Intraoperative location of muscular ventricular septal defects.
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Cardiac Surgical Procedures↗
Biomedical subjects
C Wong
Publications and source records attributed to C Wong.
Interactions and conversions of prion protein isoforms.
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Animals↗
Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: a multicenter prospective intravascular ultrasound study.
BACKGROUND: Luminal narrowing in transplant coronary artery disease is thought to be primarily caused by intimal proliferation, and the role of vascular remodeling is less certain. METHODS AND RESULTS: We studied cardiac allografts from 83 prospectively recruited patients immediately and 1 year after transplant using intravascular ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p < 0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also occurred (-0.9 +/- 3.2 mm(2), 7% of baseline total area) in segments free of detectable intimal disease at baseline and at 1 year. Using the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the large and the small coronary-segment groups. The large-segment group (n = 176) shrank more (-2.6 +/- 4.4 vs. -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal growth was similar in both groups (0.8 +/- 2.2 vs. 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 fully ultrasound matched sub-cohort showed similar results. Changes in intimal area, total vessel area, and lumen area were similar in segments with (n = 132) and segments without (n = 178) pre-existing donor disease. Despite overall shrinkage, change in total vessel area positively correlated with change in intimal area (r = 0.29, p < 0.0001). CONCLUSION: In large coronary segments, coronary artery shrinkage plays an important role in the loss of luminal diameter early after cardiac transplantation, whereas new intimal growth occurs in both large and small segments. Pre-existent donor disease does not aggravate these processes. Compensatory remodeling with increasing intimal growth retards the rate of lumen loss. As is intimal thickening, shrinkage and compensatory remodeling are important pathogenic mechanisms in transplant coronary artery disease.
Adult↗
Distinct tumour specificity and IL-7 requirements of CD56(-)and CD56(+) subsets of human gamma delta T cells.
gamma delta T cells are believed to recognize tissue injury caused by infections, tumours, as well as chemical and physical agents. The present study was carried out to study the feasibility of the ex vivo expansion of gamma delta T cells from healthy individuals, and to determine their functional capacity against tumours. We selectively expanded the peripheral gamma delta T cells of five donors against a myeloma cell line, XG-7. Under optimal conditions, the resulting bulk cultures comprised about 82% of the gamma delta T cells, more than 90% of which showed the T-cell receptor (TCR)-V gamma 9 delta 2 rearrangement. These gamma delta T-cell cultures exhibited TCR-gamma delta dependent cytotoxicity against different tumour cell lines including Molt-4, BJAB, Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL), and the nasopharyngeal carcinoma (NPC) cell lines, CNE2 and 915, in addition to the stimulator XG-7. By competitive cytotoxicity assays, the gamma delta T cells demonstrated recognition of at least three distinct target specificities expressed by Molt-4, CNE2 and LCL, respectively, which were related to that expressed by the stimulator XG-7 cells. The recognition of the specificity expressed by XG-7 and Molt-4 was further shown to require the participation of heat shock protein (HSP). The specificity expressed by CNE2 and 915 was preferentially recognized by the CD56 subset of gamma delta T cells, which could be sustained in the presence of interleukin (IL)-7. These results suggested that gamma delta T-cell immunity against tumour cell lines may be acquired in response to other types of tissue injury and, hence, implicates a role for their use in the prevention and treatment of tumours.
Burkitt Lymphoma↗
T cell antigen receptor vaccines for active therapy of T cell malignancies.
T cell lymphoproliferative disorders continue to be serious management problems, and so alternative therapeutic modalities are continuously being explored. One such strategy involves immunotherapy using the T cell receptor (TCR) as a target. Specifically we are attempting to develop a T cell receptor idiotype (TCR-Id) vaccine because the TCR-Id can serve as a tumor-specific antigen. In this article we will briefly review the rationale for TCR-Id vaccines, the preclinical models as developed in our laboratory, and a discussion of our current plans for a vaccine trial in mycosis fungoides.
Adenoviridae↗
Automated multiplex assay system for simultaneous detection of hepatitis B virus DNA, hepatitis C virus RNA, and human immunodeficiency virus type 1 RNA.
We have developed an automated multiplex system for simultaneously screening hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) in blood donations. The assay, designated AMPLINAT MPX HBV/HCV/HIV-1 Test (AMPLINAT MPX), consists of virus extraction and target sequence-specific probe capture on specimen preparation workstation GT-X (Roche Diagnostics K.K., Tokyo, Japan) and amplification and detection by TaqMan PCR on the ABI PRISM 7700 Analyzer (Perkin-Elmer Applied Biosystems, Foster City, Calif.). An internal control (IC) is incorporated in the assay to monitor the extraction, target amplification, and detection processes. The assay yields qualitative results without discrimination of the three targets. Detection limits (95% confidence interval) are 22 to 60 copies/ml for HBV, 61 to 112 IU/ml for HCV, and 33 to 66 copies/ml for HIV-1, using a specimen input volume of 0.2 ml. The AMPLINAT MPX assay detects a broad range of genotypes or subtypes for all three viruses and has a specificity of 99.6% for all three viruses with seronegative specimens. In an evaluation of seroconversion panels, the AMPLINAT MPX assay detects HBV infection an average of 24 days before the detection of HBsAg by enzyme immunoassay. HCV RNA was detected an average of 31 days before HCV antibody. HIV-1 RNA was detected an average of 14 days before HIV-1 antibody and an average of 9 days before p24 antigen. The Japanese Red Cross has been evaluating the AMPLINAT MPX system since October 1999. The clinical performance indicates that the AMPLINAT MPX system is robust, sensitive, and reproducible, with a high percentage of valid assay runs (96.8%), a low false-positive rate (0.34%), and a low IC failure rate (0.24%).
Blood Donors↗
Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.
OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.
Adult↗
Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.
OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.
Adult↗
Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers.
OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.
Adult↗
Cough in a patient with an infusion port.
In this case report, we describe a patient with a history of fallopian tube adenocarcinoma who had an infusion port in place for the past 4 years. During the course of her stay in the hospital for pneumonia, she developed a cough that became worse with the infusion of fluids through the port. A portogram done to investigate this problem revealed the presence of a portobronchial fistula. This is the first reported case of a portobronchial fistula. Various possibilities to explain the formation of portobronchial fistula are discussed.
Adenocarcinoma↗
A randomized comparison of home visits and hospital-based group follow-up visits after early postpartum discharge.
OBJECTIVE: Short postpartum stays are common. Current guidelines provide scant guidance on how routine follow-up of newly discharged mother-infant pairs should be performed. We aimed to compare 2 short-term (within 72 hours of discharge) follow-up strategies for low-risk mother-infant pairs with postpartum length of stay (LOS) of <48 hours: home visits by a nurse and hospital-based follow-up anchored in group visits. METHODS: We used a randomized clinical trial design with intention-to-treat analysis in an integrated managed care setting that serves a largely middle class population. Mother-infant pairs that met LOS and risk criteria were randomized to the control arm (hospital-based follow-up) or to the intervention arm (home nurse visit). Clinical utilization and costs were studied using computerized databases and chart review. Breastfeeding continuation, maternal depressive symptoms, and maternal satisfaction were assessed by means of telephone interviews at 2 weeks postpartum. RESULTS: During a 17-month period in 1998 to 1999, we enrolled and randomized 1014 mother-infant pairs (506 to the control group and 508 to the intervention group). There were no significant differences between the study groups with respect to maternal age, race, education, household income, parity, previous breastfeeding experience, early initiation of prenatal care, or postpartum LOS. There were no differences with respect to neonatal LOS or Apgar scores. In the control group, 264 mother-infant pairs had an individual visit only, 157 had a group visit only, 64 had both a group and an individual visit, 4 had a home health and a hospital-based follow-up, 13 had no follow-up within 72 hours, and 4 were lost to follow-up. With respect to outcomes within 2 weeks after discharge, there were no significant differences in newborn or maternal hospitalizations or urgent care visits, breastfeeding discontinuation, maternal depressive symptoms, or a combined clinical outcome measure indicating whether a mother-infant pair had any of the above outcomes. However, mothers in the home visit group were more likely than those in the control group to rate multiple aspects of their care as excellent or very good. These included the preventive advice delivered (76% vs 59%) and the skills and abilities of the provider (84% vs 73%). Mothers in the home visit group also gave higher ratings on overall satisfaction with the newborn's posthospital care (71% vs 59%), as well as with their own posthospital care (63% vs 55%). The estimated cost of a postpartum home visit to the mother and the newborn was $265. In contrast, the cost of the hospital-based group visit was $22 per mother-infant pair; the cost of an individual 15-minute visit with a registered nurse was $52; the cost of a 15-minute individual pediatrician visit was $92; and the cost of a 10-minute visit with an obstetrician was $92. CONCLUSIONS: For low-risk mothers and newborns in an integrated managed care organization, home visits compared with hospital-based follow-up and group visits were more costly but achieved comparable clinical outcomes and were associated with higher maternal satisfaction. Neither strategy is associated with significantly greater success at increasing continuation of breastfeeding. This study had limited power to identify group differences in rehospitalization and may not be generalizable to higher-risk populations without comparable access to integrated hospital and outpatient care.
Adult↗
Scrotal orchiectomy for a large testicular seminoma.
Our patient had neglected a growing left testicular mass over a 5-year period. Due to the large size of the tumor a scrotal delivery was necessary. Pathology showed a 1.6 kg pure classic seminoma. Metastatic work up revealed stage IIC disease and he was treated with primary cisplatin-based chemotherapy and remains free of recurrence after 24 months. The potential risk of scrotal violation is discussed.
Adult↗
Chronic fatigue syndrome: oxidative stress and dietary modifications.
Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear; however, a number of recent studies have shown oxidative stress may be involved in its pathogenesis. The role of oxidative stress in CFS is an important area for current and future research as it suggests the use of antioxidants in the management of CFS. Specifically, the dietary supplements glutathione, N-acetylcysteine, alpha-lipoic acid, oligomeric proanthocyanidins, Ginkgo biloba, and Vaccinium myrtillus (bilberry) may be beneficial. In addition, research on food intolerance is discussed, since food intolerance may be involved in CFS symptom presentation and in oxidation via cytokine induction. Finally, recent evidence suggests celiac disease can present with neurological symptoms in the absence of gastrointestinal symptoms; therefore, celiac disease should be included in the differential diagnosis of CFS.
Antioxidants↗
Managing the patient with psoriasis.
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Administration, Oral↗
Occupational asthma cases notified to OSH from 1996 to 1999.
AIMS: To update notifications to the Occupational Safety and Health Service of the Department of Labour (OSH) Notifiable Occupational Disease System (NODS) from June 1996 to the beginning of 1999. METHODS: All notifications received for non-asbestos related occupational respiratory disease were reviewed to confirm the clinical diagnosis, occupational causation, and to identify the causative agent where possible. RESULTS: 54 cases of asthma were notified, of which 21 (39%) were accepted as being occupationally caused. These cases arose from 'predictable' industries. CONCLUSIONS: NODS offers sentinel data from interested practitioners and workplaces. Occupational asthma and other occupational respiratory diseases remain poorly notified to this system. NODS confirms the presence of occupational asthma in New Zealand from predictable and preventable causes not dissimilar to other countries. This data collection system needs supplementation by other mechanisms.
Adult↗
Overexpression of wild-type RhoA produces growth arrest by disrupting actin cytoskeleton and microtubules.
We have investigated the role of Rho GTPase in cell growth by generating stable cells that express the wild-type RhoA (RhoA(wt)) under the control of an inducible promoter. Induction of RhoA(wt) had a biphasic effect on the actin cytoskeleton. At low levels of expression, RhoA(wt) stimulated the assembly of actin stress fibers without affecting cell growth. At high levels, there was a paradoxical disruption of the actin cytoskeleton accompanied by a growth arrest. Cell cycle analysis revealed a dual block at the G(1)/S and G(2)/M checkpoints. The G(1)/S arrest correlated with the accumulation of p21(Cip1), resulting in the inhibition of cdk2 activity, whereas the G(2)/M block correlated with the loss of microtubules. The cyclin B level and the cdc2 kinase activity, however, were increased, suggesting that the progression through mitosis rather than entry into the G(2)/M is defective when RhoA(wt) is overexpressed. Similar cell cycle defects and the loss of microtubules were observed after a cytochalasin D treatment, indicating that the ability of RhoA to regulate the integrity of actin cytoskeleton may be critical for the cell cycle transition through both the G(1)/S and M phase checkpoints.
Actins↗
A minimal ankyrin promoter linked to a human gamma-globin gene demonstrates erythroid specific copy number dependent expression with minimal position or enhancer dependence in transgenic mice.
In red blood cells ankyrin (ANK-1) provides the primary linkage between the erythrocyte membrane skeleton and the plasma membrane. We have previously demonstrated that a 271-bp 5'-flanking region of the ANK-1 gene has promoter activity in erythroid, but not non-erythroid, cell lines. To determine whether the ankyrin promoter could direct erythroid-specific expression in vivo, we analyzed transgenic mice containing the ankyrin promoter fused to the human (A)gamma-globin gene. Sixteen of 17 lines expressed the transgene in erythroid cells indicating nearly position-independent expression. We also observed a significant correlation between the level of Ank/(A)gamma-globin mRNA and transgene copy number. The level of Ank/(A)gamma mRNA averaged 11% of mouse alpha-globin mRNA per gene copy at all developmental stages. The addition of the HS2 enhancer from the beta-globin locus control region to the Ank/(A)gamma-globin transgene resulted in Ank/(A)gamma-globin mRNA expression in embryonic and fetal erythroid cells in six of eight lines but resulted in absent or dramatically reduced levels of Ank/(A)gamma-globin mRNA in adult erythroid cells in eight of eight transgenic lines. These data indicate that the minimal ankyrin promoter contains all sequences necessary and sufficient for erythroid-specific, copy number-dependent, position-independent expression of the human (A)gamma-globin gene.
Animals↗
Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain.
The route of administration influences the reinforcing effects of cocaine. Here we assessed whether there were differences in the efficacy of cocaine to block the dopamine transporters (major target for cocaine's reinforcing effects), as a function of route of administration. Positron emission tomography and [11C]cocaine, a dopamine transporter radioligand, were used to compare the levels of dopamine transporter blockade induced by intravenous, smoked and intranasal cocaine in 32 current cocaine abusers. In parallel, the temporal course for the self-reports of "high" were obtained. Cocaine significantly blocked dopamine transporters. The levels of blockade were comparable across all routes of administration and a dose effect was observed for intravenous and intranasal cocaine but not for smoked cocaine. For equivalent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self reports of "high" than intranasal cocaine and showed a trend for a greater effect than intravenous cocaine. The time to reach peak subjective was significantly faster for smoked (1.4+/-0.5 min) than for intravenous cocaine (3.1+/-0.9 min), which was faster than intranasal cocaine (14.6+/-8 min). Differences in the reinforcing effects of cocaine as a function of the route of administration are not due to differences in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the speed of cocaine's delivery into the brain on its reinforcing effects.
Administration, Inhalation↗