EPISODE

When the actual temperature-decline-with-altitude is greater than 9.8°C/1000 m, the atmosphere is unstable, the Cj s become larger, and the concentrations of poUutants lower. As the lapse rate becomes smaUer, the dispersive capacity of the atmosphere declines and reaches a minimum when the lapse rate becomes positive. At that point, a temperature inversion exists. Temperature inversions form every evening in most places. However, these inversions are usuaUy destroyed the next morning as the sun heats the earth s surface. Most episodes of high poUutant concentrations are associated with multiday inversions. 

Vasoactive and Psychoactive Amines and Alkaloids Most compounds produciag hypertensive episodes are classified as amines and are found ia greatest coaceatratioa ia banana, plantain, tomato, avocado, piaeapple, broad beans, and various cheeses. Amines that are vasoactive iaclude dopamine [31-61-6], CgH N02 tyramine (11) histamine [31-43-6], tryptamine [61-34-1], C2QH22N2 noradrenaline [31-41-2], CgH NO and... 

Anticonvulsants or antiepileptics are agents that prevent epileptic seizures or modulate the convulsant episodes eflcited by seizure activity. Certain of these agents, eg, the BZs, are also hypnotics, anxiolytics, and sedatives, reinforcing the possibiUty of a common focus of action at the molecular level (1). 

There ate many classes of anticonvulsant agent in use, many associated with side effect HabiUties of unknown etiology. Despite many years of clinical use, the mechanism of action of many anticonvulsant dmgs, with the exception of the BZs, remains unclear and may reflect multiple effects on different systems, the summation of which results in the anticonvulsant activity. The pharmacophore stmctures involved are diverse and as of this writing there is htde evidence for a common mechanism of action. Some consensus is evolving, however, in regard to effects on sodium and potassium channels (16) to reduce CNS excitation owing to convulsive episodes. 

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

C = continuous I = intermittent, ie, over discrete intervals of time E = episodic, ie, nonrandom, the result of an event. 

Asthma affects 3—5% of the population and is one of the most common chronic illnesses (7—9). Both the frequency and severity of asthma appear to be increasing (10—13). Acute, severe asthma has the potential to be fatal. The disease may first appear ia childhood and iadividuals so affected can suffer recurrent episodes throughout their Hves or they may "outgrow" the condition at puberty. On the other hand, there is also adult-onset asthma. These people show no symptoms as children or as young adults, but suddenly develop symptoms later ia life. There have been many reports of bronchial infections preceding the appearance of asthma. However it is not known whether these infections contributed to the development of the disease or whether iadividuals who are already predisposed to asthma ate more likely to experience bronchospasms as a result of a bronchial infection (14). 

Intrinsic asthma, also called idiopathic asthma, usually develops in adulthood. In intrinsic asthma allergic factors are not demonstrable. Episodes of intrinsic asthma may be triggered by a variety of stimuli, eg, emotional state, exposure to cold air, or inert dusts. Both intrinsic and extrinsic asthmatics can be prone to exercise-induced attacks. Individuals who experience a combination of extrinsic and intrinsic asthmatic reactions have mixed asthma. Status asthmaticus refers to an especially acute life-threatening asthma attack which is resistant to normal treatments and which may require hospitalization in order to stabilize the patient. 

Depression is a common psychiatric disorder. The lifetime risk of developing a depressive episode is estimated to be as high as 8—12% for men and 20—26% for women (116). Depression, one of the most widespread of all life-threatening disorders, is almost always a factor in the mote than 30,000 suicides that occur annually in the United States alone (117). 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

Herpes Simplex. There are two types of herpes simplex vims (HSV) that infect humans. Type I causes orofacial lesions and 30% of the U.S. population suffers from recurrent episodes. Type II is responsible for genital disease and anywhere from 3 x 3 x 10 cases per year (including recurrent infections) occur. The primary source of neonatal herpes infections, which are severe and often fatal, is the mother infected with type II. In addition, there is evidence to suggest that cervical carcinoma may be associated with HSV-II infection (78—80). 

Balantidiasis in humans is manifest by chronic episodes of intermittent diarrhea and constipation, symptoms similar to those of amebiasis. The patient may also have abdominal pain, tenderness over the colon, anorexia, nausea, severe weight loss, and weakness. The disease may be fatal and, before the avakabihty of a treatment, was the cause of death in approximately 30% of infected individuals. 

Other P"Adrenoceptor Blocking Agents. Carteolol hydrochloride (Table 1) is also a Class II antiarrhythmic agent. In three separate studies in patients having angina pectoris, carteolol was considered effective as evidenced by a reduction in the frequency and severity of anginal episodes, reduction in the amount of nitroglycerin consumed, improvement of ECG parameters, or an increase in the duration of trea dmill exercise (42). 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

Clinical studies with Norplant attest to its high contraceptive efficacy and safety. The main reason patients request the removal of Norplant is unpredictable vaginal bleeding episodes followed by amenorrhea. The bleeding problem is an unavoidable sequela of progestogen-only contraception. 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

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