Biomedical subjects

A Ho

Publications and source records attributed to A Ho.

At least 37 records · Page 2Linked to original sources

PubMed2001

Tear exchange under hydrogel contact lenses: methodological considerations.

PURPOSE: To characterize hydrogel lens tear exchange and to apply an optimized method to compare tear exchange of a marketed hydrogel lens to that measured with a prototype silicone hydrogel lens. METHODS: Fluorophotometry and a nonpenetrating tracer (70-kDa FITC-dextran) were used with a single extended-wear soft contact lens (EWSCL) material on 11 subjects to characterize tear-exchange kinetics. Twenty to 30 measurements were obtained over a 30-minute period to allow accurate modeling and estimation of the several tear-exchange parameters. Calculated values included tear-replenishment rate (TRR), elimination rate (ER), and the time for 95% of the signal to be eliminated (T(95)). Major experiments were (1) comparison of ER under controlled and physiological conditions, (2) comparison of right and left eyes, (3) repeatability of ER and T(95) on five occasions, and (4) comparison of a marketed lens (oxygen permeability [Dk] 28 x 10(-9) [cm/sec][ml O(2)/ml mm Hg]) to a prototype silicone hydrogel lens (Dk 140 x 10(-9) [cm/sec][ml O(2)/ml mm Hg]). RESULTS: Tracer elimination behind a hydrogel contact lens (CL), up to 30 minutes after insertion, was optimally described by double-exponential kinetics. Physiological ER (5-30 minutes after CL insertion) was optimally described by single-exponential kinetics. Overall, physiological ER was 8.8% +/- 3.8% per minute, and T(95) was 31.0 +/- 16.1 minutes (n = 76 and 72 determinations, respectively). Differences between right and left eyes in ER and T(95) were not significant at the 0.05 level. No difference in ER or T(95) was found between habitual and controlled blinking. Mean TRR was 0.67% +/- 0.26% per blink (n = 11 determinations). No differences were shown between ER or T(95) measurements over time. A prototype highly oxygen-permeable silicone hydrogel lens showed higher ER than did a marketed hydrogel lens (P < 0.01). CONCLUSIONS: Estimates of postlens tear exchange using a slit lamp fluorophotometer are similar to previously reported rates using similar fluorophotometric techniques. Fluorescent decay behind a hydrogel lens is most precisely described using a double-exponential curve equation and tear exchange may be described using ER, TRR and T(95), although the T(95) may be the least reliable of these measures. The technique appears capable of discriminating between lens types.

Adult↗

PubMed2000

Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma.

Phosphoinositide-3-OH kinases (PI(3)Ks) constitute a family of evolutionarily conserved lipid kinases that regulate a vast array of fundamental cellular responses, including proliferation, transformation, differentiation and protection from apoptosis. PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis. Thus, a model has arisen that PI(3)Ks promote development of cancers. Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice. In humans, p110gamma protein expression is lost in primary colorectal adenocarcinomas from patients and in colon cancer cell lines. Overexpression of wild-type or kinase-dead p110gamma in human colon cancer cells with mutations of the tumour suppressors APC and p53, or the oncogenes beta-catenin and Ki-ras, suppressed tumorigenesis. Thus, loss of p110gamma in mice leads to spontaneous, malignant epithelial tumours in the colorectum and p110gamma can block the growth of human colon cancer cells.

Adenocarcinoma↗

PubMed2000

Effects of the androgenic anabolic steroid, nandrolone decanoate, on adrenocorticotropin hormone, corticosterone and proopiomelanocortin, corticotropin releasing factor (CRF) and CRF receptor1 mRNA levels in the hypothalamus, pituitary and amygdala of the rat.

There is increasing abuse of androgenic anabolic steroids (AAS) by non-athletes. AAS abuse has been associated with psychiatric symptoms such as mania, major depression and aggression and the development of dependence. Little is known about the effects of AAS on hypothalamic-pituitary-adrenal axis function or corticotropin releasing factor, which may be involved in mediating some of the psychiatric symptoms associated with AAS abuse. Male Sprague-Dawley rats received one daily intra-muscular injection of the AAS nandrolone decanoate (ND, 15 mg/kg) or vehicle for 3 days. Animals were sacrificed either 1 h or 24 h after the last injection, brain regions dissected and trunk blood collected. Corticotropin releasing factor (CRF), CRF receptor1 (CRF-R1) and proopiomelanocortin (POMC) mRNAs were measured with solution hybridization/RNase protection. Circulating levels of corticosterone and adrenocorticotropin hormone (ACTH) were determined using radioimmunoassays. One hour following the last injection, ND significantly increased circulating levels of both corticosterone and ACTH levels. In the amygdala, CRF mRNA levels were unchanged 1 h after the last injection of ND but were significantly reduced at 24 h. The same was found for hypothalamic POMC. No significant AAS effects were observed on: hypothalamic CRF mRNA; POMC mRNA in the amygdala or CRF R1 mRNA in the anterior pituitary.

Adrenocorticotropic Hormone↗

PubMed2000

Chronic 'binge' pattern cocaine alters the neuroendocrine profile of pregnant rats.

Pregnant Fischer rats injected with cocaine in a 'binge' pattern (3x15 mg/kg, i.p.) from gestational days 8 through 17, had significantly higher levels of progesterone (212.12+/-22.50 vs. 91. 99+/-15.41 ng/ml) and corticosterone (257.99+/-21.76 ng/ml vs. 31. 70+/-7.93, respectively) than saline-treated dams. No significant differences in prolactin were observed (2.36+/-0.17 vs. 2.17+/-0.19 ng rPrl132/ml). Correlation analysis indicated that there is a significant relationship between plasma levels of progesterone and corticosterone and the quality of nests built by the dams. No correlation was found within animals between prolactin plasma levels and the nest quality. Thus, cocaine's effect on progesterone and corticosterone may contribute to the series of behavioral alterations associated with cocaine exposure during pregnancy.

Animals↗

PubMed2000

Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy.

BACKGROUND: The objective of this trial was to analyze the prognostic relevance of the angiogenic peptides basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in the serum of patients with advanced carcinoma of the head and neck treated by primary radiochemotherapy. METHODS: From 1992 to 1995, 26 patients with advanced head and neck cancer (25 stage IV, 1 stage III UICC) were treated according to the protocol of radiochemotherapy with carboplatin. The pretreatment serum levels VEGF, bFGF, and MMP-2 were measured by ELISA, and data were correlated with tumor characteristics and followed up (median time of follow up, 60 months). RESULTS: An increase in bFGF serum level above the upper limit of normal controls showed a significant correlation with shorter time the of locoregional control (p =.036). In covariant analysis bFGF serum concentration proved to be independent of other prognostic factors like tumor site, age, total tumor volume, and response to therapy. No prognostic relevance of VEGF and MMP-2 serum levels could be determined. CONCLUSIONS: The results of this pilot study indicate that the serum concentration of bFGF has prognostic relevance for advanced head and neck cancer.

Adult↗

PubMed2000

A study to examine the accuracy of potassium measurements in clinical laboratories across Canada.

OBJECTIVE: To assess the accuracy of potassium measurements in clinical laboratories across Canada. DESIGN AND METHOD: The flame atomic emission spectrophotometry reference method for the determination of potassium was established at the Canadian Reference Laboratory by using National Institute of Science and Technology standard reference materials. The method was subsequently used to assign target values for potassium to Canadian Reference Laboratory's External Quality Assessment human-serum-based testing material. A total of 503 laboratories participated and 9,279 individual External Quality Assessment test results were included in the study. Bias was determined by using difference plots. RESULTS: Clinically significant bias (>1.6%) was observed in 45.9% of the laboratories. Bias ranged from 0.34 mmol/L to -0.54 mmol/L. At low concentrations (<3.5 mmol/L) a positive bias was most frequently observed (14.7% of analytical systems). At high potassium concentrations (>5.1 mmol/L) a negative bias was most frequently observed (31.4% of analytical systems). CONCLUSION: Inaccuracy in potassium results can contribute to test redundancy and mismanagement of patients, while prohibiting the merger of laboratory data from disparate testing sites for the purpose of trending and consolidation within a "universal health record." Inaccurate test results and the lack of standardization among laboratories adversely impact our ability to establish common reference intervals and critical limits. This inability has an adverse effect on medical decisions and patient care.

Bias↗

PubMed2000

Cocaine affects progesterone plasma levels in female rats.

Female Fischer rats injected with cocaine in a "binge" pattern (15 mg/kg, IP, three times a day, at 1-h intervals) for 1 day had significantly higher levels of progesterone than saline-treated controls (p < 0.001). When analyzed by the stage of the estrous cycle, animals in proestrus showed significantly higher cocaine-induced progesterone plasma levels than those in other stages of the cycle (p < 0.01). Progesterone plasma levels were also increased after a single dose of cocaine (15 mg/kg). However, 3 h postinjection progesterone plasma levels had returned to normal. Thus, cocaine modulation of progesterone plasma levels appears to be an acute effect. In ovariectomized rats pretreated with estrogen, progesterone, or estrogen + progesterone, no significant differences were observed in progesterone plasma levels after acute "binge" pattern cocaine administration. Thus, acute cocaine induced increases in progesterone plasma levels in intact female rats are probably due to an increase in secretion rates of progesterone rather than an acceleration of its biotransformation. Due to the profound effects of progesterone in the modulation of CNS plasticity, the modulation of progesterone plasma level by cocaine may have implications for reproductive processes and neuronal functions of women. Moreover, cocaine may affect the progesterone levels in women utilizing progesterone-based contraception or steroid replacement treatment after menopause.

Animals↗

PubMed2000

Ovarian hormone replacement affects cocaine-induced behaviors in ovariectomized female rats.

To determine whether cocaine-induced behavioral alterations are modulated by ovarian hormones, ovariectomized rats were randomly assigned to one of two drug treatment conditions: "binge" cocaine (three 15-mg/kg intraperitoneal (ip) injections, 1 h apart) or saline administration; and four hormone pretreatment sub-groups: vehicle control, estrogen, progesterone, or estrogen+progesterone. Cocaine-treated animals displayed more locomotor activity than saline-treated animals and locomotor activity was higher after the third injection than after the first two injections. When analyzed according to hormone group, the administration of estrogen+progestrone suppressed cocaine-induced locomotion after the first injection; this effect was significant when compared to estrogen-pretreated animals. While in each condition cocaine-treated animals displayed significantly higher stereotypic activity than saline-treated animals, in the estrogen+progesterone replacement group, there was more activity after the second injection of cocaine than after the first. Interestingly, animals in the estrogen+progesterone group had significantly lower plasma levels of the cocaine metabolite, benzoylecgonine, than animals in the progesterone or estrogen groups. These results extend our earlier findings in the intact female rat, which suggest an interaction between the endocrine environment, cocaine metabolism, and cocaine-induced behaviors. These effects may underlie reported sex and estrous cycle differences in cocaine-induced behavioral activity.

Animals↗

PubMed2000

Lethal methadone intoxications in Geneva, Switzerland, from 1994 to 1998.

AIMS: To estimate the number of methadone lethal intoxications in Geneva from 1994 to 1998, where the number of patients in methadone treatment has more than doubled since 1990. DESIGN: Retrospective study of all toxicological, autopsy and clinical data. SETTING: The Geneva Department of Forensic Medicine. PARTICIPANTS: All suspected overdose deaths in Geneva from 1994 to 1998. Cases were selected on the basis that the only cause of death was a potentially lethal drug concentration in the postmortem blood sample. MEASUREMENT: Toxicology and autopsy findings, clinical and drug history. FINDINGS: There were 106 lethal drug intoxications over the period. The overall number of drug intoxication deaths went from 33 in 1994 to nine in 1998. Thirty-six cases had methadone identified in their blood. All the 36 cases but one had medications or other drugs used illicitly present in the blood or urine. Of these 36 cases, 21 were attributed to methadone lethal intoxication. Only seven of these 21 decedents were enrolled in a methadone programmes. The number of deaths attributed to methadone intoxication ranged from three to five per year. CONCLUSION: Most lethal methadone intoxication is due to diverted or illegal methadone in association with medications or other drugs used illicitly. Furthermore, the increase in methadone prescription under strict medical control with health measures aimed at drug abuse prevention did not lead, in our study, to an increase of methadone lethal intoxication and may have been partly responsible for the large decrease of overall drug intoxication deaths during the time of our study.

Adolescent↗

PubMed2000

Transient complete remission of metastasized Merkel cell carcinoma by high-dose polychemotherapy and autologous peripheral blood stem cell transplantation.

Merkel cell carcinoma (MCC) is a rare cutaneous tumour with neuroendocrine differentiation. Metastasis occurs preferentially to regional lymph nodes but distant and multiple visceral metastases may occur. Chemotherapy has been performed with a variety of protocols based largely on agents active in small-cell lung cancer. Owing to the rarity of MCC, there is no standard protocol for the treatment of metastatic disease. We report a 59-year-old patient with systemic metastatic MCC. After diagnosis of distant metastases, first-line polychemotherapy (cisplatin 80 mg m(-2), doxorubicin 50 mg m(-2), etoposide 300 mg m(-2) and bleomycin 30 mg) was administered four times at 3-weekly intervals and resulted in partial remission of metastases. Subsequently, high-dose chemotherapy according to the PEI regimen (ifosfamide 12 g m(-2), carboplatin 900 mg m(-2) and etoposide 1500 mg m(-2)) was applied, followed by autologous blood stem cell transplantation (ABSCT). This protocol resulted in a complete remission that lasted for 6 months. This is the first report on a complete remission of metastatic MCC after high-dose polychemotherapy and ABSCT. High-dose chemotherapy might be a therapeutic option in chemosensitive metastatic MCC, and further evaluation is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Quality of life of people with epilepsy following temporal lobectomy: a preliminary report.

This is a preliminary report of the quality of life of 9 people, 5 men and 4 women, in Hong Kong who underwent temporal lobectomy for seizure control. The Chinese version of World Health Organization Quality of Life Measure Abbreviated Version, validated in Hong Kong, was used as the outcome measure. Analysis suggested that the quality of life of these participants after successful temporal lobectomy was poorer than that of 157 healthy controls in the physical and psychological domains as measured. This suggests that other factors in addition to achieving complete seizure control play significant roles in promoting the quality of life of such patients.

Adult↗

PubMed2000

Letter legibility and chart equivalence.

INTRODUCTION: We tested the appropriateness of the assumption that charts, which only vary in having different sequences of five letters per line, chosen from the same 10 letter set, can be regarded as equivalent for the purpose of making valid comparisons of visual acuity. METHOD: Visual acuity findings from samples of 400 patients, for each of two nominally equivalent Bailey-Lovie charts, have been used to determine the relative legibility of individual letters and lines, using the percentage incorrect method of analysis. RESULTS: The chance of error for the hardest letter is approximately 13 times greater than for the easiest letter on each chart. Significant between-chart differences in error rates for the hardest letters ('F' and 'H') were found. Some letters that have adjacent ranks on the legibility scale were found to have significantly different legibility. Significant differences in difficulty can occur for the same nominal line on apparently equivalent charts because of chance combinations of easier or harder letters in that line. Uneven line-to-line scale intervals have been confirmed for the charts examined, by showing corresponding differences in the distributions of lines of threshold acuity. CONCLUSIONS: The use of varying examination distances may be inappropriate for Bailey-Lovie (or similar) charts that depart from their nominal interval scaling. When different versions of these charts are assumed to be equivalent, the discrepancy between repeated measurements may be significantly increased. There is the possibility of increasing measurement precision using charts having different sequences of the same 10 letters in each line to achieve equal scaling of line intervals. Equivalent charts can be validly constructed using different sequences of the same 10 letters in each line.

Equipment Design↗

PubMed2000

Effects of cocaine self-administration on plasma corticosterone and prolactin in rats.

The effects of i.v. cocaine self-administration under "naturalistic" conditions on plasma corticosterone (CORT) and prolactin (PRL) were investigated in male Sprague-Dawley rats. After the determination of plasma CORT and PRL levels under basal conditions before access to cocaine for self-administration, rats were allowed to self-administer cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg/infusion i.v.) by pressing a response lever under a continuous schedule of cocaine reinforcement during five daily consecutive 10-h sessions. Plasma CORT was significantly increased and plasma PRL was significantly reduced after each of the five self-administration sessions. The effects of cocaine on plasma CORT were intake-dependent, as demonstrated by significant positive correlations between postsession plasma CORT and total cocaine intake within the preceding sessions. The effects of cocaine on PRL were also intake-dependent but only on the first day of self-administration, on which a significant negative correlation was observed between cocaine intake and postsession PRL. In contrast, significant correlations between PRL and cocaine intake were not observed during any subsequent session, apparently reflecting adaptations to cocaine-induced PRL release. Alterations in neuroendocrine homeostasis emerged over time. Reductions in presession CORT values, as well as a persistent blunting of the diurnal CORT peak, were observed. Similarly, there was a modest but significant attenuation of plasma PRL when measured 4 days after the termination of cocaine self-administration. Alterations in neuroendocrine function associated with self-administration may be related to the development of cocaine dependence and could contribute to relapse in abstinent users.

Animals↗

PubMed2000

Reduced hypothalamic POMC and anterior pituitary CRF1 receptor mRNA levels after acute, but not chronic, daily "binge" intragastric alcohol administration.

BACKGROUND: Endogenous corticotropin-releasing factor (CRF), its pituitary CRF1 receptor, and proopiomelanocortin (POMC) may be involved in the hypothalamic-pituitary-adrenal (HPA) responses to alcohol. METHODS: Alcohol (1.5 g/kg) or water was administered intragastrically to male Fischer rats after the "binge" pattern regimen, that is, three times daily at 1 hr intervals at the beginning of the light cycle. The levels of CRF, CRF1 receptor, and POMC mRNAs in the hypothalamic-pituitary axis were measured after acute (1 day) or chronic (14 days) binge pattern alcohol administration. Plasma levels of ACTH and corticosterone were measured to examine time-dependent alterations of HPA responses. RESULTS: Plasma ACTH and corticosterone levels were elevated dramatically after 1 day of acute binge pattern alcohol administration. After 14 days of chronic alcohol, however, no elevation in plasma ACTH levels and an attenuated elevation in plasma corticosterone levels were found. CRF mRNA levels in the hypothalamus were not altered after either acute or chronic alcohol administration. CRF1 receptor mRNA levels in the anterior pituitary were decreased significantly after acute administration, with no change after chronic alcohol administration. POMC mRNA levels in the anterior pituitary were not altered by either acute or chronic alcohol administration. In the hypothalamus, POMC mRNA levels were decreased significantly after acute but not chronic binge alcohol administration. CONCLUSIONS: These results suggest that (1) rats exposed to chronic binge alcohol develop tolerance in HPA activity, as shown by no elevation of ACTH and an attenuated corticosterone response to chronic alcohol after initial dramatic elevations by acute alcohol administration; (2) a concurrent acute decrease in CRF1 receptor mRNA levels in the anterior pituitary is associated with increased HPA activity, and (3) alterations of POMC gene expression in the hypothalamic region may have implications for a molecular understanding of the neuroendocrine response to alcohol.

Administration, Oral↗

PubMed2000

Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts.

Stabilized methadone-maintained former heroin addicts (MTPs) treated with effective doses of methadone have markedly reduced drug craving; reduction or elimination of heroin use; normalized stress-responsive hypothalamic-pituitary-adrenal, reproductive, and gastrointestinal function; and marked improvement in immune function and normal responses to pain, all of which are physiological indices modulated in part by endogenous and exogenous opioids directed at the mu and, in some cases, the kappa-opioid systems. This study was performed to explore opioid receptor binding in MTPs. Fourteen normal, healthy volunteers and 14 long-term MTPs in treatment for 2 to 27 years and receiving 30 to 90 mg/day of methadone were studied with positron emission tomography using tracer amounts of [(18)F]cyclofoxy, an opioid antagonist that labels mu and kappa opioid receptors. Imaging was performed in the morning, 22 h after the last dose of methadone in patients, and concurrent plasma levels of methadone were determined. Five brain regions of specific interest for addiction and pain research (thalamus, amygdala, caudate, anterior cingulate cortex, and putamen) were among the six regions of highest [(18)F]cyclofoxy binding. Specific binding of [(18)F]cyclofoxy was lower by 19 to 32% in these regions in MTPs compared with those in normal volunteers. The degree to which specific binding was lower in caudate and putamen correlated with methadone plasma levels (P <.01 and P <.05, respectively), suggesting that these lower levels of binding may be related to receptor occupancy with methadone and that significant numbers of opioid receptors may be available to function in their normal physiological roles.

Adult↗

PubMed2000

Clinical evaluation of subgingival application of metronidazole 25%, and adjunctive therapy.

The effect of topical application of a metronidazole gel (ELYZOL DENTAL GEL), and adjunctive therapy in the treatment of adult periodontitis was assessed clinically. A single, masked examiner performed clinical assessments. Fourteen patients were involved, each one received four different treatments including control, and the four treatments were randomly applied to at least one tooth in each quadrant for each patient in a comparative split-mouth design. Clinical examinations were carried out before treatment and 90 days after treatment. All patients had at least one tooth in each quadrant with probing pocket depth of > or = 5mm. The four treatment groups were: (I) One session of one hour of scaling and root planning, (II) metronidazole 25% dental gel (ELYZOL DENTAL GEL) applied on day 0 and day 7, (III) scaling adjunctive to metronidazole 25%, and (IV) No treatment. Instruction in oral hygiene was given to all subjects at base line examination. At the end of the study (day 90), all groups had statistically significant improvement in probing pocket depth (P < 0.02), and in plaque and bleeding indices (P < 0.05) when compared to day 0. However, group III had statistically significantly greater improvement (P < 0.03) in probing pocket depth than groups I, II and IV. Both groups I and II had statistically significantly greater improvement (P < 0.05) in probing pocket depth than control group. On the other hand, both groups were not statistically significantly different from each other in probing pocket depth improvement. It is suggested that topical Elyzol treatment may improve periodontal health as well as subgingival scaling and root planning therapy, and adjunctive treatment could obtain an additional therapeutic effect.

Administration, Topical↗

PubMed1999

Role of the costimulatory molecule CD28 in the development of lupus in MRL/lpr mice.

MRL/Mpj-lpr/lpr (MRL/lpr) mice develop autoimmune disorders, including lymphoproliferation, glomerulonephritis, autoantibody production, and hypergammaglobulinemia. To investigate the role of the costimulatory molecule CD28 in the development of these disorders, MRL/lpr mice lacking CD28 were generated by gene targeting. Compared with CD28+/+ MRL/lpr mice, CD28-/- MRL/lpr mice showed decreased lymphadenopathy but increased splenomegaly associated with the expansion of abnormal B220+ TCRalphabeta+ T cells. Although levels of IgM Abs were unchanged in CD28-/- MRL/lpr mice, the production of anti-DNA IgG Abs and IgG rheumatoid factors were suppressed. IgG deposition in the glomeruli was markedly decreased, and the development of glomerulonephritis was significantly retarded. Furthermore, renal vasculitis and arthritis were absent in CD28-/- MRL/lpr mice. These results indicate that, although CD28 is not required for the generation of the abnormal T cell population in MRL/lpr mice, it does play an important role in the development of autoimmune disease in these animals.

Animals↗

PubMed1999

In vivo protein transduction: delivery of a biologically active protein into the mouse.

Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by the size and biochemical properties of the proteins. Here it is shown that intraperitoneal injection of the 120-kilodalton beta-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. These results open new possibilities for direct delivery of proteins into patients in the context of protein therapy, as well as for epigenetic experimentation with model organisms.

Animals↗