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Biomedical subjects

J Sulkes

Publications and source records attributed to J Sulkes.

At least 19 recordsLinked to original sources

Quantitation of alpha-fetoprotein messenger RNA for early detection of recurrent hepatocellular carcinoma: a prospective pilot study.

BACKGROUND: Alpha-fetoprotein (AFP) messenger RNA (mRNA) may be a potential marker of the dissemination of hepatocellular carcinoma (HCC) cells into the circulation. The aim of this prospective pilot study was to assess the prognostic value of quantitative levels of AFP mRNA in patients undergoing ablative treatment for HCC. METHODS: Peripheral blood samples were taken from seven patients before and after treatment for measurement of AFP mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR). Patients were treated with percutaneous radiofrequency thermal ablation (n=3) or transarterial chemoembolization (n=4). The level of AFP mRNA in blood was serially determined, and the time course was related to the clinical course and disease outcome. The median duration of follow-up was 14 months (range, 9-16 months). RESULTS: HCC recurred locally in four patients, and lung metastases developed in two of them. Patients were divided into three groups on the basis of the pre- and post-treatment AFP mRNA status. Group 1 included four patients with consistently high serum AFP and AFP mRNA levels (pre- and post-treatment). These patients developed distant and local recurrence. Group 2 included a patient with serum-negative AFP mRNA and normal AFP levels at entry. Although serum AFP remained within normal range, mean AFP mRNA increased from 10 to 95 copies/microg RNA. This patient had no distant metastases, but his tumor markedly increased in size. In Group 3, AFP mRNA and serum AFP remained within normal range before and after treatment. These two patients did not develop either local or distant metastases during the follow-up period. CONCLUSIONS: Although this is a small sample size pilot study these findings imply that quantitative measurement of AFP-expressing cells in peripheral blood may serve as a marker of HCC recurrence.

Aged↗

Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection.

The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage > or = 2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000-1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.

Adult↗

Risk factors for failure to extend labor epidural analgesia to epidural anesthesia for Cesarean section.

AIM: To identify parturients at risk of inability to extend labor epidural analgesia in whom alternative methods of anesthesia should be considered for Cesarean section (CS). METHODS: For 6 months, we prospectively studied women undergoing CS with a functioning epidural catheter in place from the delivery ward. All parturients received the same epidural protocol: bolus of bupivacaine 0.1% and fentanyl, followed by bupivacaine 0.1% and fentanyl (2 microg/ml) 10-15 ml/h and an additional 5 ml of bupivacaine 0.125% as top-up according to patient request. Sixteen milliliters of lidocaine 2%, 1 ml of bicarbonate and 100 microg of fentanyl were given for CS. Failed epidural analgesia was defined as the need to convert to general anesthesia. RESULTS: Of the 101 parturients studied, 20 (19.8%) required conversion to general anesthesia. In univariate analysis, the likelihood of failed epidural anesthesia was inversely correlated with parturient age (P = 0.014) and directly correlated with pre-pregnancy weight (P = 0.019), weight at the end of pregnancy (P = 0.003), body mass index at the end of pregnancy (P = 0.0004), gestational week (P = 0.008), number of top-ups (P = 0.0004) and visual analog scale (VAS) score 2 h before CS (P = 0.03). In multivariate analysis, the number of top-ups in the delivery ward was the best predictor of epidural anesthesia failure (odds ratio, 4.39; P = 0.005). CONCLUSION: Younger, more obese parturients at a higher gestational week, requiring more top-ups during labor and having a higher VAS score in the 2 h before CS are at risk for inability to extend labor epidural analgesia to epidural anesthesia for CS.

Adult↗

Risk factors for failure to extend labor epidural analgesia to epidural anesthesia for Cesarean section.

OBJECTIVE: To identify parturients at risk of inability to extend labor epidural analgesia in whom alternative methods of anesthesia should be considered for Cesarean section (CS). METHODS: For 6 months, we prospectively studied women undergoing a CS with a functioning epidural catheter in place from the delivery ward. All parturients received the same epidural protocol: bolus of bupivacaine 0.1% and fentanyl, then bupivacaine 0.1% and fentanyl (2 microg/ml) 10-15 ml/h and an additional 5 ml of bupivacaine 0.125% top-ups according to patient request. Sixteen millilitres of lidocaine 2%, 1 ml of bicarbonate, and 100 microg of fentanyl were given for CS. Failed epidural analgesia was defined as the need to convert to general anesthesia. RESULTS: Of the 101 parturients studied, 20 (19.8%) required conversion to general anesthesia. In univariate analysis, the likelihood of failed epidural anesthesia was inversely correlated with parturient's age (P = 0.014) and directly correlated with pre-pregnancy weight (P = 0.019), weight at the end of pregnancy (P = 0.003), body mass index (BMI) at the end of pregnancy (P = 0.0004), gestational week (P = 0.008), number of top-ups (P = 0.0004) and visual analog scale (VAS) 2 h before CS (P = 0.03). In multivariate analysis, the number of top-ups in the delivery ward was the best predictor of epidural anesthesia failure (odds ratio 4.39, P = 0.005). CONCLUSION: Younger, more obese parturients at a higher gestational week, requiring more top-ups during labor, having a higher VAS in the 2 h before CS are at risk of inability to extend labor epidural analgesia to epidural anesthesia for CS.

Adult↗

Neutrons and sudden cardiac death (SCD) codes 121-125 ICD 10.

Recent studies have shown that (1) monthly neutron activity (NA) (imp/min) correlates with monthly number of acute myocardial infarction (AMI); (2) NA is higher on days of automatic implantable cardioverter defibrillators (AICD) discharges for VT, VF. Here we checked the level of NA in relation to timing and type of sudden cardiac death (SCD) patients [n=848 (579, 68.28% male)] obtained from the Kaunas registry for the years 2002-2004. All underwent Forensic Medicine post mortem examination and classification according to ICD10 by code 121-125. Daily NA data were obtained from Oulu U-ty, Finland and Moscow Monitoring Station of the Russian Academy of Sciences. No difference in NA was found on days with or without SCD. In men < 65, SCD occurred on days with higher NA than in women of the same age (p = 0.01) or in > 65 y old men (p = 0.045). Days of SCD with myocardial ruptures showed the highest level of NA, significantly higher than on all days (n = 669) of SCD (p = 0.037) and all 1096 days of the study (p = 0.0048). Three groups were accompanied by significantly higher NA: repeated AMI, myocardial ruptures (codes122, 123), and coronary atherothrombosis without AMI, related to electrical heart instability. The mechanism of possible neutron role in pathophysiology needs special studies.

Adult↗

Radiation treatment for ductal carcinoma in situ (DCIS): is a boost to the tumor bed necessary?

The aim of the presented study was to evaluate the long-term outcome of breast-conserving surgery and radiation for the treatment of ductal carcinoma in situ (DCIS) and the role of the radiation boost to the tumor bed. The files of 75 women with DCIS treated by breast-conserving surgery followed by definitive radiation from 1988 to 1997 were reviewed for demographic data, prognostic variables, radiation dose, radiation boost, recurrence, and outcome. Total radiation dose was 5000 cGy delivered in 25 fractions. Twenty patients (26.7%) received an additional boost to the tumor bed of 1000 cGy in 5 fractions. Median follow-up time was 81.5 months (range, 22-145). Pearson correlation coefficient and its significance was calculated between the variables. Log rank test was used to analyze differences in local recurrence rates between patients who did or did not receive a boost, and a Cox regression model was fitted to the data to predict recurrence. Ten patients (13%) had local recurrence; one patient showed lymphatic spread. Histopathologic examination revealed DCIS in 6 cases (60%) and invasive duct carcinoma in 4 (40%)(one minimally invasive). The recurrence group included 3 of the 20 patients who received a radiation boost (15%) and 7 of the 55 who did not (12.7%) (p=0.7). Correlation analysis of patient characteristics, prognostic factors, and treatment was significant only between mastitis as the presenting symptom (n=4) and longer time to recurrence (p=0.02). The recurrence rate in the present study was similar to other series of conservative treatment for DCIS of the breast. No additional value was found for the radiation boost. Larger controlled randomized studies are needed to confirm these findings.

Adult↗

Effect of adenosine A2A receptor agonist (CGS) on ischemia/reperfusion injury in isolated rat liver.

Ischemia/reperfusion injury during liver transplantation is a major cause of primary nonfunctioning graft for which there is no effective treatment other than retransplantation. Adenosine prevents ischemia-reperfusion-induced hepatic injury via its A2A receptors. The aim of this study was to investigate the role of A2A receptor agonist on apoptotic ischemia/reperfusion-induced hepatic injury in rats. Isolated rat livers within University of Wisconsin solution were randomly divided into four groups: (1) continuous perfusion of Krebs-Henseleit solution through the portal vein for 165 minutes (control); (2) 30-minute perfusion followed by 120 minutes of ischemia and 15 minutes of reperfusion; (3) like group 2, but with the administration of CGS 21680, an A2A receptor agonist, 30 microg/100 ml, for 1 minute before ischemia; (4) like group 3, but with administration of SCH 58261, an A2A receptor antagonist. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results showed that at 1 minute of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with CGS (p < 0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p < 0.0002). The reduction in postischemic apoptotic hepatic injury in the CGS-treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p < 0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p < 0.05); and by the TUNEL assay (p < 0.05). In conclusion, the administration of A2A receptor agonist before induction of ischemia can attenuate postischemic apoptotic hepatic injury and thereby minimize liver injury. Apoptotic hepatic injury seems to be mediated through caspase-3 activity.

Adenosine↗

Cathepsin B inactivation attenuates the apoptotic injury induced by ischemia/reperfusion of mouse liver.

BACKGROUND: A major mechanism underlying warm ischemia/reperfusion (I/R) injury during liver transplantation is the activation of the caspase chain, which leads to apoptosis. Recently, it was demonstrated that the release of cathepsin B, a cysteine protease, from the cytosol in liver injury induces mitochondrial release of cytochrome c and the activation of caspase-3 and -9, thereby leading to apoptosis. The aim of this study was to ascertain if cathepsin B inactivation attenuates the apoptotic injury due to I/R in mouse liver. METHODS: A model of segmental (70%) hepatic ischemia was used. Eighteen mice were anesthetized and randomly divided into three groups: (1) CONTROL GROUP: sham operation (laparotomy); (2) Ischemic group: midline laparotomy followed by occlusion of all structures in the portal triad to the left and median lobes for 60 min (ischemic period); (3) STUDY GROUP: like group 2, but with intraperitoneal administration of a pharmacological inhibitor of cathepsin B (4 mg/100 g) 30 min before induction of ischemia. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. RESULTS: Showed that at 6 h of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with cathepsin B inhibitor (p<0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p<0.0001). The reduction in postischemic apoptotic hepatic injury in the cathepsin B inhibitor -treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p<0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p<0.05); and by the TUNEL assay (p<0.05). CONCLUSION: The administration of cathepsin B inhibitor before induction of ischemia can attenuate postischemic hepatocyte apoptosis and thereby minimize liver damage. Apoptotic hepatic injury seems to be mediated through caspase-3 activity. These findings have important implications for the potential use of cathepsin B inhibitors in I/R injury during liver transplantation.

Animals↗

Suicide-homicide temporal interrelationship, links with other fatalities, and environmental physical activity.

UNLABELLED: Homicide and suicide are extremes in human behavior. The aim of this study is to investigate the connection by time between suicide and homicide, between them and other fatalities, and their links with the level of cosmophysical activity. METHODS: Using the national database of Lithuania (1990-2002) we found that 547,875 deaths, 4,638 homicides (3,374 male) and 19,527 (16,019 male) suicides were registered in that period. Their temporal distribution over 156 months was compared with solar and cosmic-ray activity. Pearson correlation coefficients and their probabilities were established. RESULTS: There was a correlation between monthly rates of homicide and male groups. Female suicide rates correlated with male and total homicide numbers. Both homicide and suicide rates were inversely correlated with solar and cosmic-ray activity. Suicide numbers, but not homicides, were inversely related to geomagnetic activity. Suicide rates were inversely correlated with total, cardiovascular, traffic accident, and sudden deaths; homicide with total, traffic accident, and sudden deaths. CONCLUSION: Temporal distribution of homicide and suicide is significantly interrelated. Both are linked to parameters of cosmophysical activity. The influence of cosmic rays deserves special attention.

Cosmic Radiation↗

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.

Adolescent↗

Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies.

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.

Adult↗

Role of circulating soluble CD40 as an apoptotic marker in liver disease.

OBJECTIVES: To measure levels of soluble CD40, a laboratory marker of apoptosis in patients with liver disease, determine its origin, and correlate the findings with disease activity and histology. DESIGN: Laboratory research study with comparison group. SETTING: Liver Institute, Laboratory of HLA Typing and Histopathology Department, Rabin Medical Center, Israel. SUBJECTS: One hundred ten patients with liver disease and 20 healthy controls. METHODS: Serum samples were collected from all patients; in addition, paired hepatic and portal vein samples were collected from 23 patients, and bile samples from 5 patients. Soluble CD40 was measured with an enzyme-linked immunosorbent assay. Apoptotic cells in liver tissue were identified by morphological criteria and quantified with the TUNEL assay. RESULTS: Soluble CD40 concentration was significantly higher in patients with liver disease than controls (mean 112.9 +/- 197.2 pg/ml vs. 24.2 +/- 9.1 pg/ml, p = 0.0001), with highest levels in the chronic viral hepatitis group (mean 131.7 +/- 137.5 pg/ml, p = 0.0001). Levels of sCD40 were correlated with serum creatinine, alkaline phosphatase, alpha-feto protein, and the apoptotic index. In the 23 paired samples, CD40 level was higher in the hepatic vein (mean 74.9 +/- 114.5 pg/ml) than the portal vein (mean 51.6 +/- 67.9 pg/ml); it was highly detectable in bile (mean 115.6 +/- 119.6 pg/ml, p = 0.0123). Untreated patients with chronic viral hepatitis (B and C) had higher levels (mean 106.2 +/- 76.5 pg/ml) than treated patients (mean 59.3 +/- 68.6 pg/ml, p = 0.049). CONCLUSIONS: Levels of soluble CD40 increase in different types of liver disease. It probably derives from the liver and is secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble CD40 may serve as a serum marker of apoptosis in liver disease.

Apoptosis↗

Lack of plasma norepinephrine cyclicity, increased estradiol during the follicular phase, and of progesterone and gonadotrophins at ovulation in women with premenstrual syndrome.

In healthy women, plasma norepinephrine (NE) has a cycle with the highest levels occurring at ovulation and early luteal phase. We examined plasma NE cyclicity in premenstrual syndrome (PMS) patients as compared to controls, its relation to estradiol (E(2)), progesterone (P), luteinizing hormone and follicle-stimulating hormone, and the correlation of these parameters with the PMS symptoms. Lack of NE cyclicity was observed in PMS patients. In controls, peak NE levels occurred at ovulation and early luteal phase. In PMS, serum E(2) was higher during the follicular phase, while P and gonadotrophins were higher especially at ovulation and the luteal phase. In the late luteal phase, E(2) levels were lower in PMS patients than in controls. A negative correlation was observed between the area under the curve for E(2) in the luteal phase and PMS somatic and mental scores. Plasma NE showed a negative correlation with abrupt mood swings, impatience, nervousness, tiredness, weakness, apathy, and headache. These data suggest that lack of NE cyclicity characterizes PMS, some symptoms being related to low E(2) levels during the late luteal phase and decreased noradrenergic activity at ovulation and the luteal phase.

Adult↗

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗

Circulating soluble cytochrome c in liver disease as a marker of apoptosis.

OBJECTIVES: To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. DESIGN: Laboratory research study with comparison group. SETTING: Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. SUBJECTS: A total of 108 patients with liver disease and 30 healthy controls. INTERVENTIONS: Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. MAIN OUTCOME MEASURES: Soluble cytochrome c level by type of liver disease by clinical and histological findings. RESULTS: Soluble cytochrome c concentration (mean 187.1 +/- 219.5 ng x mL(-1)) was significantly higher in patients with liver disease than in controls (39.8 +/- 35.1 ng x mL(-1); P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 +/- 2844.8 ng x mL(-1); P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 +/- 297.0 ng x mL(-1)) than the portal vein (mean 169.2 +/- 143.3 ng x mL(-1)), and it was highly detectable in bile (mean 2288.0 +/-4596.0 ng x mL(-1)) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 +/-304.3 ng x mL(-1)) than treated patients (77.9 +/- 35.8 ng x mL(-1); P = 0.001). CONCLUSIONS: Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis.

Adult↗