Cerebral Digital Subtraction Angiography in Acute Intracranial Hemorrhage: Considerations in Critically Ill Children.

Cerebrovascular disorders are an important cause of morbidity and mortality in children. Although minimally invasive, cerebral digital subtraction angiography (DSA) has been shown to be safe in children and is a valuable, and perhaps underutilized, technique for the diagnosis and management of pediatric cerebrovascular disorders in the critical care setting. Through a case-based approach, we explore the utility of DSA in critically ill children with acute intracranial hemorrhage (ICH). We discuss the use of DSA in the acute management of aneurysm and arteriovenous malformation rupture as well as cerebral vasospasm. Those caring for critically ill children with acute ICH should consider cerebral DSA as part of a comprehensive approach to the diagnosis and management of these conditions.

Endoscopic ultrasonography in hepatology: focus on portal hypertension.

Portal hypertension (PHT) is more frequently caused by cirrhosis. Increase in portal pressure induces development of collateral circulation with shunting resulting in disturbances such as gastroesophageal varices (GEV). Prevention and therapy of bleeding from GEV are mandatory. Therefore, the diagnosis of PHT represents a crucial step. Endoscopic ultrasound (EUS), with its combination of endoscopic imaging and ultrasonic capabilities, can offer an almost comprehensive evaluation of portal venous system and porto-systemic collateral circulation. The improved endoscopic view of several video-echoendoscopes has filled the gap between EUS and standard video-endoscopy in diagnosing GEV and in assessing endoscopic criteria of bleeding risk. EUS combined with Color-Doppler capabilities are able to provide hemodynamic information. Furthermore, EUS data allow to stratify patients on the basis of PHT severity and first bleeding risk, monitor the results of pharmacologic and/or endoscopic therapy, predict the response to treatment, quantify the risk of variceal recurrence and recurrent bleeding after GEV obliteration and guide or assist EGD therapy. Despite having this amount of information, there is lack of scientific evidence that EUS imaging and EUS-assisted therapy can have a clear-cut clinical impact and affect patients outcome.

Peel flour of Passiflora edulis Var. Flavicarpa supplementation prevents the insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.

The increase in fructose consumption in the last decades has an important correlation with the growth of overweight population. Fructose is a monosaccharide found in fruits, vegetables and honey, however, it is widely used in processed food and beverages such as sweeteners. This monosaccharide is metabolized in the liver, so it can produce glucose, lactate, triglycerides, free fatty acids and uric acid, which are responsible for negative effects on the liver and extrahepatic tissues. One effect of the high consumption of fructose is the resistance to Insulin, which appears to be an important issue in the development of metabolic abnormalities observed in animals that were subjected to a high fructose diet. The population and, consequently, the market search for natural sources to manage metabolic abnormalities is increasing, but, adequate scientific proof still is necessary. The Passiflora edulis peel flour (PEPF) is a byproduct of the juice industry, and, represents an important source of fiber and bioactive compounds. The present study investigates the PEPF supplementation (30%) effects on insulin sensitivity, adiposity and metabolic parameters in young rats that were given beverages enriched with 10% of fructose for 8 weeks. Fructose intake induced insulin resistance, increased serum triglycerides levels, growth of fat deposits in the liver and widening of the diameter of adipocytes. In contrast, the group that received PEPF did not present such abnormalities, which could be related to the presence of fiber or bioactive compounds (phenolics compounds, e.g., caffeic acid and isoorientin) in its composition, as identified by analytical methods. Thus, for the first time, it has been demonstrated that PEPF supplementation prevents insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.

An evaluation of computer-aided disproportionality analysis for post-marketing signal detection.

To understand the value of computer-aided disproportionality analysis (DA) in relation to current pharmacovigilance signal detection methods, four products were retrospectively evaluated by applying an empirical Bayes method to Merck's post-marketing safety database. Findings were compared with the prior detection of labeled post-marketing adverse events. Disproportionality ratios (empirical Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05)) were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2, individual terms) results of signal detection using DA compared to standard methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved (40.9%). More of the adverse events detected by both methods were detected earlier using DA and grouped (versus individual) terms. With 1939-2004 data, diagnostic properties were similar to those from 1993 to 2004. DA methods using Merck's safety database demonstrate sufficient sensitivity and specificity to be considered for use as an adjunct to conventional signal detection methods.

Instruments and accessories for diagnostic endoscopic ultrasound (radial scanning and miniprobes).

Endoscopic ultrasound (EUS) is a relatively new technology developed in the early 80's, but introduced into the clinical practice only in the late 80's. Nowadays there is an increase in demand for EUS examinations and services, because this technique is more and more recognized as an important and integral part in the diagnostic and staging algorithm of many gastrointestinal (GI) and nongastrointestinal pathologies. Even if today the EUS panorama enrich itself with a large number of different instruments, mechanical and electronic scopes, radial and linear ones, several types of miniprobes and specialty probes, for diagnostic purposes the dedicated radial scanning instruments remain the more adopted choice while miniprobes can have applications only in niche areas, like superficial GI cancers staging, small subepithelial lesions evaluation or intraductal ultrasound and some technological advances are needed to solve the potential drawbacks of this miniaturized probes. At last the EUS equipment borrowed most of the electronic sophistication from the mainstream ultrasonography, this made the choice of an EUS instrument even more difficult and challenging, but you must consider that there is no right or wrong equipment, there is only the right instrument for that specific clinical need or situation.

Role of endoscopic ultrasound in biliary and unexplained pancreatitis.

In the Western world, gallstone disease accounts for approximately half of the cases of acute pancreatitis. The benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has been clearly proven for this disease. On the basis of history, laboratory, and noninvasive imaging studies, about 10-30% of patients with acute pancreatitis have no apparent aetiology. This is critical because it limits the optimal therapeutic management and the prevention of recurrence. Endoscopic ultrasound (EUS) has emerged as an important procedure to clarify the aetiology of acute pancreatitis. After extensive investigation that included EUS, 8-20% of episodes remained idiopathic. Moreover, EUS carried minimal risk when compared to ERCP. The present short review attempts to update on the indications for the employment of EUS in the diagnosis of biliary stones as well as in the clarification of aetiology in the case of unexplained pancreatitis.

Protein kinase C down-regulation, and not transient activation, correlates with melanocyte growth.

The nontumorigenic, immortal line of murine melanocytes, Mel-ab, requires the continual presence of biologically active phorbol esters for growth (R.E. Wilson et al., Cancer Res., 49:711-716, 1989). Comparable treatments of B16 murine melanoma cells result in partial inhibition of cell proliferation. The role of protein kinase C (PKC) in the modulation of growth of cells from these two melanocytic cell lines has been investigated. Significant levels of PKC were present in quiescent Mel-ab cells as determined by Western blotting, whereas no immunoreactive protein was detected in cell extracts from either proliferating Mel-ab or B16.F1 cells. Phosphorylation of a Mr 80,000 protein, which by one- and two-dimensional gel analysis comigrated with the known Mr 80,000 protein substrate of PKC in fibroblasts, was induced in 12-O-tetradecanoylphorbol-13-acetate-stimulated quiescent Mel-ab cells but not in proliferating Mel-ab cells or B16.F1 melanoma cells. Direct measurement of PKC activity in these cells demonstrated a 10-fold greater level of activity in quiescent Mel-ab cells (262 +/- 50 pmol/min/mg SD) compared with growing cells (22.8 +/- 11.8 pmol/min/mg SD). An intermediate level of activity was detected in proliferating B16.F1 melanoma cells (148.5 +/- 20.4 pmol/min/mg SD). The subcellular distribution of PKC was dependent upon the growth state of the cells such that quiescent Mel-ab cells displayed a higher level of activity in the cytosol, whereas growing Mel-ab cells displayed greater activity in the particulate fraction. Like many other transformed lines, B16.F1 melanoma cells constitutively expressed the majority of enzyme activity in the particulate fraction. Measurement of [3H]phorbol ester binding in intact cells paralleled the PKC activation data such that quiescent Mel-ab cells displayed binding of 1612 +/- 147 cpm/10(6) cells, whereas proliferating Mel-ab and B16.F1 melanoma cells displayed binding of 652 +/- 28 and 947 +/- 81 cpm/10(6) cells, respectively. Membrane-permeant diacylglycerol analogues, which activated but did not down-regulate PKC, were devoid of growth-stimulating effects on melanocytes, even in the presence of the specific diacylglycerol kinase inhibitor, R59022. Together, these data show that PKC down-regulation, and not activation, correlates with the growth of melanocytes in culture.

The clerkship in public health: a positive experience.

Cornell University Medical College's required third-year clerkship in public health offers a unique educational experience well received by faculty and students. Within a two-week period, a combination of field trips, seminars, lectures, required reading, and a research paper enables students to gain familiarity with a broad range of issues by placing them in situations exposing them to relevant problems and solutions. Nearly all students find some aspect of either the field trips or seminars provocative. Some are motivated to plan follow-up electives. A similar course using local resources could be offered elsewhere.

The influence of angiotensin converting enzyme inhibitors on lipid peroxidation in sera and aorta of rabbits in diet-induced hypercholesterolemia.

In hypercholesterolemia increased lipid and lipoprotein peroxidation occurs. The renin-angiotensin system plays an important role in atherogenesis. Angiotensin II induces smooth muscle cells proliferation and stimulates oxidation of LDL particles and foam cell accumulation. Inhibition of ang II production leads to decrease in lipid peroxide production. The aim of this study was to assess the lipid peroxidation expressed as concentration of thiobarbituric acid reactive species (TBARS) in sera and aorta homogenates after administration of two doses of angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril and quinapril) in diet-induced hypercholesterolemia in rabbits. Sixty-four New Zealand rabbits were used. Animals were fed with standard fodder, special diet (1% cholesterol content) or special diet + tested ACEI. Two doses of ACE inhibitors were used: i), equivalent to applied to humans, ii), dose 10 times higher. The animals were divided into 8 groups: control, standard fodder; B, special diet; C1, C2, special diet + captopril in doses 2.5 and 25 mg/kg/24 h, respectively; E1, E2, special diet + enalapril in doses 0.75 and 7.5 mg/kg/24 h, respectively; Q1 and Q2, special diet + quinapril in doses 0.75 and 7.5 mg/kg per day, respectively. In cholesterol-fed rabbits and in groups receiving lower doses of tested ACE inhibitors, the serum TBARS concentration at 6 months was significantly higher in comparison to the control. The higher doses of enalapril, quinapril and captopril, prevented the cholesterol-induced rise in TBARS concentration. Lower dose of captopril attenuated the rise in TBARS concentration, it was significantly lower in comparison to group B, but higher than in the control group. In animals from groups B, E1, C1, Q1 TBARS concentration in aortae was significantly higher as compared to control group. Both doses of captopril and higher doses of enalapril and quinapril inhibited the rise of lipid peroxides concentration induced by cholesterol-rich diet.

Serum total cholesterol and triglycerides levels in patients with lung cancer.

Epidemiological studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. The aim of our study was to evaluate serum levels of total cholesterol (TC) and triglycerides (TG) in patients with squamous cell and small cell lung cancer and their dependence on the histological type and the clinical stage of the neoplasm. Lung cancer patients (n=135) and healthy controls (n=39) entered the study. All lung cancer patients had higher rate of hypocholesterolemia and lower TC and TG levels than the control group. TC concentration was lower in lung cancer patients and in both histological types in comparison with the control group, TG level was lower only in patients with squamous cell lung cancer. There were no statistically significant differences of TC and TG levels between the histological types, or between the clinical stages of each histological type.

Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer.

Epidemiological studies show that people with low level of total cholesterol have a greater risk of death due to cancer, predominantly lung cancer. The aim of our study was to evaluate serum level of LDL cholesterol and lipoprotein electrophoresis pattern in patients with small cell lung cancer and their dependence on clinical stage of the neoplasm. The studied group consisted of 34 patients with newly diagnosed small cell lung cancer and 39 healthy controls. Fasting level of LDL cholesterol was analyzed and lipoprotein electrophoresis was performed. There were no statistically significant differences of evaluated serum lipid parameters between lung cancer patients and controls, and between the clinical stages of small cell lung cancer.

Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer.

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.

Diacylglycerol-induced protection against injury during ischemia and reperfusion in the rat heart: comparative studies with ischemic preconditioning.

The role of protein kinase C (PKC) activation in ischemic preconditioning remains controversial. Since diacylglycerol is the endogenous activator of PKC and as such might be expected cardioprotective, we have investigated whether: (i) the diacylglycerol analog 1,2-dioctanoyl-sn-glycerol (DOG) can protect against injury during ischemia and reperfusion; (ii) any effect is mediated via PKC activation; and (iii) the outcome is influenced by the time of administration. Isolated rat hearts were perfused with buffer at 37 degrees C and paced at 400 bpm. In Study 1, hearts (n=6/group) were subjected to one of the following: (1) 36 min aerobic perfusion (controls); (2) 20 min aerobic perfusion plus ischemic preconditioning (3 min ischemia/3 min reperfusion+5 min ischemia/5 min reperfusion); (3) aerobic perfusion with buffer containing DOG (10 microM) given as a substitute for ischemic preconditioning; (4) aerobic perfusion with DOG (10 microM) during the last 2 min of aerobic perfusion. All hearts then were subjected to 35 min of global ischemia and 40 min reperfusion. A further group (5) were perfused with DOG (10 microM) for the first 2 min of reperfusion. Ischemic preconditioning improved postischemic recovery of LVDP from 24+/-3% in controls to 71+/-2% (P < 0.05). Recovery of LVDP also was enhanced by DOG when given just before ischemia (54+/-4%), however, DOG had no effect on the recovery of LVDP when used as a substitute for ischemic preconditioning (22+/-5%) or when given during reperfusion (29+/-6%). In Study 2, the first four groups of study were repeated (n=4-5/group) without imposing the periods of ischemia and reperfusion, instead hearts were taken for the measurement of PKC activity (pmol/min/mg protein+/-SEM). PKC activity after 36 min in groups (1), (2), (3) and (4) was: 332+/-102, 299+/-63, 521+/-144, and 340+/-113 and the membrane:cytosolic PKC activity ratio was: 5.6+/-1.5, 5.3+/-1.8, 6.6+/-2.7, and 3.9+/-2.1 (P=NS in each instance). In conclusion, DOG is cardioprotective but under the conditions of the present study is less cardioprotective than ischemic preconditioning, furthermore the protection does not appear to necessitate PKC activation prior to ischemia.

Surgical treatment for incisional hernias.

BACKGROUND: A great variety of surgical techniques have been proposed to repair large abdominal incisional hernias, but the best results are achieved using synthetic grafts as in the Rives' or Ramirez' procedure. METHODS: During the period September 1993-May 2001, a total of 145 patients, 54 males and 91 females, mean age 52 (range 16-88) with large incisional hernia were observed. Ninety-two hernias were bigger than 10 cm. The average follow-up was 3 years (1-72 months). All successfully underwent surgery using the following techniques: 19 (13.1%) simple fascial sutures, 68 (46.9%) implants of retromuscolar polypropylene grafts (Rives' or Ramirez' technique), 24 (16.5%) subcutaneous meshes, 17 (11.7%) preperitoneal meshes (14 polypropylene, 2 glycolic acid, 1 Goretex), 4 (2.75%) intraperitoneal implants of polypropylene meshes, 13 (9.05%) intraperitoneal glycolic acid grafts plus retromuscular polypropylene graft. RESULTS: One patient died in postoperative for heart failure. Morbidity was 8 subcutaneous hemorrhagic suffusions, 10 seromas which were resolved by repeated percutaneous drainage, 4 suppurating wounds that did not require graft removal, 2 little recurrences treated by a new mesh repair under local anaesthesia, 2 sinus for mesh intollerance and 1 fistula requiring a new intervention. CONCLUSIONS: In this report we discuss the tolerability and reliability of mesh repair, especially in Rives' and Ramirez' technique.

Limits of aortic stop flow infusion chemotherapy in the treatment of advanced cancer.

BACKGROUND: Advanced and relapsed tumors remain a challenging disease with a poor and dismal prognosis. Our choice for inoperable tumors consists in a percutaneous treatment strategy involving intra-arterial chemotherapy and hemofiltration, with previous blood stop-flow, which allows high doses of Cisplatin-cisplatinum, cis-diammine-dichloroplatinum (CDDP) and Mitomycin C (MMC) in the tumor-bearing area with minimal systemic toxicity. METHODS: We analyse the morbidity and mortality associated with stop-flow in 20 patients with unresectable and/or metastatic thoraco- abdominal tumors, non responders to prior systemic chemotherapy. RESULTS: In our experience, the rate of major side effects of the procedure was 31% with a mortality of 5%. The side effects were related to the radiological procedure and to the chemotherapic treatment. A 74-year-old patient died for acute kidney toxicity within 15 days after the procedure. The other transient toxicity symptoms recorded were: nausea, vomiting, increasing of creatinine levels, diplopia and appearance of necrotic ulcer associated to chemotherapic drugs. Concerning the complications related to the radiological technique, the main problem was the rupture of the balloon stop-flow catheter in four patients. CONCLUSIONS: Stop-flow is a new procedure that could develop in the future, thanks to the possibility of obtaining a higher dose intensity of chemotherapic drugs in districts or organs affected by advanced tumors, with less systemic side effects. Unfortunately, the uncertain results in terms of increasing survival and the default of effective devices are to be resolved for a wider application of the procedure.

The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.

Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.

The relationship between E. coli indicator bacteria in well-water and gastrointestinal illnesses in rural families.

OBJECTIVES: To determine the relationship between consumption of E. coli contaminated well-water and gastrointestinal illness in rural families. METHODS: One hundred and eighty-one families with well-water as a drinking source participated in a one-year follow-up study. Water was tested for E. coli bacteria and health outcomes were monitored for house-hold members. RESULTS: E. coli in well-water was significantly associated with gastrointestinal illness in family members, however the relationship was modified by the distance from the septic tank to the well. E. coli had an odds ratio of 2.16 [95% CI 1.04, 4.42] if the septic tank was greater than 20 metres from the well and 0.46 [95% CI 0.07, 2.95] if the septic tank was within 20 metres. CONCLUSIONS: Consumption of contaminated well-water is associated with gastrointestinal illness. E. coli can be a useful marker for detecting wells that pose a potential public health problem in rural areas.

Surgical approach to cervical lymph node metastasis in differentiated thyroid cancer.

BACKGROUND: Precautionary locoregional lymph node dissection in thyroid carcinomas for diagnostic and/or staging purposes is useless both in differentiated (papillary and follicular) and undifferentiated forms. It is only indicated in medullary carcinomas because of their frequent spread to regional lymph nodes. The objective of lymphadenectomy is to contain tumor spread; however, the procedure may be associated with intraoperative complications and postoperative sequelae. In order to improve the therapeutic management of patients with thyroid carcinoma, diagnostic scintigraphy with 201T1 or 99mTc-sestamibi is used in the advanced and undifferentiated forms of this tumor. METHODS: We have treated a woman submitted three years previously to total thyroidectomy for papillary carcinoma (pT3) without subsequent radiometabolic treatment. On physical examination we noted a swelling on the left side of the neck. The lesion was confirmed by ultrasonography, CT scan, and scintigraphic examination with 99mTc-sestamibi 24 hours before planned lymphadenectomy. During the surgical procedure we performed radiodetection to localize metastatic lesions. RESULTS: Intraoperative radiodetection may help to identify residual disease, which is often difficult to trace in the presence of post-surgical fibrosis. In our patient, histological examination of the removed tissue specimens demonstrated that intraoperative radiolocalization had been highly accurate. The eradication of residual disease was confirmed by scintigraphic follow-up after 12 months. DISCUSSION AND CONCLUSIONS: Scintigraphy with 99mTc-sestamibi has been proposed as a means to localize metastatic spread and possible residual disease after a supposedly radical thyroidectomy. Surgical eradication of all residual tumor guarantees the best disease control without having to resort to radiometabolic therapy. This approach will reduce the incidence of iatrogenic comorbidity and consequently improve the patients' quality of life.

The sentinel node in anal carcinoma.

AIMS AND BACKGROUND: Anal cancer is a rare condition. The inguinal lymph nodes are the most common site of metastasis in this neoplasm. The inguinal lymph node status is an important prognostic indicator and the presence of metastases is an independent prognostic factor for local failure and overall mortality. Depending on the primary tumor size and histological differentiation, metastasis to superficial inguinal lymph nodes occurs in 15-25% of cases. METHODS AND STUDY DESIGN: To evaluate the inguinal lymph node status we performed a search for the sentinel node in a female patient affected by squamous and carcinoma. RESULTS: Identification and examination of the sentinel node was positive and postoperative histology showed the presence of bilateral lymph node metastases. CONCLUSIONS: We suggest that examination of the sentinel node in anal cancer could be an efficient way to establish the inguinal lymph node status, which would help the clinician to plan and perform adequate treatment.

The antioxidant enzymes activity in the conditions of systemic hypersilicemia.

The effect of an excessive inorganic silicon oral intake on the activity of basic antioxidant enzymes was studied in rats. Activities of superoxide dismutase, catalase, and glutathione peroxidase were measured in liver and kidney tissues of animals receiving per os sodium metasilicate nonahydrate (Na2SiO3.9H2O) (Sigma, [St. Louis, MO]) dissolved in their drinking water. A decrease of the activity of all the studied enzymes was found in the samples derived from the experimental group. The results obtained indicate the free oxygen radicals participation in the potential pathologic events in the conditions of systemic hypersilicemia.