Jaqueline Sulkes

Cytokine gene polymorphisms in patients infected with hepatitis B virus.

OBJECTIVE:Cytokines play a key role in the regulation of the immune response. The maximal capacity of cytokine production varies among individuals and correlates with the polymorphism in the cytokine gene promoters. The aim of this study was to characterize gene polymorphism in patients with chronic hepatitis B virus (HBV) infection and to determine the different patterns in patient subgroups.METHODS:The study population consisted of 77 patients with chronic HBV infection (23 low-level HBV replicative carriers, 23 compensated high-level HBV replicative carriers, 21 decompensated liver transplant candidates, and 10 patients with documented hepatocellular carcinoma). The genetic profile of five cytokines was analyzed by polymerase chain reaction–sequence-specific primer (SSP), and subjects were genotyped as high or low producers of tumor necrosis factor-α and interleukin (IL)-6, and as high, intermediate, or low producers of transforming growth factor-β1, interferon (IFN)-γ, and IL-10 based on single nucleotide substitutions. The control group included 10 healthy individuals who recovered from HBV infection and 48 healthy controls.RESULTS:A highly statistically significant difference in the distribution of the IFN-γ gene polymorphism (at position +879) was observed between patients with chronic HBV infection and controls. The majority of the patients (65.2%) exhibited the potential to produce low levels of IFN-γ (A/A genotype) compared with 37.5% of the control group (p = 0.003). Healthy individuals who recovered from HBV infection had a similar distribution of IFN-γ gene polymorphism as the healthy controls. No statistically significant difference in IFN-γ production was found between patients with low- and high-level HBV replication and between compensated and decompensated patients. There was also no statistically significant difference in the genetic ability to produce tumor necrosis factor-α (at position −308), IL-6 (at position −174), IL-10 (at position −1082, −819, and −592), and transforming growth factor-β1 (at position +10 and +25).CONCLUSION:These findings suggest an association between the genetic ability to produce low levels of IFN-γ and the susceptibility to develop chronic HBV infection.

Percutaneous endoscopic gastrostomy: high mortality rates in hospitalized patients

OBJECTIVE:Percutaneous endoscopic gastrostomy (PEG) is a widely used method for insertion of a gastrostomy tube in patients who are unable to eat but have a normally functioning gut. Complications have been described, especially in fragile, debilitated patients, and 30-day mortality rates of 4.1–26% have been reported. We assessed the outcome of PEG tube placement for inpatients and outpatients, based on morbidity, mortality, and long-term survival.METHODS:We reviewed the medical records of all patients who underwent PEG at our institution between January 1, 1995 and December 31, 1996. Four groups of patients were compared: Group 1, patients from nursing homes; Group 2, hospitalized patients; Group 3, hospitalized patients matched to Group 2 for diseases, except mental disorder, and not treated with PEG; and Group 4, the general hospital population matched for age.RESULTS:A total of 114 PEG tubes were inserted in 114 patients, 47 from Group 1, 67 from Group 2. Eighty-seven percent of patients in Group 1 underwent PEG because of dementia, versus 46% of Group 2 (p < 0.001). The mortality rate was five times higher in Group 2 than in Group 3 (p < 0.001). The 30-day mortality was seven times higher in Group 2 than in Group 1, twice that in Group 3, and five times higher than in Group 4 (p = 0.002 and p < 0.001, respectively). When intention-to-treat analyses were applied to the data, 19/48 patients died (39.5%) in Group 1, and 60/83 (72.0%) died in Group 2, (p < 0.001).CONCLUSIONS:Patients hospitalized with acute illness are at high risk for serious adverse events after PEG insertion and this procedure should be avoided.

Metabolic syndrome in liver transplant recipients: Prevalence, risk factors, and association with cardiovascular events

Features of metabolic syndrome are not uncommon in patients after liver transplantation. To examine the prevalence and risk factors of posttransplantation metabolic syndrome (PTMS), the files of 252 transplant recipients (mean age, 54.5 ± 2.8 years, 57.9% male) were reviewed for pretransplant and posttransplant clinical and laboratory parameters (mean follow‐up, 6.2 ± 4.4 years). Rates of obesity (body mass index >30 kg/m2), hypertriglyceridemia (>150 mg/dL), high‐density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women), hypertension, and diabetes were significantly higher after transplantation than before. Metabolic syndrome was diagnosed in 5.4% of patients before transplantation and 51.9% after. Besides significantly higher rates of the typical metabolic derangements (P < 0.0001), the patients with PTMS were older and heavier than those without PTMS, and they had a higher rate of pretransplant hepatitis C virus infection (P < 0.03) and more posttransplant major vascular and cardiac events (20 events in 15.2% of patients with PTMS versus 6 events in 4.9% of patients without PTMS; P < 0.007). There was no between‐group difference in mortality or causes of death (mainly related to recurrent disease, graft failure, and sepsis). Significant independent predictors of PTMS on logistic regression analysis were age (odds ratio [OR] = 1.04), pretransplant nonalcoholic fatty liver disease (OR = 3.4), body mass index (OR = 1.13), diabetes (OR = 5.95), and triglycerides (OR = 1.01). The rate of metabolic syndrome in liver transplant recipients is more than twice that reported for the general population. PTMS is associated with cardiovascular morbidity but not mortality, and it may be predicted by pretransplantation conditions. Prospective studies are required to determine the significance and management of PTMS. Liver Transpl 17:15–22, 2011.

A patient education program is cost-effective for preventing failure of endoscopic procedures in a gastroenterology department

OBJECTIVE:The growing use and complexity of endoscopy procedures in GI units has increased the need for good patient preparation. Earlier studies in this area have focused on the psychological benefits of patient education programs. The present study was directed at determining cost-effectiveness of a patient education program.METHODS:A prospective, randomized, controlled design was used. The patient population consisted of 142 patients aged 18–90 yr referred for an endoscopy procedure. Ninety-one (64%) participated in a targeted educational session conducted by a dedicated departmental nurse (group 1), 38 (27%) did not (group 2), and 13 (9%) received telephonic instruction (group 3). Before the endoscopy, all patients completed a questionnaire covering background data, endoscopy-related variables, anxiety level, and satisfaction. Patient cooperation and success/failure of the procedure were documented by the attending nurse.RESULTS:Male gender, previous endoscopy, and explanation from the referring physician were associated with a low level of anxiety (p < 0.05). There was a significant association between attendance in the education program and success of the endoscopy (p = 0.0009). Cancellations of procedures because of poor preparation occurred in 4.39% of group 1 in comparison with 26.31% and 15.38% of groups 2 and 3, respectively (p = 0.005). The overall cost of the procedure was reduced by 8.6%, 8.9%, and 5.5% for gastroscopy, colonoscopy, and sigmoidoscopy, respectively. All participants expressed satisfaction with the brochure.CONCLUSION:A pre-endoscopy patient education program apparently increase patient compliance, thereby decreasing both the need for repeated examinations and their attendant costs.

Expression of the apoptosis-related oncogenes bcl-2, bax, and p53 in Merkel cell carcinoma: Can they predict treatment response and clinical outcome?

Chemotherapy and radiation therapy act predominantly through the induction of apoptosis in malignancies. Merkel cell carcinoma, an aggressive malignancy with prominent apoptosis, has proved to be sensitive to both modes to a certain degree. We used immunohistochemical methods to examine 25 Merkel cell carcinomas and 8 of their lymph node metastases to assess the status of the antiapoptotic gene bcl-2 and 2 proapoptotic genes, wild-type p53 and bax. All tumors showed prominent bax immunopositivity; 76% were positive for bcl-2, and only 28% were positive for p53, the latter presumably reflecting mutated p53. No statistically significant relationship was found between tumor immunopositivity and therapy response or survival. The widespread bax immunopositivity and the apparently low rate of p53 mutations, as suggested by the low rate of p53 immunopositivity, may be related to the presence of prominent apoptosis in Merkel cell carcinoma. The finding of bcl-2 immunopositivity in 76% of the tumors suggests that some of the tumor cells may be resistant to apoptosis-inducing agents.

Prediction of the level of left anterior descending coronary artery obstruction during anterior wall acute myocardial infarction by the admission electrocardiogram

T he ability to predict the exact site of the occlusion of the infarct-related artery by a noninvasive method shortly after admission to the hospital may help the clinician in estimating the myocardial area at risk and planning therapeutic interventions. This is important especially for anterior wall acute myocardial infarction (M), because proximal left anterior descending (LAD) coronary artery disease has a poor prognosis.‘” The electrocardiogram is quite reliable in detecting anterior wall AMF9 or infarction caused by LAD coronary artery obstruction. l”,ll Based on the electrocardiogram, several subtypes of anterior wall AMI are recognized (anteroseptal, anterolateral, apical, and so forth)12; however, correlation of the various electrocardiographic patterns with the exact anatomic location of the infarct as determined by autopsy is poor.7,8,12 This study assesses the value of ST changes in the various electrocardiographic leads during evolving anterior wall AMI in predicting the location of the LAD coronary artery obstruction in relation to the origin of the tirst diagonal branch. All patients admitted to the coronary care unit with AM from July 1988 to November I992 were evaluated retrospectively. Patients who underwent coronary angi-

c-kit expression in primary and metastatic merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.

Importance of the Conal Branch of the Right Coronary Artery in Patients With Acute Anterior Wall Myocardial Infarction: Electrocardiographic and Angiographic Correlation

OBJECTIVES This study assessed prospectively the correlation between the conal branch of the right coronary artery and the pattern of ST segment elevation in leads V1 and V3R during anterior wall acute myocardial infarction (AMI). BACKGROUND The traditional electrocardiographic (ECG) definition of anteroseptal AMI-ST segment elevation in leads V1 to V3-has recently been challenged. The significance of ST segment elevation in lead V1 during anterior wall AMI is unclear. METHODS The admission 12-lead ECG with additional lead V3R and the coronary angiograms performed within 10 days of hospital admission were evaluated in 28 consecutive patients (mean age +/- SD 62 +/- 9 years) admitted to the coronary care unit with anterior wall AMI. Patients were classified into two groups according to the magnitude of ST segment elevation in lead V1: group A (elevation > or = 1.5 mm, n = 12) and group B (elevation < 1.5 mm, n = 16). Two types of conal branch were identified: small (not reaching the interventricular septum [IVS]) and large (reaching the IVS). RESULTS ST segment elevation in lead V3R was found in 11 (92%) and 6 (37%) patients from group A and group B, respectively (p < 0.001); a small conal branch was seen in 10 (83%) and 3 (19%) patients, respectively (p < 0.001). Ten patients (all from group B) had a large conal branch. CONCLUSIONS ST segment elevation in lead V1 in the admission ECG of patients with anterior wall AMI is strongly related to ST segment elevation in lead V3R and is associated with a small conal branch. Our findings suggest that lead V1 reflects the right paraseptal area supplied by the septal branches of the left anterior descending coronary artery (LAD), alone or together with the conal branch. The absence of ST segment elevation in lead V1 during anterior AMI suggests that the IVS is protected by a large conal branch in addition to the septal branches of the LAD (double circulation).

Compliance in Hemodialysis Patients: A Multivariate Regression Analysis

Successful treatment of patients with end-stage renal failure requires, in addition to dialysis, strict control of dietary, fluid and medication intake. In the present study we measured, in 50 chronic hemodialysis patients, serum potassium (K), serum phosphate (PO4) and interdialytic weight gain as indices of diet, medication and fluid compliance, respectively. Dietary compliance did not correlate with fluid or medication compliance, whereas fluid intake and medication compliance were related (p = 0.01). Age, time on dialysis, place of birth and whether the patient came accompanied or not to the dialysis unit were the main variables affecting serum K levels. Sex, ethnic origin and education significantly affected serum PO4. Sex, place of birth, marital status, number of children and years of education affected fluid intake. The compliance of the hemodialysis patient with different aspects of his regimen is thus multifactorial. Attempts to improve compliance and thus reduce morbidity and mortality should be aimed at identifying the population with low compliance and exposing them to educational programs.

Minimal Surgery for Pilonidal Disease Using Trephines: Description of a New Technique and Long-Term Outcomes in 1,358 Patients

PurposeThis study describes and reports the results of a new, minimally-invasive surgical technique for pilonidal disease.MethodsFrom March 1993 to January 2003, 1,358 patients (out of a total of 1,435 patients) with symptomatic pilonidal disease underwent treatment in a military surgical clinic dedicated for pilonidal disease. Patients were operated on under local anesthesia, utilizing trephines to excise pilonidal pits and to débride underlying cavities and tracts.ResultsOne thousand three hundred fifty-eight symptomatic patients participated in the study and were mostly male (84.3 percent) and the mean age 20.9 ± 3.6 years. Rates of postoperative infection, secondary bleeding, and early failure were 1.5, 0.2, and 4.4 percent, respectively. In patients with full postoperative clinical attendance, complete healing was observed within 3.4 ± 1.9 weeks. Phone interview included 1,165 patients (85.8 percent) with a mean follow-up interval of 6.9 ± 1.8 years. Recurrence rates after 1 year was 6.5 percent, 5 years was 13.2 percent, and 10 years was 16.2 percent. Mean time to recurrence was 2.7 ± 2.6 years postoperatively. The disease-free probability estimate was 93.5 percent at one year and 86.5 percent at 5 years.ConclusionsCompared with frequently used pilonidal operations, the trephine technique is associated with a lower recurrence rate and a low postoperative morbidity rate.