminution of the menses, or continuing solely instead of the menses; the flow is like milk, or like white, or yellow mucus, or like acrid, or sometimes like fetid, water. With a more violent flow of blood from the uterus, there are often cutting pains in the one side of the abdomen and in the groin; the cutting pain sometimes descends into the rectum and into the thigh; then she frequently cannot urinate, or sit down, on account of her pains; after these pains the abdomen aches as if it were festering. Not to mention the lesser ones (such as the itching of the pudenda and the vagina, with excoriation on the outside of the pudenda and the adjacent part of the thigh, especially in walking), hysterical states of all kinds follow the more severe cases of this troublesome flux, as also disturbances of the mind and spirit, melancholy, insanity, epilepsy, etc. Often it comes in the form of an attack, and then it is preceded by a digging in the one side of the abdomen, or by burning in the stomach, in the lower abdomen, in the vagina, or stitches in the vagina and in the mouth of the uterus, or a constrictive pain in the uterus and pressure toward the vagina as if everything were about to fall out, also at times most keen pains in the small of the back; the flatus is obstructed, causing pain, etc. Coryza at once, whenever she comes into the open air; then usually a stuffed coryza while in her room. Dry coryza and a stuffed nose often, or almost constantly, also sometimes with intermissions. Fluent coryza at the least taking of cold, therefore mostly in the inclement season and when it is wet. Fluent coryza, very often, or almost constantly, also in some cases uninterruptedly. He cannot take cold, even though there have been strong premonitory symptoms of it, simultaneously with other great ailments from the itch malady. Hoarseness, after the least amount of speaking; she must vomit in order to clear her voice. Hoarseness, also sometimes aphony (she cannot speak loud but must whisper), after a slight cold. Cough; frequent irritation and crawling in the throat; the cough torments him, until perspiration breaks out on his face (and on his hands). Cough, which does not abate until there is retching and vomiting, mostly in the morning or in the evening. Cough, causing a sensation of soreness in the chest, or at times stitches in the side of the chest or the abdomen. Often a slightly constrictive pain in the chest, which, when it does not quickly pass, causes the deepest dejection. Violent stitches in the side; with great heat of the body, it is almost impossible to breathe, on account of stitches in the chest with haemoptysis and headache; he is confined to his bed. Night-mare; he usually suddenly awakes at night from a frightful dream, but cannot move, nor call, nor speak, and when he endeavors to move, he suffers intolerable pains, as if he were being torn to pieces. Attacks of suffocation especially after midnight; the patient has to sit up, sometimes he has to leave his bed, stand stooping forward, leaning on his hands; he has to open the windows, or go out into the open air, etc. Dwindling of the breasts, or excessive enlargement of the same, with retroceding nipples. A hard, enlarging and indurating gland with lancinating pains in one of the mammae. In the small of the back, in the back and in the nape of the neck, drawing (tearing), tensive pains. Lancinating, cutting, painful stiffness of the nape of the neck; of the small of the back. In the limbs, drawing (tearing), tensive pains, partly in the muscles and partly in the joints (rheumatism). In the periosteum, here and there, especially in the periosteum of the long bones, pressive and pressive-drawing pains. After every attack, and when the inflammation is past, the joints of the hand are painful, as also those of the knee, the foot, those of the big toe when moved, when he stands up, etc. Such a tension or stretching of the muscles often then occasions long confinement to the bed, swoons, all grades of hysterical troubles,4 fever, haemoptysis, etc. Softening of the bones, curvature of the spine (deformity, hunchback), curvature of the long bones of the thighs and legs (morbus anglicus, rickets). Painful sensitiveness of the skin, the muscles and of the periosteum on a moderate pressure. It is usually woman (called a stroking woman) who makes with the tips of her thumbs passes over the shoulder blades toward the shoulders or along the spine, sometimes also from the pit of the stomach along below the ribs, only they usually exert too strong a. A crawling, or whirling, or an internally itching restlessness, especially in the lower limbs (in the evening in bed or early on awaking); they must be brought into another position every moment. Burning pains in various parts (frequently without any change in the usual external bodily temperature). Coldness, repeated or constant of the whole body, or of the one side of the body; so also of single parts, cold hands, cold feet which frequently will not get warm in bed. Frequent flushes of heat, especially in the face, more frequently with redness than without; sudden, violent sensation of heat during rest, or in slight motion, sometimes even from speaking, with or without perspiration breaking out. Warm air in the room or at church is exceedingly repugnant to her, makes her restless, causes her to move about (at times with a pressure in the head, over the eyes, not infrequently alleviated by epistaxis). Often burning, jerking, lancinating, but often also indescribable, are these pains which communicate a similar intolerable excessive sensitiveness to the mind. These pains thus affect chiefly the upper parts of the body, or the face (tic douloureux), or the skin of the neck, etc. Varices, varicose veins in the lower limbs (varices on the pudenda), also on the arms (even with men), often with tearing pains in them (during storms), or with itching in the varices. Chilblains (even when it is not winter) on the toes and fingers, itching, burning and lancinating pains. Boils (furuncles), returning from time to time, especially on the nates, the thighs, the upper arms and the body. Ulcers on the thighs, especially, also upon the ankles and above them and on the lower part of the calves, with itching, gnawing, tickling around the borders, and a gnawing pain as from salt on the base of the ulcer itself; the parts surrounding are of brown and bluish color, with varices near the ulcers, which, during storms and rains, often cause tearing pains, especially at night, often accompanied with erysipelas after vexation or fright, or attended with cramps in the calves.