Ectopic

Automa-ticity. Special cardiac cells, such as SA and AV nodal cells, His-bundle cells, and Purkinje fibers, spontaneously generate an impulse. This is the property of automaticity. Ectopic sites can act as pacemakers if the rate of phase 4 depolarization or resting membrane potential is increased, or the threshold for excitation is reduced. 

Enhanced automaticity occurs in hypoxia, hypokalemia, hypercarbia, excessive sympathetic nervous system stimulation, or high concentrations of catecholamines. These conditions may lead to arrhythmias. Decreased automaticity may also lead to production of arrhythmias by enhancing ectopic activity in latent pacemakers (ectopic foci) or by altering conductivity and refractoriness in conduction pathways of myocardium. 

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

Propafenone. Propafenone hydrochloride, an arylketone, is stmcturaHy similar to the P-adrenoceptor blocking agents. It has been in use in the former West Germany since 1977 and was introduced in the United States in 1990. Its effects may result from a combination of weak calcium channel blocking, weak nonselective -adrenoceptor blocking, and sodium channel blocking activity. Propafenone is effective in treating supraventricular tachyarrhythmias, ventricular ectopic beats, and ventricular arrhythmias. It is the most frequendy prescribed medication for ventricular arrhythmias in Europe (32). 

Antiepileptics are used in neuropathic pain resulting from lesions to the peripheral (e.g., diabetes, heipes) or central nervous system (e.g., stroke). Such syndromes have been attributed to ectopic activity in sensitized nociceptors from regenerating nerve sprouts, recruitment of previously silent nociceptors, and/or spontaneous neuronal activity. This may result in sensitization... 

Causalgia is burning pain evoked by the activation of sympathetic efferent fibres. The likely mechanism underlying this syndrome involves ectopic expression of a-adrenoceptors on nociceptive afferents following peripheral injury or disease. 

Thus, our attention should shift from the concern of potential adverse effects to the health benefits imparted by hormonal contraceptives. The use of oral contraceptives for at least 12 months reduces the risk of developing endometrial cancer by 50%. Furthermore, the risk of epithelial ovarian cancer in users of oral contraceptives is reduced by 40% compared with that on nonusers. This kind of protection is already seen after as little as 3-6 months of use. Oral contraceptives also decrease the incidence of ovarian cysts and fibrocystic breast disease. They reduce menstrual blood loss and thus the incidence of iron-deficiency anemia. A decreased incidence of pelvic inflammatory disease and ectopic pregnancies has been reported as well as an ameliorating effect on the clinical course of endometriosis. 

Extrahypothalamic OX-B-like immunoreactivity, reminiscent to that of CRF, has been described in clustered GABAergic neuronal populations, in the lateral division of central nucleus ofthe amygdala, the bednucleus of the stria terminalis, and in the hippocampus. Moreover, ectopic expression of preproorexin mRNA in the gut, ependymal cells, neuroblastomas, and of orexin receptors in adrenal gland, cancer and hematopietic stem cells suggests yet unexplored roles of orexins as paracrine factors controlling blood-brain barrier, and tumor or stem cell function. 

Syndrome of inappropriate antidiuretic hormone is defined by water retention, dilutional hyponatraemia and decreased volume of highly concentrated urine. There are several causes which can result in SIADH, neoplasms ectopic secreting AVP, ectopic release of AVP by various diseases or drugs, exogenous administration of AVP, desmopressin, lysipressin or large doses of OT (iatrogenic SLADH). 

In addition, several other organs, like the heart, ovaty, amnion, chorion, decidua, testis, epididymis and prostate, have been reported to synthesize OT, suggesting a paracrine role for this hormone in these tissues. Ectopic AVP production by lung cancer cells or other neoplasms has been described in humans, leading to the syndrome of inappropriate antidiuretic hormone secretion. 

The first clue to a role for Wnt/(3-catenin-dependent signaling in vertebrate development came from overexpression studies in the classical embryonic system, the frog Xenopus loevis. When Wntl is ectopically expressed in cells that would normally contribute to the ventral embryo (i.e. the future belly), they instead adopt... 

Headache, nausea, increased heart rate, increase in systolic blood pressure, palpitations, anginal and nonspecific chest pain Nausea, vomiting, ectopic beats, tachycardia, anginal pain, palpitations, hypotension, dyspnea Anxiety, insomnia, tenseness, restlessness, headache, light-headedness, dizziness, nausea, dysuria, pallor... 

Ovarian enlargement, nausea, vomiting, breast tenderness, ectopic pregnancy, abdominal discomfort... 

Taking the contraceptive hormones provides health benefits not related to contraception, such as regulating the menstrual cycle and decreased blood loss, and incidence of iron deficiency anemia, and dysmenorrhea Health benefits related to the inhibition of ovulation include a decrease in ovarian cysts and ectopic pregnancies. hi addition, there is a decrease in fibrocyctic breast disease, acute pelvic inflammatory disease endometrial cancer, ovarian cancer, maintenance of bone density, and symptoms related to endometriosis in women taking contraceptive hormones. Newer combination contraceptives such as norgestimate and ethinyl estradiol... 

The device prevents uterine pregnancy but it does not prevent ovulation or ectopic (implantation of the fertilized egg outside of the uterus) pregnancy. 

Lucas, P. A., Laurencin, C., Syftestad, G. T., Domb, A., Goldberg, V. M., Caplan, A. I., and Langer, R., Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a polyanhydride delivery vehicle, J. Control. Rel. In Press. 

Bone morphogenetic proteins (BMPs) A family (eight or more) of secreted proteins with a variety of actions on bone many induce ectopic bone growth. 

A patient who recently recovered from a minor heart attack is suffering from periods of ectopic ventricular beats, originating from what is believed to be a small area of post-ischaemic fibrosis in the free wall of the left ventricle. 

Immunoreactive Forms of Circulating Parathyroid Hormone in Primary and Ectopic Hyperparathyroidism". J. Clin. Invest. (1974), 175-181. 

Various conditions such as perforated peptic ulcer, cholecystitis, common bile duct and intestinal obstruction, trauma to the abdomen inducing pancreatitis and ruptured ectopic pregnancy may cause an elevated serum amylase but the levels are usually not as high as those found in acute pancreatitis. Mumps and bacterial parotitis, which block the secretion of salivary amylase are associated with mild elevations of serum amylase. 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

In addition to changes within the nerve, sympathetic afferents become able to activate sensory afferents via as yet poorly characterised a-adrenoceptors. These interactions between adjacent sensory and autonomic nerve axons and between ganglion cells result in excitation spreading between different nerve fibres. These peripheral ectopic impulses can cause spontaneous pain and prime the spinal cord to exhibit enhanced evoked responses to stimuli, which themselves have greater effects due to increased sensitivity of the peripheral nerves. 

This peripheral activity may be a rational basis for the use of systemic local anaesthetics in neuropathic states since ectopic activity in damaged nerves has been shown to be highly sensitive to systemic sodium channel blockers. This too is probably part of the basis for the analgesic effects of established effective anti-convulsants that block sodium channels such as carbamazepine, although central actions are important and may even predominate. The precise actions of excitability blockers therefore remains hazy as does any clear basis for the effectiveness of antidepressants and other adrenergic agents in the treatment of neuropathic pain as both central and peripheral actions, including sympathetic effects are possible. 

---