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Biomedical subjects

H H Chen

Publications and source records attributed to H H Chen.

At least 73 records · Page 4Linked to original sources

Cell-level finite element studies of viscous cells in planar aggregates.

A new cell-level finite element formulation is presented and used to investigate how epithelia and other planar collections of viscous cells might deform during events such as embryo morphogenesis and wound healing. Forces arising from cytoskeletal components, cytoplasm viscosity, and cell-cell adhesions are included. Individual cells are modeled using multiple finite elements, and cell rearrangements can occur. Simulations of cell-sheet stretching indicate that the initial stages of sheet stretching are characterized by changes in cell shape, while subsequent stages are governed by cell rearrangement. Inferences can be made from the simulations about the forces that act in real cell sheets when suitable experimental data are available.

Biomechanical Phenomena↗

The mechanics of heterotypic cell aggregates: insights from computer simulations.

Finite element-based computer simulations are used to investigate a number of phenomena, including tissue engulfment, cell sorting, and checkerboard-pattern formation, exhibited by heterotypic cell aggregates. The simulations show that these phenomena can be driven by a single equivalent force, namely a surface (or interfacial) tension, that results from cytoskeletal components and cell-cell adhesions. They also reveal that tissue engulfment, cell sorting, and checkerboard-pattern formation involve several discernible mechanical features or stages. With the aid of analytical arguments, we identify the conditions necessary for each of these phenomena. These findings are consistent with previous experimental investigations and computer simulations, but pose significant challenges to current theories of cell sorting and tissue engulfment.

Biomechanical Phenomena↗

Therapeutic effect of gypenoside on chronic liver injury and fibrosis induced by CCl4 in rats.

Gypenoside is a saponins extract derived from the Gynostemma pentaphyllum. The purpose of this study was to evaluate the hepatoprotective and antifibrotic potential of Gypenoside on chronic liver injury induced by CCl4 for 8 wks. The results indicated that the increase of SGOT, SGPT activities in CCl4 liver injury were significantly reduced by treatment with Gypenoside. It also elevated the A/G ratio. For the study of anti-fibrotic potential, Gypenoside reduced the collagen content by 33%. These phenomena were confirmed by pathologic observation; thinner bands of liver collagen were found. The results suggest that Gypenoside has hepatoprotective and anti-fibrotic activities.

Animals↗

A new era in the diagnosis of breast cancer.

The regular use of high-quality mammography on asymptomatic women enables most breast cancers to be detected in the preclinical phase. Earlier detection dramatically rearranges the spectrum of breast cancer outcomes, resulting in better control of breast cancer. The new era requires a shift in thinking and a re-evaluation of the traditional diagnostic and therapeutic approaches to breast diseases. Tumors are smaller, less often node-positive, and have a more favorable malignancy grade. The challenge for diagnosticians is to find as many breast cancers as possible in the preclinical phase. The challenge for therapists is to adapt the treatment guidelines accordingly, in order to avoid over-treatment.

Adult↗

Body composition in hemodialysis patients--is it different from that of normal subjects?

OBJECTIVE: Body composition assessment is an important method of evaluating nutritional and metabolic status in hemodialysis patients. PATIENTS AND METHODS: To assess the body composition of hemodialysis patients, we used dual-energy X ray absorptiometry to test 40 stable chronic hemodialysis patients and 40 normal subjects. The patients were from 38 to 70 years old, and all without diabetic mellitus. Comparing with the hemodialysis patients, the normal subjects were selected on a one-to-one base with the same sex and about the same age, body weight and height. RESULTS: The lean body mass/body weight (LBM/BW) ratio had no significant statistical difference between hemodialysis patients and normal subjects in this study (63.02 +/- 8.42% vs 64.80 +/- 7.92%, p =0.3308). The male LBM/BW ratio was higher than that of the female (71.07 +/- 4.63% vs 59.30 +/- 6.35%, p < 0.0001). According to the multiple linear regression analyses, the LBM of hemodialysis patients had positive correlation with gender (p < 0.0001), height (p = 0.0360) and weight (p < 0.0001). The total bone mineral density (BMD) of hemodialysis patients was found to be lower than that of the normal subjects (0.90 +/- 0.10 g/cm vs 0.97 +/- 0.08 g/cm, p = 0.0092). The BMD had been found to be low in the hemodialysis patients with serum intact parathyroid hormone (iPTH) > 1,700 pg/ml. The BMD had negative correlation with age in the female hemodialysis patients (r = 0.63, p = 0.0009), but no correlation in the male hemodialysis patients and in the female or male normal subjects. With the multiple linear regression analyses, the BMD of hemodialysis patients had positive correlation with weight (p = 0.0329) and negative correlation with age (p = 0.0183) and serum iPTH (p = 0.0231). CONCLUSION: We concluded that: the LBM/BW ratio of hemodialysis patients was not different from that of normal subjects. Severe secondary hyperparathyroidism hemodialysis patients had low BMD. The BMD had negative correlation with age in the female hemodialysis patients.

Adult↗

Mammographic screening in women with a family history of breast cancer: some results from the Swedish two-county trial.

BACKGROUND: The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without. In the invited arm of a randomised trial of breast cancer screening, data on family history of breast cancer were available on 29.179 women aged 40-74 attending for screening. Among those women, 358 were diagnosed with breast cancer during the trial. METHODS: Those with and without a family history were compared with respect to mammographic parenchymal pattern, interval cancer rates, mean sojourn time and sensitivity of screening. In the 358 cancers, the effect of family history was estimated on survival, incidence of advanced cancers and their relationship to screen detection. RESULTS: A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40-49. Interval cancer rates were higher in women with a family history, and in older women at least, mean sojourn time was shortened in women with a family history (1.89 years compared to 2.70). Survival was better (although not significantly so) in cancers in women with a family history (relative hazard=0.52) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers (relative hazard=2.72) independently of family history. Similarly, interval cancers tended to be larger, and worse malignancy grade in those with and without a family history of breast cancer. CONCLUSIONS: These results suggest that the policy often adopted of annual screening for woman aged 40-49, with a family history of breast cancer, is a reasonable one, and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history.

Adult↗

Some random-effects models for the analysis of matched-cluster randomised trials: application to the Swedish two-county trial of breast-cancer screening.

BACKGROUND: In the Swedish two-county trial women aged 40-74 years from two counties in Sweden were randomised to invitation to mammographic screening for breast cancer. METHODS: This paper uses random effects logistic regression models to analyse recent data from the trial. The analysis accounts for the structure of the trial, where small geographical units are randomised within larger geographical strata (blocks of two or three small units that are socio-economically similar). RESULTS: Fixed effects and a variety of random effects models show a strong degree of agreement and yield a significant 29% or 30% reduction in breast-cancer mortality. DISCUSSION: Fixed effects and random effects models agree for this example, because heterogeneity both between strata and within strata between clusters is small and because the effect of treatment does not vary much in different strata.

Adult↗

Effects of MCI-154, a calcium sensitizer, on cardiac function in endotoxemic rabbits.

AIM: To observe the effects of MCI-154, a calcium sensitizer, on cardiac function after endotoxic shock. METHODS: The rabbits were intravenously injected with MCI-154 0.1 mg.kg-1 at 10 h after the administration of endotoxin 1.0 mg.kg-1, followed by a continuous infusion of normal saline (NS) 50 mL.kg-1 + MCI-154 0.1 mg.kg-1. During this process, the parameters of cardiac function were measured. RESULTS: Ten hours after the endotoxin injection, heart rate (HR) increased noticeably while the mean arterial blood pressure (MAP), left ventricular systolic pressure (LVSP), isovolumetric pressure (IP), myocardial contractility (MC), and the area of p-dp/dtmax vector loop (Lo) were all markedly decreased. Treatment with NS 50 mL.kg-1 alone had slight effects on these parameters. LVSP, IP, MC, and Lo were all markedly increased while HR did not obviously change and left ventricular end-diastolic pressure (LVEDP) was reduced markedly following MCI-154 administration in endotoxic shock rabbits. The parameters of MC were improved nearly to the same values as in sham shock group and were markedly higher than in NS treated group. CONCLUSION: MCI-154 exerts remarkable therapeutic effects on cardiac dysfunction after endotoxic shock.

Animals↗

Effect of MCI-154, a calcium sensitizer, on calcium sensitivity of myocardial contractile system in endotoxemic rats.

AIM: To investigate the effect of MCI-154 on calcium sensitivity of myocardial contractile system in endotoxemic rats. METHODS: Skinned right ventricular papillary muscles from endotoxemic rats were prepared by saponin 500 mg/L. Forces of the skinned muscles were recorded when they were activated sequentially by different concentrations of Ca2+ with or without cardiotonic agents. The tension-pCa relationship and pCa50 of the skinned fibers were taken as the index of Ca2+ sensitivity of myocardial contractile system. RESULTS: The maximal Ca(2+)-activated tension (Tmax) was lower, and pCa50 was reduced in endotoxemia group as compared with those in sham control group. Milrinone 50 mumol/L could not counteract the above abnormalities. However, after MCI-154 10 mumol/L was added, the Tmax and pCa50 were increased to an extent similar to that of sham control group and significantly higher than those of endotoxemia group and endotoxemia + milrinone group. Furthermore, such effects of MCI-154 were concentration-dependent. CONCLUSION: The Ca2+ sensitivity of cardiac contractile system in endotoxemic rats is decreased. MCI-154 can reverse the decreased sensitivity and increase Tmax of myocardial muscles from endotoxemic rats.

Animals↗

Renal response to acute neutral endopeptidase inhibition in mild and severe experimental heart failure.

BACKGROUND: Neutral endopeptidase 24.11 (NEP) is a metalloprotease that is localized in the greatest abundance in the kidney and degrades natriuretic peptides, such as atrial natriuretic peptide (ANP). Mild congestive heart failure (CHF) is characterized by increases in circulating ANP without activation of the renin-angiotensin-aldosterone system (RAAS) or sodium retention. In contrast, severe CHF is characterized by sodium retention and coactivation of both ANP and the RAAS. METHODS AND RESULTS: We defined the acute cardiorenal actions of the NEP inhibitor candoxatrilat (8 microg. kg(-1). min(-1)) in 4 groups of anesthetized dogs (normal, n=8; mild CHF, n=6; severe CHF, n=5; and severe CHF with chronic AT(1) receptor antagonism, n=5). Mild CHF was produced by rapid ventricular pacing at 180 bpm for 10 days and severe CHF at 245 bpm for 10 days. In mild CHF, urinary sodium excretion and glomerular filtration rate were greatest in response to acute NEP inhibition compared with the response in either control animals or those with severe CHF. Furthermore, an increase in glomerular filtration rate was observed only in mild CHF in association with increases in renal blood flow and decreases in renal vascular resistance and distal tubular sodium reabsorption. Urinary ANP and cGMP excretion, markers for renal biological actions of ANP, were greatest in mild CHF. The renal actions observed in mild CHF were attenuated in severe CHF and not restored by chronic AT(1) receptor antagonism. CONCLUSIONS: The results of the present study demonstrate that acute NEP inhibition in mild CHF results in marked increases in renal hemodynamics and sodium excretion that exceed that observed in control animals and severe CHF. These studies underscore the potential therapeutic role for NEP inhibition to enhance renal function in mild CHF, an important phase of CHF that is marked by selective activation of endogenous ANP in the absence of an activated RAAS.

Acute Disease↗

The natural history of breast carcinoma: what have we learned from screening?

BACKGROUND: The availability of breast carcinoma data from trials of mammographic screening provides an opportunity to study the natural history of breast carcinoma. METHODS: The Swedish Two-County study is a randomized, controlled trial of mammographic screening for breast carcinoma in which 77,080 women were randomized to receive an invitation to mammographic screening and 55,985 were randomized to receive no invitation. During the trial, a total of 2468 breast carcinoma cases were diagnosed. The authors examined the effect of screening on the pathologic attributes of the tumors diagnosed, mortality and survival from breast carcinoma, and the consequences of arresting tumor development by screening. RESULTS: Screening reduces mortality from breast carcinoma largely through its effect in detecting tumors at a smaller size, decreasing the probability of lymph node metastases, and reducing the opportunity for worsening of the grade of malignancy of the tumor. CONCLUSIONS: Breast carcinoma is not a systemic disease at its inception, but is a progressive disease and its development can be arrested by screening. The point at which the tumor's progression is arrested is crucial. Detection of small (<15 mm) and lymph node negative invasive tumors will save lives and confer an opportunity for less radical treatment. Tumor progression in the preclinical phase occurs more rapidly in women age <50 years, suggesting the need for a shorter screening interval for this group.

Adult↗

Genotoxic effects of triphenyltin acetate and triphenyltin hydroxide on mammalian cells in vitro and in vivo.

Two organotin pesticides, triphenyltin acetate (TPTA) and triphenyltin hydroxide (TPTH), were evaluated for their ability to induce micronuclei (MN) and sister chromatid exchange (SCE) in vitro using cultured Chinese hamster ovary (CHO) cells and in vivo BALB/c mouse erythrocytes. Both pesticides induced a dose-dependent increase but only TPTH induced a significant increase in MN at the highest dose (150 ng/ml) tested in CHO cells. With adding S9 microsomal fractions, both pesticides induced a meaningful MN induction at 150 ng/ml and a dose-dependent significant increase in SCE. In vivo MN induction in erythrocytes was conducted by treating BALB/c mice orally or intraperitoneally with these pesticides either in a single or triple treatments. Oral gavage (p.o.) of TPTA resulted in a dose-related significant increase of MN induction in peripheral blood and of TPTH induced a significant increase in micronucleated reticulocyte (MNRETs) only in a single treatment. Intraperitoneal administration of TPTA or TPTH, however, resulted in meaningless random increases in MN though these increases might be attributable to toxic effects. The MNRETs levels in the treatment with both pesticides were independent to the sampling time. This study demonstrated that TPTA and TPTH was potential chromosome mutagens.

Animals↗

Effects of chronic lead (Pb) exposure on neurobehavioral function and dopaminergic neurotransmitter receptors in rats.

Sprague-Dawley rats were maternally and permanently exposed to Pb (1000 ppm in their drinking water as lead acetate). Behavioral functions were examined starting at post-natal day (PN) 84. Lead exposure did not change spatial learning in the radial arm maze, but induced higher locomotor activity as observed in the open-field and in the radial arm maze. Lead treatment did not impact motor coordination. Autoradiographic analysis of brain sections indicated that Pb-exposure did produce a decrease in [125I]sulpride (D2 receptor antagonist) binding in the cerebral cortex, but not in the striatum and thalamus nucleus. No change was found in [125I]SCH-23982 (D1 receptor antagonist) binding. Since the cortical dopaminergic system is critical for cognitive processes and motor behavior, it is possible that Pb-related change in D2 receptors may mediate to it induced hyperlocomotor activity.

Animals↗

DNA from both high-capacity and first-generation adenoviral vectors remains intact in skeletal muscle.

Previous studies of the use of adenoviral vectors in animal models of gene therapy have focused on the immune response against transduced cells as the major limiting factor to long-term transgene expression. In this study we eliminated the variable of immunity induced by expression of the transgene in order to investigate vector DNA stability of both first-generation and high-capacity adenoviral vectors after gene transfer to skeletal muscle. Transgene expression from a high-capacity adenoviral vector remained at a high level for at least 20 weeks and was accompanied by persistence of intact vector genomes. In contrast, transgene expression from a first-generation adenoviral vector markedly diminished by 6 weeks after gene transfer and was accompanied by mild and variable inflammatory cell infiltrates. Surprisingly, despite this loss of transgene expression, the first-generation adenoviral vector genomes persisted like the high-capacity adenoviral vector genomes. Therefore, in the absence of immunity to transgene proteins, loss of expression from the first-generation vector was due to inhibition of transgene expression rather than to the elimination of vector-containing cells. DNA stability and persistent expression of the high-capacity adenoviral vector supports the potential of this vector for clinical applications of muscle gene transfer.

Adenoviridae↗

Laparoscopic colectomy yields similar morbidity and disability regardless of patient age.

This study compared the outcome factors of morbidity and the length of disability in older and younger patients following laparoscopic colorectal surgery. All patients undergoing laparoscopic segmental resection during the study period were included. Morbidity was determined by reviewing the medical records, and disability by a patient-administered questionnaire. The series was divided into two age cohorts (</=64 and >/=65 years), which did not differ significantly in gender or type of procedure. Between these two groups we found no significant differences in mean duration of ileus (3.3 days in both groups), the mean length of hospitalization (5.7 vs. 6.3 days, respectively), morbidity rate (18% vs. 21%), or time until returning to partial activity (1.6 vs. 1.6 weeks) or to full activity (3 vs. 2 weeks). Our findings demonstrate that neither the morbidity rate nor the disability period after laparoscopic techniques differ between elderly and younger patients. We therefore endorse the use of laparoscopy regardless of patient age.

Activities of Daily Living↗

Microvascular vastus lateralis muscle flap for chronic empyema associated with a large cavity.

Thoracic empyema can be disabling and may need microvascular free flaps in some intractable cases. After repeated failure of conventional thoracic surgical procedures, 2 patients with empyema were treated with microvascular free vastus lateralis muscle flaps for obliteration of the large empyema cavity. The reconstruction was successful in wound closure and eradication of infection. The donor site morbidity was minimal, and the patients resumed normal daily activities. Microvascular vastus lateralis muscle flap is the best option if free flaps are required for reconstruction of empyema.

Aged↗

Microvascular prefabricated free skin flaps for esophageal reconstruction in difficult patients.

BACKGROUND: Reconstruction of the esophagus for complicated benign stricture or after resection of malignant lesion is still a challenge for surgeons. When abdominal viscera cannot be used, skin flaps are selected for esophageal reconstruction. However, skin flaps for esophageal reconstruction are notorious for leakage, and have not been widely accepted. Prefabrication before microvascular transfer to its final site can improve the result of esophageal reconstruction when skin flaps are used. METHODS: Eight patients with complicated corrosive esophagitis had been treated with prefabricated skin flaps for esophageal reconstruction. The procedures are described in detail. RESULTS: All patients healed well without leakage. The barium study showed smooth passage. There was no dysphasia or regurgitation after education. Pulmonary complication happened in only 1 patient. Revision for the distal anastomosis was required in 1 patient due to narrowing. When the skin tube is long, the patients need water (or soup) to facilitate swallowing and occasionally use their hand to help the food passage. This method has the following advantages: (1) healing of the long suture line before transfer to withstand the intestinal juice; (2) reliable viability in the distal part of the flap, especially when an extended length of the flap is required; (3) more length of stable tissue for two-layered, tension-free anastomosis at the junction of skin and gastrointestinal mucosa to prevent leakage; and (4) the flap can be placed in the substernal position to meet the aesthetic requirement of young patients. The disadvantage was the staged operations. However, after prefabrication the transfer becomes safe and free of leakage. The overall morbidity is minimal. CONCLUSIONS: In rare situations when skin flaps are used for esophageal reconstruction, prefabrication provides advantages over conventional one-stage methods, although it needs additional procedures. This method is a combination of conventional technique and microsurgery.

Adult↗