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)     

Isolation and identification of chondroitin sulfates from the mud snail

Chondroitin sulfates were isolated from the mud snail. For the quantitative analysis of enzymatic digestion products of isolated chondroitin sulfates, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitinase ABC, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-D-galactose (ΔDi-OS), 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (ΔDi-6S) and 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (ΔDi-4S) were produced from the mud snail chondroitin sulfates. The analysis showed that relative proportion of ΔDi-OS/ΔDi-6S/ΔDi-4S was 58.7/3.1/38.2. The immunomodulating activity of chondroitin sulfate was examined by cell proliferation assay and these results suggest that it might be a immunosuppressant.     

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.     

Localization of ulnar neuropathy at the elbow using new stimulator for the inching test.

OBJECTIVE: To evaluate the usefulness of the TenElectrodes, a new stimulator for inching test, in the diagnosis and localization of ulnar neuropathy at the elbow (UNE). METHODS: Sixty-two ulnar nerves in 40 control subjects and 24 ulnar nerves in 23 patients with typical symptoms and signs of UNE were studied. The inching test of ulnar motor nerve using TenElectrodes was done along 8 cm across the elbow in the extended position. RESULTS: In the inching test of the control group, the mean segmental latency difference was 0.19+/-0.08 ms. Maximal latency difference over a 1 cm segment did not exceed 0.40 ms in any of the controls but exceeded 0.5 ms or more in all clinical UNE patients. In all UNE patients, the lesion sites were identified by the inching test using TenElectrodes: the retroepicondylar groove (54.2%), the humeroulnar arcade (29.2%), and dual compression (16.6%). CONCLUSIONS: TenElectrodes is a useful stimulator for the inching test in the diagnosis of UNE. The precise localization of compression was possible in all patients with UNE and the most common site was the retroepicondylar groove.     

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.     

Polymorphonuclear leucocyte motility in patients with severe burns

Chemotaxis, chemokinesis and cellular orientation were measured for unstimulated and 10(-7) n-formyl methionyl leucyl phenylalanine (F-met-leu-phe) stimulated polymorphonuclear leucocytes (PMNS) of nine patients with recent 10-80 per cent burns using a computer-assisted image analysis technique. The technique records PMN movement, as viewed with a phase-contrast microscope on videotapes, and then uses computer programs to calculate the speed and direction of up to 50 PMNS over a 5-min period. Orientation was determined visually. Cellular adherence was also measured by attachment methods. PMNS from burn patients were slower (av. speed 16.8 microns/min), responded less well to F-met-leu-phe (av. speed 20.9 microns/min, av. McCutcheon index 0.32), were less often oriented towards the chemoattractant (av. 39 per cent) and were more adherent (av. 50 per cent) than control cells (av. speed 21.8 microns/min; av. speed F-met-leu-phe 32.2 microns/min; McCutcheon index 0.61; oriented 59 per cent adherent; 16 per cent). Thus PMNS from burn patients orient less well, are significantly slower and have less directionality in response to a chemoattractant, and are more adherent suggesting activation.     

Idiopathic hypereosinophilic syndrome terminating as disseminated T-cell lymphoma

The authors describe a case of idiopathic hypereosinophilic syndrome (HES) terminated as a T-cell lymphoma in a 3-year-old girl. The clinical course was chronic and characterized by chronic eczema, persistent peripheral blood eosinophilia, organomegaly, interstitial lung change, and pericarditis. Postmortem examination demonstrated a disseminated T-cell lymphoma involving the inguinal lymph node, liver, lung, and kidney. The findings of the current case suggest a possibility that certain abnormalities in this case of idiopathic HES per se may have triggered the development of malignant lymphoma, and it may represent a transition of idiopathic HES into a T-cell lymphoma. Other possible sequences are discussed. The development of T-cell malignancy in idiopathic HES in a girl is quite an unusual presentation.