Condet

Linda Cardozo MD FRCOG

• Professor of Urogynaecology, King? College Hospital, London

Other proteins that have been classified as part of the humoral defense system include lysozyme depressive symptoms vs depression discount geodon 80 mg online, lactoferrin mood disorder axis 3 40 mg geodon amex, tuftsin depression test in pregnancy cheap 20 mg geodon free shipping, and fibronectin depression test schön klinik discount 40mg geodon fast delivery. Immunoglobulins may be opsonic (enhance phagocytosis), or neutralizing (inhibit replication of viruses) or, with complement, may lyse microbes or cells. Patients with either primary or secondary defects or deficiencies in these proteins are at highest risk for serious infections from encapsulated bacteria and to a lesser extent the enteroviruses and Giardia lamblia. Patients with Malignant Disorders the degree of humoral impairment in multiple myeloma appears to be related to the stage of the disease and is primarily caused by malignant plasma cell induction of a protein that is synthesized by macrophages and that selectively suppresses B-cell function. Myeloma patients are most susceptible to recurrent infections from encapsulated bacteria such as S. Infections caused by enteric gram-negative rods and staphylococci are also encountered, especially in patients with refractory or advanced disease. Recurrent infection most often occurs in the upper respiratory tract, urinary tract, or skin. Patients with B-cell chronic lymphocytic leukemia appear to have unbalanced immunoglobulin chain synthesis and resultant hypogammaglobulinemia. The incidence of infection correlates with the duration and stage of the disease, as well as serum levels of immunoglobulins (particularly IgG). Encapsulated bacteria predominate, although infections by staphylococci and enteric gram-negative bacilli also occur. Upper and lower respiratory tract infections are encountered most commonly, although other sites such as the urinary tract and skin are frequently involved. Primary Deficiencies Isolated B-cell immunodeficiency states and their associated risks for infection in children include transient hypogammaglobulinemia of infancy, which is not usually associated with serious infections; sex-linked hypogammaglobulinemia, which is associated with recurrent pyogenic infections and septicemia from S. Common variable hypogammaglobulinemia is associated with respiratory tract infections with S. Many patients with B-cell deficiencies, particularly those with congenital hypogammaglobulinemia, appear to be at risk for chronic central nervous system infections by enteroviruses. Although deficiencies of the early classic pathway components (C1, C2, C4) have been reported, associated infection is rare, probably because the alternative pathway remains functional and is able to compensate. Deficiencies of C3 or C5, on the other hand, often lead to severe infections with encapsulated organisms, enteric gram-negative bacteria, and staphylococci. Absence of the later components (C5b, C6, C7, C8, C9) leads to an increase in infections, primarily with Neisseria species, both N. Although the defects in these later components may be present from birth, infectious episodes do not typically begin until the teenage years. Indeed, any patient with recurrent infections by Neisseria species should be investigated for complement deficiency. The spleen probably plays an adjunctive role in host defense by removing organisms from the blood that have been ineffectively opsonized by complement. In addition, it participates in the primary immunoglobulin response and is involved in regulation of the alternative complement pathway, with low levels of immunoglobulins and properdin reported in patients following splenectomy. A decrease in the opsonic peptide tuftsin has also been reported following splenectomy, and alternative pathway defects may be important in patients with sickle cell disease and splenic dysfunction. The risk of development of serious infection, as well as the types of infections, may vary depending on the reason for abnormal splenic function and the presence or absence of other immune abnormalities. Patients who undergo post-traumatic splenectomy appear to be at a lower risk for infection. An increased risk of Salmonella infection appears to be unique for the sickle cell population. Most asplenic patients or patients who have undergone splenectomy are at increased risk for serious bacterial infections, primarily with S. The initial manifestation of even overwhelming infection may be deceptively subtle, with fever often being the only sign of infection. Asplenic patients with an underlying hematologic disease who have fever should be managed initially as potentially septic. The overall management of neutropenic patients is based on the use of empirical antibiotics directed against a wider array of potential pathogens.

The latter can suppress gonadotropin and sex steroid hormone levels and cause a stabilization or even regression of secondary sex characteristics and a slowing of growth and bone maturation in most cases depression or adhd buy geodon 20 mg with mastercard. When therapy is discontinued at the normal time of puberty depression medication names discount geodon 20mg visa, sex steroid levels increase depression definition according to beck cheap geodon 20mg otc, secondary sexual characteristics again develop depression symptoms school discount geodon 80 mg amex, growth increases, and regular menses develop spontaneously. Structural or infiltrative lesions of the hypothalamus, such as those discussed above, can decrease the amount of dopamine reaching the lactotrophs and thus cause modest hyperprolactinemia. Prolactin elevations resulting from such lesions rarely exceed 150 ng/mL and are usually less than 100 ng/mL. Because their therapy is quite different, it is very important to differentiate non-secreting pituitary adenomas with extensive suprasellar extension causing prolactin elevations in this range from prolactin-secreting adenomas, which when of such a large size usually cause prolactin elevations 5 to 50 times higher. A number of medications can cause hyperprolactinemia primarily by interfering with central catecholamine, dopamine in particular (Table 235-2). The hyperprolactinemia itself may impair gonadal function, so efforts may also be made to lower prolactin levels with bromocriptine or other dopamine agonists. In that circumstance both bromocriptine and sex steroid replacement may be necessary. Neurogenic Chest wall lesions Spinal cord lesions Breast stimulation Other Pregnancy Hypothyroidism Chronic renal failure Cirrhosis Pseudocyesis Adrenal insufficiency Idiopathic Medications Phenothiazines Haloperidol Monoamine oxidase inhibitors Tricyclic antidepressants Reserpine Methyldopa Metoclopramide Amoxapine Cocaine Verapamil Fluoxetine 1206 hyperprolactinemia cannot be stopped, dopamine agonists may be used but might exacerbate the psychosis. In such cases and others in which fertility is not an issue, treatment with cyclic estrogen/progestin replacement can be carried out safely. In such cases, small pituitary or hypothalamic tumors could exist that are beyond the resolution of current imaging techniques, but when such patients are monitored for many years, it is very uncommon for tumors to later be visualized. Idiopathic hyperprolactinemia can cause amenorrhea, galactorrhea, impotence, infertility, and loss of libido, just as occurs with hyperprolactinemia of other causes, so the idiopathic hyperprolactinemia may need to be treated. The only possible treatment is bromocriptine or another dopamine agonist, and these agents are successful in more than 90% of cases. Alternatively, cyclic estrogen/progesterone replacement may be given, but fertility will not be restored. It may occur with the loss of other hormones but may also appear as an isolated deficiency. Diabetes insipidus can develop as a result of destructive lesions in the supraoptic and paraventricular nuclei or in the mediobasal hypothalamus in the path of the neural fibers containing vasopressin (see Chapter 102. Irritative lesions can trigger the release of vasopressin in an unregulated fashion and thereby result in the syndrome of inappropriate antidiuretic hormone (vasopressin) secretion. A number of functions that affect the internal milieu, in addition to anterior and posterior pituitary function, are regulated, at least in part, by the hypothalamus and include temperature control, behavior, consciousness, memory, sleep, food intake, and carbohydrate metabolism. Body weight is kept relatively constant in non-obese individuals through the integration of a number of factors relating to the intake of nutrients and the output of energy; these functions are also affected by hormonal, environmental, and genetic factors. As with the regulation of hormone secretion, regulation of food intake can be conceptually regarded as an adjustment of food intake and energy expenditure around "set points" that may be different for body weight, total body fat, and lean body mass. The primary regulatory system involves production of the hormone leptin by adipocytes, which binds to hypothalamic leptin receptors and feeds back negatively on food intake and energy expenditure, but a number of other peptides are involved as well (see Chapter 228). A number of areas of the hypothalamus are involved in the regulation of energy balance. Destruction of the mediobasal hypothalamus will sometimes inhibit satiety and may result in hyperphagia and hypothalamic obesity. The hyperphagia is due to destruction of noradrenergic fibers originating in the paraventricular nucleus and passing through the mediobasal hypothalamus. Because of their location, such lesions also usually produce hypopituitarism and diabetes insipidus. In a number of rare syndromes with obesity as a major characteristic, a hypothalamic etiology has been postulated. Prader-Willi is the most common of these syndromes and occurs in 1 in 25,000 births. It is characterized by hypotonia, obesity, short stature, mental deficiency, hypogonadism, and small hands and feet. In the few cases studied at autopsy, no discernible hypothalamic lesions were detected. In the other syndromes (Laurence-Moon-Biedl-Bardet, Altrom-Hallgren), no specific hypothalamic lesions have been found. Lesions of the lateral hypothalamus, which destroy nigrostriatal dopaminergic fibers that pass through this area, produce hypophagia along with an increase in peripheral norepinephrine turnover and metabolic rate.

Improvement of thyrotoxic symptoms bipolar depression support alliance buy 80 mg geodon fast delivery, in general tropical depression definition noaa buy discount geodon 40 mg line, takes 2 to 3 weeks and can lag behind the normalization of thyroid hormone values mood disorder residential treatment geodon 80 mg cheap. Thyroid hormone values are checked 4 weeks after the start of therapy and if no decrease in values occurs in spite of compliance anxiety 8 letters buy geodon 20 mg on line, the dose may be increased to 30 to 40 mg a day. A decrease in dose that is accompanied by an increase in free T4 or T3 levels and symptoms suggesting disease reactivation requires maintenance at higher dose levels for a longer time. It appears that longer duration of antithyroid therapy bodes well for patients staying euthyroid after the medication is stopped. Most relapses occur within the first 3 to 6 months after discontinuation of antithyroid therapy. In young adults, a second course of antithyroid drug therapy can be tried, but the chance of permanent remission declines. Long-term remissions have been reported to occur in more than 90% of patients treated 1239 with this regimen. Before such a protocol is adopted for routine use, however, confirmation of results in patients of a different ethnic background and iodine exposure should be obtained. These occur most frequently during the initial 3 to 6 months after the therapy is started. The most frequent complications are allergic in nature, and rashes occur in 2 to 3% of patients. The major toxic reaction is agranulocytosis, which develops suddenly and occurs in 0. Routine monitoring of leukocyte counts is not recommended, but a leukocyte count should be obtained before starting therapy. Patients need to be instructed to discontinue their medication and contact their physician when a fever occurs or infections develop, especially in the oropharynx. Other treatment modalities such as radioactive iodine should be chosen for further treatment. In either event, antithyroid drugs are the preferred initial therapy for thyrotoxicosis. The 80 muCi is then multiplied by the estimated weight of the gland and corrected for 131 I uptake. This delivers 6000 to 8000 rad to the thyroid and most frequently requires doses of 5 to 10 mCi. In patients with low uptake, large glands, and severe thyrotoxicosis leading to rapid intrathyroidal iodine turnover, larger doses often are chosen. Improvement in thyrotoxicosis occurs after 4 to 5 weeks, and 40 to 70% of patients regain normal thyroid functions within 6 to 8 weeks. The remaining need a second dose, which should not be undertaken before 6 months have elapsed. After giving radioactive iodine, antithyroid drugs can be added at day 5 to reach a euthyroid state more quickly. More than 50% of patients become hypothyroid during the first year after therapy, with an additional 2 to 3% during each subsequent year. Unless otherwise treated, transient hypothyroidism occurs 2 to 3 months after radioactive iodine treatment, with subsequent spontaneous normalization of thyroid hormone values. Patients should be informed of this risk and be followed after the acute phase of treatment every 4 to 6 months and subsequently at least once a year. Surgical removal of a large part of the thyroid (subtotal thyroidectomy) is indicated in patients with large obstructing glands or glands containing nodules that are identified as malignant or equivocal on fine-needle aspiration. Pregnant women with severe hyperthyroidism, which is difficult to control with antithyroid drugs, can be treated with thyroidectomy during the second trimester. In addition, young patients who are difficult to control on antithyroid drugs, patients with toxic reactions to antithyroid drugs, and patients who are not candidates for antithyroid drugs and refuse radioactive iodine are treated by surgery. Complications including hypoparathyroidism, recurrent laryngeal nerve paralysis, and hemorrhage should occur in less than 1 to 2% of patients. In addition, transient hypocalcemia, wound infection, and keloid formation leading to unsightly scars may occur. In some, toxic reactions preclude the use of antithyroid drugs and 131 I cannot be employed because a very low uptake occurs due to excess iodine exposure or because of pregnancy. Also, some patients may present a high surgical risk because of underlying medical problems.

The differential diagnosis includes brain or leptomeningeal metastases; fungal depression nursing definition cheap 20mg geodon with visa, parasitic depression risk factors order 40mg geodon with mastercard, or viral infections (including multifocal leukoencephalopathy); metabolic encephalopathy; and nutritional deficits bipolar depression vs clinical depression generic 20 mg geodon otc. The rapid onset of dementia in middle age accompanied by cerebellar depression negative thoughts purchase geodon 80 mg online, brain stem, or peripheral nerve dysfunction but no other focal cerebral signs suggests paraneoplastic dementia as a remote effect of cancer. No specific treatment is available for paraneoplastic dementias, but they occasionally improve spontaneously with successful treatment of the cancer. Cerebellar symptoms usually evolve over weeks, with bilateral and symmetrical ataxia of gait and the arms and legs. Severe dysarthria is usually present; vertigo and diplopia are common, but nystagmus may be absent. Some patients have neurologic signs pointing to disease outside the cerebellum. In about half of patients, the neurologic findings precede discovery of the cancer, but the clinical picture is so characteristic that cancer should be suspected. In a subset of patients with gynecologic cancers (ovarian, uterine, fallopian tube, breast), an antibody (anti-Yo) reacting with cerebellar Purkinje cells and with the underlying tumor allows a definitive diagnosis to be made before the tumor is discovered. Pathologic changes consist of loss of cerebellar Purkinje cells with or without lymphocytic cuffing of blood vessels in the deep nuclei. Cerebellar dysfunction is also caused by cerebellar or leptomeningeal metastases and by Listeria meningitis or progressive multifocal leukoencephalopathy. In alcohol-nutritional cerebellar degeneration, truncal and lower extremity ataxia is prominent, but nystagmus, dysarthria, and upper extremity ataxia are mild or absent. Cerebellar dysfunction associated with viral infections (varicella, infectious mononucleosis) or with chemotherapy (5-fluorouracil, cytosine arabinoside) may mimic paraneoplastic cerebellar degeneration. Paraneoplastic cerebellar degeneration usually runs a subacute course and then stabilizes or occasionally improves with successful treatment of the tumor. Carcinoma-associated retinopathy is characterized by rapid onset of blindness caused by retinal degeneration, usually of photoreceptors, and is associated with antibodies that recognize the retinal antigen recoverin. Optic neuritis, which does not differ clinically in any way from the idiopathic disorder, has also been described in some patients with underlying neoplasms. Opsoclonus (saccadic conjugate involuntary movement of the eyes), also called "saccadomania," is often a paraneoplastic disorder. In adults, about 20% of patients with opsoclonus probably have an underlying cancer, usually gynecologic or lung cancer, that is sometimes associated with the anti-Ri antibody. Except when this autoantibody is present, paraneoplastic opsoclonus cannot be clinically distinguished from opsoclonus caused by metabolic or structural abnormalities of the brain stem or cerebellum. The course is subacute, with progressive painless asymmetrical lower motor neuron weakness of the legs and arms. Some patients complain of sensory symptoms, but sensory loss is mild or absent despite profound weakness. Examination may also demonstrate extensor plantar (Babinski) reflexes, indicating that corticospinal tracts are also involved. Sometimes the anterior horns and ventral nerve roots are inflamed, in addition to demyelination in the white matter of the spinal cord. The clinical course is different from most remote effects of cancer in that some patients improve spontaneously, independently of the course of the underlying lymphoma. The etiology is unknown, but a similar disorder in mice with lymphomas appears to be caused by a retrovirus. Typical amyotrophic lateral sclerosis is rarely paraneoplastic, but primary lateral sclerosis, which is a variant of motor neuron disease that affects only the corticospinal tracts and hence causes weakness and spasticity, may complicate breast cancer. Clinically, rapidly ascending sensory and motor loss is present, usually to the mid-thoracic levels; the patient becomes paraplegic and incontinent within hours or days. The neurologic symptoms often precede discovery of the neoplasm, and the illness is clinically and pathologically indistinguishable from idiopathic subacute necrotic myelopathy. The stiff-person syndrome is characterized by rigidity and spasms of muscles associated with antiamphiphysin antibodies and breast cancer. Most "stiff persons" do not have cancer, but they produce antibodies against glutamic acid decarboxylase that cause both diabetes and the neurologic disorder. Peripheral Nerves and Dorsal Root Ganglia Four clinical peripheral nerve disorders occur in association with cancer. Characteristic of carcinoma is subacute sensory neuronopathy marked by loss of sensation with relative preservation of motor power. The illness usually precedes appearance of the carcinoma and progresses over a few months, and the patient is left with moderate or severe disability.

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Anderson Porphyrias are due to deficiencies of specific enzymes of the heme biosynthetic pathway and anxiety 7 weeks pregnant order geodon 80 mg without a prescription, when clinically expressed anxiety 5 weeks pregnant buy geodon 40mg online, are associated with striking accumulations of heme pathway intermediates anxiety centre generic geodon 80mg. Most porphyrias are inherited anxiety nursing interventions geodon 40 mg visa, but other factors are important in determining their severity. These conditions are more prevalent and more often manifested in adults than are most metabolic diseases and are likely to be encountered by physicians in many disciplines. The three most common porphyrias differ considerably from each other and are managed very differently. Therefore, different mutations commonly occur in unrelated families with any given type of porphyria. Heme is synthesized in the largest amounts in bone marrow and liver, where it is used primarily to make hemoglobin and cytochrome P-450 enzymes, respectively. Additional pathway enzymes and cellular uptake of iron are important in regulating heme synthesis in erythroid cells. Porphyrinogens (hexahydroporphyrins) undergo autooxidation outside cells and are excreted primarily as porphyrins. Cutaneous photosensitivity occurs in types of porphyria in which porphyrins accumulate. Porphyrins are activated by long-wave ultraviolet light and generate oxygen radicals that damage the skin. Several of the "cutaneous porphyrias" are associated with similar skin lesions but differ considerably in terms of treatment and prognosis. Traditionally, porphyrias have also been divided into erythropoietic and hepatic types. Now that these disorders are well characterized, they are best classified in terms of their specific enzyme deficiencies. It is important to appreciate that the three most common types of porphyria that are likely to be encountered periodically by any physician differ markedly from each other with regard to major clinical manifestations, exacerbating factors, tests important for diagnosis, and effective therapies (Table 219-2). Because their features are so distinct, a feature learned about one of these porphyrias will not apply to the others. On the other hand, two of these conditions are prototypic: They share some important features with the other less common porphyrias, which should be evident from the brief descriptions of each of the porphyrias that follow. Lead poisoning and hereditary tyrosinemia can cause symptoms (abdominal pain, ileus, and motor neuropathy) that are strikingly similar to those of the acute porphyrias. In hereditary tyrosinemia, a deficiency of fumarylacetoacetase leads to the accumulation of succinylacetone (2,3-dioxoheptanoic acid). The enzyme is deficient in all individuals who inherit the mutant gene and remains fairly constant over time. Its prevalence in most countries has not been precisely estimated but may be most common (perhaps 5 per 100,000) in northern European populations. The erythroid-specific isoenzyme is encoded by exons 2 to 15; the erythroid promoter, which functions only in erythroid cells, is found immediately upstream from exon 2. The non-erythroid enzyme is encoded by exons 1 and 3 to 15; the non-erythroid promoter is immediately upstream from exon 1. However, if the mutation is in or near exon 1, only the non-erythroid isoenzyme is deficient. Therefore, in individuals with this type of mutation, enzyme activity is deficient in non-erythroid tissues but is normal in erythrocytes. The initial and last three enzymes (in red) are mitochondrial and the other four (in black) are cytosolic. Intermediates in the pathway include delta-aminolevulinic acid (an amino acid), porphobilinogen (a pyrrole), and hydroxymethylbilane (a linear tetrapyrrole). However, when the demand for hepatic heme is increased by drugs, hormones, or nutritional factors, the deficient enzyme can become limiting for heme synthesis. The suggestion that heme deficiency may occur in nervous tissue in these disorders is also unproved. Symptoms rarely occur before puberty and seldom if ever recur throughout adult life. Characteristically, attacks last for several days or longer, often require hospitalization, and are followed by complete recovery. Abdominal pain is the most common symptom, is usually steady and poorly localized, but may be cramping. Tachycardia, hypertension, restlessness, fine tremors, and excess sweating may be due to sympathetic overactivity.

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