Human herpesvirus 8--let the transplantation physician beware.
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Antibodies, Viral↗
Biomedical subjects
M Ho
Publications and source records attributed to M Ho.
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↗
Raynaud's phenomenon: state of the art 1998.
Raynaud's Phenomenon (RP) is a relatively common problem which may be troublesome and difficult to treat in a minority of patients. The state of the art in 1998 focusses on three key areas: the clinical spectrum of RP; its progression and prognosis; and its treatment. RP is a systemic disease, with a multifactorial aetiology and vasospasm affects not just the digits and skin but also major organs including the heart, lungs and kidneys. It is important to distinguish primary from secondary RP. RP may predate an associated connective tissue disease by many years and markers for this include severe RP symptoms with trophic skin changes, serological abnormalities and abnormal nailfold capillaries. Repeated attacks of vasospasm may cause ischaemic reperfusion injury to the endothelium, resulting in a vicious and self propagating cycle of cause and effect. Nifedipine remains the "gold standard" of treatment but a number of new and promising drugs, eg relaxin, are currently under investigation. "Vasodilator-plus" drugs, with the ability to also modulate some of the haemorrheological abnormalities in RP, are the drugs that are going to have a major clinical impact on the disease and hold promise for the future.
Biomarkers↗
Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria.
Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 are implicated in the pathogenesis of severe Plasmodium falciparum malaria. In this study, the effect of IL-10 on their production by peripheral blood mononuclear cells (PBMC) from acutely infected patients was examined. Exogenous IL-10 inhibited malarial antigen-induced cytokine production by reducing mRNA accumulation. Maximal inhibition occurred when IL-10 was added in the first 2 h of stimulation. Conversely, the addition of anti-IL-10 markedly enhanced TNF-alpha, IL-1beta, and IL-6 production. The effect was significantly greater on PBMC from patients with uncomplicated infection than PBMC from patients with severe disease. Kinetics studies showed that TNF-alpha, IL-6, and IL-1beta were produced within 2-4 h of stimulation, while IL-10 was first detectable after 8 h. These findings suggest that IL-10 counter-regulates the proinflammatory response to P. falciparum. Severe falciparum malaria may be associated with an inadequate negative feedback response by IL-10.
Adult↗
Cytomegalovirus infection in patients with bacterial sepsis.
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Cytokines↗
Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.
The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.
Adenocarcinoma, Follicular↗
The risk of treatment. A study of rheumatoid arthritis patients' attitudes.
Despite its importance, there is no well-validated method of measuring patients' concept of 'acceptable' risk of medical treatment. Numerical methods give widely varying results depending on the methodology. We have attempted to assess 'acceptable' risk using relative comparisons. We administered a questionnaire to 67 patients with rheumatoid arthritis (RA). In general, patients' estimate of acceptable risk was less than the actual risk of treatment. Some illogical choices were made, showing poor understanding by patients of the concepts of risk and risk:benefit ratio. Patients appeared willing to accept higher levels of risk from procedures than from drug treatment. Willingness to accept risk in exchange for successful treatment of their RA did not correlate with disease severity, age, willingness to take non-medical risks or family responsibilities.
Adolescent↗
Severe classical congenital muscular dystrophy and merosin expression.
It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6-year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance. In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.
Child↗
Hyaluronic acid-receptor binding demonstrated by synthetic adhesive proteoglycan peptide constructs and by cell receptors on the marine sponge Microciona prolifera.
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Amino Acid Sequence↗
Current outlook of infectious diseases in Taiwan.
The "emerging" infectious diseases have received global attention. Taiwan is a country which is going through the process of becoming "developed" from being "developing". If we compare five leading causes of death in 1952 and in 1993, three were infectious diseases in 1952 and there was none in 1993. And yet today, infectious diseases remain a major problem in this country as well in every country in the world, whether developing or developed. Some of the problems Taiwan faces are old problems with old faces. They have never been adequately solved because the societal and environmental sanitary infrastructure does not ensure proper sewage disposal, safe potable water and freedom from dangerous vectors. Examples are the diarrheal diseases, parasitic diseases, scrub typhus and Japanese encephalitis. Some of the Taiwan's problems are caused by old agents which present a new face. Mortality from tuberculosis took a dramatic and gratifying plunge in the last fifty years. Yet tuberculosis is ever present and a constant public health threat. Dengue has become a problem again because of a world breakdown in the control of the mosquito, Aedes egypti, and it is partly contributed to by increased urbanization and world travel. The problem of antibiotic resistant bacteria causing hospital acquired and community acquired infections is probably the most serious "new" problem. The most important cause is excessive and indiscriminate use of antibiotics in the community and in hospitals. We propose the establishment of "Bacterial Infections Reference Laboratory" at the National Health Research Institutes to be a national facility to study the epidemiology and control of antibiotic resistance. All infectious diseases require a rigorous system of surveillance, and precise etiological diagnosis before they can be treated or prevented. This should be kept clearly in mind when one considers the changing role of the infectious disease physician in Taiwan in the face of unsolved disease problems and a new health care system. There is inadequate attention to precise microbiological definition of most infectious diseases in Taiwan. The community of infectious disease specialists may well redirect its attention to improving the competence and utilization of microbiological laboratory diagnosis.
Clinical Laboratory Techniques↗