By Z. Dan. Greenleaf University.

They are consequently only found in low concentrations (100 pmol/g) and after acting are broken down by peptidases into fragments that cannot be re-used buy generic avapro 300 mg line diabetes symptoms high sugar levels. It is perhaps not surprising that they have a supporting rather than a primary role best avapro 150 mg diabetes symptoms risks. In between the above two extremes are the monoamines (1±10 nmol/g) which are preformed and stored in terminals but at much lower concentrations than the amino acids and when released are removed primarily by reuptake for re-use, or intraneuronal metabolism to inactive metabolites. Those like the amino acids while having high affinity for their receptors have low potency while the peptides found at much lower concentration have high potency but low affinity. As guidelines they provide a reasonable scientific framework of the type of investigations that must be undertaken to establish the synaptic role of a substance. As rigid rules they could preclude the discovery of more than one type of neurotransmitter or one form of neurotransmission. Nevertheless, the criteria have been widely employed and often expanded to include other features which will be considered as subdivisions of the main criteria. This does not mean it cannot have an important function in other areas such as the mesolimbic system and parts of the cerebral cortex where it is present in much lower concentrations. Glycine is concentrated more in the cord than cortex and in ventral rather than dorsal grey or white matter. Section of dorsal roots and degeneration of afferent fibres produces a reduction in glutamate and substance P which can then be associated with sensory inputs. Intrinsic neurons can also be destroyed through overactivity caused by kainic acid injections. Excessive firing of a neuron may be controlled by activating a feedback inhibitory system or evoking presynaptic inhibition. Indeed the distinct patterns of distribution of ascending monoamine pathways from brainstem nuclei could probably be considered as adequate evidence alone for their neurotransmitter role. Unfortunately, although it may be possible to show the presence of a substance and some effect when it is applied directly to neurons its release may not be measurable for technical reasons. This is even more true if one strives for the ideal of demonstrating the release of an endogenous substance by physiological stimuli. Those with slow background effects will probably not be released in large amounts. For such substances we require a measure of their utilisation, or turnover, over a much longer period of time. Recordings are made either of neuronal firing (extracellularly, A) or of membrane potential (intracellularly, B). The proposed transmitter is applied by iontophoresis, although in a brain slice preparation it can be added to the bathing medium. In this instance the applied neurotransmitter produces an inhibition, like that of nerve stimulation, as monitored by both recordings and both are affected similarly by the antagonist. Thus the value of this criterion depends very much on the rigour with which it is applied and on its own is no more or less important than any other approach. Unfortunately such a detailed analysis is presently only applicable to relatively simple systems with restricted innervations. The use of antagonists is absolutely vital but even they can give false positives. On that basis every substance mentioned already and to be discussed further could be called a neurotransmitter. If, however, the response they set up (transmit) has no reasonably quick and recordable effect, i. There is no room within the definition for nitric oxide, the prostaglandins and steroids mainly because they are not released in a controlled manner by neuronal activity and only the last are preformed. Clearly, it is more important to distinguish between the different effects that a substance can produce when released from a nerve than to worry about what it is called. Nevertheless, it is unfortunate that the word neurotransmitter will inevitably be associated with the actual transmission of activity from one neuron to another and yet most of the substances we will be discussing do not actually do that. They do this using a combination of electrical signals (action potentials) and chemical signals (transmission). However, even the chemical signal has to be transduced to an electrical signal (the synaptic potential) in order to continue the process of communication from one neuron to another.

See neurological cheap 150mg avapro overnight delivery diabetes prevention news, 331–334 opioids and buy generic avapro 150mg diabete tipo 02, 297 also Receptors (Drug) nutritional, 323, 336–339 prednisone and, 1353 for opioids, 986 renal, 324 Adult Children of Alcoholics, 36–38, Agonists, 63, 1218–1219. See also respiratory, 322 176–177 Antagonists; Receptors (Drug) consumption per capita, 40–41 Adulteration of drug tests, 460–461 amantadine as, 106 creativity and, 358, 359 1824 Vol. See Wernicke-Korsakoff chlordiazepoxide as, 255 history of, 77–86 syndrome community-reinforcement approach, homelessness and, 613–618 Alcoholic cirrhosis. See Cirrhosis 1258–1259 imaging techniques and, 624 Alcoholic Control Act (Canada), 218 history of, 1123–1125 Italian use of, 670 Alcoholic dementia. See Dementia, alcohol- non-medical detoxification, 1246–1248 Jews and, 672–673 induced outpatient vs. See Liver enzymes sales, 41 antisocial personality disorder and, 138, Altered states of consciousness, 358, sensitizing agents (See Antidipsotropics) 327 587–588 temperance movement (See Temperance anxiety disorders and, 328–329 Amanita muscaria. See Fly agaric movement) benzodiazepines and, 177 Amantadine, 106, 1159, 1170–1171, 1254, treatment for abuse (See Alcoholism chronic, 102 1347 treatment) costs of, 42 Amazonian region, 266, 267 withdrawal from (See Alcohol withdrawal) craving theories of, 355 Ambien. See research and, 1276–1277 family violence and, 525–529 American Academy of Addiction Alcohol- and drug-free housing, 67–70, 585 genetics and, 36–37, 232–233, 1323 Psychiatry Alcohol abuse. See Phencyclidine Oriental Medicine, 1224 iatrogenic addiction and, 901 Angina pectoris, 1352 American Association of Advertising vs. See Peyote American Bar Association, 698, 1125 methamphetamine seizures, 117 Anhedonia, 112, 129, 224 American Board of Psychiatry and neurological complications from, 335 Anheuser-Busch Corp. See Amobarbital hallucinogens, 1024–1025 Harrison Narcotics Act of 1914 and, Anabolic steroids, 122–128, 123, 125 intracranial self-stimulation, 995–996 816–817 adolescents and, 35–36 learning factors, 996–1002 medical reforms and, 883–884 carcinogenicity of, 220 physical dependence and, 985–986 physician addiction and, 630 chemical structure of, 124 self-administration, 987–988, 993–994, treatment policy and, 1125 Anadrol. See Oxymetholone 1318–1319 on triplicate prescription, 1268 Analgesics, 128–129, 257, 829–832, 830. See Twelve step See American Psychiatric alcohol as, 336–337 programs Association buprenorphine as, 206, 828 Anorectic agents, 129 American Psychiatric Association. See also caffeine in, 210, 211 amphetamines as, 111, 385 Diagnostic and Statistical Manual cannabis as, 706 caffeine in, 210, 211 of Mental Disorders clonidine as, 263 iatrogenic addiction and, 901–902 on alcohol-related disorders, 399 comparison of, 831 Anorexia, 130 on benzodiazepines, 1019–1020 Dover’s powder, 416–417 Anslinger, Harry J. See Disulfiram American Psychological Association, 481 pain measurement and, 827–828 Antagonists, 134–135, 1219. See also American Public Health Association, 246 during pregnancy, 893–897 Agonists; Receptors (Drug) American Society of Addiction Medicine, stepwise treatment plan using, 257 for adenosine, 214–215 107–108, 933–934 Anaphylaxis for alcoholism, 1252 American Temperance Society, 1077, 1078 drug-induced, 105–106 as antidote, 136–137 American Temperance Union, 1360 immunoglobulin E and, 104–105 atropine as, 183 American Tobacco Company, 1093–1094 Anascha. See also specific for buprenorphine, 206–207 Aminergic neurotransmitters, 777–779 countries and regions, e. Greece, clonidine as, 262 Amino acid neurotransmitters, 777–779 ancient competitive (See Competitive antagonists) Aminorex, 1366 alcohol use in, 77–79, 164–165 for dopamine, 228 Amitriptyline, 439 betel nut use in, 183 flumazenil as, 941 Amnesia, alcohol-induced. See Wernicke- cannabis use in, 221, 702 for heroin, 596, 1182 Korsakoff syndrome drug policies and, 882–883 memory and, 711 Amobarbital, 108–109 opium use in, 813 for methadone, 715 Amotivational syndrome, 109–110, 227, An Ancient Physician’s Legacy to His for morphine, 743 293 Country, 416 naloxone as, 751, 802, 804 Amphetamines, 110–114, 465–466 Andean region, 265–266, 267, 372–373. See also as designer drug template, 384 dissociative (See Ketamine; Phencyclidine) specific agents, e. See Intravenous route of amphetamines for, 111 for anxiety, 139–140 administration conduct disorder and, 347 for cocaine addiction, 271, 1169, 1170, Arts. Vincent’s Hospital, 1246–1247 Antidiarrheals, 805, 820–821 Second Edition, 108 Automobile accidents. See Addiction Severity Index Autonomic effects of hallucinogens, 590–591 paregoric, 835–836 Availability, regulation of, 683–685 Asia, 142–146, 143. See Nortriptyline alcohol and, 80, 233 Aversion therapy, 238, 1227–1229, 1152–1153 betel nut use in, 182–183 disulfiram as, 410–412, 970, 1152 1257–1258. See Zidovudine Antineoplastic agents, 220 alcohol and, 254 Antipsychotics, 137, 771 Aztec civilization cultural considerations for, 505 beer use in, 77–78, 80–81 chemical structure of, 137 for cocaine addiction, 1170, 1254 Aspartate, 777–779 chocolate use in, 255–256 elderly, alcohol and, 60–61 Aspirin. See also Analgesics peyote use in, 845 for hallucinations, 586 with alcohol, 59, 60 for schizophrenia, 1016 for pain, 829–831 poisoning, 448 B withdrawal from, 1353 Antisocial personality disorder, 137–139, propoxyphene used with, 937 Bcells. See Addicted babies aggression and, 525–526 933 Babor, Thomas, 399 alcoholism genetic link, 53 Assertiveness training. See Boosting Alcohol suicide and, 1064–1066 Problems Associated with the Use of Consciousness Concerning Health of Anxiety disorders, 139–140.

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However cheap avapro 300mg on line managing your diabetes care, they all share a common theme: that disruption of some aspect of monoaminergic transmission in the brain is a causal factor in depression best avapro 150 mg diabetes insipidus while pregnant. It is remarkable that, although this theory is often challenged, it has not yet been replaced by a validated alternative and, to this day, central noradrenergic and/or serotonergic systems are primary targets for all established antidepressant drugs. One is to lookfor the neurobiological basis of depression in human subjects and animal models of this condition. The second is to investigate the pharmacology of established antidepressant agents to see whether they consistently augment some, and ideally the same, neurobiological targets in the brain. For obvious reasons, the majority has looked for changes that might affect monoamine function and so the following sections concentrate on these neurotransmitters. For instance, it is not at all certain that neurochemical changes in the plasma or urine give any reliable indication of what is happening in the brain. Measurements in post-mortem brain tissue do not have this problem but the unavoidable delay in collecting tissue samples intro- duces another. Confirmation of the diagnostic status of the subjects is often difficult (especially retrospectively) and any drug treatments they had taken could distort the results. So far, evidence for abnormal peripheral (Elliott 1992) or central (Horton 1992) monoamine function in depression is equivocal, and no consistent biochemical markers have emerged to provide a firm linkbetween the two (Table 20. However, this abnormality is now believed to be associated with a deficit in control of behavioural impulsivity, rather than depression. Evidence for a linkbetween monoaminergic transmission and the therapeutic effects of antidepressant agents is more convincing. Depletion of noradrenaline stores (achieved by administration of the noradrenaline synthesis inhibitor, a-methyl-p-tyrosine) causes a resurgence of depression in patients who are in remission following treatment with antidepressants that selectively target noradrenergic neurons. However, patients who respond to antidepressants that act primarily on serotonergic neurons are unaffected (Delgado et al. It seems that the therapeutic effects of different anti- depressants could well rest on augmenting particular components of central monoamine transmission, whether or not depression itself is explained by a deficit in the functional output of these neurons. One is to provide a behavioural model that can be used to screen potential antidepressant treatments. For this, the behaviour does not have to be an animal analogue of depression: all that is needed is for it to be consistently prevented by established antidepressant agents (i. A second objective is to produce behavioural changes in animals that are analogous to depression so that the model can be used to discover its neurobiological cause(s). This is a far more demanding problem and its success rests on satisfying at least three criteria (see Willner 1984): face validity (i. Procedures that have been suggested as models of depression and used to lookfor neurochemical changes that parallel the onset of the behavioural change, as well as to test how antidepressants affect the behaviour, are listed in Table 20. Those that have been used most, either as a drug screen or in research into the neurobiology of depression, are as follows. These changes echo many of the problems experienced by depressives (disruption of appetite and sleep patterns and cognitive deficits). Also, as in many depressed patients, the concentration of plasma corticosteroids is increased in rats after olfactory bulbectomy (see later). This pattern of changes suggests that bulbectomy disrupts links between limbic areas of the brain and the hypothalamus. Its validity as a model of depression is supported by findings that all physiological and behavioural changes resulting from bulbectomy, that have been reported so far, are normalised by antidepressants from different generic groups. Subsequent work has concentrated on rats and mice, which show a similar behavioural response. Whether or not learned helplessness really is an analogue of depression remains controversial (Maier 1993). Nevertheless, escape deficits in rats are prevented by pretreatment with antidepressants from different generic groups. One of the earliest and most consistent findings with this model was a marked depletion of noradrenaline stores in certain brain regions, particularly the cortex, hippocampus and hypothalamus, of mice that have been exposed to inescapable shock.

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It has been widely used in the treatment of cacoplastic growths buy generic avapro 300 mg on line diabetes symptoms pathophysiology, and glandular indurations of a scrofulous character effective avapro 150mg diabetic kit, also of warts, small tumors, and incipient cancers of different varieties, and goitre. Therapy—It has been used extensively by all physicians in the treatment of cancer. It is claimed to exercise an abortive influence over incipient cancer, and to retard the progress of more advanced cases. In extreme cases it will remove the fetor, retard the growth, and materially prolong the life of the patient. It should also be kept in contact with the parts externally or injected into the structures. Epithelioma, condylomata, and all simple cancerous growths should be treated with it. He used a teaspoonful in the structure at once, giving the remedy internally, in fifteen-drop doses, with the same quantity of echinacea. Jones injected from twenty to sixty drops of thuja into a rectal cancer every second day, and also where there was a cauliflower variety of cancer of the uterus. Thuja is given internally for cancer, and for the pains of cancer it is applied externally, when possible, occasionally with good results. Thuja certainly exercises a direct influence upon the glandular structures and function. In what manner this influence is exercised is unknown, but in any disease that involves the gland, this remedy must be considered, and if there are no contraindications it can be tried, and in many cases as with the ductless glands, it seems to act in a direct manner. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 433 Thuja is directly indicated, first, as a peculiar alterative, in improving diathetic conditions of the blood. Again, it acts directly upon abnormal growths-perversions, such as peculiar conditions of the cell structure of the skin, and other external structures. It exercises a specific influence upon catarrhal discharges, correcting the glandular faults that are to blame for such a condition wherever they may be. It is specific to urinary irritation in aged people especially; also in childhood. Andrews uses thuja in chronic diarrheas, and in the treatment of ulceration of the bowels. In a bad case of polyuria with great sensation of debility and weakness of the entire sexual apparatus and some loss of sexual strength, a man of 65 was given five drops of thuja every two hours with complete success. Thuja is an important remedy in the treatment of spermatorrhea, especially if from exhaustion from over-indulgence, or from masturbation. In those cases in which the mind is seriously depressed by the physical condition, it is of especial service, as it stimulates the nerve forces and delays the discharge until, by general improvement of the entire nervous system, the condition is restored. The influence of the agent will be enhanced by a combination with avena sativa, saw palmetto, or staphysagria, in cases of this character, when Thuja should be given in doses of from two to ten drops, four or five times daily. As an external application Thuja produces at first a sensation of smarting or tingling when applied to open sores or wounds and it is usually best to dilute it with one, two or four parts of water, or to combine the non- alcoholic extract with an ointment base in the above proportion. This constitutes an excellent mildly antiseptic and actively stimulating dressing to indolent, phagedenic or gangrenous ulcers. It is of much service in bed sores and in other open ulcers dependent upon local or general nerve exhaustion. In chronic skin diseases of either a non-specific or specific character, it Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 434 is a useful remedy. Vegetations of all kinds, especially those upon mucous surfaces, will yield to it readily. A small dose internally four or five times daily, with the application of fluid hydrastis in a spray, will quickly retard or remove such abnormal growths. It is also applicable to sloughing wounds, and to phagedena of the venereal organs. It causes gangrenous surfaces to dry without hemorrhage or other discharge, destroys offensive odors and influences granulation. Recent reports have been made concerning the very beneficial action of thuja on papilloma of the larynx and affections of that character in the post nasal region. Moreau Brown has reported a number of cases satisfactorily treated with this remedy. The same writer uses this agent in the treatment of growths in the posterior nares.

Staging laparotomy lymphomas is somewhat controversial and difficult safe avapro 300mg dka diabetes in dogs, if not impossi- ble purchase avapro 150 mg line diabetes symptoms swollen feet, to accomplish in the latter half of pregnancy because the large uterus obstructs the operating field (Bloss and Miller, 1995). For early stages of lymphomas in the first half of pregnancy, several options are avail- able. Obviously, therapeutic abortion is one consideration, although it is not always nec- essary. Modified radiotherapy can be utilized if done at a significant distance from the shielded pelvis, i. If chemotherapy is deemed necessary, it is best to wait until after the first trimester. For patients with early-stage disease during the latter half of pregnancy, one reason- able option is simply to wait until after delivery to initiate therapy, especially if the patient is asymptomatic. Chemotherapy after the first trimester causes little known risk to the fetus except for pancytopenia and mild to moderate growth retardation. For patients with advanced disease, early treatment is obviously much more of a concern. Some physicians recommend therapeutic abortion if the advanced-stage lymphoma is diagnosed early in pregnancy (Jacobs et al. Special considerations 145 In a review of 15 pregnancies among women with Hodgkin’s disease (Jacobs et al. One patient developed a subdiaphragmatic relapse, and her treatment was delayed until after delivery. These data suggest that the prognosis for Hodgkin’s disease during preg- nancy is reasonably good for the mother. Nineteen pregnancies (reported in 15 publications) are published with first-trimester exposure to chemotherapeutic agents for treatment of lymphomas. Of these 19 pregnan- cies, 15 (79 percent) resulted in normal infants (three were exposed to mechlorethamine, two to thiotepa, and 10 to vinblastine). Another patient who received chlorambucil delivered an infant with unilateral renal agenesis. One patient who received procarbazine gave birth to an infant with multiple hemangiomas. Another patient who received polydrug therapy dur- ing pregnancy had an infant with an atrial septal defect (Jacobs et al. Melanomas Melanomas are one of the more common cancers that occur during pregnancy, with approximately three per 1000 deliveries (Gilstrap and Cunningham, 1996; Smith and Randal, 1969; Yazigi and Cunningham, 1990). It is important to note that melanoma is the tumor type with the highest risk to metastasize to the placenta and fetus (Anderson et al. Pregnancy does not seem to affect the growth or prognosis of melanoma, although pregnancy is associated with an increased level of melanocyte-stim- ulating hormone (Gilstrap and Cunningham, 1996; Holly, 1986; Yazigi and Cunningham, 1990). There was no difference in survival of 58 pregnant women with melanoma com- pared to nonpregnant controls with melanoma (Reintgen et al. Treatment usually comprises surgical resection, with or without lymph node dissection. A variety of chemotherapeutic agents are used, but their success rate is poor, with little success whether chemotherapy is given as adjuvant or primary therapy in metastatic disease. Other nongenital cancers Other nongenital types of cancer, such as colorectal carcinoma, gastric carcinoma, pan- creatic or hepatic cancer, and sarcoma, are rare during pregnancy (Gilstrap and Cunningham, 1996; Yazigi and Cunningham, 1990). Treatment during pregnancy is similar to that of nonpregnant women, with certain chemotherapeutic and radiation limitations as consideration for the pregnancy (as mentioned above). If the patient is in the first trimester, therapeutic abortion should be considered an option. In the latter half of pregnancy, early delivery followed by treatment is a prudent option. As previously mentioned, chemotherapy carries little known risk, other than fetal growth retardation, when used in the second and third trimester. If chemotherapy is given in the first trimester, folic acid antagonists should be avoided. Pregnancy following nongenital cancer No data support the misconception that women with breast cancer should not become pregnant following initial therapy. Similarly, no scientific data support the misconcep- 146 Antineoplastic drugs during pregnancy tion that pregnancy after mastectomy for breast cancer adversely affects survival of the mother (Donegan, 1983; Gilstrap and Cunningham, 1996; Yazigi and Cunningham 1990).

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Human insulin is a double-chain protein with molecular mass around 6000 that con- tains 51 amino acids (chain A—21 amino acids discount avapro 300 mg diabetes forum, chain B—30 amino acids) purchase 150mg avapro fast delivery diabetic diet understanding, which are bound together by disulfide bridges. Currently, human and some animal insulins (pigs and large oxen) can be synthesized [10–12], and there “are methods for” making it by genetic engineering [13–16]. Rather than relying on insulin extracted from animal sources, genetic technology has permitted the production of large quantities of essentially human insulin by bacterial cells. Insulin and Synthetic Hypoglycemic Agents In the body, insulin is synthesized by β-cells of Langerhans islets in the pancreas. The rate of formation changes depending on the type of food consumed, gastrointestinal hormones, and neuronal control. It is quickly broken down by enzymes and is removed from the blood by the liver or kidneys. However, it has been proposed that insulin acts by binding with specific receptors on the sur- face of the insulin-sensitive tissues such as skeletal muscle, cardiac muscle, fatty tissue, and leukocytes. Using insulin in diabetes mellitus leads to lower levels of sugar in the blood, and a build up of glycogen in tissues. Lowering glucose in the blood stops glycosuria, thus lowering elevated diuresis and thirst, normalizing carbohydrate, protein, and fat volume, and reducing diabetic comas. Because insulin is degraded by digestive enzymes, the method of introduction is rarely parenteral. There are prolonged-action insulin drugs, which are slowly absorbed from the introduction site. First generation drugs—deriva- tives of sulfonylurea were the most popular in the early 1980s, and include tolbutamide, acetohexamide, tolazamide, and chlorpropamide. Second generation drugs—derivatives of guanidine, such as glyburide and glipizide, entered medical practice after 1984. All of these drugs have very similar chemical structures and mechanism of action, and they differ in the structure of their side chains, and accordingly, activity and pharmacokinetic characteristics. It is believed that the sulfonylamide action consists of elevated insulin secretion. It is also pre- sumed that the hypoglycemic effect of these drugs is also associated with the suppression of release of glucagon, a hormone produced by α-cells of Langerhans islets in pancreas, and which is a polypeptide made up of 29 amino acid residues. The effect of glucagon on carbohydrate vol- ume is evident by hyperglycemia, which is associated with increased glycogenogenesis (syn- thesis of glucose from non-carbohydrate precursors) in the liver. An important ability of all of the examined drugs is the possibility of peroral introduction. Many of the medicinal drugs used in various diseases are antagonists of oral hypoglycemic drugs (corticosteroids, thyroid hor- mones, thiazide diuretics, furosemide, and oral contraceptives). At the same time phenyllanta- zone, clofibrate, dicumarol and salicyclates are potentiating the action of hypoglycemic drugs. Its action is preferably connected with stimulatory action of β-cells in the pancreas, which results in intensive insulin secretion. Synonyms of this drug are mebenol, oramid, ora- bet, tolbuton, butamide, rastinon, and others. By maintaining structural similarities with first-generation drugs, this drug dif- fers from the other drugs examined in that it has a semicarbazide group instead of a urea residue, and an azepine group instead of a cyclohexyl group. Insulin and Synthetic Hypoglycemic Agents with ethyl-(p-toluenesulfonyl)carbamate (26. Tolazamide is used for non-insulin-dependent diabetes mellitus without expressed microvascular complications. It is synthesized from 2-methoxy-5-chloroben- zoic acid chloride, which is transformed into an amide 26. This undergoes subsequent sulfonylchlorination by chlorosulfonic acid, and then amination by ammonia, which gives sulfonamide 26. The resulting sulfonamide is reacted with cylclohexylisocyanate to give the desired glyburide (26. Like all of the other oral hypoglycemic drugs examined, it is a β-cell stimulant in pancreas; but on the other hand, it increases the sensitivity to insulin, the degree to which it binds with target cells. The hypoglycemic effect sets in References 347 at significantly lower doses than with first-generation drugs. Synonyms of this drug are glybenclamide, manilil, dihaben, daonil, and many others.


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