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Biomedical subjects

W Ho

Publications and source records attributed to W Ho.

At least 19 recordsLinked to original sources

Ionizing radiation reduces neurally evoked electrolyte transport in rat ileum through a mast cell-dependent mechanism.

BACKGROUND/AIMS: Mechanisms of neuroimmune regulation of intestinal electrolyte transport under pathophysiological conditions are unclear. This study investigated the effect of ionizing radiation on ileal electrolyte transport. METHODS: Rats were exposed to 10 Gy gamma-radiation and were killed 2, 24, and 48 hours later. Ileal segments were either mounted in Ussing chambers and exposed to electrical field stimulation, prostaglandin E2, leukotriene D4, or theophylline, or they were assayed for biochemical indices of inflammation. Other segments were processed for routine histological screening, mast cell counts, or immunohistochemical analysis of the distribution of vasoactive intestinal polypeptide or substance P immunoreactivity. RESULTS: Basal short-circuit current was unchanged 2, 24, or 48 hours postirradiation. However, there was a reduction of tissue responsiveness to electrical field stimulation, prostaglandin E2, and theophylline but not to leukotriene D4. Decreased responsiveness at 2-hours postirradiation was blocked by pretreatment with the H1 antagonist pyrilamine. Tissue myeloperoxidase activity and 5-hydroxytryptamine content were not altered postirradiation, but tissue histamine and mucosal mast cells were significantly reduced at 24 and 48 hours. There were no significant changes in villus-crypt architecture until 48 hours postirradiation. There was no significant alteration in the distribution of immunoreactive vasoactive intestinal polypeptide or substance P. CONCLUSIONS: Ionizing radiation reduced the transport response to neural stimulation. The effect correlated temporally with decreased mast cells and histamine, suggesting a functional role for previously reported mast cell-nerve interactions.

Animals

Circulating granulocyte colony-stimulating factor (G-CSF) levels after allogeneic and autologous bone marrow transplantation: endogenous G-CSF production correlates with myeloid engraftment.

Myeloid engraftment after bone marrow transplantation (BMT) is influenced by a number of variables, including cytoreductive chemoradiotherapy, genetic disparity, number of reinfused committed myeloid progenitor cells, healthy microenvironment, and the presence of hematopoietic growth factors. Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation of myeloid progenitor cells and enhances myeloid engraftment after BMT. We investigated the temporal relationship between endogenous G-CSF production and myeloid engraftment in both children and adults after allogeneic (ALLO) and autologous (AUTO) BMT. Circulating endogenous G-CSF levels ranged between 0 and 2552 pg/mL. The correlation coefficient between circulating serum G-CSF levels and the peripheral absolute neutrophil count (ANC) was r = -.875 (P less than .001). The endogenous serum G-CSF level was highest during the first week after BMT, when the ANC was less than or equal to 200/microL (699 +/- 82.3 pg/mL) (P less than .001). Both children and adults demonstrated a similar inverse relationship between circulating G-CSF level and degree of neutropenia. One patient failed to engraft after AUTO BMT and also failed to generate any endogenous G-CSF production. Lastly, once the serum G-CSF level decreased to less than 200 pg/mL, a mean of 6.1 +/- 0.9 days elapsed before the ANC was greater than or equal to 500/microL for 2 consecutive days. This study demonstrates that endogenous G-CSF production is associated with myeloid engraftment in both children and adults after AUTO and ALLO BMT and that the rate of increase and decrease in endogenous G-CSF may be predictive of either failure to engraft or duration of neutropenia.

Adolescent

Fatal cerebral hemorrhage due to autonomic dysreflexia in a tetraplegic patient: case report and review.

Autonomic dysreflexia is the most important specific complication of high level spinal cord injury both in tetraplegic and in paraplegic patients above the midthoracic neural segment. It is a life threatening emergency that may lead to apoplexy. We present a case of fatal cerebral hemorrhage due to autonomic dysreflexia in order to demonstrate the gravity of this particular syndrome.

Adult

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.

Adult

A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia.

The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate-dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.

Adolescent

Partially endothelium-dependent relaxing effect of ketamine on the canine basilar artery in vitro.

The influence of the endothelium on the vasodilator effect of ketamine and its possible mechanism of action on intracellular calcium levels were investigated. We conducted experiments in vitro on canine basilar arteries precontracted with 5-HT and with potassium at high concentrations. Ketamine (10(-6) to 10(-3) M), added cumulatively, relaxed both 5-HT and high-K(+)-induced contraction of basilar arteries (with or without endothelium) in a dose-dependent manner. The ED50s of ketamine for relaxation of 5-HT and high-K(+)-induced contraction for intact endothelium were 3 x 10(-4) M and 6 x 10(-4) M, respectively, and for denuded preparations, 7 x 10(-4) M and 15 x 10(-4) M, respectively. Methylene blue, which blocks the release and/or the effect of endothelium derived relaxing factor, significantly attenuated the relaxation effect of ketamine on the basilar artery. Our results indicate that the endothelium may be responsible for a part of the vasodilator effect of ketamine. We also examined the effect of pretreatment of basilar artery with ketamine (5 x 10(-4) M) on intracellular calcium levels when contraction was induced by 5-HT or by high K+ concentrations. Ketamine significantly inhibited the phase of the contraction induced by high K+. Thus, the vasodilator effect of ketamine may be mediated by inhibition of calcium influx and by the release of EDRF.

Animals

Determination of buprenorphine by high-performance liquid chromatography with fluorescence detection: application to human and rabbit pharmacokinetic studies.

A rapid, sensitive, precise and accurate high-performance liquid chromatographic assay with fluorescence detection was developed for the determination of buprenorphine in human, rabbit, pig and dog plasma. It is comprised of only a one-step extraction procedure with hexane-isoamyl alcohol at pH 9.25 and reversed-phase chromatography on a muPorasil column. The recoveries of buprenorphine and nalbuphine (internal standard) were greater than 90%. Calibration graphs were linear over the concentration range 3-300 ng/ml with a coefficient of variation, both within-day and between-day, of less than 9% at any level. The limit of detection was 1.0 ng/ml of plasma based on a signal-to-noise ratio of 3. Eight other clinically used narcotics were investigated to check for potential interferences and their analytical conditions. The possible decomposed compounds of buprenorphine were also checked for the specificity of this assay. The method has been successfully applied to the stability and pharmacokinetic studies of buprenorphine. Buprenorphine in plasma did not decompose significantly at -20 degrees C for four weeks. Pharmacokinetic application in six rabbits and a surgical patient revealed that buprenorphine followed a linear three-compartment model with two distribution phases. The two distribution and elimination half-lives and the clearance of buprenorphine were 1.32, 24.8 and 230 min and 224 ml/min in human plasma, and 0.94, 12.5 and 232 min and 30 ml/min in rabbit plasma.

Animals

Interactions of adenosine and vecuronium in neuromuscular blockade in cats.

The effect of adenosine on the neuromuscular blockade induced by vecuronium and the capacity of neostigmine to reverse this combined blockade were studied in 30 cats on a standard sciatic nerve--tibialis anterior muscle preparation. Adenosine infused to 6 cats at a constant rate (3.9 +/- 1.1 mg/kg/min) to produce a stable 50% reduction of the mean arterial pressure did not affect neuromuscular transmission. At the same 50% reduction of the mean arterial pressure by adenosine or sodium nitroprusside infusion in another 15 cats, adenosine (n = 9) significantly potentiated vecuronium-induced neuromuscular blockade, but sodium nitroprusside (n = 6) did not. Neostigmine antagonized the neuromuscular blockade of similar degrees produced either by the combination of adenosine with vecuronium in the above 9 cats or by vecuronium alone in the remaining 9 cats. There was no significant difference in the doses of neostigmine given. Because no potentiation was found at the same level of hypotension induced by sodium nitroprusside, the potentiation effect of adenosine on neuromuscular blockade is not likely to be due to the hypotensive effect of adenosine, but may be due to impairment, by adenosine, of acetylcholine release from motor nerve endings. We conclude that adenosine potentiates neuromuscular blockade by vecuronium and that neostigmine can be expected to reverse this combined blockade.

Adenosine

Determination of vecuronium in blood by HPLC with UV and electrochemical detection: a pilot study in man.

Vecuronium bromide is a non-depolarizing neuromuscular blocking agent with a rather low therapeutic level. Rapid, sensitive, and selective determination of vecuronium bromide in human blood or plasma was essential for pharmacokinetic study. We developed such a method using HPLC with electrochemical detection. Samples were first acidified, followed by a one-step liquid-liquid extraction. Tubocurarine, which has a structure similar to that of vecuronium, was used as the internal standard. The electrochemical detector, Ag/AgCl electrodes, was operated by setting the working electrodes, W1 and W2, at +0.65 V and +1.05 V, respectively. When vecuronium blood concentration was plotted versus peak area ratios (PAR) of vecuronium over tubocurarine, a linear relationship was observed over the range of 25 ng/mL to 500 ng/mL with a correlation coefficient greater than 0.997. Clinically possible sources of interference, such as atropine, apresoline, droperidol, fentanyl, labetalol, thiopentone, atracurium, and valium, were examined and none showed interference in the assay of vecuronium and tubocurarine. This method has been successfully applied in a preliminary study of the pharmacokinetics of vecuronium in a patient undergoing surgery. The low detection limit of this method in the patient was 3 ng/mL.

Chromatography, High Pressure Liquid

Effect of physostigmine on the loss of consciousness induced by midazolam, etomidate and althesin.

The effect of physostigmine, a cholinesterase inhibitor, on the loss of consciousness induced by three different intravenous induction anesthetics, namely midazolam, etomidate and althesin at ED50, was studied in three comparable groups of patients. Ten min before induction, the first and second groups received physostigmine 8 micrograms/kg and 16 micrograms/kg, respectively, and the third group received 2 ml of saline solution. Physostigmine 16 micrograms/kg resulted in a significant decrease in the percentage of unconscious patients with midazolam (from 50% to 10%), but it did not modify the incidence with etomidate or althesin. Physostigmine at doses of 8 micrograms/kg and 16 micrograms/kg could cause 6.7% and 10% nausea, respectively. Although the mechanism of the drug interaction of physostigmine and midazolam is unclear, physostigmine could be used clinically to reverse post-anesthetic somnolence induced by midazolam.

Adult

Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.

Adolescent

Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment.

Results of postremission chemotherapy for adults with acute myelogenous leukemia (AML) were assessed in two sequential prospective studies involving similar induction therapy and two courses of intensive consolidation treatment. Fifty-six patients achieving remission on the acute leukemia protocol (ALP3) study received high-dose cytarabine and daunorubicin as course one and standard-dose cytarabine and daunorubicin as course two. Results are compared with forty-six patients achieving remission on the ALP2 study who received azacitidine and doxorubicin as consolidation course one and standard-dose cytarabine, daunorubicin, and thioguanine as course two. The ALP3 regimen resulted in a significantly improved 5-year disease-free survival of 32% +/- 19% versus 20% +/- 11% for the ALP2 study (P = .03). Survival from remission was also improved, 40% +/- 14% versus 24% +/- 12% (P less than .01). Favorable prognostic factors for disease-free survival included receiving the ALP3 treatment regimen, absence of a prior preleukemic syndrome, and female sex. These factors and younger patient age were significant for survival following first chemotherapy and survival after achieving remission. Six of 34 patients who relapsed after receiving the ALP3 regimen successfully achieved prolonged second remissions with high-dose cytarabine-based chemotherapy and/or allogeneic bone marrow transplantation (BMT). Overall survival for adults less than or equal to 45 years of age was 58% +/- 19% with the ALP3 postremission chemotherapy regimen, comparable to most studies of BMT for AML in first remission. Actuarial 5-year survival for ALP3 patients greater than 60 years of age was 18% +/- 20% with no improvement compared with ALP2.

Adult

[Dose-response relationships of propofol in Chinese].

Propofol is a new intravenous anesthetic which possesses the rapid induction and recovery of anesthesia. It has been approved to be used in clinical anesthesia and critical care medicine since 1989. From the dose-response study of propofol, we can get the ED50 and induction dose of propofol and compare those with other anesthetics. Sixty young patients, ASA I-II, both sexes, were allocated into six groups of ten patients. All of patients did not receive premedicants. Groups I-VI were given intravenously over 25 sec 1.0 mg/kg, 1.2 mg/kg, 1.4 mg/kg, 1.6 mg/kg, 1.8 mg/kg and 2.0 mg/kg, respectively. Blood pressure and heart rate were monitored and recorded before and 1 min, 3 min, 5 min after the injection of propofol. Induction of anesthesia by propofol is considered to be successful as a patient closes his eyes and does not response to simple command. As a patient obeys the order to open his eyes, he is judged to emerge from anesthesia. Induction and recovery times were recorded in each successfully-induced patient. Data were analyzed using Litchfield and Wilcoxon, and Student's t tests. The ED50 of propofol was found to be 1.46 mg/kg (95% confidence interval: 1.35 mg/kg to 1.58 mg/kg). Induction and recovery times at 1.0 mg/kg, 1.2 mg/kg, 1.4 mg/kg, 1.6 mg/kg, 1.8 mg/kg and 2.0 mg/kg were 40 sec and 5.6 min, 38 sec and 6.0 min, 38 sec and 6.2 min, 36.8 sec and 6.7 min, 36.3 sec and 7.2 min, 35.5 sec and 7.2 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Humoral immune response to cytomegalovirus Towne vaccine strain and to Toledo low-passage strain.

Neutralization and immunoblot or immunoprecipitation assays of serum samples from seronegative or seropositive volunteers immunized with the attenuated Towne and challenged with the virulent Toledo cytomegalovirus strains were carried out. Titers of neutralizing antibodies differed as a function of the strain used for immunization. All serum samples with neutralizing activity detected a 58-kDa protein that is the abundant component of the major glycoprotein complex of the envelope, suggesting that this protein complex is involved in the induction of neutralizing antibodies. Complement-independent neutralizing activity was found to develop later than complement-dependent activity, and no correlation was observed between complement-independent titers of neutralizing antibodies and antibody to the 86-kDa protein, which bears a complement-independent neutralizing epitope. Antibodies to the 66-kDa major tegument protein were present early after infection but were not correlated with serum neutralizing activity.

Antibodies, Viral