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The efficacy of psychological and pharmacological approaches is broadly similar in the acute treatment of anxiety Recommendations: general aspects of psychological disorders buy sustiva 200 mg with visa. In some studies order 200mg sustiva free shipping, relapse rates are lower after an initial treatment response to cognitive therapy with exposure than after response to drug treatment purchase 200mg sustiva fast delivery. In most anxiety dis- and potential risks of specific psychological interven- orders (generalised anxiety disorder, social anxiety disorder, tions with patients before starting treatment [S] post-traumatic stress disorder, obsessive-compulsive disorder) it ● Ensure that psychological treatments are only deliv- is uncertain whether combining psychological and pharmaco- ered by suitably trained and supervised staff, able to logical treatments is associated with greater long-term benefit demonstrate that their clinical practice adheres to evi- than that which is seen with either treatment approach when dence-based treatment protocols [A] given alone. However, previous concerns that prescription of ● Remind patients that response to psychological treatment psychotropic drugs might reduce the efficacy of psychological is not immediate and that a prolonged course is usually treatment are probably unfounded: in some anxiety disorders sys- needed to maintain an initial treatment response [S] tematic reviews suggest that psychotropic drug administration ● Plan sequential steps in patient management rather can enhance the short-term efficacy of cognitive-behavioural than combining treatments from the start, as it is uncer- interventions. As with pharmacological approaches, it should be tain whether combining is associated with greater long- emphasised that response to psychological treatment is not term benefit [D] immediate; that transient worsening of symptoms can sometimes 12 Journal of Psychopharmacology 14. The role of self-help and Other complementary approaches include regular exercise and interventions drawing on meditation techniques. A system- complementary approaches in anxiety atic review indicates that exercise training reduces anxiety symp- disorders toms in sedentary patients with long-term medical conditions [I Patient preference and the often sub-optimal effects of ‘standard’ (M)] (Herring et al. Meditation and yoga practices are often advocated, as part of There have been relatively few randomised controlled trials the overall management of patients with anxiety disorders. Early of the efficacy and acceptability of self-help approaches under- systematic reviews found only minimal evidence for the effec- taken as individuals, and few studies have been conducted in tiveness of meditation therapy [I (M)] (Krisanaprakornit et al. However another systematic review indicated six randomised controlled trials found evidence for the efficacy that relaxation training (which often includes components of of self-help in primary care patients with mixed anxiety disor- meditation) is effective in reducing anxiety symptoms in non- ders, greater efficacy being seen with more detailed instruction in clinical and clinical groups [I (M)] (Manzoni et al. The the findings of two recent systematic reviews suggest that medi- findings of a systematic review of 21 studies in patients with tative therapies are effective in reducing anxiety symptoms depression or anxiety disorders suggest that guided self-help has (though their effect in anxiety disorders is uncertain) [I (M)] similar effectiveness to face-to-face psychotherapy [I (M)] (Chen et al. Costs of illness and cost- tiveness of a number of ‘phytomedicines’, including Passiflora effectiveness of treatment species extracts, Kava (Piper methysticum), and combinations of l-lysine and l-arginine (Lakhan and Vieira, 2010; Sarris Anxiety disorders are associated with a substantial economic bur- et al. There is no current den: both in health care systems (mainly direct costs of assessment, convincing evidence for the effectiveness of homoeopathic investigation, treatment and care), and in the wider society (includ- preparations in the treatment of patients with anxiety disor- ing premature mortality, unemployment, reduced productivity ders [I (M)] (Davidson et al. Using estimates to calculate the size patients with generalised anxiety disorder but have been with- of the population in the European Union that would be affected drawn in many countries due to potential hepatotoxic effects (69. Treatment costs account for a degree of functional impairment associated with generalised small proportion of the overall costs of health care, and it has been anxiety disorder is similar to that with major depression [I] argued that the increased costs of strategies to increase the recogni- (Wittchen et al. Patients with ‘co-morbid’ depression and tion and evidence-based treatment in patients that would otherwise generalised anxiety disorder have a more severe and prolonged remain undetected and untreated would be small, compared to the course of illness and greater functional impairment (Tyrer et al. However recognised as having a mental health problem, though not neces- there have been relatively few randomised controlled trials or sys- sarily as having generalised anxiety disorder [I] (Weiller et al. Acute treatment Investigations of the costs of illness and cost-effectiveness of The findings of systematic reviews [I (M)] (Baldwin et al. The cost- nificant differences in overall efficacy between active com- effectiveness of treatments for obsessive-compulsive disorder pounds. An early analysis of randomised controlled trials of has been investigated only rarely, with limited evidence for the acute treatment found an overall mean effect size of 0. It is uncertain whether antide- pressant drugs, pregabalin and benzodiazepines differ in their relative efficacy in reducing the severity of psychological or 16. The anxiety disorder findings of fixed-dose randomised placebo-controlled trials provide some evidence of a dose-response relationship for pre- 16. However it is often not recog- antidepressant, a post hoc pooled analysis of randomised pla- nised, possibly because only a minority of patients present cebo-controlled trials with pregabalin indicate that it is effica- with anxiety symptoms (most present with physical symp- cious in reducing depressive symptom severity in patients with toms), and doctors tend to overlook anxiety unless it is a pre- mild to moderate intensity of depressive symptoms [I (M)] senting complaint [I] (Munk-Jorgensen et al. Comparative efficacy of psychological, Recommendations: managing patients with general- pharmacological, and combination ised anxiety disorder treatments Detection and diagnosis Pharmacological or psychological treatments, when delivered sin- ● Become familiar with the symptoms and signs of gen- gly, have broadly similar efficacy in acute treatment [I (M)] eralised anxiety disorder [S] (Bandelow et al. Further management after non- ing treatment, as pharmacological and psychological response to initial treatment approaches have broadly similar efficacy in acute treat- Many patients do not respond to first-line pharmacological or ment [S] psychological interventions. In acute treatment, the combination of psychotherapy with antidepressants is superior to psychotherapy or an antidepressant, when either is given alone (Furukawa et al. Further management after non- some anticonvulsants (gabapentin, sodium val- proate) [A] response to initial treatment ○ psychological: cognitive-behaviour therapy [A] Many patients do not respond to first-line pharmacological or ● Avoid prescribing propranolol, buspirone and bupro- psychological interventions. The findings of a meta-analytic review of 33 randomised controlled ● Continue drug treatment for at least six months in treatment studies indicate that exposure-based therapies (particu- patients who have responded to treatment [A] larly those involving in vivo exposure) are more effective than ● Use an approach that is known to be efficacious in pre- other psychological interventions: effectiveness being seen venting relapse [S] regardless of the nature of the specific phobia, and being some- ● Monitor effectiveness and acceptability regularly over what greater with multiple rather than single sessions [I (M)] the course of treatment [S] (Wolitzky-Taylor et al. It is When initial treatments fail unclear whether concomitant use of benzodiazepines enhances or reduces the efficacy of behavioural approaches. Management of social anxiety Specific fears of objects, animals, people or situations are wide- disorder (also known as social spread in children, adolescents and adults, but only a minority of affected individuals reach the full diagnostic criteria for specific phobia) phobia. Many affected individuals have multiple through the use of screening questionnaires in psychologically fears, whose presence is associated with an earlier onset, greater distressed primary care patients [I] (Donker et al. Longer term treatment mere ‘shyness’ but can be distinguished from shyness by the higher levels of personal distress, more severe symptoms and The findings of acute treatment studies indicate that the propor- greater impairment [I] (Burstein et al. A post hoc analysis of the tions) can be substantially impaired [I] (Aderka et al. There are strong, domised placebo-controlled relapse-prevention studies in and possibly two-way, associations between social anxiety dis- patients who have responded to previous acute treatment reveal a order and dependence on alcohol and cannabis [I] (Buckner significant advantage for staying on active medication (clonaze- et al. The potential efficacy of tricyclic antidepressants is findings of small randomised placebo-controlled studies suggest unknown. A double-blind randomised con- trolled studies of acute treatment and most reveal no significant trolled dosage escalation trial found no advantage for increas- differences in overall efficacy or tolerability between active com- ing to a higher daily dosage (120 mg) of duloxetine, when pounds. The 12-month prevalence of post-traumatic ment [A] stress disorder is estimated to be 1. Suicidal ● Advise the patient that treatment periods of up to 12 thoughts are common but the increased risk of completed suicide weeks may be needed to assess efficacy [A] is probably due to the presence of comorbid depression [I (M)] Longer-term treatment (Krysinska and Lester, 2010). Post-traumatic stress disorder is associated with increased use of health services, but is often not ● Use an approach that is known to be efficacious in pre- recognised in primary or secondary care [I] (Liebschutz et al. Diagnosis can be established through eliciting the history ● Continue drug treatment for at least six months in of exposure to trauma (actual or threatened death, serious injury, patients who have responded to treatment [A] or threats to the physical integrity of the self or others); with a ● Consider cognitive therapy with exposure as this may response of intense fear, helplessness or horror; and the presence reduce relapse rates better than drug treatment [A] of ‘re-experiencing symptoms’ (such as intrusive recollections, ● Consider cognitive therapy after response to drug treat- flashbacks or dreams); avoidance symptoms (such as efforts to ment, in patients with a high risk of relapse [D] avoid activities or thoughts associated with the trauma); and ● Monitor effectiveness and acceptability regularly over hyper-arousal symptoms (including disturbed sleep, hypervigi- the course of treatment [S] lance and an exaggerated startle response). Prevention of post-traumatic disorder ● Routinely combining drug and psychological approaches is not recommended for initial treatment in the absence after experiencing trauma of consistent evidence for enhanced efficacy over There is some scope for preventing the emergence of psychologi- each treatment when given alone [A] cal post-traumatic symptoms in people subject to major trauma. Comparative efficacy of 2009); but approaches with limited efficacy include single-ses- sion ‘debriefing’ [I (M)] (Van Emmerik et al.

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A: nasal vestibule; B: inferior turbinate; C: middle turbinate; D: superior turbinate; Hatched area: the olfactory region 9 buy discount sustiva 200mg line. The olfactory region of the nose purchase sustiva 200mg amex, a small patch of tissue containing the smell receptors order 200 mg sustiva amex, is located towards the roof of the nasal cavity and is lined with non-ciliated neuro-epithelium. Approximately 20% of the air flowing through the nasal cavity is directed upwards to the olfactory region. Here, bipolar neurones react to inspired air and initiate impulses in the olfactory nerves. The anatomy of the nose permits intimate contact between the inspired air and the mucosal surfaces enabling the air to be warmed and humidified by the vasculature and secretions of the epithelium. Inspired air of 23 °C and 40% relative humidity can be brought to 32 °C and 98% relative humidity upon inhalation via the nose. An additional form of air-conditioning is concerned with the removal of particulates, such as dust, microorganisms and allergens, from the inspired air. The large cross-sectional area of the nasal cavity and relatively low air velocities are ideal for particle deposition, as is the turbulence caused beyond constrictions where changes in air flow direction occur. The efficiency of particle removal from the air-stream is dependent on a number of factors including the aerodynamic diameter of the inhaled particles: • Particles greater than 10 µm are generally filtered out by the vibrissae at the nostrils. A: ciliated columnar cell covered by cilia and microvilli of uniform length; B: basal cell; C: goblet cell packed with mucus granules; D: nonciliated columnar cell, covered by microvilli of uniform length. The mucus is then propelled by the claw-like tips of the cilia, beating in a co-ordinated manner within the periciliary fluid, towards the nasopharynx where the mucus and any entrapped particulates is either swallowed or expectorated. Electron micrographs of cilia beating beneath a mucus layer are shown in Figure 9. In the nasal cavity, mucus is moved by the cilia at a rate of approximately 10 cm min−1 and clearance of the bulk of the mucus from the nose to the nasopharynx occurs over 10–20 minutes. Efficient mucociliary clearance depends on a successful relationship between the: • cilia • periciliary fluid • mucus 219 Figure 9. Changes in any of these three parameters can alter the characteristics of clearance and those patients with compromised clearance, such as those afflicted with conditions such as cystic fibrosis or ciliary dyskinesia, appear to be more susceptible to chronic respiratory infections. The depth of the periciliary fluid dictates whether the overlying mucus layer is at the ciliary tips and thus available for clearance: • Should the periciliary fluid become too deep, it is hypothesized that the ciliary tips would be unable to reach the mucus layer and that clearance would therefore be compromised. The mucus plays a number of important physiological roles: 220 • It entraps substances entering the nasal cavity and participates in the removal of particulates via mucociliary clearance; this process protects the underlying mucosa. Mucus is mainly composed of water (90–95%), salts (1–2%), lipids (about 30% of the non-aqueous secretion) and mucins (0. The protein content of nasal secretions includes: • secretory IgA, which acts to prevent the attachment of microorganisms to the mucosa; • lysozyme, which attacks the cell walls of susceptible microorganisms and acts optimally at acidic pH (the pH of nasal secretions is generally 5. Respiratory mucins are high molecular weight glycoproteins that are polydisperse in mass (2–40×10 Da). Each monomer is comprised of a protein “backbone” core, with alternating oligosaccharide-rich regions (approximately 100 nm in length) and “naked” regions of folded protein stabilized by disulfide bonds. The naked protein regions are characterized by a high cysteine content which provides the sulfur molecules for disulfide bonding. The wide range of sizes of respiratory mucins is believed to result from a variable number of sub-units forming the polymer. A characteristic of mucins is their high carbohydrate content (up to 80% by mass), mainly in the form of short O-linked oligosaccharide chains. Small amounts of N-linked oligosaccharide are also present in mucins, which seem to be important in the correct folding of the naked regions of the core protein. The function of mucin oligosaccharides is not fully understood but, since certain bacteria bind specific oligosaccharide ligands, it is thought that oligosaccharides may aid bacterial attachment to respiratory mucus. The accessibility of such bacteria to the underlying epithelium is thus prevented or limited and the microorganisms are subsequently destroyed by enzymatic attack and/or removed from the nasal cavity by the action of mucociliary clearance. Mucus possesses both solid-like (elastic) and liquid-like (viscous) attributes simultaneously and is therefore termed a viscoelastic gel. The viscoelastic properties arise from the non-covalent interactions (entanglements) between the predominantly anionic mucin molecules, although weak hydrogen-bonding and ligand-like attractions between protein regions of adjacent molecules may also play a role. Gel properties are affected by: • mucin size; • mucin polydispersiry; • the type of mucins present. It is widely held that mucus should possess specific rheological properties for clearance from the airway to occur. Any alteration in mucus rheology that compromises clearance can predispose the individual to airway disease and infection. In addition, the state of mucus hydration (or mucin concentration) will affect the properties of the gel. Two mucin subunits, each about 500 nm in length, are joined end to end via disulfide bonds (S-S) and consist of oligosaccharide-rich regions (represented by the thickened line) and folded domains stabilized by disulfide bonds (represented by the knots). An increase in mucus viscoelasticity is also thought to occur in asthma, chronic bronchitis, chronic obstructive pulmonary disease and acute respiratory distress syndrome. The mucus blanket (c) is always propelled in the same direction as the effective stroke (d) 9. Rest phase At the end of the effective stroke the cilium disengages from the mucus gel and enters the rest phase where it lies parallel to the epithelium pointing in the direction of mucus flow. Recovery stroke The cilium “unrolls” within the periciliary fluid ready for the next effective stroke. Undergoing the recovery stroke beneath the mucus layer prevents retrograde mucus transport (Figure 9. They are packed at a density of 6–8 cilia per μm2 and cannot move without affecting neighbouring cilia. In order to perform an unhindered beat cycle the movement of each cilium is slightly out of phase with that of its neighbor, leading to a phenomenon termed “ciliary metachrony”. Metachrony results solely from hydrodynamic coupling between adjacent cilia and provides the necessary cooperation within a field of cilia to permit them to transport mucus.

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The map is used to identify areas of instrument data link 200 mg sustiva, centrifuged buy cheap sustiva 200 mg, and placed on waste where efficiency can be improved order 200 mg sustiva mastercard. Speckled directed against nucleoprotein; although they are mainly nonpathological, they are useful markers for Immunology/Identify microscopic morphology/ active disease. Plate 2 shows the electrophoresis of serum restricted electrophoretic mobility usually located proteins on a high-resolution agarose gel at in the γ or the β region. Sample 1 (in lane 1) is a normal serum accumulation of identical immunoglobulin molecules control. Which sample can be presumptively or fragments secreted by a malignant or benign classified as a monoclonal gammopathy? Chemistry/Evaluate clinical and laboratory data/ Protein electrophoresis/3 537 538 Chapter 10 | Photomicrographs and Color Plate Examination 3. Plate 3 shows a densitometric scan of a control Answers to Questions 3–6 serum for protein electrophoresis. C The fraction marker between the α2- and β-fractions these results, what is the most appropriate initial is marked improperly. Repeat the electrophoresis run using fresh α2- macroglobulin, which partially splits the control serum α2- band into two subfractions. Report the results, provided that the previous β-band may contain three subfractions run was in control corresponding to β-lipoprotein, transferrin, and C. In this scan, the valley between the redraw the scan α2-subfractions was selected incorrectly as the D. Calculate the concentration of each fraction in boundary between the α2- and β-fractions. This grams per deciliter fraction marker should be placed at the next valley to the right and the scan redrawn to determine the Chemistry/Identify sources of error/Densitometry/3 area under the α2- and β-fractions correctly. C Using high current, β lipoprotein can be separated on a high-resolution agarose gel at pH 8. The α-2 Chemistry/Evaluate clinical and laboratory data/ macroglobulin is usually anodal to the haptoglobin. Plate 5 is a densitometric scan of a serum protein increases in the α1- and α2-fractions and a decrease in electrophoresis sample. This pattern is most concentration of each fraction and reference limits often caused by increased production of acute phase are shown below the scan. What is the correct reactants such as α1-antitrypsin and haptoglobin that classification of this densitometric pattern? Polyclonal gammopathy associated with chronic is seen in myocardial infarction and other forms of inflammation acute tissue injury, the early stage of acute infection, B. Following electrophoresis, the Protein electrophoresis/3 proteins in lane 1 are precipitated and fixed by 6. Plate 6 shows an agarose gel on which overlaying sulfosalicylic acid onto the gel. Te gel contains the chain is applied to the gel over the lanes as labeled same serum sample as number 6 shown in Plate 2. IgM λ 2 reacted with anti-γ (anti-IgG), and the proteins in Chemistry/Evaluate clinical and laboratory data/ lane 5 reacted with anti-κ. Lane 5 also contains a faint Immunofixation electrophoresis/3 restricted band anodal to the IgG band. This band is not present in lane 2 (does not contain γ chains) and represents free κ light chains. Plate 7 shows the electrophoresis of hemoglobin Answers to Questions 7–10 (Hgb) samples performed on agarose gel, pH 8. Plate 8 shows the electrophoresis of Hgb samples there is no normal β-gene, and the patient can be on acid agar gel, pH 6. Te sample order is the classified as a homozygote for Hgb S, D, or G which same as for plate 7 with the A, S, C control migrate to the same position on agarose gel at a hemolysate in lanes 2 and 10. Hgb S can be differentiated electrophoretic mobility of sample 7 as seen in from Hgbs D and G by performing electrophoresis both plate 7 and plate 8, what is the patient’s on agar gel at pH 6. On plate 8, Chemistry/Evaluate clinical and laboratory data/ sample 7 shows a single large band that migrated Hemoglobin electrophoresis/3 toward the anode at the same position as the S band 9. The phialides produce Microbiology/Identify microscopic morphology/Fungi/2 jet-black conidia that obscure the vesicle surface, forming a radiated head. Plate 10 is a photomicrograph of a fungal slide produce septate macroconidia, not vesicles with culture stained with lactophenol cotton blue, phialides. Plate 11 is a photomicrograph of a fungal slide Answers to Questions 11–15 culture stained with lactophenol cotton blue, 400×. Plate 12 is a bronchoalveolar lavage sample annellides on short conidiophores with oval conidia concentrated by cytocentrifugation and stained that are tapered at one end. Plate 13 is a fecal specimen seen under 400× using same size but have a clear (hyaline) shell, flat on brightfield microscopy. They are often bile stained and may have a thick shell with a coarse Microbiology/Identify microscopic morphology/ covering (corticated). This egg demonstrates a Parasites/2 contracted embryo, leaving space between the 14. Plate 14 is a fecal specimen unstained seen under shell and the embryo at the opposing poles. Threadworm (Strongyloides) produces Parasites/2 similar ova, but these hatch in the intestine, releasing 15. Plate 15 is an iodine-stained fecal specimen the rhabditoid larvae that are found in the feces. Te Pinworm (Enterobius) ova are approximately the plate shows the ovum of which parasite?

With this purchase sustiva 200mg, as with many other remedies cheap 200mg sustiva mastercard, there are special symptoms indicating its use discount sustiva 200mg with mastercard. Thus in rheumatism, if there is a tendency to œdema, even slight puffiness of the skin, or a peculiar blanched glistening appearance, the Apocynum will be found a valuable remedy. It will also be found a valuable remedy in chronic metritis, with uterine leucorrhœa. In one case with profuse watery discharge from the uterus, it proved curative after other plans of treatment had failed. I would suggest a tincture of the recent bark, in dilute alcohol, and in the proportion of ℥viij. It undoubtedly influences the cerebro-spinal centers, controlling epileptiform movements. It has been administered in cases of epilepsy with success, though the discoloration of the skin caused by the large doses given, was a serious objection. It also exerts an influence in chronic gastritis and enteritis, and has been given in some cases of dysentery with advantage. It has been employed in ague and malarial disease, when there was marked confusion of intellect, with headache and burning of the face and eyes. In ague the chill is prolonged, with great pain in the bones, and a feeling as if bruised. In large doses it has been extensively used as a stimulant diaphoretic, and is a most excellent remedy. In small doses it is indicated by a relaxed atonic skin, cold extremities, cold perspiration, difficult respiration, and difficult deglutition. It is not necessary to refer to the common local use of this agent, or discuss the question whether a tincture of arnica is preferable to alcohol alone as a local application. It is a valuable stimulant in many grave diseases where a stimulant is most required. But if used as a general stimulant, like alcohol, it would be as apt to do harm as good. It is a specific stimulant to the spinal nervous system, and will be found useful where there is want of innervation from this. I have seen most marked benefit from it in advanced stages of disease, where there was feeble respiratory power; difficulty of sleeping from impeded respiration; want of control over the discharge of urine and feces, etc. I have frequently prescribed it for lame back, back-ache, and feelings of debility and soreness, in the small of the back. It is only useful in those cases where there is feebleness, with deficient circulation; but in these the influence is direct and permanent. The cases reported, so far as I can learn, were asthenic with an enfeebled circulation. The use of Arsenic in the early part of this century, though limited, was in large and many times poisonous doses. Being a powerful excitant to the vegetative nerves, this use, if continued long, would produce a peculiar form of fever - “febris arsenicum” - with its attendant impairment of vital function. Finally, with impaired blood-making and nutrition, there would be developed arsenical dropsy, and in some rare cases death was the result. The arsenical fever bears a very close resemblance to quinism, or quinine poisoning, in its symptoms, though there is not, in a majority of cases, such disturbance of the nervous system. We have long since determined that the mere matter of dose in medicine might be the difference between a poison and a remedy. If, for instance, we give one grain of Strychnia, we poison our patient, whilst if the dose had been but the fortieth or thirtieth of a grain, it would have proven a vital stimulant. If we administer five grains of morphia, the result is death; whilst a medicinal dose of one-fourth of a grain would have produced refreshing sleep. If we give large doses of Aconite, (say five drops of a tincture of the root,) frequently repeated, it increases the frequency of the pulse, impairs the circulation, and irritates the nervous system. But, in medicinal doses, it lessens the frequency of the pulse, gives freedom to the circulation, and relieves irritation of the nervous system. If we give large doses of Veratrum, it impairs the circulation, arrests vital processes, and produces death; whilst medicinal doses give increased freedom to the circulation and diminish the frequency of the pulse. It seems strange to me that these things have not had due consideration, and that the remedial action of drugs has not been kept distinct from their poisonous effects when given in large doses. We have already seen, that the dose of medicine should be the smallest quantity that will give the desired influence, and that in a rational system of medicine, its influence should always be to restore normal function, and not as a disturbing element. A drug which may be poisonous in health, or in some conditions of disease, will be curative in other conditions of disease. Thus we regard the disease as antagonizing the remedy, quite as much as the remedy antagonizes the disease, and the influence is toward the restoration of healthy function. Thus, if we give Quinine to cure malarial fever, its influence is kindly, but if there is no malarial disease, it causes irritation of the nervous system. If we give Belladonna when there is an enfeebled capillary circulation, the influence is kindly and curative, but it is the reverse if we already have capillary spasm. This is especially the case with the more powerful remedies, with which Arsenic should be classed, and they should never be employed unless the symptoms indicating them are very distinct. Such a brief statement of facts I have deemed necessary in this case, on account of the prejudice of our school to these agents - a prejudice which grew out of their abuse.