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Professor, Homer G. Phillips College of Osteopathic Medicine

Cell junctions in molecular layer Molecular layer contains the following cellular junctions gastritis juice diet order 40mg omeprazole. Dendrites of stellate cells and basket cells synapse with parallel fibers gastritis from diet pills cheapest omeprazole, which are the axons of granule cells ii gastritis diet buy discount omeprazole 20mg online. However gastritis symptoms come and go buy 20 mg omeprazole amex, the axon of basket cell descends down into the Purkinje layer and forms the transverse fiber, that ends on the soma of Purkinje cells. Dendrites of Golgi cells situated in inner granular layer enter the molecular layer and end on parallel fibers. Purkinje Layer Purkinje layer is situated in between outer molecular layer and inner granular layer. Dendrites of these cells ascend through the entire thickness of molecular layer and arborize there. Axons of the basket cells form the transverse fibers, which descend down and end on the soma of Purkinje cells. Axons of Purkinje cells descend into the white matter and terminate on the cerebellar nuclei and vestibular nuclei via cerebellovestibular tract. Granular Layer Granular layer is the innermost layer of cerebellar gray matter and it is in between Purkinje layer and the cerebellar white matter. Total number of interneurons in this layer is about half the number of all neurons in the whole nervous system. Axon of granule cell ascends into molecular layer and forms the parallel fiber, which synapses with dendrites of Purkinje cells, stellate cells, basket cells and Golgi cells. Dendrites of granule cells and the axon and few dendrites of a Golgi cell synapse with Mossy fiber. The synaptic area of these cells is called glomerulus and it is encapsulated by the processes of glial cells. Afferent Fibers to Cerebellar Cortex Cerebellar cortex receives afferent signals from other parts of brain through two types of nerve fibers: 1. Climbing fibers Climbing fibers arise from the neurons of inferior olivary nucleus, situated in medulla and reach the cerebellum via olivocerebellar tract. Inferior olivary nucleus relays the output signals from motor areas of cerebral cortex and the proprioceptive signals from different parts of the body to the cerebellar cortex via climbing fibers. Proprioceptive impulses from different parts of the body reach the inferior olivary nucleus through spinal cord and vestibular system. After reaching the cerebellum, the climbing fibers ascend into molecular layer and terminate on the dendrites of Purkinje cells. While passing through cerebellum, climbing fibers of olivocerebellar tract send collaterals to cerebellar nuclei. So, impulses from cerebral cortex and proprioceptors of the body are conveyed not only to cerebellar cortex, but also to the cerebellar nuclei through the climbing fibers. Mossy fibers Unlike climbing fibers, the mossy fibers have many sources of origin, namely motor areas of cerebral cortex, pons, medulla and spinal cord. Fibers arising from all these areas send collaterals to cerebellar nuclei before reaching the cerebellar cortex. So, like climbing fibers, mossy fibers also convey afferent impulses to both cerebellar nuclei and cerebellar cortex. Mossy fibers reach the granular layer of cerebellar cortex and divide into many terminals. Each terminal enters a specialized structure called glomerulus and ends in a large expanded structure that forms the central portion of the glomerulus. Dendrites of granule cells and axon and dendrites of Golgi cells synapse on the mossy fiber giving a thick bushy appearance. Neuronal Activity in Cerebellar Cortex and Nuclei Functions of cerebellum are executed mainly by the impulses discharged from cerebellar nuclei. However, cerebellar cortex controls the discharge from nuclei constantly via the fibers of Purkinje cells. It is done in accordance with the signals received by cerebellar cortex from different parts of the brain and body via climbing and mossy fibers. Climbing fibers excite the Purkinje cells directly and cerebellar nuclei via collaterals, by releasing 5. Purkinje cell is very strong because each climbing fiber ends on a single Purkinje cell (Table 150. In the glomeruli, mossy fibers release glutamate and excite the granule cells and Golgi cells.

If a patient on steroid therapy develops an infection-the steroid should not be discontinued despite its propensity to weaken host defence and delay healing gastritis symptoms belching omeprazole 40 mg with mastercard. Surgery is such a patient should be covered by intraoperative and postoperative gastritis diet buy 40mg omeprazole otc. Since corticosteroids may have to be used as a life-saving measure gastritis diet best order omeprazole, all of these are relative contraindications in the presence of which these drugs are to be employed only under compelling circumstances and with due precautions gastritis diet handout purchase omeprazole pills in toronto. After 4 weeks, the symptoms subsided and prednisolone dose was tapered at the rate of 10 mg every 2 weeks. When she was taking 10 mg prednisolone/ day, she met with a road-side accident and suffered compound fracture of both bones of the right leg. Internal fixation of the fracture and suturing of wounds under general anaesthesia is planned. Testosterone was isolated as the testicular hormone, its structure was worked out and it was synthetically prepared by the year 1935. In women ovary produces small quantity of testosterone; this together with that derived indirectly from adrenals amounts to 0. Synthetic androgens Methyltestosterone and fluoxymesterone are 17-alkyl substituted derivatives of testosterone which are orally active because of resistance to first pass metabolism, but have submaximal androgenic efficacy and potential to cause cholestatic jaundice. Other orally active compounds are testosterone undecanoate which is administered as oily solution to be absorbed through lymphatics bypassing the liver, and mesterolone. Estrogens are more potent inhibitors of Gn secretion even in males, and it is believed that the small amount of estradiol produced by testes as well as that resulting from conversion of testosterone to estradiol in liver and fat plays a role in feedback inhibition. Thickening of skin which becomes greasy due to proliferation and increased activity of sebaceous glands-especially on the face. Male libido appears to be activated by testosterone directly, and probably to a greater extent by estradiol produced from testosterone. Testosterone is also important for the intrauterine development of the male phenotype. Relatively large amounts of testosterone are produced by the foetal testes during the first half of intrauterine life. Testes Moderately large doses cause testicular atrophy by inhibiting Gn secretion from pituitary. High concentration of testosterone is attained locally in the spermatogenic tubules by diffusion from the neighbouring Leydig cells and stimulates spermatogenesis. Estradiol produced from testosterone, and not testosterone itself, is responsible for fusion of epiphyses in boys as well as in girls. Erythropoiesis Testosterone accelerates erythropoiesis by increasing erythropoietin production and probably direct action on haeme synthesis. The genital skin of both sexes and urogenital tract of male contains 5- reductase-2 which is more sensitive to inhibition by finasteride. Therefore, slowly absorbed esters of testosterone are used by this route-are hydrolysed to the active free form. The major metabolic products of testosterone are androsterone and etiocholanolone which are excreted in urine, mostly as conjugates with glucuronic acid and sulfate. Small quantities of estradiol are also produced from testosterone by aromatization of A ring in extraglandular tissues (liver, fat, hypothalamus). By cutaneous delivery, testosterone/ dihydrotestosterone circumvent hepatic first pass metabolism; uniform blood levels are produced round the clock. A gel formulation has been marketed for once daily application which has become the preferred method of androgen replacement for hypogonadism and impotence. Frequent, sustained and often painful erections in males in the beginning of therapy; subside spontaneously after sometime. Oligozoospermia can occur with moderate doses given for a few weeks to men with normal testosterone levels. Precocious puberty, premature sexual behaviour, and stunting of stature due to early closure of epiphysis-if testosterone is given continuously to young boys for increasing stature.

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It synergises with -lactam antibiotics gastritis low carb diet purchase 40mg omeprazole with amex, especially against Enterococcus (endocarditis) and Pseudomonas (meningitis) gastritis diet order 20 mg omeprazole visa. It is often added when a combination antibiotic regimen is used empirically to treat serious infections by extending the spectrum of coverage gastritis zungenbelag order 40mg omeprazole with visa. Because of low therapeutic index gastritis gurgling stomach discount omeprazole 20mg without a prescription, its use should be restricted to serious gram-negative bacillary infections. It is often combined with a penicillin/cephalosporin or another antibiotic in these situations. Another aminoglycoside (tobramycin, amikacin, netilmicin) is then selected on the basis of the local sensitivity pattern, but strains resistant to gentamicin are generally cross resistant to tobramycin and sisomicin. Aminoglycosides should not be used to treat community acquired pneumonias which are mostly caused by gram-positive cocci and anaerobes. Pseudomonas, Proteus or Klebsiella infections: burns, urinary tract infection, pneumonia, lung abscesses, osteomyelitis, middle ear infection, septicaemia, etc. It may be combined with piperacillin or a third generation cephalosporin for serious infections. Meningitis caused by gram negative bacilli: Because this is a serious condition, drug combinations including an aminoglycoside are often used. The third generation cephalosporins alone or with an aminoglycoside are favoured for this purpose. Streptomycin It is the oldest aminoglycoside antibiotic obtained from Streptomyces griseus; which was used extensively in the past, but is now practically restricted to treatment of tuberculosis. The antimicrobial spectrum of streptomycin is relatively narrow: primarily covers aerobic gram-negative bacilli. Resistance Many organisms rapidly develop resistance to streptomycin, either by one-step mutation or by acquisition of plasmid which codes for inactivating enzymes. Streptomycin dependence Certain mutants grown in the presence of streptomycin become dependent on it. This occurs when the antibiotic induced misreading of the genetic code becomes a normal feature for the organism. This phenomenon is probably significant only in the use of streptomycin for tuberculosis. Hypersensitivity reactions are rare; rashes, eosinophilia, fever and exfoliative dermatitis have been reported. Because of toxicity and narrow spectrum of activity, it has been largely replaced by other aminoglycosides for treatment of gram-negative bacillary infections; may be used only if mandated by sensitivity report of the infecting strain. It is recommended as a reserve drug for empirical treatment of hospital acquired gram-negative bacillary infections where gentamicin/tobramycin resistance is high. However, it is not useful for combining with penicillin in the treatment of enterococcal endocarditis. Sisomicin Introduced in 1980s, it is a natural aminoglycoside from Micromonospora inyoensis that is chemically and pharmacokinetically similar to gentamicin, but somewhat more potent on Pseudomonas, a few other gram-negative bacilli and haemolytic Streptococci. However, it is susceptible to aminoglycoside inactivating enzymes and offers no advantage in terms of ototoxicity and nephrotoxicity. It can be used interchangeably with gentamicin for the same purposes in the same doses. Amikacin It is a semisynthetic derivative of kanamycin to which it resembles in pharmacokinetics, dose and toxicity. The outstanding feature of amikacin is its resistance to bacterial aminoglycoside inactivating enzymes.

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Other side effects are increased appetite and weight gain (not with haloperidol); aggravation of seizures in epileptics; even nonepileptics may develop seizures with high doses of some antipsychotics like clozapine and occasionally olanzapine gastritis diet 7-up buy generic omeprazole canada. However high potency gastritis diet avocado purchase omeprazole 40mg without prescription, phenothiazines gastritis diet purchase omeprazole 10mg fast delivery, risperidone gastritis symptoms night sweats purchase omeprazole 20 mg overnight delivery, quetiapine aripiprazole and ziprasidone have little effect on seizure threshold. Excess cardiovascular mortality has been attributed to antipsychotic drug therapy. The atypical antipsychotics, except risperidone, do not appreciably raise prolactin levels. Like other drugs of the class, it benefits both positive and negative symptoms of schizophrenia, but is rated less effective than clozapine. Extrapyramidal side effects are less prominent than with typical neuroleptics, but more than clozapine. Zotepine lowers seizure threshold and incidence of seizures is increased at high doses. Zotepine is available in India for use in schizophrenia, but does not offer any specific advantage. Metabolic effects Elevation of blood sugar and triglyceride levels as a consequence of chronic therapy with certain antipsychotics is a major concern now. High potency drugs like trifluperazine, fluphenazine, haloperidol and atypical antipsychotics like risperidone, aripiprazole and ziprasidone have low/no risk. The mechanism of this effect is not clear; may be due to weight gain and/or accentuation of insulin resistance. Cardiovascular mortality among schizophrenics is higher; increased use of atypical antipsychotics may be a contributory factor. Extrapyramidal disturbances these are the major dose-limiting side effects; more prominent with high potency drugs like fluphenazine, haloperidol, pimozide, etc. If that is not possible, one of the anticholinergic antiparkinsonian drugs may be given concurrently. Though quite effective, routine combination of the anticholinergic from the start of therapy in all cases is not justified, because they tend to worsen memory and impair intellect, in addition to dry mouth and urinary retention. It is more common in children below 10 years and in girls, particularly after parenteral administration; overall incidence is 2%. The mechanism of this complication is not understood; no specific antidote is available. A central anticholinergic may reduce the intensity in some cases; but a benzodiazepine like clonazepam or diazepam is the first choice treatment of the motor restlessness. Most patients respond to reduction in dose of the neuroleptic or changeover to an atypical antipsychotic like quetiapine. It is accentuated by anticholinergics and temporarily suppressed by high doses of the neuroleptic (this should not be tried except in exceptional circumstances). The dyskinesia may subside months or years after withdrawal of therapy, or may be lifelong. Miscellaneous Weight gain often occurs due to long-term antipsychotic therapy, sugar and lipids may tend to rise. Blue pigmentation of exposed skin, corneal and lenticular opacities, retinal degeneration (more with thioridazine) occur rarely after long-term use of high doses of phenothiazines. Antihypertensive action of clonidine and methyldopa is reduced, probably due to central 2 adrenergic blockade. Phenothiazines and others are poor enzyme inducers-no significant pharmacokinetic interactions occur. Enzyme inducers (barbiturates, anticonvulsants) can reduce blood levels of neuroleptics. Psychoses Schizophrenia the antipsychotics are used primarily in functional psychoses. They have an indefinable but definite therapeutic effect in all forms of schizophrenia: produce a wide range of symptom relief. They control positive symptoms (hallucinations, delusions, disorganized thought, restlessness, insomnia, anxiety, fighting, aggression) better than negative symptoms (apathy, loss of insight and volition, affective flattening, poverty of speech, social withdrawal). They also tend to restore affective and motor disturbances and help upto 90% patients to lead a near normal life in the society.

It is also not recommended for digitalis toxicity gastritis not going away cheap 20 mg omeprazole with visa, because additive A-V block may occur gastritis diet kencing buy omeprazole in united states online. To prevent recurrences gastritis diet 90x cheap omeprazole 20 mg with visa, oral therapy with verapamil gastritis diet book buy omeprazole 40 mg cheap, diltiazem or propranolol alone or combined with digoxin may be prescribed. Almost complete elimination occurs in a single passage through coronary circulation. Dipyridamole potentiates its action by inhibiting uptake, while theophylline/ caffeine antagonize its action by blocking adenosine receptors. Bronchospasm may be precipitated in asthmatics; verapamil is the drug of choice for such patients. They may also be used in complete (3rd degree) heart block to maintain a sufficient idioventricular rate (by increasing automaticity of ventricular pacemakers) till external pacemaker can be implanted. Choice and use of antiarrhythmic drugs Mere detection of an arrhythmia does not necessitate treatment. Only propranolol and to some extent amiodarone have been shown to reduce cardiovascular mortality in the long-term. A simple clinical classification of antiarrhythmic drugs is presented in the box below. The aim is to improve cardiovascular function either by restoring sinus rhythm, or by controlling ventricular rate, or by conversion to a more desirable pattern of electrical and mechanical activity. A practical guide to the choice and use of antiarrhythmic drugs is summarized in the box on next page. Lidocaine/procainamide/amiodarone Cardioversion (if haemodynamically unstable) Propranolol/amiodarone (oral). Angina pectoris Is a pain syndrome due to induction of an adverse oxygen supply/demand situation in a portion of the myocardium. The underlying pathology is-severe arteriosclerotic affliction of larger coronary arteries (conducting vessels) which run epicardially and send perforating branches to supply the deeper tissue. Thus, a form of acutely developing and rapidly reversible left ventricular failure results which is relieved by taking rest and reducing the myocardial workload. Drugs that are useful, primarily reduce cardiac work (directly by acting on heart or indirectly by reducing preload hence end diastolic pressure, and afterload). Abnormally reactive and hypertrophied segments in the coronary arteries have been demonstrated. Antianginal drugs relieve cardiac ischaemia but do not alter the course of coronary artery pathology: no permanent benefit is afforded. Other organic nitrates were added later, but a breakthrough was achieved in 1963 when propranolol was used for chronic prophylaxis. A number of vasodilator and other drugs have been promoted from time to time, but none is as uniformly effective. Some potassium channel openers (nicorandil), metabolic modulator (trimetazidine) and late Na+ current inhibitor (ranolazine) have been introduced lately. Others Dipyridamole, Trimetazidine, Ranolazine, Ivabradine, Oxyphedrine Clinical classification A. Nitrates dilate veins more than arteries peripheral pooling of blood decreased venous return. The decrease in end diastolic pressure abolishes the subendocardial crunch by restoring the pressure gradient across ventricular wall due to which subendocardial perfusion occurs during diastole. It is through their action on peripheral veins that nitrates exert major beneficial effects in classical angina. Redistribution of coronary flow In the arterial tree, nitrates preferentially relax bigger conducting (angiographically visible) coronary arteries than arterioles or resistance vessels. This pattern of action may cause favourable redistribution of blood flow to ischaemic areas in angina patients. Dilatation of conducting vessels all over by nitrate along with ischaemia-induced dilatation of autoregulatory resistance vessels only in the ischaemic zone increases blood flow to this area. Mechanism of relief of angina the relaxant effect on larger coronary vessels is the principal action of nitrates benefiting variant angina by counteracting coronary spasm. Exercise tolerance of angina patients is improved because the same amount of exercise causes lesser augmentation of cardiac work.

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