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Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 109 records · Page 6Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

The effect of calcium supplementation on bone density during lactation and after weaning.

BACKGROUND: Women may lose bone during lactation because of calcium lost in breast milk. We studied whether calcium supplementation prevents bone loss during lactation or augments bone gain after weaning. METHODS: We conducted two randomized, placebo-controlled trials of calcium supplementation (1 g per day) in postpartum women. In one trial (the study of lactation), 97 lactating and 99 nonlactating women were enrolled a mean (+/-SD) of 16+/-2 days post partum. In the second trial (the study of weaning), 95 lactating women who weaned their infants in the 2 months after enrollment and 92 nonlactating women were enrolled 5.6+/-0.8 months post partum. The bone density of the total body, lumbar spine, and forearm was measured at enrollment and after three and six months. RESULTS: The bone density of the lumbar spine decreased by 4.2 percent in the lactating women receiving calcium and by 4.9 percent in those receiving placebo and increased by 2.2 and 0.4 percent, respectively, in the nonlactating women (P<0.001 for the effect of lactation; P= 0.01 for the effect of calcium). After weaning, the bone density of the lumbar spine increased by 5.9 percent in the lactating women receiving calcium and by 4.4 percent in those receiving placebo; it increased by 2.5 and 1.6 percent, respectively, in the nonlactating women (P<0.001 for the effects of lactation and calcium). There was no effect of either lactation or calcium supplementation on bone density in the forearm, and there was no effect of calcium supplementation on the calcium concentration in breast milk. CONCLUSIONS: Calcium supplementation does not prevent bone loss during lactation and only slightly enhances the gain in bone density after weaning.

Adult↗
PubMed1997

Promiscuity of clinical Plasmodium falciparum isolates for multiple adhesion molecules under flow conditions.

The central pathologic process in severe Plasmodium falciparum malaria is the cytoadherence of parasitized erythrocytes to capillary and postcapillary venular endothelium, with resultant tissue hypoxia, metabolic disturbances, and multiorgan dysfunction. The molecular basis of this process has been studied extensively using static adhesion assays. In the present study, we determined whether infected red blood cells (IRBC) from clinical parasite isolates would roll and adhere on CD36, ICAM-1, E-selectin, P-selectin, and VCAM-1 using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results indicate that IRBC could tether and roll on CD36, ICAM-1, P-selectin, and VCAM-1 in a shear-dependent fashion, but significant adhesion was restricted to CD36. There was no interaction with E-selectin. When both CD36 and ICAM-1 were expressed on the same cellular substratum such as C32 melanoma cells, adhesion was significantly greater than when CD36 was present alone. The adhesive interactions were different from those between leukocytes and the same adhesion molecules. Furthermore, IRBC rolling on P-selectin and VCAM-1 was not inhibitable by Abs that entirely prevented leukocyte-receptor interactions. These findings suggest that cytoadherence under physiologic conditions may be a multistep process similar to that involved in the recruitment of a number of different cell types. Further elucidation of the molecular basis of these novel interactions is crucial for the development of therapeutic interventions aimed at inhibiting or reversing the process.

Animals↗
PubMed1997

Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control.

PURPOSE: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). METHODS AND MATERIALS: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. RESULTS: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). CONCLUSION: A minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Adenocarcinoma↗
PubMed1997

Pasteurella multocida toxin activates the inositol triphosphate signaling pathway in Xenopus oocytes via G(q)alpha-coupled phospholipase C-beta1.

Pasteurella multocida toxin (PMT) has been hypothesized to cause activation of a GTP-binding protein (G-protein)-coupled phosphatidylinositol-specific phospholipase C (PLC) in intact cells. We used voltage-clamped Xenopus oocytes to test for direct PMT-mediated stimulation of PLC by monitoring the endogenous Ca2+-dependent C1- current. Injection of PMT induced an inward, two-component Cl- current, similar to that evoked by injection of IP3 through intracellular Ca2+ mobilization and Ca2+ influx through voltage-gated Ca2+ channels. These PMT-induced currents were blocked by specific inhibitors of Ca2+ and Cl- channels, removal of extracellular Ca2+, or chelation of intracellular Ca2+. Specific antibodies directed against an N-terminal, but not a C-terminal, peptide of PMT inhibited the toxin-induced currents, implicating that the N terminus of PMT is important for toxin activity. Injection with specific antibodies against PLCbeta1, PLCbeta2, PLCbeta3, or PLCgamma1 identified PLCbeta1 as the primary mediator of the PMT-induced Cl- currents. Injection with guanosine 5'-O-(2-(thio)diphosphate), antibodies to the common GTP-binding region of G-protein alpha subunits, or antibodies to different regions of G-protein beta subunits established the involvement of a G-protein alpha subunit in PMT-activation of PLCbeta1. Injection with specific antibodies against the alpha-subunits of G(q/11), G(s/olf), G(i/o/t/z), or G(i-1/i-2/i-3) isoforms confirmed the involvement of Gq/11alpha. Preinjection of oocytes with pertussis toxin enhanced the PMT response. Overexpression of G(q)alpha in oocytes could enhance the PMT response by 30-fold to more than 300-fold, whereas introduction of antisense G(q)alpha cRNA reduced the response by 7-fold. The effects of various specific antibodies on the PMT response were reproduced in oocytes overexpressing G(q)alpha.

Animals↗
PubMed1997

Differences in bimanual coordination associated with stuttering.

The motor coordination of adults who stutter was examined in the performance of a bimanual movement task. Fifteen subjects who stutter and 15 matched subjects who do not stutter performed three trials of a bimanual finger movement task. Subjects were required to produce a flexion and extension movement of the metacarpophalangeal joint of each index finger in rhythm to a metronome. The rate of movement increased during the 70 s trial. Stutterers could maintain movements at the prescribed rate as well as nonstutterers; however, stutterers moved with less amplitude and peak velocity. In addition, dynamical analysis revealed that subjects who stutter exhibited greater relative phase variability than subjects who do not stutter. These results shed new light on the mixed results of earlier studies on nonspeech motor performance of individuals who stutter and suggest that there are strategic differences as well as coordination differences that should be observable across a variety on motor tasks requiring coordination of multiple effectors.

Adult↗
PubMed1997

Giant cells in cortical tubers in tuberous sclerosis showing synaptophysin-immunoreactive halos.

We describe a characteristic pattern of immunoreactivity for synaptophysin in tuberous sclerosis. We analyzed cortical tubers from surgical specimens taken from six patients with tuberous sclerosis, which were obtained by surgical resections for the treatment of intractable seizures. The cortical tubers were characterized by blurred lamination of the cerebral cortex, hypercellularity, and gliotic changes. Neuropil in the cortex of cortical tubers showed reduced immunoreactivity for synaptophysin in all patients. 'Giant cells' were investigated in the cortex and white matter regions of cortical tubers. Some 'giant cells' had neuronal characteristics such as Nissl substance, a centrally placed chromatin-marginated nucleus, prominent nucleolus, positive immunoreactivity for microtubule-associated protein 2, and negative immunoreactivity for glial fibrillary acidic protein. Other 'giant cells' were indeterminate in cell type because they lacked Nissl bodies, distinct nucleolus, consistent immunoreactivity for microtubule-associated protein 2 and glial fibrillary acidic protein. Almost all 'neuronal giant cells' and some of the 'indeterminate giant cells' in the white matter showed intense immunoreactivity for synaptophysin: cell borders were surrounded by an intense immunoreactive halo. In conclusion, these immunohistochemical patterns for synaptophysin assist in characterizing these abnormal cells in the cortical tubers of patients with tuberous sclerosis.

Cerebral Cortex↗
PubMed1997

(+)-WAY 100135, a partial agonist, at native and recombinant 5-HT1B/1D receptors.

1. We have studied the effects of the purportedly selective 5-HT1A receptor antagonist (+)-WAY 100135 on electrically stimulated 5-hydroxytryptamine (5-HT) efflux in the ventrolateral geniculate nucleus (vLGN), and its affinity at human 5-HT1B and 5-HT1D receptors stably expressed in Chinese hamster ovary (CHO) cells. 2. On short 'pseudo single pulse' stimulations (20 pulses at 100 Hz, 190 ms train duration), (+)-WAY 100135 (1.0 microM) decreased 5-HT efflux in the vLGN to 68 +/- 8% of pre-drug values (P < 0.01). This decrease could be blocked by the 5-HT1D/1B receptor antagonist GR 127935 (50 nM). Conversely, when long stimulations (20 pulses at 20 Hz, 950 ms train) were used, (+)-WAY 100135 had no effect on 5-HT efflux (84 +/- 8% of pre-drug values) although both methiothepin (200 nM) and GR 127935 (50 nM) caused significant increases (to 175 +/- 18 and 130 +/- 10% of pre-drug values, respectively). 3. Paroxetine (100 nM), the selective 5-HT reuptake inhibitor, increased stimulated 5-HT efflux and reuptake half-life (to 145 +/- 18% and 649 +/- 121%, respectively) on pseudo single pulse stimulations. When (+)-WAY 100135 was added in combination with the uptake blocker, the effect of paroxetine on stimulated 5-HT efflux was potentiated to 282 +/- 48% (P < 0.01) without further effect on the 5-HT reuptake half-life. 4. The affinity and intrinsic activity of (+)-WAY 100135 were determined at recombinant human 5-HT1B and 5-HT1D receptors expressed in CHO cells, by use of radioligand binding and [35S]-GTP gamma S binding (+)-WAY 100135 was a partial agonist at human 5-HT1B and 5-HT1D receptors with moderately high affinity for 5-HT1D receptors (pEC50 = 7.61). 5. In conclusion, (+)-WAY 100135 was found to be not a selective 5-HT1A autoreceptor antagonist but may act as a partial agonist at the 5-HT1B/1D receptor, displaying agonist or antagonist properties depending on the stimulation protocol used and the resultant 5-HT 'tone' at the receptor.

Animals↗
PubMed1997

Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease.

Epstein-Barr virus (EBV) plays a major role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD). Patients who undergo primary EBV infection after transplantation are at greater risk of developing PTLD. In this retrospective study, the incidence of EBV infection and associated PTLD in 40 consecutive adult recipients who were seronegative for EBV at the time of liver transplantation were investigated, and risk factors for PTLD were analyzed. Of 37 patients with available timely posttransplant serum samples, 35 (95%) developed primary EBV infection. Of the 40 patients, 13 (33%) developed PTLD a median of 126 days (range, 48-776) after liver transplantation. The factor significantly associated with the development of PTLD was cytomegalovirus disease (relative risk, 7.3; 95% confidence interval, 2.36-22.6; P = .0006). Cytomegalovirus disease is a predictor for the development of PTLD in primary EBV infection after liver transplantation, and it may be a target for prophylactic intervention.

Adult↗
PubMed1997

Hepatitis A virus infections in urban children--are preventive opportunities being missed?

To determine the prevalence of hepatitis A virus (HAV) infections in children in a large urban center, a point prevalence survey was conducted using a novel, ultrasensitive assay for HAV-specific IgG in saliva. A structured sample of 224 grade-six students (5.8% of grade registrants) was obtained from 23 schools throughout Vancouver. All students provided saliva samples adequate for testing. The anti-HAV prevalence rate was 7.1% (95% confidence interval, 4.1%-11.3%). Among 167 Canadian-born students, only 5 (3%) were positive, whereas among 57 students born elsewhere, 11 (19.3%) were positive (P < .001), with circumstances in the latter group supporting infection prior to emigration. No clustering of positive persons was evident. The cumulative risk of HAV infection in Canadian-born children was low through age 11-12 years even in less affluent parts of the city, speaking against a need for routine use of HAV vaccine in this setting.

Antibodies, Viral↗
PubMed1997

Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria.

Sequential gastrointestinal permeability in patients with Plasmodium falciparum malaria was determined by measuring the permeation of sucrose, lactulose, and mannitol to assess both gastric and small intestine permeability. Sucrose absorption (gastroduodenal permeability) was increased in patients with severe malaria (defined as either >5% parasitemia or a serum bilirubin level of >50 micromol/L) and became normal by day 2 following treatment. A similar proportion of patients with uncomplicated malaria had increased gastroduodenal permeability initially, which resolved by day 7 of treatment. During acute malarial illness, the lactulose: mannitol (L:M) ratio in urine was increased and was found to be higher in patients with severe malaria than in those with uncomplicated malaria and in controls, but this ratio reverted to normal during convalescence. At the time of admission, the L:M ratios in patients with uncomplicated malaria were increased but became normal by day 2 after treatment. Conversely, the duration of increased L:M ratios in patients with severe malaria was longer. By day 7, the L:M ratios in patients with severe malaria were higher than those in patients with uncomplicated malaria and in controls. We conclude that gastrointestinal permeability is increased during severe and uncomplicated falciparum malaria but reverts to normal during convalescence.

Adolescent↗