Stefano Schena, M.D., Ph.D.

https://www.hopkinsmedicine.org/profiles/results/directory/profile/10004105/stefano-schena

The prognosis is generally good; patients should avoid further exposure to the offending drug managing diabetes type 1 cheap repaglinide 2 mg free shipping. Polyuria and nocturia are the result of tubular damage in the medullary area of the kidney diabetic tea order repaglinide 2 mg visa, leading to defects in the renal concentrating ability diabetes test on your arm 2 mg repaglinide purchase fast delivery. Necrosis of the papillae diabetes type 1 impact on health care resources purchase repaglinide online from canada, which may subsequently slough off and be passed in the urine diabetes mellitus type 2 drug therapy buy repaglinide 2 mg fast delivery, sometimes causes ureteric colic or acute ureteral obstruction. In cases of analgesic nephropathy the drug should be stopped and replaced if necessary with paracetamol or dihydrocodeine. Investigations should be performed on all patients, although renal imaging is usually unnecessary. Essential hypertension Hypertension leads to characteristic histological changes in the renal vessels and intrarenal vasculature over time. These include intimal thickening with reduplication of the elastic lamina, reduction in kidney size and an increase in the proportion of sclerotic glomeruli. The changes are usually accompanied by some deterioration in renal function, which is much more common in black Africans. Accelerated or malignant-phase hypertension is marked by the development of fibrinoid necrosis in afferent glomerular arterioles and fibrin deposition in arteriolar walls. A rapid rise in blood pressure may trigger these arteriolar lesions, and a vicious circle is then established whereby fibrin deposition leads to renal damage, increased renin release and a further increase in blood pressure. There is progressive uraemia and, if untreated, fewer than 10% of patients survive 10 years. Renal hypertension Bilateral renal disease Hypertension commonly complicates bilateral renal disease, such as in chronic glomerulonephritis, reflux nephropathy or analgesic nephropathy. Two main mechanisms are responsible: Activation of the renin­angiotensin­aldosterone system Retention of salt and water, leading to an increase in blood volume and hence blood pressure. These drugs confer an additional renoprotective effect for a given degree of blood pressure control when compared with other hypotensive drugs. In younger patients, particularly women, it is more commonly due to fibromuscular hyperplasia. Renal perfusion pressure is reduced and renal ischaemia results in a reduction in the pressure in afferent glomerular arterioles. If non-invasive imaging is inconclusive and clinical suspicion is high, conventional arteriography is necessary. Management Standard medical therapy for atherosclerotic vascular disease is indicated in all patients and includes lifestyle modification (increased exercise and smoking cessation), statins, antiplatelet therapy (p. Transluminal angioplasty (to dilate the stenotic region) and stent placement is used in patients with fibromuscular hyperplasia but does not offer any additional benefit (to medical treatment) in most patients with atheromatous stenosis. Prevalence of stone disease is much higher in the Middle East due to a higher oxalate- and lower calcium-containing diet (see below) and increased risk of dehydration in hot climates. Aetiology Most stones are composed of calcium oxalate and/or calcium phosphate: other types are uric acid, magnesium ammonium phosphate (struvite) and cystine stones. Calcium stones Hypercalciuria Increased urinary calcium excretion is the most common metabolic abnormality in calcium stone-formers. Causes of hypercalciuria are: Hypercalcaemia, of which the most common cause (p. Renal calculi and nephrocalcinosis 381 Primary renal disease, such as medullary sponge kidney and polycystic renal disease, is also associated with calcium stones. The alkaline urine seen in the renal tubular acidoses favours the precipitation of calcium phosphate. Hyperoxaluria Increased oxalate excretion favours the formation of calcium oxalate, even if calcium excretion is normal. The main causes are: Dietary hyperoxaluria: a high dietary intake of oxalate-rich foods. Low dietary calcium intake can also result in hyperoxaluria via decreased intestinal binding of oxalate (by calcium) and the resulting increased oxalate absorption and urinary excretion. Dehydration secondary to fluid loss from the gut also plays a part in stone formation. There is widespread calcium oxalate crystal deposition in the kidneys, and later in other tissues (myocardium, tissues and bone). Patients with ileostomies are also at risk of developing urate stones, as loss of bicarbonate from gastrointestinal secretions results in the production of an acid urine and reduced solubility of uric acid. These stones are often large and fill the pelvicalyceal system, producing the typical radiopaque staghorn calculus. Cystine stones these stones occur with cystinuria, an autosomal recessive condition affecting cystine and dibasic amino acid transport (lysine, ornithine and arginine) in the epithelial cells of renal tubules and the gastrointestinal tract. Excessive urinary excretion of cystine, the least soluble of the amino acids, leads to the formation of crystals and calculi. Clinical features Most people with urinary tract calculi are asymptomatic; pain is the most common symptom (Table 9. The pain is felt anywhere between the loin and the groin and may radiate into the scrotum or labium or into the tip of the penis. There will be features of acute pyelonephritis or Gram-negative septicaemia if there is associated infection in an obstructed urinary system. Urethral stones may cause bladder outflow obstruction, resulting in anuria and painful bladder distension. Pain from an ectopic pregnancy or leaking aortic aneurysm may be mistaken for renal colic. Investigations Investigations include a mid-stream specimen of urine for culture and measurement of serum urea, electrolytes, creatinine and calcium levels. A detailed history may reveal possible aetiological factors for stone formation. A further work-up to look for underlying metabolic risk factors is indicated in all patients other than the elderly with a single episode (Table 9. Patients are managed at home if there is no evidence of sepsis and they are able to take oral medications and fluids. Indications for intervention include persistent pain, infection above the site of Renal calculi and nephrocalcinosis 383 Table 9. Prevention of recurrence Further treatment depends on the type of stone and any underlying condition identified during screening investigations (Table 9. For prevention of all stones, whatever the cause, a high intake of fluid (to produce a urine volume of 2­2. Patients should be encouraged to consume a normal calcium diet and avoid foods containing large amounts of oxalate. Meticulous control of bacteriuria, if necessary with long-term, low-dose, prophylactic antibiotics and a high fluid intake, helps to prevent recurrent stone formation. Oral sodium bicarbonate supplements to maintain an alkaline urine, and hence increased solubility of uric acid, are an alternative approach in those patients unable to tolerate allopurinol. A very high fluid intake (5 L of water in 24 hours) is needed to maintain solubility of cystine in the urine. An alternative is D-penicillamine, which chelates cystine, forming a more soluble complex. Nephrocalcinosis Nephrocalcinosis is diffuse renal parenchymal calcification that is detectable radiologically. Eventually there is compression and thinning of the renal parenchyma, with a decrease in size of the kidney. Aetiology In adults the common causes are prostatic obstruction (hypertrophy or tumour), gynaecological cancer and calculi (Table 9. Clinical features Upper urinary tract obstruction results in a dull ache in the flank or loin, which may be provoked by an increase in urine volume. Partial obstruction causes polyuria as a result of tubular damage and impairment of concentrating mechanisms. Retention with overflow is characterized by the frequent passage of small quantities of urine. Depending on the site of obstruction an enlarged bladder or hydronephrotic kidney may be felt on examination. Pelvic (for malignancy) and rectal examination (for prostate enlargement) is essential in determining the cause of obstruction. Investigations Imaging studies are performed to identify the site and nature of the obstruction and, together with serum creatinine, to assess function of the affected kidney. Excretion urography identifies the site of obstruction and shows a characteristic appearance (a delayed nephrogram, which eventually becomes denser than the non-obstructed side). Management Surgery is the usual treatment for persistent urinary tract obstruction. Elimination of the obstruction may be associated with a massive post-operative diuresis, resulting partly from a solute diuresis from salt and urea retained during obstruction and partly from the renal concentrating defect. In some cases, definitive relief of obstruction is not possible and urinary diversion may be required. This may be simply an indwelling urethral catheter, a stent placed across the obstructing lesion or the formation of an ileal conduit. It is important to consider situations when urea and creatinine are less accurate predictors of deteriorating renal function. These criteria indicate an increasing degree of renal damage and have a predictive value for mortality. This might either be due to changes in the circulation or intrarenal vasomotor changes that drop glomerular perfusion pressures. Common causes with a falling effective circulating volume include: Hypovolaemia of any cause, including dehydration or haemorrhage Hypotension without hypovolaemia, including cirrhosis or septic shock Low cardiac output, including cardiac failure or cardiogenic shock Combinations of the above. Where uncertain as to the volume state of a patient, a fluid challenge of 250 mL crystalloid will often prove whether hypotension is fluidresponsive. Heart rate, blood pressure and urine output will all guide response to resuscitation. It is not the accumulation of urea itself that causes symptoms, but a combination of many different metabolic abnormalities. Recovery of renal function typically occurs after 7­21 days and in the recovery phase, which may last some weeks, there is often passage of large amounts of dilute urine. Breathlessness occurs from a combination of anaemia and pulmonary oedema secondary to volume overload. Pericarditis occurs with severe untreated uraemia and may be complicated by a pericardial effusion and tamponade. Impaired platelet function causes bruising and exacerbates gastrointestinal bleeding. Investigation of the uraemic emergency the purpose of investigation, together with clinical examination, is three-fold: 1. To document the degree of renal impairment and obtain baseline values so that the response to treatment can be monitored. Hypovolaemia (prerenal) and obstruction (postrenal) must be excluded as contributing factors in all patients. Fluid balance, as intake and output (particularly urine output), will be key to recovery. Daily weights, lying and standing blood pressure, medication review to withhold nephrotoxins, collateral history and past results will all form part of the management plan. Establish the aetiology and treat the underlying cause History, including family history, systemic disease, use of nephrotoxic drugs Examination includes assessment of haemodynamic status, pelvic and rectal examination Investigations (p. Management of established renal failure Seek advice from a nephrologist Once fluid balance has been corrected, the daily fluid intake should equal fluid lost on the previous day plus insensible losses (approximately 500 mL) Diet ­ enteral nutrition is preferred over parenteral; sodium and potassium is restricted Nursing care. The most common cause of death is sepsis as a result of impaired immune defence (from uraemia and malnutrition) and instrumentation (dialysis and urinary catheters and vascular lines). In patients who survive, renal function usually begins to recover within 1­3 weeks. Diabetes mellitus, hypertension and atherosclerotic renal vascular disease are the most common causes in European countries (Table 9. East, schistosomiasis is a common cause due to a ureterovesical stricture causing urinary tract obstruction. Regardless of the underlying cause, fibrosis of the remaining tubules, glomeruli and small blood vessels results in progressive renal scarring and loss of renal function in some individuals. Clinical features and investigations the early stages of renal failure are often completely asymptomatic. Anaemia Anaemia is primarily due to reduced erythropoietin production by the diseased kidney. Shortened red cell survival, increased blood loss (from the gut, during haemodialysis and as a result of repeated sampling) and dietary deficiency of haematinics (iron and folate) also contribute. Oedema may be due to a combination of primary renal salt and water retention and heart failure. Autonomic dysfunction presents as postural hypotension and disturbed gastrointestinal motility. Median nerve compression in the carpal tunnel is common and is usually caused by 2-microglobulin-related amyloidosis (a complication of dialysis). This occurs due to an increased frequency of hypertension, dyslipidaemia and vascular calcification. Renal disease also results in a form of cardiomyopathy with both systolic and diastolic dysfunction. Other complications these include an increased risk of peptic ulceration, acute pancreatitis, hyperuricaemia, erectile dysfunction and an increased incidence of malignancy. A normochromic anaemia, small kidneys on ultrasonography and the presence of renal osteodystrophy favour a chronic process. Management the aims of treatment are: Specific therapy directed at the underlying cause of renal disease. Renoprotection the goal of treatment should be to maintain the blood pressure at less than 120/ 80 mmHg and to maintain a urinary protein concentration of less than 0. Reduce cardiovascular risk Optimal control of blood pressure and reduction of proteinuria (as above) Statins to lower cholesterol to <4.

Their patients are required to have financial resources or employment that provide third-party coverage blood sugar sex magik purchase repaglinide 2 mg overnight delivery, social indicators of a better prognosis in contrast to programs that accept patients with a host of social diabetes mellitus in dogs prognosis repaglinide 2 mg buy without a prescription, psychological diabetes symptoms for toddlers discount repaglinide 2 mg mastercard, and economic problems diabetes symptoms for type 2 buy repaglinide uk. Programs and studies vary in their definitions and measurement of recovery diabetes insipidus epocrates 2 mg repaglinide with mastercard, of success and failure, even of the term alcoholism itself (McElrath 1995). Most studies have failed to include control groups (a near impossibility because of the availability of A. In his research, Robert Fiorentine (1999) reports that any participation in twelve-step programs is associated with lower levels of drug and alcohol use and that the magnitude of the association is about the same for both illicit drug and alcohol use. Less-than-weekly participants, who were more likely to be problematic drinkers, had levels of drug and alcohol use that were no different from those of nonparticipants. However, commitment to attend a twelve-step program might be a predictor of success; the program itself might actually do little or nothing to generate abstinence. This contrasts with the use of drugs such as Antabuse and naltrexone, which research has found effective with those having a problem with alcohol, especially used in conjunction with behavioral therapy (Glaser 2015). Why is it misleading to focus on the purported success of some peer programs that have reduced the number of youngsters who experiment with drugs How might a treatment response be based on the societal definition of "abuse" rather than the properties inherent in a drug What medications are used for the treatment of nicotine addiction, alcohol abuse, heroin abuse, and prescription painkiller abuse Why would a heroin addict who has not been coerced and does not want to discontinue heroin use go into treatment How does the strength of psychoactive substances as reinforcers explain the difficulty in treating drug abusers No nation remains spared, but these crimes flourish in unstable countries where law enforcement and border controls are weak, poverty is endemic and corruption is rampant, with a devastating impact on the rule of law, security and development. Instability in one country can easily spill over to neighbouring countries and then to the wider region, becoming a threat to international security" (United Nations Office on Drugs and Crime 2014: 10). The connection between poverty and drug trafficking can be seen in the Mexican state of Guerrero, known for the famous beaches of Acapulco. On its steep mountainsides, young adolescents whose size and agility are an advantage earn more in one day harvesting opium from poppy fields than their parents do in a week (Ahmed 2015). This article examines the international and domestic traffic in illegal drugs that, by any estimate, is a multibillion-dollar-a-year industry with enormous profit-to-cost ratios. For example, heroin can be purchased in 700-gram units in Bangkok, Thailand, for between $7,500 and $9,500 and sold in the United States for between $60,000 and $70,000. A kilo of Colombian heroin that can be purchased for $6,000 is sold wholesale in the United Sates for $80,000 (Ahmed 2016c). Because the product is illegal but nevertheless in great demand, a level of free enterprise that Adam Smith never envisioned characterizes drug trafficking: a market totally devoid of legal constraints in which prices and profits are governed only by the law of supply and demand. The drug business shares many elements with the business of selling legal products: "It requires lots of working capital, steady supplies of raw materials, sophisticated manufacturing facilities, reliable shipping contractors and wholesale distributors, the all-important marketing arms and access to retail franchises for maximum market penetration" (Brzezinski 2002: 26). Sylvia Longmire (2011: 10) notes that drug "cartels are run like profit-seeking corporations; so when the market makes a move, so do they. As in any major industry there are various functional levels: manufacturers, importers, wholesalers, distributors, retailers, and consumers. Workers in the drug business range from leaders of powerful international cartels to street dealers whose activities Copyright 2018 Cengage Learning. At the manufacturing and importation levels, the drug business is usually concentrated among a relatively few people who head major trafficking organizations; at the retail level, it is filled with a large, fluctuating, and open-ended number of dealers and consumers. Because people at the highest levels of the drug trade are often connected by kinship and ethnicity, we will frequently refer to the ethnicity of criminal organizations. For decades, the American Mafia controlled heroin trafficked into the United States. In a drug-trafficking network that became known as the "French Connection," New York City­based American Mafia Families purchased heroin from Corsican sources working with French sailors operating from Marseilles to transship the drug directly to the United States where it was distributed to drug dealers working in low-income, minority communities. The demise of the French Connection coupled with the subsequent emergence of criminal syndicates based in Mexico and Colombia marked a significant evolution in the international drug trade. These new traffickers introduced cocaine into the United States on a massive scale, launching unparalleled waves of drug crimes and violence. Throughout the 1980s and 1990s, the foreign crime syndicates continued to increase their wealth and dominance over the U. Today, at the highest levels of trafficking in illegal drugs destined for the United States are organizations based in Colombia and Mexico who produce and export unprecedented volumes of cocaine, methamphetamine, heroin, marijuana, and various novel psychoactive substances such as K2. The main source of chemicals needed to manufacture drugs such as methamphetamine is China. The trafficking hierarchy maintains control of workers through highly compartmentalized cell structures that separate production, shipment, distribution, money laundering, communications, security, and recruitment. They have at their disposal the most technologically advanced aircraft, vessels, vehicles, radar, communications equipment, and weapons that money can buy. They have established vast counterintelligence capabilities and transportation networks. Traffickers and terrorists have similar logistical needs in terms of material and the covert movement of goods, people, and money. Both bring corrupt officials whose services provide mutual benefits, such as greater access to fraudulent documents, including passports and customs papers. Drug traffickers can also gain considerable freedom of movement when they operate in conjunction with terrorists who control large amounts of territory (Beers and Taylor 2002). This gives rise to the term narcoterrorism-terrorist acts carried out by groups that are directly or indirectly involved in cultivating, manufacturing, transporting, or distributing illegal drugs. Links between drug trafficking and terrorist organizations can range from protection, transportation, and taxation to direct trafficking by terrorists to finance activities. Terrorist and drug-trafficking groups share some attributes, in particular organizational structure such as compartmentalization. Terrorist groups and trafficking organizations often have similar requirements for moving people, money, material, and weapons across borders and often operate under a similar set of contingencies. The distinction between drug trafficking and terrorism is becoming increasingly blurred, with an overlapping, symbiotic relationship between terrorism and drug trafficking. Taliban insurgents in Afghanistan, for example, have been using heroin to finance their efforts. The Taliban tax poppy farmers and the traders who collect opium paste from them for transport to labs where it is converted into heroin. By 2016, a change in the drug trafficking role of the Taliban was becoming apparent- instead of taxation and protection, the organization is taking a more direct role and it has become difficult to distinguish the group from a dedicated drug cartel (Ahmed 2016b; Shah and Mashal 2016). In return for cash payments, or possibly in exchange for weapons, some units protect drug laboratories and clandestine airstrips in southern Colombia. The propensity to use violence has led to the domination of potential Bolivian and Peruvian rivals in the cocaine business. Colombia is the only country in the world where the three main plant-based illegal drugs-cocaine, heroin, and marijuana-are produced in significant amounts (Thoumi 2002). The high Andes divide the colombians have been able to dominate the cocaine industry for a number of reasons such as geography and a violent reputation. It is a nation that has been torn by political strife, with civil wars in 1902 and 1948. La Violencia, as the civil war of 1948­1958 is known, cost the lives of about 300,000 people (Riding 1987). It ended when the Liberals and the Conservatives formed the National Front, but several Marxist insurgencies continued to threaten the stability of the central government. Not only was murder frequent, but the methods that used were often sadistic, such as the corte de corbata-the infamous "Colombian necktie"-in which the throat is cut longitudinally and the tongue is pulled through to hang like a tie. It also contains "chop-up houses" where victims of drug-related violence are murdered and dismembered-sometimes while they are still alive (Neuman 2015b). Laboratories have relocated to cities far from cultivation sites to be closer to sources of precursor chemicals and because improved law enforcement methods have facilitated the detection of jungle laboratories. Precursor chemicals are usually manufactured in the United States and Germany; Panama and Mexico serve as major transit sources. Colombian cartels, using dummy companies and multiple suppliers, pay up to ten times the normal prices for these chemicals. Traffickers have also been stealing precursor shipments in transit from the point of entry into Colombia en route to a legitimate end user. Some Colombian traffickers set up laboratories in other Latin American countries and even in the United States in response to increased law enforcement in Colombia and the increasing cost of ether, sulfuric acid, and acetone in Colombia. Acetone, sulfuric acid, and ether are widely available for commercial purposes in the United States. While sulfuric acid and acetone have wide industrial use in Colombia, ether does not, and each kilo of cocaine requires 17 liters of ether. The cost of these chemicals has increased as a result of controls imposed by the Colombian government on their importation and sale and of U. Colombia is a relatively large country, and many regions have only a weak federal presence. The vacuum left by the central government has proved ideal for coca cultivation and cocaine manufacture because it left areas where only local officials had to be bribed, a cheaper and less risky action than bribery at the federal level (Thoumi 1995). The militias have reinforced this support by building roads and schools in the areas from which they have driven out the guerillas. Pushed westward by Colombian military successes into jungle areas populated primarily by indigenous Indians, some former paramilitary and drug-trafficking groups-the two often overlap-abandoned their ideological bent and have forged alliances with their former left-wing enemies. The same groups in other parts continue their violent struggles, but now the goal is control over the drug trade (Romero 2009a). The paramilitaries reached an accommodation with the government and many leaders were extradited to the United States. In the United States, trafficking groups are organized around "cells" that operate within a given geographic area. Because these cells are based on family relationships or close friendships, outsiders who attempt to penetrate the cell run a high risk of arousing suspicion. Some cells specialize in a particular facet of the drug trade, such as cocaine transport, storage, wholesale distribution, or money laundering. Each cell, which may comprise ten or more individuals, operates Copyright 2018 Cengage Learning. Cell: Compartmentalization involves cells with about ten members, each operating independently-members of one cell typically do not know members of other cells. Operating within a geographic area, the head of each cell reports directly to a controller. Controller: Responsible for overall operations of the several cells within a region, the controller reports to central command via cell phone or Internet. Central command: Located in a relatively safe haven, the central command oversees and coordinates operations through the controllers. The head of each cell reports to a regional director, who is responsible for the overall management of several cells. The regional director, in turn, reports directly to one of the top drug lords or his designate, based in Colombia. Trusted lieutenants of the organization in the United States have discretion in day-to-day operations, but ultimate authority rests with the leadership in Colombia (Ledwith 2000). Traffickers from Colombia use state-of-the-art encryption devices to translate their communications into indecipherable code. This evolving technology presents a significant impediment to law enforcement investigations of criminal activities. In the past, the necessity for frequent communication between drug lords in Colombia and their surrogates in the United States made the drug-trafficking organizations vulnerable to law enforcement wiretaps. Now, however, through the use of encryption technology, the traffickers can protect their electronic business communications from law enforcement interception and hide information that could be used to build criminal cases against them. Colombian managers dispatched to the Dominican Republic and Puerto Rico operate these command and control centers and are responsible for overseeing drug trafficking in the region. Puerto Rico, a 110-mile-long island with the third busiest seaport in North America, is ideal for smugglers, who have fewer problems getting their goods to the United States because customs agents do not search shipments from Puerto Rico. Colombians direct networks of transporters that oversee the importation, storage, exportation, and wholesale distribution of cocaine destined for the continental United States. They have franchised to criminals from the Dominican Republic a portion of the mid-level wholesale cocaine and heroin trade on the East Coast of the United States. The Dominican traffickers operating in the United States, not the Colombians, are the ones who are subject to arrest, while the top-level Colombians control the organization with international drugtrafficking organizations are often structured in a compartmental fashion. This mode of operation reduces profits somewhat for the syndicate leaders but reduces their exposure to U. If arrested, the Dominicans will have little damaging information that can be used against their Colombian masters. Colombian Heroin Trafficking Colombian entry into heroin is based on demographics. During the 1980s, the popularity of cocaine began to fade among urban professionals, and "cokeheads" tend to burn out after five years. With this dwindling consumer base, the Colombians expanded into Europe but with only limited success-heroin was the hard drug of choice and that market was dominated by Pakistani and Turkish groups. By 1999, Colombians had become major heroin wholesalers, often selling cocaine and heroin to wholesalers as part of a package deal. Colombian market advantages include geographic proximity to the United States and established distribution networks. They required their Dominican cells in the United States to take a couple of kilos of heroin for every 100 kilos of cocaine to give out free samples to customers-and the strategy worked, creating an entirely new client base for heroin. Smoking is a less efficient way of ingesting than intravenous use because a lot of the drug literally goes up in smoke. Therefore, only when it is relatively cheap and therefore plentiful will smoking heroin predominate. Since the 1980s Colombia has become a leading poppy grower, and Colombians have become major heroin wholesalers. At the end of 1991, police raids in Colombia disclosed thousands of acres of poppy plants ("Colombian Heroin May Be Increasing" 1991).

Law enforcement has discovered Web site-affiliated doctors who authorize hundreds of prescriptions a day diabetes mellitus hypoglycemia repaglinide 1 mg with amex. In addition to paying the pharmacy for the cost of the medicine blood glucose app buy generic repaglinide canada, the Internet facilitator will also pay the pharmacy an agreed upon amount that may reach into the millions of dollars diabetes diet bernstein cheap 1 mg repaglinide with amex. It is estimated that Tijuana alone has about 1 diabetes type 2 ketones urine order repaglinide from india,700 pharmacies type 1 juvenile diabetes life expectancy buy repaglinide 1 mg on-line, many of which sell controlled substances illegally over the counter. Diversion from lawful sources, often the result of "doctor shopping" or overprescribing, has gained more attention in recent years (Querna 2005). One aspect of this problem is trafficking in the synthetic opiate OxyContin, particularly in rural areas of the United States that have not heretofore had a drug problem. In the rural Appalachian region, which has many miners with injuries and a shortage of doctors, prescribing the drug has often been indiscriminate. In these areas, a number of doctors have been convicted for overprescribing (Bowman 2005). With little or no physical examination, each paid $200 and was given a prescription for OxyContin. In 2002, a 55-year-old Florida medical doctor received a sentence of sixty-two years in prison after a manslaughter conviction that involved running an OxyContin "pill mill" that was linked to several overdose deaths (Associated Press 2002). In 2003 it was revealed that methadone, often prescribed for treating chronic pain, is being diverted to the black market and abused by recreational drug users, often with deadly consequences. There have been an alarming number of methadone overdose fatalities, which since 1997 have surpassed those from heroin. Methadone is usually taken when the drug of choice, heroin or OxyContin, is not readily available (Belluck 2003). Massive amounts of prescription opiates are being stolen prior to medical dispensing and potentially being fed into Copyright 2018 Cengage Learning. In 2012, authorities in New York City arrested fourteen persons for selling prescription medicine in an open-air market. Participants would stand outside a busy train station pretending to be on their way to work. Instead, they would approach persons carrying bags from local pharmacies and offer to buys the drugs from them (Wilson 2012). But a doctor prescribing high doses of pain medication, such as OxyContin, runs the risk of scrutiny by state and federal officials concerned with prescription fraud, doctor shopping, overprescribing, and the diversion of prescription drugs to the black market. Doctors receive little training in medical school about dealing with pain and there are relatively few doctors who specialize in pain management. And prescription monitoring by government agencies threatens to compromise the pain treatment practices which have taken a long time to be realized, bringing the war on drugs directly in opposition to the war on pain (Fischer, Gittins, and Rehm 2008). There is growing concern over the use of prescription opioids by the elderly suffering with chronic pain. While addiction and overdoses have historically been lower among older users, they do not metabolize drugs as well as those decades younger, so the medication stays in their system longer. Elderly opioid users suffer from greater side effects than their younger counterparts: nausea and vomiting, which often leads to constipation requiring additional medications, creating cycles of constipation and diarrhea. Long-term use can cause kidney and cardiac damage, and opioids affect balance, increasing the danger of falls and fractures in the elderly (Span 2016). The death of Michael Jackson in 2009 cast a spotlight on propofol (Diprivan), a widely used, short-acting intravenous sedative-hypnotic used in the induction and maintenance of anesthesia or sedation that does not produce post-operative grogginess or nausea. The substance was introduced two decades ago to replace sodium pentothal that has unpleasant side effects. A white milky liquid that is not a federally controlled substance, propofol is typically abused by medical professionals, anesthesiologists, in particular, for its ability to induce relaxation or sleep; it can also produce mild euphoria, hallucinations, and disinhibition. Propofol is extremely dangerous-depresses respiration and blood pressure to the point of death if not constantly monitored ("Propofol Abuse Growing Problem for Anesthesiologists" 2007; Belluck 2009). Side effects include blurred vision, loss of coordination, abdominal pain, and rapid heartbeat. Passing out is a protective mechanism that stops people from drinking when they are approaching potentially dangerous blood alcohol concentrations. But if a person takes stimulants when drinking, the combination can potentially override this protective mechanism and lead to life-threatening consequences (Ashton 2008). These prescription drugs include Adderall, Concerta, Focalin, Ritalin, Provigil (monafinil), and Vyvanse; the two most popular are reportedly Adderall and Provigil. According to Margaret Talbot (2009: 32), these neuroenhancers are used by "high-functioning, overcommitted people to become higher-functioning and more overcommitted. Alan Schwarz (2012: 1) reports that pressure over grades and competition for college admissions are encouraging high school students to resort to the nonmedical use prescription stimulants. What are the natural substances that produce effects similar to those of the synthetic hallucinogens Since the discovery of drugs as a social problem (discussed in Chapter 2), attempts have been made to explain why some people misuse psychoactive substances, while most others do not. Furthermore, why do some persons become dependent on chemicals, while others who use the same substances do not. Like other explanations for shaping human behavior, the misuse of psychoactive substances can be understood in terms of nature v. Supporters of the nature position suggest that we can understand behavior primarily by genetic, biological, or other properties inherent in the individual. Proponents of the nurture position look to the social environment for causal factors; they believe human behavior is largely the product of social interaction. A third view considers drug misuse as determined by the interaction of nature and nurture. Explanations for drug misuse often depend on the discipline of the observer: biology, psychology, and sociology. Although many theories of drug use presented by these disciplines might seem competitive or even conflicting, each provides a partial explanation for drug misuse and has important treatment and policy implications. Indeed, the "real" explanation may be a combination of biological, psychological, and sociological factors. The sociology of drug misuse notes that the phenomenon tends to be clustered in environments that are characterized by social conditions and relationships that cause despair, frustration, hopelessness, and general feelings of alienation. However, in these environments, drug users are only a small fraction of the populace. Why do people who are exposed to the same physical environment react differently to the use and abuse of drugs PsychOlOgy Of Drug use anD abuse Psychology examines individual human behavior, and clinicians attempt to treat abnormal or dysfunctional behavior. Some psychological theories of drug use and abuse are based on personality: "Drug addiction is primarily a personality disorder. It represents one type of abortive adjustment to life that individuals with certain personality predispositions may choose under appropriate conditions of availability and sociocultural attitudinal tolerance" (Ausubel 1978: 77). Robert Craig (1987: 31) notes that the psychological literature supports such a conclusion: "Drug addicts have a paucity of major psychiatric syndromes and Copyright 2018 Cengage Learning. Part of the psychological explanation for drug abuse has been a presumed addictive personality, a psychological vulnerability resulting from problematic family relationships, inappropriate reinforcement, the lack of healthy role models, contradictory parental expectations, and/or an absence of love and respect. The psychologically immature drugdependent personality seeks gratification on a primitive level or, according to the pleasure principle, finds drug use and its attendant behavior reinforcing. He or she ignores the longterm negative consequences of behavior and instead opts for the short-term positive reinforcement that drugs provide. Unfortunately, the search for the addictive personality-psychological variables that can predict future drug abuse-has not been fruitful (Lang 1983). Peter Nathan (1988) points out that the search for predictors of drug dependence has discovered a variety of overt acts by prealcoholic and predrug abusers that reveal an unwillingness to accept societal rules. Beyond that, however, few consistent links have been found between other behaviors or personality factors and later abuse of alcohol and drugs. Furthermore, Nathan (1988) notes large numbers of abusers have never demonstrated antisocial behavior in childhood and that a substantial number of antisocial or conduct-disordered children never develop alcohol or drug problems as adults. Psychological theories can be broadly categorized into those based on a Freudian or psychoanalytic strain and those based on behaviorism or learning theory. PsychOanalytic theOry anD Drug use anD abuse Psychoanalytic theory refers to a body of work fathered by Sigmund Freud (1856­1939). Preconscious: thoughts and memories that can easily be called into consciousness 3. Unconscious: feelings and experiences that have been repressed and that can be made conscious only with a great deal of difficulty and that nevertheless exert a dominant influence over our behavior Rather than being driven by reason, that is, rational thought, human behavior is largely controlled by our unconscious. Simply put, this concept argues that the most important determinants of our behavior are not available to our conscious thought (Cloninger 2013). Psychoanalytic theory posits the importance of the unconscious and stages of psychological development: oral, anal, and genital. Stages of Psychological Development Freud posited that unconscious feelings and thoughts relate to stages of psychosexual development from infancy to adulthood. Psychoanalytic theory "conceives of the human being as a dynamic energy system consisting of basic drives and instincts which in Copyright 2018 Cengage Learning. Individuals from birth are pushed by these largely unconscious and irrational drives toward satisfaction of desires which are largely unconscious and irrational" (Compton and Galaway 1979: 90). Although we lack conscious memory of these stages, in later life they serve as a source of anxiety and guilt, psychoneurosis, and psychosis. During the oral stage, the infant organizes his or her primitive impulses around the mouth, lips, and tongue, which are the predominant sexual organs during this stage. When this gratification is lacking, narcissism remains predominant, and in the narcissistically disturbed adult, drugs become a substitute for deprivation of maternal warmth. The anxiety experienced in the helpless state of infancy is ameliorated by the discovery of a maternal object capable of providing nurture. The absence of warm mother­ infant interaction and sensory deprivation during this stage causes the adult to use drugs as a means of reducing anxiety; drugs serve as a substitute for absent maternal attachment, and drug abuse is a regression back to an unfulfilled oral stage. Experiments conducted on animals reveal that the young of many species experience separation anxiety that can be ameliorated by opiates. During this stage, the infant attempts to reach a state of homeostatic peacefulness, and this requires a responsive and supportive maternal object. Because of trauma or deficiencies experienced during this stage of development, "the infant may fail to achieve homeostatic balance in the context of an attachment to a maternal object," and this can lead to drug abuse in the adult-a reversion to gratifications associated with the oral stage (Greenspan 1978: 74). As the infant moves into his or her second year, the "instinctual organization is beginning to organize around the mental representations concerned with anality" (Greenspan 1978: 76). The anus becomes the center of sexual desire and gratification during this stage, with pleasure closely associated with the retention and expulsion of feces. The child typically experiences toilet training and becomes partially socialized, the beginning of a parental internalizing process that is completed during the genital stage that follows. During the anal stage, children may act out destructive urges such as breaking toys or even injuring living organisms, insects, or small animals. A great deal of adult psychopathology, including violent antisocial behavior and sociopath personality disorders, is traced back to this stage. Depressants such as heroin, alcohol, barbiturates, and sedatives can provide a way of managing sadistic and masochistic impulses-self-medication-that were not successfully dealt with during the anal stage. To gain greater independence, the infant must relinquish the dependent attachment to the maternal object, and if successful, he or she can then move into the genital stage. For adults who have failed to accomplish this anal-stage transition, substance use "is a defense against separation anxiety and its accompanying depression" (Greenspan 1978: 78). Drugs provide solace to the adult who as a child was unable to deal with the depression of separation. In this stage, which anticipates adulthood, the main sexual interest is assumed by the genitals and in normal people is thereafter maintained there. During this period, boys experience strong attachments to their mothers (Oedipus complex) and girls to their fathers (Electra complex); both boys and girls have incestuous fantasies, although they do not fully understand the mechanics of adult sexual relations. In anticipation of adulthood, the child must begin to relinquish the dependent maternal or paternal attachment despite feelings of sadness in doing so. There is a lessening of interest in sexual organs as well as an expanded relationship with playmates of the same gender and age. This is often reinforced by culture-girls expected to play together with dolls, while boys play sports. In this stage, the individual experiences a dramatic reawakening of genital interest and awareness, and becomes capable of reproduction. Incestuous feelings are repressed and sexual interest is expressed in terms of mature (adult) sexuality, directed toward an appropriate partner. As was noted in previous chapters, psychoactive drugs affect sexual performance, enhancing or depressing desire and/or performance. Drugs provide solace to the adult who as a child was unable to deal with the anal-stage depression of maternal separation. Drugs can provide a chemical means of dealing with genital-stage disturbances that now impact the adult. Drugs use can substitute for or enhance sexual desire allowing the user to either avoid or overcome the reawakening of incestuous sexual feelings that were never successfully reconciled during the genital stage. Heroin and other powerful depressants suppress a sexual drive fixated in the genital stage; depressants help the person deal with unconscious and guilt-provoking incestuous feelings that were not adequately resolved during the genital stage. Their use is autoerotic, a substitute for sex, bypassing genital sex in favor of infantile oral-stage eroticism (Yorke 1970). On the other hand, the intensity of arousal caused by powerful stimulants such as cocaine and methamphetamine enables the user to overcome genital-stage-based unconscious guilt-provoking incestuous feelings. While the individual is experiencing each of these stages of development, corresponding psychic phenomena develop.

That part of the tooth embedded in the jaw is the root metabolic diseases in children buy repaglinide, and the root and crown are connected by a constricted neck diabetes 02190 cheap repaglinide 0.5 mg free shipping. The outermost surface of the root is covered by cement managing diabetes 3 month repaglinide 0.5 mg low price, which is similar to bone in composition diabetes insulin pump buy repaglinide canada. The cementum attaches the tooth to the periodontal membrane (ligament) definition of diabetic foot ulcer repaglinide 2 mg low price, which holds the tooth in the alveolar socket. Dentin, which comprises the bulk of the tooth, is the bonelike material located deep to the enamel and cement. Submandibular glands: Located along the medial aspect of the mandible in the floor of the mouth, and ducting under the tongue close to the frenulum. Sublingual glands: Small glands located most anteriorly in the floor of the mouth and emptying under the tongue via several small ducts (Plate 37 in the Histology Atlas). Saliva is a mixture of mucus, which moistens the food and helps to bind it together into a mass, and a clear serous fluid containing the enzyme salivary amylase. Pulp, connective tissue liberally supplied with blood vessels, nerves, and lymphatics, occupies this cavity and provides for tooth sensation and supplies nutrients to the tooth tissues. Activity 6 Locating the Salivary Glands Identify each of the salivary glands discussed previously on an anatomical chart or torso model. As noted earlier, it hides the stomach in a superficial view of abdominal contents. Bile has no enzymes but is important to fat digestion because of its emulsifying action (the physical breakdown of larger particles into smaller ones) on fat. This creates a larger surface area for fat-digesting enzymes (lipases) to work on. When digestive activity is not occurring, bile backs up in the cystic duct and enters the gallbladder, a small, green sac on the inferior surface of the liver. The liver is very important in the initial processing of the nutrient-rich blood draining the digestive organs. Special phagocytic cells remove debris such as bacteria from the blood as it flows past, while the liver parenchyma cells pick up oxygen and nutrients. In addition, bile, destined for the small intestine, is continuously being made by the hepatic cells. Also identify the pancreas, pancreatic duct, and if possible, the hepatopancreatic ampulla and duodenal papilla. Activity 8 Examining the Histology of the Liver Go to station 2 at the demonstration area, and examine a slide of liver tissue. Identify as many of the structural features illustrated in Plate 39 in the Histology Atlas as possible. Notice the central canals and how the liver cells form cords that radiate from those canals. If possible, identify a triad-a region containing a branch of the hepatic artery, a branch of the hepatic portal vein, and a bile duct. The liver units, called lobules, are six-sided, and a triad is found at each corner. The pancreas has both an endocrine function (it produces the hormones insulin and glucagon) and an exocrine (enzyme-producing) function. It indicates the enzymes involved and their source, site of action, and path of absorption. Acquaint yourself with the flowchart before beginning these experiments, and refer to it as necessary during the laboratory session. Enzymes are large protein molecules produced by body cells, that act as biological catalysts. Their substrates, or the molecules on which they act, are organic food molecules which they break down by adding water to the molecular bonds, thus breaking the bonds between the building blocks, or monomers. Each enzyme hydrolyzes only one or a small group of substrate molecules, and certain environmental conditions are necessary for it to function optimally. Because digestive enzymes and bile actually function outside the body cells while in the digestive tract, their activity can also be studied in a test tube. Such in vitro studies provide a convenient laboratory environment for investigating the effect of such variations on enzyme activity. Functional Anatomy of the Digestive System 323 Foodstuff Starch and disaccharides Enzyme(s) and source Site of action Path of absorption Monosaccharides (glucose, galactose, and fructose) enter the capillaries of the villi and are transported to the liver via the hepatic portal vein. Stomach Small intestine Small intestine Absorbed primarily into the lacteals of the villi and transported in the lymph to the systemic circulation via the thoracic duct and then to the liver via the hepatic artery. Glycerol and short-chain fatty acids are absorbed into the capillary blood in the villi and are transported to the liver via the hepatic portal vein. Because the covalent bond between the dye molecule and the amino acid is the same as the peptide bonds that link amino acids together, the appearance of a yellow color indicates the activity of an enzyme that is capable of cleaving peptide bonds and is direct evidence of hydrolysis. Activity 9 Assessing Protein Digestion by Trypsin Work in groups of three or four, with each person in the group taking responsibility for setting up some of the experimental samples. One student should prepare the controls (tubes 1T and 2T), and two should prepare the experimental samples (tubes 3T to 5T). The fourth person can set up the samples for the next activity, "Demonstrating the Action of Bile on Fats. Upon completing the experiments, each group should communicate its results to the rest of the class by recording them in a chart on the chalkboard. All members of the class should observe the controls* as well as the positive and negative results of all experimental samples. Additionally, all members of the class should be able to explain the tests used and the results anticipated and observed for each experiment. Describe the function(s) of bile in the treatment that fats and oils go through during digestion in the small intestine is more complicated than that of carbohydrates or proteins-pretreatment with bile to physically emulsify the fats is required. Although bile, a secretory product of the liver, is not an enzyme, it emulsifies fats, which provide a larger surface area for enzymatic activity. To demonstrate the action of bile on fats, mark one of the test tubes as #1 and the other as #2 with a wax marker, and prepare them as follows: To tube 1 add 10 drops of water and 2 drops of vegetable oil. If emulsification has not occurred, the oil will be floating on the surface of the water. If emulsification has occurred, the fat droplets will be suspended throughout the water, forming an emulsion. From supply area 1, obtain two test tubes and a test tube rack, plus one dropper bottle of vegetable oil, bile salts, a wax marker, and two squares of Parafilm. Although enzyme activity is very important in the overall food breakdown process, foods must also be processed physically (churning and chewing), and moved by mechanical means along the tract if digestion and absorption are to be completed. From supply area 2, obtain a pitcher of water, a stethoscope, a paper cup, an alcohol swab, and an autoclave bag to prepare for the following observations. While swallowing a mouthful of water, consciously notice the movement of your tongue, which initiates the voluntary buccal phase of deglutition (swallowing). Before donning the stethoscope, your lab partner should clean the earpieces with an alcohol swab. Then, he or she should place the diaphragm of the stethoscope over your abdominal wall, approximately 1 inch below the xiphoid process and slightly to the left, to listen for sounds as you again take two or three swallows of water. There should be two audible sounds-one when the water splashes against the cardioesophageal sphincter, and the second when the peristaltic wave (the propulsive movement of the involuntary pharyngeal­esophageal phase) arrives at the sphincter and the sphincter opens, allowing water to gurgle into the stomach. Repeat the swallowing process while your laboratory partner watches movements of your larynx that are visible externally. Interval between arrival of water at the sphincter and the opening of the sphincter: sec this interval gives a fair indication of the time it takes for the peristaltic wave to travel down the 10-inch-long esophagus. Although several types of movements occur in the digestive tract, segmentation and peristalsis are most important as mixing and propulsive mechanisms. Segmental movements are local constrictions of the organ wall that occur rhythmically. However, segmentation is also important in propelling food through the small intestine. Peristaltic movements are the major means of propelling food through most of the digestive viscera. Essentially they are waves of contraction followed by waves of relaxation that squeeze foodstuffs through the alimentary canal. Wall layer Mucosa Subdivisions of the layer Major functions Submucosa N/A Muscularis externa Serosa Organs of the Alimentary Canal 2. The tubelike digestive system canal that extends from the mouth to the anus is the 3. Using the key letters, match the items in column B with the descriptive statements in column A. The dental formula for permanent teeth is Key: cement crown dentin enamel gingiva periodontal membrane pulp root; the number of permanent teeth is. Match the glands listed in column B with the function/locations described in column A. Column B gastric glands liver pancreas salivary glands Review Sheet 25 331 Digestion of Foodstuffs: Enzymatic Action 12. Fill in the following chart about the various digestive system enzymes described in this exercise. Name the end products of digestion for the following types of foods: proteins: fats: and carbohydrates: Organ producing it Site of action Substrate(s) Optimal pH 16. In the exercise concerning trypsin function, how could you tell protein hydrolysis occurred Trypsin is a protein-digesting enzyme similar to pepsin, the protein-digesting enzyme in the stomach. In the procedure concerning the action of bile salts, how did the appearance of tubes 1 and 2 differ Pancreatic and intestinal enzymes operate optimally at a ph that is slightly alkaline, yet the chyme entering the duodenum from the stomach is very acid. In the space below, draw the pathway of a peanut butter sandwich (peanut butter 5 protein and fat; bread 5 starch) from the mouth to the site of absorption of its breakdown products, noting where digestion occurs and what specific enzymes are involved. In its excretory role, the urinary system is primarily concerned with the removal of carbon-containing / nitrogenous wastes from the body. The perform(s) the excretory and homeostatic functions of the urinary system. As the renal artery approaches a kidney, it is divided into branches known as the segmental arteries / afferent arterioles. During tubular reabsorption, components of the filtrate move from the bloodstream into the tubule. Materials Human dissectible torso model and/or anatomical chart of the human urinary system Three-dimensional model of the cut kidney and of a nephron (if available) Dissecting tray and instruments Pig or sheep kidney, doubly or triply injected Disposable gloves Demonstration area: Longitudinal section of the kidney set up for microscopic examination under low power; pointer on a glomerulus Student samples of urine collected in sterile containers at the beginning of the lab or "normal" artificial urine provided by the instructor Numbered "pathologic" urine specimens provided by the instructor Wide-range pH paper Urinometer Disposable gloves Disposable autoclave bags Laboratory buckets containing 10% bleach solution Combination dipsticks (Multistix preferred) etabolism of nutrients by the body produces wastes that must be removed from the body. Although excretory processes involve several organ systems (the lungs excrete carbon dioxide, and skin glands excrete salts and water), it is mainly the urinary system that removes nitrogenous wastes from the body. The kidney also maintains the electrolyte, acid-base, and fluid balances of the blood and is thus a major, if not the major, homeostatic organ of the body. To properly do its job, the kidney acts first as a blood "filter," and then as a blood "processor. The kidneys perform the functions described above and manufacture urine in the process. The remaining organs of the system provide temporary storage or transportation channels for urine. Activity 1 Identifying Urinary System Organs Examine the human torso model, a large anatomical chart, or a threedimensional model of the urinary system to locate and study the anatomy and relationships of the urinary organs. Notice that the right kidney is slightly lower than the left kidney Text continues on next page. In a living person, fat deposits (the perirenal fat capsules) hold the kidneys in place in a retroperitoneal position against the muscles of the posterior trunk wall. Observe the renal arteries as they diverge from the descending aorta and plunge into the indented medial region (hilum) of each kidney. Note also the renal veins, which drain the kidneys (circulatory drainage) and the two 3. Functional Anatomy of the Urinary System 335 muscles that control the outflow of urine from the bladder. The more superior internal urethral sphincter is an involuntary sphincter composed of smooth muscle. The external urethral sphincter consists of skeletal muscle and is voluntarily controlled. In the male, it is approximately 20 cm (8 inches) long, travels the length of the penis, and opens at its tip. Its three named regions are the prostatic, membranous, and spongy (penile) urethrae (described in more detail in Exercise 27). The male urethra has a dual function: it conducts urine to the body exterior, and it provides a passageway for semen ejection from the body. Thus, in the man, the urethra is part of both the urinary and reproductive systems. In women, the urethra is very short, approximately 4 cm (1½ inches) long, and it serves only to transport urine. Its external opening, the external urethral orifice, lies anterior to the vaginal opening. Observe the kidney to identify the fibrous capsule, a smooth transparent membrane that adheres tightly to the surface of the kidney and prevents infections in surrounding areas from spreading to the kidneys. If the kidney is doubly injected with latex, you will see a predominance of red and blue latex specks in this region indicating its rich blood supply. The medulla is segregated into triangular areas that have a striped appearance-the renal (medullary) pyramids. Renal columns: Areas of tissue, more like the cortex in appearance, which separate the renal pyramids. Renal pelvis: Medial to the hilum; a relatively flat, basinlike cavity that is continuous with the ureter, which exits from the hilum region.

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