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By F. Milok. Bluffton University.

Practice Evidence Based Medicine cheap nebivolol 2.5mg with visa heart attack feat thea austin, appreciating the rationale for different therapeutic modalities and be familiar with the administration of “essential drugs” and their common side effects; 4 buy cheap nebivolol 2.5mg on-line pulse pressure greater than 40. Appreciate the psycho-social purchase 2.5mg nebivolol with amex arteria facialis linguae, cultural purchase nebivolol 2.5 mg mastercard blood pressure is, economic, and environmental factors affecting health, and develop humane attitude towards the patients/relatives, in discharging one’s professional responsibilities; 5. Be familiar with the various National Health Programs, and the ways in which they are being implemented; 6. Acquire basic management skills in the area of materials, financial and human resources; 7. Demonstrate communication skills, both verbal and written to establish effective communication with the clients (patients, relatives, and general public), health team partners, and scientific community; 8. Develop attitude for self learning and acquire necessary skills including the use of appropriate technologies, for pursuing self directed learning for a life time. Distribution of teaching hours for theory and practicals are as follows : Subject Approximate No. He/She should be able to locate the site of gross lesions according to the deficits encountered. The student should recognise the critical stages of normal development and the effects of common teratogens, genetic mutations and environmental hazards on it. He/She should be able to explain the developmental basis of the occurrence of major variations, abnormalities and congenital anomalies. Gross Anatomy Introduction to Anatomy, nomenclature, anatomical position, planes, tissues and movements. Osteology (a) Names of the bones of the body and their position; classification of the bones with examples; general features of the bone and normal development; microscopic anatomy of bone; general pattern of blood supply; ossification of the bones of the limbs for age determination. Muscular System (a) Classification and identification of the muscles of the body: main attachments, nerve supply and action(s), microscopic anatomy of muscles and the nerve terminations. Arthrology (a) Definition and classification of joints, general features of different types of joints; detailed study of major joints of the limbs and movements performed at various joints in the body. Anatomy 3 (b) Microscopic anatomy of articular cartilage; maintenance of articular cartilages; blood supply and nerve supply of the joints. Cardio Vascular System (a) Normal position, external features and parts of the heart; internal features of the chambers of heart, names of the blood vessels and venous drainage of the organs, structures and body as a whole, conducting system of heart, fibroskeleton of heart. Respiratory System (a) Position, parts, relations, blood supply of upper and lower respiratory tract. Pleura, its reflection, nerve supply, pleural recesses and their significance, bronchopulmonary segments, their importance. Digestive System (a) Position, extent, parts, relations, blood supply, nerve supply, lymphatic drainage and sphincters of the gastrointestinal system. Genito-Urinary System (a) Parts, position, relations, blood supply, nerve supply and lymphatic drainage of uterus, cervix, vagina, ovary, ovarian duct, testes, epididymis, seminal vesicle, ductus deferens, prostate, kidney, ureter, urinary bladder and urethra (b) Innervation of urinary bladder in detail 8. Endocrine System and Individual Endocrine Glands (a) Various endocrine glands, their location, relations, blood supply, nerve supply and lymphatic drainage. Motor and sensory pathways, cranial nerves, thalamus, cerebellum, limbic and autonomic pathways. Lymphatic System (a) Location of the major groups of the lymphnodes of the body and their drainage areas. Gross anatomy of the major lymphatics specially thoracic duct and its tributaries. Surface Anatomy (a) Surface features of the body and projection of the outline of heart, its borders, surfaces and valves, lungs, their borders, fissures and hila, pleura, liver, kidneys and various abdominal and pelvic organs and important vessels and nerves 13. Cross Sectional Anatomy Cross sections of thorax, abdomen and pelvis to understand the interrelationship of organs and structures. Microanatomy Microscope and basic principles of microscopy, commonly used stains, basophilic and acidophilic staining reactions and their significance. Brief principle of electron microscopy and interpretation of ultrastructural features. Four primary tissues Epithelium : Microscopic characteristics, types, functions, distribution, basal lamina, cell junctions, specialization of the cell surface and their structural details and functions; metaplasia. Intercellular substances, amorphous ground substance, types of connective tissue (loose areolar tissue, dense connective tissue) and their distribution. Specialized connective tissue : different types of cartilages and their functions and distribution. Bone : Cells, bone matrix, structural features of compact and cancellous bone, their distribution and functions, ossification, blood supply of a long bone. Different types of neurons and their specific structural and functional features and distribution. Axonal transport, synapse, morphological and functional characteristics of different types of synapses. Sensory and autonomic ganglia, peripheral nerves, myelin and myelination, degeneration and regeneration in peripheral nerves. Histology of various organs/organ systems Anatomy 5 Exocrine glands : Characteristics, simple and compound glands; types of secretions, modes of secretion, detailed structural features of a serous secreting cell and mucous secreting cell, serous and mucous acini, duct system, features of salivary glands, exocrine pancreas, sweat and sebaceous glands, mammary gland, bulbourethral gland etc. Circulatory system : Structural features of heart; conducting and distributing arteries and arterioles; types of capillaries, their structural features and distribution and microcirculation, detailed structure of endothelium; structural characteristics of large and small veins and venules arterio-venous shunts, lymphatics. Respiratory system : Structural features of nose, nasopharynx, larynx, trachea, principal brochi, lung including intrapulmonary bronchi, bronchioles, alveolar ducts, atria, alveoli, blood-air-barrier. Skin and nerve-end-organs : Thick, thin and hairy skin, cell renewal and pigmentation of skin, skin appendages, healing of skin wounds, sensory receptors of skin. Thymus, lymph nodes, spleen, tonsils and other mucous associated lymphoid follicles. Layers of tubular digestive tract, esophagus, stomach, small intestine, gastroesophageal junction, gastroduodenal junction, large intestine, anal canal and rectoanal junction. Liver, internal organization of liver, liver lobule, liver acinus, significance of zonation in liver acinus, liver sinusoids, detailed structure of hapatocyet, bile canaliculi, bile ducts, gall bladder, bile duct and pancreas. Endocrine glands : Thyroid, parathyroid, Islets of Langerhan’s gland, adrenal cortex and medulla, their structural details, functional mechanisms, hypophysis cerebri, cell types secretion and their functions, hypophyseal portal circulation, common endocrine disorders Urinary system : Detailed microscopic structure of kidney, cortex, medulla, pyramids, medullary rays, cortical columns, glomerulus, nephron, glomerular filtration juxtaglomerular apparatus, its structural features and functions, renal interstitium, collecting ducts, renal sinus, minor and major calyces, microcirculation of kidney, histophysiology of the kidney, renal pelvis and ureters, urinary bladder and urethra. Female reproductive system : Ovary, ovarian stroma, primary and secondary graafian follicles, functions of various constitutents and structural details of graafian follicles, atretic follicles, corpuluteum and its functions, corpus albicans. Oviducts, uterus, arterial supply of uterus, cyclic changes in uterine endometrium, fertilization, vagina, female external ganitalia and mammary glands. Male reproductive system : Thestes, spermatogenesis, spermatozoon, cycle of seminiferous epithelium, sertoli cells, interstitial tissue Leydig cells, histophysiology of testes, epididymus, vas deferns, prostrate, seminal vesicles, penis. A General Embryology (a) Definition of embryology; gestation period: definition of gamete sperm, Ovum; gametogenesis, migration of primordial germ cells into gonadal ridge; spermatogenesis; structure of sperm, oogenesis; structure of ovum; growth of ovarian follicles, ovarian and uterine cycles. Implantation; formation of decidua, types of implantation and abnormal sites of implantation (e) Third Week of Development Appearance of primitive streak and primitive node; formation of intraembroynic mesoderm resulting in trilaminar germ disc; gastrulation formation of notochord, buccopharyngeal and cloacal membranes, paraxial, intermediate and lateral plate mesoderm, secondary yolk sac, intraembryonic coelom and allantoic diverticulum; derivatives of ectoderm, mesoderm and endoderm. Development from third month to birth (Fetal period) (g) Maturation of tissues and organs and rapid growth of body. Placenta (i) Formation of placenta and chorionic villi, decidua basalis; features and functions of placenta; placental circulation; abnormalities; placental barrier; placentome, types of placenta. Amniotic Cavity (k) Amniotic cavity and membrane; amniotic fluid – functions, expansions of amniotic cavity and fusion with chorion; chorion laeve with decidua capsularis; decidua capsularis with parietalis; obliteration of chorionic and uterine cavities; function of fused foetal membranes to dilate cervical canal. Theratology (o) Genetical and environmental factors as causative factors for congenital malformations. B Systemic Embryology (a) Development of the individual organs of digestive system, genital system, urinary system,, respiratory system, cardiovascular system. Abdomen: Dissection: Anterior abdominal wall and inguinal region, external genitalia. Lower Limb: Dissection: Gluteal region, front and back of thigh popliteal fossa, front back and lateral side of leg and dorsum of foot. Prosected Parts: Sole of the foot and joints Head & Neck: Dissection: Superficial and deep dissection of face and neck, orbit and eye ball. Submandibular region temporal and infratemporal fossa, cranial cavity, naso and oropharyngeal regions.

Chocolate agar (most bacteria order 2.5 mg nebivolol with visa blood pressure band, especially Neisseria gonorrhoeae and Haemophilus species) iii purchase nebivolol 5mg visa heart attack music video. Previous corneal surgery (including refractive surgery and penetrating keratoplasty) including loose corneal sutures B cheap 2.5mg nebivolol fast delivery arteria pancreatica magna. Adjacent infections (blepharitis cheap 2.5 mg nebivolol fast delivery arteria occipital, conjunctivitis, dacryocystitis, or canaliculitis) 5. Fluoroquinolones (including ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, besifloxacin) i. Fortified antibiotics with gram positive activity (Cefazolin or Vancomycin) and fortified antibiotic with gram negative activity (aminoglycoside or extended spectrum cephalosporin) b. Monotherapy with fluoroquinolone (only for small, non-vision threatening ulcers) 4. Avoid if causative microorganism is uncertain and effective antibacterial therapy is not assured ii. Consider if individual risk-benefit assessment suggests possible value in: i) Reducing corneal inflammation ii) Preventing further stromal ulceration iii) Decreasing risk of corneal graft rejection iv) Minimizing corneal neovascularization and opacification v) Improving reepithelialization iii. Start with frequent dosing (and/or loading dose) and taper depending on clinical response 6. Consolidation and sharper demarcation of the perimeter of the infiltrate (with cessation of progression) iii. Consider additional or alternative antibacterial agent if insufficient response or stabilization b. Methicillin Resistant Staphylococcus Aureus i) Two forms (i) Hospital-Acquired (a) Found commonly in health care workers or chronically hospitalized, institutionalized or immunocompromised patients (b) More commonly multi-drug resistant (ii) Community-Acquired (a) Increasing percentage of community acquired ocular infections e. Nontuberculous mycobacteria i) Amikacin ii) Clarithromycin iii) Moxifloxacin, Gatifloxacin iii. Complications of therapeutic or tectonic penetrating keratoplasty (See Penetrating keratoplasty) 1. Epidemiology of contact lens-related inflammation and microbial keratitis: a 20-year perspective. Influence of fluoroquinolone susceptibility on the therapeutic response of fluoroquinolone-treated bacterial keratitis. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Its relative frequency as a cause of keratomycosis increases in temperate zones C. Foreign body sensation, conjunctival injection, photophobia and decreased vision 4. More insidious onset than with bacterial keratitis with gradually increasing pain 5. Fungal keratitis tends to have fewer inflammatory signs and symptoms during initial periods compared to bacterial keratitis 6. Frequently a gray-white, dry-appearing infiltrate with delicate filamentous or feathery, edge b. Penetration of fungus through intact Descemet membrane results in progressive anterior chamber inflammation 2. Focal dense, creamy suppuration that may resemble keratitis induced by gram-positive bacteria b. Gram, Giemsa, Gomori-methenamine silver, acridine orange, and calcofluor white stains c. Corneal biopsy if clinical suspicion with negative smear/culture or if vision threatening keratitis with lack of clinical improvement a. Confocal microscopy, looking for filamentous forms or spores in the corneal stroma 4. Anterior chamber paracentesis, if strong clinical suspicion of fungal invasion into eye and negative smear/culture of corneal specimen 5. Sensitivities of isolated fungi to various antifungal agents only available at few centers a. Trauma to the cornea with plant material commonly associated with filamentary fungal keratitis B. Corticosteroid therapy- appears to reduce the resistance of the cornea to fungal infection and potentiate existing fungal keratitis D. Use of broad spectrum antibiotics- provides a noncompetitive environment for fungus G. Antifungal agents are mostly fungistatic (except for amphotericin B at high doses). First line i) Topical amphotericin or voriconazole ii) Consider adding oral fluconazole or voriconazole if severe, unresponsive candidal keratitis ii. Second line i) Topical fluconazole or rarely miconazole ii) Poor response of candidal keratitis to topical natamycin c. First line i) Topical natamycin (See Clinical trials in cornea external disease) ii) Consider adding oral itraconazole, voriconazole or posaconazole if deep, progressive keratitis ii. Second line i) Topical voriconazole, clotrimazole, fluconazole, or amphotericin B iii. Beware of natamycin-resistant isolates, including Scedosporium, Paecilomyces, and Colletotrichum 2. Not recommended for patients with fungal keratitis, early or late in the disease B. Mechanical debridement or superficial keratectomy, especially for superficial fungal keratitis and for exophytic proliferation during therapy a. Debridement increases the penetration of topical antifungals but may increase scarring 2. Therapeutic penetrating keratoplasty for progressive keratitis despite antifungal therapy a. Anterior chamber washout with antifungal medication if penetration/extension suspected 5. Topical antifungal toxicity, with conjunctivitis and persistent corneal epithelial defect 1. Minimize use of corticosteroid; consider cyclosporine as adjunctive agent following keratoplasty 3. Intraocular and scleral extension, with fungal endophthalmitis or fungal keratoscleritis B. Patient needs to be counseled that the therapy may need to be prolonged Additional Resources 1. A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. Pathogen widespread in nature and in soil, tap water, swimming pools, hot tubs, contact lens cases C. Smears of corneal scrapings (cysts easier to recognize than trophozoites, which may resemble mononuclear leukocytes) a. Therapeutic keratoplasty (but high risk of recurrent Acanthamoeba keratitis in corneal graft) C. Patients with active, infectious keratitis should be followed closely during treatment (every day to once a week initially, depending on clinical features and clinical course). Stinging and limited epithelial toxicity (reduce frequency of applications or discontinue) 2.

This has resulted in the accurate classification of individual probiotic organisms nebivolol 2.5mg on-line hypertension guidelines, as well as detailed descriptions of their genetic 2.5mg nebivolol overnight delivery arteriovascular malformation, microbiological and immunological properties buy generic nebivolol 2.5mg on line blood pressure chart emt, and has led to extensive in vivo and in vitro studies of the impact of various probiotics on a variety of biological systems 422 E discount nebivolol 2.5mg visa arteria mesenterica inferior. Shanahan and, most recently, to well conducted clinical trials of probiotics in specific clinical scenarios in man and domestic animals. Despite all of this progress several problems persist in relation to these areas that continue to sully the image of probiotics and muddy the field. Two issues deserve special emphasis: the focus on “live” organisms and the insistence on conferring “a health benefit on the host”. Firstly, while it is readily acknowledged that studies in a number of animal models have demonstrated efficacy for killed bacteria, or even bacterial products or components [49–51], in generating a number of anti-inflammatory and anti-infective effects, this strategy has not, as yet, been explored or validated in man. It seems improbable that effects of probiotics in man will be confined to live organisms so this aspect of the definition will ultimately have to be refined or the term abandoned completely. Secondly, it is obvious from the latter part of this definition that clinical claims in man be they in the augmentation of health or in the treatment of disease, must be supported by credible clinical trial data. Up until the last few years, probiotics were not regulated as drugs and had been able to come on to the market as food supplements or under other designations that have allowed them, to a greater or lesser extent, to make a variety of “health” claims in the absence of supporting data. It seems that those who developed and widely promulgated the current definition of a probiotic have now been hoist on their own petard; truly a case of man bites dog. A similar level of scrutiny is now being leveled on these products in North America and elsewhere. At present the consumer is not being served, not only by the aforementioned issues relating to “health” claims, but also by major problems with quality control. Firstly, it is not unusual for the benefits of a given species or organism to be touted based on evidence derived from studies involving other organisms and species, despite the fact that detailed studies have demonstrated that, in terms of a probiotic property, be it immune modulation [52– 55] or anti-bacterial activity [50, 53, 56], there are tremendous differences between different lactobacilli and bifidobacteria, not to mind between lactobacilli and bifidobacteria, for example. No two probiotics are the same and extrapolations from one to another should be resisted at all times. Secondly, an individual who is about to consume a given probiotic preparation should know exactly what he or she is about to take: is it live (if that is necessary for its benefit), what is it’s concen- tration, will the organism survive as it makes contact with acid, bile and digestive enzymes as it transits the gut and what will be the actual concentration of the 19 The Future of Probiotics for Disorders of the Brain-Gut Axis 423 organism at its desired site of action? Few probiotic preparations have been characterized and formulated with sufficient rigor to allow the manufacturer to provide answers to these critical questions. Of further concern, critical examina- tions of the actual constituents of commercially-available probiotic preparations have, in the past, revealed worrying deviations from those included in the product label [57–61]. Nevertheless, evidence for efficacy for specific probiotics in certain clinical conditions continues to accumulate. Several studies have reported that probiotics may be effective in short- ening of the duration of acute diarrheal illnesses in children, such as that related to rotavirus infection [62]. Probiotics also appear to be effective in antibiotic- associated diarrhea [63–65], pouchitis [66, 67], some instances of inflammatory bowel disease [68, 69], and, as already described above, irritable bowel syndrome [55, 70, 71]. The Future of Probiotics Rather than make wild speculations regarding the future, or even risking modest predictions, we will now attempt to identify those areas where, we believe, the greatest challenges persist and the most important questions remain unanswered. Quality Control and Regulation If the field of probiotics is to progress further and gain acceptance within the hallowed halls of science, quality control and appropriate regulation must occur. Inevitably, this will take place on a nation-by-nation basis but, however accom- plished, must ensure that the consumer or the prescriber is sufficiently informed of the nature of any given product and assured of the accuracy of its label, including its shelf life, and the validity of health claims. It is incumbent on the medical and scientific communities to actively engage in these processes and to thereby ensure that new requirements and regulations in relation to quality control have scientific credibility and validity. This is a matter of great urgency; failure may result in a gradual ebbing away of confidence in the entire area and the loss of valuable products because the public simply cannot differentiate them from impostors. Probiotic Characterization As individual probiotic organisms are subjected to genomic analysis [72] the stage is set for both the accurate definition of each individual organism and the 424 E. Shanahan identification, on the genome, of areas of interest in relation to a particular property or action. This must be the way forward for both the definition of individual organisms and the comparison of their individual characteristics. Parallel develop- ments such as the various collaborative projects defining the human microbiome in health and disease will ultimately lead to a complete description of the microbiome and its metabolic properties and in so doing will facilitate a complete delineation of the interactions (good and bad) between bugs and the host. In so doing, considerable progress should be made in defining the basis for the beneficial actions of probiotic bacteria. Mechanism of Action While genomics and metabolomics may suggest certain roles for certain probiotics, these must, ultimately, be further elucidated in appropriate biological systems, including man. Indeed, a further component of the characterization of a probiotic must be the definition of it effects, if any, in a variety of contexts. Does the organism exert anti-bacterial or anti-viral properties, what are its effects on immune responses or metabolic processes? Again a standardized and validated approach to the interrogation of a given organism in relation to a particular use must be developed, where possible. Proposals to use a probiotic in man must have a plausible scientific rationale; hype and appeals to “being natural” should no longer be sufficient. Waking the Dead As emphasized at the outset of this chapter, the current definition of probiotics insists on the inclusion of live organisms. This will undoubtedly change; bacteria are metabolically active organisms that produce a variety of molecules with bio- logical activity [51, 75]. The whole area of bacterial components and bacterial products will be an exceptionally active one in the coming years. In clinical terms, this approach has already shown dividends through 19 The Future of Probiotics for Disorders of the Brain-Gut Axis 425 the isolation of probiotic products with specific anti-bacterial activities [76, 77]. Quite apart from the afore- mentioned issues in relation to strain selection for a given indication, the clinical investigator is faced with significant obstacles in choosing formulation, dose and duration of study. Dose is, for the most part, a “black box” in this field, very few dose ranging studies have been attempted and extrapolations from animal studies must always remain mindful of the fact that, weight for weight, probiotic doses used in the mouse or the rat exceed by several orders of magnitude those used in man. Here, however, we encounter the issue of formulation; what may be most acceptable to the patient (e. These challenges must and will be met; our obligation then is to ensure the performance of clinical trials whose design is optimal for the given indication. Probiotics could, in the future act as vehicles for the targeted delivery of therapeutic molecules to the gut. One great advantage that probiotics currently enjoy in the clinical arena, and in comparison to conventional pharmaceuticals, is that of safety. Here again genomic analysis will provide an important supportive role by identifying pathogenicity islands or features that suggest the potential for transference of antibiotic resistance [72]. If it is decided that a given probiotic product is to be regarded as a food, profit margins will be slim and the target population will, by definition, be the healthy population. Such trials will by virtue of their endpoints require very large numbers of participants and be very expensive. For the food industry, ideal endpoints should be validated biomarkers of risk, of which there are few (e. Both issues, size of study population and need for validated biomarkers of risk, pose huge problems for the food industry which is unlikely to be in a position to fund such trials. Shanahan drugs within the pharmaceutical sector (paradoxically lower costs and higher margins on licensable product) unless new microbial biomarkers of risk emerge. For obvious reasons, including their source and the well-documented interactions between the microbiota and the gut, studies of probiotics have, to date, concentrated in large part on intestinal disorders. Hints to suggest efficacy for probiotics in disorders beyond the gut accumulate with studies illustrating the ability of orally administered probiotics to modulate systemic cytokine patterns in man towards an anti-inflammatory phenotype being of particularly interesting [83, 84]. Experimen- tal and limited clinical data suggest the potential for probiotics to impact on such extra-intestinal disorders as non-alcoholic fatty liver disease [85, 86], arthritis [87], allergy [88], obesity [89] and, as has been amply illustrated in this volume, symptoms arising from and disorders of the central nervous system. The latter is in keeping with very recent and exciting data on the ability of orally administered probiotics and other modifications of the microbiota to influence behavior, mood, cerebral function and morphology in experimental animals [90–92]. Indeed, some preliminary data suggests that probiotics may be able to modulate brain activity in man [47]. Given the pro-inflammatory phenotype associated with such psychiatric disorders as depression and schizophrenia [93, 94] the aforementioned anti- inflammatory actions of some probiotics may be relevant here also.

To help families cope nebivolol 5 mg low price pulse pressure 60, they need support and reassurance from healthcare professionals and other sources cheap nebivolol 5 mg otc demi lovato heart attack mp3, where appropriate 2.5mg nebivolol with visa blood pressure definition. Information should be offered continuously throughout the patient journey by the appropriate member of the multidisciplinary team discount nebivolol 5mg fast delivery pulse pressure youtube. This information should balance the need for people to have adequate time to consider potential changes in the condition and/ or its treatment before they happen with the need to avoid unnecessary concern. Healthcare professionals should use their judgement to assess the level and pace of information required at each stage. A narrative review which identifies some of the issues with which people with Parkinson’s disease are concerned is included in section 3. Discuss parkinsonism with the person and their carer, advising them that their symptoms may also be symptoms of other disorders. Diagnosis emphasise to the person with a probable or confirmed diagnosis of Parkinson’s disease that the condition affects individuals differently and not all patients will experience all symptoms. Discuss parkinsonism with the person and their carer, reminding them that their symptoms may also be symptoms of other disorders and that the diagnosis may change in future. Highlight the availability of the non-motor symptoms questionnaire from the Parkinson’s Disease Society’s website which can help patients report symptoms to healthcare professionals. If patients ask for specific information on non-motor symptoms eg dementia, this should be offered. Mechanisms should be in place to review care provided against the guideline recommendations. The reasons for any differences should be assessed and addressed where appropriate. Successful implementation and audit of guideline recommendations requires good communication between staff and multidisciplinary team working. The guideline development group has identified the following as key points to audit to assist with the implementation of this guideline: recommendation audit point options c Patients with suspected Parkinson’s Was the patient referred Record drug class disease should be referred untreated untreated to a hospital if treatment has to a hospital clinician with sufficient clinician with sufficient already started expertise in movement disorders to expertise in movement make the diagnosis. Searches were carried out for the period 1998-2008, with some covering the period 1980-2008. Of these 640 were identified as having the potential to form part of the evidence base and were reviewed in detail. This search focused on the identification of qualitative literature relevant to the following themes in Parkinson’s disease: communication, information needs, family/carer needs, attitudes to drug therapy, non-motor symptoms and multidisciplinary team working. An initial sift of the results aimed at removing clearly irrelevant papers and focusing on research journals reduced this number to 55 references. Two pairs of reviewers independently reviewed this list of abstracts to identify relevant papers. At the end of this process, the number of papers considered to be of relevance was reduced to 10. At the conclusion of this process the papers included as evidence were split into six themes: communication, information needs, family/carer needs, attitudes to drug therapy, non-motor symptoms and multidisciplinary team working. The national open meeting for this guideline was held on 18 September 2008 and was attended by 131 representatives of all the key specialties relevant to the guideline. The guideline group addresses every comment made by an external reviewer, and must justify any disagreement with the reviewer’s comments. However, other problems can sometimes occur as part of the condition or its treatment. It is important that the doctor knows about these, particularly if they are troublesome for you. You should answer ‘No’ even if you have had the problem in the past but not in the past month. Your personal data will be processed and held in accordance with the Data Protection Act 1998. The range of drugs involved and the differences in severity and frequency of adverse reactions make it difficult to present universal advice for limiting harm across all potential combinations. To minimise adverse effects prescribers should initiate a low dose of drug, be aware of key effects and monitoring requirements and discuss possible side effects with patient and carer/family. Some manufacturers rank adverse reactions under headings of frequency, the most frequent first, using the following convention: very common (>1/10 number of patients expected to experience the reaction); common (>1/100<1/10); uncommon (>1/1,000< 1/100); rare (>1/10,000<1/1,000); very rare (<1/10,000) including isolated reports. Care must be taken to differentiate between symptoms which may be drug related or related to the disease or current comorbidities. This list does not distinguish between adverse effects at different stages of the disease process. In patients on high doses of apomorphine these may persist and give rise to areas of erythema, tenderness and induration. Pruritis may occur at injection site, nausea and vomiting particularly when apomorphine treatment is first initiated usually as a result of the omission of domperidone, somnolence, transient sedation, neuropsychiatric disturbance including transient mild confusion and visual hallucinations ♦ uncommon impulse control responses to pramipexole include compulsive shopping, hypersexuality, libido disorder and pathological gambling. Geographical difference in multiple system atrophy with predominant parkinsonian features. Accuracy of Parkinson’s disease diagnosis in 610 general imaging in patients with mild parkinsonism and tremor disorders: practice patients in the West of Scotland. Slower progression of Parkinson’s disease with ropinirole versus changes in Parkinson’s disease. Dropping the bomb: the experience of being diagnosed including clinical criteria for diagnosis. Spousal perspective of Parkinson’s disease in middle secondary to right temporal lobe haemorrahage. J Neurosci Nurs parkinsonism due to a midbrain arteriovenous malformation: 2006;38(6):422-7. Gaenslen A, unmuth b, Godau J, liepelt I, Di Santo A, Schweitzer in Parkinson’s disease. J in the differential diagnosis of Parkinson’s disease: a prospective Neurosci Nurs 1991;23(5):325-9. Righini A, Antonini A, ferrarini M, de Notaris R, Canesi M, Triulzi 2004;329(7466):611-4. Accuracy of clinical diagnosis between striatonigral degeneration and Parkinson diagnosis in parkinsonism--a prospective study. Accuracy of the clinical diagnoses of lewy body A simple and accurate method of differentiating between Parkinson disease, Parkinson disease, and dementia with lewy bodies: a disease and progressive supranuclear palsy. Radiology 2008;246(1):214- clinical diagnosis of idiopathic Parkinson’s disease: a clinico- 21. Practice Parameter: diagnosis and prognosis of the pathogenesis of idiopathic Parkinson’s disease. J Neurol new onset Parkinson disease (an evidence-based review): report Neurosurgery Psychiatry 1988;51:745-52. Accuracy of diagnosis in patients A systematic review of prevalence studies of depression in with presumed Parkinson’s disease. Depression rating scales in Parkinson‘s disease: diagnosis of Parkinson’s disease in the community? Antidopaminergic therapy for of depression, psychosis, and dementia in Parkinson disease managing comorbidities in patients with Parkinson’s disease. Am (an evidence-based review): report of the quality Standards J Health Syst Pharm 2008;65(5):414-9. An analysis of published contribution of somatic symptoms to the diagnosis of depressive case series. Clin Reliability and validity of the beck depression inventory in patients Neuropharmacol 1995;18(4):338-47. Pergolide monotherapy in the treatment of early depression scale performance in Parkinson‘s disease.

Brighthope I: Nutritional medicine tables discount nebivolol 2.5 mg line arrhythmia magnesium, J Aust Coll Nutr Env Med 17:20-5 purchase 2.5 mg nebivolol with amex blood pressure ranges for dogs, 1998 generic nebivolol 5mg fast delivery arrhythmia etiology. A report from the General Practitioner Research Group nebivolol 2.5 mg low cost pulse pressure range normal, Practitioner 224(1340):208-11, 1980. Vitamin B6 is found in six forms—pyridoxine, pyridoxal, pyridoxamine, and their respective 5′-phosphates. The pyridoxine, pyridoxal, and pyridoxam- ine derivatives are oxidized to pyridoxal, which is rapidly phosphorylated in the liver. Formation of the metabolically active form of vitamin B6, pyri- doxal-5-phosphate, requires vitamin B2 and magnesium. Pyridoxal-5-phos- phate is the most direct clinically relevant measure of vitamin B6 status. Its par- ticipation in many vital metabolic pathways has created potential interest in its use in the management of diverse conditions ranging from carpal tunnel syndrome and diabetic neuropathy, through premenstrual syndrome and morning sickness, to cardiovascular disease and asthma. Pyridoxal 5′-phosphate–dependent enzymes are involved in the following1: ● Decarboxylation of amino acids to yield amines, many of which are impor- tant neurotransmitters and hormones. Pyridoxamine is a potent inhibitor of both advanced glycation end products and advanced lipid peroxidation formation. It may prove useful for limiting chemical modification of tissue proteins and associated pathology of aging and chronic diseases, including diabetes and atherosclerosis. Although some forms of vitamin B6 are lost from food during ordinary cooking, pyridoxine is unaffected. The typ- ical therapeutic dose is 50 to 200 mg/day, but the therapeutic dose range is 10 to 1000 mg/day. The plasma level of B6 reflects intake, while red cell transaminase enzyme reactivation reflects function and tissue status. Homocysteine has toxic effects on vascular endothelial cells, and plasma pyridoxal-5-phosphate lev- els below 20 nmol/L are found in 10% of patients with coronary artery dis- ease but only 2% of controls. Pooled data of nine trials suggest doses of pyridoxine up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms, including premenstrual depression. A double-blind trial using pyridoxine (25 mg every 8 hours for 3 days) in the treatment of morning sickness resulted in a significant reduction in vomiting and an improvement in nausea in those who initially reported severe nausea. From a therapeutic point of view, pyridoxal-5-phosphate should be tried in all cases of symp- tomatic primary sideroblastic anemia that have shown no response to pyridoxine. Potentially toxic levels in adults can result either from prolonged daily intake of vitamin B6 in excess of 100 mg or consumption of 2 g/day over a shorter period. Chronic pyridoxine intake may cause sensory neuropathy by exceeding the liver’s ability to phosphorylate pyridoxine to the active coenzyme pyridoxal 706 Part Three / Dietary Supplements phosphate. The resultant high pyridoxal level may be either be directly neu- rotoxic or cause toxicity through competition with pyridoxal binding sites. Other antiparkinsonian drugs, benserazide and carbidopa, cause vitamin B6 depletion by forming hydrazones. There have been many reports of abnormal tryptophan metabolism in women tak- ing either oral contraceptive or menopausal hormone replacement therapy. This probably reflects hormonal stimulation of tryptophan catabolism rather than a deficiency of vitamin B6 per se. The antituberculosis drug iso- niazid can also result in a functional vitamin B6 deficiency. Vitamin B6 enhances absorption of zinc picolinate, and vitamin C defi- ciency may increase vitamin B6 excretion. Seborrheic dermatitis, neuropathy, epilep- tiform convulsions, microcytic anemia, and glossitis have been reported. Chronic deficiency may lead to hyperoxaluria and an increased risk of kid- ney stones. Brighthope I: Nutritional medicine tables, J Aust Coll Nutr Env Med 17:20-5, 1998. Ambrosch A, Dierkes J, Lobmann R, et al: Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus, Diabet Med 18(3):185-92, 2001. Vitamin B6 (pyridoxine and pyridoxal 5′-phosphate)—monograph, Altern Med Rev 6(1):87-92, 2001. Sahakian V, Rouse D, Sipes S, et al: Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study, Obstet Gynecol 78(1):33-6, 1991. Vitamin B12 is essential for myelination of nerves, hematopoiesis, and syn- thesis of nucleic acids. The requirement for vitamin B12 is increased in pregnancy, celiac disease, and gastrointestinal disorders involving intrinsic factor production in the stomach or absorption in the ileum, as in pernicious anemia. Vitamin B12 deficiency is also reported to be a risk factor for heart disease, stroke, Alzheimer’s disease, and accelerated aging. Along with folic acid, pyridoxine, and riboflavin, vitamin B12 is a source of coenzymes that partic- ipate in one carbon metabolism. A carbon unit from serine or glycine is trans- ferred to tetrahydrofolate to form methylene-tetrahydrofolate. Formyl-tetrahydrofolate is used for the synthesis of purines, the building blocks nucleic acids. Methyl-tetrahydrofolate is used to methylate homocysteine to form methionine, a reaction catalyzed by a B12- containing methyltransferase. Homocysteine is a product of methionine metabolism and a precursor of methionine synthesis. Elevated plasma homocysteine is a risk factor for cardiovascular disease, stroke, thrombosis and is associated with loss of neurocognitive function as in Alzheimer’s dis- ease. Much of the methionine that is formed is converted to S-adenosylmethionine, a universal donor of methyl groups. Vitamin B12 is also a coenzyme for conversion of methylmalonyl-CoA to succinyl-CoA, an intermediate in the tricarboxylic acid cycle. Vegetarians can obtain vitamin B12 from yeast grown on a special B12-enriched medium. Intestinal bacteria synthesizes vitamin B12, but B12 produced in the colon is not absorbed. Active absorption of vitamin B12 requires intrinsic factor, a glycoprotein secreted by gastric pari- etal cells. Supplemental doses range from 5 to 50 μg/day, although a therapeutic dose range of 10 to 5000 μg/day has been suggested. The prevalence of vitamin B12 deficiency, which is higher than previously reported, increases with age, especially in persons over 65 years. Since many elderly people have a degree of atrophic gastritis, it has been suggested they meet their daily vitamin B12 requirements from fortified food or supplements rather than relying entirely on natural sources. There are a number of reasons, including cardiovascular health, to support a food fortification policy based on vitamin B and folic acid. Early evidence of deficiency is fatigue, weakness, lack of appetite, and glossitis. Subacute combined degeneration of the spinal cord presents with paresthesia, sensory loss, and ataxia. Major changes include sensory disturbances with tingling and numbness that is worst in the lower limbs, loss of vibration sense, an abnormal gait, and cognitive changes, including poor concentration, mem- Chapter 104 / Vitamin B12 (Cobalamin) 711 ory impairment, and frank dementia. Visual changes, impaired bladder and bowel control, and impotence have also been reported. The hematologic changes of megaloblastic anemia are indistinguishable from folic acid deficiency. While folate supplementation will normalize the blood picture, neurologic damage progresses and the patient develops overt subacute combined degeneration of the spinal cord. Ideally, intervention with vitamin B12 occurs early while the condition is reversible.

Assessment of conjunctival filtration blebs and glaucoma implants for function/scarring or patency and assessment of non-penetrating glaucoma surgical procedures 5 generic nebivolol 2.5 mg fast delivery blood pressure chart conversion. Ability to image an eye immediately preoperatively and postoperatively without contact with the eye 7 buy discount nebivolol 5 mg on-line blood pressure chart bhf. Avoids potential mechanical distortion of the anterior segment of the eye and change in angle/iris anatomy 9 buy nebivolol 5mg low price arteria jugularis externa. Can be used intra-operatively or post Descemet stripping and Descemet membrane endothelial keratoplasty to assess donor/host apposition 13 cheap 5 mg nebivolol free shipping arteria epigastrica superficialis. Can assess potential depth of corneal pathology prior to phototherapeutic keratectomy, automated lamellar keratoplasty etc. Dynamic investigation of anatomical angle variation and occludability with changes in illumination intensity 15. Potential for large scale, population screening at the primary care setting, in areas where angle closure glaucoma is highly prevalent D. Tumors in locations such as caruncle, inferior or superior fornix difficult to image 6. Cannot image structures behind the iris such as the ciliary body, ciliary processes, lens equator, zonules, and lesions or tumors in these areas 7. Inability to perform dynamic compression to discriminate appositional from synechial angle closure 8. Employs low coherence interferometry to compare the time delay of tissue reflections against a reference reflection, with image correction for the effect of refraction at the cornea-air interface C. Obtains images by scanning a beam of light laterally, creating a series of axial scans (A-scans) 1. Each A-scan contains information on the strength of a reflected signal as a function of depth 2. Archive and/or print the scan image for appropriate interpretation of the scan results for clinical assessment and billing purposes V. Conventional slit-lamp gonioscopy with a gonioprism and clinical grading of the angle by the Shaffer, Scheie or Spaeth classification systems C. Clinical and research applications of anterior segment optical coherence tomography - a review. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia. Diagnosis and management of conjunctival and corneal intraepithelial neoplasia using ultra high-resolution optical coherence tomography. Ultra high-resolution anterior segment optical coherence tomography in the evaluation of anterior corneal dystrophies and degenerations. Detection of primary angle-closure using anterior segment optical coherence tomography in Asian eyes. Reproducibility of anterior chamber angle measurements obtained with anterior segment optical coherence tomography. Anterior segment imaging: ultrasound biomicroscopy and anterior segment optical coherence tomography. Clinical and research applications of anterior segment optical coherence tomography—a review. Prior to intraocular surgery i) Cataract surgery ii) Secondary intraocular lens implantation b. If stromal opacification prevents endothelial cell imaging with specular microscopy, confocal microscopy can be used. Uses spatial filtering techniques to eliminate or reduce out-of-focus light, thus minimizing image degradation, when performing serial optical sectioning of the cornea 2. Based on imaging of the light reflected from an optical interface, such as the corneal endothelium and the aqueous humor 2. Degree of corneal opacification i) Unable to visualize endothelium in cases of corneal opacification 2. Mode i) Automated - appropriate when endothelial mosaic well-visualized ii) Manual - appropriate when endothelial cell borders not well visualized or endothelial mosaic interrupted by guttae ii. Endothelial cell density i) Normal adult endothelial cell density is 2000-3000 cells/mm2 iii. Endothelial cell morphology - cell shape and size i) Coefficient of variation - Average cell size divided by the standard deviation of the average cell size (i) Normally < 0. Less than 50% hexagonal cells may be an indication of poor cell function Additional Resources 1. Current state of in vivo confocal microscopy in management of microbial keratitis. The relative value of confocal microscopy and superficial corneal scrapings in the diagnosis of Acanthamoeba keratitis. Application of in vivo laser scanning confocal microscopy for evaluation of ocular surface diseases: lessons learned from pterygium, meibomian gland disease, and chemical burns. Presents an illuminated series of concentric rings and views the reflection from the corneal surface (handheld Placido disc, collimating keratoscopes) a. Collects reflected data points from the concentric rings and creates a map of the cornea 3. Uses color-coded map to present the data with warmer (red and orange) colors representing steeper curvature of the cornea and cooler (blue and green) colors representing flatter curvature. Instantaneous radius of curvature (tangential power): better sensitivity to peripheral changes iii. Useful in detecting irregular astigmatism or multifocal corneas- irregular corneal reflex, scissoring reflex 2. Helpful in determining etiology for unexplained decreased vision or unexpected post-surgical results including: under corrected aberrations, induced astigmatism, decentered ablations, irregular astigmatism, etc 9. Quality and reproducibility of images is operator dependent and dependent on quality of tear film 11. Non-standardized data maps; user can manipulate appearance of data by changing scales; colors may be absolute or varied (normalized) 12. Reflex is neutralized using appropriate spherocylindrical lenses yielding information on sphere and astigmatism 4. Non-linear or multiple reflexes that cannot be fully neutralized are seen in irregular astigmatism 5. Decreased light reflex may also indicate cataract or other optic pathway obstruction (i. The front of the cornea acts as a convex mirror whose reflection generates a virtual image of a target 2. The keratometer measures the size of the images reflected from at least four points of the central 2. A vergence formula is used to report the radius of curvature in millimeters or refracting power in diopters 4. Useful in detecting irregular astigmatism or multifocal corneas- irregular corneal reflex, scissoring reflex 2. Not useful for changes outside the central cornea (radial keratotomy, keratoconus) Additional Resources 1. The anterior segment is imaged by a rotating Scheimpflug camera, which measures thousands of elevation points to create a 3D image 2. Wavefront sensing devices measure the cumulative sum of optical aberrations induced by each structure in the visual pathway 3. Light rays from a single (safe) laser beam are aimed into the eye and the light rays reflect back from the retina in parallel rays 5.

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