Female Sprague Dawley rats given L-proline in drinking water for 1 month (mean dose 50 mg/kg body weight/d) did not exhibit any adverse effects (Kampel et al purchase 2 mg trihexyphenidyl mastercard. Genetically hyperprolinemic mice have 6 to 7 times the concentration of proline in the brain as control animals and 10 times the concentration of proline in plasma (Baxter et al buy trihexyphenidyl 2mg overnight delivery. Hyperprolinemic hybrid mice took longer than control mice to make an initial avoidance response to foot shock in a T-maze and required more trials before learning of the avoidance response (Baxter et al generic trihexyphenidyl 2 mg online. No other studies in experimental animals relevant to the evaluation of the toxicity of orally administered L-proline or hydroxyproline could be found. The only study in humans on the effects of long-term oral administration of proline was a clinical study on the efficacy of proline (isomer not specified) to alter the progression of gyrate atrophy of the choriod and retina (Hayasaka et al. Four patients (aged 4 to 32 years) were treated with doses of proline between 2 and 10 g/d (mode = 3 g/d) for up to 5 years. No overt adverse effects were reported; however, it was uncertain from the paper which effects were studied. Serine Serine is a dispensable amino acid that is synthesized endogenously from D-3 phosphoglycerate or glycine. Men 31 through 50 years of age had the highest intakes at the 99th percentile of 7. In rats given 100 mg/d of L-serine via stomach tube for 14 days, there was a decrease in food consumption but no other effects were noted (Artom et al. In four healthy adults given a single oral dose of 15 g of serine, no adverse effects were reported (Pepplinkhuizen et al. There are no studies in humans that would permit an evalua- tion of the possible adverse effects of repeated administration, thus the safety of repeated dose oral administration of supplemental serine cannot be assessed. Simi- lar to L-lysine, L-threonine does not take part in transamination reactions. Men 51 through 70 years of age had the highest intakes at the 99th percentile of 7. No data were found on apparently healthy humans given oral L-threonoine supplements. However, L-threonine has been used clinically with the aim of increasing glycine concentrations in the cerebral spinal fluid of patients with spasticity. In a study of 163 low birth weight infants, threonine serum concentrations were directly related to the threonine concentra- tions of the formula (Rigo and Senterre, 1980). The authors suggested that threonine intakes should not exceed about 140 mg/kg body weight/d for premature infants. Tryptophan L-Tryptophan, an indispensable amino acid, serves as a precursor for several small molecules of functional significance including the vitamin niacin, the neurotransmitter serotonin, the metabolite tryptamine, and the pineal hormone melatonin. Increases in tryptophan have been shown to increase synthesis of the neurotransmitters in brain, blood, and other body organs (Fregly et al. Men 51 through 70 years of age had the highest intakes at the 99th percentile of 2. Funk and coworkers (1991) found that rats given a 20 percent casein diet supple- mented with 14. No cancers were observed over an 80-week period when rats were fed diets containing 2 percent added L-tryptophan (Birt et al. Several developmental studies have shown that maternal weight gain is impaired and fetal weight is reduced when maternal rat diets are supple- mented with 1. Decreased brain weights were observed when 1 percent L-tryptophan was added to diets of male and female rats beginning 2 weeks before mating (Thoemke and Huether, 1984). Over three successive gen- erations, brain weights decreased with each generation. However, Benedict and coworkers (1983) conducted a double-blind, placebo-controlled trial in six normal men fed 3 g/d of L-tryptophan in divided doses with meals for 3 days, and found a 113 percent elevation in plasma tryptophan, but no changes in platelet or plasma sero- tonin or in plasma catecholamines. Additionally, they found no changes in blood pressure, heart rate, plasma sodium levels or 24-hour sodium excretion in urine. L-Tryptophan administration (2 g) as a single dose before a meal has been found to decrease subjective hunger ratings, food intake, and alert- ness in men (Hrboticky et al. Hrboticky and coworkers (1985) also tested 15 humans only once with 0, 1, 2, and 3 g of L-tryptophan. Individuals receiving 2 and 3 g of L-tryptophan had decreased hunger and alertness and increased faintness and dizziness. Administration of 1 g of L-tryptophan with 10 g of carbohydrates before each meal (3 g L-tryptophan/d) for 3 months did not affect body weight of obese humans (Strain et al. Ten healthy adults given 5 g of L-tryptophan in a double-blind, placebo-controlled study reported severe nausea and headache and increased drowsiness soon after ingestion (Greenwood et al. Smith and Prockop (1962) reported sustained nystagmus and drowsiness in seven adults given 70 and 90 mg/kg of body weight of L-tryptophan orally in single doses, but found that these effects were absent at 30 or 50 mg/kg. However, Lieberman and coworkers (1985) reported decreased self-ratings of vigor and alertness and increased subjective fatigue in 20 men treated with a single oral dose of 50 mg/kg of tryptophan. Yuwiler and coworkers (1981) also reported that five individuals given 50 or 100 mg/kg/d of L-tryptophan as a single dose or 50 mg/kg/d for 14 days experienced prolonged lethargy and drowsiness within 30 minutes of inges- tion under all loading conditions. Newborns (2 to 3 days of age) given infant formula supplemented with L-tryptophan (about 20 mg) were found to enter active and then quiet sleep sooner than those newborns given unsupplemented formula (Yogman and Zeisel, 1983). In a later study, these same investigators found that low doses of L-tryptophan have sleep-inducing properties in full-term infants (Yogman and Zeisel, 1985). Blauvelt and Falanga (1991) examined the history of L-tryptophan use in 49 patients with cutaneous fibrosis. Eleven of 17 patients reported using L-tryptophan prior to onset of eosinophilic fasciitis, as did two of ten patients with localized scleroderma, but use of L-tryptophan was not reported in any of 22 patients with systemic sclerosis. L-tryptophan use in individuals with localized scleroderma occurred for 3 or 10 months before onset of symptoms, and intake was 1. Hibbs and coworkers (1992) found that 9 of 45 patients with eosinophilic fasciitis used 0. It is unknown whether or not these results occurred because of impurities in the L-tryptophan supplements. Dose–Response Assessment Taken together, the above studies in humans indicate that relatively short-term (acute and subacute) use of L-tryptophan is associated with appetite suppression, nausea, and drowsiness. Tyrosine L-Tyrosine is considered a conditionally indispensable amino acid because it can be synthesized from L-phenylalanine in the liver. L-Tyrosine is a precursor of several biologically active substances, including catecholamine neurotransmitters, hormones, and melanin skin pigments. Men 31 through 50 years of age had the highest intakes at the 99th percentile of 6. In the mouse with elevated tissue concentra- tions of tyrosine, decarboxylation to tyramine becomes increasingly impor- tant, reducing lethality (David et al. Evidence has been provided that hepatic biotransformation of tyrosine yields a toxic metabolite, possibly an epoxide (David, 1976). In rodents, feeding studies document the toxicity of large supplements of L-tyrosine (Benevenga and Steele, 1984; Harper et al. Effects of tyrosine on weight-gain suppression are a function of the protein content of the diet. For example, feeding rats a low-protein diet, 6 or 9 percent casein, retarded weight gain over a 3-week period. This effect of an inadequate protein intake was exacerbated by the addition of 3 to 8 per- cent L-tyrosine in the diet (Ip and Harper, 1973). With higher protein intakes of 15 or 24 percent, the toxicity of L-tyrosine was reduced, although 8 percent L-tyrosine still resulted in mortality. Subsequently, Rich and coworkers (1973) reported that young adult Simonson albino or Long-Evans pigmented rats fed diets containing 5 or 10 percent L-tyrosine for 15 days developed elevated serum tyrosine levels and experienced reduced weight gain. Corneal disease was the first sign of toxicity; keratopathy was evident by 1 day and progressed in severity. The change began as haziness of the cornea, followed by opacities, and vascularization. The corneal changes were accompanied by elevations of tyrosine concentration in the aqueous humor. Rats were fed the diet for 2 weeks prior to mating and continually for three generations.

It measures the degree of agreement beyond chance between two observers purchase trihexyphenidyl 2mg online, called the inter-rater agreement buy trihexyphenidyl 2 mg with amex, or between multiple measurements made by a single observer purchase trihexyphenidyl 2 mg on-line, called the intra-rater agreement. The kappa statistic applies because physicians and researchers often assume that all diagnostic tests are precise. However, many studies have demonstrated that most non-automated tests have a degree of subjectivity in their interpre- tation. It is also present in tests commonly consid- ered to be the gold standard such as the interpretation of tissue samples from autopsy, biopsy, or surgery. Abnormal 10 0 10 100 0 Here is a clinical example of how the kappa statistic applies. He didn’t really feel like reading these and knew that all of his read- ings would be reviewed by the attending. He also reasoned that since this was a screening clinic for young women with an average age of 32, there would be very few positive studies. This particular radiology department had a computerized reading system where the resident pushes either the “normal” or the “cancer” button on a console and that reading would be entered into the file. After read- ing the first three as negative, he fell asleep on the “negative” button, making all one hundred readings negative. The second resident, Number 2, was really interested in mammography and had slept all night, since she was not on call. Assuming that there are 90% normals and 10% abnormals, we can assume that each read their films with that proportion of each result and do the same 2 × 2 table (Fig. Kappa is the ratio of the actual agreement beyond chance and the potential agreement beyond chance. The actual agreement beyond chance is the differ- ence between the actual agreement found and that expected by chance. The potential agreement beyond chance is the difference between the highest possible agreement (100%) and that expected by chance alone. Interpretation of the kappa statistic Actual agreement between measurements beyond chance Kappa = Potential agreement between measurements beyond chance Range: 0–1 (0 = no agreement; 1 = complete agreement) Numerical level of kappa Qualitative significance 0. You should use the kappa statistic when you want to know the precision of a measurement or the inter-observer or intra-observer consistency. The “easier” it is to make a measurement, the more likely that two different observers will agree on the result and that agreement is not just due to chance. Some experts have Instruments and measurements: precision and validity 79 related the value of kappa to qualitative descriptors, which are given in Table 7. Kappa ranges from 0 to 1 where 0 means that there is no agreement and 1 means there is complete agreement beyond that expected by chance alone. You can see from making a 2 × 2 table that if there is an equal number in each cell the agreement occurs purely by chance (Fig. Similarly if there is perfect agree- ment, it is very unlikely that the agreement occurred completely by chance. How- ever, it is still possible: if there are only a few readings in each cell, 100% agree- ment could occur by chance, even though the chance of this happening is very small. Confidence intervals, which we will discuss later in the book, should be calculated to determine the statistically feasible range within which 95% of pos- sible kappa values will be found. There are other statistics that more or less measure the same thing as the kappa statistic. These are the standard deviation of repeated measurements, coefficient of variation, correlation coefficient of paired measurements, intraclass correla- tion coefficient and Cronbach’s alpha. Alexander Pope (1688–1744): Essay on Criticism Learning objectives In this chapter you will learn: r sources of bias r threats to internal and external validity r how to tell when bias threatens the conclusions of a study All studies involve observations and measurements of phenomena of interest, but the observations and instruments used to make these measurements are subject to error. Bias introduced into a study can result in systematic error which may then affect the results of the study and could invalidate the conclusions. Since there is no such thing as a perfect study, in reading the medical litera- ture you should be familiar with common sources of bias in clinical studies. By understanding how these biases could affect the results of the study, it is possible to detect bias and predict the potential effect on the conclusions. You can then determine if this will invalidate the study conclusions enough to deter you from using the results in your patients’ care. This chapter will give you a schema for looking for bias, and present some common sources of bias. Overview of bias in clinical studies Bias was a semilegendary Greek statesman who tried to make peace between two city-states by lying about the warlike intention of the enemy state. His ploy 80 Sources of bias 81 failed and ultimately he told the truth, allowing his city to win the war. His name became forever associated with slanting the truth as a means to accomplish an end. Bias is defined as the systematic introduction of error into a study that can distort the results in a non-random way. It is almost impossible to eliminate all sources of bias, even in the most carefully designed study. It is the job of the researcher to attempt to remove as much bias as possible and to identify poten- tial sources of bias for the reader. It is the job of the reader to find any sources of bias and assess the importance and potential effects of bias on the results of the study. Virtually no study is 100% bias-free and not all bias will result in an invalid study and in fact, some bias may actually increase the validity of a study. After identifying a source of bias, you must determine the likely effect of that bias on the results of the study. If this effect is likely to be great and potentially decrease the results found by the research, internal validity and the conclusions of the study are threatened. If it could completely reverse the results of the study, it is called a “fatal” flaw. The results of a study with a fatal flaw should generally not be applied to your current patients. If the bias could have only small potential effects, then the results of these studies can be accepted and used with caution. Bias can be broken down into three areas according to its source: the population being studied, the measurement of the outcome, and miscellaneous sources. Bias in the population being studied Selection bias Selection bias or sampling bias occurs when patients are selected in a man- ner that will systematically influence the outcome of the study. Subjects who are volunteers or paid to be in the study may have different characteristics than the “average person” with the disease in question. Another form of selection bias occurs when patients are chosen to be in a study based upon certain physical or social characteristics. Commonly, selection bias exists in studies of therapy when patients chosen to be one arm of the study are ‘selected’ by some characteristics determined by the physicians enrolling them in the study. An investigator offered free psychiatric counseling to women who had just had an abortion if they took a free psychological test. He found the incidence of depression was higher in these women than in the general population. It is very likely that women who had an abortion and were depressed, therefore needing counseling, would 82 Essential Evidence-Based Medicine preferentially sign up to be in the study. Women who had an abortion and were not depressed would be less likely to sign up for the study and take the free psy- chological test. This is a potentially fatal flaw of this study, and therefore, the conclusion is very likely to be biased. This is a fatal flaw and would seriously skew the results, so the results of this study should not change a physician’s approach to these patients. Studies performed in tertiary care or referral centers often use only patients referred for specialty care as subjects. This eliminates cases that are milder and more easily treated or those diagnosed at an earlier stage and who are more likely to be seen in a primary care provider’s office. Overall, the subjects in the study are not like those patients with similar complaints seen in the primary care office, who will be much less likely to have unusual causes for their symptoms. This limits the external validity of the study and the results should not be generalized to all patients with the same complaint. The study patients reflected only those who were referred to the neurologist, who therefore had persistent problems from their head injury. The results, even if significant in this selected population, would not apply to the general population of all head-injured patients.

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Be alert for signs of illness such as elevated temperature 2 mg trihexyphenidyl amex, skin rashes buy trihexyphenidyl 2 mg low cost, inflamed eyes generic trihexyphenidyl 2 mg amex, flushed, pale or sweaty appearance. If a child shows these or other signs of illness, pain or physical distress, he/she should be evaluated by a health care provider. Children or staff with communicable diseases should not be allowed to attend or work in a school or child care setting until they are well. Recommendations for exclusion necessary to prevent exposure to others are contained in this document. Please report all suspected cases of communicable disease promptly to your city, county or state health department. Additional information concerning individual communicable diseases is contained in the Communicable Disease Investigation Reference Manual located on the Department of Health and Senior Services website at: http://health. A variety of infections have been documented in children attending childcare, sometimes with spread to caregivers and to others at home. Infants and preschool-aged children are very susceptible to contagious diseases because they 1) have not been exposed to many infections, 2) have little or no immunity to these infections, and 3) may not have received any or all of their vaccinations. Close physical contact for extended periods of time, inadequate hygiene habits, and underdeveloped immune systems place children attending childcare and special needs settings at increased risk of infection. For instance, the spread of diarrheal disease may readily occur with children in diapers and others with special needs due to inadequate handwashing, environmental sanitation practices, and diaper changing. This manual contains 54 disease fact sheets for providers about specific infectious disease problems. These fact sheets have been designed to provide specific disease prevention and control guidelines that are consistent with the national standards put forth by the American Public Health Association and the American Academy of Pediatrics. In addition to the provider fact sheets, 47 of the fact sheets are available in a format specifically for parents/guardians of childcare and school-aged children. This manual contains information for both staff and parents/guardians on numerous topics. This document replaces all previous versions of the “Prevention and Control of Communicable Diseases, A Guide for School Administrators, Nurses, Teachers, and Child Care Providers”. Practitioners and users of this manual should not limit their judgment on the management and control of communicable disease to this publication and are well advised to review the references that are listed, and remain informed of new developments and resulting changes in recommendations on communicable disease prevention and control. Excluding an ill child may decrease the spread of the disease to others in the childcare and school settings. Children with the symptoms listed below should be excluded from the childcare or school setting until symptoms improve; or a healthcare provider has determined that the child can return; or children can participate in routine activities without more staff supervision than can be provided. These policies should be placed in the student handbook or on the childcare or school website. Parents/guardians and staff should be given or directed to these resources at the beginning of each school year or when the child is enrolled or the staff member is hired. Exclude children with any of the following: Illness Unable to participate in routine activities or needs more care than can be provided by the childcare/school staff. Most medical professionals define fever as a body core temperature elevation above 100. If a child is younger than three months of age and has a fever, it’s important to always inform the caregiver immediately so they can call their healthcare provider right away. When determining whether the exclusion of a child with fever is needed, a number of issues should be evaluated: recorded temperature; or is the fever accompanied by behavior changes, headache, stiff neck, difficulty breathing, rash, sore throat, and/or other signs or symptoms of illness; or if child is unable to participate in routine activities. Any child that has an elevated body temperature that is not excluded should be closely monitored for possible change(s) in their condition. When measuring ear temperatures follow the manufacturer’s instructions to ensure accurate results. Signs/Symptoms Until a healthcare provider has done an evaluation to rule out severe illness when the of Possible Severe child is unusually tired, has uncontrolled coughing, unexplained irritability, Illness persistent crying, difficulty breathing, wheezing, or other unusual signs for the child. Diarrhea Until the child has been free of diarrhea for at least 24 hours or until a medical exam indicates that it is not due to a communicable disease. Mouth Sores with Until a medical exam indicates the child may return or until sores have healed. Drooling Rash with Fever Until a medical exam indicates these symptoms are not those of a communicable or Behavior disease that requires exclusion. Change Eye Drainage When purulent (pus) drainage and/or fever or eye pain is present or a medical exam indicates that a child may return. Unusual Color of Until a medical exam indicates the child does not have hepatitis A. Symptoms of Skin, Eyes, Stool, hepatitis A include yellow eyes or skin (jaundice), gray or white stools, or dark (tea or Urine or cola-colored) urine. Acute Bronchitis (Chest Until fever is gone and the child is well enough to participate in routine Cold)/Bronchiolitis activities. Campylobacteriosis Until the child has been free of diarrhea for at least 24 hours. Children who have Campylobacter in their stools but who do not have symptoms do not need to be excluded. No one with Campylobacter should use swimming beaches, pools, spas, water parks, or hot tubs until 2 weeks after diarrhea has stopped. Exclude symptomatic staff with Campylobacter from working in food service or providing childcare. Chickenpox Until all the blisters have dried into scabs; usually by day 5 after the rash began. Therefore, exclude children who:  appear to have chickenpox regardless of whether or not they have received varicella vaccine, or  develop blisters within 10 to 21 days after vaccination. These are referred to as “breakthrough infections” and are usually less severe and have an atypical presentation. The rash may be atypical in appearance with fewer vesicles and predominance of maculopapular lesions. Persons with breakthrough varicella should be isolated as long as lesions persist. Although extremely rare, the vaccine virus has been transmitted to susceptible contacts by vaccine recipients who develop a rash following vaccination. Therefore, exclude vaccine recipients who develop a rash after receiving varicella vaccine, using the above criteria. Conjunctivitis (Pinkeye) Purulent Conjunctivitis (redness of eyes and/or eyelids with thick white or yellow eye discharge and eye pain): Exclude until appropriate treatment has been initiated or the discharge from the eyes has stopped unless doctor has diagnosed a non-infectious conjunctivitis. Adenoviral, Enteroviral, Coxsackie) should be allowed to remain in childcare once any indicated therapy is implemented, unless their behavior is such that close contact with other children cannot be avoided. Nonpurulent conjunctivitis (redness of eyes with a clear, watery eye discharge but without fever, eye pain, or eyelid redness): None. Cryptosporidiosis Until the child has been free of diarrhea for at least 24 hours. No one with Cryptosporidium should use swimming beaches, pools, water parks, spas, or hot tubs for 2 weeks after diarrhea has stopped for 24 hours. Exclude symptomatic staff with Cryptosporidium from working in food service or providing childcare until 24 hours after diarrhea has stopped. Diarrhea (Infectious) Until the child has been free of diarrhea for at least 24 hours. For some infections, the person must also be treated with antibiotics or have negative stool tests before returning to childcare. Enteroviral Infection Until the child has been free of diarrhea and/or vomiting for at least 24 hours. None, for mild, cold-like symptoms, as long as the child is well enough to participate in routine activities. Fifth Disease None, if other rash-causing illnesses are ruled out by a healthcare (Parvovirus) provider. Giardiasis When a child is infected with Giardia who has symptoms, the child should be excluded until free of diarrhea for at least 24 hours. Children who are treated in an outbreak should be excluded until after treatment has been started and they have been free of diarrhea for at least 24 hours. No one with Giardia should use swimming beaches, pools, spas, water parks, or hot tubs for 2 weeks after diarrhea has stopped.

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Complications Infection above the level of obstruction can cause Management pyelonephritis (pyonephrosis is the term for an infected discount 2mg trihexyphenidyl with mastercard, It is important to diagnose and treat urinary tract ob- obstructed hydronephrosis) or cystitis purchase trihexyphenidyl 2mg with visa, and patients can struction quickly buy trihexyphenidyl 2 mg overnight delivery, as delayed treatment can cause irre- become very unwell due to pain, fever and sepsis. Therefore, if there is doubt, one of the ing is needed, to avoid hypotension or prerenal failure following may be required: during this phase. This is very useful, par- ticularlyinacuteobstructionbeforethereisdilatation, Pelviureteric junction obstruction as it shows contrast ‘held up’ by the obstruction and (idiopathic hydronephrosis) may show the lesion as a space-filling defect such as a radio-lucent stone or a papilla. Aetiology/pathophysiology r As part of the management percutaneous nephros- The cause is unknown. The mechanism of development of which may be exacerbated by drinking large amounts ‘myeloma kidney’ is via a direct toxic effect on re- of fluid, for example it may become symptomatic for nal tubular cells and blockage of the tubules and col- the first time in students who drink large quantities of lecting ducts by the paraprotein. Occasionallythe may develop amyloidosis and renal tubular acidosis as hydronephrosis is so marked that it can mimic ascites. In some cases, it is asymptomatic and diagnosed in- r Amyloidosis: This condition may be systemic or con- cidentally when an ultrasound is performed for another fined to the kidneys and is an important cause of reason. Itcancauseproteinuria,nephrotic trasound scan, or in childhood during investigation of syndrome and renal failure. There is delayed passage of glomerulonephritis from minimal change disease, to contrast, which is not overcome by administration of membranous nephropathy, to proliferative glomeru- diuretics. Early treatment with immunosup- pression regimes such as plasmapheresis, high dose Prognosis steroids and cyclophosphamide can improve renal It is not possible to predict how much function will re- function. Thrombotic thrombocytopenic purpura – haemolytic uraemic The kidney in sytemic disease syndrome r Hypertension: See page 73. Often both ends of the spectrum are Chapter 6: Disorders of the kidney 259 present in the same patient. This causes a focal segmen- toxin (also called Shiga toxin) produced by Escherichia tal glomerulonephritis. Some This has markedly improved with the advent of plasma develop proteinuria later in life due to progressive exchange. Chronic renal failure occurs in a substantial glomerulosclerosis, occasionally leading to renal fail- number of patients. However, the prognosis for these patients is ex- cellent with no reduction in life expectancy. Congenital disorders of the kidney Renal hypoplasia r Simple renal hypoplasia is when the kidney is smaller Congenital malformations of the than normal, but the structure and histology of the kidney kidney is normal, although the nephrons may be Definition slightly small. Congenital malformations of the kidney are not uncom- r Oligonephronic renal hypoplasia (also called oligo- monly found on antenatal screening and in newborns. The prog- and the risk is higher in those with a previous family nosis is poor for these patients, although there may history. Chromosomal abnormalities account for a pro- be some initial improvement in renal function over portion, but most are sporadic. The fetal kidneys develop when the ureteric bud comes into contact with the metanephric blastema caudally Dysplasia (failure of differentiation) (in the ‘pelvic’ area), signalling it to form nephrons The kidney develops abnormally with primitive tubules and the collecting system. By 14–16 weeks, most r Horseshoe kidney – the kidneys remain fused at of the amniotic fluid consists of fetal urine. Then the the upper (10%) or lower (90%) poles to form a kidneys have to migrate rostrally, to lie in the lumbar horseshoe-shapedstructure. These anatomical abnormalities may be symptomless, r Bilateral agenesis is rare and incompatible with life. About 50% tive uropathy and predisposition to urinary stones and Chapter 6: Disorders of the bladder and prostate 261 infections. In pregnancy, low pelvic kidneys can interfere Disorders of the bladder with labour. Age r Atresia: Failure of the ureteric bud to canalise, associ- Increases with age ated with renal dysplasia. An ectopic M > F ureter often arises from a duplex kidney, which may be associated with vesicoureteric reflux. The causes of bladder outflow obstruction are shown in Surgical re-implantation of the ureter may be indi- Table 6. Overtime,theblad- Benign prostatic hyperplasia der distends, then the ureters (causing hydroureters) and Definition finally the renal pelvises. Often there may be an un- Hyperplasiaoftheprostateisacommoncauseof bladder derlying chronic obstruction for example an enlarged outflow obstruction. Clinical features The symptoms depend on the speed of onset and degree Age of obstruction. Acute obstruction (acute urinary retention) causes se- vere discomfort, due to a wish to void urine, without Sex the ability to do so. There is complete anuria, although there may be small amounts of urine voided due to overflow in- Aetiology continence. However, polyuria and/or nocturia may Pathophysiology be symptoms of the loss of concentrating ability of the Androgens appear to act on the periurethral area of the tubules, which can occur in long-standing obstruc- prostate ‘McNeal’s transition zone’ to stimulate hyper- tion. At 30–40 years there is microscopic evidence, by 50 years it Macroscopy is macroscopically visible, by 60 years the clinical phase Dilation above the obstruction. The obstruction is due to both direct impingement Complications of the enlarged prostate on the urethra and also the dy- As aresultofchronicobstruction,thebladderdilatesand namic smooth muscle contraction of the prostate, pro- fails to empty fully, defined as >50 mL residual urine static capsule and bladder neck. Nodules Management formedofhyperplasticglandularacinidisplaceandcom- Relief of the obstruction is usually by insertion of a uri- press the true prostatic glands peripherally forming a nary catheter, followed by treatment of the underlying false capsule. Chapter 6: Disorders of the bladder and prostate 263 Microscopy symptoms than α-blockers. It seems to be more effec- Benign epithelial proliferation with large acini, smooth tive in those with very large prostates and its effects muscleandfibroblastproliferation. The procedure involves removal Complications of prostatic tissue using electrocautery via a resecto- Bladder decompensation – due to chronically increased scope from within the prostatic urethra, under general residualvolumes(urineretainedaftervoiding),theblad- or spinal anaethesia. Post-operatively patients require der may become less contractile, lowering flow rates fur- a three-way catheter and continuous bladder irrigation ther. Obstruction may lead to dilated ureters and kid- to reduce the risk of clot retention until haematuria is ney(hydroureter,andhydronephrosis). Investigations Antibiotic prophylaxis is usually given to prevent Itisimportanttoexcludeothercausesof bladderoutflow urinary tract infection. Between10and15mL/second,combined bladder neck contracture or urethral stricture requir- pressure/flow studies may be done to exclude those ing surgery or dilatation, incontinence. The disad- Other options (not widely available) include: vantage of the latter, is that urinary catheterisation is r Stent which is cost-effective in those with a short required. Definition r Finasteride is a 5 alpha reductase inhibitor which in- Urinary incontinence is the involuntary loss of urine hibits the conversion of testosterone to dihydrotestos- from the urethra. It is also useful, but generally less effective for and functional impact on the individual. This is mainly due to detrusor instability/over- 30% of women <65 years but only up to 5% of men <65 activity. Rates are much higher in certain settings such as care of r Overflow incontinence is continual or unprecipitated the elderly institutions (up to 45%) and psychiatric care leakage without urge. Bladder outflow obstruction may lead Age to overflow incontinence due to bladder decompen- Increases with age. Rare causes include spinal cord compression affecting the sacral segments (S2, 3 and 4) or the conus medullaris. F > M Acomprehensive examination is important and can avoid the need for specialist tests. It is important to as- Aetiology sess fluid balance, mobility, cognitive ability and relevant Incontinence has been associated with many conditions neurology. Rectal examination for constipation, rectal and risk factors such as chronic cough, depression, de- masses and vaginal speculum examination for atrophy, mentia, pregnancy, vaginal delivery (particularly with masses, cystocele or rectocele. Toremaincontinentthere r Avoiding diary is useful to record the time, volume must be: and relevant events, e. This is due to poor sphincter func- Stress incontinence: Initially non-surgical options tion. This r Pelvic floor (Kegel) exercises (with or without weigh- may be precipitated by the sound of running water, tedcones) may be used but are dependent on the Chapter 6: Urinary tract infections 265 motivation of the patient. Systemic or topical oestro- r Inspinalcordcompressionemergencydecompression gen therapy may be of benefit. Ring tions intermittent self-catheterisation is the preferred pessaries are useful for those with uterine prolapse.

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