Pharmacokinetic-pharmacodynamic information regarding warfarin is used to produce a predictive model based on the idea that pharmacodynamic variability is more important than pharmacokinetic variability in the overall dose-response variability to warfarin. A modification of the maximum effect model is tested on a group of patients initiating oral anticoagulation with warfarin. Results indicate that the model can account for at least half of the total variation in maintenance doses observed (sample coefficient of determination, 0.53) and offer the physician a framework for dose requirements at the onset of therapy. The basic prediction equation is as follows: Maintenance dose = (11/international normalized ratio)-1, with a coefficient of correlation of 0.73 (95% confidence limits, 0.46-0.88). Application of this model may improve on the traditional empiric approach to warfarin dose adjustment.
Herpes gestationis is a rare disease in pregnancy. A 35-year-old G3P2 presented during her third trimester with erythematous pruritic papular eruptions. Direct immunofluorescence of a skin biopsy confirmed the diagnosis of herpes gestationis. The patient responded well to predniosolone treatment.
A typical case of chronic pericardial effusion resulting in cardiac tamponade is presented. A pericardiocentesis was done for diagnosis and drainage, followed by a pleuro-pericardial window as definitive therapy. The minimal cumulative dose expected to produce pericardial disease is about 4000 rads, and the disease usually manifests within 12 months of such radiation exposure, as in this patient. It is concluded that for symptomatic pericardial effusions, available evidence justifies a subtotal pericardiectomy, a window procedure being reserved to tide over ill patients as in this patient. No strong evidence exists for the efficacy of steroid therapy; such therapy is reserved for asymptomatic mild effusions, which may also resolve spontaneously.
We review our experience with 27 cases of pulmonary and meningeal cryptococcosis at the University Hospital, (Kuala Lumpar, Malaysia) where this is the most common cause of adult meningitis in patients without debilitating illnesses. Of the 27 cases analysed, six presented primarily with pulmonary symptomatology which usually were mainly cough, chest pain and low grade fever. The rest presented with primarily central nervous system (CNS) symptomatology of which headaches and fever were the most consistent symptoms although a third of these patients also had pulmonary lesions noted on chest radiographs. Treatment in all cases was with amphotericin B and 5-fluorocytosine and usually till a total cumulative dose of 1.5 g of amphotericin had been reached (an average of 10 weeks). Primary pulmonary presentations, if symptomatic, were treated as per CNS cryptococcosis due to the high likelihood of CNS dissemination. Incidental pulmonary cryptococcoma found on routine chest radiographs were confirmed by biopsy under ultrasound or fluoroscopy guidance and booked for surgical resection. Death usually occurred early in patients who presented late. Once patients responded to therapy, mortality was usually avoided. The only cause of morbidity in survivors was visual impairment or blindness, and this was attributed mainly to intracranial hypertension with residual deficits determined by the measures taken to lower intracranial pressures. Our experience suggests that: (i) symptomatic patients should have combination therapy with 5-fluorocytosine and amphotericin B till at least a cumulative dose of 1.5 g amphotericin B is reached irrespective of whether they have primary CNS or pulmonary symptomatology; (ii) non-symptomatic pulmonary cryptococcoma could be treated primarily by surgical resection; (iii) visual failure or papilloedema should be treated aggressively; and (iv) prognosis is good with adequate therapy and early presentation.
To evaluate the effects of simple compensated fixed-dose iodine-131 therapy for thyrotoxicosis, the long-term results for 74 patients treated with a fixed dose of iodine-131 ranging from 5 to 12 mCi (185 to 444 MBq) were evaluated in the first 2 years of a trial. The dose selected was loosely based on the gross size of the thyroid gland. Routine antithyroid drug therapy was given for a minimum of 3 months after iodine-131 therapy. The mean (+/- SD) duration of follow-up was 74.5 +/- 42 months. The results indicated that roughly 25% of patients treated in this way will become hypothyroid after 5 years and that 85% are cured (need no further therapy during the follow-up period) using a single dose of iodine-131. Of those cured using a single iodine-131 dose, 81% were no longer receiving drugs after 6 months and 85% after 1 year. Such a regimen seems currently to be among the best available where prolonged periods of medication-free euthyroidism after therapy are sought.