Gina T. Eubanks, BA
- Supervisor, Research Project Coordinator
- Division of Cardiovascular Medicine
- Emory University
- Atlanta, Georgia
End of Life Diabetes Prescribing may be modifed in patients with advanced life-limiting illness erectile dysfunction treatment vitamins buy super viagra 160 mg on line. Tailor glucose-lowering therapy and minimise diabetes-related adverse treatment effects erectile dysfunction ultrasound protocol super viagra 160 mg online. Hypoglycaemia is particularly hazardous for elderly patients (reduced awareness) or those living alone erectile dysfunction pills philippines order 160mg super viagra mastercard. Prevention includes using metformin or acarbose erectile dysfunction doctors albany ny order generic super viagra online, shorter-acting sulphonylureas and/or titrated doses of long acting insulins. Consider (by self-testing) the possibility of undetected night-time or other hypoglycaemia, especially if HbA1c is lower than average and. Nocturnal hypoglycaemia Nocturnal hypoglycaemia can be improved by careful attention to glucose-lowering therapy: Consider:. Train carers to use glucagon if hypoglycaemia is a recurrent problem and ensure supplies remain in date. Individuals with diabetes are two to four times more likely to develop cardiovascular disease relative to the general population and have a two- to fve- fold greater risk of dying from these conditions37. Diabetes is a signifcant cause of blindness in adults, non-traumatic lower limb amputations and end-stage renal disease resulting in transplantation and dialysis1,37. In patients with diabetes Life expectancy may be reduced by fve to ten years, mainly because of premature cardiovascular disease. Based on patient characteristics and response to therapy, higher or lower systolic blood pressure targets may be appropriate. Do not offer antiplatelet therapy for patients with type 2 diabetes without Anti-Platelet cardiovascular disease11. Patients should be encouraged to lose weight if necessary, exercise regularly, eat healthily (see section on lifestyle management) and all patients should Lifestyle be encouraged to stop smoking and given access to prescription medications which encourage smoking cessation. All patients should have feet checked at each visit and classifed as either low, Foot Care moderate, high risk or active according to National Model of Foot Care (see appendix 5). All patients with diabetes should have eyes examined at diagnosis and Eye Care regularly thereafter by Diabetic RetinaScreen - the National Diabetic Retinal Screening Programme Flu All patients with diabetes should be offered fu vaccination annually and Vaccination offered pneumovax. Early Detection of Complications the key to the management of complications is early detection and prompt intervention. Therefore systematic screening for complications forms part of a diabetes integrated care programme. The management of the risk factors associated with the development of these complications has already been outlined. Detection of Macrovascular Complications the risk of cardiovascular disease is increased 2- 4 fold in patients with diabetes. The underlying pathology is usually atherosclerosis which develops insidiously over many years and is usually advanced by the time symptoms occur. Examine feet at intervals according to Foot Protocol (see section on foot care Page 50 and Appendix 5) 1. All international evidence and research shows that there is no advantage to screening for retinopathy before the age of 12. There will be timely referral, assessment and treatment of abnormalities discovered. See section on Painful Peripheral Neuropathy Page 56 Neuropathy Please refer to Model of Care for the Diabetic Foot for foot screening Please refer also to further guidance on eye care and renal care. Hypertension Tight control of blood pressure reduces diabetes related micro- and macrovascular complications and is central to the overall management of diabetes. In their review of hypertension in Type 2 diabetes Vijan and Hayward 44found that. Improved control of blood pressure leads to substantially reduced risks for cardiovascular events and death. In patients with diabetes, aggressive blood pressure control also reduces the risk for microvascular events, including end-stage functional impairment (such as decreased visual acuity and end-stage renal disease). The risk reduction seen with hypertension control in patients with diabetes is substantially greater than that seen in persons in the general population who have similar blood pressure levels. It is also clear that blood pressure targets for patients with diabetes should be more aggressive. Monitoring Blood pressure should be measured at each visit in an adult with type 2 diabetes. For an adult with type 2 diabetes on antihypertensive drug treatment when diabetes is diagnosed, review blood pressure control and medications used. Make changes only if there is poor control or if current drug treatment is not appropriate because of microvascular complications or metabolic problems11. These targets should be seen as guides and a patient?s individual circumstances need to be considered when setting and agreeing targets. Based on patient characteristics and response to therapy, higher or lower systolic blood pressure targets may be appropriate. Add medications if lifestyle advice does not reduce blood pressure to below 140/80 mmHg (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage). Monitor blood pressure every 1?2 months, and intensify therapy if the person is already on antihypertensive drug treatment, until the blood pressure is consistently below 140/80 mmHg (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage). Non-Pharmacotherapy Low salt diet, reduced alcohol intake, exercise and weight loss are all benefcial in reducing blood pressure and should be instituted whenever appropriate in all patients with high blood pressure but should not delay commencement of pharmacotherapy (A). Do not use as frst line therapy in African or Caribbean family origin risk of angioedema 1. Add the other drug (that is, the calcium-channel blocker or diuretic) if the target is not reached with dual therapy. Check for possible adverse effects of antihypertensive drug treatment including the risks from unnecessarily low blood pressure. Patients with Type 2 diabetes frequently have refractory or resistant hypertension despite the use of 3 or 4 blood pressure agents. If this is the case then seek expert advice from a consultant endocrinologist as per national model of care. All treatment should again be given in conjunction with advice on diet, reduced alcohol intake, exercise and weight loss where appropriate. Type 2 diabetes is associated with an increased risk of cardiovascular and cerebrovascular events. Aspirin (75-150mg/day) should be prescribed in patients with diabetes and a history of cardio or cerebrovascular disease (secondary prevention). Clopidogrel (75mg/day) should be used instead of aspirin only in those with clear aspirin intolerance and aspirin allergy. Combination therapy with Aspirin (75mg/day) and Clopidogrel (75mg/day) can be maintained for up to 12 months after an acute coronary syndrome. Source: National Clinical Programme Diabetes Smoking It has been shown that smokers have poorer glycaemic control than non-smokers or ex- smokers. Smoking affects the body?s metabolic control, increases insulin resistance and interferes with the action of insulin in the body. Research has shown that smokers with diabetes have a heightened risk of morbidity and premature death associated with the development of macrovascular complications. Smoking is also related to the premature development of microvascular complications. Monitoring Patients should be asked about their smoking habits at each clinic visit. Treatment Non Pharmacotherapy Some of the most effective methods of helping smokers to quit include brief intervention advice. One of the most important aspects about advising or giving support is to determine where the person is in relation to the cycle of change as outlined by Prochaska and Diclemente (1983), Cycle of Change. Smoking cessation counselling and other forms of treatment should be included in routine care. To date there is no evidence of the impact of pharmacotherapy specifc to diabetic smokers. However the research suggests that the extensive benefts of quitting versus the heightened risks of continuing to smoke, should guide the decision regarding use of nicotine replacement therapy and other pharmacological aides for cessation. Therapy in a form acceptable to the patient should be offered for appropriate length of time. Rigorous studies of their short and long-term effects are needed in determining their safety and effcacy and their cardiopulmonary effects in comparison with smoking and standard approaches to smoking cessation7. Lipids the guidance in relation to primary prevention of vascular risk factors is previously outlined. Lifestyle modifcation focusing on the reduction of saturated fat, trans fat, and cholesterol intake; increase of omega-3 fatty acids, fbre, and plant stanols/sterols; weight loss (if indicated); and increased physical activity should be recommended to improve the lipid profle in patients with diabetes7.
New England Journal of Medicine erectile dysfunction l-arginine discount super viagra 160 mg visa, Vol 354 erectile dysfunction injection dosage cheap 160mg super viagra with amex, No 2 erectile dysfunction drugs causing order super viagra 160 mg with visa, Jan 2006 erectile dysfunction homeopathic drugs generic super viagra 160mg online, pp 166?178 174 A New Look at Hypothyroidism Pui C. Vol 69, No 5, Nov 2008, pp 819-827 10 Congenital Hypothyroidism and Thyroid Cancer Minjing Zou and Yufei Shi Dept. Girls are more frequently affected than boys (female to male ratios ranging from 2:1 to 4:1)(4). The mental retardation and neurodevelopmental impairment include poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span (5). Consequently, most countries operate neonatal screening programs to enable early detection of cases and therapeutic intervention. Treatment consists of a daily dose of thyroid hormone (thyroxine) by mouth (6, 7). Often a technetium (Tc-99m pertechnetate) thyroid scan is performed to detect a structurally abnormal gland. The Tc-99m pertechnetate exam will help differentiate thyroid dysgenesis from thyroid dyshormonogenesis. Even most of those with athyreosis and undetectable T4 levels at birth develop with normal intelligence. Glorieux et al reported that 27 patients with congenital hypothyroidism diagnosed by neonatal screening were examined at the age of 12 years. The 12 patients with severe hypothyroidism at diagnosis (thyroxine < 26 nmol/L, and area-of-the-knee epiphyses < 0. The study by Henry et al showed the prevalence of 1 in 2759 live births with 121,404 newborn infants screened in the same Central region (Riyadh), the predominant cause of congenital hypothyroidism found in the study being athyreosis (45%), followed by thyroid ectopia (24%) and dyshormonogenesis (17%) (13). However, the number of the newborn infants screened is smaller in these two studies. However, molecular characterization of underlying genetic defects has not been systematically conducted yet among the patients. There is also a paucity of data on clinical treatment and follow-up of the patients. First, many do not fully understand the seriousness of the disease, refuse to participate in the neonatal screening or otherwise show poor compliance in diagnosis, treatment and follow-up. Inadequate treatment can lead to poor academic performance and learning problems which tend to be overlooked by the child?s parents (2) 3. The etiology of congenital hypothyroidism the etiology of congenital hypothyroidism is heterogeneous and is caused by either thyroid dysgenesis (75-80%) or dyshormonogenesis (15-20%) (1, 20). The disorder is usually sporadic but up to 2% of familial cases have been reported (23-25). The extrathyroid genes involved in the control of migration of the median thyroid bud during embryogenesis, such as adhesion molecules, and vascular factors involved in the stabilization of the bi-lobed structure of the thyroid may also play a role (22). In thyroid dyshormonogenesis (defects of thyroid hormone biosynthesis), patients have a normal sized or enlarged thyroid gland (goitre) in the normal position and are often recessively inherited (1). Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis. Thyroid hormone synthesis and the genes involved in the process Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are critical determinants of brain and somatic development in infants and of metabolic activity in adults; they also affect the function of virtually every organ system(33). The synthetic process occurs in three major steps as shown in Figure 1(33, 34): production and accumulation of the raw materials, biosynthesis of the hormones on a backbone of Tg, release of the free hormones from Tg and secretion into blood. Tyrosines are provided from Tg, a large glycoprotein which is synthesized by thyroid epithelial cells and secreted into the lumen of the follicle forming colloid (essentially a pool of Tg). A molecule of Tg contains 134 tyrosines, although only a handful of these are actually used to synthesize T4 and T3. Another important component in the synthesis of thyroid hormones is iodine, which is taken up from blood by sodium-iodide symporters located on the outer plasma membrane of thyroid epithelial cells. To release T4 and T3, thyroglobulin is engulfed 178 A New Look at Hypothyroidism by the thyrocytes through pinocytosis, digested in lysosomes, and then secreted into the bloodstream. In contrast, monoiodotyrosine and diiodotyrosine are found only in minute amounts in the bloodstream. The major form of thyroid hormone in the blood is thyroxine (T4) (approximately 80%), which has a longer half life than T3. The preprotein is composed of a 19-amino acid signal peptide, followed by a 2749-residue polypeptide (42). The 780 amino acid transmembrane protein (pendrin) expressed in the thyroid gland, inner ear, endometrium, and kidney, where it is involved in iodide, chloride, formate, and nitrate transport (63). In the thyroid gland, pendrin acts at the apical pole of thyrocytes to transport intracellular iodide into the follicular lumen (64). Loss of pendrin function causes a failure in iodine supply and an organification defect often leading to euthyroid goitres (65). To ensure that iodine is available for thyroid hormone biosynthesis, two highly specialized systems evolved in the thyroid gland. One accumulates iodide in thyroid cells by active membrane transport via the sodium- iodide symporter (67). The gene is 36 kb and contains an 867 bp coding sequence divided into 5 exons and is located on chromosome 6 (6q24-25)(69-71). Mutation of the gene has been recently reported in patients with severe hypothyroidism (32). Thyroid dysgenesis and the genes involved in the process Thyroid dysgenesis is a defect in the organogenesis of the gland resulting in hypoplastic, ectopic or absent-thyroid gland and the underlying pathogenesis is largely unknown. Although the disorder is usually sporadic, a minority of cases are transmitted as Mendelian diseases (21-25, 72). The extrathyroid genes involved in the control of migration of the median thyroid bud during embryogenesis, such as adhesion molecules, and vascular factors involved in the stabilization of the bi-lobed structure of thyroid may also play a role (22). More than 20 cases of thyroid cancer have been reported in the literature with similar frequency of either papillary or follicular cancer type (Table1) (27). Induction of papillary thyroid carcinoma following subtotal thyroidectomy has also been reported in rats (80). However, genetic defect in the genes involved in this signalling pathway has not been investigated in thyroid cancers derived from dyshormonogenic goitres. In our previous studies, we have reported two cases of metastatic thyroid carcinoma derived from congenital dyshormonogenic goitres (Figure 2) from two consanguineal families (27, 86). They were non- compliant with L-thyroxine treatment and had multiple surgeries since childhood due to recurrence of dyshormonogenic goitres and pressure problems. It is unfortunate to see goitres and cancer development in these patients given that these complications can be easily prevented if proper L-thyroxine treatment is given. The health care cost for treating these complications, and physical and mental sufferings for the patients are huge as compared to L-thyroxine replacement therapy. However, inadequate treatment or poor compliant with treatment can lead to poor academic performance, and in severe cases, thyroid goitre and cancer. Education and close follow-up are warranted for patients with poor response to L-thyroxine replacement therapy. Adequate amounts of L-thyroxine treatment are essential to prevent cancer development. Cooper et al reported a large kindred of patients with congenital goitre, in which two siblings developed metastaticfollicular thyroid carcinoma and a leak of nonhormonal iodide from the thyroid. Medeiros-Neto and Stanbury reviewed 109 patients with dyshormonogenesis, 15 patients had thyroid follicular cancer with unknown genetic defects (92). Based on rigid criteria of malignancy such as vascular invasion, 8 of the 15 reported casesin the literature appear to be clear examples of thyroid malignancy. Monoiodotyrosine and diiodotyrosine are synthesized from the iodination of tyrosyl residues within thyroglobulin. After organification, iodinated donor and acceptor iodotyrosines are fused in the coupling reaction to form either triiodothyronine (T3) or thyroxine (T4), a process that involves only a small fraction of iodotyrosines. Thyroglobulin is then engulfed by thyrocytes through pinocytosis and digested in lysosomes, and T4 and T3 are secreted into the bloodstream. Monoiodotyrosine and diiodotyrosine are deiodinated by iodotyrosine deiodinase, and the released iodide is recycled (68). The non-tumor area shows hyperplastic thyroid micro-and macro-follicles without colloid, and cytological atypia, which are consistent with dyshormonogenesis (C, x20; F, x40). Whole body images were acquired in anterior and posterior projections before I 131 ablation. The scan showed large neck uptake and multiple foci in the chest, skull, and pelvis suggestive of lung and bone metastasis (a).
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Additionally erectile dysfunction drugs class purchase super viagra paypal, the evidence on valproate is from small studies erectile dysfunction keeping it up cheap super viagra 160 mg free shipping, and valproate is associated with undesirable adverse effects erectile dysfunction drug has least side effects cheap super viagra 160 mg with mastercard. Gabapentin + nortriptyline impotence unani treatment in india purchase super viagra 160 mg free shipping, gabapentin + oxycodone, imipramine, lacosamide, levetiracetam, oxycodone, venlafaxine the analyses showed that these drugs either do not appear more effective than placebo or there is a lack of evidence and/or inconsistent evidence about whether they are better than placebo at reducing pain. This could be due to the reporting of average change in pain across all patients in the study and the subsequent use of this in the syntheses. If the response to pain is bimodal (that is, patients either respond well or do not respond at all), the average change in pain score across all patients may not be the most appropriate measure of pain response. Economic A systematic review of published cost?utility analyses found considerations inconsistent and, at times, contradictory results from a heterogeneous group of studies, each of which addressed a small subgroup of potentially relevant comparators. Seventeen treatments were assessed in the model, which could be configured to rely on either dose-adjusted or non-dose-adjusted effectiveness evidence. The model suggested that capsaicin cream is likely to have the highest expected net benefit. Its recommendation therefore emphasises the importance of the patient?s attitude to topical treatment in defining whether it is likely to be an acceptable, and therefore cost effective, form of treatment. Although the model suggested that amitriptyline is associated with slightly poorer value for money than gabapentin, the difference is small. In this instance, treatment with amitriptyline was associated with lower net costs than treatment with gabapentin in 100% of model iterations, and it was found to have greater net benefit than placebo 85% of the time. Therefore, it would be appropriate to recommend these treatments in a context where other options were removed from the decision-space that is, when they are contraindicated or when they have been tried and proved ineffective or were not tolerated. However, the uncertainty inherent in the estimate of nortriptyline?s effectiveness, coupled with its comparatively high acquisition cost, makes it difficult to exclude the possibility that it is a poor choice of treatment: it was no more cost effective than placebo in 43% of model iterations. However, it was also not convinced that sufficient evidence had been adduced to enable them to make a recommendation suggesting that nortriptyline should not be used. The health economic model provided no support for the use of cannabis sativa extract, capsaicin patch, lacosamide, levetiracetam or oxcarbazepine. In all analyses, these treatments were dominated by a number of other alternatives and, in some cases, they were dominated by placebo (that is, they were predicted to have higher costs and lower net health gains than treatment with placebo). It also acknowledged that it had not been possible to explore the cost effectiveness of combination therapies and specified sequences of treatments. Quality of Overall, the quality of most of the evidence for different outcomes was evidence low and very low. The evidence on patient-reported global improvement was of low and very low quality, the evidence on sleep was of moderate to low quality, and the evidence on adverse effects was of low to very low quality. The evidence on 30% and 50% pain relief was of low quality, whereas the evidence on mean continuous pain was considered very low quality. Most of the studies did not have sufficient follow-up periods to assess the long-term effect of different drugs, which is considered to be important for chronic conditions such as neuropathic pain. In addition, the included studies used different methods for dealing with missing data. Most of the studies that dealt with missing data used the last observation carried forward, which has been reported to produce bias in the results (please see the discussion on the approach to missing data in appendix D). A further complexity is that the included studies had differential allowances of concomitant medications, with some studies excluding some drugs but not others. The reasons for not providing separate recommendations for peripheral and central pain are provided in sections 3. However, current evidence is not sufficient to warrant any recommendation on combination therapies. Group members also noted that, in their experience, amitriptyline can be an effective treatment, and the adverse effects with which it is associated are well recognised and managed in non-specialist settings. In addition, the Lyrica (Pfizer) brand of pregabalin has patent protection until July 2017 for its licensed indication of treatment of peripheral and central neuropathic pain; until such time as this patent expires generic pregabalin products will not be licensed for specific indications and their use may be off-label and may infringe the patent, see summaries of product characteristics of pregabalin products for details. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. See the General Medical Council?s Good practice in prescribing and managing medicines and devices for further information. Research recommendations See appendix B for full details of research recommendations. Research recommendation B1 What is the clinical effectiveness, cost effectiveness and tolerability of pharmacological monotherapy compared with combination therapy for treating neuropathic pain? Research recommendation B2 Is response to pharmacological treatment predicted more reliably by underlying aetiology or by symptom characteristics? Research recommendation B4 What are the key factors, including additional care and support, that influence participation9 and quality of life in people with neuropathic pain? Research recommendation B6 Is there a potential for dependence associated with pharmacological agents for neuropathic pain? These are included in Table 4 above (studies where the ?type of pain? is listed as peripheral). Network meta-analyses were performed for all but 3 outcomes: for 2 of these outcomes, data were only available on 1 drug compared with placebo (for at least moderate improvement in patient-reported global improvement at 28?7days and sleep interference on a normalised 10-point scale at 56?7 days) and the third had a pairwise analysis to pool 2 studies comparing gabapentin with placebo (sleep interference on normalised 10-point scale at 56?7 days). As with ?all neuropathic pain?, it was not possible to perform meta-analyses for the outcomes ?patient-reported improvement in daily physical and emotional functioning, including sleep? (except for a continuous measure of sleep disturbance) and ?use of rescue medication? because of the heterogeneity in the reporting of the outcomes across the literature. Results from the analyses of individual adverse effects were performed for ?all neuropathic pain? only and are included in appendix J (see the methods used in this guideline in appendix D for an explanation of why this was only performed for ?all neuropathic pain?). Network meta-analyses of 15 studies at 4, 8, and 12 weeks follow-up show uncertainty about which treatment is best at improving patient-reported global improvement. As a result, it was not possible to synthesise the results from many of these studies in a meaningful way. Network analyses and a pairwise meta-analysis of 10 studies at 4, 8 and 12 weeks follow-up show that a number of drugs may be better than placebo at improving sleep on a continuous scale. However, it is not clear if this is clinically significant and there is considerable uncertainty about which drugs were the best at improving sleep. However, it was difficult to draw conclusions on which particular drugs were best or worst for particular adverse effects. However, there is considerable uncertainty about which treatment is best at providing these levels of pain relief. These outcomes are available for only a limited number of drugs and at different follow-up periods. However, network meta-analyses of 22 studies at 4 weeks, 17 studies at 8 weeks, and 13 studies at 12 weeks show improvement in mean pain but it is not clear if these differences are clinically significant. However, the confidence in these results and in the overall ratings of different drugs is low. Trade-off As with ?all neuropathic pain?, there was considerable uncertainty in between the results from the network meta-analyses and pairwise benefits and meta-analyses about the outcomes that should guide decision making harms on the best pharmacological treatment. A reason could be that a large proportion of evidence on ?all neuropathic pain? came from studies on peripheral neuropathic pain. The main differences between pharmacological treatments for ?all neuropathic pain? and peripheral neuropathic pain were: Amitriptyline there is slightly less evidence (2 studies) included in the analyses on the efficacy of amitriptyline in peripheral pain. Gabapentin the analyses on the efficacy of gabapentin were consistent for peripheral pain because the very-low-quality study that showed negative effect of gabapentin was not on peripheral pain. Levetiracetam and morphine there is no evidence on global improvement or pain relief for peripheral pain. Nortriptyline although the evidence on nortriptyline that was included in the effectiveness analyses came from the same single trial that was included in the ?all neuropathic pain? analyses, greater effectiveness was estimated in the peripheral-only analyses. This is because nortriptyline is joined to the wider network via gabapentin, so it also benefits from the raised estimate of gabapentin?s effectiveness. Tramadol there is no evidence on global improvement but some efficacy evidence on 30% and 50% pain relief at 4 weeks. Therefore, it felt that the recommendations on ?all neuropathic pain? should also apply to peripheral neuropathic pain. Quality of As with ?all neuropathic pain?, the quality of most of the evidence for evidence different outcomes was low and very low. The evidence on patient-reported global improvement was of moderate, low and very low quality, the evidence on sleep was of moderate to very low quality, and the evidence on adverse effects was of low to very low quality. The evidence on 30% and 50% pain relief and mean continuous pain were both considered very low quality. As with ?all neuropathic pain?, most of the studies did not have sufficient follow-up periods to assess the long-term effect of different drugs, which is considered to be important for a chronic condition such as neuropathic pain. There was also differential usage of concomitant medications among the included studies.
Most of these contents were indigestible remains of teleost fish such as bones erectile dysfunction caused by steroids purchase 160 mg super viagra visa, eye lenses and otoliths erectile dysfunction treatment chandigarh cheap super viagra master card, and an occasional squid beak erectile dysfunction oil treatment best order super viagra. Incidentally the two known bycatch Hector?s dolphins had the most undigested remains erectile dysfunction drugs kamagra buy super viagra 160 mg with mastercard. The dolphin caught in Blueskin Bay had an undigested fish in its stomach while the dolphin caught in Kaikoura had fish bones as well as otoliths. The Maui?s dolphin had also eaten relatively recently and intact fish, invertebrates, bones and otoliths were found in both the first and second chambers of the stomach. The male common dolphins had evidence of recent feeding with a range of food items in the stomachs including intact fish, otoliths, bones and squid, squid mantles, and squid beaks. The bottlenose dolphin had been entangled for some time and was severely emaciated. Because of technical problems with the sectioning equipment the sections obtained from some teeth (asterisks on Table 5) were not of high enough quality to determine the age with certainty. A second tooth sample from each of these animals is being processed at the time of writing, and the results will be included in an amended report. For the Hector?s dolphins with teeth (n = 11) the mean tooth weight and size was similar to that reported previously (Slooten 1991; Duignan et al. The accepted protocol for small cetaceans is that one dark band (stained) and one light band (unstained) constitute one year?s growth (Perrin & Myrick 1980; Slooten 1991). Based on this assumption, the Hector?s dolphins ranged in age from one and a half years to 15 years old. The common dolphins ranged from animals three or four years old to one male that was eight years old. The bottlenose dolphin is one of the animals for which a second tooth is being sectioned. The ovaries were present, however they were inactive, without evidence of ovulation or corpora (Table 6). These findings are similar to those for female Hector?s dolphins, 6 years and younger, reported by Slooten (1991) and also consistent with those of immature female 14 Duignan & Jones?Autopsy of cetaceans, 2002/03 dolphins, 5 years or younger, from previous bycatch reports (Duignan et al. The gonads of three dolphins (H58/02 and H60/02) had been scavenged or decomposed and were not available for examination. The common dolphin had a 13 mm corpus albicans in the left ovary but the uterus was not well developed and milk was not present in the mammary glands. This dolphin was estimated to be four years old and may be at the end of puberty and showing the first evidence of ovarian activity. Males the gonads were examined for four male Hector?s dolphins and one Maui?s dol- phin. The summed testicular weight of 198 g is below the range previously found for fully mature combined testicular mass (266 g?1210 g) as reported by Slooten (1991) and Duignan et al. Although the gradation between imma- ture, pubertal and mature is probably indistinct, pubescent males would be ex- pected to have an intermediate combined testicular mass. The remaining dol- phins were definitely immature with summed testicular mass ranging from 21 g to 30 g. In previous studies the combined testicular mass for the gonads of im- mature dolphins ranged from 10. Active gonads are consistent with its capture date in mid October as most reproductive activity for this species occurs in spring and summer (Watson 1981; Leatherwood et al. The two remaining dolphins were shorter in body length and had markedly smaller testes at 56 g and 66 g summed mass respectively. The gonads were mature but inactive and consistent with their time of death in the autumn as both were caught on 30 April. It should be noted that freezing can compromise the interpretation of subtle pathological changes and make the determination of cause of death difficult. Of the four female Hector?s dolphins, only one (H59/02) showed clear evidence of having died as a result of fishing operations. This animal had net marks on its skin, subcutaneous trauma, and respiratory congestion and oedema characteristic of asphyxiation. The remaining females were either too autolysed to permit detection of possible entanglement related pathology or had been badly scavenged. Both had evidence of blunt trauma with the juvenile H61/02 having trauma to the head and neck that may have been the result of boat strike or aggression from other dolphins, predator attack (killer whales), or trauma in rough seas. Their pathology is consistent with this in that all have epidermal net marks, evidence of acute blunt trauma, and acute pulmonary and tracheal congestion, oedema, and haemorrhage. The bottlenose dolphin was found beachcast with fishing gear entangled around its rostrum and embedded in the gingival at the commisures of the mouth. The latter, along with drag caused by the mass of gear, prevented feeding and this animal was severely emaciated. Its ultimate cause of death was respiratory failure as indicated by markedly congested and oedematous lungs. Discussion the dolphins examined for this contract were received frozen and double bagged. The orange tags around the tail-stock of Hector?s dolphins were very effective for animal identification. It was beneficial having a list of animals being shipped forwarded by e-mail to allow a cross check between animals shipped and those received. From a health and safety perspective the packaging was sufficient to prevent contamination of the environment by the carcasses provided they are maintained frozen. This is ideal for pathology and is recommended for animals originating on the North Island where shipping chilled carcasses should be possible logistically. A second originated in Timaru, but was transported personally by Al Hutt to avoid having it frozen and to facilitate a speedy diagnosis. The three male dolphins had not attained full adult length and only the largest appears to have attained gonadal maturity. The female common dolphin was the largest of the four common dolphins submitted and she had attained gonadal maturity at four years. The common dolphins were all caught as a result of commercial fishing activities and had cutaneous, soft tissue, and pulmonary lesions suggestive of blunt trauma, entanglement and asphyxiation. The Hector?s dolphins caught by commercial or recreational nets and those found beachcast were from areas of the west and east coasts of the South Island, areas which have a high Hector?s dolphin population (Slooten & Dawson 1994; Slooten et al. A single Maui?s dolphin from the west coast of the North Island where a relict population occurs (Ferreira & Roberts 2003), was also submitted for necropsy. Morphological features of these animals were consistent with those reported previously for Cephalorhynchus hectori (Morzer-Bruyns & Baker 1973; Slooten 1991; Slooten & Dawson 1994). The life history data collected from these dolphins complements data from 12 animals examined in 1999, 16 examined in 2000, and 18 in 2001, and 10 from 2002 (Duignan et al. The sex ratio of dolphins submitted was equal, as compared to a bias in previous years with males comprising 62% of the animals submitted in 2001, 56% in 2000, and 83% in 1999. This male bias over the previous three years differs from a female bias reported by Slooten (1991). There was also a bias towards younger and immature animals as in previous studies based on bycatch and beachcast animals (Slooten 1991; Dawson 1991; Duignan et al. Determination of the species of fish and invertebrates ingested by the dolphins was beyond the scope of this investigation, but all hard parts removed from the 18 Duignan & Jones?Autopsy of cetaceans, 2002/03 stomachs have been archived for future studies. As in previous years, the stomach contents of Hector?s and Maui?s dolphins have been archived for Kirsty Russell, Auckland University, for studies on foraging. Stomach contents of Hector?s dolphins were similar to those examined by Duignan et al. The remains predominately consisted of indigestible teleost fish bones and otoliths and invertebrate carapaces. Fish predominated in the stomachs of Hector?s and Maui?s dolphins, but fish and squid were equally represented in the stomach of common dolphins. The bottlenose dolphin was so emaciated that there were no recognizable food remains in its stomach. The principle of age determination in cetaceans based on counting growth layers or annuli in teeth is commonly used on a variety of species (Perrin & Myrick 1980). Although widely used the technique is subject to difficulties in methodology, interpretation, reader variability, variability among teeth, and the lack of known age animals (Dapson 1980).
The drug binds to which antithyroid agents cause agranulocytosis is unknown impotence for males cheap super viagra amex, but anti- neutrophil cytoplasmic antibodies have been identifed erectile dysfunction treatment by exercise buy super viagra australia. The antibodies then attach by Cooper and coworkers erectile dysfunction with ms purchase super viagra 160mg line, agranulocytosis occurred more frequently to the complex erectile dysfunction ginkgo biloba quality super viagra 160mg, and cell toxicity occurs. More recently, Takata and colleagues found the prev- alence of neutropenia to be signifcantly greater in patients receiving methimazole 30 mg/day compared with those receiving 15 mg/day. However, another study demonstrated no antibodies form complexes with the causative drug, and the immune relationship between age or dose and the incidence of thionamide- induced agranulocytosis. This is the proposed mechanism of agranulocytosis induced by quinidine Ticlopidine is an antiplatelet agent indicated for the treatment and quinine (eFig. In this reaction, the causative drug is not directly involved patients and agranulocytosis in 0. Agranulocytosis most commonly occurs activation, and phagocytic elimination through the mononuclear within 1 to 3 months from the initiation of ticlopidine. Typically, in immune-mediated mechanisms, the drug is the best treatment option, with counts usually returning agranulocytosis occurs within days to a few weeks after drug expo- to normal within 2 to 4 weeks. For some drugs, though, the risk may be 15 weeks after the initiation of therapy, with a peak onset between 3 and 4 weeks. These agents include antithyroid medications, ticlopidine, clozapine, sulfasalazine, trimethoprim?sulfamethoxazole, and drug-induced agranulocytosis has been studied primarily with chlor- promazine,62 which is thought to affect cells in the cell cycle phase? The incidence of appears to have no cellularity (aplastic), but over time, it becomes drug induced hemolytic anemia is estimated to be about one in 1 to hyperplastic. It is believed that toxic effects of the phenothiazines are 2 million individuals, although a clear incidence has been diffcult to not seen in all patients taking the medications because most patients ascertain because of diffculty in establishing a clear diagnosis and have enough bone marrow reserve to overcome the toxic effects. Those in the frst cat- the incidence of neutropenia was signifcantly higher in patients egory may operate much like the process that leads to immune- who had intact spleens. The mechanism of toxicity is largely mediated agranulocytosis, or they can suppress regulator cells, unknown. Suggested mechanisms have included inhibition of which can lead to the production of autoantibodies. Extravascular hemolysis refers to the chotic medications and has received much attention over recent years. Symptoms of agranulocytosis and because of its reversible nature if detected early hemolytic anemia can include fatigue, malaise, pallor, and shortness in therapy, clozapine is currently only available through a limited of breath. In vitro studies have suggested that the formation of a nitrenium ion unstable metabolite may be responsible for clozapine-induced agran- ulocytosis. Levofoxacin the only prospective, randomized trial to date did not confrm the methyldopa 73 minocycline beneft of these growth factors. One systematic review found that patients with Phenazopyridine a neutrophil nadir less than 100 cells/mm3 (0. The frst drug associated with this type of reaction was are found even in the absence of the drug. The laboratory and clinical fndings may be indistinguishable 12 months of initiating therapy. After 2 by having a direct effect on the immune system in a mechanism the withdrawal of the drug, results of the Coombs test can remain similar to microbial or viral infections. Other drugs associated with the production of means to diagnose drug-induced immune hemolytic anemia. The direct Coombs test involves combining the leading to a positive antiglobulin test result. Patients with hemolysis had no impairment of the mononu- the frst mechanism is the ?hapten mechanism? or ?drug clear phagocytic system. In this mechanism, patients make an anti- cause a positive result on the indirect Coombs test and hemolytic body against a stable complex of the drug with some soluble noncel- anemia. When the drug is administered again, an mune hemolytic anemia include levodopa, mefenamic acid, and immune complex of drug?antidrug forms and attaches nonspecif- diclofenac. The direct Coombs test result may remain positive Hemolytic Anemia for several weeks. The penicillin and cephalosporin derivatives, A hereditary condition, drug-induced oxidative hemolytic ane- when given in high doses, are primarily associated with this type mia, most often accompanies a glucose-6-phosphate dehydroge- of immune reaction. In this mechanism, drugs bind to an anti- glutathione is a substrate for glutathione peroxidase, an enzyme that body, usually IgM, to form an immune complex. Patients with these enzyme defcien- Hemolytic Anemia cies should be advised to avoid medications capable of inducing the Observational study evidence hemolysis. Primaquine Defciencies in either vitamin B12 or folate are responsible for the Sulfacetamide impaired proliferation and maturation of hematopoietic cells, resulting Sulfamethoxazole in cell arrest and subsequent sequestration. Examination of peripheral Sulfanilamide blood shows an increase in the mean corpuscular hemoglobin con- 24 centration. Dihydrofolate reduc- the degree of hemolysis depends on the severity of the enzyme tase is an enzyme responsible for generating tetrahydrofolate, an defciency and the amount of oxidative stress. One case of drug-induced oxidative cause drug-induced megaloblastic anemia with both low and high hemolytic anemia has been reported in a nursing child when dap- doses,99,100 particularly in patients with a partial vitamin B or folate 12 sone (an oxidizing agent) was transferred from the breast milk of the defciency. It has been postulated that phenytoin, primidone, and phenobarbital cause drug-induced megaloblastic anemia by either inhibiting folate absorption or by increasing folate catabolism. Hemolytic anemia caused by drugs Anemia through the hapten or adsorption and autoimmune mechanisms Case report evidence (probable or defnite causality rating) tends to be slower in onset and mild to moderate in severity. Con- azathioprine versely, hemolysis prompted through the immune complex mecha- Chloramphenicol nism (innocent bystander) phenomenon can have a sudden onset, Colchicine lead to severe hemolysis, and result in renal failure. The treatment Cotrimoxazole Cyclophosphamide of drug-induced immune hemolytic anemia includes the immedi- Cytarabine ate removal of the offending agent and supportive care. In severe 5-Fluorodeoxyuridine cases, glucocorticoids can be helpful, but their use outside of auto- 5-Fluorouracil immune hemolytic anemia is not supported by strong evidence. Nonimmune-mediated mechanisms, such as direct- Drug-Induced Megaloblastic Anemia toxicity-type reactions, are associated with medications that cause bone marrow suppression. This results in suppressed thrombopoiesis When drug-induced megaloblastic anemia is related to chemother- and a decreased number of megakaryocytes. This type of reaction is apy, no real therapeutic option is available, and the anemia becomes commonly associated with chemotherapeutic agents. If drug-induced megaloblastic Several mechanisms have been proposed for the development anemia results from cotrimoxazole, a trial course of folinic acid, 5 to of immune-mediated drug-induced thrombocytopenia. After the binding of antibodies to the platelet surface, tal, but some clinicians suggest that folic acid supplementation can lysis occurs through complement activation or through clearance decrease the effectiveness of the antiepileptic medications. The annual incidence of drug-induced thrombocy- topenia is about 10 cases per 1,000,000 population (excluding cases Quinine, anticonvulsants, and nonsteroidal antiinfammatory associated with heparin). However, the drug contains structural elements that 98 drugs identifed that had reports associated with thrombocyto- are noncovalently complementary to regions of the antibody and penia. In clinical trials reaction that usually occurs within the frst 2 days of therapy. However, a plausible immune-mediated but more severe and can be associated with more complications. In contrast to the two previously discussed immune-mediated 50% or more decrease in platelet count from baseline, and thrombo- mechanisms (hapten type and drug dependent), the drug is not pres- sis can occur. Certain patient populations eptifbatide, is also associated with thrombocytopenia. Therefore, it is not surprising that medical, obstetric, and pediatric patients, especially those receiv- this molecule may exhibit some immunogenic properties. For those with a delayed response (6?8 days coagulant microparticles are also released that increase the risk of later), drug-specifc antibodies are produced during this time, and thrombosis. A heparin-induced platelet aggregation let recovery, and continued anticoagulation with an alternative study can help to determine the offending agent. In contrast, the drug-dependent antibody reac- tion requires the presence of the drug to allow antibody binding. TreaTmenT Although several mechanisms of drug-induced thrombocytopenia have been proposed, it is often not possible to determine the mecha- Drug-Induced Thrombocytopenia nism for an individual drug or patient, and more than one mecha- nism can be responsible for the condition. The primary treatment of drug-induced thrombocytopenia is the fnal type of immune-mediated thrombocytopenia has removal of the offending drug and symptomatic treatment of the been categorized as immune complex?induced thrombocytope- patient. The most sometimes helpful when clinicians are initially trying to distinguish common, type I, occurs in about 10% to 20% of patients treated between drug-induced thrombocytopenia and idiopathic thrombo- with heparin. In some Heparin-like cases, however, thrombocytopenia can persist for weeks or molecules months, especially in the case of chemotherapy-induced thrombocytopenia or thrombocytopenia caused by immune mechanisms. In this setting, limited options are available to maintain platelets in a safe range while awaiting count recovery. Historically, transfusions were used to maintain 1 platelet counts until bone marrow recovery.
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