Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin

Study Objective . To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. Design . Randomized, double-blind, two-period, crossover study. Setting . University hospital clinical research unit. Patients . Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment. Interventions . Volunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later. Measurements and Main Results . Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording. Conclusions . Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.     

A case report of the limited form Wegener's granulomatosis]

The classical from of Wegener's granulomatosis (WG) is a necrotizing granulomatous angiitis that involves the upper and lower airways, and kidneys. A limited form of WG is characterized by pulmonary lesions identical to those of classical form WG without renal involvement. The authors report a case of limited form WG. A 58-year-old Japanese woman was admitted because of an abnormal pulmonary shadow. Pathological examination revealed granulomatous angiitis consistent with WG. No other organ involvement was found. The pulmonary shadow improved with cyclophosphamide therapy. The patient is now well and without evidence of exacerbation of the disease 18 month after the discharge.     

Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide

Quinidine, procainamide and disopyramide are antiarrhythmic drugs in the class 1A category. These drugs have a low toxic to therapeutic ratio, and their use is associated with a number of serious adverse effects during long term therapy and life-threatening sequelae following acute overdose. Class 1A agents inhibit the fast inward sodium current and decrease the maximum rate of rise and amplitude of the cardiac action potential. Prolonged Q-T interval and, to a lesser extent, QRS duration may be observed at therapeutic concentrations of quinidine. With increasing plasma concentrations, progressive depression of automaticity and conduction velocity occur. 'Quinidine syncope' (a transient loss of consciousness due to paroxysmal ventricular tachycardia, frequently of the torsade de pointes type) occurs with therapeutic dosing, often in the first few days of therapy. Extracardiac adverse effects of quinidine include potentially intolerable gastrointestinal effects and hypersensitivity reactions such as fever, rash, blood dyscrasias and hepatitis. Procainamide produces electrophysiological changes that are similar to those of quinidine, although Q-T interval prolongation with the former is less pronounced at therapeutic concentrations. Hypersensitivity reactions including fever, rash and (more seriously) agranulocytosis are associated with procainamide, and a frequent adverse effect requiring cessation of therapy is the development of systemic lupus erythematosus. Of the 3 drugs, disopyramide has the most pronounced negative inotropic effects, which are especially significant in patients with pre-existing left ventricular dysfunction. As with quinidine, unexpected 'disopyramide syncope' at therapeutic concentrations has been described. Anticholinergic side effects are common with this drug and may require cessation of therapy. Disopyramide therapy may unpredictably induce severe hypoglycaemia. Severe intoxication with the class 1A agents may result from acute accidental or intentional overdose, or from accumulation of the drugs during long term therapy. Acute overdose can result in severe disturbances of cardiac conduction and hypotension, frequently accompanied by central nervous system toxicity. Decreased renal function can cause significant accumulation of procainamide and its active metabolite acecainide (N-acetyl-procainamide), resulting in severe intoxication. Mild to moderate renal dysfunction is less likely to lead to quinidine or disopyramide intoxication, unless renal failure is severe or concurrent hepatic dysfunction is present. Management of acute intoxication with class 1A drugs includes gut decontamination with provision of respiratory support and treatment of seizures as needed. Hypertonic sodium bicarbonate, by antagonising the inhibitory effect of quinidine on sodium conductance, may reverse many or all manifestations of cardiovascular toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pathobiology of canine cyclic hematopoiesis (review)

Canine cyclic hematopoiesis (CH) was first described in Gray Collies as the lethal gray syndrome, and was subsequently shown to be a counterpart of human cyclic neutropenia (CN). The disease is characterized by a recurrent cyclic change in the levels of neutrophils and other blood elements at approximately 12-day intervals. It is caused by an autosomally recessive gene with pleiotropic effects or a CH gene which is closely linked to a gray color gene. The infectious insult on affected animals is periodic but its clinical and pathologic effects are continual and cumulative Affected dogs die after weaning and rarely survive over 6 months of age. There is evidence of immunoregulatory defects in these dogs. Reciprocal bone marrow transplantation indicates that the defect resides in the bone marrow, but the actual site and mechanism of the defect has not been established. The disease in Gray Collies represents a unique model system for studying the mechanism of cyclic hematopoiesis and hematopoietic regulation. Studies of the disease have made conceptual contributions toward understanding and treatment of human cyclic neutropenia.     

Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI.

Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI.     

Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild-to-moderate childhood asthma.     

Health-related quality of life in Taiwanese patients with bronchial asthma.

BACKGROUND AND PURPOSE: Health-related quality of life (HRQOL) is primarily an assessment of how domains of life are affected by health. This study investigated the factors influencing HRQOL of Taiwanese patients with bronchial asthma. METHODS: A cross-sectional study was conducted to assess the factors influencing HRQOL. The sample consisted of 242 outpatients with bronchial asthma. The Chinese language version of the St. George's Respiratory Questionnaire was used to measure HRQOL. Data were analyzed using simple regression and multiple regression. RESULTS: Age, marital status, level of education, asthma severity, peak expiratory flow, and previous hospital admissions were found to be predictors of HRQOL. Gender, duration of disease, and history of emergency visits were not correlated with HRQOL. The variables entered in the HRQOL model accounted for 17.4% of the total variance (adjusted R(2)). The regression coefficients indicated that the mean scores increased 7.68 in patients with moderate to severe disease severity, and increased 7.34 in patients with a history of hospital admissions. The mean scores decreased 7.60 in married patients. CONCLUSION: This study found that marital status, asthma severity, and history of hospital admissions were major predictors of HRQOL in Taiwanese patients with bronchial asthma.     

Retropharyngeal lymph node metastasis from olfactory neuroblastoma: a report of two cases

Olfactory neuroblastoma is a rare, malignant neoplasm arising from the olfactory epithelium. It has an aggressive biological behavior that is characterized by local recurrence, atypical distant metastasis, and poor long-term prognosis. The incidence of cervical lymph node metastasis in olfactory neuroblastoma is variable, and treatment modalities are controversial. Moreover, few reports have been published concerning retropharyngeal lymph node metastasis from olfactory neuroblastoma. We present two cases of olfactory neuroblastoma with retropharyngeal lymph node metastasis. In addition, we provided a review of the current literature regarding olfactory neuroblastoma and retropharyngeal lymph node metastasis from olfactory neuroblastoma.