Burden of cancers attributable to modifiable risk factors in Malaysia.

BACKGROUND: This is a systematic assessment of the burden of cancers in Malaysia in 2018 using epidemiologic approach. The purpose of this study was to identify the proportion of cancers in Malaysia that were attributable to the modifiable risk factors of excess weight, alcohol intake, physical inactivity, tobacco smoking and to estimate the number of cancer cases that could be prevented if the exposure to the modifiable risk factor was reduced. METHODS: We estimated the Population Attributable Fraction (PAF) of the modifiable risk factors to cancers incidences in Malaysia. The two parameters used for the estimation were exposure prevalence from national representative surveys and the relative risk of getting the cancers from worldwide literature review. RESULTS: Among 38,426 cancer incidences in 2018 from Globocan data, we estimated that 22.2% (95% confidence interval (CI):14.9 to 29.6%) of the cancer incidences included in this study were attributable to the investigated modifiable risk factors. 39.1% (95% CI:27.2 to 49.7%) and 10.5% (95% CI:5.8 to 15.7%) of cancers in male and female respectively, were attributable to the studied modifiable risk factors. The top main cancers attributed by the risk factors were lung cancer (65.1%; 95% CI:56.4 to 72.9%), laryngeal cancer (63.6%; 95% CI:39.9 to 80.5%), and oesophageal cancer (51.5%; 95% CI:39.9 to 62.0%). For each risk factor studied across genders, tobacco smoking contributed the most (14.3%; 95% CI:9.9 to 17.3%), followed by excess weight (7.0%; 95% CI:4.1 to 10.2%), physical inactivity (1.0%; 95% CI:0.4 to 1.7%) and alcohol intake (0.6%; 95% CI:0.2 to 1.0%). CONCLUSION: Findings from this study suggests that tobacco smoking and excess weight are the two predominant factors out of the four studied risk factors for cancer cases in Malaysia. Nationwide public health prevention campaigns tailored to these risk factors are recommended. However, the other risk factors such as physical inactivity and alcohol intake shall not be neglected. PAFs are estimated based on the best available data that we have currently. Regular collection of other risk factor exposure prevalence data is vital for future analyses.

Clinics in diagnostic imaging (138). Emphysematous pyelitis.

We present the case of a 49-year-old woman with poorly controlled diabetes mellitus of ten years' duration. She presented to the emergency department with nonspecific left lower abdominal pain. Ultrasonography showed mild left renal hydronephrosis, but the cause was not demonstrated. Computed tomography (CT) showed a swollen left kidney with a mildly dilated collecting system containing gas and dense fluid, confirming the diagnosis of emphysematous pyelitis. Management consisted of emergency antegrade nephrostomy drainage and parenteral antibiotics. Subsequently, the patient made a good recovery and was well when discharged home after two weeks. Gas-forming infections of the genitourinary tract carry high mortality and morbidity, and usually occur in patients with poorly controlled diabetes mellitus. Escherichia coli is the most common microorganism. This case emphasises the importance of CT in making an early diagnosis of emphysematous pyelitis, which allows prompt treatment and improves prognosis.

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience.

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies. OBJECTIVE: To evaluate the purity, recovery and viability of CD34+ cells selected from harvested peripheral blood stem cells using the CliniMACS device, as well as to evaluate the T and B cell contents of these products. METHOD: Eight adult patients with malignant haematological diseases (5 non-Hodgkin's lymphomas in 2nd complete remission (CR) and 3 acute myeloid leukaemias in 1st CR) were mobilised with granulocyte colony-stimulating factor (G-CSF) with or without chemotherapeutic regimens. A total of nine leukaphereses for peripheral blood stem cell harvest using the Cobe Spectra cell separator (Cobe BCT Lakewood, CO) were performed. The harvested PBSC were then positively selected for CD34+ cells using the CliniMACS device (Milteny Biotech, Germany). RESULTS: A total of nine leukapheresis products from eight adults with a median pre-selection total CD34+ cell count of 282.2 x 10(6) (range 103.7 - 738.2 x 10(6)) were positively selected with CliniMACS. The median post-selection total CD34+ cell count was 99.5 x 10(6) (range 7.7 - 443.9 x 10(6)) with the median recovery was 66.0% (range 2 - 94%) and median purity of products of 79% (range 18 - 86%). The median total T cell count was reduced dramatically from 3.1 x 10(9) pre-selection to 7.9 x 10(6) post-selection. The selection did not affect the viability of selected cells that was tested with trypan blue exclusion method with a median pre and post selection viabilities of 98% (range 95 - 98%). CONCLUSION: We conclude that positive selection of CD34+ cells using magnetic separation technology by CliniMACS device results in low T-cell content stem cell with acceptable purity and recovery for autologous peripheral blood stem cell transplantation.

Improving B mode ultrasound evaluation of breast lesions with real-time ultrasound elastography--a clinical approach.

Ultrasound elastography using the extended combined auto-correlation method of tissue elasticity allows for real-time strain image visualisation using a free-hand probe with concurrent conventional B mode imaging. Four hundred and fifteen consecutive women with 550 breast lesions confirmed on B mode ultrasound were assessed with elastography using the elasticity score. There were 119 malignant and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was 98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and that for benign lesions was 2. There was good correlation with B mode BIRADS category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8-99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions with an elasticity score of 3 were malignant. Real-time ultrasound elastography is user-friendly with a high accuracy rate, thereby improving B mode ultrasound assessment.

Randomised, open label, controlled trial of celecoxib in the treatment of acute migraine.

INTRODUCTION: Migraine is a common disabling condition that results in considerable socioeconomic loss. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in acute migraine has been well-established. We compared the efficacy of the cyclooxygenase-2 inhibitor celecoxib with the NSAID, naproxen sodium, in the treatment of acute migraine. METHODS: This was a randomised, open label, controlled trial. We selected patients with a diagnosis of migraine, based on the International Headache Society revised criteria. 60 patients were randomised to either celecoxib 400 mg (30 patients) or naproxen sodium 550 mg (30 patients). Patients took the study medicine for the first acute migraine episode that occurred during the study period and reported the headache reduction based on a visual analogue score (VAS). Patients were reviewed after a month to check on VAS at one and two hours, compared to the baseline. Any side effects of the medication were also recorded. RESULTS: Of the 52 patients who completed the study, eight did not experience any headaches. The mean VAS in the celecoxib group improved significantly from baseline (6.48 +/- 1.53) to one hour (4.28 +/- 2.11) and two hours (2.24 +/- 2.57) (p-value is less than 0.0005). The mean VAS in the naproxen sodium group also improved significantly from baseline (7.30 +/- 1.66) to one hour (4.81 +/- 2.50) and two hours (2.63 +/- 2.65) (p-value is less than 0.0005). However, there was no significant difference between the magnitudes of improvement between the treatment groups. The incidence of gastric pain was significantly higher in the naproxen sodium group (p-value is equal to 0.029). CONCLUSION: In comparison with naproxen sodium, celecoxib was equally effective in relieving pain in acute migraine and caused significantly less gastric pain.

Leukoaraiosis as a predictor for mortality and morbidity after an acute ischaemic stroke.

INTRODUCTION: Leukoaraiosis (LA) is a term that defines an abnormal appearance of the subcortical white matter of the brain on neuroimaging. This study was done to evaluate the predictive value of LA in terms of mortality, disability and cognitive decline at three months post-stroke and also to identify the risk factors that are independently associated with LA in a stroke population. METHODS: This was a prospective observational study of all patients with acute ischaemic stroke who were admitted to Hospital Universiti Kebangsaan Malaysia from June to November 2004. A single observer using the pre-defined diagnostic criteria recorded the information on demography, Barthel Index and mini-mental state examination. LA was diagnosed on brain computed tomography alone. RESULTS: 60 patients were recruited into the study. Three patients (five percent) died and LA was present in 29 patients (48 percent). There was no significant association between LA and mortality (p-value equals 0.89). The independent risk factors that were associated with LA were age (odds-ratio [OR] 4.43; 95 percent confidence interval [CI] 1.28-15.27) and hypertension (OR 14.3; 95 percent CI 1.40-147.42). There was a significant association between LA with early dementia (OR 3.53; 95 percent CI 1.19-10.49). However, LA did not significantly predict any functional disability (Barthel Index is less than 60) in the study population (p-value equals 0.45). CONCLUSION: Development of LA correlates significantly with ageing and hypertension. The presence of LA can also predict early cognitive dysfunction but is not associated with functional disability at three months post-stroke.

Transverse myelopathy following intrathecal administration of chemotherapy.

Transverse myelopathy is one of the rare complications following administration of intrathecal chemotherapy. We report two cases of transverse myelopathy following administration of intrathecal methotrexate and cytarabine arabinoside. One patient was a 17-year-old Malay man who had lymphoblastic lymphoma in the leukaemic phase, while the other patient was a 40-year-old Malay man with relapsed Hodgkin's lymphoma. Both cases demonstrated variability in onset of symptoms, clinical progression and final outcome from the complication.

Short QTc in epilepsy patients without cardiac symptoms.

Epilepsy patients have a higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality for these patients. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many previous studies. This study compared the QT interval in epilepsy patients and normal controls, and identified the factors that affected the QT interval. Standard 12-lead ECGs were recorded from 70 consecutive epilepsy patients from the neurology clinic of HUKM and 70 age, race and gender matched controls. The mean QT interval corrected for heart rate (QTc) was calculated and compared. The mean QTc among the epilepsy patients was 0.401 +/- 0.027s. It was significantly shorter than the QTc (0.420 +/- 0.027s) in the control group (p<0.0005). Thirty five epilepsy patients (50%) and 17 matched controls (24.3%) had a mean QTc shorter than 0.40s (p=0.001). Among the epilepsy patients, the mean QTc did not significantly differ between patients in the duration (F=0.836, p=0.438) of the epilepsy, frequency (F=0.273, p=0.845) and types of seizures (p=0.633). There was no significant difference in the mean QTc between the epilepsy patients on different number of antiepileptic agents (F=0.444, p=0.643). Patients with cryptogenic epilepsy had a mean QTc of 0.392 +/- 0.029s, which was significantly shorter than patients with symptomatic epilepsy (QTc = 0.410 +/- 0.027s, p = 0.015). The mean QTc of the same subjects showed no significant interobserver difference (p=0.661). This study, for the first time, demonstrates that epilepsy patients have a significantly shorter QTc than controls, particularly in the subgroup of patients with cryptogenic epilepsy.

Molar pregnancy and glomerulonephritis.

A 17-year-old, sexually active, single, nulliparous young woman presented to us with one week history suggestive of nephrotic syndrome. She was found to have a benign hydatidiform mole confirmed by histopathological examination after suction and curettage. Renal biopsy revealed focal segmental glomerulosclerosis. The renal pathology was most probably due to molar pregnancy due to the close temporal relationship. To our knowledge, this is the first case of focal segmental glomerulosclerosis associated with a gestation trophoblastic disease described in the literature.

The role of computed tomography in clinically-suspected but equivocal acute appendicitis.

INTRODUCTION: To study the role of contrast-enhanced computed tomography (CT) of the abdomen and pelvis in the evaluation of patients with clinically-suspected but equivocal acute appendicitis. METHODS: The medical records of 206 consecutive patients who had CT of the abdomen and pelvis for equivocal signs and symptoms of acute appendicitis were reviewed. 7 mm collimated axial sections from the diaphragm to the iliac crest and 5mm collimated sections of the pelvis with intravenous and oral contrast were obtained. The criteria used to diagnose acute appendicitis were: (a) a thickened appendix of more than 7 mm or (b) inflammatory changes in the periappendiceal fat. The CT findings were correlated with the histological diagnosis at appendectomy. If the CT findings were negative for acute appendicitis and surgery not performed, the results were correlated with other corroborating diagnostic investigations or clinical follow-up. RESULTS: A total of 206 patients were scanned, of which 39 were excluded due to lack of any follow-up. Of the final 167 that were studied, there were 36 true positives, 127 true negatives, 4 false negatives and no false positives, resulting in a sensitivity of 93.9 percent, specificity of 100 percent and accuracy of 98.5 percent. CONCLUSION: We have found CT to be a safe, reliable and accurate modality in the diagnosis of acute appendicitis in patients with equivocal presentation.

Supernumerary testicle in a case of polyorchidism.

INTRODUCTION: The presence of more than 2 testicles is called polyorchidism. It is a rare anomaly. Less than 100 cases have been reported in the literature. CLINICAL PICTURE: A 51-year-old man complained of a painless right groin lump for a year. Physical examination revealed a discrete ovoid non-tender, firm but mobile lump. No cough impulse was demonstrated. Sonography demonstrated a soft tissue structure within the tunica vaginalis inferior to the deep inguinal ring. It demonstrated similar echotexture and vascular flow as the normal testis, but smaller in size. The findings were compatible with a diagnosis of polyorchidism. TREATMENT: The patient was not keen for surgery and was followed up conservatively. CONCLUSION: Differential diagnosis of a solid extratesticular mass should include polyorchidism.

A case of right loin pain: septic ovarian vein thrombosis due to Campylobacter fetus bacteraemia.

INTRODUCTION: Septic ovarian venous thrombosis is an uncommon condition. Diagnosis is often not immediately apparent clinically and there are many that mimic this condition. We described an unusual case of septic ovarian vein thrombosis associated with Campylobacter fetus (C. fetus) bacteraemia. CLINICAL PICTURE: A 46-year-old female presented with fever and acute right loin pain. Right ovarian venous thrombosis was demonstrated on sonography and confirmed with computed tomography and magnetic resonance imaging. C. fetus was isolated from the blood. TREATMENT AND OUTCOME: The patient was given antibiotics and anticoagulation therapy with good response. CONCLUSION: Septic ovarian vein thrombosis should be considered as a differential diagnosis in female patients presenting with fever associated with lower abdominal pain. C. fetus bacteraemia also predisposes to thrombophlebitis, including septic ovarian vein thrombosis. When they are diagnosed in a timely manner and treated appropriately, the response is good and potential serious complications, including thromboembolism, and death could be averted. Radiological imaging is useful in the diagnostic work-up of this condition.

Penile colour duplex ultrasonography as a screening tool for venogenic erectile dysfunction.

INTRODUCTION: Vasculogenic impotence is one of the major causes of erectile dysfunction. Cavernosometry and cavernosography is traditionally the gold standard for evaluation of venogenic impotence. However, it is invasive and there are potentially significant complications. Penile colour flow Doppler imaging (PCDI) is non-invasive and can be used to assess venous incompetence. MATERIALS AND METHODS: One hundred and sixty-eight patients were referred for PCDI assessment from March 1998 to February 2001. Forty-three of these also had cavernosogram and cavernosometry done and were included in the study. RESULTS: The sensitivity was 93.9%, the specificity was 90.0%, the accuracy was 93.0% with a negative predictive value of 81.8% and a positive predictive value of 96.9%. Kappa value of 0.81 was obtained, indicating excellent agreement between PCDI and cavernosogram and cavernometry. CONCLUSIONS: Penile colour flow Doppler imaging is accurate in the assessment of venogenic erectile dysfunction. It can replace cavernometry and cavernosogram as a screening tool. Cavernometry and cavernosogram should only be done in cases when PCDI suggests venogenic impotence, and when surgery is contemplated.

To establish the normal bone mineral density reference database for the Singapore male.

INTRODUCTION: The objective of this study was to establish the normal bone mineral density (BMD) reference curve for the Asian Singapore male. MATERIALS AND METHODS: Three hundred and eighty-three male subjects were enrolled; comprising of 309 Chinese, 44 Malays and 30 Indians resident in Singapore. Bone mineral density was measured at the lumbar spine and left hip using a Hologic QDR 4500 Elite dual-energy X-ray absorptiometry (DXA) scanner. RESULTS: The mean peak BMD for the average lumbar spine and the neck of femur was 1.006 g/cm2 and 0.97 g/cm2, respectively. The mean peak BMD was taken at the 20 to 24 years age group at both the hip and spine based on data distribution for the various age groups. The BMD corresponding to -2.5 standard deviations from the peak adult value was 0.719 g/cm2 for the average lumbar spine and 0.655 g/cm2 for the neck of femur. CONCLUSION: This Asian male BMD reference database, which is 10% and 5% lower than corresponding values from the Caucasian reference database, allows for more accurate diagnosis of osteoporosis in Asian males.

The p38 mitogen-activated protein kinases can have opposing roles in the antigen-dependent or endotoxin-stimulated production of IL-12 and IFN-gamma.

The p38 mitogen-activated protein kinases (p38 MAPK) are activated in lymphocytes and acessory cells during innate and antigen-specific responses. We show that an inhibitor of two isoforms of p38 MAPK, SB 203580, inhibited the antigen-initiated production of IL-12, and IFN-gamma by cultures of splenic APC and naive CD4(+) T cells. Paradoxically, SB 203580 enhanced the LPS plus IFN-gamma-initiated production of IL-12 by peritoneal exudate macrophages, and the LPS-initiated of the production of both IL-12 and IFN-gamma by non-T non-B (scid) splenocytes. The enhancing effect of SB 203580 on the production of IL-12 by peritoneal exudate macrophages stimulated by LPS and IFN-gamma was dose dependent (EC(50) 0.3 microM), was only seen at lower concentrations of IFN-gamma and was due, at least in part, to a dose-dependent (IC(50) 0.3 microM) inhibition of the production of IL-10. These results indicate first, that p38 MAP kinase activity is required for the production of IL-10, as well as that of proinflammatory cytokines such as IL-12 and IFN-gamma, and, second, that the net effects of SB 203580 on the production of IL-12 and IFN-gamma can be positive or negative, depending on stimuli, cell populations, and levels of cytokines such as IFN-gamma and IL-10.

TNF type 2 receptor (p75) lowers the threshold of T cell activation.

T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8(+) T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75(-/-) T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-gamma. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75(-/-)CD8(+) T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.

TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells.

Mature CD4-CD8- alphabeta+ T cells (DNTC) in the periphery of TCR transgenic mice are resistant to clonal deletion in cognate Ag-expressing (Ag+) mice. Previously, we have characterized DNTC populations bearing the alloreactive 2C TCR in Ag-free (Ag-) and Ag+ mice. Despite appearing functionally anergic when challenged with cognate Ag in vitro, Ag-experienced DNTC exhibit markers of activation/memory, a lowered threshold of activation, ex vivo cytolytic activity, and the ability to rapidly secrete IFN-gamma. Remarkably, these memory-like DNTC also possess potent immunoregulatory properties, competing effectively for bystander-produced IL-2 and suppressing autoreactive CD8+ T cell proliferation via a Fas/FasL-dependent cytolytic mechanism. The fact that DNTC recovered from Ag+ mice possess markers and attributes characteristic of naive CD8+ T cells that have undergone homeostasis-induced proliferation suggested that they may be derived from a similar peripheral expansion process. Naive DNTC adoptively transferred into Ag-bearing hosts rapidly acquire markers and functional attributes of DNTC that have continually developed in the presence of Ag. Thus, the peripheral selection and maintenance of such autoreactive cells may serve to negatively regulate potential autoimmune T cell responses.

Tight skin mouse subcutaneous hypertrophy can occur in the absence of alphabeta T cell receptor-bearing lymphocytes.

OBJECTIVE: The tight skin (TSK) mouse has been proposed to be a murine model for heritable fibrotic disorders, and studies have implicated immune dysregulation in TSK pathogenesis. We evaluated the core features of TSK cutaneous pathology to ascertain whether cutaneous features were altered in TSK mice deficient in alphabeta T cell receptor (TCR)-bearing lymphocytes. METHODS: Blinded qualitative evaluations of cutaneous and subcutaneous tissues were performed to determine the effect of the TSK mutation and whether the TCR-alpha-/- mutation had any influence on TSK mediated pathology. RESULTS: Analysis by light microscopy revealed no difference in the thickness or any obvious changes in dermal architecture in 2 to 4-month-old TSK mice compared to age and sex matched littermate controls. The most consistent feature of TSK dermatohistopathology is the substantially expanded superficial fascia with accentuated "lamellar" architecture. We found that this reliable pathological marker and the characteristic skin tightness were not abrogated when the TSK mutation was crossed onto the TCR-alpha-/- background. CONCLUSION: The results dispute assertions that cutaneous and subcutaneous sclerosis in the TSK mouse are dependent upon the presence of CD4+ cells and that skin tightness can be dissociated from these pathological changes.

The affinity/avidity and length of exposure to the deleting ligand determine dependence on CD28 for the efficient deletion of self-specific CD4+CD8+ thymocytes.

Whether the CD28/B7 signaling pathway is essential for the negative selection of immature CD4+CD8+ (DP) thymocytes expressing self-specific alphabeta TCRs is a controversial issue. In this study we examined the role of CD28 in the deletion of thymocytes that express either the H-Y or the 2C transgenic TCR. In H-2(b) male mice that expressed the H-Y TCR, negative selection of DP H-Y TCR+ thymocytes occurred very efficiently and this deletion was unaffected by the CD28(-/-) mutation. In H-2(b) 2C mice, where the deletion of DP 2C TCR+ thymocytes occurred less efficiently, the CD28(-/-) mutation led to a higher recovery of DP thymocytes. Using an in vitro deletion assay, a requirement for the CD28 signaling pathway in the deletion of DP H-Y TCR+ thymocytes was evident at low, but not high, densities of the antigenic ligand. Similar results were also observed in an in vivo assay for the deletion of these thymocytes. Intraperitoneal administration of an anti-CD3epsilon mAb led to the intrathymic deletion of DP H-Y TCR+ thymocytes in a CD28-dependent manner at the 24-h time point. However, the CD28 dependence was less evident at the 40-h time point. These results indicate that the dependence on CD28 for the efficient deletion of self-specific thymocytes is determined by the concentration, affinity/avidity, and length of exposure to the deleting ligand.

p59fyn (Fyn) promotes the survival of anergic CD4-CD8- alpha beta TCR+ cells but negatively regulates their proliferative response to antigen stimulation.

T cell anergy is characterized by alterations in TCR signaling that may play a role in controlling the unresponsiveness of the anergic cell. We have addressed questions regarding the importance of the Src kinase p59(fyn) (Fyn) in this process by using Fyn null mice. We demonstrate that a mature population of CD4(-)CD8(-) alphabeta TCR(+) anergic T cells lacking Fyn have a substantial recovery of their proliferation defect in response to Ag stimulation. This recovery cannot be explained by ameliorated production of IL-2, and the improved proliferation correlates with an enhanced ability of the Fyn(-/-) anergic T cells to up-regulate the high affinity IL-2 receptor. We also observe that anergic CD4(-)CD8(-) alphabeta TCR(+) T cells have a heightened survival ability that is partially dependent on the elevated levels of Fyn and IL-2 receptor beta-chain expressed by these cells. The enhanced survival correlates with an increased capacity of the anergic cells to respond to IL-15. We conclude that Fyn plays an important role in aspects of T cell anergy pertaining to TCR signaling and to cell survival.