William C. Mabie, MD

• GHS Professor of Clinical Obstetrics and Gynecology
• University of South Carolina School of Medicine-Greenville
• Greenville Hospital System University Medical Center
• Greenville, South Carolina

Laboratory Studies A complete blood count and a pregnancy test should be done as well as thyroid function studies impotence treatment vacuum devices order 80 mg super cialis fast delivery. For adolescents with heavy menstrual bleeding and adults with a positive screening history erectile dysfunction miracle shake purchase 80 mg super cialis mastercard, coagulation studies should be consid ered erectile dysfunction medication contraindications super cialis 80 mg buy lowest price, since up to 1 8 % of women with severe menorrhagia may have a coagulopathy erectile dysfunction tea order super cialis 80 mg overnight delivery. Imaging Ultrasound may be useful to evaluate endometrial thickness or to diagnose intrauterine or ectopic pregnancy or adnexal masses erectile dysfunction protocol free copy discount 80 mg super cialis mastercard. Sonohysterography or hysteroscopy may be used to diagnose endometrial polyps or subserous myomas. Cervical Biopsy and Endometrial Sampling the primary role of endometrial sampling is to determine whether carcinoma or premalignant lesions are present, even though other pathology related to bleeding may be found. Polyps, endometrial hyperplasia, and submucous myomas are commonly identified in this way. If the Papanicolaou smear abnormality requires it, or a gross cervical lesion is seen, colposcopic-directed biopsies and endocervical curettage are usually indicated. The history, physical examination, labo ratory findings, imaging, and endometrial sampling should identify such patients, who require definitive therapy. Progestins, which limit and stabilize endometrial growth, are generally effective. For patients with irregular or light bleeding, medroxyprogesterone acetate, 10 mg/day orally, or noreth indrone acetate, 5 mg/day orally, should be given for 1 0 days, following which withdrawal bleeding (so-called medical curettage) will occur. If successful, the treatment can be repeated for several cycles, starting medication on day 15 of subsequent cycles, or it can be reinstituted if amenorrhea or dysfunctional bleeding recurs. In women who are experiencing heavier bleeding, any of the combi nation oral contraceptives (with 30-35 meg of estrogen estradiol) can be given four times daily for 1 or 2 days fol lowed by two pills daily through day 5 and then one pill daily through day 20; after withdrawal bleeding occurs, pills are taken in the usual dosage for three cycles. These therapies require 2-4 weeks to down regulate the pituitary and stop bleeding and will not stop bleeding acutely. In cases of heavy bleeding requiring hospitalization, intravenous conjugated estrogens, 25 mg every 4 hours for three or four doses, can be used, followed by oral conjugated estrogens, 2. If the abnormal bleeding is not controlled by hormonal treatment, hysteroscopy with tissue sampling or saline infu sion sonohysterography is used to evaluate for structural lesions (such as polyps, submucous myomas) or neoplasms (such as endometrial cancer). Endometrial ablation may be performed through the hysteroscope with laser photocoagulation or electrocautery. Nonhysteroscopic techniques include bal loon thermal ablation, cryoablation, free-fluid thermal ablation, impedence bipolar radiofrequency ablation, and microwave ablation. If endometrial hyperplasia with atypia or if carcinoma of the endometrium is found, hysterectomy is necessary. When to Admit If bleeding is uncontrollable with first-line therapy or the patient is not hemodynamically stable. Although not every woman experiences all the symptoms or signs at one time, many describe bloating, breast pain, ankle swell ing, a sense of increased weight, skin disorders, irritability, aggressiveness, depression, inability to concentrate, libido change, lethargy, and food cravings. Careful evaluation of the patient, with understanding, explanation, and reassurance. Advise the patient to keep a daily diary of all symptoms for 2-3 months, such as the Daily Record of Severity of Problems, to evaluate the timing and characteristics of her symptoms. General Considerations Vaginal bleeding that occurs 6 months or more following cessation of menstrual function should be investigated. The most common causes are atrophic endometrium, endometrial proliferation or hyperplasia, endometrial or cervical cancer, and administration of estrogens with or without added progestin. Other causes include atrophic vaginitis, trauma, endometrial polyps, friction ulcers of the cervix associated with prolapse of the uterus, and blood dyscrasias. Diagnosis the vulva and vagina should be inspected for areas of bleeding, ulcers, or neoplasms. If available, trans vaginal sonography should be used to measure endome trial thickness. A measurement of 4 mm or less indicates a low likelihood of hyperplasia or endometrial cancer. For mild to moderate symptoms, a program of aerobic exercise; reduction of caffeine, salt, and alcohol intake; the use of alternative therapies, such as an increase in dietary calcium (to 1 200 mg/day), vitamin D, or magne sium, and complex carbohydrates in the diet, acupuncture, and herbal treatments may be helpful, although these interventions remain unproven. Medications that prevent ovulation, such as hormonal contraceptives, may lessen physical symptoms. When mood disorders predominate, several serotonin reuptake inhibitors (such as fluoxetine, 20 mg orally, either daily or only on symptom days) have been shown to be effective in relieving tension, irritability, and dys phoria with few side effects. First-line medication therapy includes serotonergic antidepressants (citalo pram, escitalopram, fluoxetine, sertraline, venlafaxine). A review of treatment and management modalities for premenstrual dysphoric disorder. The pain is produced by uterine vasoconstriction, anoxia, and sus tained contractions mediated by prostaglandins. The pelvic examination is normal between menses; examination dur ing menses may produce discomfort, but there are no pathologic findings. Continuous use of oral contraceptives can be used to suppress menstruation completely and prevent dysmenorrhea. For women who do not wish to use hormonal contraception, other therapies that have shown at least some benefit include local heat; thiamine, 100 mg/day orally; vitamin E, 200 units/day orally from 2 days prior to and for the first 3 days of menses; and high-frequency transcutaneous electrical nerve stimulation. Clinical Findings the history and physical examination may suggest endo metriosis or fibroids. Careful review of associated bowel or bladder symptoms should be consid ered to rule out other pelvic organ origination. Diagnosis Pelvic imaging is useful for detecting the presence of uterine fibroids or other anomalies. Cervi cal stenosis may result from induced abortion, creating crampy pain at the time of expected menses with obstruc tion of blood flow; this is easily cured by passing a sound into the uterine cavity after administering a paracervical block. Laparoscopy may be used to diagnose endometriosis or other pelvic abnormalities not visualized by imaging. Pri ma ry Dysmenorrhea Primary dysmenorrhea is menstrual pain associated with menstrual cycles in the absence of pathologic findings. The pain usually begins within 1 -2 years after the menarche and may become more severe with time. The frequency of cases increases up to age 20 and then decreases with age and markedly with parity. Fifty to 75 percent of women are affected at some time and 5-6% have incapacitating pain. Specific Measures the combined oral contraceptive pill alleviates the symp toms of dysmenorrhea. Clinical Findings Primary dysmenorrhea is low, midline, wave-like, cramp ing pelvic pain often radiating to the back or inner thighs. Adenomyosis may respond to the levonorgestrel-releasing intrauterine sys tem, uterine artery embolization, or hormonal approaches used to treat endometriosis, but hysterectomy remains the definitive treatment of choice for women for whom child bearing is not a consideration. Normal secretions during the middle of the cycle, or during pregnancy, can be confused with vaginitis by con cerned women. The physical examination should include careful inspection of the vulva and speculum examination of the vagina and cervix. It can be used if microscopy is not available or for confirmatory testing of microscopy. Surgical Measures If disability is marked or prolonged, laparoscopy or explor atory laparotomy is usually warranted. Definitive surgery depends on the degree of disability and the findings at operation. Hysterectomy may be done if other treatments have not worked but is usually a last resort. Study finds convincing evidence that the combined oral con traceptive pill helps painful periods. Dysmenorrhea in adolescents and young adults: an update on pharmacological treatments and management strategies. Vu lvovaginal Candidiasis Pregnancy, diabetes, and use of broad-spectrum antibiotics or corticosteroids predispose patients to Candida infec tions. Cultures with Nickerson medium may be used if Candida is suspected but not demonstrated. Trichomonas vagina/is Vaginitis this protozoal flagellate infects the vagina, Skene ducts, and lower urinary tract in women and the lower genitouri nary tract in men. General Considerations Inflammation and infection of the vagina are common gyne cologic problems, resulting from a variety of pathogens, allergic reactions to vaginal contraceptives or other products, vaginal atrophy, or the friction of coitus. In recurrent non-albicans infections, 600 mg of boric acid in a gelatin capsule intravaginally once daily for 2 weeks is approximately 70% effective. Single-dose regimens-Effective single-dose regimens include miconazole (1200-mg vaginal suppository), tiocon azole (6. Motile organisms with flagella are seen by microscopic examination of a wet mount with saline solution. Bacterial Vag inosis this condition is considered to be a polymicrobial disease that is not sexually transmitted. An overgrowth of Gardner ella and other anaerobes is often associated with increased malodorous discharge without obvious vulvitis or vaginitis. An amine-like ("fishy") odor is present if a drop of discharge is alkalinized with 1 0 % potassium hydroxide. Three-day regimens-Effective 3-day regimens include butoconazole (2% cream, 5 g vaginally once daily), clotrim azole (2% cream, 5 g vaginally once daily), terconazole (0. Seven-day regimens-The following regimens are given once daily: clotrimazole (1 % cream), miconazole (2% cream, 5 g, or 100 mg vaginal suppository), or tercon azole (0. Fourteen-day regimen-An effective 14-day regimen is nystatin (1 00,000-unit vaginal tablet once daily). Recurrent vulvovaginal candidiasis (maintenance therapy)-Clotrimazole (500 mg vaginal suppository once weekly or 200 mg cream twice weekly) or fluconazole (1 00, 1 50, or 200 mg orally once weekly) are effective regimens for maintenance therapy for up to 6 months. Vulvovaginal Candidiasis A variety of regimens are available to treat vulvovaginal candidiasis. Women with uncomplicated vulvovaginal can didiasis will usually respond to a 1- to 3-day regimen of a topical azole. Women with complicated infection (includ ing four or more episodes in 1 year [recurrent vulvovaginal candidiasis], severe signs and symptoms, non-albicans Treatment ofboth partners simultaneously is recommended; metronidazole or tinidazole, 2 g orally as a single dose or 500 mg orally twice a day for 7 days, is usually used. If treatment failure occurs again, give metronidazole or tinidazole, 2 g orally once daily for 5 days. Women infected with T vagina/is are at increased risk for concurrent infection with other sexually transmitted diseases. However, abnormal bleeding should not be ascribed to a cervical polyp without sampling the endocer vix and endometrium. Cervical polyps must be differentiated from polypoid neoplastic disease of the endometrium, small submucous pedunculated myomas, large nabothian cysts, and endo metrial polyps. Bacterial Vag inosis the recommended regimens are metronidazole (500 mg orally, twice daily for 7 days), clindamycin vaginal cream (2%, 5 g, once daily for 7 days), or metronidazole gel (0. Alternative regimens include clindamycin (300 mg orally twice daily for 7 days), clindamycin ovules (1 00 g intravaginally at bedtime for 3 days), tinidazole (2 g orally once daily for 3 days), or tinidazole (1 g orally once daily for 7 days). Vulvar lesions may be obviously wart-like or may be diagnosed only after applica tion of 4% acetic acid (vinegar) and colposcopy, when they appear whitish, with prominent papillae. Recommended treatments for vulvar warts include podophyllum resin 1 0-25% in tincture of benzoin (do not use during pregnancy or on bleeding lesions) or 80-90% trichloroacetic or bichloroacetic acid, carefully applied to avoid the surrounding skin. Surgical removal may be accomplished with tangential scissor excision, tangential shave excision, curettage, or electrotherapy. The pain of bichloroacetic or trichloroacetic acid application can be lessened by a sodium bicarbonate paste applied immedi ately after treatment. Freezing with liquid nitrogen or a cryoprobe and electrocautery are also effective. Patient applied regimens, useful when the entire lesion is accessi ble to the patient, include podofilox 0. Vaginal warts may be treated with cryotherapy with liquid nitrogen or trichloroacetic acid. Extensive warts may require treatment with C0 2 laser under local or general anesthesia. Treatment Cervical polyps can generally be removed in the office by avulsion with uterine packing forceps or ring forceps. The infection usually resolves and pain dis appears, but stenosis of the duct outlet with distention often persists. A fluctuant swelling 1 -4 em in diameter lateral to either labium minus is a sign of occlusion of Bartholin duct. Pus or secretions from the gland should be cultured for Chlamydia and other pathogens and treated accord ingly (see Chapter 3 3); frequent warm soaks may be helpful. If an abscess develops, aspiration or incision and drainage are the simplest forms of therapy, but the prob lem may recur. Marsupialization (in the absence of an abscess), incision, and drainage with the insertion of an indwelling Word catheter, or laser treatment will estab lish a new duct opening. The recommendation to start screening at age 2 1 years regardless of the age of onset of sexual intercourse is based in part on the very low inci dence of cancer in younger women. The recommendation is also based on the potential for adverse effects associated with follow-up of young women with abnormal cytology screening results. General Considerations the squamocolumnar junction of the cervix is an area of active squamous cell proliferation. In childhood, this junc tion is located on the exposed vaginal portion of the cervix.

Cognitive deficits erectile dysfunction exam video order super cialis 80 mg with mastercard, such as the executive dysfunction that is common to schizophrenia impotence australia discount 80 mg super cialis with mastercard, also do not appear as responsive to anti psychotics as do positive symptoms erectile dysfunction treatment injection cost purchase super cialis no prescription. Unfortunately impotence genetic super cialis 80 mg buy mastercard, both negative symptoms and cognitive deficits appear to con tribute more to long-term disability in schizophrenic patients than do positive symptoms impotence viriesiem order 80 mg super cialis mastercard. Unavailability of structured work situations and lack of family therapy are two other reasons why the prognosis is so guarded in such a large percentage of schizophrenic patients. Psychosis connected with a history of serious drug abuse has a guarded prognosis because of the central nervous system damage, usually from the medications themselves and associated medical illnesses. Uncovering the hidden risk architecture of the schizophrenias: c onfirmation in three independent genome -wide association studies. General Considerations Depression is extremely common, with up to 30% of pri mary care patients having depressive symptoms. Depres sion may be the final expression of (1) genetic factors (neurotransmitter dysfunction), (2) developmental problems (personality problems, childhood events), or (3) psychosocial stresses (divorce, unemployment). It frequently presents in the form of somatic complaints with negative medical workups. Patients experiencing normal grief tend to produce sym pathy and sadness in the clinician caregiver; depression often produces frustration and irritation in the clinician. Grief is usually accompanied by intact self-esteem, whereas depression is marked by a sense of guilt and worthlessness. Mania is often combined with depression and may occur alone, together with depression in a mixed episode, or in cyclic fashion with depression. Clinical Findings In general, there are four major types of depression, with similar symptoms in each group. Adjustment Disorder with Depressed Mood Depression may occur in reaction to some identifiable stressor or adverse life situation, usually loss of a person by death (grief reaction), divorce, etc; financial reversal (crisis); or loss of an established role, such as being needed. Anger is frequently associated with the loss, and this in turn often produces a feeling of guilt. The disorder occurs within 3 months of the stressor and causes significant impairment in social or occupational functioning. The symptoms range from mild sadness, anxiety, irritability, worry, and lack of concentration, discouragement, and somatic complaints to the more severe symptoms of frank depression. When the full criteria for major depressive disorder are present, then that diagnosis should be made and treatment instituted even when there is a known stressor. The presence of a stressor is not the determining diagnostic driver, it is the resultant syndromal complex. One should not neglect treatment for major depression simply because it may appear to be an understandable reac tion to a particular stress or difficulty. Melancholic maj or depression is characterized by a lack of mood reactivity seen in atypical depression, the presence of a prominent anhedonia and more severe vegetative symptoms. Major depression with a seasonal onset (seasonal affective dis order) is a dysfunction of circadian rhythms that occurs more commonly in the fall and winter months and is believed to be due to decreased exposure to full-spectrum light. Common symptoms include carbohydrate craving, lethargy, hyperphagia, and hypersomnia. Major depres sion with postpartum onset usually occurs 2 weeks to 6 months postpartum. Most women (up to 80%) experience some mild let down of mood in the postpartum period. For some of these (1 0 - 1 5%), the symptoms are more severe and similar to those usually seen in serious depression, with an increased emphasis on concerns related to the baby (obsessive thoughts about harming it or inability to care for it). When psychotic symptoms occur, there is frequently associated sleep deprivation, volatility of behavior, and manic-like symptoms. Postpartum psychosis is much less common (less than 2%), often occurs within the first 2 weeks, and requires early and aggressive management. Biologic vul nerability with hormonal changes and psychosocial stress ors all play a role. The chances of a second episode are about 25% and may be reduced with prophylactic treatment. Sadness, loss of interest, and withdrawal from activities over a period of 2 or more years with a relatively persistent course is necessary for this diagnosis. Generally, the symptoms are milder but longer-lasting than those in a major depressive episode. Premenstrual dysphoric disorder-Depressive symp toms occur during the late luteal phase (last 2 weeks) of the menstrual cycle. Depressive Disorders the subclassifications include maj or depressive disorder and dysthymia. Major depressive disorder-A major depressive disor der consists of a syndrome of mood, physical and cognitive symptoms that occurs at any time of life. Com plaints vary widely but most frequently include a loss of interest and pleasure (anhedonia), withdrawal from activi ties, and feelings of guilt. Also included are inability to concentrate, some cognitive dysfunction, anxiety, chronic fatigue, feelings of worthlessness, somatic complaints (unexplained somatic complaints frequently indicate depression), loss of sexual drive, and thoughts of death. Vegetative signs that frequently occur are insomnia, anorexia with weight loss, and consti pation. Psychotic major depression occurs up to 14% of all patients with major depression and 25% of patients who are hospitalized with depression. Psychotic symptoms (delusions, paranoia) are more common in depressed persons who are older than 50 years. Paranoid symptoms may range from general suspiciousness to ideas of reference with delusions. The somatic delusions fre quently revolve around feelings of impending annihilation or somatic concerns (eg, that the body is rotting away with cancer). Hallucinations are less common than unusual beliefs and tend not to occur independent of delusions. In addition to psychotic major depression, other sub categories include major depression with atypical features that is characterized by hypersomnia, overeating, lethargy, C. Bipolar Disorder Bipolar disorder consists of episodic mood shifts into mania, maj or depression, hypomania, and mixed mood states. The ability of bipolar disorder to mimic aspects of many other coincident major mental health disorders and a high comorbidity with substance abuse can make the initial diagnosis of bipolar disorder difficult. Mania-A manic episode is a mood state characterized by elation with hyperactivity, overinvolvement in life activities, increased irritability, flight of ideas, easy distract ibility, and little need for sleep. The overenthusiastic quality of the mood and the expansive behavior initially attract others, but the irritability, mood lability with swings into depression, aggressive behavior, and grandiosity usually lead to marked interpersonal difficulties. Atypical manic episodes can include gross delu sions, paranoid ideation of severe proportions, and audi tory hallucinations usually related to some grandiose perception. The episodes begin abruptly (sometimes pre cipitated by life stresses) and may last from several days to months. Generally, the manic episodes are of shorter duration than the depressive episodes. In almost all cases, the manic epi sode is part of a broader bipolar (manic-depressive) disor der. Patients with four or more discrete episodes of a mood disturbance in 1 year are called "rapid cyclers. Manic patients differ from patients with schizophrenia in that the former use more effective interpersonal maneu vers, are more sensitive to the social maneuvers of others, and are more able to utilize weakness and vulnerability in others to their own advantage. Creativity has been posi tively correlated with mood disorders, but the best work done is between episodes of mania and depression. Cyclothymic disorders- these are chronic mood dis turbances with episodes of subsyndromal depression and hypomania. The symptoms must have at least a 2-year duration and are milder than those that occur in depressive or manic episodes. One study associated the use of beta-blockers with a sig nificant reduction in risk of depressive symptoms 1 year after a percutaneous coronary intervention. Infrequently, disulfiram and anticholinesterase medications may be associated with symptoms of depression. Alcohol, sedatives, opioids, and most of the psyche delic drugs are depressants and, paradoxically, are often used in self-treatment of depression. Differential Diagnosis Since depression may be a part of any illness-either reac tively or as a secondary symptom-careful attention must be given to personal life adjustment problems and the role of medications (eg, reserpine, corticosteroids, levodopa). Schizophrenia, partial complex seizures, organic brain syndromes, panic disorders, and anxiety disorders must be differentiated. Malignancies, including central and gastrointestinal tumors are sometimes associ ated with depressive symptoms and may antecede the diagnosis of tumor. Strokes, particularly dominant hemi sphere lesions, can occasionally present with a syndrome that looks like maj or depression. Conditions such as rheumatoid arthritis, multiple sclerosis, stroke, and chronic heart disease are particularly likely to be associated with depression, as are other chronic illnesses. Depression is common in cancer, as well, with a particularly high degree of comorbidity in pancreatic can cer. Varying degrees of depression occur at various times in schizophrenic disorders, central nervous system disease, and organic mental states. The classic model of drug-induced depression occurred with the use of reserpine, both in clinical settings and as a pharmacologic probe in research settings. Cortico steroids and oral contraceptives are commonly associated with mood changes such as depression and hypomania. Antihypertensive medications such as methyldopa, gua nethidine, and clonidine have been associated with the development of depressive syndromes, as have digitalis and antiparkinsonism medications (eg, levodopa). Interferon is strongly associated with depressed mood and fatigue as a side effect; consultation with a psychiatrist prior to pre scribing these agents is indicated in cases where there is a history of depression. It is unusual for beta-blockers to produce depression when given for short periods, such as in the treatment of performance anxiety. Complications the most important complication is suicide, which often includes some elements of aggression. Suicide rates in the general population vary from 9 per 1 00,000 in Spain to 20 per 1 00,000 in the United States to 58 per 1 00,000 in Hun gary. In individuals hospitalized for depression, the life time risk rises to 1 0- 1 5%. In patients with bipolar I disorder, the risk is higher, with up to 20% of individuals dying of suicide. Men over the age of 50 are more likely to complete a suicide because of their tendency to attempt suicide with more violent means, particularly guns. On the other hand, women make more attempts but are less likely to complete a suicide. An increased suicide rate is being observed in the younger population, aged 1 5 - 3 5. These individuals may be acutely distressed by a recent breakup in a relationship or another type of disappointment. This group also includes those who may not be diagnosed as having depression but who are overwhelmed by a stressful situation often with an aspect of public humiliation (eg, victims of cyber-bullying). A suicide attempt in such cases may be an impulsive or aggressive act not associated with significant depression. In such cases, a suicide attempt is clearly a stratagem for controlling or hurting others or an attempted escape. Another high-risk group are individuals with psychotic illness who tend not to verbalize their concerns, are unpredictable, and are often successful in their suicide attempt, although they make up only a small percentage of the total. Finally, suicide is 10 times more prevalent in p atients with schizophrenia than in the general population, and jumping from bridges is a more common means of attempted suicide by patients with schizophrenia than by others. The immediate goal of psychiatric evaluation is to assess the current suicidal risk and the need for hospitaliza tion versus outpatient management. Perhaps the one most useful question is to ask the person how many hours per day he or she thinks about suicide. Further assessing the risk by inquiring about intent, plans, means, and suicide-inhibiting factors (eg, strong ties to children or the church) is essen tial. The intent is less likely to be truly suicidal, for example, if small amounts of poison or medication were ingested or scratching of wrists was superficial, if the act was per formed in the vicinity of others or with early notification of others, or if the attempt was arranged so that early detec tion would be anticipated. Alcohol, hopelessness, delu sional thoughts, and complete or nearly complete loss of interest in life or ability to experience pleasure are all posi tively correlated with suicide attempts. Other risk factors are previous attempts, a family history of suicide, medical or psychiatric illness (eg, anxiety, depression, psychosis), male sex, older age, contemplation of violent methods, a humiliating social stressor, and drug use (including long term sedative or alcohol use), which contributes to impul siveness or mood swings. Successful treatment of the patient at risk for suicide cannot be achieved if the patient continues to abuse drugs. Measurement of mood is often facili tated by using a standardized instrument such as the Ham ilton or Montgomery-Asberg clinician-administered rating scales or the self-administered Patient Health Question naire-9. Blood tests are being developed to diagnose depression and predict antidepressant response. However, more testing is needed to determine the usefulness in rou tine clinical practice. Suicide risk can be specifically assessed using an instrument such as the Columbia-Suicide Severity Risk Scale. If hospitalization is not indicated (eg, gestures, impul sive attempts; see above), the clinician must formulate and institute a treatment plan or make an adequate referral. The problem is often worsened by the long-term complications of the suicide attempt, eg, brain damage due to hypoxia, peripheral neu ropathies caused by staying for long periods in one posi tion causing nerve compressions, and medical or surgical problems such as esophageal strictures and tendon dysfunctions. Medical Milder forms of depression usually do not require drug therapy and can be managed by psychotherapy and the passage of time. In severe cases-particularly when vegeta tive signs are significant and symptoms have persisted for more than a few weeks-antidepressant drug therapy is often effective. Drug therapy is also suggested by a family history of major depression in first-degree relatives or a past history of prior episodes. Hospitalization is necessary if suicide is a major consid eration or if complex treatment modalities are required.

Targeted therapy- Targeted therapy refers to agents that are directed specifically against a protein or molecule expressed uniquely on tumor cells or in the tumor microenvironment erectile dysfunction drug has least side effects 80 mg super cialis purchase amex. In these regimens impotence with blood pressure medication order genuine super cialis on line, trastuzumab is given with chemotherapy and then contin ues beyond the course of chemotherapy to complete a full year erectile dysfunction after radical prostatectomy treatment options purchase 80 mg super cialis with visa. At least one study (N983 1) suggests that concurrent erectile dysfunction at age 64 order super cialis 80 mg on line, rather than sequential erectile dysfunction pills super cialis 80 mg purchase overnight delivery, delivery of trastuzumab with che motherapy may be more beneficial. Another question being addressed in trials is whether to treat small (less than 1 em), node-negative tumors with trastuzumab plus chemotherapy. A meta analysis evaluating more than 1 8,000 women with early-stage breast cancer treated with bisphosphonates or placebo showed that bisphosphonates reduce the risk of cancer recurrence (especially in bone) and improve breast cancer-specific survival primarily in postmenopausal women. Side effects associated with bisphosphonate ther apy include bone pain, fever, osteonecrosis of the jaw (rare, less than 1 %), esophagitis or ulcers (for oral bisphospho nates), and renal failure. Postoperatively, all patients should continue to receive trastuzumab to complete a full year. Adjuvant therapy in older women-Data relating to the optimal use of adjuvant systemic treatment for women over the age of 65 are limited. Moreover, individual studies do show that older women with higher risk disease derive benefits from chemotherapy. One study compared the use of oral chemotherapy (capecitabine) to standard chemotherapy in older women and concluded that standard chemotherapy is preferred. The ben efits of endocrine therapy for hormone receptor-positive disease appear to be independent of age. Neoadjuvant Therapy the use of chemotherapy or endocrine therapy prior to resection of the primary tumor (neoadjuvant) is gaining popularity. A complete pathologic response at the time of surgery is associated with improvement in event-free and overall survival. Neoadjuvant chemotherapy also increases the chance of breast conservation by shrinking the primary tumor in women who would otherwise need mastectomy for local control. Survival after neoadjuvant chemotherapy is similar to that seen with postoperative adjuvant chemotherapy. Studies are ongoing to evaluate hormonally targeted regimens in the neoadjuvant setting. Outside of the clinical trial setting, the use of neoadjuvant hormonal therapy is generally restricted to postmenopausal patients who are unwilling or unable to tolerate chemotherapy. Neoadjuvant chemotherapy leads to pathologic complete response in up to 40-50% of patients with triple negative breast cancer. Patients who achieve a pathologic complete response seem to have a similar prognosis to other breast cancer subtypes with pathologic complete response. However, those patients with residual disease at the time of surgery have a poor prognosis. Those patients with triple neg ative disease who received carboplatin had a pathologic complete response rate of 53. Several stud ies have shown that sentinel node biopsy can be done after neoadjuvant therapy. Some physicians recom mend performing sentinel lymph node biopsy before administering the chemotherapy in order to avoid a false negative result and to aid in planning subsequent radiation therapy. Others prefer to perform sentinel lymph node biopsy after neoadjuvant therapy to avoid a second opera tion and assess post-chemotherapy nodal status. If a com plete dissection is desired, this can be performed at the time of the definitive breast surgery. No study has evaluated the impact of no axillary treatment for node-positive patients who become node-negative after neoadjuvant therapy. Important questions remaining to be answered are the timing and duration of adjuvant and neoadjuvant chemo therapy, which chemotherapeutic agents should be applied for which subgroups of patients, the use of combinations of hormonal therapy and chemotherapy as well as possibly targeted therapy, and the value of prognostic factors other than hormone receptors in predicting response to therapy. In addition to radiotherapy, bisphosphonate therapy has shown excellent results in delaying and reducing skel etal events in women with bony metastases. Caution should be exercised when combining radiation therapy with chemotherapy because toxicity of either or both may be augmented by their concurrent administra tion. In general, only one type of therapy should be given at a time unless it is necessary to irradiate a destructive lesion of weight -bearing bone while the patient is receiving chemotherapy. This is especially difficult to determine for patients with destructive bone metastases, since changes in the status of these lesions are difficult to determine radiographically. Endocrine therapy for metastatic disease- the first targeted therapy for cancer was the use of antiestrogen therapy in hormone receptor-positive breast cancer. The following therapies have all been shown to be effective in hormone receptor-positive metastatic breast cancer: administration of drugs that block or downregulate hor mone receptors (such as tamoxifen or fulvestrant, respec tively) or drugs that block the synthesis of hormones (such as Ais); ablation of the ovaries, adrenals, or pituitary; and the administration of hormones (eg, estrogens, androgens, progestins); see Table 1 7-6. A favorable response to hormonal manipulation occurs in about one-third of patients with metastatic breast cancer. Because the quality of life during endocrine manipu lation is usually superior to that during cytotoxic chemotherapy, it is best to try endocrine manipulation. Palliative Treatment Palliative treatments are those to manage symptoms, improve quality of life, and even prolong survival, without the expectation of achieving cure. In the United States, it is uncommon to have distant metastases at the time of diag nosis (de novo metastases). However, most patients who have a breast cancer recurrence after initial local and adju vant therapy have a metastatic rather than local (in breast) disease. Breast cancer most commonly metastasizes to the liver, lungs and bone, causing symptoms such as fatigue, change in appetite, abdominal pain, cough, dyspnea, or bone pain. Headaches, imbalance, vision changes, vertigo, and other neurologic symptoms may be signs of brain metastases. Radiotherapy and Bisphosphonates Palliative radiotherapy may be advised for primary treat ment of locally advanced cancers with distant metastases to control ulceration, pain, and other manifestations in the breast and regional nodes. Irradiation of the breast and chest wall and the axillary, internal mammary, and supra clavicular nodes should be undertaken in an attempt to cure locally advanced and inoperable lesions when there is no evidence of distant metastases. A small number of patients in this group are cured in spite of extensive breast and regional node involvement. Palliative irradiation is of value also in the treatment of certain bone or soft-tissue metastases to control pain or avoid fracture. However, when receptor status is unknown, disease is progressing rapidly or is threatening visceral organs, chemotherapy may be used as first-line treatment. There is no significant difference in survival or response between tamoxifen therapy and bilateral oophorectomy. Bilateral oophorectomy is less desirable than tamoxifen in premenopausal women because tamoxifen is so well toler ated. Oophorectomy presumably works by eliminating estrogens, progestins, and androgens, which stimulate growth of the tumor. Ais should not be used in a patient with functioning ovaries since they do not block ovarian production of estrogen. Whether to opt for chemotherapy or another endocrine measure depends largely on the sites of metastatic disease (visceral being more serious than bone-only, thus sometimes warranting the use of chemotherapy), the disease burden, the rate of growth of disease, and patient preference. Patients who take chemotherapy and then later have pro gressive disease may subsequently respond to another form of endocrine treatment (Table 17 -6). The optimal choice for secondary endocrine manipulation has not been clearly defined for the premenopausal patient. Tamoxifen also increases the risk of venous thromboembolic events and uterine hyperplasia and cancer. The main side effects of Ais include hot flushes, vaginal dry ness, and joint stiffness; however, osteoporosis and bone fractures are significantly higher than with tamoxifen. The com bination of fulvestrant plus anastrozole may also be more effective than anastrozole alone, although two studies evalu ating this question have yielded conflicting results. In general, palbociclib is well tolerated; however, it is associated with grade 3/4 leukopenia and neutropenia, thus monitoring patients closely is required. Longer follow-up revealed a significant overall survival benefit associated with pertuzumab as well. The combination of trastuzumab plus lapatinib has been shown to be more effective than lapa tinib alone for trastuzumab-resistant metastatic breast cancer. This study showed that the two ado-trastuzumab containing arms were noninfe rior (but not superior) to the trastuzumab plus taxane arm. Thus, for the time being, ado-trastuzumab is primarily used in the second-line setting and beyond. This type of "triple-negative" breast cancer, while heterogeneous, generally behaves aggres sively and is associated with a poor prognosis. Newer classes of targeted agents are being evaluated specifically for triple-negative breast cancer, although none have been shown to improve outcomes to date. Research in this area is rapidly expanding with multiple clinical trials of molecu larly targeted agents ongoing. Prior adjuvant chemotherapy does not seem to alter response rates in patients who relapse. A number of che motherapy drugs (including vinorelbine, paclitaxel, docetaxel, gemcitabine, ixabepilone, carboplatin, cisplatin, capecitabine, albumin-bound paclitaxel, eribulin, and lipo somal doxorubicin) may be used as single agents with first line obj ective response rates ranging from 30% to 50%. Combination chemotherapy yields statistically signifi cantly higher response rates and progression-free survival rates, but has not been conclusively shown to improve overall survival rates compared with sequential single agent therapy. Patients should be encouraged to participate in clinical trials given the number of promising targeted therapies in development. It is generally appropriate to treat willing patients with multiple sequential lines of therapy as long as they tolerate the treatment and as long as their performance status is good (eg, at least ambulatory and able to care for self, up out of bed more than 50% of waking hours). Axillary dissection can be avoided in the major ity of clinically node- negative patients undergoing breast conserving therapy. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomized trials. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metas tasis: a randomized clinical trial. Axillary lymph node status is the best-analyzed prognostic factor and correlates with sur vival at all tumor sizes. When cancer is localized to the breast with no evidence of regional spread after patho logic examination, the clinical cure rate with most accepted methods of therapy is 75% to more than 90%. In fact, patients with small mammographically detected biologically favorable tumors and no evidence of axillary spread have a 5-year survival rate greater than 95%. When the axillary lymph nodes are involved with tumor, the survival rate drops to 50-70% at 5 years and probably around 25-40% at 10 years. Gene analysis studies, such as Oncotype Dx, can predict disease-free survival for some subsets of patients. The mortality rate of breast cancer patients exceeds that of age-matched normal controls for nearly 20 years. Thereafter, the mortality rates are equal, though deaths that occur among breast cancer patients are often directly the result of tumor. Dis paraties in treatment outcome for different racial and eth nic backgrounds have been reported by several studies. These differences appear to be not only due to different socioeconomic factors (and a resulting difference in access to healthcare) but also due to differences in the subtype of breast cancer diagnosed. For those patients whose disease progresses despite treat ment, studies suggest supportive group therapy may improve survival. As they approach the end of life, such patients will require meticulous palliative care (see Chapter 5). Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States. Racial and ethnic differences in breast cancer survival: mediating effect of tumor characteristics and sociodemographic and treatment factors. During the first 2 years, most patients should be examined every 6 months then annually thereafter. Special attention is paid to the contralateral breast because a new primary breast malignancy will develop in 20-25% of patients. In some cases, metastases are dormant for long periods and may appear 1 0- 1 5 years or longer after removal of the primary tumor. Although studies have failed to show an adverse effect of hormonal replacement in disease-free patients, it is rarely used after breast cancer treatment, particularly if the tumor was hor mone receptor-positive. Even pregnancy has not been associated with shortened survival of patients rendered disease free-yet many oncologists are reluctant to advise a young patient with breast cancer that it is safe to become pregnant. The use of estrogen replacement for conditions such as osteoporosis, vaginal dryness and hot flushes may be considered for a woman with a history of breast cancer after discussion of the benefits and risks; however, it is not routinely recommended, especially given the availability of nonhormonal agents for these conditions (such as bisphos phonates and denosumab for osteoporosis). Vaginal estro gen is frequently used to treat vaginal atrophy with no obvious ill effects. Loca l Recurrence the incidence of local recurrence correlates with tumor size, the presence and number of involved axillary nodes, the histologic type of tumor, the presence of skin edema or skin and fascia fixation with the primary tumor, and the type of definitive surgery and local irradiation. Local recurrence on the chest wall after total mastectomy and axillary dissection develops in as many as 8% of patients. When the axillary nodes are not involved, the local recur rence rate is less than 5%, but the rate is as high as 25% when they are heavily involved. A similar difference in local recurrence rate was noted between small and large tumors. Factors such as multifocal cancer, in situ tumors, positive resection margins, chemotherapy, and radiother apy have an effect on local recurrence in patients treated with breast-conserving surgery. Chest wall recurrences usually appear within the first several years but may occur as late as 15 or more years after Table 1 7-7. Local excision or localized radiotherapy may be feasible if an isolated nodule is present. If lesions are multiple or accompanied by evidence of regional involve ment in the internal mammary or supraclavicular nodes, the disease is best managed by radiation treatment of the entire chest wall including the parasternal, supraclavicular, and axillary areas and usually by systemic therapy. Local recurrence after mastectomy usually signals the presence of widespread disease and is an indication for studies to search for evidence of metastases. Distant metas tases will develop within a few years in most patients with locally recurrent tumor after mastectomy.

It is an acceptable alternative when xanthine oxidase inhibitors cannot be used and can be added when monotherapy with a xanthine oxidase inhibitor fails to reach the target serum uric acid impotence icd 9 cheap super cialis 80 mg overnight delivery. Proben ecid should not be used in patients with a creatinine clearance of less than 50 mL/min due to limited efficacy; contraindications include a history of nephrolithiasis (uric acid or calcium stones) and evidence of overproduction of uric acid (ie erectile dysfunction caused by vascular disease cheap 80 mg super cialis fast delivery, greater than 800 mg of uric acid in a 24-hour urine collection) blood pressure drugs erectile dysfunction discount super cialis 80 mg mastercard. To reduce the development of uric acid stones (which occur in up to 1 1 %) erectile dysfunction in 20s buy genuine super cialis on line, patients should be advised to increase their fluid intake and clinicians should consider prescribing an alkalinizing agent (eg erectile dysfunction over the counter super cialis 80 mg low cost, potassium citrate, 30-80 mEq/day orally) to maintain a urine pH > 6. Chronic Tophaceous Arthritis With rigorous medical compliance, allopurinol or febuxo stat or pegloticase shrinks tophi and in time can lead to their disappearance. Resorption of extensive tophi requires maintaining a serum uric acid below 6 mg/dL. Surgical excision of large tophi offers mechanical improvement in selected deformities. Often the best approach for monarticular gout-after excluding infection-is inj ecting corticosteroids into the j oint (see above). For polyarticular gout, increasing the dose of systemic corticosteroid may be the only alternative. Since transplant patients often have multiple attacks of gout, long-term relief requires lowering the serum uric acid with allopurinol or febuxostat. Prognosis Without treatment, the acute attack may last from a few days to several weeks. The intervals between acute attacks vary up to years, but the asymptomatic periods often become shorter if the disease progresses. Chronic gouty arthritis occurs after repeated attacks of acute gout, but only after inadequate treatment. The younger the patient at the onset of disease, the greater the tendency to a progres sive course. Destructive arthropathy is rarely seen in patients whose first attack is after age 50. Patients with gout are anecdotally thought to have an increased incidence of hyp ertension, kidney disease (eg, nephrosclerosis, interstitial nephritis, pyelonephritis), diabetes mellitus, hypertriglyceridemia, and atherosclerosis. Part 1: systemic nonpharmaco logic and pharmacologic therapeutic approaches to hyperuricemia. Pseudogout is most often seen in persons age 60 or older, is characterized by acute, recurrent and rarely chronic arthritis involving large joints (most commonly the knees and the wrists) and is almost always accompa nied by radiographic chondrocalcinosis of the affected j oints. The crowned dens syndrome, caused by pseudo gout of the atlantoaxial junction associated with "crown like" calcifications around the dens, manifests with severe neck pain, rigidity, and high fever that can mimic meningitis or polymyalgia rheumatica. Identification of calcium pyrophosphate crystals in joint aspirates is diagnostic. Aspiration of the inflamed j oint and intra- articular inj ection of triamcinolone, 1 0-40 mg, depending on the size of the j oint, are also of value in resistant cases. In both conditions, radiographs demonstrate chondrocalcinosis and degenerative changes such as asymmetric joint space narrowing and osteophyte formation. General Considerations Rheumatoid arthritis is a chronic systemic inflammatory disease whose maj or manifestation is synovitis of multiple j oints. It has a prevalence of 1 % and is more common in women than men (female:male ratio of 3: 1). Rheumatoid arthritis can begin at any age, but the peak onset is in the fourth or fifth decade for women and the sixth to eighth decades for men. Susceptibility to rheumatoid arthritis is genetically determined with multi ple genes contributing. Untreated, rheumatoid arthritis causes joint destruc tion with consequent disability and shortens life expec tancy. The pathologic findings in the j oint include chronic synovitis with formation of a pannus, which erodes carti lage, bone, ligaments, and tendons. In the late stage, organization may result in fibrous ankylosis; true bony ankylosis is rare. Joint symptoms-The clinical manifestations of rheu matoid disease are highly variable, but j oint symptoms usually predominate. Although acute presentations may occur, the onset of articular signs of inflammation is usu ally insidious, with prodromal symptoms of vague periar ticular pain or stiffness. Symmetric swelling of multiple j oints with tenderness and pain is characteristic. Stiffness per sisting for longer than 30 minutes (and usually many hours) is prominent in the morning. Stiffness may recur after daytime inactivity and be much more severe after Filippucci E et al. Entrapment syndromes are common-particularly of the median nerve at the carpal tunnel of the wrist. Rheumatoid arthritis can affect the neck but spares the other compo nents of the spine and does not involve the sacroiliac joints. Felty syndrome must be distinguished from the large granular lymphoprolifera tive disorder, with which it shares many features. Aortitis is a rare late complication that can result in aor tic regurgitation or rupture and is usually associated with evidence of rheumatoid vasculitis elsewhere in the body. Rheuma toid factor can occur in other autoimmune disease and in chronic infections, including hepatitis C, syphilis, subacute bacterial endocarditis, and tuberculosis. The prevalence of rheumatoid factor positivity also rises with age in healthy individuals. The white cell count is normal or slightly elevated, but leukopenia may occur, often in the presence of splenomegaly (eg, Felty syn drome). The platelet count is often elevated, roughly in proportion to the severity of overall joint inflammation. Initial joint fluid examination confirms the inflammatory nature of the arthritis (see Table 20-2). Arthrocentesis is needed to diagnose superimposed septic arthritis, which is a common complication of rheumatoid arthritis and should be considered whenever a patient with rheumatoid arthritis has one joint inflamed out of proportion to the rest. Nodules correlate with the presence of rheumatoid factor in serum ("seropositivity"), as do most other extra articular manifestations. Ocular symptoms-Dryness of the eyes, mouth, and other mucous membranes is found especially in advanced disease (see Sj ogren syndrome). Other ocular manifesta tions include episcleritis, scleritis, and scleromalacia due to scleral nodules. Other symptoms- Interstitial lung disease is not uncom mon (estimates of prevalence vary widely according to method of detection) and manifests clinically as cough and progressive dyspnea. Occasionally, a small vessel vasculitis develops and manifests as tiny hem orrhagic infarcts in the nail folds or finger pulps. A small subset of patients with rheumatoid arthritis have Felty syndrome, the 836 C. Radiographs obtained during the first 6 months of symptoms, however, are usually normal. The earliest changes occur in the hands or feet and consist of soft tissue swelling and juxta-articular demineralization. The erosions are often first evident at the ulnar styloid and at the juxta articular margin, where the bony surface is not protected by cartilage. Characteristic changes also occur in the cervi cal spine, with C 1 -2 subluxation, but these changes usually take many years to develop. Differential Diagnosis the differentiation of rheumatoid arthritis from other j oint conditions and immune-mediated disorders can be diffi cult. In 2010, the American College of Rheumatology updated their classification criteria for rheumatoid arthri tis. Osteoarthritis is not associated with constitutional manifestations, and the j oint pain is characteristically relieved by rest, unlike the morn ing stiffness of rheumatoid arthritis. Signs of articular inflammation, prominent in rheumatoid arthritis, are usu ally minimal in degenerative joint disease. Although gouty arthritis is almost always intermittent and monarticular in the early years, it may evolve with time into a chronic poly articular process that mimics rheumatoid arthritis. Gouty tophi can resemble rheumatoid nodules but are not associ ated with rheumatoid factor, whose sensitivity for rheuma toid nodules approaches 100%. The early history of intermittent monoarthritis and the presence of synovial urate crystals are distinctive features of gout. Spondyloar thropathies, particularly earlier in their course, can be a source of diagnostic uncertainty; predilection for lower extremities and involvement of the spine and sacroiliac j oints point to the correct diagnosis. Chronic Lyme arthritis typically involves only one joint, most commonly the knee, and is associated with positive serologic tests (see Chapter 34). However, arthralgias are more promi nent than arthritis, fever is common, IgM antibodies to parvovirus B 19 are present, and the arthritis usually resolves within weeks. Polymyalgia rheumatica occasionally causes polyarthralgias in patients over age 50, but these patients remain rheumatoid factor-negative and have chiefly proximal muscle pain and stiffness, centered on the shoulder and hip girdles. Joint pain that can be con fused with rheumatoid arthritis presents in a substantial minority of patients with granulomatosis with polyangiitis (formerly Wegener granulomatosis). This diagnostic error can be avoided by recognizing that, in contrast to rheuma toid arthritis, the arthritis of granulomatosis with polyan giitis preferentially involves large j oints (eg, hips, ankles, wrists) and usually spares the small joints of the hand. Rheumatic fever is characterized by the migratory nature of the arthritis, an elevated antistreptolysin titer, and a more dramatic and prompt response to aspirin; carditis and erythema marginatum may occur in adults, but chorea and subcutaneous nodules virtually never do. Finally, a variety of cancers produce paraneoplastic syndromes, including polyarthritis. One form is hypertrophic pulmo nary osteoarthropathy most often produced by lung and gastrointestinal carcinomas, characterized by a rheuma toid-like arthritis associated with clubbing, periosteal new bone formation, and a negative rheumatoid factor. Diffuse swelling of the hands with palmar fasciitis occurs in a vari ety of cancers, especially ovarian carcinoma. Treatment the primary objectives in treating rheumatoid arthritis are reduction of inflammation and pain, preservation of func tion, and prevention of deformity. In advanced disease, surgical intervention may help improve function of damaged joints and to relieve pain. Corticosteroids Low-dose corticosteroids (eg, oral prednisone 5-10 mg daily) produce a prompt anti-inflammatory effect in rheu matoid arthritis and slow the rate of articular erosion. No more than 10 mg of prednisone or equivalent per day is appropriate for articular disease. When the corticosteroids are to be discontinued, they should be tapered gradually on a planned schedule appropriate to the duration of treatment. Intra-articular corticosteroids may be helpful if one or two j oints are the chief source of difficulty. Intra-articular triamcinolone, 1 0-40 mg depending on the size of the j oint to be injected, may be given for symptomatic relief but not more than four times a year. It is generally well tolerated and often produces a beneficial effect in 2-6 weeks. If the patient has toler ated methotrexate but has not responded in 1 month, the dose can be increased to 15 mg orally once per week. Cytopenia, most commonly leukopenia or thrombocytopenia but rarely pancytopenia, due to bone marrow suppression is another important potential problem. The risk of devel oping p ancytopenia is much higher in patients with elevation of the serum creatinine (greater than 2 mgldL [1 76. Hepatotoxicity with fibrosis and cirrho sis is an important toxic effect that correlates with cumula tive dose and is uncommon with appropriate monitoring of liver function tests. Heavy alcohol use increases the hepatotoxicity, so patients should be advised to drink alcohol in extreme moderation, if at all. Diabetes mellitus, obesity, and kidney disease also increase the risk of hepatotoxicity. Liver function tests should be monitored at least every 12 weeks, along with a complete blood count. The dose of methotrexate should be reduced if aminotransferase levels are elevated, and the drug should be discontinued if abnormalities persist despite dosage reduction. Gastric irritation, stomatitis, cytopenias, and hepatotoxicity are reduced by prescribing either daily folate (1 mg orally) or weekly leucovorin calcium (2. Because methotrexate is teratogenic, women of childbearing age as well as men must use effective contraception while taking the medica tion. The combination of methotrexate and other folate antagonists, such as trimeth oprim-sulfamethoxazole, should be used cautiously since pancytopenia can result. Probenecid also increases methotrexate drug levels and toxicity and should be avoided. Side effects, particularly neutropenia and thrombocy topenia, occur in 10-25% and are serious in 2-5%. Patients taking sulfasalazine should have complete blood counts monitored every 2-4 weeks for the first 3 months, then every 3 months. The most frequent side effects are diarrhea, rash, reversible alopecia, and hepatotoxicity. Thus, it is contraindicated in premenopausal women or in men who wish to father children. Antimalarials-Hydroxychloroquine sulfate is the anti malarial agent most often used against rheumatoid arthri tis. Monotherapy with hydroxychloroquine should be reserved for patients with mild disease because only a small percentage will respond and in some of those cases only after 3-6 months of therapy. The advantage of hydroxychloroquine is its comparatively low toxicity, especially at a dosage of 200-400 mg/day orally (not to exceed 5 mg/kg/day). The prevalence of the most impor tant reaction, pigmentary retinitis causing visual loss, is a function of duration of therapy, occurring in less than 2% of patients (dosed properly) during the first 1 0 years of use, but rising to 20% after 20 years of treatment. Other reactions include neuropathies and myopathies of both skeletal and cardiac muscle, which usually improve when the drug is withdrawn.

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