Time Course of Symptoms

Diagnosis If signs and symptoms spelled out above are noted in large numbers of geographically clustered patients, exposure to aerosolized ricin is the suggested cause. The rapid time course of severe symptoms and death would be unusual for infectious agents. Laboratory findings are nonspecific except for specific serum ELISA (enzyme-linked immunosorbent assay). Acute and convalescent sera (plural of serum ) should be collected. 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

Using paralytic shellfish toxins extracted from mass cultures of Bay of Fundy excavata, we have found the symptoms of poisoning and the time course of their appearance to be similar in Atlantic herring, American pollock, winter flounder, Atlantic salmon, and cod (10). 

Unlike the abrupt discontinuation study, severity and time course of withdrawal symptoms were similar for both short and long half-life agents. 

Time course of events during the alcohol withdrawal syndrome. The signs and symptoms that manifest earliest are tremor, anxiety, and insomnia as well as (in severe syndromes) hallucinations and seizures. Delirium tremens—with its associated delirium, hallucinations, and autonomic instability—develops 48-72 hours after alcohol discontinuation. 

CVST generally shows a subacute onset and course of symptoms. Clinical symptomatology is dependant on the cause, localization, extension and time of development of the venous occlusion. The leading symptom is headache in 70%-90% of all cases... 

These studies show that it is possible to predict the time course of drug effects in vivo in situations in which complex homeostatic control mechanisms are operative. As such, they form the basis for the development of an entirely new class of pharmacokinetic-dynamic models. These models are important for the development of new drugs and the application of such drugs in clinical practice. For example, on the basis of this kind of model, it becomes possible to predict whether withdrawal symptoms will occur on cessation of (chronic) drug... 

What is further missing are longitudinal studies on children allergic to A. alternata and C. herbarum, epidemiologic studies and a sufficient number of well-documented case histories to draw conclusions about the typical symptoms and time course of the mold-allergic patient. 

Single Intramuscular Doses. BZ doses of 5.0-6.4 pg/kg were used in 15 subjects. These subjects were treated at various times with the antidotes mentioned above. The time course of action of the drug by this route was similar to that by Intravenous injection in fact, more symptoms were reported with this route, but this may have been due to differences in the completeness of reporting The time course was approximately as follows ... 

An alternative in the diuretic-resistant patient is the use of continuous infusions of loop diuretics rather than bolus diuretic therapy. Such infusions can also be given with a small volume of hypertonic saline, with good effect (39). The reasons why continuous infusions of loop diuretics work when bolus doses have failed may relate to a more efficient time-course of diuretic delivery and/or less activation of the renin-angiotensin system (40). Furosemide and torasemide may be the safest loop diuretics to be given as infusions, in that infusion of bumetanide has been associated with severe musculoskeletal symptoms (41). 

Fig. 1 shows the time courses of growth and decline, both for SARS-CoV as well as its antibody to 351 sera of SARS cases that were only identified by clinical symptoms. Comparing with antibody detection, this technique also represented more satisfactory method for early diagnosis of SARS. 

The time course of poisoning is dependent on the type of agent, the dose incorporated, and the route of exposure. Symptoms appeared minutes after inhalation of nerve agents and minutes to hours after incorporation of OP pesticides. Death can be observed (without treatment) within minutes after nerve agent inhalation and within hours to days after OP pesticide exposure. Description of the course of poisoning with OP and nerve agents can be found in many publications, either national or international, and it is mentioned in various different publications (B29, Ml, M2, LI5, and others). 

Time Course of Inhibition. After very large amounts of nerve agent (multiple LD50s [ie, multiples of the dose that is lethal to 50% of the exposed population]) are placed on the skin, signs and symptoms occur within minutes, and inhibition of blood ChE activities occurs equally quickly. However,... 

A 56-year-old man taking lithium earbonate 400 mg three times daily for a bipolar disorder was admitted to hospital with bronchitis. He was started on levofloxacin 300 mg daily, and within 2 days was noted to have developed gait ataxia, dysarthria, coarse tremor, dizziness, vomiting, and confusion. Lithium toxicity was suspected, and because of the time course of the symptoms, an interaction with levofloxacin was considered responsible. Serum-lithium levels were found to have risen from 0.89 mmol/L (measured 2 weeks previously) to 2.53 mmol/L, and a reduction in his renal function was noted. Both drugs were stopped and the patient recovered over the following 4 days. His lithium level was found to be 1.12 mmol/L at that time. ... 

Some patients report different patterns of symptoms in response to individual foods or increasing doses of the same food. The time course of... 

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