Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment?

The worldwide prevalence of hepatitis C virus (HCV) infection in pregnant women is estimated to be between 1 and 8% and in children between 0.05% and 5%. While parenteral transmission is still common in children living in developing countries, perinatal transmission is now the leading cause of HCV transmission in developed countries. The absence of an HCV vaccine or approved therapy during pregnancy means that prevention of vertical transmission is still not possible. However, a low vertical transmission rate of 3-5%, a high rate of spontaneous clearance (25-50%) and delayed morbidity have resulted in HCV being overlooked in pregnant women and their infants. Yet a study of the natural history in mothers and children demonstrates that the prognosis of HCV can vary greatly and should be taken seriously. Factors known to increase the risk of perinatal transmission include HIV coinfection and higher maternal viral loads, while elective C-section and withholding breastfeeding have not been demonstrated to reduce vertical transmission. Current guidelines for the diagnosis of persistent perinatal infection require a positive anti-HCV test in infants born to infected mothers after 12 months or two positive HCV RNA tests at least 6 months apart. Current HCV treatment options using pegylated interferon and ribavirin are both unsuitable for use in pregnancy and infancy. However, new agents currently in preclinical phases of development, along with the recently identified association between single-nucleotide polymorphisms within the IL28 gene and treatment response, may serve to create a therapeutic window for these patients.

Pregnancy outcomes associated with viral hepatitis.

The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre-eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy-related complications including GDM, PTB, IUGR, pre-eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297 664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co-infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre-eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted.

Open-label, ascending dose, prospective cohort study evaluating the antiviral efficacy of Rosuvastatin therapy in serum and lipid fractions in patients with chronic hepatitis C.

HMG CoA reductase inhibition suppresses in vitro HCV replication through depletion of cellular sterol proteins such as geranylgeraniol. Our aims were to prospectively evaluate the changes in serum and lipid fraction HCV RNA with Rosuvastatin in non-responder (NR) patients with CHC. A total of 11 patients with CHC genotype-1 received Rosuvastatin at 20 mg qd (weeks 0-4), 40 mg qd (weeks 5-12), with 4 week follow up. Lipid fractions were separated by a sucrose density gradient ultracentrifugation, HCV RNA determined at wks 0, 2, 4, 8, 12, 16 in serum, and in selected very low- (VLDF) to high-density (HDF) lipid fractions. A reduction in LDL and total cholesterol (TC) was not accompanied by significant decline in HCV RNA. At baseline, there was an inverse correlation between HDL and HCV RNA (ρ = -0.45, P = 0.036). At 20 mg, there was correlation between change (Δ) in TG and Δ HCV RNA (ρ = 0.75, P = 0.007), Δ ALT and Δ TC (ρ = -0.64, P = 0.03) and Δ LDL (ρ = -0.67, P = 0.02). At 40 mg, Δ TG maintained a positive correlation with Δ HCV RNA (ρ = 0.65, P = 0.03). There was a group difference for HCV RNA in relation to lipid fractions (P = 0.04) but not study time intervals (P = 0.17); mean log HCV RNA was greater in VLDF compared to HDF (5.81 ± 0.59 vs 5.06 ± 0.67, P = 0.0002) with no other differences to study time intervals (P = 0.099). Short-term Rosuvastatin monotherapy is not associated with significant changes in serum or lipid fraction HCV RNA in NR patients. HCV co-localizes with the lowest density lipid fractions in serum.

Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding.

Patent ductus arteriosus is common among premature neonates, especially those with birth weights less than 1,500 g. In vitro, room light inhibits the contraction of immature piglet's ductal rings. Because phototherapy is used frequently from the first days of life to treat jaundice in preterm neonates, we compared the occurrence of patent ductus arteriosus among premature infants exposed to this intense light source with those whose chests were shielded. Seventy-four babies with respiratory distress syndrome were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy, 36 babies) or control group (no shield, 38 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields model PTU 78-1) from day 1 of life. Irradiance was maintained at greater than 4.0 microW/cm2/nm in all cases. Although both groups had similar birth weights, gestational ages, severity of respiratory distress syndrome, intravenous fluid intake, and duration of phototherapy, the incidence of patent ductus arteriosus was significantly less in the shield group (shield 11/36 v No shield 23/38; P = .009). Patent ductus arteriosus murmurs developed in shielded patients at a later date, they required less vigorous treatment (ie, indomethacin), and they had shorter hospitalizations (74 v 85 days; P less than .05). The significant reduction of patent ductus arteriosus with shielding suggests that phototherapy may play a role in the occurrence of patent ductus arteriosus in premature infants. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

Amikacin pharmacokinetics in the therapy of childhood urinary tract infection.

Amikacin, a new aminoglycoside antibiotic with a spectrum similar to that of gentamicin, has been used mainly in adults. This report summarizes the first use of this drug in children with urinary tract infection. Organisms were eradicated in all cases and recurrent infection occurred in one half after one week. No evidence of ototoxicity or nephrotoxicity was found. Four children developed transient elevation of serum glutamic oxaloacetic transaminase. Serum level (17 mug/ml) of the drug at one hour and its urinary excretion in six hours (60% of the dose) was comparable to those of adults. This antibiotic is potentially valuable and has thus far not shown major toxicity when given for up to 11 days in patients with normal renal and liver functions.

Effects of methadone on thyroid function in mother, fetus, and newborn.

The effects of maternal use of methadone during pregnancy on tests of thyroid function were studied in 14 women and their offspring. Twelve normal nonaddicted women and their infants served as a control group. Concentrations of thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) were not significantly different in maternal and cord serum, and in infant serum at age 24 hours. There was no significant difference in infants' TSH concentrations at 2, 3, and 7 days of age. At 2 and 7 days, T3 levels were significantly higher in the methadone than in the control group (P = .01 and less than .01, respectively). At 3 days, differences were of borderline significance (P = .08). Increased T4 levels in the methadone group of infants were statistically significant at 2 days (P less than .01) and at 3 and 7 days (P = .05). The mechanisms responsible for the biochemical evidence of hyperthyroidism were not determined, but may have been related to altered autonomic function and/or increased metabolic activity which occurs during neonatal narcotic withdrawal.

Cat-eye syndrome with unusual marker chromosome probably not chromosome 22.

An unusual supernumerary chromosome with a single satellite on the long arm was found in a child with manifestations of the cat-eye syndrome including apparently low-set and malformed ears, preauricular tags, micrognathia, and imperforate anus. Although G-banding suggested that this extra material was chromosome 22, this was not confirmed by several other banding techniques. After examination of the parents' chromosomes, the nature and origin of this extra chromosome remains obscure. We conclude that patients previously diagnosed as having "partial trisomy 22" with incomplete cat-eye syndrome may have a different chromosome constitution when studied by various banding techniques.

Double trisomy 48,XXX,+ 18 in a newborn.

We report the 6th case of double trisomy X and 18 ie, 48,XXX,+ 18. The infant lacked overlapping fingers, simian creases, and structural heart disease and is alive at 275 days. Two X chromosomes were late replicating. Anomalies of the hands and kidneys involved only the right side in the present case; review of the five previous cases of 48,XXX, +18 also showed that anomalies of kidneys, hands, and ears affected predominantly the right side in three patients.

Duplication 3q: severe manifestations in an infant with duplication of a short segment of 3q.

A patient with duplication of a short segment of 3q (3q21 leads to 26) without apparent deletion of 3 or of other chromosomes provided a further opportunity to study manifestations of this abnormality. The proposita had a broad nasal bridge, anteverted nostrils, webbed neck, and clinodactyly V in addition to congenital heart disease, limb abnormalities, cleft palate, and severe developmental delay. The infant did not have the hirsutism and synophrys present in other cases.

Erythema migrans after ceftriaxone treatment of aseptic meningitis caused by Borrelia burgdorferi.

Erythema migrans is the characteristic exanthem of Lyme disease. The rash initially occurs at the site of inoculation; subsequently satellite lesions can occur. We describe an adolescent girl in whom the rash appeared after the initiation of ceftriaxone therapy for aseptic meningitis. We suggest that the occurrence of rash in this patient was a result of liberated toxin from local bacterial lysis.

Intrauterine exposure to narcotics and cord blood prolactin concentrations.

Umbilical cord serum prolactin concentrations were determined in 17 full-term infants of mothers using narcotic agents during pregnancy and in 18 infants of similar birth weight and gestational age whose mothers did not use narcotics. The median value for the narcotic-exposed group was 266.6 ng/ml (range, 157.5 to 448.7 ng/ml); in the normal group the median was 193.7 ng/ml (range, 69.8 to 693.1 ng/ml). These differences were statistically significant (P less than .05). Although only full-term and borderline premature infants who were not appreciable risk for respiratory distress syndrome (RDS) were studied, it may be speculated that elevated prolactin blood levels in fetuses of addicted mothers may at least in part explain the reported decrease in the incidence of RDS in this group.

Lung transplantation for primary and secondary pulmonary hypertension.

BACKGROUND: Single lung transplantation (SLT) and bilateral lung transplantation (BLT) are routinely performed in patients with primary pulmonary hypertension (PPH) and secondary pulmonary hypertension (SPH). It is unclear which procedure is preferable. We reviewed our experience with lung transplants for PPH and SPH to determine if any advantage exists with SLT or BLT for either PPH or SPH. METHODS: We reviewed the outcomes of all lung transplants performed for PPH or SPH for 4.5 years (July 1995 to January 2000). Survival was reported by the Kaplan-Meier method, and log rank analysis was used to determine significance. Statistical analyses of clinical data were performed using analysis of variance and chi2 analysis. RESULTS: A total of 57 recipients met criteria for pulmonary hypertension with a mean pulmonary artery pressure of greater than or equal to 30 mm Hg. There were 15 patients with PPH and 40 patients with SPH. There were 6 patients who had SLTs and 9 patients who had BLTs in the PPH group; and there were 9 patients who had SLTs and 21 patients who had BLTs in the SPH group. We found a survival advantage for PPH patients who underwent BLTs at all time points up to 4 years (100% vs 67%; p < or = 0.02). There was no clear advantage to SLTs or BLTs for SPH. At 4 years there was a trend toward improved survival with SLTs (91% vs 75%) in SPH patients with a mean pulmonary artery pressure less than or equal to 40 mm Hg (p < or = 0.11) with equivalent survival (80%) in patients with a mean pulmonary artery pressure greater than or equal to 40 mm Hg. There was also a trend toward improved survival in patients with a mean pulmonary artery pressure greater than or equal to 40 mm Hg (PPH and SPH) with BLTs (88% vs 62%; p = 0.19). The incidence of rejection, infection, and other complications was comparable between SLTs and BLTs in each group. CONCLUSIONS: We believe that BLT is the procedure of choice for PPH. The procedure of choice is less clear for SPH. Patients with SPH and a mean pulmonary artery pressure greater than 40 mm Hg may benefit from a BLT and those with a mean pulmonary artery pressure less than or equal to 40 mm Hg may do better with an SLT; however, no clear advantage is seen.

Congenital bladder perforation and urinary ascites caused by posterior urethral valves: a case report.

Neonatal urinary ascites caused by bladder perforation is rare, with fewer than 20 cases reported in earlier literature. Congenital bladder perforation can be associated with bladder outlet obstruction such as posterior urethral valves, urethral atresia, presacral mass, and neurogenic dysfunction of the bladder. The bladder perforation in these cases is most commonly intraperitoneal, which leads to congenital urinary ascites. However, intrauterine perforation of the bladder in a newborn infant with posterior urethral valves is extremely rare, as is evident from the three cases in previous literature. The present case report describes an unusual case of congenital bladder perforation and urinary ascites caused by posterior urethral valves.

Freeman-Sheldon syndrome with unusual hand and foot anomalies.

A newborn with the characteristic facies of Freeman-Sheldon syndrome (whistling face syndrome) and unusual hand and foot anomalies is reported. Flexion contractures of fingers were so severe as to prevent their extension. Previously reported patients with similar hand anomalies had only mild to moderate limitation of extension. Over 75 percent of the 29 previous cases of this syndrome had equinovarus deformity. Not only was this deformity absent but the patient had polysyndactyly of the big toe, an anomaly not previously associated with this syndrome.

Analysis of the medical records in a pediatric emergency room.

A prospective evaluation of Pediatric Emergency Room records permitted analysis of major errors and of factors contributing to them. All records from July 1973 to June 1975 were reviewed daily by a board certified pediatrician using a previously established protocol. Patients had been seen by pediatric house staff from 4 PM to 8 AM on weekdays and from 8 AM to 8 AM on weekends and 25,907 records were reviewed. Errors were detected in 9.5 percent of these. The most common was an incomplete set of vital signs which accounts for 68 percent of all errors. Failure to arrange for appropriate follow-up care occurred in 16 percent of cases. Other errors ranged from two to four percent and included inadequate use of laboratory, incomplete physical examination, inappropriate diagnosis or therapy. Major omissions in the history were uncommon (1.3 percent). The frequency of errors was significantly greater at the start of each academic year (July to October), and at the start of each month (P<0.001). The errors occurred significantly more often at the first year level than the second year level (P<0.01). This study suggests a means of improving record keeping and house staff education, ie, attending-level supervision should be emphasized at the start of each month and academic year. Daily reviews of errors with the house staff as well as modification of chart design may bring about more complete patient evaluation and detailed recording of findings, diagnosis, and disposition.

Chromosomal abnormality in the newborns of hepatitis B surface antigen (HBsAg) carrier mothers.

The association of maternal hepatitis B surface antigen carriers (HBsAg) and chromosomal abnormalities in their newborns has been previously suggested. This is a report on two female infants with abnormalities of chromosome 18 and trisomy 3q syndrome who were born to HBsAg carriers. These cases indicate that a possible relationship exists between the HBsAg carrier state in the mother and chromosome abnormalities in her offspring. It is suggested that the parents of all newborns with a structural chromosomal abnormality be tested for HBsAg.

Congenital eversion of the eyelids: a report of two cases treated with conservative management.

Congenital eversion of the upper eyelids is rare. Most previous cases were associated with Down's Syndrome, difficult labor and delivery, or underlying skin disorders. The two present cases occurred in normal patients with unremarkable deliveries. They responded promptly to conservative treatment, including use of a horizontal grid of tape on each lid, which successfully repositioned the lids and facilitated instillation of antibiotic solutions.

Breast cancer after radiation exposure in childhood.

Reports in the literature link radiation in childhood to some form of breast cancer in later life. The authors present a report on the carcinogenic effects of chemotherapy and radiation on the pubescent breast of a 12-year-old female treated for Wilms' tumor of the left kidney.

Treatment of upper airway obstruction associated with goiter.

The authors examined the resolution of spirometric indices of upper airway obstruction (UAO) following surgical treatment for goiter. The results of a recent study suggest that the integrity of the upper airway remains intact but prolonged recovery is required.