Colin Ball

Low Complication Rate Associated with Cesarean Section under Spinal Anesthesia for HIV-1–Infected Women on Antiretroviral Therapy

Background Elective cesarean section decreases the likelihood of vertical human immunodeficiency virus (HIV) transmission from mother to infant. This study aimed to determine whether cesarean section done with spinal anesthesia on HIV-1–infected pregnant women taking antiretroviral therapy is associated with intraoperative hemodynamic instability, postoperative complications, or changes in immune function or HIV-1 viral load. Methods A case-controlled study was conducted over a 3-year period in a London academic hospital. Forty-four women infected with HIV-1 and a control group of 45 HIV-negative women undergoing cesarean sections were included. The main outcome measures included intraoperative blood pressure, heart rate, blood loss, and ephedrine requirements, and postoperative infective complications, blood transfusion, changes in blood HIV-1 viral load and lymphocyte subsets, and time to hospital discharge. Results There were no differences in hemodynamic stability and postoperative complications between the HIV-infected group and the controls. There was an acute postoperative increase in the CD4T lymphocyte count (P = 0.01), but the CD4T:CD8T ratio and viral load did not change. Conclusions Elective cesarean section under spinal anesthesia for women infected with HIV-1 taking antiretroviral therapy was not associated with intraoperative or postoperative complications.

Endoscopic retrograde cholangiopancreatography in infantile cholestasis.

The difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily, and others may be referred for surgery too late. In an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results, we have been using prototype paediatric duodenoscopes (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde cholangiopancreatography (ERCP). From 159 infants with conjugated hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In four in whom bile ducts were definitely visualised laparotomy was avoided. Operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain. Three of four in whom bile ducts were not seen had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded atresia. No major complications ensued but there was radiological evidence of gall bladder perforation in one (common hepatic duct block) and overinflation with air was a problem until finer cannulae (Wilson-Cook) were introduced. In appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with paediatric duodenoscopes in experienced hands may provide useful diagnostic information.

Effect of rifampicin in the treatment of pruritus in hepatic cholestasis.

Pruritus in hepatic cholestasis has been suggested to be secondary to a high concentration of serum bile acids. Rifampicin, which inhibits the uptake of bile acids by hepatocytes, has been used to treat pruritus. To determine the efficacy of rifampicin as a treatment for refractory pruritus, the medical records of 33 children (median age 25 months, range 4-135; 19 boys) with chronic cholestasis liver disease (21 with Alagilles syndrome, eight with progressive intrahepatic cholestasis, one with extrahepatic biliary atresia, one with an inborn error of bile acid metabolism, and one with cryptogenic cirrhosis) were reviewed retrospectively. The median dose of rifampicin was 5(4-10) mg/kg/day. The median duration of intake was 36(4-120) weeks. Complete relief of pruritus was noted in five (15%) patients and a partial response in 12 (36%). Overall, no significant difference was noted in the laboratory parameters before and after treatment with rifampicin. In the 21 patients with Alagilles syndrome, however, a significant decrease in alkaline phosphatase was seen before and after one and six months of starting treatment. No adverse side effects were seen. Rifampicin appears to be effective in the treatment of refractory pruritus. A prospective study is warranted to assess further the effect of rifampicin treatment in children with hepatic cholestasis.

Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.

Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency

Objective  Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin–aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification.

Global issues in pediatric nutrition : AIDS

Nutrition is a final common pathway in chronic disease, and weight loss is a major manifestation of acquired immunodeficiency syndrome (AIDS). In sub-Saharan Africa, studies have shown that 25% of children with malnutrition have human immunodeficiency virus (HIV) infection, although patterns of malnutrition are indistinguishable from those who are HIV negative. Breast-feeding increases the risk of vertical transmission, and the overall risk versus benefit needs continuing careful consideration in relation to local mortality from gastroenteritis and malnutrition. Chronic diarrhea is much more common in HIV-infected children in Africa and may have a multiplicity of causes, including infection with adherent forms of Escherichia coli, protozoa, and even direct HIV infection of intestinal mucosal cells. The HIV wasting syndrome produces reduction in bioelectrical impedence, fat, lean body mass, and body cell mass, but the changes can be predicted from equations used in starvation states. Micronutrients may be important, but observed changes may be due to immune mediator activation, rather than malnutrition. Calorie supplementation is beneficial when delivered by any route, but is likely to produce the greatest positive change when CD4 counts are highest in relation to calorie intake. Paradoxically, HIV-infected children may be obese early in the disease until AIDS develops. There is an inextricable link between disease and nutritional status. In children with AIDS wasting syndrome, a low CD4 count and high viral load are likely so that effective antiviral treatment may ultimately produce the greatest improvement in health, including nutritional status.

A paediatric case of acute liver failure associated with efavirenz-based highly active antiretroviral therapy and effective use of raltegravir in combination antiretroviral treatment after liver transplantation

patients without severe meningeal inflammation, even when high daily doses of up to 4 g are used. Therefore, some authors advocate intrathecal administration of vancomycin, although a comprehensive evaluation of the benefits has yet to be made and the associated risks, such as ototoxicity, remain unclear. Treatment of ampicillin-resistant enterococcal infections is further complicated by the fact that the activity of vancomycin is bacteriostatic. The CSF may not be sterilized unless bactericidal activity is established by the addition of gentamicin. These factors, and the desire to avoid further surgery to establish intrathecal access, made linezolid an attractive treatment option for our patient. Linezolid is the first licensed member of the oxazolidinone class of antibiotics with activity against almost all Gram-positive pathogens. Excellent tissue penetration and 100% oral bioavailability are notable properties of linezolid and it is approved in Europe and the USA for the treatment of nosocomial pneumonia, skin and soft tissue infections and, in the USA, vancomycin-resistant E. faecium and methicillin-resistant Staphylococcus aureus (MRSA) infections. Linezolid has also been shown to have good penetration into the CNS. A 2007 review of the evidence regarding the use of linezolid for the treatment of patients with CNS infections identified 42 relevant cases. In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%) and MRSA (3; 7.7%). Of the 42 patients treated with linezolid, 38 were either cured or showed clinical improvement. Case reports of other authors have found that enterococci disappeared from the CSF after as little as 2 days of iv linezolid treatment. This case shows that linezolid may not reliably treat postneurosurgical intracranial infections caused by enterococci even in the absence of prosthetic material.

Rituximab in chronic, recurrent HIV-associated immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is associated with human immunodeficiency virus (HIV) infection (Scaradavou, 2002). In children, it usually follows a benign course, and the small risk of intracranial bleeding is the main justification for treatment (Lilleyman, 2003). A 9-year-old girl with HIV presented with bleeding in her mouth. She was being treated with zidovudine and abacavir and had a total white cell count 3Æ69 · 10/l, haemoglobin 8Æ4 g/dl, platelets 3 · 10/l, CD4 0Æ72 · 10/l, CD8 1Æ131 · 10/l. Her platelet count was previously normal. Her clotting was normal and she had strongly positive antinuclear antibodies. A bone marrow biopsy showed mild HIV myelopathy with normal megakaryocyte numbers and morphology. A diagnosis of HIV-associated ITP was made. She was treated with intravenous immunoglobulin and 2 days after admission, when her platelet count was 7 · 10/l, she had a generalized seizure. A computed tomography scan of the brain revealed two new haemorrhages in the left temporal lobes and magnetic resonance (MR) imaging/MR angiography showed no other abnormalities. She was treated with twice daily platelet transfusions and prednisolone for 7 days. The antiretroviral treatment was changed to didanosine and stavudine. She made a rapid, full neurological recovery, but her platelet count remained below 10 · 10/l. A number of therapeutic options were then discussed with her family, including high-dose methyl prednisolone, splenectomy and rituximab. High dose steroids were rejected because of her failure to respond to lower doses of corticosteroids and fears concerning immunosuppression. The family were against splenectomy because a relative had died from sepsis following this operation. She was, therefore, started on rituximab, a chimaeric mouse/human antibody against CD20 (375 mg/m weekly for 4 weeks). After 4 weeks, the platelet count had risen to 39 · 10/l, and by 8 weeks it was 183 · 10/l (Fig 1). The platelet count remained normal for 12 months, until a count of 29 · 10/l was found at a routine appointment. In view of her history, she was given a further course of rituximab. The platelet count initially fell to 7 · 10/l but rose to 116 · 10/l at 2 weeks and 197 · 10/l at 4 weeks. Twelve months later her platelet count again fell with associated mucosal bleeding. A repeat bone marrow aspiration was consistent with ITP and she responded to a third course of rituximab (Fig 1). The rituximab caused no side effects. Her viral load and CD4 counts have remained stable following the treatment, and she has not suffered from any unexpected or opportunistic infections. This girl suffered two intracranial bleeds despite treatment, illustrating the difficulties of managing ITP in children (Lilleyman, 2003). The high anti-nuclear antibody titres suggest she may have a coexistent autoimmune condition, but she has no other features of this at the moment. Rituximab has previously been shown to work in some cases of ITP without adverse consequences, and particularly without significant immunosuppression (Stasi et al, 2001). As far as we are aware, this is the only description of the use of rituximab in HIV-associated ITP and the only case in which the patient has responded to three separate courses of rituximab over 2 years. This highlights the benefit of rituximab in the treatment of acute and chronic ITP. Although repeated courses of rituximab may be associated with immunosuppression (Tsokos, 2004), this is true of most other potentially effective treatments for ITP, and has not been a problem in this case.

Functional residual capacity related to hepatic disease.

Functional residual capacity was measured in 20 children (aged 3.1-11.2 years) with liver disease. Children with severe liver disease, regardless of diagnosis, had reduced functional residual capacities (less than 80% of expected). Children with alpha-1 antitrypsin deficiency had higher functional residual capacities than those with other hepatic diagnoses. Three children had a functional residual capacity greater than 120% of expected, all had alpha-1 antitrypsin deficiency.

Dehydrated hereditary stomatocytosis is associated with neonatal hepatitis

Dehydrated hereditary stomatocytosis (DHSt) is an inherited haemolytic anaemia associated with increased red cell membrane permeability to Na+ and K+. It is increasingly recognized that a syndrome of self‐limiting perinatal ascites can accompany the haemolysis. The cause of the perinatal ascites is unknown, and it has been argued that this could be due to cardiovascular, hepatic or lymphatic problems. We describe the case of a 16‐year‐old girl who presented neonatally with abnormal liver function tests and ascites. She was extensively investigated at that time. A liver biopsy showed hepatitis and fatty changes. Her ascites resolved within 6 months. At the age of 15 years, she developed an episode of acute haemolysis and was re‐investigated. A diagnosis of DHSt was made. Pseudohyperkalaemia, due to ex vivo loss of K+ from red cells, was present. This study confirms the previously noted association of DHSt, pseudohyperkalaemia and perinatal ascites, and suggests that the latter is of predominantly hepatic origin.