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Biomedical subjects

C Tan

Publications and source records attributed to C Tan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Glomerular function of lead-exposed workers.

Among lead-exposed workers, there is evidence of increased mortality from chronic renal diseases (nephritis and nephrosis). Epidemiological studies using early markers of nephropathy among lead-exposed workers failed to demonstrate early renal changes. This study is aimed at assessing the glomerular function of 137 lead-exposed subjects and at evaluating whether changes in markers of glomerular function are related to exposure indices derived from longitudinal blood lead data. A control group of 153 postal workers was also investigated. Several exposure indices were derived for the exposed workers, including a time-integrated index Pb in blood (PbB)int and the number of times the PbB was above critical values (PbB400, PbB500, PbB600). Through multiple linear regression analysis, PbBint was the best predictor of variation in serum beta 2-microglobulin (S beta 2m) and alpha 1-microglobulin (S alpha 1m) and urinary albumin (UA1b). A small but statistically significant difference in the mean beta 2m was found. S beta 2m was also the only marker showing a significantly higher prevalence rate ratio (PRR) of abnormalities among lead-exposed workers. Though there was no clear dose-response relationship with PbBint as the index of dose, all the 15 subjects with abnormal S beta 2m in the older age group were found in the highest PbBint group. Furthermore, of the 8 subjects with low 4-h creatinine clearance (CrCl4h), 6 had abnormal levels of beta 2m. Two subjects with CrCl4h of less than 75 ml/min/1.74 m2 had high PbBint values, thus suggesting that high blood lead levels over a prolonged time may be associated with decreased CrCl4h. Though the long-term significance of elevated S beta 2m and UA1b is unclear, their association with high PbBint and decreasing CrCl4h indicate a potentially adverse effect. Their relationship with PbB400 and PbB600 suggests that the threshold of 700 micrograms/l for PbB may not prevent the occurrence of lead nephropathy.

Adolescent↗
PubMed1995

Molecular characterization of a lipid-modified virulence-associated protein of Rhodococcus equi and its potential in protective immunity.

Virulent strains of Rhodococcus equi produce plasmid-mediated 15- and 17-kDa proteins, which are thermoregulated and apparently surface-expressed. We demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that R. equi produce three antigenically-related virulence-associated proteins, a diffuse 18-22-kDa, a 17.5-kDa and a 15-kDa protein. Phase partitioning of whole cells of R. equi strain 103 with Triton X-114 (TX-114) and labelling with [3H]-labelled palmitic acid showed that the two higher molecular weight proteins are hydrophobic and lipid modified. The 15-kDa protein did not partition into TX-114 and was not lipid modified. Cloning and expression of a fragment of the R. equi virulence plasmid in Escherichia coli showed that the three proteins were expressed from a single gene. Sequence analysis of this gene (designated vapA) revealed a 570-bp open reading frame encoding a polypeptide of 189 amino acids with a calculated molecular mass of 19,175 Da. The mature, nonlipid modified protein had a calculated mass of 16,246 Da. The 17.5- and 18-22-kDa forms of the protein are therefore due to lipid modification. No significant sequence homology of the vapA gene with other reported nucleotide sequences were found. Opsonization of virulent R. equi with an IgG1 mouse monoclonal antibody (MAb103) to the VapA protein significantly enhanced uptake in the murine macrophage cell line IC-21. Intraperitoneal injection of mice with Mab103 enhanced initial clearance from the liver of mice challenged intravenously with R. equi. Immunization of mice with the lipid-modified VapA purified by SDS-PAGE fractionation or with acetone precipitated VapA protein following TX-114 extraction resulted in significantly enhanced clearance from the liver and spleen following intravenous challenge. The VapA protein of R. equi appears therefore to be a protective immunogen.

Actinomycetales Infections↗
PubMed1995

Paediatric pacemaker implant using the transvenous endocardial approach.

The advent of the pacemaker has opened a whole new dimension to management in cardiology. Although its use has been well described in adults, its role in paediatric cardiology has proven to be equally exciting and challenging. We describe a case of a child with complex cyanotic heart disease who had an insertion of a cardiac pacemaker via the transvenous route, one of the youngest to be performed locally. This article also highlights the pertinent features of paediatric pacemaker therapy, including its indications and implantation technique.

Child↗
PubMed1994

Selective transfer of cholesteryl ester over triglyceride by human plasma lipid transfer protein between apolipoprotein-activated lipid microemulsions.

The substrate-specific rate of the human plasma lipid transfer protein (LTP) reaction was studied using pyrene-labeled substrate lipid analogues as probes for various lipids, by monitoring the ratio of the fluorescence intensities of their excimers to those of their monomers as an indicator of pyrene concentration in the microenvironment. Transfer of cholesteryl ester (CE) and triglyceride (TG) was demonstrated between human high-density lipoproteins, between low-density lipoproteins, and between these two lipoprotein, and the specific fractional transfer rate of CE was always higher than that of TG by a factor of 2.4-7.9. On the other hand, the transfer by LTP of CE, TG, and phosphatidylcholine (PC) was also demonstrated between lipid microemulsions having an average diameter of 25-26 nm using the same probes, but only when the emulsions were activated by apolipoproteins A-I, A-II, E, or C-III. The maximally activated rates of the transfer of CE and TG were the same when measured between the emulsions with cores composed exclusively of either lipid. The specific fractional transfer rate of pyrene-CE, however, was inversely proportional to the percentage of CE in the TG core of the emulsions, and the initial transfer of TG was almost completely inhibited by the presence of small percentages of CE in the TG core. Thus, the transfer of CE between the emulsions is highly selective over that of TG by orders of magnitude, much more selective than the reaction between any natural plasma lipoproteins, but this selectivity is not a rate-limiting step of the overall LTP reaction. The maximally activated LTP-catalyzed transfer rate of PC between the emulsions was somewhat higher than that of CE or TG and was not affected by the composition of the core lipids of the emulsion, TG or CE. When an excess amount of LTP was incubated with emulsion containing a small percentage of pyrene-CE in the TG core in the absence of the acceptor particles, excimer fluorescence rapidly decreased to the base line, and this change was suppressed when pyrene-CE was diluted with CE in the core. This result may indicate that LTP selectively disrupts pyrene-CE excimer formation on the basis of its selective interaction with the CE molecule over TG in the emulsion system as a putative background mechanism for the selective transfer of CE.

Apolipoprotein A-I↗
PubMed1994

Urinary N-acetyl-beta-D-glucosaminidase activity in workers exposed to inorganic lead.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) had been shown to be a useful early marker of renal injury. In workers exposed to lead it seems to be the only early marker but the dose response and dose effect relations are weak. Furthermore, the significance and underlying mechanism of increased urinary NAG activity is far from clear. By studying the isoenzyme profiles of urinary NAG, the significance and underlying mechanism may be further clarified. The heat labile (NAG-A) and heat stable (NAG-B) isoenzyme profiles of 128 workers exposed to lead from a lead stabiliser factory were analysed. NAG activity was expressed as total NAG, NAG-A, and NAG-B activity as well as ratios (NAG-B/total NAG and NAG-B/NAG-A). Exposure indices included the recent concentration of blood lead (BPb), a cumulative blood lead index (TBPb), and the recent change in concentration of blood lead (CBPb). The NAG indices correlated best with CBPb. Nearly 50% of the variation in NAG-B activity could be explained by the combination of all three exposure indices but only the CBPb was highly significant. When these exposure indices were entered separately into the regression equation, CBPb accounted for 36.3% of the variation in NAG-B activity, 5.7% was accounted for by TBPb and 2.7% by BPb. There was also no dose-effect or dose-response relation between the NAG variables and BPb or TBPb groups. With CBPb, there were dose-effect and dose-response relations. With CBPb, there was an increase in NAG variables in the group with more than 25% increase in blood lead over the past six months. The increase in NAG activity in this study is likely to be due to a recent increase in concentration of blood lead and hence presumably a recent rise in renal burden of inorganic lead. This suggests that the increase in urinary NAG activity is a form of acute response to a sharp increase in renal burden of lead, rather than to a cumulative dose. Heat stable NAG is part of the lysosomal membrane and is present in the urine when there is breakdown of lysosomes. Our data therefore contradict suggestions that the increase in urinary NAG activity is due to exocytosis.

Adult↗
PubMed1994

Urinary excretion of tubular brush-border antigens among lead exposed workers.

The brush-border of the human renal proximal tubule is extremely sensitive to toxic, ischaemic and inflammatory insults. A monoclonal antibody to a brush-border antigen (BB-50) had been shown to identify increased urinary excretion of BB-50 (UBB-50) among workers exposed to heavy metals and hydrocarbons as well as patients on cisplatin and patients with early diabetic nephropathy. This study describes the use of this antibody to quantify UBB-50 among lead exposed workers. The study population consisted of 154 workers from a factory manufacturing lead stabilisers. Of these 91 workers had less than 6 months of exposure and formed the control group. The remaining 63 workers with a median exposure of 3 years formed the exposed group. Several blood lead (PbB) indices were used as exposure indices. These include the most recent PbB (PbBrec), a time-integrated blood lead index (PbBint), an absolute change in recent PbB (PbB delta), a relative change in PbB (PbB delta%), as well as the number of times the PbB measurements were above 40, 50 and 60 micrograms/100 ml (PbB40, PbB50, PbB60 respectively). Urinary levels of beta-2-microglobulin (U beta 2m), alpha-1-microglobulin (U alpha 1m), retinol binding protein (URBP), albumin (UAlb), activity of total N-acetyl-D-beta-glucosaminidase (NAG-T) and heat stable NAG isoenzyme (NAG-B) were measured along with the serum beta 2m (S beta 2m). Through stepwise analysis, UBB-50 was best correlated with PbBint, PbB40 and PbB delta% (r2, 0.271). Of these, PbBint and PbB40 had about twice the contribution to the variation in UBB-50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Development of a new intensive therapy for acute lymphoblastic leukemia in children at increased risk of early relapse. The Memorial Sloan-Kettering-New York-II protocol.

BACKGROUND: Improved survival of children with acute lymphoblastic leukemia (ALL) has made it more difficult to develop new protocols to further improve results. The authors report the pilot experience with the Memorial Sloan-Kettering-New York-II (MSK-NY-II) protocol, based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity. METHODS: Forty-four of 46 consecutive patients were randomized to one of four regimens varying only in the sequence and mode of administration of the drugs during the first 48 hours of therapy, while the kinetics of the disappearance of the leukemic cells from the bone marrow was monitored with bone marrow aspirates and biopsies on days 0, 2, 7, and 14. RESULTS: Thirty-two high-risk and 12 average-risk patients were randomized. The marrow contained less than 25% blasts in 74.4% and 92.9% by day 7 and 14, respectively. Ninety-three percent achieved remission. Regimens beginning with daunorubicin achieved a greater and more rapid reduction in leukemic cells than those starting with cyclophosphamide. Daunorubicin infusion produced a more rapid cytoreduction than daunorubicin bolus. Two of 41 patients who achieved remission relapsed, and there was one death in remission. With a median follow-up of 54+ months, the event-free survival (EFS) rate was 86% +/- 10%. Disease-free survival (DFS) rate at 48 months was 93%. The estimated 4-year EFS rate for the high-risk and average-risk patients were 83 +/- 14% and 93 +/- 10%, respectively. Four of 18 patients given daunorubicin bolus and 0 of 18 patients given daunorubicin infusion who were monitored with serial echocardiograms had significant decrease in cardiac function (P = 0.10). The major toxicity of the therapy was infections, with 35% of patients developing serious infections during induction and consolidation. Half the patients had an episode of bacteremia from the venous catheter during the 2 years of maintenance. CONCLUSIONS: Close monitoring of kinetics of cytoreduction can rapidly distinguish between similar therapies, and the surrogate end-point may reduce the need for the long follow-up periods that may still be required to demonstrate differences in EFS. Continuous infusion of daunorubicin had less cardiotoxicity with faster antileukemic activity than bolus infusion. The MSK-NY-II protocol with a 86% 4-year EFS rate and a 95% DFS rate was a promising new regimen for the treatment of average-risk and high-risk ALL.

Adolescent↗
PubMed1993

Consumer-operated drop-in centers: evaluation of operations and impact.

Research on self-help for consumers of psychiatric services has focused on the operation of voluntary groups and largely ignored service programs operated by consumers. This evaluation study focused on six consumer-operated drop-in centers, each established for at least two years. These centers served a combined total of 1,445 consumers and were funded as demonstration projects by the Michigan Department of Mental Health. Structured interviews of consumer-users of these centers indicated that the program was meeting its funding intents of serving people with serious mental illness and of creating an environment promoting social support and shared problem solving. Levels of satisfaction were uniformly high; there were few differences across centers. Issues that emerged for future policy and research considerations included funding constraints, enhancing accessibility (particularly for women and people needing frequent hospitalization), variable levels of support from catchment area community mental health agencies, and determining the long-term benefits of drop-in center participation.

Community Mental Health Centers↗
PubMed1993

Proteinuria and enzymuria in non-insulin-dependent diabetics.

Urine albumin, alpha 1- and beta 2-microglobulins, retinol-binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in early morning urine samples from 99 non-insulin-dependent diabetic (NIDDM) patients receiving ambulatory care at a primary health care polyclinic. Elevated NAG levels were found in 90% of diabetics regardless of the duration of their disease. Almost half (43.4%) of the subjects had microalbuminuria. Over a third of the subjects without albuminuria had elevated alpha 1-microglobulin levels in their urine. The proportion of subjects with elevated alpha 1 levels increased significantly with the presence of albumin, poor glycaemic control and increased duration of disease. These findings suggest that proximal tubular as well glomerular dysfunction coexist in the NIDDM patients studied.

Acetylglucosaminidase↗
PubMed1993

Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease.

We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.

Adult↗
PubMed1992

Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia.

Although the mechanisms of resistance to methotrexate (MTX) are known in experimental tumors made resistant to this drug, little information is available regarding acquired resistance to MTX in patients. A competitive displacement assay using the fluorescent lysine analogue of MTX, N-(4-amino-4-deoxy-N10-methylpteroyl)-N epsilon-(4'-fluorescein-thiocarbamyl)-L-lysine (PT430), was developed as a sensitive method of detection of transport resistance to MTX in cell lines, as well as in blast cells from patients with leukemia. Rapid uptake of PT430 at high concentrations (20 mumol/L) in leukemic blasts resulted in achievement of steady-state levels within 2 hours. Subsequent incubation with the folate antagonists, MTX and trimetrexate (TMTX), which differ in the mode of carrier transport, produced characteristic patterns of PT430 displacement. Flow cytometric analysis of the mean fluorescence intensity in the human CCRF-CEM T-cell lymphoblastic leukemia cell line and its MTX-resistant subline clearly identified the presence of transport deficiency in the resistant subline. Analysis of blasts from 17 patients with leukemia, nine with no prior chemotherapy and eight previously treated with chemotherapy, found evidence of MTX transport resistance in two of the four patients who were treated with MTX and considered to be clinically resistant to the drug. The finding that blast cells of some patients with leukemia considered clinically resistant to MTX is due to decreased MTX transport has important implications for clinical use of this drug and for new drug development.

Adolescent↗
PubMed1992

An advocacy intervention program for women with abusive partners: initial evaluation.

Experimentally tested the hypotheses that (1) battered women are in need of numerous community resources upon exit from a domestic violence shelter, (2) working with advocates increases women's effectiveness in obtaining needed resources and social support, and (3) success in obtaining resources and social support increases women's levels of life satisfaction and decreases their risk of further abuse. The initial findings of a short-term intervention project designed to provide postshelter advocacy services to women with abusive partners are presented. One-hundred forty-one battered women were interviewed immediately upon their exit from a domestic violence shelter as well as 10 weeks thereafter. Half the sample was randomly assigned to receive the services of trained advocates who assisted them in accessing needed community resources. Women who worked with advocates reported being more effective in accessing resources and had higher levels of social support and overall quality of life postintervention. Although all women reported some decrease in postshelter abuse, there were no differences between those with and those without advocates, and abuse continued to be a problem for many women.

Adolescent↗
PubMed1992

Lives in a balance: perceived family functioning and the psychosocial adjustment of adolescent cancer survivors.

Childhood cancer patients have a greater likelihood of long-term survival than ever before. This study examined both the perceived family functioning of adolescents who had successfully completed treatment for pediatric cancer and the relationship between family functioning and post-treatment adjustment. Eighty-eight adolescent survivors of hematologic malignancies were assessed regarding their family functioning, mental health, self-esteem, global competence, and problem behaviors. Contrary to expectations about the influence of cancer on these families, adolescent cancer survivors reported lower levels of family cohesion than the normative sample of healthy adolescents and their families. While current age, gender, age at diagnosis, and time since treatment completion were generally not associated with adolescents' adjustment, perceived family cohesion and adaptability were strongly related to post-treatment psychological adjustment.

Adaptation, Psychological↗
PubMed1992

After the crisis: a needs assessment of women leaving a domestic violence shelter.

The current study presents the results of a needs assessment of 141 women exiting an emergency shelter for women with abusive partners. Extensive in-person interviews were conducted. Results indicate that battered women need numerous community resources upon their shelter exit, including legal assistance, employment, and housing. Race, age, and whether a woman was returning to her assailant influenced which resources she reported needing at shelter exit. Most of the women had experienced severe abuse and injuries, and required physical protection. Implications of these findings as they relate to program development and integration of social services are discussed.

Adaptation, Psychological↗
PubMed1991

A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors.

A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.

Adult↗
PubMed1991

Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.

The basis of intrinsic resistance of blasts from patients with acute non-lymphocytic leukemia (ANLL) to methotrexate was studied. MTX polyglutamate formation was measured in blast cells from 19 patients with ANLL and in 7 pediatric patients with acute lymphocytic leukemia (ALL), after in vitro incubation for 24 h with 3H-methotrexate. There was no significant differences seen in the total amount of MTX plus polyglutamates measured between ANLL and ALL blasts, indicating that transport defects do not account for intrinsic MTX resistance in ANLL. However, there were significant differences between the amounts of long chain MTX polyglutamates found in ANLL cells as compared to ALL cells. Most, but not all, ANLL blasts were unable to form long chain polyglutamates. In as much as the level of MTX polyglutamates found in blast cells after MTX administration allows for retention of this drug, this property may explain, at least in part, the refractoriness of most patients with ANLL to methotrexate.

Adolescent↗
PubMed1991

Correction of constriction rings.

A refinement in the correction of deep and shallow constriction rings, in which subcutaneous fat and fascial flaps are advanced into the defect to prevent recurrent contour deformities, is presented. A straight-line dorsal closure is preferred, with Z-plasties placed along the side of the digits, forearm, or arm. Long-term follow-up is presented in 58 patients with 116 constriction rings corrected by either traditional serial Z-plasties of skin (n = 61 rings) or this new method of contour correction (n = 55 rings). Specific correction of soft tissue is recommended when tissue is available.

Adipose Tissue↗