Safety and immunogenicity of hepatitis A vaccine in healthy children.

The immunogenicity and reactogenicity of an inactivated hepatitis A (HA) vaccine in children were investigated. One hundred three healthy children who lacked antibody to HA virus (anti-HA virus), aged between 3 months and 6 years 8 months, were enrolled in this study. They received three doses of 360 enzyme-linked immunosorbent assay units of HA vaccine in a 0-, 1- and 6-month schedule. Blood tests for aminotransferase and anti-HA virus were performed 7 days before and 1, 6 and 7 months after the first dose. Anti-HA virus was tested by radioimmunoassay and also by enzyme immunoassay for titer determination. The seroconversion rates measured by enzyme immunoassay were 95.1% (98 of 103) at Month 1 and 100% at Months 6 and 7. Nine percent (28 of 309) of the injections were followed by local symptoms, usually mild soreness and swelling at the site of injection, and 12% (37 of 309) by minor general symptoms. We conclude that HA vaccine is highly immunogenic and safe in children. It may replace immunoglobulin as an effective method to prevent HA virus infection in children. We also suggest that the HA vaccine be administered to children in endemic areas.

Ethanol stimulates apolipoprotein A-I secretion by human hepatocytes: implications for a mechanism for atherosclerosis protection.

Ethanol intake in humans has been shown to have a protective effect against coronary heart disease. The specific mechanism by which ethanol is cardioprotective has not been elucidated. Apolipoprotein (apo) A-I, the major protein of high-density lipoprotein (HDL), takes up cellular cholesterol, thus initiating reverse cholesterol transport whereby excess tissue cholesterol is eliminated. Using highly specific antibodies, we have found that ethanol increases apo A-I secretion and the incorporation of radiolabeled leucine into apo A-I by human hepatocytes (Hep-G2 cells). In addition, we have found that apo A-I molecules induced by ethanol have the ability to efflux cholesterol from human fibroblasts in vitro, and that apo A-I mass directly correlates with cholesterol efflux levels. At 10, 20, and 100 mmol/L, ethanol stimulated apo A-I secretion by 130%, 136%, and 162% of control, respectively (control, 3.71 micrograms apo A-I/micrograms DNA), also stimulating the incorporation of 3H-leucine into newly synthesized apo A-I by 115%, 131%, and 159% of control (control, 111 cpm/micrograms DNA/h). The ethanol-induced apo A-I from Hep-G2 cells (incubated with 0, 10, 20, and 100 mmol/L ethanol) effluxed 2%, 14%, 16%, and 32% label (per h/mL incubation medium), respectively. Apo A-I mass correlated linearly with cholesterol efflux (r = .99, P less than .01). This data indicates that the cardioprotective role of moderate ethanol intake in humans is mediated by its stimulatory action on hepatic apo A-I secretion, thus defining the physiological basis for increased plasma apo A-I levels in vivo.

Umbilical venous line related pericardial effusion in a premature neonate: report of a case.

Cardiac tamponade occurs very rarely, but is life-threatening in the newborn. This paper reports a premature newborn who developed profound shock 25 hours after undergoing umbilical venous catheterization. Echocardiography taken later, showed marked pericardial effusion. An umbilical venous catheter was located in the left atrium. Immediate pericardiocentesis was performed, 11 mL of a clear straw-colored fluid was removed and the umbilical venous catheter was withdrawn into the inferior vena cava. The heart rate and blood pressure recovered immediately. Analysis of the pericardial fluid showed a high glucose level of 2,451 mg/dL. There was no pericardial effusion reaccumulation thereafter. Rapid diagnosis and treatment of pericardial effusion are mandatory to prevent subsequent morbidity and mortality when disastrous episodes, such as in the present case, occur.

Congenital factor VII deficiency complicated with hemoperitoneum and intracranial hemorrhage: report of a case.

Hypoproconvertinemia, or factor VII deficiency, is a rare congenital coagulopathy. We report on a female infant with congenital factor VII deficiency complicated by hemoperitoneum and intracranial hemorrhage. Most reports indicate that the bleeding of victims tends to be mild and confined to the superficial mucosa area. However, other reports and our experience with this patient suggest that it can result in fatal cerebral hemorrhage and necessitate early diagnosis, effective treatment and careful genetic counseling.

Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus.

The purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.

Infantile endodermal sinus tumor presenting with vaginal bleeding: report of a case.

Endodermal sinus tumor (EST) of the vagina is extremely rare and primarily affects infants. We report on a six-month-old female infant with EST of the vagina who presented with vaginal spotting of one month's duration. Pelvic ultrasound and computerized tomography showed a 3.8 x 3.5 cm heterogeneous mass between the bladder and the rectum. The serum alpha-fetoprotein (AFP) level was high (1270 ng/mL) and the beta-human chorionic gonadotropin was undetectable. She received surgical intervention followed by chemotherapy. The patient was disease-free and serum AFP remained undetectable during the eight-month follow-up period.

L-asparaginase-related pancreatic pseudocyst: report of a case.

Pancreatitis following the administration of L-asparaginase (L-asp) has been well documented. However, the progression of such pancreatitis to pseudocyst formation in some patients has been rarely reported. The few reported cases have been teenagers, with the exception of one adult. All pseudocysts required surgical management. This report documents a pancreatic pseudocyst in a seven-year-old girl with acute lymphoblastic leukemia whose treatment regimen included L-asp. The pseudocyst was managed medically with nasogastric decompression, intravenous hyperalimentation, and antibiotics. The pseudocyst resolved spontaneously in one month without complication.

Mechanistic studies of methane biogenesis by methyl-coenzyme M reductase: evidence that coenzyme B participates in cleaving the C-S bond of methyl-coenzyme M.

Methyl-coenzyme M reductase (MCR), the key enzyme in methanogenesis, catalyzes methane formation from methyl-coenzyme M (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoBSH). Steady-state and presteady-state kinetics have been used to test two mechanistic models that contrast in the role of CoBSH in the MCR-catalyzed reaction. In class 1 mechanisms, CoBSH is integrally involved in methane formation and in C-S (methyl-SCoM) bond cleavage. On the other hand, in class 2 mechanisms, methane is formed in the absence of CoBSH, which functions to regenerate active MCR after methane is released. Steady-state kinetic studies are most consistent with a ternary complex mechanism in which CoBSH binds before methane is formed, as found earlier [Bonacker et al. (1993) Eur. J. Biochem. 217, 587-595]. Presteady-state kinetic experiments at high MCR concentrations are complicated by the presence of tightly bound CoBSH in the purified enzyme. Chemical quench studies in which (14)CH(3)-SCoM is rapidly reacted with active MCRred1 in the presence versus the absence of added CoBSH indicate that CoBSH is required for a single-turnover of methyl-SCoM to methane. Similar single turnover studies using a CoBSH analogue leads to the same conclusion. The results are consistent with class 1 mechanisms in which CoBSH is integrally involved in methane formation and in C-S (methyl-SCoM) bond cleavage and are inconsistent with class 2 mechanisms in which CoBSH binds after methane is formed. These are the first reported pre-steady-state kinetic studies of MCR.

Essential myoclonus: report of four cases.

Four cases of essential myoclonus in childhood are reported. These include three males and one female, whose age-at-onset ranged from 2 months to 16 years. All manifested as involuntary movement of face, neck, or extremities without any known etiology. Only one case has a family history of myoclonus. They showed no other neurological abnormalities. The image or electrophysiological studies of nervous systems were within normal limits except that electromyogram (EMG) showed myoclonic discharge. All were treated by clonazepam with or without valproic acid. No significant effects were noted.

Neonatal lupus erythematosus with negative anti-Ro and anti-La antibodies: report of one case.

Since 1981 when anti-Ro (SS-A) and/or anti-La (SS-B) antibodies were described to be present in infants with neonatal lupus erythematosus (NLE) and their mothers, subsequent studies have demonstrated the almost universal association of NLE with either or both of these autoantibodies. To our best knowledge, three cases of NLE were reported to be negative in anti-Ro (SS-A) and anti-La (SS-B) antibodies. We report one infant born to a mother with systemic lupus erythematosus (SLE). He had neonatal pancytopenia (thrombocytopenia, anemia, and leukopenia) which got resolved after intravenous immunoglobulin (IVIG) administration. Both anti-Ro (SS-A) and anti-La (SS-B) antibodies were not detectable in his serum by immunodiffusion method while other such as RNP (nonspecific, including U1,U2,U3,...,U6), Sm and Scl-70 antibodies were all positive. This mother had all the above antibodies detectable in her serum. After excluding other possibilities, his pancytopenia was most likely to be attributed to neonatal lupus. We suggest that autoantibodies such as RNP and Sm antibodies may play an important role in the pathogenesis of thrombocytopenia of NLE.

Cryoreduction of methyl-coenzyme M reductase: EPR characterization of forms, MCR(ox1) and MCR (red1).

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methyl-coenzyme M (CH(3)S-CH(2)CH(2)SO(3)) from methane. The active site is a nickel tetrahydrocorphinoid cofactor, factor 430, which in inactive form contains EPR-silent Ni(II). Two such forms, denoted MCR(silent) and MCR(ox1)(-)(silent), were previously structurally characterized by X-ray crystallography. We describe here the cryoreduction of both of these MCR forms by gamma-irradiation at 77 K, which yields reduced protein maintaining the structure of the oxidized starting material. Cryoreduction of MCR(silent) yields an EPR signal that strongly resembles that of MCR(red1), the active form of MCR; and stepwise annealing to 260-270 K leads to formation of MCR(red1). Cryoreduction of MCR(ox1)(-)(silent) solutions shows that our preparative method for this state yields enzyme that contains two major forms. One behaves similarly to MCR(silent), as shown by the observation that both of these forms give essentially the same redlike EPR signals upon cryoreduction, both of which give MCR(red1) upon annealing. The other form is assigned to the crystallographically characterized MCR(ox1)(-)(silent) and directly gives MCR(ox1) upon cryoreduction. X-band spectra of these cryoreduced samples, and of conventionally prepared MCR(red1) and MCR(ox1), all show resolved hyperfine splitting from four equivalent nitrogen ligands with coupling constants in agreement with those determined in previous EPR studies and from (14)N ENDOR of MCR(red1) and MCR(ox1). These experiments have confirmed that all EPR-visible forms of MCR contain Ni(I) and for the first time generated in vitro the EPR-visible, enzymatically active MCR(red1) and the activate-able "ready" MCR(ox1) from "silent" precursors. Because the solution Ni(II) species we assign as MCR(ox1)(-)(silent) gives as its primary cryoreduction product the Ni(I) state MCR(ox1), previous crystallographic data on MCR(ox1)(-)(silent) allow us to identify the exogenous axial ligand in MCR(ox1) as the thiolate from CoM; the cryoreduction experiments further allow us to propose possible axial ligands in MCR(red1). The availability of model compounds for MCR(red1) and MCR(ox1) also is discussed.

Safety and immunogenicity of hepatitis A vaccine in healthy adult volunteers.

The immunogenicity and adverse reaction of an inactivated hepatitis A (HA) vaccine were investigated. Sixty healthy adult volunteers who lacked antibody to HA virus (anti-HAV) received three doses of vaccine containing 720 enzyme-linked immunosorbent assay (ELISA) units (EL.U) according to a 0, 1 and 6 month schedule. Blood tests for serum liver enzymes and anti-HAV were performed at screening 7 days prior to, and 1, 6 and 7 months after the first dose. Anti-HAV was tested by radio immunoassay and ELISA for titre determination. The seroconversion rates measured by ELISA were 98.3% (59/60) at months 1 and 6 and 100% at month 7. Sixty-one per cent (109/180) of the documented injections were followed by local symptoms, essentially mild soreness at the site of injection; and 22.2% (40/180) by minor general symptoms including malaise, fatigue and lethargy. It is concluded that HA vaccine is highly immunogenic and safe. It may replace immunoglobulin as an effective method of preventing HA virus infection in adults.