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Biomedical subjects

H Ho

Publications and source records attributed to H Ho.

At least 19 recordsLinked to original sources

Esophageal cancer after distal gastrectomy.

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated. Duodenogastroesophageal reflux is thought to be common in patients after distal gastrectomy, but whether this contributes to the development of esophageal cancer in such patients is controversial. We retrospectively evaluated 153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer between January 2002 and July 2005. They were divided into two groups, according to whether or not they had previously undergone a gastrectomy: group 1, comprising 14 patients who had undergone gastrectomy and group 2, comprising 139 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6 years) compared with Billroth II (29.7 +/- 3.2 years), although the difference did not reach its statistical significance (P = 0.11). Moreover, the proportion of lower third tumors in patients after gastrectomy was significantly higher compared with that of the patients with intact stomach. These findings suggest that a history of gastrectomy is associated with more lower-third squamous cell esophageal carcinoma.

Adenocarcinoma↗

Palmar plate fixation of AO type C2 fracture of distal radius using a locking compression plate--a biomechanical study in a cadaveric model.

The stability of palmar plate fixation using a locking compression T-plate was compared with that of a conventional palmar T-plate and a dorsal T-plate in a cadaveric model of an AO type C2 fracture of distal radius. The wrist axial load transmission through the radius was tested for each fixation. The results show that, under 100N axial load, the palmar locking compression T-plate restores stability comparable to that of the intact radius, and is superior to conventional palmar or dorsal T-plates.

Biomechanical Phenomena↗

Comparison of the bactericidal activities and post-antibiotic effects of the Des-F(6)-quinolone BMS-284756, levofloxacin, and ciprofloxacin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

The bactericidal activities and post-antibiotic effects of BMS-284756 (T-3811ME), levofloxacin, and ciprofloxacin were evaluated against a methicillin-susceptible and a methicillin-resistant Staphylococcus aureus strain. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations, post-antibiotic effects, and post-antibiotic sub-MIC effects were determined and time-kill studies were performed for BMS-284756, levofloxacin, and ciprofloxacin. At 4-times and 10-times the MIC, time-kill kinetics over 3 h and over 24 h were similar for all three quinolones when effects were considered as multiples of the MIC. All three quinolones achieved a 3 log10 reduction in cfu/ml within 2 h. At 10-times the MIC, the post-antibiotic effects of BMS-284756, levofloxacin, and ciprofloxacin were 1.6-2.6 h for the methicillin-susceptible Staphylococcus aureus strain and 1.5-1.9 h for the methicillin-resistant Staphylococcus aureus strain. When actual concentrations were considered, BMS-284756 achieved results comparable to levofloxacin and ciprofloxacin at concentrations nearly 10-fold less. When relating the pharmacokinetic properties of the three quinolones to their in vitro activities, the resulting Cmax/MIC and AUC/MIC ratios were. respectively, 120-240.7 and 1,321.7-2,643 for BMS-284756, 22.8 and 190 for levofloxacin, and 5.9-11.9 and 54.8-109.6 for ciprofloxacin. The greater in vitro activity and favorable human pharmacokinetics of BMS-284756 may translate to improved clinical effectiveness of this agent compared to currently marketed quinolones.

Anti-Infective Agents↗

Influence of wet granulation and lubrication on the powder and tableting properties of codried product of microcrystalline cellulose with beta-cyclodextrin.

The individual influence of wet granulation and lubrication on the powder and tableting properties of codried product of microcrystalline cellulose (MCC) with beta-cyclodextrin (beta-CD) was examined in this study. Avicel PH 101 and 301 were included for comparison. The codried product, Avicel PH 101 and 301 were granulated with water, and the granules were milled to retain three different size fractions: 37-60 microm, 60-150 microm, and 150-420 microm. The original Avicels and codried product were lubricated with magnesium stearate in three different percentages (0.2, 0.5, and 1.0%). The results showed that the powder flowability and disintegration of codried product and Avicels were significantly improved after wet granulation. However, the compactibility of codried product and Avicels decreased with increasing particle size. Nevertheless, the compactibility of the codried excipient after granulation was still better than the non-granulated Avicel PH 101 and 301. On the other hand, codried product and Avicels were sensitive to lubrication and resulted in decreasing compactibility and increasing disintegration. Because of the rounder shape of particles, the codried excipient was more sensitive to magnesium stearate and produced weaker tablets than did Avicels.

Analysis of Variance↗

Sustained-release effect of codried excipients of microcrystalline cellulose and Ganoderma fiber.

The sustained-release effects of codried excipient of modified Ganoderma (treated with alkaline solution) and microcrystalline cellulose at different ratios were examined using acetaminophen (ACT) as a model drug. Results demonstrate that the crushing strength of most ACT tablets made with codried powder at all ratios increased as compaction force increased; but a rapid decline was observed when compression force exceeded 2 tons. Drug release from tablets compressed at 0.5 ton increased as modified Ganoderma fiber content increased. But when the compression force exceeded 1 ton, the release rate was not influenced by the compaction force or the increasing content of Ganoderma fiber. However, the dissolution of ACT from these tablets could be sustained for longer than 24 h. The extent of drug release was shown to increase with increasing amounts of modified Ganoderma in the codried excipient. The addition of disintegrants could further accelerate the drug release from the tablet. Drug release was also dependent upon the amount and kind of disintegrant used. The influence was in the following order: primojel>crospovidone>starch 1500.

Acetaminophen↗

Myocardial protection during ventricular fibrillation by reduction of proton-driven sarcolemmal sodium influx.

Although the inhibition of proton-driven sarcolemmal sodium influx ameliorates ischemic injury in the quiescent myocardium, the effects when ventricular fibrillation is present are largely unknown. We used an isolated rat heart model to investigate whether inhibition of the sodium-hydrogen exchanger isoform-1 (with the benzoylguanidine derivatives HOE-694 and cariporide) with or without concomitant inhibition of the sodium-bicarbonate co-transporter (with perfusate buffered with N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid [HEPES]) during ischemia and ventricular fibrillation could ameliorate functional myocardial abnormalities presumed to limit cardiac resuscitability. Ischemic contracture, which typically develops during ventricular fibrillation, was ameliorated by HOE-694 when either a bicarbonate-buffered (20 +/- 7 mm Hg vs 15 +/- 5 mm Hg, P <.05) or a HEPES-buffered (14 +/- 5 mm Hg vs 10 +/- 3 mm Hg, P <.04) perfusate was used. Maximal amelioration occurred when cariporide and HEPES-buffered perfusate were used simultaneously (25 +/- 14 mm Hg vs 11 +/- 3 mm Hg, P <.01), and this was accompanied by lesser leftward shifts of the end-diastolic pressure-volume curves after defibrillation. Intramyocardial sodium increases of 76% during ischemia and ventricular fibrillation (P <.05) were ameliorated by the sodium-influx-limiting interventions. Thus interventions limiting sarcolemmal sodium influx during ischemia and ventricular fibrillation may facilitate successful resuscitation from ventricular fibrillation.

Animals↗

Postoperative staphylococcal toxic shock syndrome due to pre-existing staphylococcal infection: case report and review of the literature.

Staphylococcal postoperative toxic shock syndrome (PTSS) has been associated with a variety of surgical procedures. It is generally believed that the source of infection is acquired at or near the time of surgery. PTSS has been specifically associated with nasal packing, insertion of hardware, surgical drains, retained foreign materials, and breaks in sterile technique. Although PTSS has been associated with postoperative abscesses, development of PTSS after surgery of a pre-existing source of infection has not been described. We report a case of PTSS that developed after vertebral abscess drainage, and we review the literature to determine the incidence of PTSS due to preexisting staphylococcal infection.

Abscess↗

Perinatal ontogeny of brain growth in the domestic pig.

The perinatal development of the brain is highlighted by a growth spurt whose timing varies among species. The growth of the porcine cerebrum was investigated from the third trimester of gestation (70 days postconception) through the first 3.5 weeks of postnatal life (140 days postconception). The shape of the growth curves for cerebrum weight, total protein mass, total cell number (estimated by DNA content), and myelination (estimated by cholesterol accretion) were described. The growth velocity of cerebrum weight had two peaks, one at 90 days and the other at 130 days postconception, whereas that of total protein was greatest from 90 to 130 days postconception, and that of total DNA was greatest between 90 and 110 days and again at 130 days postconception. The growth velocity for total cholesterol continued to increase during the entire period, suggesting that myelination continued after the growth spurts for cells (protein and DNA). The growth velocity patterns observed in these contemporary pigs suggest that this species may be an appropriate model for human brain development, not only in the perinatal pattern of increase in mass of the cerebrum, as established previously, but also with regard to the patterns of cellular development and myelination.

Aging↗

Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene.

Resistance to thyroid hormone (RTH) is a syndrome of variable tissue hyposensitivity to TH. In 191 families, the RTH phenotype has been linked to mutations located in the ligand-binding or hinge domains of the TH receptor (TR) beta gene. The defective TRbeta molecules interfere with the function of the normal TRs to produce dominantly inherited RTH. Of the 65 families with RTH studied in our laboratory, 59 had mutations in the mutagenic region of the TRbeta gene that encompasses exons 7-10. Isolation of a TRbeta PAC (P1 derived artificial chromosome) clone provided the intronic sequences necessary to amplify and sequence the entire TRbeta gene from genomic DNA. Not a single nucleotide substitution, deletion, or insertion was found in all coding and noncoding TRbeta1- and TRbeta2-specific and common exons of the five families with RTH reported herein. Furthermore, linkage analysis using polymorphic markers excluded involvement of the TRbeta and TRalpha genes in two and three of the five families, respectively. The phenotype of RTH in patients without TRbeta gene defects was not different from that in patients with RTH due to TRbeta gene mutations in terms of clinical presentation and reduced responsiveness of the pituitary and peripheral tissues to TH. However, the degree of thyrotroph hyposensitivity to TH appeared to be among the more severe, similar to that of patients with mutant TRbetas that have more than 50-fold reduction of T3 binding affinity and strong dominant negative effect. In these five families and another with non-TRalpha/non-TRbeta RTH, previously identified in our laboratory, evidence for dominant inheritance was secured in two families, and the appearance of a new defect or recessive inheritance was found in the remaining four families. RTH without a structural TRbeta defect occurs in about 10% of families expressing the classic phenotype of TH hyposensitivity, and TRbeta and TRalpha gene involvement has been excluded in 5%. We postulate that a cofactor that interacts with TR is potentially responsible for the manifestation of RTH in these families. As affected subjects are not infertile, the high prevalence of putative neomutations and the low rate of transmission in this non-TR form of RTH may be due to reduced survival of embryos harboring the defect.

Adult↗

Human interferon-gamma-inducible protein 10 (IP-10) inhibits constitutive signaling of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.

A G protein-coupled receptor (GPCR) is encoded within the genome of Kaposi's sarcoma- associated herpesvirus (KSHV)/human herpesvirus 8, a virus that may be involved in the pathogenesis of Kaposi's sarcoma and primary effusion lymphomas. KSHV-GPCR exhibits constitutive signaling activity that causes oncogenic transformation. We report that human interferon (IFN)-gamma-inducible protein 10 (HuIP-10), a C-X-C chemokine, specifically inhibits signaling of KSHV-GPCR. In contrast, monokine induced by IFN-gamma (HuMig), which like HuIP-10 is an agonist of C-X-C chemokine receptor 3, does not inhibit KSHV-GPCR signaling. Moreover, HuIP-10, but not HuMig, inhibits KSHV-GPCR-induced proliferation of NIH 3T3 cells. These results show that HuIP-10 is an inverse agonist that converts KSHV-GPCR from an active to an inactive state. Thus, a human chemokine inhibits constitutive signaling and cellular proliferation that is mediated by a receptor encoded by a human disease-associated herpesvirus.

3T3 Cells↗

Use of the International Knee Documentation Committee guidelines to assess outcome following anterior cruciate ligament reconstruction.

The purpose of this project was to determine if guidelines established by the International Knee Documentation Committee (IKDC) could distinguish differences in outcome, as indicated by the patients' subjective rating of knee function following ACL reconstruction, and to determine if all subgroups included in the IKDC rating system contribute to the prediction of the overall final IKDC rating. A total of 133 patients undergoing ACL reconstruction were evaluated according to IKDC guidelines 1-5 years postoperatively. Each subject was rated in each of four subgroups on the IKDC scale: patient subjective assessment, symptoms, range of motion (ROM), and laxity. The worst rating for the subgroups defined the overall final rating. The outcome from the patient's perspective was determined by asking them to rate the function of their knee on a scale from 0 to 100 with 100 being the level of function before injury. Average length of follow-up was 3.2 years (range 1.1-6.3 years). ANOVA indicated that the patients' subjective rating of knee function on a scale from 0 to 100 differed according to the overall final IKDC rating (F = 16.1, P < 0.001). The average subjective rating of knee function for those with a normal IKDC rating was 95.2, nearly normal was 91.2, abnormal was 84.9, and severely abnormal was 75.4. The average subjective rating of knee function for those who were severely abnormal was significantly different from those rated normal, nearly normal, and abnormal, and the average subjective rating for those who were abnormal was significantly different from those who were normal or nearly normal. There was no significant difference in average subjective rating between those who were rated as normal or nearly normal. Regression analysis indicated that all four subgroups contributed significantly to the prediction of the final IKDC rating (r2 = 0.70), but the majority of the variance (62%) was accounted for by symptoms and laxity. These results appear to indicate that the IKDC guidelines are useful for describing the outcome following ACL reconstruction. Further testing of the IKDC guidelines is necessary to determine if they are capable of detecting a change in the patients over time following treatment and/or surgery of the knee.

Adolescent↗

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.

Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.

APACHE↗

Cloning and characterization of the chicken thyrotropin-releasing hormone receptor.

We report on the cloning of the full-length complementary DNA for the chicken TRH receptor. Although the TRH receptor has been cloned from several mammalian species, this is the first report from another vertebrate class. The ligand binding pocket, which is situated in the transmembrane helices of the mouse and rat TRH receptors, is completely conserved in the chicken receptor. Pharmacological studies (receptor binding and signaling) employing several TRH analogs revealed that there are no significant differences between the chicken and mouse receptors. These findings show that there have been considerable evolutionary constraints on TRH receptor structure and function. Several truncated forms of the chicken TRH receptor that appear to retain a part of an intron and are truncated in the putative third intracellular loop were also cloned, but were nonfunctional. This study provides a useful tool for further studies on the roles of TRH in avian growth and TSH regulation.

Amino Acid Sequence↗

Procedures for reproducible detection of rabies virus antigen mRNA and genome in situ in formalin-fixed tissues.

Procedures allowing the reproducible in situ detection of rabies virus antigen and RNAs (both genome and message) in formalin-fixed tissue are described. These procedures can be used on sequential tissue sections and thereby permit comparison of results from tests detecting both antigen and RNA in the same tissue. This antigen-detecting procedure has also been used to identify both the phylogenetically distant rabies viruses from silver-haired bat and vampire bat and the rabies-related viruses Mokola, Duvenhage, and Lagos bat. One of the critical steps in these procedures is the digestion (and the resulting exposure of the target molecules) with proteinase K. These methods may be useful for the identification of other viruses of public health importance. Because in many situations only formalin-fixed tissue is available for postmortem diagnosis, the technical ability to identify a virus antigen and nucleic acid in such tissues greatly extends potential diagnostic capabilities.

Animals↗

Biomembrane permeation of nicotine: mechanistic studies with porcine mucosae and skin.

In the present study, the permeation and partitioning of nicotine as a function of pH was investigated with various regions of skin and absorptive mucosae that were freshly excised from domestic pigs. As an ionizable compound (pKa values of 3.04 and 7.84), nicotine in solutions of different pH values provides a model for determining the influence of the charge status of a molecule on permeation. The permeation of nicotine across porcine mucosae and skin followed zero-order kinetics. The rate of permeation was dependent on donor solution pH and increased exponentially as the pH increased. With an exception of the nasal mucosa, which showed similar permeabilities for all species of nicotine, the permeability of nicotine across various skin and mucosal specimens was significantly higher (p < 0.001) for the un-ionized species (NN) than for the ionized species (NNH+, NH+NH+). It was also seen that un-ionized nicotine molecules were more permeable through absorptive mucosae (nasal, buccal, sublingual, and gingival) than through skin (abdominal, dorsal, thigh, and ear pinna). Partition studies were performed and the results further confirmed that biomembrane permeation of nicotine follows the pH-partition theory.

Animals↗