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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 235 records · Page 13Linked to original sources

In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis.

OBJECTIVE: To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis. DESIGN: Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis. SETTING: University hospital in Hong Kong. SUBJECTS: 21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis. MAIN OUTCOME MEASURES: Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading. RESULTS: Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01). CONCLUSIONS: Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia.

Adult↗

Subxiphoid partial pericardiectomy with or without sclerosant instillation in the treatment of symptomatic pericardial effusions in patients with malignancy.

Twenty-two patients with malignant pericardial effusions were treated with subxiphoid partial pericardiectomy between 1984 and 1989. Thirteen patients also had a sclerosing agent instilled intrapericardially. Tamponade was relieved by pericardiocentesis before administration of general anesthesia. In 18 patients (82%), the effusions were controlled for longer than 30 days, and two patients died before 30 days without effusion. There were two recurrences at 1.5 and 7 months. There was one death due to hemorrhage from a laceration in a heavily infiltrated pericardium, and one patient had persistent dyspnea after the procedure. Complications included transient atrial arrhythmias (two patients), chest pain after sclerosant instillation (three patients), and fever greater than 37.5 degrees C after sclerosant (five patients). The survival range was 0.1 to 18 months (median, 5 months). Subxiphoid partial pericardiectomy with or without intrapericardial sclerosant is a safe and efficacious treatment for malignant pericardial effusions.

Adult↗

Pregnancy outcomes in primigravid women aged 35 years and over in South Australia, 1986-1988.

The South Australian perinatal data collection for 1986-1988 was used to compare the characteristics and outcomes of singleton pregnancies in 515 primigravid women aged 35 years and over with those in 4175 younger primigravid women aged 20-29 years. Notable differences observed were a higher prevalence of medical, obstetric and labour complications and assisted deliveries in the older group. Breech presentations were almost twice as common in the older women, as were caesarean sections. Only 27% achieved a spontaneous vaginal delivery. The mean duration of hospital stay for the older women was longer for both vaginal and caesarean deliveries. However, although their babies were more likely to be premature or of low birthweight, the perinatal mortality rate was not significantly increased and the great majority of older primigravid women managed by modern obstetric methods can expect a good pregnancy outcome.

Adult↗

Predominant rearrangements of the T cell receptor beta-chain gene in blood lymphocyte populations stimulated with autologous tumor cells suggest clonal T cell expansion in two of fourteen cases.

T cell responses against autologous tumors with samples from patients with a variety of tumors were examined. The abilities of T lymphocytes to lyse the autologous tumor cells were analyzed after short-term mixed lymphocyte/tumor cell cultures (MLTC). Southern blot analysis was used to evaluate whether particular rearrangements of the TCR beta-chain gene predominate in these cultures. Tumor specific lysis could be induced in a proportion of the mixed cultures. In two cases enrichment of T lymphocytes with similar TCR beta-chain gene rearrangements was detected after repeated stimulations with autologous tumor cells.

Blotting, Southern↗

Teenage pregnancy in South Australia, 1986-1988.

Teenage pregnancies accounted for 6.0% of confinements and 24.8% of legal abortions in South Australia in 1986-1988. The teenage pregnancy rate has declined by 28.5% since the early 1970s, associated with a 52.6% decline in the confinement rate. The abortion rate rose in the 1970s but fell slightly in the 1980s; nearly half the teenage pregnancies now end in legal abortion: abortion was a more likely pregnancy outcome for younger teenagers and for teenagers resident in metropolitan areas. Compared with women confined in their twenties, confined teenagers were more likely to be single, primigravid and Aboriginal, to have few antenatal visits and to have a medical or obstetric complication during their pregnancy. They were less likely to have an induction of labour or an elective Caesarean section. They had higher frequencies of preterm deliveries (8.9%) and low birth-weight babies (9.3%). The youngest teenagers had the most risk factors and the worst outcomes. In the small group of Aboriginal teenagers aged 16 years and under, about a third of the babies were low birth-weight or premature and one in 12 babies was a perinatal death. Comparison of singleton pregnancies of teenagers with women in their twenties all of whom were single, Caucasian and primigravid, with 7 or more antenatal visits, showed similarity in outcomes. This suggests that being teenage is not in itself a risk factor. Continued support and extension of teenage counselling and antenatal care services is essential.

Adolescent↗

Early and late surgical complications of subtotal oesophagectomy for squamous carcinoma of the oesophagus.

The use of stapling devices in oesophagogastric anastomosis has markedly reduced the incidence of anastomotic leakage, but may be associated with a higher incidence of stricture formation. The purpose of this study was to review the incidence, morbidity, management and outcome of leakage and stricture in patients undergoing subtotal oesophagectomy. Seventy-two consecutive patients with proven squamous carcinoma of the thoracic oesophagus who underwent subtotal oesophagectomy and gastric pull-up with stapled anastomosis were studied. Thirty-six patients had the anastomosis constructed using the EEA size 25 mm circular stapler (group 1). Thirty-six patients had oesophagogastric reconstruction using the EEA size 28 mm circular stapler (group 2). Data were collected prospectively, but the groups were not randomized. One clinical/radiological anastomotic leak (3%) occurred using the 25 mm gun (group 1), but no dehiscence was demonstrated in group 2. There was no 30-day mortality, but two patients died before leaving hospital (overall hospital mortality rate, 3%). Early complications included anastomotic bleed, respiratory failure, chylothorax, transient bilateral recurrent laryngeal nerve palsy, and severe chest infections. After surgery, the patients were followed up at 1 month, at 3 months and then at 3-monthly intervals up to 1 year. Stricture formation occurred in 11 patients in group 1 and only four patients in group 2 (chi 2 test P less than 0.05). All benign strictures presented within 6 months of surgery. These strictures were satisfactorily treated by endoscopic dilatation. Two patients (one from each group) suffered anastomotic recurrence of their tumour at 8 and 10 months respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Expression of a T cell receptor gamma-chain (V gamma 1.1J gamma 4C gamma 4) transgene in mice influences T cell receptor ontogeny and thymic architecture during development.

In this report, we have characterized T cell ontogeny in mice transgenic for the V gamma 1.1J gamma 4C gamma 4 (TcR gamma 4) TCR chain gene by analyzing the T cell surface phenotype and microarchitecture of the transgenic lymphoid organs during development. The first wave of V gamma 3J gamma 1C gamma 1 TCR+ thymocytes that appear in the thymus at day 14 of gestation were virtually absent in the TCR gamma 4 transgenic mice. However, comparable levels of total gamma delta+ thymocytes were present in the TCR gamma 4 transgenic mice, suggesting that these thymocytes expressed a transgene receptor. In addition, the appearance of significant numbers of TCR alpha beta+ T cells occurred earlier (day 17 of fetal development) in the transgenic thymus. After birth, thymuses from TCR gamma 4 transgenic mice were characterized by a consistent increase in the number of TCR gamma delta+ thymocytes and a transient increase (between 2 and 4 wk of age) in the absolute number of TCR+ thymocytes (2- to 4-fold) compared with thymuses from normal mice. Immunohistologic analysis of the thymus, spleen, and lymph nodes from 2-day and 3-wk-old transgenic mice showed significant differences to controls only in regions harboring mature, functional T cell subsets which may be the result of bidirectional signaling between lymphocyte subsets (influenced by transgene expression) and stromal elements. The results demonstrate that striking differences, leading to the earlier appearance of mature T cells, occurred in both the fetal and neonatal thymus and periphery of mice that expressed a TCR gamma 4 transgene. These findings are consistent with the hypothesis that expression of the TCR gamma 4 chain gene, early in ontogeny, has a positive influence on the development of the T cell compartment.

Animals↗

Pregnancy and perinatal factors associated with persistently low Apgar scores: an analysis of the birth records of infants born in South Australia.

This study included all newborns with Apgar scores below seven at one minute after birth who were born in 1986 and whose births were notified to the South Australian Perinatal Statistics Collection. Univariate comparisons were made of the demographic, obstetric and pregnancy outcome characteristics of the 301 newborns whose Apgar scores remained below seven at five minutes and the 3165 whose scores recovered to seven or more. The results provide a general risk profile of the 301 newborn infants who perform poorly at birth, as indicated by a low Apgar score at both one and five minutes. Adverse risk factors identified in this study were similar to those for intellectual disability (mental retardation) and cerebral palsy in South Australia. It is suggested that persisting low Apgar scores, when combined with the other risk factors demonstrated in this and previous studies, would provide more reliable prognostic information than would Apgar scores alone. The study also shows that the majority of infants with low Apgar scores at one minute scored seven or better at five minutes. This demonstrates, that although a low one minute Apgar score has value in identifying newborns in need of immediate attention, it must be supplemented by the five minute score's stronger association with perinatal morbidity.

Apgar Score↗

Early controlled active mobilization with dynamic splintage for treatment of extensor tendon injuries.

Early controlled active mobilization with a dynamic splint for treatment of repaired extensor tendon injuries was studied prospectively. Postoperative dynamic splintage started on the third postoperative day and involved elastic band extension and active flexion of the digits. Mobilization of the digits within the splint was done immediately under supervision. Range of motion was stepped up progressively and splintage was stopped after 5 to 6 weeks. Thirty-eight patients with 48 digits were reviewed. The average follow-up was 6.7 months (range, 4 to 10 months). Injuries involving the fingers showed an average final total active motion of 229 degrees (range, 95 to 270 degrees), whereas injuries involving the thumb was 118 degrees (range, 78 to 150 degrees). Lesions distal to the knuckles (zones II, III, IV) showed the worst results with an average total active motion of only 188 degrees (range, 95 to 270 degrees). The duration out of work was 8.5 weeks (range, 4 to 25 weeks). There was no infection or acute tendon rupture. One patient required reconstruction of a persistent button-hole deformity; two required tenolysis and capsulotomy. Of the six unsatisfactory results with poor total active motion, four had injuries distal to the metacarpophalangeal joint, three of which were crushing injuries.

Adolescent↗

Studies on prostaglandin and luteolysis in the pseudopregnant rabbit.

The ability of pulsatile infusion of prostaglandin F2 alpha (PGF2 alpha) or 13, 14-dihydro prostaglandin F2 alpha to induce corpus luteum regression was examined in the pseudopregnant rabbit. Each prostaglandin was infused in 5, 1-hour pulses (1 per 6 hours) during a 25-hour period starting day 9 or 10 of pseudopregnancy. Although both prostaglandins were capable of inhibiting progesterone secretion, pulse administration was no more effective than continuous infusion. To determine if PGF2 alpha was released into the systemic circulation during spontaneous luteolysis, starting day 12 of pseudopregnancy serial blood samples were collected every 90 minutes from the jugular vein. Prostaglandin F levels remained steady (1-2 ng/ml over the collection period with no apparent increase associated with functional luteolysis. Although prostaglandins may be involved in luteolysis in the rabbit, the present results suggest that it is unlikely that PGF2 alpha by itself is responsible for the sustained fall in progesterone secretion at the end of the pseudopregnancy.

Animals↗

Human T cell receptor V alpha gene polymorphism.

The T cell receptor (TcR) is a heterodimer composed of an alpha,beta- or a gamma,delta-chain. The receptor is expressed on the cell surface in association with the CD3 complex, which in turn is composed of at least four chains (gamma, delta, epsilon, and zeta). In this review, we will summarize the recent findings on the genomic organization of the four T cell receptor genes, and the polymorphisms detected in the variable regions of these genes.

DNA Probes↗

Oxidative damage in murine tumor cells treated in vitro by recombinant human tumor necrosis factor.

Treatment of three murine tumor cell lines, L929, P388, and Pan-02, in vitro with recombinant human tumor necrosis factor (rhTNF) produced evidence of oxidative damage as measured by (a) increases in intracellular glutathione levels, (b) the formation of intracellular oxidized glutathione and (c) the formation of thymine glycols in DNA. L929, the most sensitive of the three cell lines to the cytotoxic activity of rhTNF, had the lowest total glutathione content and was observed to have the highest levels of oxidized glutathione and thymine glycol formation. In addition, the radical buffering capacity of these cells was significantly compromised within 7 h of treatment with rhTNF. The P388 and Pan-02 cell lines, with total glutathione levels about 50-fold higher than L929, also showed evidence of oxidative attack, although to a lesser extent than L929. The radical buffering capacity of these cell lines was not altered by rhTNF treatment. A rhTNF-resistant subline of L929 (L929r), produced by successive passaging in vitro in the presence of TNF, increased its glutathione and oxidized glutathione levels in response to a subsequent rhTNF challenge. Meth A, a cell line resistant to rhTNF in vitro but not in vivo, showed no evidence of oxidative damage following rhTNF treatment, despite having a low radical scavenging capacity and a sensitivity to H2O2. The results with Meth A suggest that the interaction of rhTNF with this cell line does not occur in the same manner as the other cell lines, perhaps due to receptor differences or to some type of "uncoupling" of the signal-response network between the TNF receptor and a putative secondary messenger(s). These results are consistent with the hypothesis that: (a) the mechanism of action of rhTNF involves the production of oxidative damage, including damage to the DNA; (b) the sensitivity to rhTNF in vitro is related to the radical scavenging capacity of the cell; and (c) cells can respond to rhTNF challenge by increasing their free radical scavenging capacity.

Animals↗

The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action.

The intracellular glutathione levels of two human tumor lines and seven murine tumor lines were determined in order to investigate the role of oxidant injury in tumor cell sensitivity to human rTNF (rhTNF). Correlations were found between high intracellular glutathione levels and in vivo tumor resistance to rhTNF, and on the other hand, low glutathione levels and rhTNF sensitivity. The transplantable murine fibrosarcoma, Meth A, a TNF-sensitive line in vivo, was less sensitive to rhTNF and host toxicity was reduced when the hosts were pretreated with uric acid, a major reactive oxygen scavenger in humans and certain other primates. Conversely, pretreatment of the tumor-bearing hosts with DL-buthionine-(S,R)-sulfoximine, an inhibitor of GSH biosynthesis, resulted in an increased sensitivity of Meth A to rhTNF. This effect was not limited to tumor-bearing mice, as rats pretreated with diethyl maleate, a compound which irreversibly binds glutathione, were more sensitive to rhTNF toxicity than control rats. On the other hand, pretreatment with N-acetyl cysteine, an oxidant scavenger, reduced the toxicity of rhTNF treatment in rats. The data are consistent with the hypothesis that tumor cell sensitivity to rhTNF in vivo is dependent on its capacity to buffer oxidative attack. In addition, host toxicity is also related to the production of reactive oxygen species. Activated effector cells such as granulocytes and macrophages are hypothesized to produce most of this damage by their respiratory burst and oxidant release, although the direct action of rhTNF may also contribute to oxidative injury in vivo.

Acetylcysteine↗

Sequence dependence of administration of human recombinant tumor necrosis factor and interleukin-2 in murine tumor therapy.

Simultaneous administration of recombinant human tumor necrosis factor (rhTNF) and interleukin-2 (rhIL-2) has been shown to block tumor take in murine models. We investigated the effects of sequence and schedule of administration as a function of tumor burden with two tumor models (B16 and Meth A). rhTNF followed by rhIL-2 had extraordinary antitumor efficacy, but rhIL-2 followed by rhTNF was much less effective. Sequential rhTNF/rhIL-2 therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in complete tumor regression, whereas simultaneous therapy resulted in only reduced growth rate. Experiments with genetically immunodeficient mice suggested that T cell factors may be required for synergistic antitumor activity.

Animals↗

Pregnancy and birth risk factors for intellectual disability in South Australia.

It is generally accepted that developmental handicaps can often be minimized through early detection and intervention. For this reason, it is normal practice in many hospitals to follow-up and screen infants who present at birth with established risk factors. Clinical judgement will always be important when selecting children for follow-up. However, as hospital data systems improve, automated systems could be developed for listing children potentially "at risk". Where initial clinical decisions not to follow-up individual children prove to be at odds with this automated output, the individual child could be re-assessed clinically. This process could increase the level of quality control. An initial risk-factor model for intellectual disability has been developed, based on the South Australian Perinatal Statistics Collection, for use in this context.

Australia↗

Allelic T-cell receptor alpha complexes have little or no influence on susceptibility to type 1 diabetes.

We performed a multiple-affected-sib study to determine if T-cell receptor alpha-chain alleles affect susceptibility to insulin-dependent diabetes mellitus. Restriction fragment length polymorphisms were used to follow the segregation of allelic T-cell receptor alpha complexes within the families. The segregation of T-cell receptor alpha alleles in 29 multiplex families revealed no significant tendency for affected sibs to share T-cell receptor alpha-chain alleles more often than would be expected by chance alone (p greater than 0.2). In contrast, the same type of analysis for HLA alleles easily detected the well-known linkage of insulin-dependent diabetes mellitus susceptibility to the HLA complex (p = 0.003). We suggest that the importance of HLA alleles in insulin-dependent diabetes mellitus susceptibility and the lack of importance of T-cell receptor alpha alleles result from the different strategies by which HLA and T-cell receptor molecules achieve antigen-binding diversity: multiple loci and allelic diversity in the case of HLA; combinatorial, junctional, and N-region diversity in the case of the T-cell receptor. In this paper we also describe three new restriction fragment length polymorphisms of the T-cell receptor alpha complex and a new method for testing the significance of linkage in multiple-affected-sib studies.

Alleles↗

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma.

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.

Aged↗