Biomedical subjects

W K Wong

Publications and source records attributed to W K Wong.

At least 19 recordsLinked to original sources

PubMed2001

Tubulitis after renal transplantation: demonstration of an association between CD103+ T cells, transforming growth factor beta1 expression and rejection grade.

BACKGROUND: Tubulitis is a defining feature for the diagnosis and management of acute renal allograft rejection. Lymphocytes extracted from rejecting renal tissue are known to express the alphaEbeta7-integrin (CD103), a receptor for E-cadherin expressed on epithelial cells. In this study, expression of CD103 was examined in situ in tubulitis associated with acute rejection. METHODS: Immuno-labeling detected CD8+ and CD103+ lymphocytes and E-cadherin on epithelial cells in cryostat sections from 34 diagnostic biopsy specimens and a limited number of transplant nephrectomies. CD8+ and CD103+ intratubular cells were enumerated as mean numbers per tubular crosssection and median values were compared between rejection grades as were median ratios of CD103+ to CD8+ cells. Active transforming growth factor (TGF) beta1 was quantified in paraffin sections by immunofluorescence and confocal microscopical analysis. A parallel in vitro study quantified CD103+ T cells after allospecific activation with and without exogenous TGFbeta1. RESULTS: CD8+ T cells were present in tubules and tubular interstitium in acute rejection. CD103+ T cells were restricted exclusively to the tubules. The numbers of intratubular CD8+ and CD103+ cells and the ratio of intratubular CD103+ to CD8+ cells increased significantly with tubulitis score (P values 0.005, 0.009, and 0.02, respectively). TGFbeta1 expression was wide-spread in tubules also increasing significantly with tubulitis score (P=0.034). In chronic rejection, CD103+ T cells and TGFbeta1 were present within both tubules and interstitial cell populations. The in vitro study demonstrated that addition of TGFbeta1 to activated, alloantigen-specific T cells increased the proportion of CD8+ cells that also expressed CD103. CONCLUSIONS: These data indicate that specific upregulation of the alphaEbeta7-integrin by activated, intratubular T cells in acute renal allograft rejection could be a consequence of exposure to high local concentrations of TGFbeta1. The capacity of CD103+ T cells to bind E-cadherin on tubular epithelial cells may be an important factor in the pathogenesis of specific tissue damage observed in acute renal allograft rejection.

Antigens, CD↗

PubMed2001

Treatment with a consensus peptide based on amino acid sequences in autoantibodies prevents T cell activation by autoantigens and delays disease onset in murine lupus.

OBJECTIVE: To test the hypothesis that an artificial peptide, based on an algorithm describing T cell stimulatory sequences from the VH regions of murine IgG antibodies to DNA, is an effective tolerogen in vivo in the (NZB/NZW)F1 (BWF1) mouse model of systemic lupus erythematosus. METHODS: Using proliferative T cell responses to 439 Ig peptides, an algorithm was constructed that describes the amino acid sequences likely to stimulate BWF1 T cells. Stimulatory (pConsensus [pCONS]) or nonstimulatory (pNegative [pNEG]) peptides were synthesized. Groups of 10-week-old (healthy) or 20-week-old (diseased) BWF1 mice received monthly intravenous injections of 1,000 microg of peptide or saline. Ex vivo splenic T cell responses and in vivo clinical effects were measured. RESULTS: Tolerance was induced by pCONS, but not by pNEG, with respect to ex vivo T cell proliferation and T cell help for antibodies to DNA. T cell help for IgG anti-DNA was impaired not only after T cell stimulation by pCONS but also after stimulation by some peptides from nucleosomal and Ro antigens. Treatment with pCONS significantly delayed the onset of nephritis and inhibited increases in the plasma levels of total IgG, IgG antibodies to DNA, nucleosome, cardiolipin, interferon-gamma, and interleukin-4. In contrast, antibody responses to an exogenous antigen were not impaired. Survival was significantly prolonged in both healthy and diseased mice treated with pCONS. CONCLUSION: Induction of immune tolerance in response to treatment with pCONS in autoreactive T cell helper populations is highly effective in delaying the appearance of multiple autoantibodies, cytokine increases, and nephritis in BWF1 mice, and dramatically prolongs survival. A striking effect is the ability of the peptide to tolerize T cell help for anti-DNA that is induced by multiple, structurally unrelated self antigens.

Algorithms↗

PubMed2000

Molecular characterization of human tensin.

Tensin is a focal-adhesion molecule that binds to actin filaments and interacts with phosphotyrosine-containing proteins. To analyse tensin's function in mammals, we have cloned tensin cDNAs from human and cow. The isolated approx. 7.7-kb human cDNA contains an open reading frame encoding 1735 amino acid residues. The amino acid sequence of human tensin shares 60% identity with chicken tensin, and contains all the structural features described previously in chicken tensin. This includes the actin-binding domains, the Src homology domain 2, and the region similar to a tumour suppressor, PTEN. Two major differences between human and chicken tensin are (i) the lack of the first 54 residues present in chicken tensin, and (ii) the addition of 34- and 38-residue inserts in human and bovine tensin. In addition, our interspecies sequencing data have uncovered the presence of a glutamine/CAG repeat that appears to have expanded in the course of evolution. Northern-blot analysis reveals a 10-kb message in most of the human tissues examined. An additional 9-kb message is detected in heart and skeletal muscles. The molecular mass predicted from the human cDNA is 185 kDa, although both endogenous and recombinant human tensin migrate as 220-kDa proteins on SDS/PAGE. The discrepancy is due to the unusually low electrophoretic mobility of the central region of the tensin polypeptide (residues 306-981). A survey of human prostate and breast cancer cell lines by Western-blot analysis shows a lack of tensin expression in most cancer cell lines, whereas these lines express considerable amounts of focal-adhesion molecules such as talin and focal-adhesion kinase. Finally, tensin is rapidly cleaved by a focal-adhesion protease, calpain II. Incubation of cells with a calpain inhibitor, MDL, prevented tensin cleavage and induced morphological change in these cells, suggesting that cleavage of tensin and other focal-adhesion constituents by calpain disrupts maintenance of normal cell shape.

3T3 Cells↗

PubMed2000

Optimal treatment allocation in comparative biomedical studies.

In clinical trials involving several treatment protocols, there are usually several objectives of different importance. A general method for finding an optimal design which reflects this practical need is discussed. In particular, we show that the graphical method of Cook and Wong can be applied when there are two objectives. Several illustrative examples are discussed, including multiple-objective designs for comparing several treatment groups with a placebo group.

Humans↗

PubMed2000

Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial.

OBJECTIVE: To study the clinical implications of a skin thickness score > or =20 at first visit and of softening of sclerodermatous skin in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: Skin and visceral involvement were assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD duration of SSc 10 +/- 4 months) as they entered a multicenter drug trial and again at 2 years of followup. Advent of mortality and scleroderma renal crisis (SRC) were assessed during a followup of 4.0 +/- 1.1 years (mean +/- SD). Logistic and linear regression were used to examine the relationship of baseline skin score to morbidity, mortality, and visceral involvement and the relationship of changes in skin score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline skin score > or =20 was associated with heart involvement at baseline (odds ratio [OR] 3.10, 95% confidence interval [95% CI] 1.25-7.70) and was predictive of mortality (OR 3.59, 95% CI 1.23-10.55) and SRC (OR 10.00, 95% CI 2.21-45.91) over 4 years. Multivariate linear regression demonstrated that a model with skin score at baseline (P = 0.0078) and changes in large joint contractures (P = 0.0072), tender joint counts (P = 0.0119), handspread (P = 0.0242), and Health Assessment Questionnaire disability index (HAQ-DI) (P = 0.0244) explained the change in skin score over 2 years (R2 = 0.567). Multivariate logistic regression demonstrated that the investigator's global assessment of improvement was best explained by a model with skin score and HAQ-DI (R2 = 0.455). CONCLUSION: A baseline skin score > or =20 was associated with heart involvement at baseline and predicted mortality and SRC over the subsequent 4 years. Improvement in skin score in these patients with diffuse cutaneous scleroderma was associated with improvement in hand function, inflammatory indices, joint contractures, arthritis signs, overall functional ability, and the examining investigator's global assessment of improvement.

Adult↗

PubMed2000

Relative contributions of the components of the American College of Rheumatology 20% criteria for improvement to responder status in patients with early seropositive rheumatoid arthritis.

OBJECTIVE: To evaluate factors that influence the responses defined by the American College of Rheumatology (ACR) 20% criteria for improvement in rheumatoid arthritis (RA). METHODS: ACR 20% and 50% response rates were calculated from data collected for the intervals 0-6, 0-12, and 0-24 months for 180 RA patients participating in the Western Consortium of Practicing Rheumatologists long-term observational study of early seropositive RA (mean +/- SD duration of RA at study entry 6.0 +/- 3.4 months). Analyzable cases were patients with paired data for tender and swollen joint counts plus at least 3 of the following criteria: physician's and patient's global assessments of disease activity and patient's score for pain (by visual analog scale), physical function score on the Health Assessment Questionnaire (HAQ), and levels of an acute-phase reactant. Response rates were then recalculated by 3 different methods: 1) using only cases with complete paired data for all criteria, 2) sequentially assuming no improvement in each of the 5 secondary criteria, and 3) substituting grip strength for HAQ scores. RESULTS: Using 464 paired observations for all analyzable cases, ACR 20% (50%) improvement rates were 52.6% (33.0%), compared with 55.6% (34.8%) for 365 paired observations from the cases with complete data. Decreases in ACR response rates when secondary criteria were sequentially set at "no improvement" ranged from 11.7% (pain at 0-6 months) to 1.2% (C-reactive protein at 0-12 months), but these were not statistically different by the kappa statistic. Overall numerical rankings of the relative contributions of the secondary criteria to the ACR 20% or 50% response rates were physician's global assessment, pain, HAQ, patient's global assessment, and acute-phase reactant. Only 7.8% of paired grip strength observations showed > or =20% improvement, compared with 71% of paired HAQ observations. CONCLUSION: The use of all "analyzable" cases (paired data for tender and swollen joint counts plus > or =3 of the 5 secondary criteria) increases the number of subjects and only slightly decreases the ACR response rate compared with analyses limited to cases with complete data. The contributions of the secondary criteria are not statistically different, supporting their equal weighting in the ACR definition of improvement. The ACR 20% response rates are higher when the HAQ, rather than grip strength, is used to measure physical function.

Adult↗

PubMed2000

Effects of Manduca diuresin on neonates of the tobacco hornworm, Manduca sexta.

Manduca diuresin (MD), a 30 amino acid peptide, was isolated and identified from the type IIb median neurosecretory cells in the brain of adult Manduca sexta (Blackburn et al., Biochem. Biophys. Res. Commun., 181, 927-932, 1991). The synthetic hormone stimulates water loss in the adult moth both in vitro using isolated Malphigian tubule preparations and in vivo using decapitated adult moths as bioassay animals (Blackburn and Ma, Arch. Insect Biochem. Physiol., 27, 3-10, 1994). In the present study, MD was shown to have adverse physiological effects on neonates of Manduca sexta when fed synthetic hormone-treated leaf discs. With a sustained diet of MD-treated discs, neonates exhibited symptoms of reduced food consumption and marginal weight increases. In addition to slowed growth and reduced developmental rates, a high percentage of these neonates failed to molt into second instar larvae and death usually followed shortly thereafter. This is a first report that a synthetic insect neuropeptide has shown detrimental effect on insect larvae by ingestion. The possibility of utilizing this peptide in plant protection is discussed.

Animals↗

PubMed2000

Extracellular expression, purification, and characterization of a winter flounder antifreeze polypeptide from Escherichia coli.

HPLC6 is the major component of liver-type antifreeze polypeptides (AFPs) from the winter flounder, Pleuronectes americanus. To facilitate mutagenesis studies of this protein, a gene encoding the 37-amino acid mature polypeptide was chemically synthesized and cloned into the Tac cassette immediately after the bacterial ompA leader sequence for direct excretion of the AFP into the culture medium. Escherichia coli transformant with the construct placIQpar8AF was cultured in M9 medium. The recombinant AFP (rAFP) was detected by a competitive enzyme-linked immunosorbent assay (ELISA). After IPTG induction, a biologically active rAFP was expressed. The majority of the rAFP was excreted into the culture medium with only trace amounts trapped in the periplasmic space and cytoplasm. After 18 h of induction, the accumulated rAFP in the culture medium amounted to about 16 mg/L. The excreted AFP was purified from the culture medium by a single-step reverse-phase HPLC. Mass spectrometric and amino acid composition analyses confirmed the identity of the purified product. The rAFP, which lacked amidation at the C-terminal, was about 70% active when compared to the amidated wild-type protein, thus confirming the importance of C-terminal cap structure in protein stability and function.

Amino Acid Sequence↗

PubMed2000

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Aged↗

PubMed2000

Diagnostic failures in endoscopy for acute upper gastrointestinal haemorrhage.

BACKGROUND: Oesophagogastroduodenoscopy (OGD) is the diagnostic tool of choice in acute upper gastrointestinal haemorrhage. However, the factors causing diagnostic failure are not well documented or discussed. METHODS: OGDs performed by a single surgeon for acute upper gastrointestinal haemorrhage were reviewed retrospectively for 'missed' diagnosis. RESULTS: There were nine cases (1.4 per cent) of 'missed' diagnosis in 638 OGDs performed over a 3-year period. Incomplete examination caused by a fundal pool precluded three examinations in which two Dieulafoy's lesions and one chronic gastric ulcer were later found. Other difficult examination sites were the cardia/high lesser curve (three cases), the stomal line of a gastrojejunostomy anastomosis (two) and at the junction of the first and second part of the duodenum (one). Four of the overlooked diagnoses were Dieulafoy's lesions. CONCLUSION: OGD was able to diagnose the cause of bleeding in 98.6 per cent of patients with acute upper gastrointestinal haemorrhage. The factors that caused diagnostic failure were a difficult examination site and failure to recognize lesions (Dieulafoy's).

Diagnostic Errors↗

PubMed2000

Regulation of T-cell apoptosis: a mixed lymphocyte reaction model.

Despite the capacity for antigen-specific activation and rapid clonal expansion, homeostatic mechanisms ensure that the mature immune system contains a relatively stable number of T cells. In recent years, it has become apparent that this stability is a consequence of apoptotic death of most of the specific T cells generated during an immune response. Clearly this process must be tightly regulated in order to retain sufficient T-cell progeny to mediate an effective response, whilst allowing the rapid deletion of these cells at the end of the response to prevent lymphadenopathy and cross-reactive autoimmunity. In this study, the factors that regulate the sensitivity of T cells to apoptosis were investigated in vitro after the induction of primary T-cell activation within a mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly acquire the expression of both Fas and Fas ligand (FasL) on their surface and contain high levels of the precursor form of the pro-apoptotic enzyme, caspase 8 (FLICE). However, these T cells were resistant for up to 5 days to apoptosis following the stimulation of Fas; a maximal apoptotic response was observed after 7 days. This time point coincided with a marked reduction in expression of the FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points beyond day 7, the number of viable cells in the MLR decreased further despite a reduction in the expression of FasL. However, the expression of interleukin-2 (IL-2) at these late time points was low, resulting in a decrease in expression of the anti-apoptotic protein Bcl-2. This can produce apoptosis by allowing leakage of cytochrome-c from mitochondria resulting in direct activation of the caspase cascade. In this study, it is shown that T cells are resistant to apoptosis for the first 5 days after activation as a consequence of insensitivity of the Fas pathway and the presence of intracellular Bcl-2. After between 5 and 7 days, the cells become sensitive to Fas-mediated apoptosis while retaining Bcl-2 expression. At later time points, Fas ligation is reduced but the cells respond to a decreased availability of IL-2 by reducing Bcl-2 expression; this encourages further apoptosis by allowing the direct activation of caspase enzymes.

Adult↗

PubMed2000

Significance of a positive oesophageal margin in stomach cancer.

BACKGROUND: A positive oesophageal margin is frequently encountered in total and proximal gastrectomies. It is controversial as to whether a positive oesophageal margin in gastrectomy predisposes to anastomotic dehiscence and loco-regional recurrence. Its independent impact on survival has not been fully addressed. METHODS: A retrospective review of 137 total and proximal gastrectomies for adenocarcinoma was undertaken. Independent prognostic factors were identified in a bivariate and Cox proportional hazards regression model. RESULTS: The prevalence of positive oesophageal margin was 18.2%. A positive oesophageal margin was not associated with increased anastomotic leak (8.0 vs 10.7%; P = 0.51), operative morbidity (32.0 vs 27.7%; P = 0.85) or 30-day mortality (8.0 vs 5.4%; P = 0.48) rates when compared with a negative margin. In addition, it did not predispose to anastomotic (13.0 vs 10.4%; P = 0.47) or regional (22.7 vs 24.5%; P = 0.51) recurrences. In the multivariate analysis the TNM stage and status of the oesophageal margin were the only independent prognostic factors for survival. CONCLUSIONS: A positive oesophageal margin is an independent poor prognostic factor for long-term survival in stomach cancer. All efforts should therefore be made to clear the oesophageal margin in total and proximal gastrectomies.

Adenocarcinoma↗

PubMed2000

Multiple-objective designs in a dose-response experiment.

This article is an extension of the work of Huang and Wong (1), who found dual-objective designs for models with a continuous outcome. We consider quantal dose-response experiments with a binary outcome and develop multiple-objective designs for two or more Bayesian optimality criteria. Using the logit model as an illustrative example, we construct numerically optimal designs for estimating model parameters and percentiles, with possibly unequal interest in each of the objectives. We also show that the popular equal dosage assignment rule can be a rather inefficient design for estimating model parameters under a Bayesian setup.

Bayes Theorem↗

PubMed2000

A graphical method for finding maximin efficiency designs.

We consider the problem of designing an experiment when there are two competing optimality criteria. Designs that maximize the minimum efficiencies under the two criteria are proposed along with a graphical method for finding these maximin designs.

Antihypertensive Agents↗

PubMed2000

Minimax D-optimal designs for the logistic model.

We propose an algorithm for constructing minimax D-optimal designs for the logistic model when only the ranges of the values for both parameters are assumed known. Properties of these designs are studied and compared with optimal Bayesian designs and Sitter's (1992, Biometrics, 48, 1145-1155) minimax D-optimal kk-designs. Examples of minimax D-optimal designs are presented for the logistic and power logistic models, including a dose-response design for rheumatoid arthritis patients.

Algorithms↗

PubMed2000

Results of surgical resection of oesophageal carcinoma in Singapore.

INTRODUCTION: The 5-year survival rate after resection of oesophageal cancer is still poor, reported to be between 5% to 34% in the literatures. We conducted this retrospective study to determine the prognostic factors and long-term survival rate for surgical resection of oesophageal carcinoma in Singapore. MATERIALS AND METHODS: Sixty-seven consecutive patients who underwent surgical resection of oesophageal carcinoma from January 1989 to December 1996 were reviewed. RESULTS: Majority of the patients were Chinese (94%), males (81%) with a history of dysphagia (96%), cigarette smoking (84%) and alcohol ingestion (58%). The median age at surgery was 63.6 (range 29 to 81) years. Sixty-four patients had squamous cell carcinoma of the oesophagus and 3 patients had adenocarcinoma. The lower one-third of the oesophagus was the most common site (48.6%) followed by the middle third (46%). Postoperative complications included pneumonia (43.3%), vocal cord paralysis/paresis (19.4%) and anastomotic leakage (17.9%). Thirty-day postoperative mortality was 7.5%. There was an almost equal number of patients undergoing transhiatal (34 patients) and transthoracic approach (33 patients). There was no significant difference in postoperative complications and survival outcome for both approaches. The median survival was 15.3 months after surgery. Tumour features such as depth of involvement and TNM stage were useful in predicting survival (P < 0.05, log-rank test). CONCLUSIONS: We conclude that the poor outcome of surgical resection (5-year survival rate was 18% by Kaplan-Meier survival plots) was mainly attributed to late presentation (80% patients had T3 or T4 tumour).

Adenocarcinoma↗

PubMed2000

Direct and indirect costs associated with the onset of seropositive rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To examine the direct and indirect costs of rheumatoid arthritis (RA) during the first year of disease. METHODS: As part of a longitudinal observational study, 150 patients with seropositive RA of 5.9 +/- 2.9 mo duration were recruited through the Western Consortium of Practicing Rheumatologists. Subjects completed questionnaires about health care services and resources utilized and about the number of days of usual activity lost as a result of RA during the 6 month period prior to enrolment. RESULTS: Study participants had active RA as evidenced by mean tender and swollen joint counts of 24.9 +/- 13.5 and 20.6 +/- 11.6, respectively, and moderate functional impairment reflected by a mean Health Assessment Questionnaire (HAQ) score of 1.24 +/- 0.7. The average total direct cost of RA was $200/month. Health care visits, medications, and radiographs accounted for 78% of the total direct cost, while expenditures for hospitalizations accounted for only 3.5% of the total. The average number of days of usual activity lost per month because of RA was 3.8 +/- 7.7, translating into an average indirect cost of $281/month. Of the 95 subjects who were gainfully employed prior to disease onset, 12 were disabled and 5 were on sick leave as a result of RA, corresponding to a work disability rate of 18%. Work disabled subjects reported significantly lower total household incomes and higher HAQ disability and global disease activity scores than subjects who continued working. CONCLUSION: In this group of patients with seropositive RA substantial costs, both direct and indirect, were incurred during the first year of disease.

Arthritis, Rheumatoid↗

PubMed2000

Adverse operative risk factors for perforated peptic ulcer.

INTRODUCTION: Mortality from perforated peptic ulcer still remains high as a result of more perforations in the elderly who are generally more ill. We conducted this retrospective study to determine the adverse operative risk factors for perforated peptic ulcers. MATERIALS AND METHODS: Two hundred and six consecutive patients operated for perforated peptic ulcers from 1 January 1993 to 31 December 1997 were reviewed. RESULTS: Majority (n = 194) of the patients had perforations at the pyloroduodenal region and the remaining 10 patients had perforated benign gastric ulcers. The median age at surgery was 58 years (range 18 to 91 years). Forty-four patients (21.4%) were more than 70 years old. The 30-day operative mortality rate was 10.7% (n = 22). Advanced age (> 70 years), female gender, concurrent major medical illness, perforation developed while hospitalised for other medical illnesses, prolonged perforation (> 24 hours) and preoperative hypotension (systolic blood pressure < 90 mmHg) were indicators for operative mortality by univariate analysis. By logistic regression analysis, only concurrent major medical illness, prolonged perforation and preoperative hypotension were independent adverse risk factors. The operative mortality rate for patients with 0, 1, 2 and 3 independent adverse risk factors were 0%, 11%, 30% and 88%, respectively. CONCLUSIONS: As concurrent medical illness is a non-modifiable factor and preoperative hypotension is usually resulting from treatment delay and inadequate resuscitation, emphasis should place on shortening the time to surgery as well as prompt resuscitation.

Adolescent↗