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Biomedical subjects

A Ho

Publications and source records attributed to A Ho.

At least 145 records · Page 8Linked to original sources

Availability of reliable serum methadone determination for management of symptomatic patients.

Methadone, when used in the appropriate dose, prevents opioid withdrawal during the 24-hour period following medication. However, the appropriate dose for a given patient may be difficult to determine due to variations in methadone metabolism which is affected by many factors. Early opioid withdrawal, requiring a higher dose of methadone, is often difficult to diagnose because many of the symptoms are also symptoms of other syndromes common in the methadone maintenance population. In this study, ten patients in stable methadone maintenance treatment reporting > or = 4 Himmelsbach signs of abstinence were compared with ten patients reporting fewer symptoms. Until recently, accurate, precise, and affordable determination of serum methadone level has not been readily available from commercial laboratories. This study has found that such measures are now available. Serum specimens from each subject were sent to three commercial laboratories for determination of serum methadone level. Results from the three laboratories were highly correlated. No statistical correlation was found between serum methadone level and number of Himmelsbach signs. Of the subjects reporting four or more symptoms, 40% had low serum methadone levels ( < 150 ng/ml); 60% did not. Of the subjects reporting fewer than four symptoms, 90% had serum methadone levels > or = 150 ng/ml. Subjects with > or = 4 Himmelsbach signs had lower dose-adjusted serum methadone levels, the amount of methadone circulating per mg dose, (t = 1.54, p < .0702). Thus, for patients who report symptoms which could be attributable to opioid withdrawal, measurement of serum methadone level may help to differentiate complaints due to early abstinence from those due to other medical conditions.

Adult↗

Color Doppler imaging: a new technique to assess orbital blood flow in patients with diabetic retinopathy.

PURPOSE: Color Doppler imaging is a new noninvasive technique that enables measuring blood flow velocity in small orbital vessels, arteries as well as veins. Because hemodynamic changes are seen in patients with diabetic retinopathy by other techniques, the authors compared 61 eyes with proliferative, 59 eyes with nonproliferative, and 26 eyes with preproliferative diabetic fundus changes with a matched control group of 70 patients without diabetes (128 eyes). METHODS: The central retinal artery (CRA), short posterior ciliary artery (PCA), and ophthalmic artery (OA) of all patients were examined, and the systolic, diastolic, and mean velocities were measured for each vessel. RESULTS: Differences between the groups were most prominent in the CRA. The perfusion velocity was significantly lower (P < 0.001) in proliferative eyes (Vsystolic 5.7 +/- 1.8 cm/sec) than in the control group (Vsystolic 9.4 +/- 1.2 cm/sec) or in nonproliferative eyes (Vsystolic 8.4 +/- 1.8 cm/sec). In the preproliferative group, there was greater variability in velocity distribution. Consequently, no statistically significant difference could be deduced, either in the group with background retinopathy or in the group with proliferative diabetes. In the OA and PCA, neither group showed significant differences from normal. CONCLUSIONS: Measurements indicate a correlation between severity of diabetic retinopathy and decreased flow velocity in the CRA.

Adult↗

Chronic administration of a cocaine "binge" alters basal extracellular levels in male rats: an in vivo microdialysis study.

The purpose of this study was to determine the effects of chronic "binge" administration of cocaine (hourly x 3 i.p.). Male Fisher rats were treated for 13 days with cocaine (3 x 10 or 15 mg/kg) or saline (3 x 1 ml/kg). On day 14, microdialysis was performed on the rats and all received cocaine (3 x 10 or 15 mg/kg). Dialysate samples were collected from the ventromedial (nucleus accumbens and immediate surrounding striatum) and dorsolateral striata. After 13 days of daily cocaine "binges," estimated basal dopamine levels were lowered in the ventromedial striatum: 10 mg/kg x 3: 3.32 +/- 0.52 nM (n = 9) vs. 5.50 +/- 1.28 nM (n = 7) (t test, P < .1), and 15 mg/kg x 3: 3.50 +/- 0.37 nM (n = 6) vs. 5.66 +/- 0.58 nM (n = 7) (P < .01); and in the dorsolateral striatum 10 mg/kg x 3: 7.17 +/- 0.55 nM (n = 9) vs. 9.54 +/- 1.08 nM (n = 7) (t test, P < .05), and 15 mg/kg x 3: 6.88 +/- 0.22 nM (n = 5) vs. 10.00 +/- 1.04 nM (n = 7) (t test, P < .03). In cocaine-pretreated animals the cocaine "binge" on day 14 resulted in a lower elevation in extracellular DA levels than their corresponding values in saline-pretreated animals (pretreatment effect, P < .04 in the ventromedial striatum; P < .05 in the dorsolateral striatum), although the percent increases over baseline were of similar magnitude. In addition, the acute tolerance phenomenon observed during an initial cocaine binge was abolished after chronic exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Digital indocyanine green videoangiography of central serous chorioretinopathy.

BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) is poorly understood. Abnormalities in the choroidal circulation have been hypothesized to be causative factors. Fluorescein angiography has not been particularly useful in identifying specific choroidal defects in CSC, largely because of inherent limitations in imaging with this technique. Recent technologic advances in digital indocyanine green videoangiography allow enhanced imaging of the choroid and other subretinal structures in comparison with fluorescein angiography. METHODS: We performed digital indocyanine green videoangiography in 29 consecutive eyes with CSC and compared our results with clinical and fluorescein angiographic findings. RESULTS: Several newly recognized subretinal abnormalities in CSC were noted with digital indocyanine green videoangiography, including (1) presumed hyperpermeability of the choroidal circulation surrounding active retinal pigment epithelial leaks, (2) additional focal and multifocal areas of presumed choroidal hyperpermeability not associated with abnormalities detectable by fluorescein angiography or clinical examination, and (3) multiple presumed "occult" serous retinal pigment epithelial detachments with a characteristic indocyanine green videoangiographic pattern. CONCLUSION: We suggest that the pathogenesis of CSC may be due to a choroidal vascular hyperpermeability with and without associated active pigment epithelial leaks and multiple presumed "occult" serous retinal pigment epithelial detachments. Based on these findings, a hypothetical model can be constructed related to the pathogenesis of CSC, beginning with choroidal abnormalities that secondarily affect the retinal pigment epithelium and neurosensory retina.

Acute Disease↗

Experimental allergic encephalomyelitis (EAE) in mice lacking CD4+ T cells.

Like most experimental autoimmune disease experimental allergic encephalomyelitis (EAE) has been shown to be mediated by CD4+ helper T cells. In vivo antibody blocking studies with anti-CD4 and adoptive transfer of activated CD4+ T cells indicate the importance of CD4+ cells in disease induction. Fourth backcross generation mutant CD4-/-PL/J mice were immunized with myelin basic protein. Despite the lack CD4+ T cells some of these mice developed EAE, albeit, at a considerably reduced frequency and with variable severity. Furthermore, antigen-specific T cell proliferation can be demonstrated, indicating some residual helper activity that is major histocompatibility complex class II restricted. This demonstrated that, although the CD4+ T cell is the prime effector cell in EAE, in mice developmentally lacking in CD4, the expanded double-negative T cells may subserve helper and effector functions.

Animals↗

Effects of ethanol on human natural killer cell activity: in vitro and acute, low-dose in vivo studies.

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4-hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the 51Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose-dependent decrease (p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/dl and above.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.

Animals↗

Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti-Hu-associated paraneoplastic encephalomyelitis.

Using immunohistochemistry, we studied the IgG subclass distribution of the anti-Hu antibody in serum, nervous system, and tumor of patients with anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN). The nervous system was also examined for deposits of complement and the distribution and type of inflammatory cells. IgG1 and IgG3 were the predominant isotypes of the anti-Hu IgG in serum, nervous system, and tumor. A few patients also had anti-Hu IgG2, but this isotype was not consistently present in all the regions of the nervous system studied. There was no correlation between neurologic symptoms and specific anti-Hu isotype, nor was there evidence that different anti-Hu isotypes recognized specific brain regions. Although IgG1 and IgG3 can activate complement, only weak complement reactivity was found, and that only in a few areas of the nervous system. This finding, in addition to the absence of natural killer (NK) cells, suggested that complement-mediated toxicity and antibody-dependent cell cytotoxicity mediated by NK cells are not pathogenic in PEM/PSN. Inflammatory infiltrates included CD19+ (B cells) and CD4+ (helper/inducer) cells in the perivascular spaces, and lymphocytes bearing CD8+CD11b- markers (cytotoxic T cells) in the interstitial spaces. Infiltrates of EBM11+ (monocyte/macrophage) cells were identified in the perivascular spaces (macrophage phenotype) and in those interstitial regions (microglial phenotype) with severe pathologic changes. The ability of the IgG1 and IgG3 isotypes to bind Fc receptors may have played a role in the recruitment of these monocyte/macrophage cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Time course of the development of behavioral sensitization and dopamine receptor up-regulation during binge cocaine administration.

Cocaine is a widely abused psychomotor stimulant that potentiates dopaminergic neurotransmission by inhibiting the re-uptake of dopamine. This study investigated whether cocaine administered in a paradigm that mimics the human pattern of cocaine abuse produces behavioral sensitization and if there are concomitant changes in dopamine receptor levels. The time course of alterations in cocaine-induced locomotor activity and dopamine receptor densities was determined. Male Fischer rats were injected with saline or cocaine (15 mg/kg) three times daily at 1-hr intervals at the beginning of the light cycle to approximate the manner in which cocaine is often abused by humans both in terms of temporal pattern and in relation to circadian rhythm. Cocaine administered in this binge-like regimen produced an increase in locomotor activity during each hour postinjection. The increase in activity was significantly greater on the 13th day of drug administration than on the first day indicating sensitization to the locomotor-activating effects of cocaine. D1 and D2 dopamine receptors were measured after 2, 7 and 14 days of saline or cocaine injections using quantitative in vitro receptor autoradiography. Up-regulation of D1 receptors occurred in the olfactory tubercle, nucleus accumbens, ventral pallidum and substantia nigra after 14 days of cocaine treatment. Transient increases in D2 receptor number were found in the olfactory tubercle, rostral nucleus accumbens and rostral caudate putamen after 7 days of cocaine injections which returned to baseline levels after 14 days of cocaine treatment. The temporal pattern of receptor up-regulation suggests that D1 receptors are involved in the development of behavioral sensitization to cocaine.

Animals↗

Influence of corneal shape on limbal light focusing.

PURPOSE: Light incident at the temporal cornea is focused by the peripheral anterior eye to the nasal limbus, the usual site of pterygium formation. Parameters that may contribute to observed individual variations in the degree of limbal light focusing were assessed. METHODS: Computer-assisted optical ray tracing techniques were applied to a human anterior segment model. The angle of incident light (theta, 95 degrees to 108 degrees posterior to the sagittal plane), corneal central radius of curvature (ro, 7.2 to 8.4 mm), and shape factor (p) were varied, and the effect on distal limbal intensity (I) was calculated. RESULTS: The magnitude of intensity peaks (Ipeak) is dependent on theta and ro. Steeper corneas have higher intensity peaks (Ipeak approximately 21.5X at ro = 7.2 mm, p = 0.75), and flatter corneas have lower intensity peaks (Ipeak approximately 8X at ro = 8.4 mm, p = 0.75) (cf Ipeak approximately 14X for a standard cornea, ro = 7.8 mm, p = 0.75). Anteroposterior location of intensity peaks is dependent on theta and ro. Steeper corneas have intensity peaks situated more anteriorly, whereas flatter corneas have more posteriorly placed peaks. Distal light distribution profiles demonstrate that intensity peaks are not always centrally located. At lower angles of incidence (theta = 100 degrees, ro = 7.8 mm, p = 0.75), peak intensity is located approximately 1 mm above and below the horizontal plane. The overall distribution (envelope) of light at the distal limbus is apparently independent of corneal shape. CONCLUSIONS: Differences in corneal topography can account for the clinical observation of individual variation in the degree of limbal light focusing. Whether individuals with corneas capable of developing intense limbal foci may be more predisposed to developing pterygium requires further study.

Anterior Eye Segment↗

[Color duplex ultrasound. A new procedure in the study of orbital blood vessels in diabetic retinopathy].

Color Doppler imaging is a new noninvasive technique that allows the measurement of flow velocity in small orbital vessels (both arteries and veins). We compared 59 eyes with proliferative, 47 eyes with nonproliferative and 24 eyes with preproliferative diabetic fundus changes with a control group of non-diabetic patients. The central retinal artery, short ciliary artery and ophthalmic artery of each patient were examined. The systolic, diastolic and mean velocity was obtained for each vessel. Differences between the groups were most prominent in the central retinal artery. The perfusion velocity was significantly lower (P < 0.01) in proliferative eyes (Vsyst 5.7 +/- 1.9 cm/s) than in the control group (Vsyst 9.4 +/- 1.4 cm/s) or the nonproliferative eyes (Vsyst 8.3 +/- 1.9 cm/s). In the preproliferative group the velocity distribution varied widely. Consequently, no statistically significant difference could be deduced in relation to either the control group or the group with proliferative diabetic changes. In the ophthalmic artery and ciliary artery no group showed significant differences from normal. Our measurements indicate a definite correlation between the severity of diabetic retinopathy and a decreased flow velocity, particularly in the central retinal artery. Thus, color Doppler imaging may help to identify those diabetic patients who are at high risk of developing severe diabetic retinopathy so that early photocoagulation treatment can be initiated.

Adult↗

Opioid receptor density changes in Alzheimer amygdala and putamen.

Since opioids can influence the release of acetylcholine, substance P and a number of other neurotransmitters that have been implicated in the pathogenesis of Alzheimer's disease (AD), it is of interest to assess opioid receptor levels in AD. We have examined mu, delta and kappa opioid receptor binding parameters, binding sensitivity to a GTP analog and distribution in amygdala, frontal cortex and putamen of AD brain. Control brains were matched according to age, sex, post-mortem interval and storage time. Kd values and GTP analog binding sensitivity did not differ in AD and control brains. Bmax values for mu ([3H]DAMGE) sites also appeared unaffected by in vitro binding assays. In contrast, kappa ([3H]U69593) and delta ([3H]DSLET) opioid receptor levels, were significantly changed. In AD amygdala kappa Bmax values increased from control levels of 123 +/- 12 to 168 +/- 13 fmol/mg protein, whereas densities of kappa and delta sites were decreased from 94 +/- 8 to 48 +/- 8 and 102 +/- 3.6 to 69 +/- 8.5 fmol/mg protein, respectively, in putamen. Autoradiography revealed corresponding differences in the distribution of kappa opioid receptors. The findings indicate that the kappa binding site, which is quantitatively the major opioid receptor class in human brain, undergoes marked changes in AD amygdala and putamen.

Aged↗

Novel opioid binding sites associated with nuclei of NG108-15 neurohybrid cells.

Nuclear opioid binding sites have been discovered in NG108-15 neurohybrid cells. Marker enzyme analyses as well as electron and fluorescence microscopy studies attested to the high degree of purity of the nuclear preparations. Immunohistochemical studies on cryostat sections of NG108-15 cells with an antibody to the opioid receptor corroborated a nuclear localization. 3H-[D-Pen2,D-Pen5]enkephalin (3H-DPDPE), 3H-[D-Ala2,D-Leu5]enkephalin (3H-DADLE), and 3H-diprenorphine binding parameters, Kd and Bmax values, and heterologous competition binding and stereospecificity data satisfied criteria for the presence of delta-opioid sites in purified nuclear preparations. Neither mu-([D-Ala2,mephe4,gly-ol5] enkephalin), dihydromorphine, nor kappa-(U69593) specific binding was detectable in purified nuclear preparations. Rates of association and dissociation of 3H-[D-Ser2,L-Leu5]enkephalyl-Thr were comparable to values obtained previously for opioid receptors. Opioid binding was also shown in subnuclear preparations from NG108-15 cell cultures. Agonists, 3H-DADLE and 3H-DPDPE, bind with high affinity to nuclear membranes and with lower affinity to chromatin. In contrast, partial agonist 3H-diprenorphine high-affinity binding sites were predominant in chromatin, while low-affinity binding was found in the nuclear membrane. Accordingly, 5'-guanylylimidodiphosphate sensitivity of 3H-DADLE binding was detected in nuclear membranes but not in chromatin. Both agonist and partial agonist opioid binding to nuclear membrane and chromatin were abolished upon cycloheximide treatment of NG108-15 cells. Taken together, the results suggest that NG108-15 cells contain newly synthesized GTP binding regulatory protein (G-protein)-coupled delta-opioid receptors in nuclear membranes and uncoupled opioid binding sites in chromatin.

Binding Sites↗

Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice.

Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model.

Animals↗

Color Doppler imaging of the eye and orbit. A synopsis of a 400 case experience.

Color Doppler imaging (CDI) is a recent advance in ultrasonography that allows simultaneous two-dimensional imaging of structure and blood flow. Doppler information is superimposed in color over a conventional gray-scale ultrasound image. Using this technique we have examined 400 eyes. The central retinal artery, posterior ciliary arteries, ophthalmic artery, the central retinal vein and the vortex veins could be located in all normal eyes. Using the color image as a guide, Doppler spectral analysis is used for quantitative assessment of blood flow velocity in these vessels. We also studied patients with intraocular tumors, arterial and venous retinal occlusions, orbital vascular anomalies and tumors. Color Doppler imaging is a new and promising modality for the study of ocular and orbital hemodynamics.

Blood Flow Velocity↗

Regional cerebral glucose metabolism and attention in adults with a history of childhood autism.

Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway.

Adolescent↗

A successful pregnancy from the oocyte donation programme in Singapore General Hospital.

A 41-year-old Chinese woman was seen in our centre in June 1989 with 5 years of premature menopause, requesting ovum donation. She was placed on cyclical hormonal therapy and put on the waiting list for ovum donation. Excess ova became available through one of our IVF patients and were fertilised with her husband's semen. Four pre-embryos resulted and these were cryopreserved using 1,2 propanediol. Embryo transfer in her second cycle of trying on 16 March 1990 of 2 pre-embryos was successful and a singleton pregnancy resulted. The pregnancy was supported with estradiol valerate and intramuscular progesterone till 17 weeks of gestation. The pregnancy went on uneventfully and she delivered a healthy baby boy by Caesarean section on 21 December 1990.

Adult↗

Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid.

We present what we believe is the first case of rickets following prolonged treatment with aluminum containing antacids that bind phosphate, in an 18-year-old mentally retarded boy with cerebral palsy and spastic quadriplegia. As expected, serum calcitriol was increased and urinary phosphate excretion was very low. However, in contrast to all published cases of antacid induced hypophosphatemic osteomalacia in adults, despite a substantial increase in bone resorption reflected by urinary total hydroxyproline excretion, urinary calcium excretion was low rather than high, and significant hypocalcemia occurred after antacids were ceased and a phosphate salt administered. We suggest that the skeleton was so under-mineralized because of growth during prolonged phosphate deficiency, possibly augmented by anticonvulsant administration and immobilization, that increased bone resorption did not release enough calcium to cause hypercalciuria, or to prevent hypocalcemia during resumption of normal mineralization.

Adolescent↗