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Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 91 records · Page 5Linked to original sources

Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric oncology ward: clinical features and identification of different plasmids carrying both SHV-5 and TEM-1 genes.

Thirteen patients who had 16 episodes of bacteremia were observed between 1993 and 1997 in a pediatric oncology ward with a high background isolation rate of cefotaxime- or aztreonam-resistant gram-negative bacteria. Four blood isolates were Escherichia coli and 12 were Klebsiella pneumoniae, and these isolates harbored extended-spectrum beta-lactamases (ESBLs). All episodes of bacteremia were nosocomial, all except one of the episodes occurred in neutropenic patients, and all patients were treated with piperacillin or ceftazidime with amikacin and cefazolin prior to the onset of bacteremia. Nine of 13 patients were receiving extended-spectrum beta-lactam treatment when the bacteremias caused by ESBL producers occurred. Molecular studies revealed that four K. pneumoniae SHV-2-producing isolates from 1994 were of the same clone. Other ESBL producers, including six that carried both TEM-1 and SHV-5, five that carried SHV-5, and one that carried SHV-2 alone, were unrelated. In conclusion, SHV-5 was present in 11 of the 16 isolates and coexisted with TEM-1 in 6 isolates. Acquisition of resistance genes probably occurred under antibiotic selection pressure. This study highlights the importance of routine checks for and detection of ESBL producers. Effective therapy against ESBL producers should be considered early for children who have malignancies and neutropenia and who are septic, despite treatment with a regimen that includes an extended-spectrum beta-lactam, in a clinical setting of an increased incidence of ESBL-producing bacteria.

Adolescent↗

Molecular mechanisms of cytoadherence in malaria.

Microbial pathogens subvert host adhesion molecules to disseminate or to enter host cells to promote their own survival. One such subversion is the cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBC) to vascular endothelium, which protects the parasite from being removed by the spleen. The process results in microcirculatory obstruction and subsequent hypoxia, metabolic disturbances, and multiorgan failure, which are detrimental to the host. Understanding the molecular events involved in these adhesive interactions is therefore critical both in terms of pathogenesis and implications for therapeutic intervention. Under physiological flow conditions, cytoadherence occurs in a stepwise fashion through parasite ligands expressed on the surface of IRBC and the endothelial receptors CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular adhesion molecule-1. Moreover, rolling on ICAM-1 and P-selectin increases subsequent adhesion to CD36, indicating that receptors can act synergistically. Cytoadherence may activate intracellular signaling pathways in both endothelial cells and IRBC, leading to gene expression of mediators such as cytokines, which could modify the outcome of the infection.

Animals↗

Effects of calcium supplementation on calcium homeostasis and bone turnover in lactating women.

Lactation is a time of calcium flux, because women secrete approximately 210 mg calcium/day in breast milk, and they experience a transient bone loss. The objectives of this study were to determine the effect of calcium supplementation on adaptive responses in calcium homeostasis during lactation and after weaning. Two cohorts of women participated in a 6-month randomized calcium supplementation trial. Lactation cohort women (97 lactating, 99 nonlactating) were studied during the first 6 months post partum, and weaning cohort women (95 lactating, 92 nonlactating) were studied during the second 6 months post partum. Lactating women in the weaning cohort weaned approximately 1.5 months after enrollment. PTH was 18-30% lower in lactating than in nonlactating women (P < 0.01). Serum 1,25-dihydroxyvitamin D was 11-16% higher in lactating than in nonlactating women and remained elevated for approximately 1.5 months after weaning (P = 0.06). Calcium supplementation decreased serum PTH and 1,25-dihydroxyvitamin D in lactating and nonlactating women similarly. At 6 months, the calciuric response to calcium supplementation was less in lactating (compared with nonlactating) women (P = 0.06). Biomarkers of bone turnover were higher in lactating than in nonlactating women during lactation and after weaning but were not effected by calcium supplementation. Calcium supplementation has little effect on lactation-induced changes in the calcium economy.

Adult↗

Longitudinal study of calcium intake, physical activity, and bone mineral content in infants 6-18 months of age.

Although increased physical activity early in life is recommended for optimizing bone health, no controlled trials on the effect of activity on bone mass accretion during periods of rapid growth have been reported. The purpose of this study was to determine whether infants randomized to a 1 year gross motor activity program had a greater bone mass accretion than infants randomized to a fine motor activity program. The gross motor program included activities that focused on loading the skeleton and were performed for 15-20 minutes/day, 5 days/week by study personnel. Infants (n = 72) were enrolled at 6 months of age, and total body bone mineral content (BMC), 3-day diet records, and activity levels were obtained at 6, 9, 12, 15, and 18 months. BMC was associated with weight, length, and bone area at all ages and correlated with earlier calcium intakes. Calcium intake appeared to modify the effect of gross motor activity on bone mass accretion; infants in both groups had similar bone accretion at moderately high calcium intakes, but at low calcium intakes infants in the gross motor program had less bone accretion than infants in the fine motor program. Compliant infants in the gross motor group had lower BMC at 18 months compared with noncompliant infants. These results indicate that BMC in infants is related to calcium intake, and we speculate that participation in a gross motor program during rapid bone growth may lead to reduced bone accretion in the presence of a moderate to moderately low calcium intake.

Bone Density↗

Surveillance of antibiotic resistance in Taiwan, 1998.

For the first national surveillance of antibiotic resistance in Taiwan, we collected in 1998 from 22 hospitals (6 medical centers, 15 regional hospitals, and 1 local hospital) 3,211 isolates in all parts of the country. Besides 50 random successive isolates from inpatients, each hospital was requested to collect 25 isolates each from positive blood cultures, hospital-acquired infections, outpatients and the pediatric department. We re-speciated all the submitted specimens and determined their antibiotic susceptibility patterns. The most common isolates were Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae), Staphylococcus aureus, and Pseudomonas aeruginosa. Among hospital-acquired infections, Acinetobacter spp. were among those which accounted for over 10% of the isolates. The oxacillin resistance of S. aureus was 82% in isolates from hospital-acquired infections, and 40% from outpatients. Among Enterococcus spp., 85% were either E. faecalis or E. faecium. They were 14% resistant to vancomycin. Among gram-negative bacteria, K. pneumoniae and Acinetobacter baumanii were hospital-acquired isolates that were most clearly more resistant than community acquired isolates. This difference was less apparent in the case of Enterobacter cloacae, Serratia marcescens, and P. aeruginosa. These bacteria were generally more resistant from all sources. Fifty-one percent of Salmonella were resistant to ampicillin; however, these were all sensitive to ciprofloxacin. Isolates from the East were least resistant. Plotting the disc zone diameters of antibiotics within the susceptible range, we identified subpopulations with smaller diameters in the case of vancomycin against S. aureus, ciprofloxacin against E. coli, and ciprofloxacin against Salmonella spp. These findings represent one of the purposes of this surveillance as they may portend developing resistances which bear careful watching in the future.

Ciprofloxacin↗

Efficacy of cutting balloon angioplasty for lesions at the ostium of the coronary arteries.

We evaluated 37 patients (39 lesions, 11 women/26 men, median age of 66 years old) with coronary ostial lesions who underwent cutting balloon angioplasty (CB). Seventy-four patients (78 lesions, 18 women/56 men, median age of 65 years old) who had undergone plain old balloon angioplasty (POBA) for coronary ostial lesions were also enrolled as the control group. At clinical diagnosis, unstable angina was seen in 8.1% of the CB group and in 9.5% of the POBA group. Post myocardial infarction silent ischemia was seen in 28.3% of the POBA group and 32.4% of the CB group. The success rate was 94.8% in the CB group and 84.6% in the POBA group. The frequency of intimal dissection was not significantly different between the two groups. However, all cases of intimal dissection in the CB group were mild (either type A or B), whereas the POBA group included many cases of severe intimal dissection (types B through F). No cardiac event was observed in the CB group. However, in the POBA group, cardiac death occurred in 1.4% and emergency bypass surgery occurred in 0.7% of the patients. Calculating the restenosis rate based on the cumulative percent diameter stenosis curve resulted in 43% for the CB group and 53% of the POBA group. We concluded that the cutting balloon was useful for ostial lesions as compared to plain old balloon angioplasty.

Aged↗

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Adenocarcinoma, Follicular↗

Prospective multicenter study of thyroiscarcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group.

BACKGROUND: A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with other available staging classifications. METHODS: Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation. RESULTS: Between 1987 and 1995, 1607 patients were registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were more likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. Five-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage IV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1%for Stage II, 77.8% for Stage III, and 24.6% for Stage IV). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type. CONCLUSIONS: The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma.

Adenocarcinoma, Follicular↗

Characterization of Plasmodium falciparum-infected erythrocyte and P-selectin interaction under flow conditions.

Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule P-selectin in vitro under flow conditions that approximate the shear stress in capillary and postcapillary venules in which cytoadherence occurs in vivo. The pathological significance of this adhesive interaction is currently unknown. In this study, we further investigated the molecular interactions between IRBC and P-selectin by using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results showed that the IRBC-P-selectin interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a trypsin-resistant IRBC ligand that adheres selectively to chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated platelets that express both CD36 and P-selectin showed that inhibition of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact directly with CD36. Thus, cytoadherence under physiological flow conditions may be mediated by multiple IRBC ligands that interact with different adhesion molecules in a cooperative fashion. These findings underscore the complexity of the interactions betweeen IRBC and vascular endothelium.

Animals↗

Axonal injury and the neuropathology of shaken baby syndrome.

We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who lacked skull fracture. Evidence of axonal injury was sought using immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta-amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the cerebral white matter of all cases of SBS but were also present in 6 of 7 children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP-positive axons were present in both groups in the midbrain and medulla. The cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5 of 7 contained swollen axons within the white matter tracts; in 2 immunoreactivity was localized to spinal nerve roots; in all 7 there was a predilection for staining at the glial head of the nerve root. Among cases of HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical cord white matter. We conclude that cerebral axonal injury is common in SBS, and may be due in part to hypoxic/ischemic injury. Cervical cord injury is also common, and cannot be attributed to HIE. These findings corroborate suggestions that flexion-extension injury about the cervical spinal column may be important in the pathogenesis of SBS.

Amyloid beta-Protein Precursor↗

Confirmation of the beneficial effects of brief coincubation of gametes in human in vitro fertilization.

OBJECTIVE: To confirm whether brief exposure of human oocytes to spermatozoa in vitro results in equivalent fertilization rates and possibly better quality embryos than overnight coincubation and to determine if there was a difference in outcome with regard to the type of culture medium used. DESIGN: Prospective distribution of gametes between treatments in sequential patients. SETTING: Assisted reproductive technology program in private hospital. PATIENT(S): Consecutively treated subfertile couples entering an infertility program. INTERVENTION(S): Assisted reproductive technology treatment for infertility involving oocyte retrieval and in vitro fertilization. MAIN OUTCOME MEASURE(S): When possible, the outcome of fertilization and embryo quality were compared when gametes were coincubated for 1 hour or overnight. Two different formulations of human tubal fluid were compared in some cases. RESULT(S): There was no statistically significant difference in fertilization rates between a brief or overnight coincubation of gametes or between the two treatment groups with regard to the type of culture medium used. The quality of the embryos was significantly better in the 1-hour exposure group. The embryos in Basal XI human tubal fluid medium were of significantly better morphological quality than their siblings in D3+ human tubal fluid medium. CONCLUSION(S): Coincubation of oocytes and spermatozoa for a shorter period produced embryos of superior morphological quality than the generally accepted overnight protocol. A simple glucose and phosphate-free human tubal fluid medium resulted in early cleavage embryos of better morphological quality than a medium supplemented with glucose, taurine, and glutathione.

Embryo Transfer↗

Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases.

STUDY OBJECTIVE: To determine the safety of intramuscular ketamine when administered by emergency physicians for pediatric procedures in accordance with a defined protocol. METHODS: We assembled a consecutive case series of children aged 15 years or younger who were given ketamine in the emergency departments of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine use (4 mg/kg, intramuscularly) was followed. Treating physicians were instructed to complete data forms recording complications and adequacy of sedation concurrent with patient care. Subsequent chart review was used to determine indications, adjunctive drugs, time to discharge, and adverse reactions for all patients. RESULTS: Intramuscular ketamine was administered 1,022 times, mainly for laceration repair and fracture reduction. Physicians completed data forms for 431 of treated children (42%). Transient airway complications occurred in 1.4%: airway malalignment (n = 7), laryngospasm (n = 4), apnea (n = 2), and respiratory depression (n = 1). All were quickly identified and treated without intubation or sequelae. Emesis occurred in 6.7%, without evidence of aspiration. Mild recovery agitation occurred in 17.6%, moderate to severe agitation in 1.6%. No child required hospitalization for complications caused by ketamine. Ketamine produced acceptable sedation in 98% of patients. The median time from injection to emergency department discharge was 110 minutes for children given a single dose of ketamine. CONCLUSION: Intramuscular ketamine may be administered safely by emergency physicians to facilitate pediatric procedures in accordance with a defined protocol and with appropriate monitoring. Ketamine is highly effective, has a wide margin of safety, does not require intravenous access, and uniquely preserves protective airway reflexes.

Adolescent↗

Dietary supplementation with omega 3 and omega 6 fatty acids reduces induced white blood cell aggregation in healthy volunteers.

Twenty healthy, non-smoking subjects were enrolled into a study to look at the effects of 3 months' dietary supplementation with long chain polyunsaturated essential fatty acids (EFAs) on white blood cell (WBC) aggregation. Ten subjects received 3 months' supplementation with long chain polyunsaturated omega 3 and omega 6 fatty acids, 10 received 3 months of placebo (sunflower oil). Venous blood was sampled at 0 and 12 weeks; whole blood WBC aggregation in response to formyl-methionyl-leucyl-phenylalanine (FMLP) was measured. The results showed that the 3 months' dietary supplementation with a combination of omega 3 and omega 6 fatty acids significantly reduced WBC aggregation to FMLP in healthy volunteers when compared to placebo. Since WBC aggregation to FMLP is dependent on the activity of WBC surface receptors and independent of eicosanoid production, we suggest EFAs may have other anti-inflammatory actions in addition to their role as modulators of mediator production.

Adult↗

SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity.

1. Human 5-HT1B (h5-HT1B) and human 5-HT1D (h5-HT1D) receptors show remarkably similar pharmacology with few compounds discriminating the receptors. We report here on a novel compound, SB-224289 (1'-Methyl-5-[[2'-methyl-4'-(5-methyl- 1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro spiro [furo [2,3-f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT1B receptors (pK1=8.16+/-0.06) and displays over 75 fold selectivity for the h5-HT1B receptor over all other 5-HT receptors including the h5-HT1D receptor and all other receptors tested thus far. 2. Functional activity of SB-224289 was measured in a [15S]GTPgammaS binding assay on recombinant h5-HT1B and h5-HT1D receptors expressed in Chinese Hamster Ovary (CHO) cells. SB-224289 displayed negative intrinsic activity at both receptors with higher potency at h5-HT1B receptors. SB-224289 caused a rightward shift of agonist concentration response curves consistent with competitive antagonism and generated affinities comparable with those obtained from competition radioligand receptor binding studies. 3. SB-224289 potentiated [3H]5-HT release from electrically stimulated guinea-pig cerebral cortical slices to the same extent as as the non-selective 5-HT1 antagonist methiothepin. SB-224289 also fully reversed the inhibitory effect of exogenously superfused 5-HT on electrically stimulated release. 4. Using SB-224289 as a tool compound, we confirm that in guinea-pig cerebral cortex the terminal 5-HT autoreceptor is of the 5-HT1B subtype.

Animals↗

Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors.

Xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-me thylpyridine] has been reported to act as a functionally selective muscarinic partial agonist with potential use in the treatment of Alzheimer's disease. This study examined the functional activity of xanomeline at 5-HT1 and 5-HT2 receptors in native tissue and/or human cloned receptors. Xanomeline had affinity for muscarinic receptors in rat cortical membranes where the ratio of the displacement affinity of [3H]-Quinuclidinyl benzilate vs that of [3H]-Oxotremorine-M was 16, indicative of partial agonist activity. Radioligand binding studies on human cloned receptors confirmed that xanomeline had substantial affinity for M1, M2, M3, M4, M5 receptors and also for 5-HT1 and 5-HT2 receptor subtypes. Carbachol and xanomeline stimulated basal [35S]-GTPgammaS binding in rat cortical membranes with micromolar affinity. The response to carbachol was attenuated by himbacine and pirenzepine with pA2 of 8.2, 6.9 respectively consistent with the response being mediated, predominantly, via M2 and M4 receptors. Xanomeline-induced stimulation of [35S]-GTPgammaS binding was inhibited by himbacine with an apparent pKb of 6.3, was not attenuated by pirenzepine up to 3 microM and was inhibited by the selective 5-HT1A antagonist WAY100635 with an apparent pKb of 9.4. These data suggest the agonist effect of xanomeline in this tissue is, in part, via 5-HT1A receptors. Similar studies on human cloned receptors confirmed that xanomeline is an agonist at human cloned 5-HT1A and 5-HT1B receptors. In studies using the fluorescent cytoplasmic Ca2+ indicator FLUO-3AM, xanomeline induced an increase in cytoplasmic Ca2+ concentration in SH-SY5Y cells expressing recombinant human 5-HT2C receptors. Atropine antagonized this response, consistent with mediation via endogenously-expressed muscarinic receptors. In the presence of atropine, xanomeline antagonized 5-HT-induced cytoplasmic changes in Ca2+ concentration in cells expressing h5-HT2A, h5-HT2B and h5-HT2c receptors with potencies similar to its affinity at these receptors. These studies indicate that xanomeline is a potent agonist at 5-HT1A and 5-HT1B receptors and an antagonist at 5-HT2 receptor subtypes.

Animals↗