Chronologic changes in serum hepatitis B virus DNA, genotypes, surface antigen mutants and reverse transcriptase mutants during 25-year nationwide immunization in Taiwan.

We investigated breakthrough infection and hepatitis B virus (HBV) genetic changes in immunized subjects after 25 years of a universal infant immunization. Specifically, serum HBV DNA, genotypes, surface antigen mutants and nucleoside analog-resistant (NAr) mutants were assessed in 2853 subjects (<25 years old) surveyed in 2009, and these data were compared with the data from previous serosurveys. A comparison across different age-stratified groups using the 2009 data revealed a significant increase in the seropositive rate of anti-HBc (5.51% vs 12.38%, P=.001) and HBV DNA (1.13% vs 3.96%, P=.007) between those 17-22 and 23-24 years of age, possibly due to selective infant immunization in 1984-1986. Well-characterized NAr mutants, potential NAr mutants and surface "a" determinant mutants were detected in none, 15 (45.5%) and nine (27.3%) of 33 HBV DNA-positive subjects, respectively. Of 15 immunized, HBV DNA-positive young adults (18-24 years), three (20%) carried "a" determinant mutants. Amongst 1176 HBsAg-negative subjects evaluated for occult HBV infection, those seropositive for anti-HBc had a higher seropositive rate for HBV DNA (10/110, 9.1% vs 7/1066, 0.66%; P<.001) and "a" determinant mutants (4/110, 3.6% vs 0/1066; P<.001) than those seronegative for anti-HBc. Overall, the HBsAg-positive subjects in six serosurveys showed no significant increase in genotype C frequency in the comparison between the vaccinated and unvaccinated cohorts (25/98, 25.5% versus 14/79, 17.7%, P=.188). Over the 25-year programme, there was no increase in the prevalence of genotype C in HBsAg carriers and no increase in breakthrough HBV infection or surface mutant prevalence beyond adolescence. Nucleic acid amplification should still be considered the primary screening method for occult hepatitis B detection in high-risk recipients.

Identification and characterization of IgA antibodies against ß2-glycoprotein I in childhood Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a common IgA-mediated vasculitis in children. The antigenic target for IgA is to be determined. OBJECTIVE: To test whether ß2-glycoprotein I (ß2GPI) is an antigenic target for IgA in childhood HSP, and to evaluate the clinical implications and pathogenic role of such IgA autoantibodies. METHODS: The reactivity of patients' plasma samples and purified polyclonal IgA with ß2GPI, ß2GPI-derived peptides and endothelial cells was tested by enzyme-linked immunosorbent assay. The association between clinical manifestations and IgA anti-ß2GPI antibodies was also analysed. Finally, IgA-mediated cytotoxicity on endothelial cells was further evaluated. RESULTS: At the acute stage, patients with HSP had significantly higher plasma levels of IgA antibodies against ß2GPI than healthy controls [reference units (RU) 1.14 ± 0.8 vs. 0.42 ± 0.24, P < 0.001]. IgA anti-ß2GPI antibodies were associated with the presence of joint manifestations (with vs. without joint involvement, 1.15 ± 0.64 vs. 0.85 ± 0.47, P = 0.0341) and heavy proteinuria (with vs. without heavy proteinuria, 2.09 ± 2.02 vs. 1.04 ± 0.62, P = 0.0028). Polyclonal IgA from plasma samples positive for IgA anti-ß2GPI antibodies bound well not only to ß2GPI with Kd values < 10(-5) mol L(-1), but also to some ß2GPI-dereived linear peptides (P3, P5, P7, P11 and P12). Moreover, ß2GPI-reactive polyclonal IgA also bound well to endothelial cells and induced complement-dependent cell lysis. CONCLUSION: These findings reveal the clinical and pathogenic relevance of IgA anti-ß2GPI antibodies in childhood HSP and suggest that ß2GPI may be an important autoantigen for HSP.

Decreased chewing activity during mouth breathing.

This study examined the effect of mouth breathing on the strength and duration of vertical effect on the posterior teeth using related functional parameters during 3 min of gum chewing in 39 nasal breathers. A CO(2) sensor was placed over the mouth to detect expiratory airflow. When no airflow was detected from the mouth throughout the recording period, the subject was considered a nasal breather and enrolled in the study. Electromyographic (EMG) activity was recorded during 3 min of gum chewing. The protocol was repeated with the nostrils occluded. The strength of the vertical effect was obtained as integrated masseter muscle EMG activity, and the duration of vertical effect was also obtained as chewing stroke count, chewing cycle variation and EMG activity duration above baseline. Baseline activity was obtained from the isotonic EMG activity during jaw movement at 1.6 Hz without making tooth contact. The duration represented the percentage of the active period above baseline relative to the 3-min chewing period. Paired t-test and repeated analysis of variance were used to compare variables between nasal and mouth breathing. The integrated EMG activity and the duration of EMG activity above baseline, chewing stroke count and chewing cycle significantly decreased during mouth breathing compared with nasal breathing (P<0.05). Chewing cycle variance during mouth breathing was significantly greater than nasal breathing (P<0.05). Mouth breathing reduces the vertical effect on the posterior teeth, which can affect the vertical position of posterior teeth negatively, leading to malocclusion.

Role of assessment tests in the stability of intelligence scoring of pre-school children with uneven/delayed cognitive profile.

BACKGROUND: As part of an ongoing clinical service programme for pre-school children with developmental delay in an Asian developing country, we analysed the effect of three assessment tests, that is, Bayley Scale of Infant Development-II, Leiter International Performance Scale - Revised and Wechsler Preschool and Primary Scale of Intelligence - Revised - Chinese, on the stability of intelligence quotient (IQ) of children from pre-school through early childhood. METHODS: The participants were 313 Taiwanese pre-school children with uneven or delayed cognitive profile and they were followed through early childhood. IQ stability was explored by different tests and among children of different clinical diagnosis: 168 children with non-autistic intellectual disability, 73 children with autism spectrum disorder, 58 children with mixed receptive-expressive language disorder and 14 children of other heterogeneous diagnoses. Stability of scores was evaluated using the r-squared for Pearson's coefficients to see the correlation between initial IQ (IQ1) and follow-up IQ (IQ2). Multiple linear regressions were also applied to see whether IQ1 had predictive ability for IQ2 and test-test difference in the total 313 children and each diagnostic subgroup. RESULTS: Results revealed that mean IQ1 was 65.8 ± 15.4 while mean IQ2 was 73.2 ± 17.9 for the total 313 children. The IQs were stable across an average follow-up duration of 38.6 ± 22.1 month from pre-school into early childhood. Patterns of positive correlations between IQ1 and IQ2 were noted by all the tests (r-squared = 0.43-0.5, all P < 0.001) and in the majority of diagnostic subgroups. Multiple regressions analysis also revealed that IQ1 could predict IQ2 significantly in all the tests (all P < 0.001). DISCUSSION: After careful choice of appropriate initial test, stability of IQ in children with developmental delay was noted from pre-school through early childhood. In addition, the translated version of cognitive assessment was valid for the required context of an Asian developing country. With the current emphasis on early identification and intervention for pre-school children with developmental delay, this information bears merit in clinical practice.

Low viraemia at enrollment in children with chronic hepatitis C favours spontaneous viral clearance.

The significance of hepatitis C viral (HCV)-RNA levels in long-term clinical outcomes of children with chronic HCV infection is not well understood. We conducted a long-term follow-up study of 42 children with chronic HCV infection that included clinical evaluation, biochemical tests, HCV genotyping and repeated quantitative HCV-RNA detection. Patients were divided into low and high viraemia groups according to RNA levels at enrollment (below/above 4.5 x 10(4) IU/mL), and clinical, biochemical and virological factors were evaluated. Overall, 14.3% (6/42) of patients developed spontaneous viral clearance during a median 10.1 years of follow-up. HCV-RNA levels at enrollment and mean RNA levels during follow-up for each patient were significantly correlated (R = 0.9018, 95% CI: 0.6637-0.9038, P < or = 0.001). HCV-RNA level fluctuation was within two log units in 76% of patients. Cumulative viraemia probability during follow-up could be predicted by viraemia levels at enrollment (P = 0.0092). Chronic HCV-infected children, with an RNA level below 4.5 x 10(4) IU/mL at enrollment, have a higher spontaneous viral clearance rate.

Jar-opening challenges. Part 2: estimating the force-generating capacity of thumb muscles in healthy young adults during jar-opening tasks.

This study discusses the force-generating capacity of thumb muscles during jar-opening tasks using two grip patterns: the power grip and the precision grip. This study develops a three-dimensional biomechanical model of the thumb to predict muscle forces in jar-opening activities based on external forces measured by a custom-designed jar device. Ten healthy subjects participated in the study. Each participant turned a jar lid of 66 mm diameter counterclockwise with maximal effort and preferred speed using both grip patterns. The average normal and tangential forces applied by the thumb to the jar lid show that the normal force is the primary contributive force for opening a jar. This normal force is approximately three times the tangential force. Muscular force-generating capacity measurements show that the major active muscles during a jar-opening activity for both grips include the flexor pollicis longus, flexor pollicis brevis, abductor pollicis brevis, adductor pollicis, and opponens pollicis. The total muscle force ratios for the precision grip and power grip with respect to externally applied forces are 5.6 and 4.7 respectively. These ratios indicate that the power grip pattern produces less muscle force per unit of external applied load. The technique proposed in this study provides a proper apparatus and model for measuring three-dimensional loads and estimating the force-generating capacity of each muscle and tendon of the thumb during jar-opening tasks.

Strategic information technology alliances for effective health-care supply chain management.

To gain and sustain competitive advantage, health-care providers have to continuously review and renovate their operational and information technology (IT) strategies through collaborative and cooperative endeavour with their supply chain channel members. This paper explores new ways of enhancing a health-care organization's responsiveness to changes and increasing its competitiveness through implementing strategic information technology alliances among channel members in a health-care supply chain network. An overview of issues and problems (e.g. bullwhip effect, negative externalities and free-riding phenomenon in multichannel supply chains) presented in the health-care supply chains is first delineated. This paper further goes over the issues of health-care supply chain coordination and integration for strategic IT alliances, followed by the discussion of the spillover effect of IT investments. A number of viable IT practices (such as information sharing and Internet-enabled supply chain portal) for effective health-care supply chain collaboration and coordination are then examined in this research. Finally, the paper discusses how strategic IT alliances can help improve the effectiveness of health-care supply chain management.

Immunodetection of pentamer and modified C-reactive protein using surface plasmon resonance biosensing.

In clinical practices, the examination of pentamer C-reactive protein (pCRP) is commonly used as a prognostic indicator of the risk of a patient developing cardiovascular disease (CVD). Structural modification of pCRP produces a modified CRP (mCRP) which exhibits different biological activities in the body. In recent years, mCRP has come to be regarded as a more powerful inducer than pCRP, and hence mCRP measurement has emerged as an important indicator for assessing the risk of developing CVD. The surface plasmon resonance (SPR) biosensing technique can be employed to increase the detection accuracy and real-time response when sensing pCRP or mCRP. In this study, three monoclonal antibodies (Mabs), C8, 8D8, and 9C9, are immobilized on a protein G layer for subsequent CRP detection. The experimental results reveal that the Mab C8 reacts with both pCRP and mCRP, the Mab 8D8 with pCRP, and the Mab 9C9 with mCRP. No false signals caused by non-specific binding are observed. When detecting pCRP using Mab C8, the SPR bioassay provides sufficient sensitivity to evaluate whether or not a patient is at risk of developing CVD. SPR biosensing provides a viable and accurate approach for the real-time evaluation of pCRP and mCRP levels, and is therefore of considerable benefit in clinical examinations of CPR.

Lack of formation of heterocyclic amines in fumes from frying French fries.

The formation of heterocyclic amines (HAs) in the fumes from frying French fries in soybean oil or lard was studied. A high-pressure liquid chromatography method was used to determine the various HAs in fumes. Results showed that the yields of fumes produced from soybean oil when heated alone for 2 or 4 h were higher than from lard; however, a reversed trend was found when frying French fries in soybean oil and lard. Most fumes from soybean oil and lard while frying French fries were adsorbed onto the condensation apparatus, while the other portions were adsorbed onto the wool and glass beads, which were incorporated in our experimental design for collecting the fumes. The fumes from soybean oil when heated alone were found to contain three HAs, namely, 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), and 1-methyl-9H-pyrido[4,3-b ]indole (Harman), whereas two more HAs, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b ]indole (Trp-P-1), were generated in lard. Lard was more susceptible to the formation of HAs than soybean oil when both were heated alone. No HAs were detected in the fumes from French fries fried in soybean oil and lard.

Low dietary zinc intake attenuates the efficacy of 2,4-thiazolidinedione on reducing hyperglycemia in db/db mice (Short communication).

Zinc (Zn) has the potential of regulating the action of thiazolidinedione (TZD), an anti-diabetic drug. Since some diabetic patients cannot achieve optimal glycemic control when receiving TZD, we investigated if Zn deficiency affects TZD's efficacy in glucose metabolism. Diabetic mice were fed diets containing 3 or 30 mg/kg Zn for 6 weeks. Thereafter, all mice were oral gavaged with 2,4-thiazolidinedione. Our results showed that blood glucose values at fasting and during the glucose tolerance test were significantly higher in low-Zn mice than those of adequate-Zn mice. Thus, low Zn intake may attenuate TZD's efficacy on reducing diabetic hyperglycemia.

The androgen receptor in spermatogenesis.

Androgens are steroid hormones that are necessary for normal male phenotype expression, including the outward development of secondary sex characteristics as well as the initiation and maintenance of spermatogenesis. Many physiological actions of androgens are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. AR functions as a ligand-dependent transcription factor, regulating expression of an array of target genes that are important in male pubertal development and fertility. In this review, the expression and necessity of AR in specific testicular cell types that are important in spermatogenesis will be discussed, and recent information obtained through the study of complete and cell type-specific AR null mouse models will be presented.

Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice.

Two triterpene acids, oleanolic acid (OA) and ursolic acid (UA) were examined for their ability to inhibit the tumor growth and modify hematopoiesis after irradiation in three experimental systems: (a) in vivo anti-tumor activity of implanted tumor by ascitic cells was found to be augmented by addition of OA and UA at a high concentration and inhibited in a dose-dependent manner; (b) in the sublethal whole-body irradiated mice treated with the drugs in the 30 min preirradiation period, enhanced effects of OA and UA on peripheral leukocytes were observed by a different significance, and (c) when these chemicals were administered i.p. to mice 30 min before 4 Gy irradiation, both OA and UA enhanced the postirradiation responses of splenic blastogenesis by PHA. UA was a more potent tumorigenic inhibitor than OA. Combining with the gamma-irradiation, however, there was no significant synergetic effect on their anti-tumor activity. The beneficial effects of OA and UA on hematopoiesis and immunocompetence under this study, suggested they might partially play a role in anti-cancer and, furthermore, with the ability to decrease undesirable radiation damage to the hematopoietic tissue after radiotherapy.

Comparisons of geniposidic acid and geniposide on antitumor and radioprotection after sublethal irradiation.

The antitumor effects of two iridoid compounds, geniposidic acid (GA) and geniposide (GP), were investigated in mice along with their possible effects on radioprotection after sublethal X-irradiation. Decreases in the growth of the implanted tumor by ascitic cells were a result of intraperitoneal administration of GA and GP at high concentrated levels. This result was achieved by exerting the levels of dosage in a dose-dependent manner. Except on the 12th day after treatment by the dosage of 500 mg/kg, reduced radiation effects of mice treated with the drugs in the 30 min preirradiated period by GA and GP on peripheral leukocytes were not observed significantly by the sublethal whole-body X-irradiation. And except on the 7th day after treatment, when these two compounds were administered i.p. to mice 30 min before 4 Gy irradiation, neither GA nor GP enhanced significantly the postirradiation responses of splenic blastogenesis by PHA. In addition, GA might be a more potent tumor growth inhibitor than GP when combined with the X-irradiation, though there was no significant synergetic effect on their combined antitumor activity. The preliminary results of GA and GP on hematological and blastogenic observations in this study suggested that they may very well, partially, play a role in an effective anticancer product with the ability to decrease undesirable radiation damage to the hematologic tissue after high dose irradiation.

Molecular and electrophysiological characterizations of fGluR3 alpha, an ionotropic glutamate receptor subunit of a teleost fish.

Here we report the cloning and functional analysis of a cDNA encoding a functional glutamate receptor subunit of Oreochromis sp., a freshwater teleost fish. The deduced amino acid sequence of this cDNA clone, fGluR3 alpha, displays the highest sequence identity to that of the mammalian GluR3 subunit. Results of quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis indicated that the expression level of fGluR3 alpha in the cerebellum was much less than that in the telencephalon and optical lobe. Similar to its mammalian counterpart, variants of fGluR3 alpha were created by alternative splicing and RNA editing at the R/G site. The channel properties of homomeric fGluR3 alpha expressed in Xenopus oocytes were similar to those of the mammalian alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors. The rank order of agonist potency of the expressed fGluR3 alpha is AMPA > or = glutamate > or = quisqualate > domoate > or = kainate. This is the first functional glutamate receptor of teleost fish being demonstrated to be sensitive to AMPA. Furthermore, this study suggested a strong functional conservation of AMPA-preferring receptors in vertebrates.

Long term immune response of universal hepatitis B vaccination in infancy: a community-based study in Taiwan.

OBJECTIVES: To evaluate the long term immunity provided by a universal hepatitis B vaccination program in infancy and the booster effect on school age children who had no protective antibody titers to hepatitis B surface antigen. METHODS: We conducted a community-based seroepidemiologic study of 1337 healthy 7-year-old children in Taiwan one decade after the implementation of a mass hepatitis B vaccination program. A booster vaccination was suggested for noncarrier children who did not have protective titers of surface antibody. Serologic responses and infection rates were compared with those of the nonboostered children. In a nonselected group of 39 volunteer noncarrier vaccinees, quantitative serologic response was determined before, 1 month after a booster vaccination and 1 year later. RESULTS: A total of 572 children (42.8%) had low concentrations of surface antibody, and 9 were hepatitis B surface antigen carriers (0.7%). Eighty-two percent of "nonprotected" vaccinees showed immunologic memory to a booster dose and developed protective antibody titers 1 month later; 60.6% maintained protective titers 1 year later. The frequency of new hepatitis B virus infection was similar for those who received a booster and those who did not as investigated by the core antibody seroconversion during 1-year follow-up. However, the risk was low, with annual incidences of <1% in both groups, and none became chronic carriers. CONCLUSION: According to these data a universal vaccination program in infancy provides adequate protection against hepatitis B virus infection for school age children and a booster vaccination is not recommended.

Viral etiology of intussusception in Taiwanese childhood.

BACKGROUND: Adenovirus infection and lymphoid hyperplasia have been associated with childhood intussusception. However, the extent of other viruses involved in this condition remains unclear. This prospective study investigates the relationship between some lymphotropic viruses and current childhood intussusception. METHODS: Patients with intussusception encountered in a pediatric emergency department in a recent 3-year period were studied. Healthy infants and toddlers of comparable age served as controls. Throat and rectal viral cultures were performed in patients and controls. Viral antibodies against adenovirus, cytomegalovirus, human herpesvirus (HHV)-6, HHV-7 and Epstein-Barr virus (EBV) were tested in paired sera from the patients. Acute stage serum from each patient and mesenteric lymph nodes from patients requiring surgery were studied for the presence of adenovirus genome by PCR. RESULTS: Twenty-seven of 61 (44.3%) intussusception patients, but only 2 of 52 (3.8%) healthy controls shed nonenteric adenovirus in throat and rectal specimens (P < 0.001). Of the 27 (74.1%) patients who shed adenovirus, 20 were older than 1 year old, whereas only 1 of 15 (6.7%) similarly aged patients in a previous study from the same area three decades ago did so (P = 0.001). Among 43 patients with available paired sera, acute primary viral infection was found in 17 (39.5%) by adenovirus, 4 (9.3%) by HHV-6, 5 (11.6%) by HHV-7, 2 (4.7%) by EBV and none by cytomegalovirus. Multiple viral infections occurred in 6 patients. Adenovirus genome was detected in 4 of 9 mesenteric lymph nodes and in only 3 of 60 (5%) acute phase sera. CONCLUSIONS: Primary nonenteric adenovirus infection contributes to current childhood intussusception. Acute primary HHV-6, HHV-7 and EBV infections also play etiologic roles.

A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy.

OBJECTIVES: To characterize and quantitate optic nerve histopathologic and morphometric differences between optic nerve hypoplasia (ONH) as an early and congenital form of intrinsic axonal loss and Leber hereditary optic neuropathy (LHON) as a late and acquired form of intrinsic axonal loss. MATERIALS AND METHODS: Optic nerves from 3 sources were examined: a 42-year-old healthy woman (control), a 53-year-old woman with ONH diagnosed postmortem, and a 74-year-old woman with LHON. The optic nerves were processed, embedded, and stained with a 1% solution of paraphenylene diamine. Histopathologic and morphometric analyses were performed via light microscopy and a semiautomatic computer image analysis system. RESULTS: The ONH showed severe axonal depletion without degenerated profiles in an inferonasal sector, with only a small superotemporal sector having a near normal appearance. The LHON revealed general axonal depletion centrally, fibrocytic scarring, scattered "degeneration dust," and evidence of minimal inflammation, with residual axons limited to superior and temporal peripheral clusters. Morphometric analysis revealed total fiber populations of 98,000 in the ONH optic nerve and 48,000 in the LHON optic nerve, representing 90% and 95% reductions, respectively, compared with the control optic nerve (1.2 million fibers). CONCLUSIONS: Optic nerve hypoplasia and LHON present 2 distinguishable and distinctive patterns of nerve fiber distribution and axonal dropout. The lack of degenerated axons in ONH indicates that any axonal death probably occurred through apoptosis during development. In LHON, degenerated axons and minimal grade of inflammation were obvious, implicating a more "active" pathologic process. This study describes distinctions between these 2 optic neuropathies.

Radiation-induced muscle damage in rats after fractionated high-dose irradiation.

Muscle damage in the legs of male Wistar rats after exposure to high-dose radiation was evaluated by observations of biopsied tissue made with light and transmission electron microscopy. Both legs of about 40 mature male Wistar rats were exposed to 80 Gy 6 MV X rays from a linear accelerator given in 40 fractions of 2 Gy. At intervals starting from the first day to 12 months after irradiation, serial muscle biopsies were obtained by sacrificing the rats on different days according to the experimental design. The irradiated gastrocnemius muscle displayed a progressive structural change that began immediately after the completion of the exposures. Morphological changes in irradiated muscles were characterized by hemorrhage, lymphocytic infiltration and obvious vascular destruction. Increased amounts of collagen between the muscle fibers were present even at 12 months after irradiation. There were significant changes in the number, size and structure of mitochondria in the muscle cells from the first day until 1 year after irradiation. Even 12 months after the final exposure, no recovery of muscle tissue was seen by light and transmission electron microscopy.

Least microtransfusion from mother to fetus in elective cesarean delivery.

OBJECTIVE: To examine the variability of maternal-fetal microtransfusion in different modes of delivery, as measured by hepatitis B surface antigen (HBsAg) and placental alkaline phosphatase. METHODS: We recruited 97 HBsAg-positive pregnant women. The mode of delivery included elective cesarean in 16, normal spontaneous vaginal delivery in 56, vacuum or forceps delivery in 12, and emergency cesarean after labor in 13. We measured HBsAg and placental alkaline phosphatase levels in 97 pairs of maternal and fetal blood samples collected at delivery. RESULTS: The mean maternal placental alkaline phosphatase levels did not differ among these four groups. The mean cord placental alkaline phosphatase level of the elective cesarean group was the lowest (P < .05). All samples of cord sera for this group were negative for HBsAg, compared with 38 of 56, eight of 12, and seven of 13 in the spontaneous vaginal, vacuum or forceps, and emergency cesarean groups, respectively (P < .05). CONCLUSION: The level of mother-to-fetus microtransfusion least in the elective cesarean group, as revealed by both the lowest cord placental alkaline phosphatase and HBsAg levels. These observations may have implications for reducing perinatal transmission of blood-borne viruses.

The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy.

The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber's). The mechanism of EMB-induced optic neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve. Before attempting to use therapeutic copper to replenish endogenous stores in an attempt to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is still effective against mycobacteria in the presence of copper. EMB and copper, alone and in combination, were tested against six strains of Mycobacterium tuberculosis and five strains of Mycobacterium avium using a radiometric broth macrodilution assay. Copper did not effect EMB's antimicrobial actions against either species of mycobacteria. This in vitro study suggests that if copper were given to patients to prevent EMB-induced optic neuropathy, it would not compromise EMB's bacteriostatic properties.