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Resection of the caudate lobe of the liver for primary and recurrent hepatocellular carcinomas [see comments] antibiotic 7169 order minocycline 50 mg with amex. Bilan d’une experience de la chirurgie d’exerese hepatique pour cancer par la technique d’hepatectomie reglee par voie transparenchymateuse: a propos de 941 hepatectomies antimicrobial workout clothes order generic minocycline line. Hilar cholangiocarcinoma: patterns of spread antibiotic resistance animal agriculture minocycline 50 mg lowest price, the importance of hepatic resection for curative operation antibiotics tired discount 50mg minocycline mastercard, and a presurgical clinical staging system. Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors. J Clin Oncol 1997; 15:947–54 4 Ex-vivo resection for liver tumours J Peter A Lodge Introduction these days it seems that virtually no liver tumour should be considered to be unresectable, even though the majority of patients continue to present at a late stage in their disease. Many experts have challenged the old dogma relating to hepatic resection and candidates with multiple and bilobar hepatic tumours as well as patients with limited extrahepatic tumour infiltration are now considered for resection. In addition, patients with metastases from tumours other than colorectal cancer are also regularly undergoing liver resection. Improvements in anaesthesia have been integral to the success of hepatic surgery, primarily through the use of low central venous pressure techniques for liver resection. This is despite the fact that 85% of our current resection practice is hemihepatectomy or more and the majority is trisectionectomy (extended hepatectomy) and bilateral resection work. In the majority of hepatobiliary centres, Pringle’s manoeuvre and total vascular isolation (hepatic vascular exclusion) are used routinely, 1 – 16 and this short-term warm ischaemia is reported to be well tolerated. However, it has been our preference in recent years to avoid ischaemia whenever possible as we had noticed an increased postoperative morbidity and longer hospital stay in those patients in whom vascular isolation techniques had been used for prolonged periods. In our experience, the use of hepatic ischaemia techniques and blood transfusion is more often necessary for the more complex resections. Recent internal audit of the first 22 left hepatic trisegmentectomies carried out by this author has shown that 11 required Pringle’s manoeuvre and five needed a period of total vascular isolation. Eleven of the 22 patients required blood transfusion, although the median requirement was only 1. This may partly be explained by a high proportion of cholangiocarcinoma cases (32%) in this series as resection of these tumours is associated with a greater degree of operative difficulty. In this group of 22 patients, six of the seven patients with major postoperative morbidity had required either Pringle’s manoeuvre or total vascular isolation, confirming our previous observation. It is also true to say that increasing experience helps to reduce the use of Ex-vivo resection for liver tumors 67 ischaemia and blood transfusion, and there has been little morbidity in a further 15 left trisectionectomies carried out recently by this author. Although orthoptic liver transplantation and cluster resection are the most radical forms of tumour clearance, results for otherwise unresectable tumours have been uniformly disappointing. Tumours account for only 3% of our liver transplant programme in terms of primary indication. However, transplantation remains a valuable option for patients with tumours as secondary indications: principally small hepatomas within cirrhosis. Our centre has been investigating cluster resection and multivisceral grafting as an alternative for extensive tumours and the neuroendocrine group lends itself neatly to this concept. These are most often tumours of midgut origin with foregut metastases and adequate lymphadenectomy involves both the coeliac and superior mesenteric arterial distributions, and if purely foregut (pancreatic tail) then a lesser cluster resection can also be appropriate. These concepts will be discussed at the end of this chapter as they are helpful in defining the place of ex-vivo liver resection in the spectrum of hepatic surgical techniques. In addition there are many lessons to be learnt from the practice of liver transplantation, not least anaesthesia and the role of veno-venous bypass. The short-term survival of untreated patients with both primary and secondary liver tumours, the unpredictability of chemotherapy response on an individual patient basis and the disappointing results of transplantation for cancer provide adequate impetus for attempts to extend the boundaries of liver resection as far as possible. Hilar involvement can be adequately dealt with by short periods of vascular isolation and warm ischaemia and this can often be done without caval or hepatic vein isolation. This fraction is expected to increase as more advanced cases are being considered and it accounts for 6% of cases during the past 12 months in our centre. Ex-vivo resection 18 – 20 offers a potential lifeline for this group of patients and this technique deserves discussion, although it accounts for less than 2% of this author’s total hepatic resection experience. The processes of patient selection and operative assessment of operability by more conventional yet advanced techniques have meant that we have found ex-vivo resection to be necessary in only five of 28 cases (21%) considered during the past 7 years. Before considering a surgical procedure of this scale it is essential to be as sure as possible that the patient is fit enough to withstand the operation. It is important to take a detailed history of previous cardiovascular disease, including myocardial infarction, angina pectoris and hypertension. Clearly, a history of smoking or peripheral vascular disease should raise the clinical suspicion of coronary artery disease. Respiratory diseases, particularly emphysema and chronic bronchitis, are quite prevalent in the Surgical management of hepatobiliary and pancreatic disorders 68 elderly population and clinical examination with chest radiology can be helpful. Patient selection Cardiorespiratory assessment Resting and exercise electrocardiography are the standard cardiological objective assessment tests in our centre. Failure to achieve an adequate heart rate for true stress testing can be a problem in the elderly population, most often due to osteoarthritis of the hips and knees. In this situation a great deal of useful information can be gained from echocardiography, with measurement of end diastolic and systolic volumes to calculate left ventricular ejection fraction, or by radioisotope assessment with dobutamine stress. This procedure is carried out in 10% of major liver surgery candidates in our experience, ruling out surgery in 3% but providing reassuring information in the rest. Only five patients in our experience have been suitable for preoperative coronary artery angioplasty, stenting or bypass grafting prior to liver surgery, but these are clearly potential treatment options to consider. Routine lung function tests including vital capacity and forced expiratory volume form part of our standard assessment as well as chest radiology. In cases where severe pulmonary hypertension is suspected a pulmonary artery wedge pressure line is placed at the commencement of anaesthesia before definitely deciding to proceed with the resection. If there is a very high index of suspicion then we prefer to check the pulmonary artery pressures as a day case procedure in advance of the planned surgical date so that the patient can be advised more accurately about operative risk. Hepatic reserve Preoperative blood tests necessary before proceeding to major resection include full blood count, urea and electrolytes, liver function tests, clotting screen and tumour marker studies. Prothrombin time, bilirubin and albumin give a fairly accurate indication of global hepatic function, but in some cases a liver biopsy of the residual tumour-free liver will also be necessary if there is a doubt about hepatic reserve, in particular in hepatoma. This is particularly important in the group of patients with a previous history of excess alcohol consumption or if there is serological evidence of hepatitis B or C. It is also useful when dealing with cholangiocarcinoma, as there may be underlying sclerosing cholangitis. Some consideration needs to be given to the number of viable tumour-free hepatic segments that will be reimplanted, but this should not usually be less than two, unless there is considerable hypertrophy of the tumour-free liver (Fig. It is inevitable that a degree of temporary hepatic failure will be induced in some patients undergoing very major resection. If the tumour-free segments are affected by biliary obstruction, it is our current practice to attempt biliary decompression by endoscopic or percutaneous techniques a few days in advance of surgery as this may speed up the postoperative recovery. Surgical management of hepatobiliary and pancreatic disorders 70 Tumour type It is reasonable to consider any malignant tumour of the liver, primary or secondary, for ex-vivo liver resection if there is an acceptable chance of clearance of all the disease. It is not our routine to biopsy the tumour unless there is a serious doubt about the diagnosis after radiological assessment. A biopsy can be useful if a benign tumour is suspected, for example hepatic adenoma occurring as a result of a glycogen storage disease, as liver transplantation may be more appropriate in that case. Small metastases or hepatomas not detected by other methods will rule out some candidates and variations in hepatic arterial anatomy can be helpful in some cases, particularly in cholangiocarcinoma. Venography to examine the inferior vena cava and hepatic veins is occasionally useful if all three major hepatic veins are involved with tumour as an adequate inferior or middle right hepatic vein (Fig. An isotope bone scan may be useful in hepatoma, cholangiocarcinoma and some metastatic tumours, and we have recently found it to be of use in colorectal metastatic disease. This is at variance with our usual practice for patients with hepatic metastases from colorectal cancer and may reflect the late stage of presentation of the ex-vivo candidates. New surgical techniques such as resections that rely on the presence of an inferior or middle right hepatic vein and the possibility of hepatic venous reconstruction in situ will mean that ex-vivo liver resection will rarely be performed. In-situ hypothermic perfusion and the ‘ante situm technique’, which do not require hepatic arterial or biliary reconstruction, may be preferable in some cases where it is anticipated that the parenchymal dissection will be difficult. Careful thought must be given to these techniques both preoperatively and during the eventual operation as these methods are Ex-vivo resection for liver tumors 71 widely thought to have a greater applicability than the exvivo technique. However, the only disadvantage of the ex-vivo method is the number of necessary vascular anastomoses and the associated thrombotic risk and in this author’s opinion this is outweighed by the advantages of superb exposure and adequate hypothermic protection in some cases. In-situ hypothermic perfusion the techniques involved in in-situ hypothermic perfusion (Fig.

In infants and young children virus 7912 order minocycline pills in toronto, the clinical picture dysuria virus protection software buy 50 mg minocycline visa, and occasional bleeding virus map buy minocycline with a visa. Phimosis is when the foreskin may be nonspecifc infection definition medical cheap minocycline american express, with fever and other symptoms present in cannot be retracted because of scarring or narrowing of the preupper or lower tract disease. Paraphimosis is the also show pyelonephritis but is not as sensitive; however, it is incarceration of the prepuce behind the glans, ofen afer forcible adequate to detect obstructive uropathy or high-grade refux retraction of the foreskin. Balanitis is an infammation of the prethat may be associated with pyelonephritis. Chapters 114, 116 Neurogenic bladder may develop secondary to a lesion of 4 the central or peripheral nervous system. A careful neuroChapter 31 logic examination should be included, assessing strength, tone, sensation and refexes of the lower extremities, and anal wink. The voiding cystourethrogram demonstrates a trabeculated bladder with a “Christmas tree” or “pine cone” Enuresis is urinary incontinence at an age when most children appearance. Nocturnal enuresis, the most common form, is malities when the cause of the neurogenic bladder has not the involuntary passage of urine during sleep. Primary nocturnal enure5 ful examination may indicate labial fusion in which there sis refers to a child who has never been continent at night and is retention of urine behind the fused labia. Secondary enuresis refers to a child cially obese or preschool-aged girls who do not open the labia who was successfully toilet trained for at least 3 to 6 months and when voiding, there may be “refux” of the urine into the vabecomes incontinent once again. Some girls who have postvoid (new sibling, school trauma, physical or sexual abuse). Urethral obstruction may appear as abnormal urinary symp6 It is most important to distinguish between monosymptoms such as dribbling, poor stream, needing to push, or 1 tomatic nocturnal enuresis (which is usually benign) and weak thin stream. Chilurethritis) or trauma (traumatic catheterization, urethral foreign dren with overactive bladder (pediatric unstable bladder) may body. Hinman syndrome (detrusor-sphincter dyssynergia) is enuresis associated with giggling, laughing, coughing, strainan extreme form of this in a child without neurologic abnoring, or physical activity may indicate the cause. In children with nocturnal enuresis, lated bladder, a signifcant amount of residual urine afer voida history of snoring and mouth breathing may indicate sleep ing, and may show vesicourethral refux, upper urinary tract apnea. In Overactive bladder (urge syndrome, pediatric unstable bladder) 8 patients with urethral obstruction, the bladder and kidneys may is a common cause of daytime wetting. A frst morning urine sample with specifc gravity above Giggle incontinence is associated with laughing and is 9 1. Hematuria may be noted in children with hypercalcuria or common in preschool-aged children who are engrossed in acsickle cell disease or trait. Constipation is ofen associated with bladder dysfunction, Ectopic ureter is a rare congenital anomaly. Incontinence 3 10 because anorectal and lower urinary tract function are inoccurs when the ureter is inserted distal to the external terrelated. It is more common in girls, and there is constant der function is known as dysfunctional elimination syndrome. It is more common in boys and ofen shows sis, constant wetness, neurologic signs or symptoms, or abnora familial pattern. Tese children have a normal examination mal urine stream may indicate an organic cause and prompt (including careful neurologic exam), no associated daytime further evaluation, as in the case of diurnal enuresis. A lateral neck x-ray may be helpful to document textbook of pediatrics, ed 19, Philadelphia, 2011, Saunders, Chapters 21, 537. Neveus T, Eggert P, Evans J, et al: Evaluation of and treatment for monosymplarge adenoids, and a sleep study to evaluate for obstructive sleep tomatic enuresis: A standardization document from the International apnea. Gross hematuria is visation, trauma due to catheterization, and sexual abuse may ible to the naked eye. Injury to the bladder and posterior urethra may be History should include urinary symptoms such as dysuria, associated with pelvic fractures and may be diagnosed by retro1 frequency, and urgency, as well as fank or abdominal pain. A history of exercise or trauma, including a foreign body, catheterization, or sexual/physical abuse, may indicate the cause of Idiopathic hypercalciuria most ofen occurs as persistent 6 the hematuria. A medication, drug, and dietary history should microscopic hematuria or as recurrent gross hematuria or be obtained. If this is sion, as well as systemic illnesses ofen associated with renal present, a 24-hour urine collection for calcium should be obdisease. Autosomal dominant polycystic kidney disease ofen include renal abnormalities, hematuria, deafness, renal failure, appears as gross hematuria. Symptoms may begin in childhood hypertension, nephrolithiasis, sickle cell disease or trait, dialysis, but more ofen occur in adulthood. Stress hematuria occurs afA positive reagent strip (dipstick) in the absence of ter exercise. Patients with benign familial hematuria (thin basemoglobinuria occurs with hemolysis. It may occur in hemoment membrane nephropathy) have an excellent prognosis but lytic anemias, hemolytic-uremic syndrome, mismatched must be followed. Nutcracker syndrome is due to carbon monoxide, fava beans, venoms, mushrooms, naphthathe compression of the distal segment of the lef renal vein belene, quinine, and many other substances. Papillary will ofen show fragmented cells, and the reticulocyte count necrosis may result in hematuria in patients with sickle cell may be elevated. Myoglobinuria occurs with rhabdomyolysis afer viral myositis and in children with inborn errors of energy metabolism, Acute postinfectious glomerulonephritis occurs 4 days to 7 ofen afer exercise. The clinical picture as well as elevated 3 weeks afer a febrile illness just with hematuria, but also muscle enzyme levels may aid in distinguishing myoglobinuria with oliguria, edema, and hypertension. If needed, Hgb and myoglobin may be meainfection causing either pharyngitis or impetigo is the most sured in the urine. Laboratory fndings include a decrease in C3 and C4 levels and laboratory evidence of a preceding group A Microscopic hematuria is ofen found on routine screen3 streptococcal infection (Streptozyme, antistreptolysin, antihyaling. If proteinuria is present, the port syndrome is associated with a family history of renal disevaluation is the same as for gross hematuria (see algorithm). Proteinuria suggests glomerular involvemay be due to associated renal cysts and angiomyolipomas. Chapter 163 122 Part V u Genitourinary System particularly in focal segmental sclerosis and membranoproBibliography liferative glomerulonephritis. It may also Pediatrics textbook of pediatric care, Elk Grove Village, Ill, 2009, American be associated with other diseases, such as systemic lupus Academy of Pediatrics, pp 1566–1569. It may also be done by quantitative assessment of proteinuria in ambulatory and recumbent urine specimens. The amount in the ambulatory specimen may vary but is usually 2 to 4 times that of the recumbent specimen. In patients who have persistent asymptomatic proteinuria, Proteinuria is a common laboratory fnding that is ofen a symp4 further evaluation may proceed as in symptomatic patients. It may also be found in normal, healthy It is reasonable to refer even the patient with normal test results children. It is therefore important to distinguish between pathoto a nephrologist, because there are diferent opinions regarding logic and nonpathologic causes of proteinuria. Because this is a transient fnding in a majority of children, it is Patients with proteinuria who are symptomatic (edema, 5 important to retest the urine before making a diagnosis. Trace proteinuria is usually not signifcant; tory of glomerulonephritis or renal failure should have further 11 proteinuria (30 mg/dl) may be signifcant. In most cases, referral to the nephrologist may be repeated and viewed in the context of the urine Sp gr. This evaluation includes assessment of renal function negative results may occur with urine that is too dilute (,1. Nephrotic synand false-positive results may occur with overlong dipstick imdrome consists of proteinuria, hypoalbuminemia, edema, and mersion, alkaline urine, pyuria, bacteriuria, mucoprotein and hyperlipidemia. Total serum protein, albumin, as well as cholesquaternary ammonium compounds, and detergents. Tests for antistreptococcal Quantitative testing for proteinuria is done by a timed 12to antibodies (Streptozyme) as well as complement levels (C3, C4) 24-hour urine collection for protein: less than 4 mg/m2/h is norare done to exclude poststreptococcal glomerulonephritis. The mal, 4-40 mg/m2/h is abnormal, and over 40 mg/m2/h is in the diagnosis of poststreptococcal glomerulonephritis is made in a nephrotic range. An early morning spot testing of urine protein/Cr child with acute nephritic syndrome, evidence of recent strepratio (in mg/dL) correlates well with 24-hour urine protein extococcal infection, and a low C3 level. Antinuclear antibody testing may be considered, especially 2 years; for children 6 months to 2 years, over 0. Minimal change nephrotic syndrome is more common in 6 History should include questions about recent exercise, red boys and usually appears between ages 2 and 6 years.

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By distending the urinary bladder or allowing it to antibiotic classifications buy line minocycline distend by limiting the opportunity to antibiotic resistance buy 50 mg minocycline with amex void antimicrobial cutting board generic minocycline 50mg otc, the prostate will be pulled anteriorly out of the pelvic canal treatment for dogs collapsing trachea minocycline 50mg generic, and this may permit prostatic evaluation. The full urinary bladder also will displace the small bowel away from the pelvic inlet, limiting gas interference with prostate scanning. In large dogs, an intrapelvic prostate may be examined by placing a lineararray or small electronic sector transducer within the rectum. Ultrasonographic evaluation of prostatic size is subjective but can be compared with the radiographic measurements. The testicles usually are not evaluated radiographically, but they should be evaluated using ultrasonography. The normal testicle is uniformly heteroechoic and is hyperechoic when compared with most abdominal organs except the spleen (Fig. The mediastinum testis produces a central hyperintense line with some slight shadowing. Within the abdomen certain vascular structures may be seen in some normal animals. In animals with large amounts of fat, the aorta and, in some cases, the caudal vena cava may be seen on the lateral view. The aorta is slightly ventral to the spine and branches at the level of L5, the deep circumflex iliac arteries, and at the level of L6-L7, the external iliac arteries. The caudal vena cava runs obliquely from the caudal dorsal abdomen in a cranioventral direction toward the liver. In most vessels, flow can be observed when high-resolution transducers are used with relatively high gain settings. Color-flow Doppler techniques facilitate flow detection and qualitative characterization of flow direction, velocity, and uniformity. The aorta and caudal vena cava can be examined in both longitudinal and transverse planes. The wall of the aorta is slightly thicker than that of the caudal vena cava, but in smaller dogs the wall usually is not identified. Compression of the vessels using the ultrasonographic transducer helps discriminate between the aorta and the vena cava, because the cava is more easily compressed. They can be followed a short distance from their origin before being obscured by intestines. The phrenicoabdominal artery can be identified just cranial to the left kidney and is used as a landmark to locate the left adrenal gland. The renal arteries may be seen at their origin; however, they are rarely seen in the renal hilus. Renal arteries can be detected using Doppler imaging even though they cannot be identified specifically. The terminal branches of the aorta can be seen most readily when the aorta is followed in the transverse plane. The caudal vena cava is wider than the aorta and lacks the pulsations observed in the aorta. The vena cava may be followed in the transverse or longitudinal planes to the liver, where the hepatic veins can be observed to join the vena cava. The portal vein can be traced from the confluence of the mesenteric veins to the liver, where it branches in the porta hepatis. The portal vein, hepatic vein, and extrahepatic bile ducts come together at the porta hepatis. Because of the small size of the extrahepatic bile ducts compared with that of the portal veins, it is usually easy to recognize the difference between these structures. The echogenicity of the walls of the portal vein is helpful in recognizing the intrahepatic portal branches. The hepatic veins course toward the caval hiatus of the diaphragm, facilitating differentiation of these from dilated intrahepatic bile ducts. Doppler ultrasonography can facilitate characterization of these three structures. A scanning plane through the right eleventh or twelfth intercostal space is recommended. The value and predictability of this technique are unproved in veterinary medicine; however, it is helpful in ruling out thrombi, hepatofugal portal venous flow, and dirofilariasis. Many different special procedures may be performed to evaluate the abdominal organs. Recommended methods 276 Small Animal Radiology and Ultrasonography for these procedures vary; however, the principles of interpretation are the same regardless of technique. The described methods of performing the procedures are those preferred by the authors. Radiographic definition of peritoneal structures or the diaphragm may be improved by the use of either a positivecontrast peritoneogram or pneumoperitoneum. The pneumoperitoneum is performed by placing a needle or catheter through the abdominal wall and inflating the peritoneal cavity with gas. Carbon dioxide or nitrous oxide are preferred because they are more soluble in blood and more quickly absorbed. The amount of gas needed varies, but the abdomen should be tympanitic after inflation. Positioning should cause the air to surround the organ of interest, keeping in mind that air will rise to the highest point within the abdomen. For example, if the right lateral liver lobe is of interest, the preferred positioning would be either lateral with the left side down so that the air would rise to the right side, or a ventrodorsal view performed using a horizontally directed x-ray beam and having the animal held in an erect standing position. If there is a risk of diaphragmatic hernia, positive-contrast peritoneography is preferred due to the risk of pneumothorax if large amounts of gas are used in a negative-contrast technique. Positive-contrast peritoneography is most useful when peritoneal fluid is present. The contrast will mix with the fluid and outline the soft tissue–dense abdominal viscera. Positive-contrast peritoneography also can be used for evaluation of the integrity of the diaphragm, but these procedures are used infrequently because ultrasonography is a much easier technique and because there may be false-negative peritoneogram findings. Both normal and abnormal structures within the abdomen can be obscured by overlying intestines. Selective abdominal compression is a technique that uses a wooden spoon or paddle to isolate these structures by displacing the intestines away from the area of interest. A radiolucent wooden spoon or paddle is placed over the structure to hold it in place and prevent the intestines from moving back into the area. The individual who is performing the examination can then have the hand shielded and out of the primary x-ray beam, and the radiographic exposure can be made. The portion of the abdomen that is of interest will be compressed or thinner than normal, so the radiographic technique must be reduced to compensate for the reduced thickness. As in any technique that requires someone to be in the radiology room at the time of the x-ray exposure, protective devices such as lead gloves and aprons must be worn. In addition, the x-ray beam must be collimated to the area of interest rather than exposing the whole abdominal area. This technique can be used very effectively to displace the intestines away from the kidney when a renal or ureteral calculus is suspected, to isolate the uterine horns or body, or to isolate an intestinal mass that can be palpated but cannot be identified because of overlying gas or ingesta-filled bowel. Several special procedures are available to evaluate portal blood flow to the liver. These include the operative mesenteric portogram, the splenoportogram, or the venous washout phase of the cranial mesenteric arteriogram. At this time, a manometer may be attached to the system to determine splenic pulp pressure, a reflection of the pressure in the portal system. After this, water-soluble iodinated contrast medium (at a dosage of 1 to 2 ml/kg) is injected as rapidly as possible, and a radiograph is taken as the last part of the injection is completed. Placement of the needle within the spleen and stability of the needle during the contrast Chapter Three the Abdomen 277 injection, to ensure that the contrast is injected into the spleen and not into the peritoneal cavity, are the major difficulties in this procedure. Another method of demonstrating these structures is the operative mesenteric portogram.

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This can be elucidated in 750% of children infection tooth discount 50mg minocycline with mastercard, with chromosomal disorders being the largest group virus updates buy minocycline 50 mg low cost. Referral to antibiotics for uti new zealand generic minocycline 50 mg without a prescription clinical genetics should be considered for all children with unexplained severe global developmental delay/mental retardation broad spectrum antibiotics for sinus infection discount minocycline 50mg visa. The referring paediatrician may undertake some basic diagnostic genetic testing, including the following: • Chromosome analysis: investigation with the highest yield for children with unexplained developmental delay. As it is often difcult to diagnose on clinical grounds, genetic testing should be offered to all children with developmental delay. If this result was normal (need conrmation), repeat investigation is not required unless there are clinical signs suggestive of hypothyroidism. Plasma and urine samples should be arranged if there is developmental regression, episodic decompensation, parental consanguinity, a family history, or physical examination ndings consistent with a metabolic disorder. Presents after age 1yr usually with developmental regression and loss of purposeful hand movements. May develop seizures, scoliosis, erratic breathing with episodes of breath-holding and hyperventilation, and stereotypic hand-wringing. In addition to accurate assessment and examination of the child, a detailed family history and examination of parents may sometimes be very helpful in establishing the diagnosis. Congenitally affected infants usually have a huge expansion of the triplet repeat with >1000 repeats. In the early phase of the disease, boys have difculty rising from the oor (Gower’s manoeuvre sign where the child climbs up his thighs with his hands to get up off the oor). Diagnosis is often possible by genetic testing, avoiding the need for muscle biopsy. Clinical examination may show fasciculations of the tongue, an important clinical indicator. The skin is soft and hyperextensible with easy bruising and thin, atrophic ‘cigarette paper’ scars, joint hypermobility, varicose veins, and a risk of premature delivery in affected fetuses. Angiobromata occur in later childhood in a buttery distribution over the nose and cheeks. Other cutaneous features include forehead brous plaque, shagreen patches, ungual bromata, and dental pits. Girls present in the neonatal period with blistering lesions, cropping circumferentially on the trunk and in a linear distribution on the limbs. Ultimately, lesions regress by late childhood/adult life to leave atrophic streaky areas of pigmentation or hypopigmentation (often most noticeable on the back of the calves). Typically children have an insatiable appetite with food-foraging and other behavioural problems. Uniparental disomy 11p15 analysis requires blood testing of child and both parents. Characterized by prenatal overgrowth (birth weight 74200g in males; 74000g in females), which persists in childhood, especially through the pre-school years. Affected children typically have a tall skull with a prominent broad forehead and pointed chin. Maternal valproate causes a 10x increased incidence of neural tube defects therapy in pregnancy Goldenhar syndrome Asymmetric facial hypoplasia, eye coloboma/dermoid, ear hypoplasia, preauriUnknown. Usually sporadic Potter’s sequence Depressed nasal bridge, crumpled low set ears, talipes equinovarus, joint Severe oligohydramnios due to contractures, lung hypoplasia and respiratory failure. A useful approach is to consider certain ‘syndromes’ and use this as a framework for investigation (Table 26. Chronic encephalopathy Grey matter: developmental delay, psychomotor retardation Developmental delay is a common problem (see b pp. Myopathy • Acute intermittent muscle weakness: hyperkalaemic periodic paralysis; paramyotonia congenita; hypokalaemic periodic paralysis. Accumulation of organic anion When metabolic acidosis is due to accumulated organic anion: • It is associated with failure to thrive (b p. Peroxisomal disorder the characteristic features of the Zellweger phenotype are: • psychomotor retardation; • hypotonia and weakness; • seizures; • hepatocellular dysfunction; • impaired special senses. Some causes with distinguishing features in infancy • Galactosaemia: hyperbilirubinaemia; haemolytic anaemia; coagulopathy (see b p. Fatty acid metabolism (dilated cardiomyopathy) • Systemic carnitine deciency: presents with skeletal myopathy, hypotonia encephalopathy, hepatic syndrome (hepatomegaly, hypoglycaemia, hepatocellular dysfunction). Organic acidopathy (dilated cardiomyopathy) Propionic acidaemia— intermittent metabolic acidosis; ketosis; hyperammonaemia; neutropenia. Hyperammonaemia (usually severe) results in: • coma; • convulsions and vomiting. In the older child, patients may present with: • psychomotor retardation; • growth failure; • vomiting; • behavioural abnormalities; • recurrent cerebellar ataxia and headache. It is essential to monitor the blood ammonia in any patient with unexplained neurological symptoms. Individuals with childhood or adult onset disease may have a partial enzyme deciency Diagnosis Plasma concentrations of ammonia are elevated, glutamine and alanine (the major nitrogen-carrying amino acids) are usually high, and arginine is low. Specic urea cycle defects can be diagnosed by their characteristic plasma and urine amino acid proles. Treatment Management of dietary protein intake with essential amino acids and restriction of protein intake to suppress ammonia formation. Diagnosis is established by detecting abnormal plasma and urinary amino acid proles. Untreated, brain development is impaired leading to progressive mental retardation and seizures, usually evident by 6–12mths of age. Homocystinuria Due to deciency in cystathionine beta-synthase, resulting in increased urinary homocystine and methionine excretion. Treatment with high-dose pyridoxine and low-methionine diet, supplemented with cysteine. Includes developmental delay, poor growth, and episodic illnesses with vomiting and metabolic acidosis. Commonly presents in the newborn period with: • severe metabolic acidosis; • acute encephalopathy; • hyperammonaemia; • neutropenia and thrombocytopenia. Glutaric aciduria • GluA type 1 is caused by deciency of mitochondrial glutaryl-CoA dehydrogenase. The condition presents in infancy with episodes of hypotonia, dystonia, opisthotonus, grimacing, sting, tongue thrusting, and seizures. Often presenting with one or more of the following—episodic hypoglycaemia; lactic acidosis; poor growth and hypotonia; mental retardation/developmental delay; and vomiting; cramps, myoglobinuria, and muscle weakness. Failure to thrive; cataracts; hepatomegaly; jaundice, vomiting and diarrhoea; mental retardation (if untreated). Disorders of lipoprotein metabolism this is a heterogeneous group of disorders resulting in abnormalities of blood lipid prole. Affects bone, cartilage, tendons, eyes, skin, and connective tissue, leading to accumulation of glycosaminoglycans and progressive cellular and tissue damage. Clinical features are not apparent at birth, but progress with time as storage of glycosaminoglycans impacts on tissues and organs. Variants of Gaucher and Niemann–Pick disease that do not affect the nervous system are termed non-neuronopathic. Due to a deciency of alpha galactosidase A, resulting in the accumulation of globotriaosylceramide within blood vessels and other tissues. Clinical features become evident in early childhood and increase in severity with age—anhidrosis; fatigue; skin lesions (angiokeratomas: tiny, painless papules); and burning pain of the extremities. It is due to decient activity of beta-glucocerebrosidase and leads to intracellular accumulation of glucosylceramide (glucosylcerebroside) within cells of mononuclear phagocyte origin (producing characteristic ‘Gaucher cells’). Usually presents in childhood with hepatosplenomegaly, pancytopenia, and bone marrow inltration. Severe orthopaedic complications, including vertebral compression, avascular necrosis of the femoral head, and pathological fractures of long bones. Patients are usually normal at birth, but develop hepatosplenomegaly, developmental regression, and growth arrest within a few months of age. A spectrum of phenotypes include neurological deterioration, growth retardation, visceromegaly, and seizures. Also coarse facial features, angiokeratoma corporis diffusum, spasticity, and delayed development. A positive family history or a history of previous acute metabolic crisis during trivial intercurrent illness may be present. During intercurrent illness, administration of high carbohydrate diet is required.