Parenteral nutrition admixtures for pediatric patients compounded with highly refined fish oil-based emulsion: assessment of physicochemical stability.

Fish oil-based emulsion is increasingly used in pediatric patients receiving Parenteral Nutrition (PN). However, its unique use in children on long-term PN is nutritionally debatable as some patients are better off with a mixture of long-chain (LCT) or long-chain + medium-chain (LCT + MCT) triglycerides along with Fish Oil (FO). Lipid emulsions are safely infused when particle diameter ranges between 0.4 and 1.0 micron (like chylomicra), according to European guidelines. No data exist on Fish Oil stability when added to other PN components typically present in pediatric formulations such as other lipids or micronutrients. Our goal is to evaluate the stability of a highly refined FO-emulsion in PN admixtures containing LCT or LCT + MCT triglycerides and different calcium content. Stability studies were carried out on six PN admixtures having two levels of calcium concentration compounded with olive oil LCT + FO, LCT + MCT + FO emulsion and pure FO alone, respectively. The analyses were performed immediately at time 0 (t = 0) and 24, 48, 72, 96 (t = 96) hours after compounding. Particle diameters were determined by Light Scattering-Reverse Fourier Optics Technique by means of a Laser Granulometer. Every sample was stored at 4 °C and triple tested. Statistical significance was verified by f-test. In all admixtures, physicochemical stability did not change between t = 0 and t = 96 and particle diameters were in the expected range of 0.4-1.0 micron provided calcium concentration remained below 4.5 mmol/L. When calcium exceeded that level, 12% of particle diameters was larger than 1.0 micron and 2% exceeded 5.0 micron immediately after compounding. In particular, admixtures compounded with olive oil LCT + FO emulsion or FO emulsion alone showed lower particle diameters compared to admixture with olive/soybean LCT alone, probably due to a different steric encumbrance of oleic acid and omega-3 fatty acid. In the PN admixtures tested, containing FO-emulsion alone or in combination with olive LCT or LCT + MCT, the fat emulsion appears to be stable and safe for infusion when calcium concentration is maintained below 4.5 mmol/L. If calcium level exceeds 4.5 mmol/L, as often required in premature patients, it is advisable to infuse FO emulsion alone through a second intravenous line.

How to predict a high rate of inappropriateness for upper endoscopy in an endoscopic centre?

BACKGROUND: Inappropriateness of upper endoscopy (EGD) indication causes decreased diagnostic yield. Our aim of was to identify predictors of appropriateness rate for EGD among endoscopic centres. METHODS: A post-hoc analysis of two multicentre cross-sectional studies, including 6270 and 8252 patients consecutively referred to EGD in 44 (group A) and 55 (group B) endoscopic Italian centres in 2003 and 2007, respectively, was performed. A multiple forward stepwise regression was applied to group A, and independently validated in group B. A <70% threshold was adopted to define inadequate appropriateness rate clustered by centre. RESULTS: discrete variability of clustered appropriateness rates among the 44 group A centres was observed (median: 77%; range: 41-97%), and a <70% appropriateness rate was detected in 11 (25%). Independent predictors of centre appropriateness rate were: percentage of patients referred by general practitioners (GP), rate of urgent examinations, prevalence of relevant diseases, and academic status. For group B, sensitivity, specificity and area under receiver operating characteristic curve of the model in detecting centres with a <70% appropriateness rate were 54%, 93% and 0.72, respectively. CONCLUSIONS: A simple predictive rule, based on rate of patients referred by GPs, rate of urgent examinations, prevalence of relevant diseases and academic status, identified a small subset of centres characterised by a high rate of inappropriateness. These centres may be presumed to obtain the largest benefit from targeted educational programs.

Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service?

BACKGROUND: This prospective study examined the appropriate use of colonoscopy in an open-access system with the American Society for Gastrointestinal Endoscopy guidelines and determined whether the American Society for Gastrointestinal Endoscopy guidelines were associated with relevant endoscopic findings. METHODS: In a cohort of 2221 consecutive patients referred for colonoscopy, the proportion of patients who underwent colonoscopy for appropriate indications was prospectively assessed. The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the positive and negative likelihood ratio of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the American Society for Gastrointestinal Endoscopy criteria. RESULTS: The rate for 'generally not indicated' colonoscopies was 37%. Relevant endoscopic diagnoses were present in 28.5% of cases with American Society for Gastrointestinal Endoscopy indications versus 20.1% of patients without appropriate indications. However, the risk of finding relevant diagnoses was significantly increased by American Society for Gastrointestinal Endoscopy criteria application (odds ratio (OR) 1.58; 99% CI 1.20-2.07; p<0.01). Furthermore, in both endoscopic situations (appropriate and not appropriate), the likelihood ratio, positive and negative, varied very little, suggesting a low predictivity for serious pathologies by the appropriate procedure. CONCLUSIONS: The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected.

Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy.

BACKGROUND/AIMS: In the natural history of gastric cancer, non-invasive neoplasia (NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability (MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer. PATIENTS/METHODS: Fifty five consecutive cases (indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci (BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: (1) no instability in the analysed loci; (2) low frequency MSI (MSI-L); and (3) high frequency MSI (MSI-H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases. RESULTS: Overall, MSI was found in 11 of 55 cases (indefinite for NiN, five of 29 (MSI-L, four; MSI-H, one); low grade NiN, three of 17 (MSI-L, one; MSI-H, two); high grade NiN, three of nine (MSI-L, one; MSI-H, two). CONCLUSIONS: In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non-invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.

Computed tomography study of pineal calcification in schizophrenia.

Computed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21-25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with 'non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear.

Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn's disease and ulcerative colitis.

Polyamines, as well as ornithine decarboxylase (ODC), the enzyme involved in their synthesis, were reported to be closely related to cell proliferation. In Crohn's disease and ulcerative colitis, cell destruction and proliferation increase in the active stage. The aim of the present study was to determine the ODC in both involved and uninvolved areas of the colonic mucosa of active Crohn's disease and ulcerative colitis patients. The patients were divided in two groups, owing to the different level of activity (severe or moderate), by means of clinical endoscopy, laboratory, and histology evaluations. Subjects with suspected disease, but endoscopically unconfirmed, were used as controls. In all ulcerative colitis and Crohn's disease patients the ODC values both in involved and uninvolved mucosa were significantly lower than in controls. In severe Crohn's disease ODC was significantly reduced versus moderate Crohn's disease only in affected tissues. In all ulcerative colitis patients (moderate or severe) the ODC was significantly decreased in involved mucosa compared with uninvolved mucosa. Severe ulcerative colitis showed the significantly lowest ODC. We suggest that the significant decrease of ODC in the bowel mucosa is closely related to the severity of the disease. The highest decrease of ODC in ulcerative colitis patients would be due both to the enhanced cell destruction, and to the feed-back from exogenous increased polyamine production (bowel bacteria, cell desquamation). Therefore ODC would be considered a sensitive index of the inflammatory derangement of the mucosa, especially in acute ulcerative colitis. We conclude that this behaviour may result in an enhanced risk of neoplasia.

Choroid plexus calcification as a possible clue of serotonin implication in schizophrenia.

Choroid plexus calcification (CPC) was measured on computed tomography (CT) scans of 87 schizophrenics and 46 controls divided into age subgroups. We studied the relationship between presence and size of CPC and age in both groups, whilst in the schizophrenic group we also investigated the possible correlation between CPC size and age of onset and duration of illness, duration of formal education, psychopathological features of the illness as well as some neuroradiological brain measures. CPC size correlated with age in healthy controls but not in schizophrenics. In the schizophrenic group, left choroid plexus calcification size correlated with the Scale for the Assessment of Positive Symptoms (SAPS) subscales scores of 'formal thought disorder' whilst right choroid plexus calcification size correlated with the ventricular brain ratio at frontal horns (VBRFH). The data are not conclusive, but a possible correlation with a dysgenetic or functional 5-HT alteration can be hypothesized.

Mortality among workers in an Italian cigarette factory.

A cohort study was conducted to evaluate the mortality pattern among female and male workers in a cigarette factory. The study followed 972 female workers and 761 male workers with at least 6 months of cumulative employment from 1 January 1962 through 1 July 1996. Among women, mortality from all causes of death [standardized mortality ratio (SMR) = 0.9; 95% confidence interval (CI) = 0.8-1.1] and mortality from all malignant neoplasms (SMR = 1.1; CI = 0.9-1.3) were consistent with reference rates. Male workers had a significantly reduced overall mortality (SMR = 0.8; CI = 0.7-0.9), while mortality from all malignant neoplasms was as expected (SMR = 0.9; CI = 0.7-1.0). Among female workers the frequencies of deaths from diseases of nervous system (SMR = 2.0; CI = 1.1-3.4) and from non-Hodgkin's lymphoma (NHL) (SMR = 2.7; CI = 1.0-5.6) were elevated at a statistically significant level. No association between duration of employment and diseases of nervous system was observed. A higher risk for NHL, based on three deaths, was reported among female workers with 15 or more years of employment (SMR = 8.1; CI = 2.2-21.0). Although based on small numbers, the excess of NHL here reported suggests that potential exposure to foliar residues of pesticides should be thoroughly considered in tobacco manufacturing.

Massive screening for colorectal cancer. A single institution's public commitment.

Data from three massive screening programs for the detection of colorectal cancer and adenomatous polyps were reproducible through the collaboration of several departments at Roswell Park Memorial Institute, Buffalo, NY. The majority of carcinomas detected had demonstrated no lymph node metastases. The percentage of screenees with positive stool occult blood tests discovered to have colorectal cancer and adenomatous polyps was 19%, 24%, and 21% in 1982, 1984, and 1987, respectively. The cost-effectiveness of this large-scale screening effort by centers such as Roswell Park Memorial Institute has been demonstrated in accordance with high public acceptance and the high incidence of colorectal cancer.

Reduced natural killer cell activity in major depression: neuroendocrine implications.

Natural killer cell activity (NKCA) was significantly reduced in a group of depressed patients, melancholic subtype, compared to sex- and age-matched controls. Corticotropin and cortisol values were significantly higher in the depressed subjects than in the controls, but no correlation between high hormone levels and low immunological activity was found in the patients.

Effectiveness of a community program to promote early breast cancer detection.

There are no known means of preventing breast cancer, and efforts to control the disease must be directed toward early detection and improved treatment. To assist in achieving this, we developed a two-tier educational program aimed at educating women regarding breast cancer facts and the proper performance of breast self-examination (BSE). Educational efforts are first directed at nurses who are then encouraged to transmit this information to women and their partners in the community. The program combines a lecture and demonstration with more informal small group discussions that allow for individual demonstrations of the technique of BSE. Follow-up of both nurse and lay participants by means of telephone interviews has shown that women can be motivated to practice BSE, and be made aware of proper techniques.

Circulating antibodies in malignant melanoma patients.

Sera from 46 patients with malignant melanoma (MM) in different clinical stages and from 25 healthy blood donors were studied by an indirect conventional immunofluorescent technique (IIT) and by an immunofluorescent complement-fixation test (ICFT). No specific and reliable serological reactivity could be demonstrated against autologous and homologous MM and other nonmalignant pigmented tissues. An increased incidence of diffused antinuclear (ANA; 41%) and cytoplasmic epidermal cell autoantibodies (A-CYT; 71%) was observed in the patients by IIT. Statistical evaluation of the results gave significant values in the chi 2 test in patients for ANA (chi 2 = 5.2061; p less than 0.05) and for A-CYT (chi 2 = 8.9176; p less than 0.01) versus age-matched controls. Thyroid microsomal, gastric parietal cell, smooth muscle and mitochondria autoantibodies were, respectively, detected in 4.3, 4.3, 4.3 and 0% of patients' sera.

Epidermal cytoplasmic antibodies. (Incidence and clinical significance).

Antibodies to epidermal cytoplasmic antigens were detected by the indirect immunofluorescence (IF) technique in 36% of 100 adult healthy subjects and in 17.6% of 17 normal newborn infants. This type of autoantibody occurred in 33% of 100 cases with vitiligo, in 32.5% of 40 cases with psoriasis, in 55.3% of patients with malignant tumours and in 72.7% of subjects with malignant melanoma. The frequency of the autoimmune reactions was statistically significant only in patients with malignant neoplasms. In the majority of positive cases the IF pattern involved the upper layers of the epidermal cells (U-CYT). The basal layer was generally negative. Only a few cases showed a pattern involving both the upper and the basal layers (G-CYT). However, a wide variation in staining was noted when sera were tested on different skin specimens or different sections of the same skin. To identify the nature of the target antigen(s), absorption experiments of sera were attempted with lyophilized and particulate antigens. Animal and human blood cells and lyophilized homogenates of malignant tumours failed to absorb the autoimmune activity of positive sera. Only a powder preparation of keratin induced a decrease in antibody titres. It is postulated that they are the result of an antigenic stimulation by exogenous substances commonly present in the environment.