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Biomedical subjects

R Tsang

Publications and source records attributed to R Tsang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.

Records of 73 patients with medullary thyroid cancer were reviewed to assess prognostic factors and the role of external beam radiation therapy. Patients were treated between 1954 and 1992. The median age was 49 years (range 15-85), M:F ratio 1.6:1, and the median follow-up was 7.9 years. (2.5-34.6). The primary tumor size was < 1 cm in 10%, 1-4 cm in 53%, and > 4 cm in 37%. Multifocality was noted in 32%, and 23% had metastasis at presentation. Eight patients presented with inoperable tumors, 40% had gross, and 37% microscopic residual disease postthyroidectomy. Extraglandular extension was present in 56%, and 74% had pathologically involved lymph nodes. Treatment was by total or near total thyroidectomy in 41 patients; 37 had a lymph node dissection. Forty-six patients were irradiated, the dose of radiation ranging from 20 to 75.5 Gy; median was 40 Gy, treatment time median was 28 days and the median number of fractions was 20. The overall cause specific survival (CSS) was 70% and 57% at 5 and 10 years, respectively. In a univariate analysis, the following factors predicted for lower CSS: age as a continuous variable (p = 0.003), male gender (p = 0.008), presence of distant metastasis (p < 0.0001), lymph node involvement (p = 0.03), gross residual disease (p < 0.0001), tumor size > 4 cm (p = 0.05), extraglandular invasion (p < 0.004), vascular invasion (p = 0.007), diarrhea (p < .0007), and abnormal postoperative calcitonin (p = 0.02). On multivariate analysis only two factors were significant: the presence of extraglandular invasion, and postoperative gross residual disease. There was no difference in local/regional relapse free rate between patients receiving external radiation and those that did not, but in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse.

Adolescent↗
PubMed1996

Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma.

BACKGROUND: Patients with Hodgkin's disease (HD) and intermediate or high-grade non-Hodgkin's lymphoma (NHL) who fail to achieve a complete remission (CR) with standard induction therapy have a poor prognosis with conventional-dose salvage therapy alone. We examined the role of subsequent intensive therapy and autologous bone marrow transplantation (ABMT) in patients who demonstrated a response to conventional-dose therapy. PATIENTS AND METHODS: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwent intensive therapy with etoposide (60 mg/kg), intravenous melphalan (160-180 mg/m2) followed by infusion of unpurged autologous bone marrow and/or blood cells. All patients had advanced stage or bulky disease at diagnosis and failed to achieve a CR after an anthracycline-containing front-line chemotherapy regimen (NHL) or ABVD or equivalent regimen (HD). Patients who achieved a CR after involved-field radiotherapy were excluded. All patients demonstrated sensitivity to conventional-dose salvage treatment before advancing to intensive therapy and ABMT. RESULTS: The CR, partial response (PR) and overall response rate (RR) following ABMT for HD patients was 48%, 17% and 65%, respectively. At a median follow-up of 35 months, the predicted three-year overall survival (OS) is 51% (95% CI: 44%-60%) and event-free survival (EFS) is 34% (95% CI: 26%-54%). For patients with NHL, the CR, PR and RR were 68%, 9% and 77%, respectively. At a median follow-up of 28 months, the predicted three-year OS is 51% (95% CI: 35%-66%) and EFS is 39% (95% CI: 21%-57%). CONCLUSIONS: Intensive therapy with etoposide and melphalan followed by ABMT results in prolonged survival in selected patients with lymphoma who fail to achieve a complete remission to front-line chemotherapy. Based on our previous studies of outcome to conventional-dose salvage chemotherapy, we estimate that of all patients failing induction therapy, 28% with HD and 15% with NHL will be event-free at three years after ABMT.

Adolescent↗
PubMed1996

The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport.

The effect of gastric inhibitory polypeptide (GIP) and the related glucagon-like peptides-1 and -2 (GLP-1 and GLP-2) on jejunal basolateral membrane glucose transport was investigated to determine if the upregulation produced by luminal hexoses could be explained by the release of one or more of these peptides. Luminal perfusion of the rat jejunum for 4 h, under pentobarbital sodium anesthesia, with 100 mM D-glucose produced a significant increase in plasma GIP levels. Vascular infusion of saline containing 100-800 pM GIP also increased the maximal transport rate for carrier-mediated glucose uptake in jejunal basolateral membrane vesicles. The effect of vascular 400 pM GIP was maximal after 1 h and maintained out to 4 h. The effect of luminal glucose could be blocked by preinjection with anti-GIP antibodies, whereas an antineurotensin antibody had no effect. Vascular infusion with 800 pM GLP-1-(7-36) amide had no effect, but GLP-2 (400 and 800 pM) increased the D-glucose maximal transport rate. An anti-GLP antibody was able to block the response to luminal glucose.

Animals↗
PubMed1996

Effect of cholecystokinin and related peptides on jejunal transepithelial hexose transport in the Sprague-Dawley rat.

An in situ dual vascular and luminal perfusion technique was used to study the effect of cholecystokinin octapeptide (CCK-8) on the transport of hexoses by the jejunum of the Sprague-Dawley rat from the lumen to the vascular bed. The lumen of the jejunum was perfused with hexoses in oxygenated Krebs buffer, while the superior mesenteric artery was infused with Krebs buffer containing Ficoll 70 as a plasma expander. CCK-8 (0.8-8 pM) in the vascular infusate selectively reduced hexose transport in a dose-dependent manner by 20-47%, although having no effect on L-glucose or L-leucine absorption. Vascular tetrodotoxin did not block CCK-8 inhibition, whereas a specific CCK-A receptor antagonist, lorglumide, did. The CCK-B receptor agonist cholecystokinin tetrapeptide had a small effect on hexose absorption, whereas somatostatin-14 and -28 had no effect. These results suggest that cholecystokinin can decrease intestinal absorption of hexoses in the small intestine, acting via CCK-A-type receptors.

3-O-Methylglucose↗
PubMed1996

Common clinical manifestations of maternal diabetes in newborn infants: implications for the practicing pediatrician.

Even though perinatal mortality of infants of diabetic mothers has decreased remarkably in recent years and now approaches that of the general population, these infants still face a multitude of potential complications and the propensity for increased morbidity, both in utero and postnatally. Many of these complications are clearly related to the metabolic status of the diabetic mother. Increasing awareness among insulin-dependent diabetic patients and health providers of the need for glycemic control and the ever-growing understanding of the peculiarities of diabetic pregnancies eventually should combine to provide the best possible outcome for these infants.

Abnormalities, Multiple↗
PubMed1996

Nicotinamide as a repair inhibitor in vivo: studies using single and fractionated X-ray doses in mouse skin and kidneys.

Inhibitors of adenosine diphosphoribosyl transferase, like nicotinamide, 3-aminobenzamide and other analogues, can inhibit repair of radiation-induced sublethal and/or potentially lethal damage in some in vitro systems. Therefore, we have tested the effect of nicotinamide on repair parameters in vivo in two rodent normal tissues. In skin, the sensitivity to dose fractionation (1, 2, 5 or 10 X-ray fractions in 5 days) was monitored by defining the alpha/beta ratio in the presence or absence of nicotinamide (0.5 mg g-1) in air or carbogen. Pre- and postirradiation sensitization were investigated using an X-ray schedule of 5 fractions/5 days in carbogen alone or combined with nicotinamide given 1 h before, immediately after or 8 h after irradiation. Also, changes in the steepness of the underlying X-ray survival curve for the target skin clonogens, reflected by a change in the alpha/beta ratio, were investigated using the neutron top-up design. Underlying survival curves for oxygen +/- nicotinamide were obtained over the X-ray dose range 2.5 to 25 Gy, by administering single X-ray doses and following these with single top-up doses of d(4)-Be neutrons. Finally, in mouse kidney, recovery half-times (t1/2) were obtained by determining the time-dependent disappearance of X-ray damage using a split-dose design of two 6-Gy fractions separated by an interval which varied from 0 to 48 h and followed by two top-up doses from a neutron beam. No increase in alpha/beta for epidermal damage was seen with nicotinamide alone and, although sensitization was observed when the drug was given 1 h before irradiation, no postirradiation sensitization was detected. In kidney, there was no significant difference in the proportion of total repairable damage or in the half-life of recovery between treatments given with or without nicotinamide. Therefore, no decrease in normal tissue tolerance should be observed with the use of nicotinamide in clinical radiotherapy resulting either from reduced sparing with dose fractionation or from an increase in residual damage when shortening the interfraction interval. Finally, unless repair of radiation damage in normal tissues in vivo differs markedly from that of tumors, it is unlikely that the large sensitization seen in rodent tumors at 1.5 to 2 Gy per fraction, with carbogen and nicotinamide, can be attributed to nicotinamide acting as a repair inhibitor.

Animals↗
PubMed1995

Biotinylated lipopolysaccharide binds to endotoxin receptor in endothelial and monocytic cells.

Endotoxin or lipopolysaccharide (LPS), a major cell surface component of gram-negative bacteria, which could bind to different cell types when released into the bloodstream, plays a central role in the pathogenesis of septic shock syndromes. We have established a biotinylation procedure for labeling purified LPS molecules from Salmonella minnesota R595 and Escherichia coli J5 bacteria. The biotin group was conjugated to the bacterial LPS either by chemical oxidation of the LPS carbohydrate moiety (inner core region), followed by reduction with biotin-LC-hydrazide (biotinamido hexanoyl hydrazide), or by photoactivatable cross-linking with biotin-LC-ASA [1-(4-azidosalicylamido-)-6(biotinamido)-hexane], which was randomly attached to the carbohydrate and fatty acid (lipid A) groups of the LPS. Both labeled products retained biological activity (or endotoxicity) as evidenced by coagulation of the Limulus amoebocyte lysate. To determine its ability to bind avidin/streptavidin which in turn could be conjugated with enzymatic and fluorescent probes, the biotinylated LPS was used in enzyme immunoassay, Western blot, and flow cytometry. These assays were also used to analyze the binding of LPS ligand to its counterreceptor(s) on whole cell surface, membrane fragments, and in detergent lysates from human endothelial and monocytic cells. The described biotinylated LPS probes can be applied in a wide variety of techniques in receptor biochemistry, immunohistochemistry, and molecular cell biology.

Avidin↗
PubMed1995

Biochemical modulation of iododeoxyuridine by N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2,6-diaminobenz[cd]indole glucuronate (AG-331) leading to enhanced cytotoxicity.

Inhibition of thymidylate synthase (TS) may increase incorporation of thymidine analogues into DNA, leading to increased inhibition of colony formation in tumor cells. We have reported previously that TS inhibition by N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6,-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid (ICI D1694 or Tomudex), a folate-based TS inhibitor, increases the cytotoxicity of iododeoxyuridine (IdUrd), a thymidine analogue, in MGH-U1 human bladder and HCT-8 human colon cancer cells. N6-[4-(Morpholinosulfonyl)benzyl]-N6-methyl-2,6-diaminobenz[ cd]-indole glucuronate (AG-331) differs from ICI D1694 in that it is a de novo designed lipophilic TS inhibitor, it does not require a specific carrier for cellular uptake, and it does not undergo intracellular polyglutamation. Exposure of MGH-U1 cells to 5 microM AG-331 for 24 hr decreased clonogenic survival by 30%, but almost completely inhibited TS activity. IdUrd is a cytotoxic thymidine analogue, with IC50 and IC90 values after 24-hr exposures in MGH-U1 cells of 13 and 81 microM, respectively. The combination of IdUrd and AG-331 resulted in an enhanced antitumor effect, as compared with the effect of either agent alone. The cytotoxic IC50 of IdUrd decreased from 13 to 1.5 microM, and the IC90 decreased from 81 to 5 microM with the addition of 5 microM AG-331. Biochemical studies of the combination revealed that pretreating MGH-U1 cells with 5 microM AG-331 increased IdUrd incorporation into cellular DNA by 3.8-fold. This increased incorporation was associated with a greater proportion of DNA single-strand breaks than observed with either agent alone, and the combination of 5 microM AG-331 plus IdUrd produced up to a 2.5-fold increase in DNA single-strand breaks as compared with IdUrd alone. The effects of AG-331, IdUrd, and the combination of IdUrd and AG-331 on the colony-forming ability of normal human bone marrow CFU-GM cells was determined as a measure of myelosuppression. The combination of IdUrd and AG-331, at the same concentrations as those used in the MGH-U1 cells, produced a wider therapeutic index relative to that of IdUrd alone, and the therapeutic index for the combination was 6.5, as compared with 4.0 for IdUrd plus ICI D1694 in previous studies from this laboratory. These observations suggest that the combination of IdUrd and AG-331 may enhance antitumor effects with minimal myelosuppression in vivo.

Antimetabolites, Antineoplastic↗
PubMed1995

Possible limited bone loss with suppressive thyroxine therapy is unlikely to have clinical relevance.

To determine the effect of suppressive doses of thyroxine (T4) on bone mass, we studied 50 women on suppressive doses of T4 for 3-27 years (mean of 11 years). Twenty-five had nontoxic goiter and 25 had well-differentiated thyroid carcinoma. Fifty controls were matched for age, menopausal status, and body mass index. Bone mineral density (BMD) was measured in the lumbar spine (LS), femoral neck (FN), trunk (TK), and extremities (EXT) by dual-energy X-ray absorptiometry (DXA). In addition, the trunk area was measured by neutron activation analysis and recorded as a calcium bone index (CaBI). Twenty-one patients were restudied with DXA measurements at a mean of 1.5 +/- 0.5 (1 SD) years. The total population of 50 patients showed no difference in bone mass from controls. In patients with nontoxic goiter, there was no evidence of any loss in bone mass. Cancer patients showed insignificant reductions of 2-5% in BMD of LS, FN, and TK and a significant 5% reduction in BMD of EXT, compared to controls, and a 12% reduction in CaBI compared to goiter patients. Cancer patients had a slightly higher (p < 0.001) mean daily dose of T4 than goiter patients (0.23 vs 0.15 mg/day) but had a similar degree of TSH suppression. BMD and CaBI values did not correlate with free T4 index) with the daily T4 dose, accumulative dose, or with duration of T4 therapy. There were no significant changes in bone mass in either goiter or cancer patients restudied after a mean of 1.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Influence of vascular and luminal hexoses on rat intestinal basolateral glucose transport.

The influence of luminal and vascular hexoses in rats on glucose transport across the jejunal basolateral membrane (BLM) was measured using isolated membrane vesicles prepared from infused animals. In vivo vascular infusions of glucose produced an increase in glucose transport across BLM vesicles. Sucrose, mannose, galactose, and fructose had no significant effect. Plasma glucose concentrations were unaffected by galactose and sucrose vascular infusions, while mannose and fructose produced a modest rise, and glucose increased plasma glucose to 20 mM. Insulin release was significantly increased by vascular infusion of glucose and fructose, while mannose produced only a small sustained rise. Sucrose and galactose had no effect. Perfusion through the lumen of the rat jejunum in vivo, for up to 4 h, with glucose, fructose, sucrose, or lactate (100 or 25 mM) produced a significant increase in the maximal rate of glucose transport (up to 4- to 5-fold) across BLMs. Galactose and mannose had no effect. Luminal glucose perfusion produced a small nonsignificant increase in glucose inhibitable cytochalasin B binding to BLM vesicles, and no change was seen in the microsomal pool of binding sites. The abundance of GLUT2 in the jejunal BLM, as determined by Western blotting, was unaffected by luminal perfusion of 100 mM glucose for 4 h. Fructose almost completely inhibited the carrier-mediated uptake of glucose in control and upregulated jejunal BLM vesicles. These results are discussed in relation to the physiological role of the upregulation of GLUT2 activity by luminal and vascular hexoses.

Animals↗
PubMed1993

Squamous cell carcinoma of the lip: analysis of the Princess Margaret Hospital experience.

We reviewed 117 patients with squamous cell carcinoma of the lip who were treated at the Princess Margaret Hospital between 1976 and 1985. Ninety-eight cancers arose from the lower lip, 18 from the upper lip and 1 from the commissure. Two patients had lymph node metastases at presentation. Sixty-one patients were treated with radiation therapy following a biopsy, 28 underwent surgery followed by post-operative radiation, and 28 had surgery alone. With a median follow-up time of 5.4 years, the 5-year actuarial overall and cause-specific survival rates were 81% and 99%, respectively. Local failure developed in 4 patients after radiation treatment, 3 of whom were salvaged by surgery. Six patients developed regional metastases after initial treatment, 4 of whom were salvaged with surgery and/or radiotherapy. Two patients died from lip cancer. After a univariate analysis, the only factor which predicted for nodal failure was T stage of the primary lesion, with a 4% risk of nodal failure for T1 lesions vs. 20% for T2/3 lesions (p = 0.03). No other patient, tumour or treatment variables influenced loco-regional control or survival in a statistically significant manner. Cosmetic and functional outcome were evaluated in 8 patients whose radiation treatments were administered 13 years ago. No patients had compromised lip function, and the majority had minimal cosmetic sequelae from their radiation therapy. Based on the excellent results of this review, we would continue to recommend radiation therapy as an effective treatment modality for patients with lip cancer because of the ease by which the entire tumour can be encompassed whilst maintaining excellent cosmetic and functional outcome.

Adult↗
PubMed1992

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.

Adolescent↗
PubMed1989

Insulinoma complicating pregnancy presenting with hypoglycemic coma after delivery: a case report and review of the literature.

The incidence of insulinoma in pregnancy is unknown. All of the eight previously reported cases presented in the first trimester with hypoglycemic episodes. We report a case of a 24-year-old multigravida who presented with hypoglycemic coma after delivery. We discuss the possible protective role of pregnancy counter-regulatory hormones in keeping the patient asymptomatic until delivery, and present the difficulties in both diagnosis and differential diagnosis of insulinoma in the peripartum period. Chronic hypoglycemia in pregnancy has been associated with intrauterine growth retardation and increased perinatal mortality. However, this infant was at the 90th percentile for body weight, suggesting that asymptomatic maternal hypoglycemia had not been present during the gestation. Insulinoma complicating pregnancy, though very rare, should now be included in the differential diagnosis of postpartum hypoglycemia.

Adenoma, Islet Cell↗
PubMed1988

In vitro effects of magnesium on ionized calcium concentration in serum.

Hypermagnesemic neonates, born to mothers receiving magnesium (Mg) sulfate before delivery, have elevated ionized calcium (iCa) concentrations in serum. We hypothesized that this elevation might be due in part to competition of Mg with calcium (Ca) bound to proteins or complexed to salts. Serum and its ultrafiltrate were obtained from five placental blood samples. The iCa concentration was measured in both serum and its ultrafiltrate at five incremental Mg concentrations (delta Mg) up to 6.58 mmol/L. In both serum and ultrafiltrate, incremental iCa (delta iCa) correlated significantly with delta Mg. By multiple regression analysis, delta ica in serum correlated positively with delta Mg in serum and negatively with albumin concentration in serum. Thus, iCa concentration in serum is increased in vitro by hypermagnesemia; it appears that Mg may compete with Ca bound to albumin and complexed to salts.

Blood↗
PubMed1987

Eicosanoid formation by mammalian intestine. Effects of some intestinal secretagogues.

Intestinal tissues of man, rat, mouse, guinea-pig and rabbit were preincubated with laxatives, homogenised, and incubated with [14C]arachidonic acid. After extraction into chloroform, the eicosanoids were separated by thin layer chromatography. Metabolism of [14C]arachidonic acid into prostaglandins (PGs), and the lipoxygenase products LTB4 and 5-HETE, was stimulated by ricinoleic acid (100 micrograms/ml) or phenolphthalein (100 micrograms/ml), and to a lesser extent by picosulphate (125 micrograms/ml) and sulfosuccinate (200 micrograms/ml). Mannitol (500 micrograms/ml) had no effect. Indomethacin (1 microgram/ml) inhibited the stimulation of PG formation. The dual pathway inhibitor BW755C (1 microgram/ml) reduced the formation of prostaglandins, LTB4 and 5-HETE. In some experiments on rat colon, prostanoids were separated from lipoxygenase products, characterised by their chromatographic mobility and quantitated (relative amounts PGE2 greater than PGF2 alpha greater than TXB2 greater than PGD2). Their formation was enhanced by ricinoleic acid (100 micrograms/ml) and inhibited by either indomethacin or BW 755C (1 microgram/ml). The present results indicate that mammalian isolated gut tissue can convert [14C]arachidonic acid into both cyclo-oxygenase and lipoxygenase products, and support the suggestion that eicosanoids may participate in the laxative effect of some secretagogues.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Comparison of reverse transcriptase assay with the Retro-Tek viral capture assay for detection of human immunodeficiency virus.

The reverse transcriptase (RT) assay for human immunodeficiency virus (HIV) is tedious, expensive, and nonspecific for HIV activity. Because the Retro-Tek viral capture assay (VCA) (Cellular Products, Inc., Buffalo, NY) is relatively quick, inexpensive, and specific for HIV antigens, we compared the sensitivity and specificity of the two assays in a blinded fashion to see if the VCA could replace the RT assay. Specifically, peripheral mononuclear cells were cocultured from 11 Western blot-positive acquired immunodeficiency syndrome (AIDS) patients. The culture supernatant fluids were tested every 4-7 days for at least 28 days by VCA for HIV antigens, and by RT assay for retrovirus activity. Ten seronegative healthy donors with no risk factors were also cocultured and tested. Seven (64%) of 11 AIDS patients were positive by VCA and confirmed by RT assay in each instance. Concordance between VCA and RT assay was 100% in each patient. Time-to-positive detection was 7-28 days for both assays. Once a culture became positive by either assay, subsequent culture supernatant fluids remained positive by both assays until the culture was discarded, usually at day 28. The ten healthy seronegative donors were negative by both assays. These results suggest that the VCA is preferable to the RT assay for detection of HIV.

Acquired Immunodeficiency Syndrome↗