Mark Corson

By H. Gorn. The Johns Hopkins University.

The major structural difference of this drug from the other examined first-generation cephalosporins is the replacement of the 3-acetoxymethyl group to a 1 cheap keftab 375mg on line,3 trusted keftab 250 mg,4-thiadiazol-2-ylthiomethyl group [79–81] order keftab 500 mg otc. Synonyms of this drug are cefacidal, cefazol, cefamezin, cefazil, zolin, ancef, and many others. Besides, the structure of the given drug, as well as a number of other cephalo- sporins examined below, are somewhat simplified by the replacement of the 3-acetoxymethyl group with a methyl group. Reducing this product with hydrogen using a palladium on barium sulfate catalyst results in the deacetoxylation at the third position of 7-aminocephalosporanic acid, making the desired cephalexin (32. It is ineffective with respect to blue-pus bacillus, mycobacteria tuberculosis, and anaerobic microorganisms. It is used for bacterial infections of the upper and lower respiratory tract, urinary tract, skin, and soft tissues. Antibiotics analog of cephalexin and differs in that the phenyl group in phenylglycine is partially hydrated to a 1,4-cyclohexadienyl moiety. It is synthesized from phenylglycine, which is partially reduced by lithium in liquid ammonia, which forms 1,4-cyclohexadienylglycine (32. Like all of the other drugs described above, it acts as a bactericide by disrupting the process of restoring the membranes of bacteria. Second-generation cephalosporins Second-generation cephalosporins (cefuroxime, cefamandole, cefonicid, ceforanide) are char- acterized by more expressed activity with respect to Gram-negative bacteria in comparison 32. They have high beta-lactam resistance, although they do not have a noticeable effect on enterococci, Pseudomonas aeruginosa. In addition, drugs belonging to the second-generation cephalosporins are cefoxithin, synthesized from cefamicin C, cefotetan, a semisynthetic derivative of organomycin G, and also cefaclor. Their unique chemical feature is the presence of an additional methoxy group in position C7 of the aminocephalosporanic acid frag- ment, and the unique chemical feature of cefaclor, the absence of a substituted group at posi- tion C3 of the aminocephalosporanic acid fragment is also characteristic of all cephalosporins. Finally, removal of the benzhydryl protection using trifluo- roacetic acid gives the desired cefuroxime (32. Antibiotics Another simpler way of the synthesis of cefuroxime is by direct acylation of 7-amino- 3-aminocarbonyloxymethyl-3-cefem-4-carboxylic acid (32. It is highly active with respect to Gram-negative microorgan- isms (intestinal and hemophilial bacilli, salmonella, shigella, enterobacteria, and gonococci). It is also active with respect to Gram-positive microorganisms (staphylococci, streptococci). It is inactive with respect to various types of Pseudomonas, most strains of enterococci, many strains of Enterobacter cloacae, methylcillin-resistant staphylococci, and L. It is used for bacterial infections caused by microorganisms that are sensitive to the drug. These may be abdominal and gynecological infections, sepsis, meningitis, endocarditis, infec- tions of the urinary and respiratory tracts, bones, joints, skin, and soft tissues. It is widely used for pneumonia as well as bacterial meningitis in children, and for post-operational infectious complications. Protecting free amino group in 7-aminocephalosporanic acid by formylation with formic acid in the presence of acetic anhydride produces 7-formamidocephalosporanic acid (32. The acetoxy group of this compound is replaced by a reaction with 1-methyl- 1,2,3,4-tetrazol-5-thiol, after which the N-formyl protection is removed by hydrochloric acid, giving 7-amino-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cefem-4-carboxylic acid (32. Reacting this with a mixed anhydride synthesized from mandelic acid and phosgene gives the desired cefamandole (32. It is synthesized by a method analogous to that of the synthesis of cefamandole [120–123]. It is also synthesized by methods analogous to the synthesis of cefamandole [124–128]. Cefoxitin and cefotetan, which are cephamicins and differ from other cephalosporins principally in the presence of a methoxy group at position 7 of the cephalosporanic sys- tem, which significantly increases their resistibility with respect to beta-lactamases, belong to the second-generation cephalosporins. In one of the examples of the synthesis of cefox- itin starting from cefamicin C, the free amino group is initially protected via tosylation, and the product in the form of a well-crystallizing dicyclohexylamine salt is isolated (32. Next, the carbonyl group at position 2 of the cephalosporanic system is ester- ified using methylchloromethyl ether. When reacted with nitrous acid, the product is diazotized, giving the diphenyl methyl ester of 7-diazocephalosporanic acid (32. A subsequent reaction of the resulting compound with triethylammonium azide in dichloromethane and then with bromine azide gives the diphenyl methyl ester of 7-bromo-7-azidocephalosporanic acid (32. Treating this with methanol in the presence of silver borofluoride results in the replacement of the bromine atom, giving the diphenylmethyl ester of 7-methoxy-7-azidocephalosporanic acid (32. Acylation of this compound with 2-(2-thienyl)acetylchloride gives the ben- zhydryl ester of 7-methoxy-7-[2-(2-thienyl)-acetamido]cephalosporanic acid (32. The resulting product is then hydrolyzed by the enzyme Citrusi acetylesterase to the potassium salt of 3-hydroxymethyl-7-methoxy-7-[2-(2-thienyl)acetamido]-3-cefem- 4-carboxylic acid (32. Antibiotics is accomplished not with 2-(2-thienyl)acetylchloride, but with bromoacetyl bromide. This drug is synthesized from the most accessible antibiotic of this series, cefalotin (32. Reacting this with potassium ethyl xantogenate replaces the acetoxy group in the third position of the cephalosporin sys- tem, giving the corresponding S-derivative (32. Upon reducing this compound using zinc in formic acid, the product is desulfurized, giving the 4-nitrobenzyl ester of 3-exo-methylen-7-(2-thienylacetamido)-cefem-4-carboxylic acid (32. The exo- methylene group is oxidized by ozone and the resulting dicarbonyl derivative tautomerizes to the enol form (32. Then, the hydroxyl group is replaced with a chlorine atom upon reaction with thionyl chloride, giving the 4-nitroben- zyl ester of 3-chloro-7-(2-thienylacetamido)-3-cefem-4-carboxylic acid (32. The resulting product undergoes deacylation upon reaction with a mixture of pyridine with phosphorous pentachloride in isobutanol, forming the hydrochloride of 4-nitrobenzyl ester of 7-amino-3-chloro-3-cefem-4-carboxylic acid (32. This is acylated with an N-protected derivative of phenylglycine, (N-tert-butoxycarbonyl)-D-α-phenylglycine in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in tetrahydrofuran, giving 32.

Taking symptom-masking drugs can be likened to shooting out the indicator lights on the dashboard of your car to reassure yourself that all is well keftab 250mg with amex. A much wiser approach is to look under the hood and see where the problem lies in the first place keftab 750 mg without prescription. Believe it or not generic keftab 750mg free shipping, most problems, including hormone imbalance, can be largely relieved through lifestyle changes alone. Happily, we now have far more sophisticated methods for identifying and testing for hormone and energy imbalances than were available even ten years ago. The science of psychoneuroimmunology and epigenetics has advanced light-years in a short time. She practices what is known as “functional” or integrative medicine, which works to optimize the minute-to- minute processes and functions of the body before diagnosable diseases develop. Since most symptoms are the end result of cellular inflammation left unchecked for years, we now know it is possible to short-circuit most chronic degenerative disease in its early stages or prevent it altogether. Be assured that the kind of medicine in The Hormone Cure is the medicine of the future—now. Gottfried’s approach will require you to be an active participant in your own health care. Gottfried knows in her own body and mind the incredibly satisfying results you can get from consciously and mindfully working with the wisdom of your body. If you want to regain the lost sense of optimism and vitality that you had in your youth—or attain even more optimism and vitality than you ever had—your answers are here. Or if you simply want to continue to stay as vital and youthful as possible for as long as possible, your answers are also here. In The Wisdom of Menopause (Bantam 2012), I referred to the perimenopausal years as the big wake-up call—a time when we reach a crossroads in our lives. Gottfried will take you by the hand and show you exactly how to follow the path that says Grow! Unremitting stress, superwoman expectations, and misinformation about hormones have led to a full- blown crisis. Now, one in four women in the United States takes a prescription medication for mental health reasons, the majority of which are women aged forty and older. We’re told that it’s normal to feel fatigued, anxiety ridden, unsexy, fat, and cranky. Maybe you are struggling with moodiness, focus, sleeplessness, brain fog, excess weight, or waning sex drive. You should know that there’s a different way to live: You can feel delicious, vital, and genuinely content. I’m here to show you that you can live an extraordinary life and that you can feel great—regardless of your age, even if it sounds unlikely or unimaginable. I’ve helped many women transform hormonal problems using simple yet powerful techniques. The good news: It’s easier to rebalance your hormones than to live with the misery of hormonal imbalance. In fact, it’s totally realistic to feel better in middle age than you did in your twenties as a perfect hormonal specimen. You no longer need to be disappointed in the medical system—and you don’t need to settle for anything less than feeling fully alive and joyous before, during, and after middle age. When I first met Diane, age forty-six, in my integrative medicine practice, she was overweight and drinking two glasses of wine a night to cope with her stress-crazed emotions, amped-up hormonal system, and marital discord. She had always been a runner, she told me, but now she felt depleted after each run, rather than brimming with feel-good endorphins as she used to. She often felt cold, her hair fell out in chunks, and she was extremely irritable. On a scale of 1 to 10 (10 being sex of the dreamy/creamy variety), she gave herself a 1. She didn’t have to accept that her sex life was over, that she was destined to have a muffin top forever, or that collapsing in bed after dinner each night was the new “normal. Based on The Gottfried Protocol— my step-by-step, integrative approach to hormonal balance—Diane began a new way of eating (no gluten or sugar for three months) and targeted exercise that lowered her cortisol rather than raised it (studies show that running raises cortisol levels). She set aside fifteen minutes each day for conscious de-stressing, in this case relaxing yoga, and we mended her hormonal imbalance with three supplements: fish oil, phosphatidylserine, and rhodiola. When I saw Diane again, three months later, the change was remarkable: Her energy was clear and focused. She told me that she had easily lost the 20 pounds and felt comfortable in her body once more. And, in that riveting woman-to-woman way, she described passionately how she felt sensual again and desired attractive men, particularly the one she had been married to for ten years. You may not have exactly Diane’s problems—that is, your symptoms and your story may be different—but the final goal is the same. It is possible to reset your hormones and to reclaim a satisfying and downright enchanting life—as an individual and as a woman— and it can be done without synthetic drugs or expensive therapies. Your progress through all stages of your life, and especially premenopause and perimenopause, doesn’t have to be a tortuous slog through hormonal hell. Your body deserves and prefers to be in hormonal homeostasis —a state of equilibrium. Sometimes it’s just a few tweaks; sometimes return to homeostasis entails major changes.

On one side of the spectrum is mainstream medicine buy cheap keftab 375 mg on line, where women see a doctor who offers them the same treatment regardless of their symptoms buy 250 mg keftab. Generally discount keftab 500mg without a prescription, this means birth control pills for the younger patients and hormone therapy for women in their midforties and older. Or, since 2002, when women got scared silly about taking hormones, more mainstream doctors have been prescribing an antidepressant for anything ailing their middle- aged female patients—from anxiety to obsessive compulsive disorder to just feeling overwhelmed. Here’s the catch: have you read the warning label that comes with your prescription? On average, antidepressants come with seventy possible adverse reactions, and for some, as many as five hundred. Occasionally they conflict: one drug causes drowsiness, but read a bit further and it also causes insomnia. The other end of the spectrum disavows medication, enamored with the idea that extreme lifestyle vigilance can get a woman through perimenopause. Scratch that: Eat only three meals, no snacks, and certainly no food after seven p. In fact, have sex a minimum of three times a week—preferably more, because it burns 200 calories in thirty minutes! I read the same more sex recommendation from most of the prominent male doctor/authors advising women on how to cope with low libido—this advice is plain wrong, patronizing, and inaccurate. Blaming the woman and bypassing the root causes without considering the relationship issues leaves women cold and misses the point. Dear Reader, I’m exhausted just writing this— all the prescriptions and proscriptions by well- intended people do not address the root of the problem, which is hormonal impairment. More willpower isn’t the solution; rather, the solution is understanding and then fine-tuning your hormones. My mission is to recommend the important lifestyle choices—such as exercise, nutrient-dense food, proven contemplative practice, and nutraceuticals— as part of a way of life that can be relaxed, without excess tension or stress, and specific to your hormonal needs. Neither of the aforementioned options— medicine bottle or daily deprivation—appeals to me, nor have I seen them help women in the long term. Let’s define what hormonal balance looks like for you (preferably before you hit perimenopause, but I’ll help you regroup if you’re there). We hunt for root causes and implement needle-moving changes, rather than settle for the superficial symptom smooshers your doctor may try to persuade you to take. Your response to stress is mediated primarily by glucocorticoids, including cortisol, combined with your genetics, the status of your ovaries and thyroid, and how adeptly you manage what’s on your plate. Cortisol, the “stress hormone,” is the most complex and misunderstood hormone in my practice. But in later stages of long-standing stress, cortisol can swing too high and too low, and everything in between, sometimes within a matter of hours in the same day. That’s why I’ve included both extremes in this chapter as well as the proven lifestyle management that helps regardless of your cortisol level. Ultimately, if stress is unaddressed and unremitting, the adrenal glands, which produce cortisol and the stress neurotransmitters epinephrine (also known as adrenaline) and norepinephrine, cannot keep up, and cortisol becomes persistently low. Although I’m necessarily simplifying complex information, here’s the main point: you may experience several of the high-cortisol symptoms, plus low-cortisol symptoms. Optimally, you want the Goldilocks experience of getting your cortisol just right: not too high and not too low. If you recognize your symptoms in the questionnaires of Part A and/or Part B of chapter 1, I urge you to manage your cortisol as if your life depended on it (it does), because most mainstream doctors don’t look for gradations in adrenal problems, which is a characteristic of both high and low cortisol. Even if you have fewer than five symptoms in Part A or Part B, but five or more when the two parts are combined, consider getting your cortisol level checked. Cortisol 101 Cortisol is the hormone that governs your hunger cravings, digestion, blood pressure, sleep/wake patterns, physical activity, and capacity to cope with stress. It belongs to the glucocorticoid family—a fancy name for substances that can raise your glucose. This is cortisol’s main job: to increase your glucose and store the excess in the liver, through a process called glycogen storage. As the most potent of the glucocorticoids, cortisol keeps us alive via three key properties. It • raises blood sugar • increases blood pressure • modulates inflammation The Pendulum of Stress and Cortisol: Short Version Stress is unavoidable, rampant, and growing. It’s part of life, and if anyone knows how to live without it, please phone me immediately. It’s not a bad thing in itself: under normal conditions, your body produces a brief surge of cortisol—the hormone released when you’re under stress—that is beneficial and protective and, ideally, infrequent. The stress reaction is an appropriate alarm; perhaps a friend has a medical emergency or your house was burglarized. Once you respond and cope with the situation, your cortisol should return to normal levels, similar to the rise and fall of a tide. When your cortisol is functioning properly and proportionally, so is your alarm system, and vice versa. Far too many of us struggle with symptoms of unrelenting stress and hypervigilance that are listed in Part A of the questionnaire in chapter 1 (such as chocolate cravings, lousy sleep, belly fat, anxiety). If you’re reading this chapter, chances are you’re feeling the ravages of unremitting stress. You may think you can’t make radical changes to your lifestyle in the pursuit of good health, but I am here to tell you that small shifts in how you approach the many roles you’re juggling can start you on a path to a revitalized you.

Some notes on this recipe: this herbal tea purchase 375 mg keftab with mastercard, as well as the parsley cheap 500 mg keftab with visa, can easily spoil cheap keftab 750mg line. Heat it to boiling every fourth day if it is being stored in the refrigerator; this resterilizes it. If you ster- ilize it in the morning you may take it to work without refriger- ating it (use a glass container). If the ones you buy are barely fragrant, they have lost their active in- gredients; switch to a different supplier. If you can only find several of those in the recipe, make the recipe anyway; it will just take longer to get results. Remember that vitamin B6 and magnesium, taken daily, can prevent oxalate stones from forming. Phosphate levels are high in meats, breads, cereals, pastas, and carbonated drinks. You can dissolve all your kidney stones in 3 weeks, but make new ones in 3 days if you are drinking tea and cocoa and 68 Taken from Food Values 14ed by Pennington and Church 1985. Liver Herbs Don’t confuse these liver herbs with the next recipe for the Liver Cleanse. This recipe contains herbs traditionally used to help the liver function, while the Liver Cleanse gets gallstones out. Liver Cleanse Cleansing the liver of gallstones dramatically improves di- gestion, which is the basis of your whole health. But it should not be done before the parasite program, and for best results should follow the kidney cleanse. The liver is full of tubes (biliary tubing) that deliver the bile to one large tube (the common bile duct). The gallbladder is attached to the common bile duct and acts as a storage reser- voir. Eating fat or protein triggers the gallbladder to squeeze itself empty after about twenty minutes, and the stored bile fin- ishes its trip down the common bile duct to the intestine. For many persons, including children, the biliary tubing is choked with gallstones. Not only that, most are too small and not calcified, a prerequi- site for visibility on X-ray. There are over half a dozen varieties of gallstones, most of which have cholesterol crystals in them. Other stones are compos- ites–made of many smaller ones–showing that they regrouped in the bile ducts some time after the last cleanse. At the very center of each stone is found a clump of bacte- ria, according to scientists, suggesting a dead bit of parasite might have started the stone forming. Much less water would flow, which in turn would decrease the ability of the hose to squirt out the marbles. With gallstones, much less cho- lesterol leaves the body, and cholesterol levels may rise. Gallstones, being porous, can pick up all the bacteria, cysts, viruses and parasites that are passing through the liver. In this way “nests” of infection are formed, forever supplying the body with fresh bacteria and parasite stages. No stomach infection such as ulcers or intestinal bloating can be cured permanently without removing these gallstones from the liver. For best results, ozonate the olive oil in this recipe to kill any parasite stages that may be released during the cleanse. Zap daily the week before, or get through the first three weeks of the parasite killing program before attempting a liver cleanse. If you are on the maintenance parasite program, you are always ready to do the cleanse. You want your kidneys, bladder and urinary tract in top working condition so they can efficiently remove any undesirable substances inci- dentally absorbed from the intestine as the bile is being excreted. Ingredients Epsom salts 4 tablespoons Olive oil half cup (light olive oil is easier to get down), and for best results, ozonate it for 20 to 30 minutes, first Fresh pink grapefruit 1 large or 2 small, enough to squeeze 2/3 to 3/4 cup juice Ornithine 4 to 8, to be sure you can sleep. Pint jar with lid Black Walnut Tincture, any 10 to 20 drops, to kill parasites strength. Choose a day like Saturday for the cleanse, since you will be able to rest the next day. Eat a no-fat breakfast and lunch such as cooked cereal, fruit, fruit juice, bread and preserves or honey (no butter or milk). Set the jar in the refrigerator to get ice cold (this is for convenience and taste only). Close the jar tightly with the lid and shake hard until watery (only fresh grapefruit juice does this). Take 4 orni- thine capsules with the first sips to make sure you will sleep through the night. You may use oil and vinegar salad dressing, cinnamon, or brown sugar to chase it down between sips. As soon as the drink is down walk to your bed and lie down flat on your back with your head up high on the pillow.

Therapy—It is of benefit in neuralgia 125mg keftab, tic douloureux purchase keftab 500 mg on line, gonorrheal rheumatism 750mg keftab visa, inflammation of the bladder, irritation of the prostate gland, dysuria, sexual excitement in male or female, spermatorrhea without impotency, acute articular rheumatism, migraine, sciatica, diabetes, diphtheria, chronic mucous discharges and toothache (locally). Asthmatic breathing of a non-paroxysmal character is relieved by this remedy, as is asthmatic cough, and cough characterized by constriction or tightness at the supra-sternal notch. In the cough of asthmatic bronchitis, or in dry, harsh, persistent bronchial or phthisical cough, this agent acts nicely. It is a serviceable remedy in hepatic congestion, and in congestion of the glandular structures of the entire gastro-intestinal tract. In ovarian conditions inducing too frequent menstruation, with Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 223 congestion of the pelvic circulation, in addition to the conditions above named, as in enlargement of the uterus, with a swollen, engorged condition of the cervix, it is directly useful. The oil is now freely used externally in the treatment of articular rheumatism and also in chorea with excellent results. In the latter disorder it is applied, if necessary, over the upper and lower limbs, alternately, and over the spine. An ointment made of ichthyol and the oil of gaultheria in a proper vehicle, rubbed together thoroughly, makes an excellent application to the joints in acute, and in gonorrheal rheumatism. If given in conjunction with gelsemium and cimicifuga in the first stages, it will probably shorten or even abort the disease. Dose, from one-third to ten minims, prescribed, ten minims to five drachms in four ounces of water. Administration—Gelsemium is a prompt remedy if given in sufficiently active dosage. The excellent results obtained by the older physicians were obtained from full doses. Children are more susceptible to its action than adults, and with them the smaller dosage is applicable. If toxic effects are obtained, they can be readily observed and antagonized with no harm to the patient. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 224 Gelsemium is quickly eliminated from the system, largely through the kidneys, consequently the effects of single doses are quickly dissipated, and medicinal doses must thus be given frequently, especially in childhood, to insure good results. The remedy can be given in single doses of from fifteen to twenty minims, but any dose of three drops or more must be watched for physiological effects, and diminished when these appear. Physiological Action—Usually upon the administration of an overdose of this agent there is at first some excitement, followed by depression of the nervous system, with dizziness, amblyopia, double vision, dilated pupils, exophthalmos, complete prostration, with drooping of the, upper eyelids from paralysis of the levator palpebrae superioris and inability to keep the jaw closed. The temperature is reduced, the force and frequency of the pulse is lowered, with dyspnea, the breathing being accomplished with much effort, and death usually results from paralysis of the respiratory muscles, including the diaphragm. The influence appears to be exercised upon the base of the brain, on the brain, on the splanchnic nerves and on the spinal cord. It inhibits the nerve force of all the visceral organs and relaxes the sphincters. In man, while there is loss of sensation and motion, the patient is conscious of what is going on around him, unless the symptoms are prolonged, when deficient oxygenation of the blood, with accumulation of carbonic acid, will produce coma. In experiments made upon pigeons the effects are very similar to those resulting from destruction of a portion of the cerebellum. There are irregular backward movements, tremblings, flutterings of the wings, preceding complete paralysis. The motor nerves are first influenced, the paralysis of sensation more slowly following. The writer observed a case of poisoning where the patient had taken sixty minims of the fluid extract within forty-five minutes. The patient rose to her feet, noticed that vision had failed almost completely, walked two or three steps, then fell in a mass upon the floor in a state of complete muscular relaxation. There was no alarm or fear, a rather tranquil feeling mentally, and in this case there was no great difficulty of breathing, although we have observed dyspnea from single Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 225 doses of two or three minims of the fluid extract. The recovery of this patient was rapid, although muscular weakness was present for several days. The primary influence of gelsemium—that which probably always underlies its remedial influence upon any condition—should be borne steadily in mind in its administration. It diminishes the blood supply of the brain and spinal cord by lessening nerve power, inhibiting the nerve control, slowing, retarding or staying the functional action of the nerve centers over the nerves themselves, influencing them steadily in the line of their physiological activities. It thus subdues all forms of nerve excitation of whatever character, or wherever located. There must be, then, increased nerve tension, with its consequent irritation, and usually, local hyperemia or increased and undue blood supply in sthenic conditions. It may be well to introduce a caution which is most important, if good results be secured from the action of this remedy. Gelsemium, more than perhaps any other of our agents, suffers from the fact that the market may be supplied by worthless preparations of the remedy. Any fluid extract or tincture made from the dried drug does not contain the full virtues of the plant, and if the drug has been long gathered will be almost inert. The green root should be gathered in the early spring, and its medicinal virtues should be immediately extracted. The green root fluid extracts, normal tinctures, and the specific medicine gelsemium represents the fullest possible virtues of the drug. Specific Symptomatology—The characteristic syndrome which demands the administration of gelsemium is found in acute determination of blood to the brain—acute cerebral hyperaemia— manifested by a bright flush upon the face, bright eyes with contracted pupils, with a busy restlessness and excitability. With these there is a high degree of nerve tension and consequent irritation, with increased heat of the head and face. There is present in acute cases, elevated temperature, hot skin, usually dry, a sharp and quick pulse, but not always hard.