By W. Kippler. Franciscan University of Steubenville.

Definition Chronichyperglycaemiaandothermetabolicabnormal- Investigations ities seen in diabetes mellitus due to another identifiable The diagnostic criteria are as for type 1 diabetes cheap norvasc 5 mg visa. Causes include chronic pancreatitis cheap 5 mg norvasc otc, post- duced numbers of insulin receptors due to muta- pancreatectomy, pancreatic cancer, cystic fibrosis or tions in the allele for the receptor gene. Older patients with antibodies to insulin receptors Insulin counter-regulatory hormones inhibit insulin reducing their affinity for insulin. Various insulins have been r Glucagon (glucagonoma) ‘designed’ with different pharmacokinetic effects (see r Catecholamines (phaeochromocytoma) Table 11. Drugs may inhibit insulin secretion or cause damage to r Abolus of short or immediate acting insulin given the pancreatic islets. Instead, lower amounts Long acting should be used with careful monitoring, or the patient will need to be admitted for intravenous glucose and insulin to avoid either diabetic ketoacidosis or hyperos- molar non-ketotic coma. Complications of diabetes Diabetic microvascular disease Definition Microvascular diabetic complications includes diabetic retinopathy, nephropathy and the neuropathies. Aetiology It is thought that microvascular complications are sec- ondary to the metabolic derangements of diabetes, in particular hyperglycaemia. Good glycaemic control of diabetes and control of hypertension can reduce the in- cidence of complications. This may impair the uous intravenous infusion via a tunelled line may also function of the proteins. An infusion pump controls the rate and pre- prandial boosts can be given simply and easily. They are vessels and the lens which do not require insulin expensiveandiftheyfail,theycancausediabeticketoaci- for glucose uptake. Exercise include smoking (at least as common in diabetics as also increases the use of glucose and hence reduces the non-diabetics) and hypertension. Hypogly- caemia may result from having too much insulin and not Definition eating enough, or exercising. If a patient is not eating, Diabetes can affect almost all the structures of the eye e. Scar formation leads to Leading cause of blindness under the age of 65 in the atraction retinal detachment. After 20 years of diabetes almost all pa- theirisareaccompaniedbyobstructionatthedrainage tients have some retinopathy. Around 40% of type 1 and angle causing a neovascular or thrombotic glaucoma 20% of type 2 diabetics have proliferative retinopathy. Aetiology Complications Control of blood sugars and concomitant hypertension Proliferative retinopathy may cause sudden loss of vi- has been shown to reduce risk of retinopathy and other sion from extensive haemorrhage or retinal detachment. Investigations Pathophysiology Screening is by fundoscopic or retinal camera examina- There is a thickening of the capillary basement mem- tion. Acu- haemorrhages) occur in some vessels while others be- ity testing should be performed to detect early macular come occluded. The obliteration of capillaries causes Management retinalischaemia(cottonwoolspots)whichinturnstim- r No specific treatment is required for background ulates the formation of new vessels at the surface of the retinopathy except to maximise diabetic control and retina and iris. All patients with diabetes should be screened regularly r Proliferative retinopathy is treated by panretinal pho- for diabetic retinopathy. There is then reduction in the growth neurysms later accompanied by blot haemorrhages factors which promote neovascularisation and hence and scattered hard exudates. Extensive obliteration of macular capillaries Prognosis r Pre-proliferative retinopathy is seen most commonly Prevention is the best management, by regular screening in young patients on insulin for about 10 years. Fifty per cent of patients with pre-proliferative Diabetic nephropathy changes develop proliferative retinopathy within a year. Definition r Proliferative retinopathy: New vessels develop most Diabetic nephropathy is a microvascular disease of type commonlyattheopticdisconthevenoussideadjacent 1 and 2 diabetes. They grow into the vitreous and round to the front of the eye when they are visible Incidence on the iris. These vessels may bleed either as vitreous Patient individual risk is falling however due to increas- (blue-greyopacity)orpre-retinalhaemorrhages(usu- ing rates of diabetes the overall prevalence of diabetic ally flat upper surface), which may cause obscuring of nephropathy is rising. Chapter 11: Diabetes mellitus 457 Age Diabetic patients may have other causes for proteinuria Increases with age. Management r Microalbuminuria and proteinuria require aggres- Pathophysiology sive treatment of hypertension (<130/75), better gly- In addition to the other microvascular mechanisms caemic control and cessation of smoking. It leads to diffuse sclerosis of the glomeru- ropathy which exacerbates postural hypotension. Hy- lus, which later condenses into nodular lesions, called poglycaemia may occur because insulin and sulpho- Kimmelstiel-Wilson lesions. The glomerular filtration rate is initially normal, but falls with progressive renal damage and chronic renal failure occurs around 5–7 years after macroalbuminuria Diabetic neuropathy occurs. Definition Nervedamage is one of the microvascular complications Clinical features of diabetes mellitus. The condition is asymptomatic until chronic renal fail- ure or nephrotic syndrome develops. Patients should be Incidence/prevalence screened annually for all diabetic complications and hy- Diabetesisthemostcommonmetabolicdisordercausing pertension.

Contra-indications cheap 2.5mg norvasc amex, adverse effects order norvasc 10mg amex, precautions – Avoid prolonged administration in patients with peptic ulcer, diabetes mellitus or cirrhosis. Contra-indications, adverse effects, precautions – Do not administer to patients with benign prostatic hyperplasia, urinary retention, closed-angle glaucoma, tachycardia. For each preparation, onset and duration vary greatly according to the patient and route of administration. Indications – Insulin-dependent diabetes – Diabetes during pregnancy – Degenerative complications of diabetes : retinopathy, neuropathy, etc. Duration – Insulin-dependent diabetics: life-time treatment – Other cases: according to clinical response and laboratory tests Contra-indications, adverse effects, precautions – Do not administer in patients with allergy to insulin (rare). Rotate injection sites systematically and use all available sites (upper arm, thighs, abdomen, upper back). Diabetes is controlled when: • there are no glucose and ketones in urine; • before-meal blood glucose levels are < 1. Treatment includes: insulin administration, specific diet, education and counselling under medical supervision (self-monitoring of blood glucose, self-administration of insulin, knowledge about signs of hypoglycaemia and hyperglycaemia). Also comes in solution containing 100 Iu/ml, administered only with calibrated syringe for Iu-100 insulin. Dosage – 20 to 40 Iu/day divided in 2 injections for intermediate-acting insulin, in 1 or 2 injections for long-acting insulin. Short-acting insulin is often administered in combination with an intermediate-acting or long-acting insulin. Examples of regimens: Insulin Administration • Short-acting insulin • 2 times/day before breakfast and lunch • Intermediate-acting insulin •at bedtime • Short-acting insulin • 3 times/day before breakfast, lunch and dinner • Long-acting insulin • at bedtime or before breakfast • Intermediate-acting with or without short- • 2 times/day before breakfast and dinner acting insulin Contra-indications, adverse effects, precautions – See "insulin: general information". Remove from the refrigerator 1 hour before administration or roll the vial between hands. Remarks – Storage: to be kept refrigerated (2°C to 8°C) – • do not freeze; discard if freezing occurs. Indications – As for insulin in general, particularly in cases of diabetic ketoacidosis and diabetic coma. Dosage – Emergency treatment of ketoacidosis and diabetic coma • Child: initial dose 0. Correct cautiously acidosis with isotonic solution of bicarbonate and, if necessary, post-insulinic hypokalaemia. When hyperglycemia is controlled, an intermediate-acting insulin may be substituted in order to limit injections. Short-acting insulin may be mixed with intermediate-acting insulin in the proportion of 10 to 50%. Contra-indications, adverse effects, precautions – See "Insulin: general information". Remarks – The terms "cristalline insulin" and "neutral insulin" are used either for soluble insulin or intermediate and long-acting insulin. If hypertension remains uncontrolled 5 and 10 minutes after injection, administer another dose of 20 mg (4 ml). Administer additional doses of 40 mg (8 ml) then 80 mg (16 ml) at 10 minute intervals as long as hypertension is not controlled (max. If the implant is inserted later (in the absence of pregnancy), it is recommended to use condoms during the first 7 days after the insertion. Contra-indications, adverse effects, precautions – Do not administer to patients with breast cancer, severe or recent liver disease, unexplained vaginal bleeding, current thromboembolic disorders. Use a copper intrauterine device or condoms or injectable medroxyprogesterone or an oral contraceptive containing 50 micrograms ethinylestradiol (however there is still a risk of oral contraceptive failure and the risk of adverse effects is increased). Remarks – Implants provide long term contraception, their efficacy is not conditioned by observance. However, the etonogestrel implant (one rod) is easier to insert and remove than the levonorgestrel implant (2 rods). Contra-indications, adverse effects, precautions – Do not administer if known allergy to lidocaine, impaired cardiac conduction. Contra-indications, adverse effects, precautions – Reduce the dose in patients with renal impairment; do not administer to patients with severe renal impairment. In the event of decreased urine output (< 30 ml/hour or 100 ml/4 hour), stop magnesium sulfate and perform delivery as soon as possible. If delivery cannot be performed immediately in a woman with eclampsia, stop magnesium sulfate for one hour then resume magnesium sulfate perfusion until delivery. The following injections may be administered within the 2 weeks before the scheduled date and up to 2 weeks after, without the need for additional contraception. In post-partum period, it is better to wait until the 5th day if possible, as the risk of bleeding is increased if the injection is administered between D0 and D4.

Insulin resistance and β-cell dysfunction in aging: The importance of dietary carbohydrate buy norvasc 10mg with visa. Effect of moderate levels of dietary fish oil on insulin secretion and sensitivity cheap 5mg norvasc fast delivery, and pancreas insulin content in normal rats. Effect of short-term consumption of a high fat diet on glucose tolerance and insulin sensitivity in the rat. The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. Heart rate vari- ability and fatty acid content of blood cell membranes: A dose-response study with n-3 fatty acids. Dietary lipids and blood cholesterol: Quantitative meta-analysis of metabolic ward studies. Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans. Patterns of weight change and their relation to diet in a cohort of healthy women. Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines. Coudray C, Bellanger J, Castiglia-Delavaud C, Rémésy C, Vermorel M, Rayssignuier Y. Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Deleterious metabolic effects of high-carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus. A prospective study of dietary calcium and other nutrients and the risk of kidney stones in men: 8 Year follow-up. Calcium intake influences the association of protein intake with rates of bones loss in elderly men and women. Macronutrients, energy intake, and breast cancer risk: Implications from different models. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Mediter- ranean diet, traditional risk factors, and the rate of cardiovascular complica- tions after myocardial infarction. Effect of fermentable fructo-oligosaccharides on mineral, nitrogen and energy diges- tive balance in the rat. Effects of feeding fermentable carbo- hydrates on the cecal concentrations of minerals and their fluxes between the cecum and blood plasma in the rat. The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. Influence of dietary levels of fat, cholesterol, and calcium on colorectal cancer. Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart Study. Epidemiological evidence of relationships between dietary poly- unsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. The effects of high and low energy density diets on satiety, energy intake, and eating time of obese and nonobese subjects. The effects of isocaloric exchange of dietary starch and sucrose on glucose tolerance, plasma insulin and serum lipids in man. Short-term effects of energy density on salivation, hunger and appetite in obese subjects. Long-term metabolic effects of n-3 polyunsaturated fatty acids in patients with coronary artery dis- ease. The association of plasma high-density lipoprotein cholesterol with dietary intake and alcohol consumption. The effects of sugar-beet fibre and wheat bran on iron and zinc absorption in rats. Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic vari- ables and the signal-averaged electrocardiogram. Nutrient intake and food group consumption of 10-year-olds by sugar intake level: The Bogalusa Heart Study. Fasching P, Ratheiser K, Waldhäusl W, Rohac M, Osterrode W, Nowotny P, Vierhapper H. Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance. No effect of short-term dietary supplementation of saturated and poly- and monounsaturated fatty acids on insulin secretion and sensitivity in healthy men. Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distri- bution when fed diets varying in animal protein, soluble fiber, or cholesterol content. Carbohydrate intake and body mass index in relation to the risk of glucose tolerance in an elderly population.

See also Obesity and overweight generic norvasc 2.5 mg line; 266 purchase norvasc 10mg free shipping, 294, 344, 346, 391, 479, 771, 882 Reference weights and heights; U. Department of Health, Education, and age/aging and, 143, 167 Welfare, 882 amino acids and, 697, 698, 700, 707, U. The plus (+) symbol indicates a change from the prepublication copy due to a calculation error. This book contains information obtained from authentic For orders, foreign rights, © 2013 European Society for Medical Oncology and highly regarded sources. Reprinted material is and reprint permissions, quoted with permission and sources are indicated. Product or corporate names For detailed prescribing information on the use of any may be trademarks or registered trademarks, and are product or procedure discussed herein, please consult used only for identifcation and explanation without intent the prescribing information or instructional material to infringe. Indeed, it is a key theme for oncologists in general, and in all aspects of medicine. Integrating research and innovation directed towards personalised care is also an objective of the European Union’s “Horizon 2020” science funding programme. Therefore, this book is produced in a timely fashion to provide unbiased information on the current understanding of personalised cancer medicine, and the achievements and strengths of medical professionals in the fght against cancer. Our goal was not to present the personalised medicine achievements in every tumour type or to elaborate on situations where it is not yet a part of standard practice. Instead, in this material we provide a state of the art on governing principles, illustrating them through examples of personalised medicine approaches in several tumour types. To make it a reality in the near future and to offer improved treatments, the patient’s active role is crucial. The statements from the book cannot be taken as medical advice and so, for any question about your disease or treatment, please consult your doctor. Basically, personalised medicine in cancer refers to the possibility to deliver the right treatment based on the characteristics of the individual’s tumour and genetics, using targeted therapies directed at effciently killing tumour cells. The goal is to shed light on the complexity of molecular pathways and give practical guidance to clinicians on applying this knowledge towards personalised treatment for their patients. Professor Piccart recalls that the predecessor of personalised medicine as we understand it now was frst applied in the feld of breast cancer, following the recognition of hormone-dependent cancers and the consequent development of agents that targeted their receptors. Furthermore, resistance to this drug was recognised early, making research and development of new therapies crucial even for this highly targetable cancer. For example, where treatment relies heavily on the evaluation of critical receptors in the tumour, these delicate tests must be done in laboratories using high-quality control procedures,” stresses Professor Piccart. We need to collaborate very intensively with partners in and outside of Europe and make sure we don’t sit back in the myth that personalised cancer medicine is already here. Personalised Medicine: General Defnition Personalised management is considered as the future of cancer care: medicine aiming at giving patients the best treatment according to their personal medical history, their physiological status, and the molecular characteristics of their tumours. Recent Approach to Cancer Until recently researchers and clinicians thought that all cancers deriving from the same site were biologically similar and they classifed the disease based on cell type (as determined by microscope assessment), size and presence/absence of regional nodes or distant metastases, as well as other features that may be observed on the tumour sample. Surgery has been, and still is, the cornerstone of treatment for the majority of cancer patients, together with chemotherapy and radiation therapy. These treatments may have drawbacks and side effects, particularly chemotherapy and radiotherapy, which, by killing cells that divide rapidly, kill cancer cells but also heavily affect healthy cells, resulting in partial effcacy and unwanted side effects. New Evidence in Cancer Biology It is now clear that tumours derived from the same organ can differ in extremely important ways, although the “old” diagnostic parameters are still essential elements for treatment decisions. One step forward is represented by the possibility to classify cancers based on critical molecular targets identifed by the high-quality translational research of the last decades. Drugs specifcally acting against molecular targets in cancer cells – called targeted therapies – have been developed and are used to counteract some types of cancer in selected patients, but many targets still need to be discovered and many drugs must yet be developed or improved. What Needs to be Done From Now On It is so essential to pursue efforts in cancer research and gather comprehensive information on each tumour in order to be able to identify all involved targets and hence determine the most appropriate treatment for each tumour and patient – be it used to cure, to slow down the growth of cancer cells, or to relieve symptoms. What Patients Should be Aware of Important information about the patient’s disease can be identifed by tissue and blood sampling. Despite possibly delaying treatment, these examinations are extremely valuable to characterise the tumour and thus determine the most appropriate treatment. The time at which samples are taken depends on the cancer type and stage of the disease. Biological samples can indeed be very useful in the initial phases of disease; however, it is also very important for patients to know that they can be just as useful in case cancer comes back, but it may also happen that if cancer returns a new sample is needed. Patients have to make sure that their donated biological samples will be kept at a biobank that can be accessed any time. In addition, patients help future patients when they give permission to use their blood and tissue samples in experimental research. However, the need for patients to re-consent every time their data is used is a hurdle that is currently limiting researchers’ efforts.

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