Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors: supplementary presentation.

A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary.

Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: a randomized controlled trial.

AIMS: To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM). METHODS: This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36 weeks' gestation (Group 1, CGM, n = 25) or usual antenatal care without CGM (Group 2, control, n = 25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3 days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG < 3.5 mmol/l; non-fasting < 4.0 mmol/l). HbA1c was measured at 28, 33 and 37 weeks. In Group 1, both CGM and CBG data were used to manage diabetes, whereas mothers in Group 2 were managed based on CBG data alone. RESULTS: Baseline characteristics (age, pre-pregnancy BMI, HbA1c , total insulin dose) were similar between groups. There was a lower increase in HbA1c from 28 to 37 weeks' gestation in the CGM group [∆HbA1c : CGM + 1 mmol/mol (0.09%), control + 3mmol/mol (0.30%); P = 0.024]. Mean HbA1c remained unchanged throughout the trial in the CGM group, but increased significantly in controls as pregnancy advanced. Mean HbA1c in the CGM group was lower at 37 weeks compared with controls [33 ± 4 mmol/mol (5.2 ± 0.4%) vs. 38 ± 7 mmol/mol (5.6 ± 0.6%), P < 0.006]. Some 92% of the CGM group achieved an HbA1c ≤ 39 mmol/mol (≤ 5.8%) at 37 weeks compared with 68% of the control group (P = 0.012). Neither group experienced severe hypoglycaemia. CONCLUSION: CGM use may be beneficial in insulin-treated GDM because it improves HbA1c compared with usual antenatal care without increasing severe hypoglycaemia. (Clinical Trials Registry No.: NCT02204657).

Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors.

A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary. PURPOSE: The aim of the study is to systematically review published literature on the prevalence of osteopenia/osteoporosis and its associated risk factors in HIV-infected individuals. METHODS: A literature search was conducted from 1989 to 2015 in six databases. Full text, English articles on HIV-infected individuals ≥ 18 years, which used dual X-ray absorptiometry to measure BMD, were included. Studies were excluded if the prevalence of osteopenia/osteoporosis was without a comparison group, and the BMD/T-score were not reported. RESULTS: Twenty-one cross sectional and eight longitudinal studies were included. The prevalence of osteopenia/osteoporosis was significantly higher in both HIV-infected [odds ratio (OR) = 2.4 (95%Cl: 2.0, 2.8) at lumbar spine, 2.6 (95%Cl: 2.2, 3.0) at hip] and ART-treated individuals [OR = 2.8 (95%Cl: 2.0, 3.8) at lumbar spine, 3.4 (95%Cl: 2.5, 4.7) at hip] when compared to controls. PI-treated individuals had an OR of 1.3 (95%Cl: 1.0, 1.7) of developing osteopenia/osteoporosis compared to controls. A higher proportion of tenofovir-treated individuals (52.6%) had lower BMD compared to controls (42.7%), but did not reach statistical significance (p = 0.248). No significant difference was found in the percent change of BMD at the lumbar spine, femoral neck, or total hip from baseline to follow-up between HIV-infected, PI-treated, tenofovir-treated, and controls. Older age, history of bone fracture, low BMI, low body weight, being Hispanic or Caucasian, low testosterone level, smoking, low CD4 cell count, lipodystrophy, low fat mass, and low lean body mass were associated with low BMD. CONCLUSIONS: The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was two times more compared to controls. However, evidence concerning bone loss within the first year of HIV infection and ART initiation was preliminary.

Acute effects of a single dose of tocotrienols on insulinemic and inflammatory responses in metabolic syndrome subjects after a high-fat challenge.

BACKGROUND/OBJECTIVES: Evidence shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. SUBJECTS/METHODS: Thirty metabolic syndrome subjects (15 men and 15 women) were recruited to a randomized, double-blinded and crossover study. The subjects were administered a single dose of 200 mg or 400 mg γδ-T3 emulsions or placebo incorporated into a glass of strawberry-flavored milkshake, consumed together with a high-fat muffin. Blood samples were collected at 0, 5, 15, 30, 60, 90, 120, 180, 240, 300 and 360 min after meal intake. RESULTS: Plasma vitamin E levels reflected the absorption of γδ-T3 after treatments. Postprandial changes in serum C-peptide, serum insulin, plasma glucose, triacylglycerol, non-esterified fatty acid and adiponectin did not differ between treatments, with women displaying delayed increase in the aforementioned markers. No significant difference between treatments was observed for plasma cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha) and thrombogenic markers (plasminogen activator inhibitor type 1 and D-dimer). CONCLUSIONS: Supplementation of a single dose of γδ-T3 did not change the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects.

Hypopituitarism in a Dengue Shock Syndrome Survivor without known Pituitary Adenoma.

Dengue infection is endemic in South East Asia and parts of the Americas. Dengue hemorrhagic fever is characterized by vascular permeability, coagulation-disorders and thrombocytopenia, which can culminate in hypotension i.e. dengue shock syndrome. Hypopituitarism arising as a complication of dengue is extremely rare. Hemorrhagic pituitary apoplexy of pre-existing pituitary adenomas has been rarely reported in dengue. We describe an uncommon case of hypopituitarism in a dengue shock syndrome survivor without known pituitary adenoma. A 49 years old nulliparous lady (from Kuala Lumpur, Malaysia) presented with typical symptoms of hypocortisolism. Postural hypotension was evident with normal secondary sexual characteristics. Further history revealed that she survived an episode of dengue shock syndrome 6 years ago where premature menopause developed immediately after discharge, and subsequently insidious onset of multiple hormonal deficiencies indicative of panhypopituitarism. There were no neuro-ophthalmological symptoms suggestive of pituitary apoplexy during hospitalization for severe dengue. Magnetic resonance imaging of the pituitary 6 years later revealed an empty sella. Autoimmune screen and anti-thyroid peroxidase antibodies were negative. We describe a rare possible causative association of severe dengue with panhypopituitarism without known pituitary adenoma, postulating pituitary infarction secondary to hypotension (mimicking Sheehan's syndrome), or a direct viral cytopathic effect. Subclinical pituitary apoplexy secondary to asymptomatic pituitary hemorrhage however cannot be excluded. Future research is required to determine the need for and timing of pituitary axis assessment among dengue shock syndrome survivors.

Hypopituitarism in a Dengue Shock Syndrome Survivor without known Pituitary Adenoma

Dengue infection is endemic in South East Asia and parts of the Americas. Dengue hemorrhagic fever is characterized by vascular permeability, coagulation-disorders and thrombocytopenia, which can culminate in hypotension i.e. dengue shock syndrome. Hypopituitarism arising as a complication of dengue is extremely rare. Hemorrhagic pituitary apoplexy of pre-existing pituitary adenomas has been rarely reported in dengue. We describe an uncommon case of hypopituitarism in a dengue shock syndrome survivor without known pituitary adenoma. A 49 years old nulliparous lady (from Kuala Lumpur, Malaysia) presented with typical symptoms of hypocortisolism. Postural hypotension was evident with normal secondary sexual characteristics. Further history revealed that she survived an episode of dengue shock syndrome 6 years ago where premature menopause developed immediately after discharge, and subsequently insidious onset of multiple hormonal deficiencies indicative of panhypopituitarism. There were no neuro-ophthalmological symptoms suggestive of pituitary apoplexy during hospitalization for severe dengue. Magnetic resonance imaging of the pituitary 6 years later revealed an empty sella. Autoimmune screen and anti-thyroid peroxidase antibodies were negative. We describe a rare possible causative association of severe dengue with panhypopituitarism without known pituitary adenoma, postulating pituitary infarction secondary to hypotension (mimicking Sheehan’s syndrome), or a direct viral cytopathic effect. Subclinical pituitary apoplexy secondary to asymptomatic pituitary hemorrhage however cannot be excluded. Future research is required to determine the need for and timing of pituitary axis assessment among dengue shock syndrome survivors.

Using microfluidics to investigate tumor cell extravasation and T-cell immunotherapies.

Understanding the mechanism of tumor cell extravasation, cell migration and the role of the immunosystem is crucial in creating targeted and patient-specific cancer therapies. We created an in-vitro microfluidic cell extravasation assay, incorporating a microvascular network and demonstrated its use to study cancer cells extravasation. Separately, we developed an assay for screening T-cell migration and cytotoxicity as a means to evaluate the efficiency of adoptive immunotherapies against cancer. Similar devices using a similar platform can be used to recreate a tumor liver microenvironment, taking in consideration the hypoxic and inflammatory conditions in the liver. These platforms show considerable potential as efficient pre-clinical models for testing the efficiency of cancer drugs and engineered T-cell functionality for personalized medicine.

Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors.

PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors. METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function. RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01. CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.

Myocardial infarction in Singapore: a nationwide 10-year study of multiethnic differences in incidence and mortality.

INTRODUCTION AND METHODS: Cardiovascular diseases have progressively increased in importance as a major contributor of morbidity and mortality in Asia. However, many countries in Asia do not have nationwide systematically-collected and standardised data on myocardial infarction (MI). To accurately document the extent of atherosclerotic coronary heart disease in Singapore, a nationwide myocardial infarct registry was established in the mid-1986. Possible myocardial infarct events were identified through daily national lists of cardiac enzymes, hospital discharge codes, mortuary records and the national death registry. Data obtained from clinical history, cardiac enzymes and 12-lead electrocardiogram Minnesota codes were entered into an algorithm based on the WHO MONICA study. Cases identified as "definite" MI were included in the decade's review for this study. RESULTS: From 1988 to 1997, 13,048 myocardial infarct events were diagnosed with 3367 deaths. There was a 39.1% decline in mortality, with an average decline of 6.5% per year [95% confidence intervals (CI), -3.9% to -9.1%]. However, the decline in incidence was only 20.8% with an average decline of 2.4% per year (95% CI, -6.6% to -1.2%). The highest incidence and mortality rates for both genders were seen in the Indians, followed by the Malays and the Chinese. CONCLUSION: Over 10 years, from 1988 to 1997, we documented a significant fall in mortality from MI in Singapore. There was a smaller decline in the incidence of infarction. Singapore implemented a National Healthy Lifestyle Programme in 1992 as a 10-year effort. The disparity in the incidence and mortality may suggest that a more dramatic and immediate impact has taken place in mortality through therapeutic programmes; primary preventive programmes would be more difficult to evaluate and have a more gradual impact. Only with continual accurate data collection through the whole country, over a much longer period, can the relative value of preventive and therapeutic programmes in coronary heart disease be assessed.

A comparison of indices of respiratory failure in ventilated preterm infants.

AIM: To compare indices of respiratory failure in terms of their ability to predict adverse respiratory outcomes in preterm infants. The indices evaluated were: (a) the alveolar-arterial oxygen tension difference (A-aDO(2)); (b) the ratio of arterial to alveolar oxygen tension (a/A ratio); (c) the oxygenation index (OI); (d) the fractional inspired oxygen concentration (FIO(2)). METHODS: Details of respiratory support and arterial blood gas data in the first 24 hours of life were collected in ventilated infants below 34 weeks gestation. The worst single value of a particular index in the first 24 hours was chosen to quantify the severity of respiratory failure in each infant. Receiver operating characteristic curves were constructed and areas under the curve (AUC) calculated to compare the performance of the indices in predicting death from respiratory failure and/or the development of chronic lung disease (CLD). RESULTS: A total of 155 preterm infants were studied, of whom 35 (23%) died primarily from respiratory failure and 53 of the 120 survivors (44%) developed CLD. The overall performance of the four indices in predicting death from respiratory failure ranged from 0. 77 (AUC for maximum FIO(2)) to 0.88 (AUC for minimum a/A ratio). The corresponding AUCs for gestational age and birth weight were 0.75 and 0.76 respectively. In contrast, demographic variables tended to perform better than indices of respiratory failure in predicting CLD/death. CONCLUSIONS: There was no evidence of a significant difference between the performance of the a/A ratio, A-aDO(2), and OI in predicting adverse respiratory outcomes. Use of the OI is recommended because of its ease of calculation.

Technetium-99m sestamibi for the assessment of myocardial salvage following reperfusion therapy in acute myocardial infarction.

INTRODUCTION: Reperfusion therapy with either thrombolysis or angioplasty has been shown to be beneficial in acute myocardial infarction. Tc-99m sestamibi is a myocardial tracer that can be used to assess myocardial salvage because of its property of very limited redistribution. MATERIALS AND METHODS: To assess the feasibility of this technique locally, Tc-99m sestamibi was injected before and after reperfusion therapy with angioplasty (n = 11) or streptokinase (n = 18) in 29 patients with acute myocardial infarction (anterior = 25, inferior = 4). Single-photon emission computed tomography (SPECT) was performed within 4 hours of reperfusion and repeated 5 to 7 days later. RESULTS: Initial perfusion defect size ranged from 6% to 78% (mean 36.3 +/- 18.7%), and final defect size from 0% to 50% of the left ventricle (mean 23.7 +/- 14.8%, P < 0.001). Patients with proximal left anterior descending artery (LAD) lesions had larger defects compared to those with mid LAD lesions (mean defect size 52% for pLAD versus 28% for mLAD, P < 0.013). However, there were wide variations in initial defect size (myocardium at risk) for a given infarct-related artery location. The mean decrease in defect size was 12% in the 28 patients with patent arteries compared to only 2% in the patient with an occluded artery (47% to 45%). There was no significant difference in amount of salvage between patients who had thrombolysis (mean 13%, P = 0.0003) and patients who had percutaneous transluminal coronary angioplasty (PTCA) (mean 12%, P = 0.005). CONCLUSIONS: Assessment of myocardial salvage is feasible using Tc-99m sestamibi SPECT imaging. It allows for quantitation of myocardium at risk and the amount of myocardial salvage, which is not possible by angiography alone.

Ovarian response after laparoscopic ovarian cystectomy for endometriotic cysts in 132 monitored cycles.

OBJECTIVE: To investigate the follicular response of ovaries after laparoscopic ovarian cystectomy for endometriotic cysts. DESIGN: A retrospective, controlled study. SETTING: Obstetrics and Gynaecology Department of a university hospital. PATIENT(S): Patients with history of infertility who had laparoscopic ovarian cystectomy for endometriotic cysts. INTERVENTION(S): Laparoscopic ovarian cystectomy, transvaginal ultrasound monitoring of follicles in natural cycles, stimulated cycles using clomiphene citrate (CC), chronic low-dose FSH, and "flare down" regimen. MAIN OUTCOME MEASURE(S): Follicular response of postcystectomy and normal ovaries. RESULT(S): For women < 35 years of age, the mean follicular response of postcystectomy ovaries was reduced significantly when compared with normal ovaries in natural cycles (0.30 versus 1.00 follicle per cycle) and in CC-stimulated cycles (0.87 versus 1.27 follicles per cycle). The mean follicular response was not statistically significantly different when the ovaries were stimulated with chronic low-dose FSH or with the flare down regimen. For women > or = 35 years, postcystectomy ovaries responded with a comparable number of follicles as the normal ovaries in natural cycles and the three different ovarian stimulation regimens. CONCLUSION(S): Postcystectomy ovaries showed reduced follicular response in natural and CC-stimulated cycles for women < 35 years of age. Postcystectomy ovaries produced a comparable number of follicles as normal ovaries when stimulated with gonadotropins.

Factors related to outcome after pneumonectomy: retrospective study of 62 patients.

OBJECTIVE: To find out which risk factors affect outcome after pneumonectomy. DESIGN: Retrospective study. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 62 patients who were treated for bronchial cancer by pneumonectomy between 1984 and 1995. MAIN OUTCOME MEASURE: Hospital mortality and postoperative complications. RESULTS: Hospital mortality increased with age, being 5/51 (10%) in the 40-69 age group and 4/11 (36%) in patients aged 70 or more. In the American Society of Anesthesiologists (ASA) class I group hospital mortality was 8% (2/26), in class II 12% (3/26) and in class III 40% (4/10). Hospital mortality was highest when the FEV1:FVC-ratio was below 55%. Cardiac arrhythmias developed in 8 (13%), early bronchopleural fistulas in 7 (11%), and postpneumonectomy syndrome in 5 (8%). These major complications had a high mortality. CONCLUSION: Respiratory function, ASA class, and age over 70 years are the main prognostic factors for hospital morbidity and mortality after pneumonectomy.

Lovastatin induces apoptosis in malignant mesothelioma cells.

Malignant mesothelioma causes profound morbidity and nearly universal mortality that is refractory to conventional treatment with aggressive surgery, radiotherapy, or chemotherapy. We report that pharmacologic concentrations of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, induced apoptosis in human malignant mesothelioma cell lines. Mesothelioma cell viability was decreased in a dose-dependent manner by lovastatin (5 to 30 microM). These effects were not reversed by exogenous growth factors or cholesterol, but were reversed by addition of 100 microM mevalonate, confirming that lovastatin affected mesothelioma viability by inhibiting mevalonate synthesis. Lovastatin appeared to decrease mesothelioma viability by inducing apoptosis, as indicated by morphologic changes, histologic evidence of nuclear condensation and degeneration, and flow-cytometric analysis of DNA content. Lovastatin's effects on cell viability were partially reversed in the presence of farnesol, and treatment of mesothelioma cells with a specific farnesyl-protein transferase (FTP) inhibitor decreased cell viability and induced morphologic changes indistinguishable from those caused by lovastatin. In addition, lovastatin-treated cells showed translocation of ras guanosine triphosphate (GTP)-binding proteins from membrane to cytosolic fractions on Western blots, suggesting that lovastatin's effects on mesothelioma were mediated in part by disrupting acylation of GTP-binding proteins. Thus, lovastatin is a commercially available and clinically well-tolerated agent that reduces viability and induces apoptosis of mesothelioma cells, and may provide the basis for adjunctive treatments of patients with mesothelioma.

The clinical impact of platelet glycoprotein IIb/IIIa receptor blockade in cardiovascular medicine.

Several of the adverse events that occur in acute coronary syndromes and after percutaneous coronary revascularization procedures are believed to be mediated by platelets. Recently, using molecular biology techniques, the platelet glycoprotein IIb/IIIa receptor was identified as the final common pathway for platelet aggregation. Thus, blocking the action of this receptor would seem to be an attractive proposition for reducing ischemic complications. A monoclonal antibody was the first agent in this new pharmacological family to be designed, but several peptide and peptide-like substances have subsequently been developed. This paper reviews the development of this class of agents and the various preclinical and clinical trials that have been undertaken. Early studies evaluated such agents during percutaneous coronary revascularization procedures. Because of the overwhelming benefits observed in such patients, together with the current limitations of treatments for acute coronary syndromes, the scope of investigations has been extended. Preliminary reports have been encouraging.

Comparison of treatment of supraventricular tachycardia by Valsalva maneuver and carotid sinus massage.

STUDY OBJECTIVE: To compare the efficacy of the Valsalva maneuver with that of carotid sinus massage (CSM) in terminating paroxysmal supraventricular tachycardia (SVT) in the ED. METHODS: This prospective, randomized case study was performed in the ED of a tertiary care institution. Patients were at least 10 years of age with regular narrow complex tachycardia and had an ECG diagnosis of SVT. Patients with regular narrow complex tachycardia were randomly assigned to undergo either the Valsalva maneuver or CSM. If the tachycardia was not terminated by the method chosen by randomization, then the alternative method of vagal maneuver was used. If the tachycardia was not converted by both methods of vagal stimulation, patients would undergo either synchronized electrical cardioversion or a pharmacologic method of conversion at the discretion of the treating physician, depending on the patient's hemodynamic status. RESULTS: One hundred forty-eight instances of SVT were studied Sixty-two patients underwent Valsalva maneuver first with conversion in 12 (success rate of 19.4%). Eighty-six underwent CSM first with conversion in 9 (success rate 10.5%). Carotid sinus massage was used in the 50 cases of SVT in which conversion was not achieved with the Valsalva maneuver. Conversion occurred in 7 cases (success rate 14.0%). For the 77 cases of SVT in which initial CSM did not achieve conversion, conversion occurred in 13 with the Valsalva maneuver (success rate 16.9%). The Valsalva maneuver and CSM achieved conversion in a total of 41 instances of SVT (success rate 27.7%). CONCLUSION: Vagal maneuvers are efficacious in terminating about one quarter of spontaneous SVT cases. There is no detectable difference in efficacy between the Valsalva maneuver and CSM.

Translational control of programmed cell death: eukaryotic translation initiation factor 4E blocks apoptosis in growth-factor-restricted fibroblasts with physiologically expressed or deregulated Myc.

There is increasing evidence that cell cycle transit is potentially lethal, with survival depending on the activation of metabolic pathways which block apoptosis. However, the identities of those pathways coupling cell cycle transit to survival remain undefined. Here we show that the eukaryotic translation initiation factor 4E (eIF4E) can mediate both proliferative and survival signaling. Overexpression of eIF4E completely substituted for serum or individual growth factors in preserving the viability of established NIH 3T3 fibroblasts. An eIF4E mutant (Ser-53 changed to Ala) defective in mediating its growth-factor-regulated functions was also defective in its survival signaling. Survival signaling by enforced expression of eIF4E did not result from autocrine release of survival factors, nor did it lead to increased expression of the apoptosis antagonists Bcl-2 and Bcl-XL. In addition, the execution apparatus of the apoptotic response in eIF4E-overexpressing cells was found to be intact. Increased expression of eIF4E was sufficient to inhibit apoptosis in serum-restricted primary fibroblasts with enforced expression of Myc. In contrast, activation of Ha-Ras, which is required for eIF4E proliferative signaling, did not suppress Myc-induced apoptosis. These data suggest that the eIF4E-activated pathways leading to survival and cell cycle progression are distinct. This dual signaling of proliferation and survival might be the basis for the potency of eIF4E as an inducer of neoplastic transformation.

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease.

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile (99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (MI), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with 99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patient without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1%. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between 99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that 99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and 99mTc sestamibi for the extent of coronary artery disease was also satisfactory.