A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up.

BACKGROUND: Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains unclear. METHODS: This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. RESULTS: Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. CONCLUSION: Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.

Extraction and phytochemical investigation of Calotropis procera: effect of plant extracts on the activity of diverse muscles.

CONTEXT: Calotropis procera (Ait.) R.Br. (Asclepiadaceae) is a shrub or small tree that grows wild in Egypt. Calotropis acts as a purgative, anthelmintic, anticoagulant, palliative (in problems with respiration, blood pressure), antipyretic, and analgesic, and induces neuromuscular blocking activity. Little research has been done to study the electrophysiological effects of this plant's extracts on cardiac, smooth, and skeletal muscle activities. OBJECTIVE: The present study was conducted to determine the phytochemical composition and the effect of the total alcohol extract of the shoot of the plant, which contains almost all of C. procera's cardiac glycosides, flavonoids, and saponins. Also, this study attempted to throw more light on the electrophysiological effects of the plant extracts on cardiac, smooth, and skeletal muscle activities and to clarify the mechanism(s) of their observed action(s). MATERIALS AND METHODS: The aerial parts of the plant were air dried and their ethanol extracts partitioned with successive solvents. Cardiac, smooth, and skeletal muscles were used in this study to investigate the physiological and pharmacological effects of the plant extracts from different solvents. The data were analyzed by paired t-test. RESULTS: The phytochemical investigation of Calotropis procera revealed the presence of cardenolides, flavonoids, and saponins. The effects of ethanol, n-butanol, and ethyl acetate (EtOAc) extracts were each evaluated on isolated toad heart and their mechanisms of action determined. Perfusion with 2 µg/mL ethanol, 0.2 µg/mL butanol, and 0.2 µg/mL EtOAc extracts caused a significant decrease in heart rate (bradycardia), significant increase in the force of ventricular contraction, and increase in T-wave amplitude. In addition, the effects of different extracts of the studied plant on smooth muscle and skeletal muscle were investigated in this study. The different extracts and latex of C. procera induced a negative chronotropic effect and decreased the heart rate (HR) of isolated toad heart. The different extracts increased the power of contraction of the duodenum (trace a). Pretreatment with atropine sulfate as a muscarinic receptor blocker abolished the stimulatory effect of the different plant extracts and latex of C. procera (trace b). DISCUSSION: The present data suggest that ethanol, butanol, and EtOAc extracts of Calotropis procera have negative chronotropism and positive inotropism. Verapamil could abolish the inotropic effect of ethanol as well as that of butanol and EtOAc extracts. Meanwhile, atropine did not abolish the observed negative chronotropic effect. The ethanol extract increased the power of contraction of rabbit duodenum, but atropine abolished this effect. It also decreased the skeletal muscle contraction; this effect could be through blocking of the nicotinic receptors. Butanol and EtOAc extract data for smooth and skeletal muscles are very close to those for the corresponding ethanol extract of the studied plant. The present data for C. procera indicate its direct action on the myocardium, its increase of smooth muscle motility, and its relaxation of skeletal muscle contraction. The chemical constituents could directly affect the cell membrane probably through receptors coupling to G proteins. They regulate the ion channel physiology as in the myocardium. CONCLUSION: The present data on the extracts of C. procera indicate a direct action on the myocardium, stimulatory effect on smooth muscle motility, and relaxant action on skeletal muscle contraction. Chemical constituents could directly affect the cell membrane probably through receptors coupling to G proteins. They regulate the ion channel physiology as in the myocardium.

Biochemical and morphological analysis of cell death induced by Egyptian cobra (Naja haje) venom on cultured cells

We investigated the in vitro process of cell death caused by Egyptian cobra venom on primary human embryonic kidney (293T) and mouse myoblast (C2C12) cell lines. The aim of these studies was to provide further information about triggering cell death, and suggest methods for eliminating unwanted cells, such as tumour cells. Both cell lines were treated with 10, 20, and 50 m g/ml of Egyptian cobra (Naja haje) venom in serum free media (SFM) and incubated for 8 hours. Total activities of the lactate dehydrogenase (LDH) and creatine kinase (CK) released in the culture during venom incubation were used as an indicator of the venom in vitro cytotoxicity. Cell injury was morphologically recognized and apoptosis determined by a Fluorescing Apoptosis Detection System and confirmed by staining nuclear DNA with DAPI. Our data clearly demonstrated marked cytotoxic effects and acute cell injury for both cell lines. Release of LDH and CK into the culture media induced by the venom correlates well with the morphological changes and extent of cell death. Mostly, these consequences were time and dose-dependent in both cell lines. The results obtained from this study indicated that cobra venom cause cell death by two different mechanisms: necrosis and induction of apoptosis. The apoptotic mechanism, accompanied by cell necrosis, mediated cell destruction of both tested cell lines; however, necrosis was predominant in the C2C12 cell line while apoptosis, in 293T cells. This unusual form of cell death induced by cobra venom may represent a combination of apoptosis and necrosis within the same cell. This is a first-hand investigation showing the apoptotic effects of N. haje venom at the cellular level. However, the contribution of the apoptotic pathway may be dependent on concentration and/or time of exposure to snake venom.(AU)

Changes in the arterial blood pressure, heart rate and normal ECG parameters of rat after envenomation with Egyptian cobra (Naja haje) venom.

1. The effect of Egyptian cobra (Naja haje) venom on the normal electrical activity of the cardiac muscles (ECG) and arterial blood pressure of envenomated rats were investigated in this study. 2. Rats were divided into three groups. The first group was injected im with saline and considered as control group. Rats of the second and third groups were injected IM with 0.02 micrograms and 0.04 micrograms cobra venom/gim b.wt, respectively. 3. Mean blood pressure (MBP), heart rate (HR) and four different ECG parameters (PR and QT intervals, R and T wave amplitudes) were measured over 1 h following envenomation. 4. The low dose (0.02 micrograms/g) of N. haje venom caused hypotension accompanied by an increase in the HR, whereas hypertension and bradycardia developed after injection of the high dose (0.04 micrograms/g) of venom. 5. There was a decrease in the P-R interval after administration of the low dose and prolongation of it after the high dose. The Q-T interval and R-wave amplitude were significantly increased after injection of both doses. T-wave amplitude was significantly elevated only after injection of the high dose. 6. The present results indicate that the Egyptian cobra (N. haje) venom significantly alters the arterial blood pressure and ECG parameters of envenomated rats. The suggests that impairment of the electrical activity of cardiac muscle may be one of the reasons why victims of cobra bite die.

The role of propranolol and atropine in mitigating the toxic effects of scorpion venom on rat electrocardiogram.

The effects of the scorpion Leiurus quinquestriatus (H.&E.) venom on electrocardiogram (ECG) parameters such as P-R and Q-T intervals and R and T wave amplitudes were investigated in anesthetized rats. Venom was administered intramuscularly (i.m.) at three doses (100, 200 and 400 micrograms/kg). ECG limb lead II was recorded for 4-h sessions. Because autonomic nervous system tone plays an important role in influencing ECG findings, another study was completed with concomitant pharmacologic autonomic nervous system blockade. Propranolol or atropine was injected 20 min before venom administration in two groups of rats. The results indicated that the venom has drastic effects on the electrical activity of the heart. The Q-T interval developed a dose-response relationship after venom administration. Propranolol abolished the toxic effects of the venom on P-R and Q-T intervals as well as on R wave amplitude, while atropine had no effect on the ECG changes produced by the venom.

Effect of scorpion Leiurus quinquestriatus (H&E) venom on rat's heart rate and blood pressure.

The effects of scorpion Leiurus quinquestriatus (H&E) venom collected from the South Sinai region, Egypt, on heart rate (HR) and mean arterial pressure (MAP) were studied after intramuscular administration of 3 different doses (100, 200 and 400 micrograms/kg) to anesthetized rats. The effects of adrenergic and cholinergic blocking agents on the venom-induced HR and MAP changes were also evaluated. In two groups of rats, propranolol or atropine were given before the venom administration. In the third group the venom was given before the injection of propranolol and atropine in combination. HR was measured by using a cardiotachometer coupler connected to an ECG coupler. MAP was calculated from the recorded arterial blood pressure (ABP) after catheterization of the left common carotid artery. Venom doses of 100 and 200 micrograms/kg produced tachycardia with a dose-response relationship, whereas 400 micrograms/kg evoked sinus tachycardia followed by bradycardia then tachycardia. MAP was elevated after the administration of each dose and reached its maximum value after 60 min with a dose-response relationship. Sinus, atrial and ventricular arrhythmias were observed from the recorded ECG during the time studied. This study revealed that the venom has pressor and depressor effects which are mediated through the autonomic nervous system. Propranolol reduced the stimulatory effects of the highest dose of the venom while atropine was effective in eliminating the depressor effect of the venom on HR. The arrhythmias induced by the venom were blocked by the injection of the two blockers and are assumed to be due to the release of catecholamines and acetylcholine.

Effect of scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat.

Egyptian scorpion venom was collected by electrical stimulation of the telson. Rats were injected with the lyophilized venom in 3 different doses (100, 200 and 400 micrograms/kg). Blood samples were drawn by heart puncture before and 4 h after venom administration. Serum was separated and collected for determination of glucose, blood urea nitrogen (BUN), creatinine, uric acid (UA), total proteins, cholesterol, sodium, potassium, calcium, inorganic phosphorus, alkaline phosphatase, aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), lactate dehydrogenase and creatine phosphokinase (CPK). Serum glucose, creatinine, GOT, GPT and LDH were increased significantly in all treatments. At the same time serum BUN and CPK were elevated significantly with a dose-response relationship. On the other hand, serum total proteins, uric acid, cholesterol, calcium and potassium were significantly decreased 4 h after administration of the 3 doses. These changes in clinical chemistry parameters are most probably related to the toxic effect of the venom on the target organs.