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Biomedical subjects

S Marin

Publications and source records attributed to S Marin.

At least 19 recordsLinked to original sources

Mapping of Aspergillus Section Nigri in Southern Europe and Israel based on geostatistical analysis.

Geostatistical analysis was applied to the incidence of Aspergillus Section Nigri and A. carbonarius in Southern Europe and Israel for the 3-year period 2001-2003 to facilitate identification of regions of high risk from contamination with these fungi and production of ochratoxin. The highest incidence of black aspergilli was normally observed at harvesting. At this grape growth stage, spatial variability of black aspergilli was significantly related to latitude and longitude, showing a positive West-East and North-South gradient. Predictive maps of infected berries incidence were drawn and showed the same trend in the 3 years, but incidence was highest in 2003, followed by 2001 and 2002. The highest incidence was always observed in Israel, Greece and Southern France, associated with the highest incidence of A. carbonarius. Southern Spain and Southern Italy also had relevant incidence of black aspergilli. The thermo-wetness maps for the 3 years showed a trend similar to the incidence of black aspergilli. The coldest and wettest year was 2002, while 2003 was the hottest and driest, particularly during August, with Israel being the hottest and driest country, followed by Greece and Southern Italy. This indicates that meteorological conditions can contribute to explain spatial distribution variation of black aspergilli within the Mediterranean basin.

Aspergillus niger↗

Role of visceral proteins in detecting malnutrition in the elderly.

OBJECTIVE: In the clinical practice, visceral proteins are used as indirect markers of protein energy malnutrition (PEM), but their reliability could be reduced with advancing age. The aim of this work is to investigate the reliability of albumin, prealbumin, retinol-binding protein (RBP) and transferrin in evaluating nutritional status in old patients and their relationship with fat-free mass (FFM). DESIGN: Cross-sectional study. SETTING: Padua, Italy. SUBJECTS: In 44 underweight (body mass index < 20 kg/m(2)) (66-97 years) and 69 normal weight or overweight elderly subjects (62-98 years), albumin, prealbumin, transferrin and RBP were determined in the plasma. Body composition and particularly FFM was obtained by dual X-ray absorptiometry. FFM was also expressed as FFM index (FFMI) calculated as FFM divided by height squared. Subjects affected by acute illnesses and inflammatory states were excluded. RESULTS: Albumin, prealbumin and RBP mean values were significantly lower in underweight subjects. No differences between two groups were found for transferrin. Albumin prealbumin and RBP resulted under the normal range in 55, 25 and 54% of underweight subjects, respectively. Transferrin's values were low in about 40% of underweight and normal weight subjects, respectively. In all subjects, FFMI shows a significant correlation with albumin (r: 0.52), prealbumin (r: 0.64) and RBP (r: 0.57). No correlation between FFMI and transferrin was found. CONCLUSIONS: Visceral proteins, except for transferrin, seem to be useful indexes in detecting malnutrition in the elderly; low values still in the normal range should also be carefully evaluated because they could suggest a poor nutritional status.

Absorptiometry, Photon↗

Major surgery in a severe haemophilia A patient with high titre inhibitor: use of the thrombin generation test in the therapeutic decision.

Summary. In haemophilia patients with inhibitor, elective orthopaedic surgery is usually performed under recombinant activated factor VII (rFVIIa). We report here the case of a severe haemophilia A patient with a high inhibitor who needed a bilateral total knee arthroplasty. Recombinant FVIIa was previously shown to be ineffective for the treatment of muscle and joint bleedings, and he had a history of excessive postoperative bleeding under activated prothrombin complex concentrate (APCC). Thrombin generation test (TGT) was used to assess the efficacy of Factor Eight Inhibitor Bypassing Activity (FEIBA). Insufficient correction of thrombin-generating capacity was observed after administration of 75 U kg(-1) FEIBA. In a multidisciplinary environment, a bilateral total knee arthroplasty was performed using a protocol combining immunoadsorption of inhibitors preoperatively associated with FVIII replacement during a first phase followed by FEIBA when the inhibitor reappeared. To our knowledge this is the first direct application of TGT in the management of haemophilia patients with inhibitor, which indicated that a sequential use of immunoadsorption, FVIII and FEIBA was the most appropriate treatment to perform this major elective surgery. This case demonstrates that this combined protocol can be safely used to cover major surgery in inhibitor patients. In addition, it also suggests that TGT may have a major contribution in the decision-making process of the most adapted therapy for the treatment of such high-risk patients.

Adult↗

Dermatofibrosarcoma protuberans with onset in early childhood: a case report.

Dermatofibrosarcoma protuberans is a tumour that grows locally, infiltrating the subcutaneous tissue; it is uncommon in children. We report the case of a 27-year-old man who had had such a lesion from the age of 3 years, and it had enlarged during his lifetime. A wide local excision with margins of 3.0 cm was performed, but the lesion was not entirely removed. This is a new report of infantile dermatofibrosarcoma protuberans, and this case reflects the need for Mohs micrographic surgery.

Adult↗

Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.

Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13C2]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 microm STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m1/Sigma(m)n ratio in RNA. Based on the in vitro proliferation data, the IC50 of STI571 in K562 cultures is 0.56 microm. The decrease in 13C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m2/Sigma(m)n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.

Antineoplastic Agents↗

Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells.

The fermented wheat germ extract with standardized benzoquinone composition has potent tumor propagation inhibitory properties. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2-13C2]glucose isotope is used as the single tracer with biologic gas chromatography-mass spectrometry. MIA cells treated with 0.1, 1, and 10 mg/mL wheat germ extract showed a dose-dependent decrease in cell glucose consumption. uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 28.0%), and release of 13CO2. Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also significantly increased with all doses of wheat germ extract. The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules. Wheat germ extract treatment is likely associated with the phosphorylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell proliferation-related structural and functional macromolecules (RNA, DNA) and the direct oxidative degradation of glucose, which have devastating consequences for the proliferation and survival of pancreatic adenocarcinoma cells in culture.

Adenocarcinoma↗

[Natural contamination with mycotoxins in forage maize and green coffee in Nayarit State (Mexico)].

The presence of mycotoxins in forage maize (zearalenone, fumonisin B1, T-2 toxin and diacetoxyscirpenol) and green coffee (ochratoxin A) from Nayarit State (Mexico) has been studied. All maize samples analyzed showed fumonisin B1 contamination, with an average concentration of 2,541 microg/kg. Fifteen percent of the samples contained zearalenone, with an average concentration of 1,610 microg/kg. Only one sample showed T-2 toxin contamination (7 microg/kg), and no diacetoxyscirpenol was detected. Sixty-seven per cent of green coffee samples were contaminated with ochratoxin A, with an average concentration of 30.1 microg/kg. This is the first study about mycotoxins developed in Nayarit and it has shown that mycotoxin contamination is a real problem in both foodstuffs studied.

English Abstract↗

Association of CagA-positive and CagA-negative Helicobacter pylori strains with patients' symptoms and gastritis in primary care patients with functional upper abdominal complaints.

BACKGROUND: CagA-positive Helicobacter pylori strains have been reported to be associated with peptic ulcer or malignancy more often than cagA-negative strains. Less is known about the relation of H. pylori serology (CagA-negative or CagA-positive) to histologic changes in the stomach of patients with functional upper abdominal complaints. The association of H. pylori status with patient symptoms or with different subgroups of non-organic dyspepsia is also obscure. In the present study patients' symptoms and their relation to H. pylori serology (H. pylori-negative, H. pylori-positive but CagA-negative, and H. pylori-positive and CagA-positive) were evaluated in general practice patients who had functional upper abdominal complaints. The association of H. pylori serology with different symptom-based subgroups of functional upper abdominal complaints was also assessed. The severity and activity of inflammation and the presence of atrophy and intestinal metaplasia in the antrum and body were evaluated and compared with H. pylori status. METHODS: Four hundred consecutive unselected dyspeptic patients in primary care were investigated by means of gastroscopy, upper abdominal ultrasound, laboratory screening including H. pylori and CagA serology, and other examinations if needed. Of these patients 193 with functional upper abdominal complaints were enrolled in this study. RESULTS: Of the study patients 87 (45%) were H. pylori-negative, 70 (36%) were H. pylori- and CagA-positive, and 36 (19%) were H. pylori-positive but CagA-negative. There were no differences in the occurrence of any dyspeptic symptoms between H. pylori-related subgroups. Nor was there an association between H. pylori status and symptom-based subgroups in our study patients. Inflammation of the stomach was related to H. pylori infection, but CagA-seropositive patients did not have moderate or severe inflammation more often than CagA-seronegative ones. CagA-seropositive patients with functional upper abdominal complaints did not have atrophic changes or intestinal metaplasia in the stomach more often than those who were CagA-negative. CONCLUSIONS: H. pylori or more specific CagA serology is not associated with any specific symptom profile of dyspepsia or with any symptom-based subgroups in patients with functional upper abdominal complaints in primary care. The study patients with CagA seropositivity did not have more severe histologic changes in the stomach than the patients who were H. pylori-seropositive but CagA-seronegative.

Abdominal Pain↗

Hypermethylation of the APC (adenomatous polyposis coli) gene promoter region in human colorectal carcinoma.

Germline mutations of the putative tumor suppressor gene APC are associated in high frequency with the familial adenomatous polyposis, predisposing the patients to colorectal neoplasia. Similarly, sequence analyses have revealed that in more than half of patients with sporadic colorectal carcinoma or adenoma, the APC gene was mutated. By employing genomic sequencing, i.e., base-specific analysis of methylated cytosines, we show here that the promoter region of the APC gene is heavily methylated at CpG sites in patients with colorectal carcinoma in comparison with normal colonic mucosa and premalignant adenomas. Our results suggest that cytosine methylation of the regulatory sequences of the APC gene could be involved in the progression of human colorectal cancer.

Adenoma↗

Nuclear morphometry as a predictor of disease outcome in gastric cancer.

Nuclear morphometric features including nuclear area (NA), nuclear perimeter (PE), their variation (SDNA, SDPE), and mean largest and smallest nuclear diameters (Dmax, Dmin) were examined in 116 patients with stage I-II gastric adenocarcinoma. Morphometric measurements were compared with tumour differentiation, depth of invasion (pT), lymph node status (pN), and Lauren classification. All morphonuclear features were significantly larger in the intestinal type than in the diffuse type of cancer. None of the morphometric variables was related to TNM status or tumour size. Nuclear area and perimeter and their variation were closely related to survival in univariate analysis, patients with small and regular nuclei surviving longer. In the multivariate analysis, pT, pN, perineural invasion, and the standard deviation of nuclear perimeter (SDPE) were independent predictors of survival. Nuclear morphometry is a quantitative, objective, and highly reproducible method of revealing malignant features in several neoplasms. The results of the present study suggest that nuclear morphometric data may help in defining prognosis in gastric cancer.

Adenocarcinoma↗

Hypermethylation of the WT1 and calcitonin gene promoter regions at chromosome 11p in human colorectal cancer.

The short arm of the chromosome 11, known to harbour a number of putative and established tumour-suppressor genes, is frequently hypermethylated in various human neoplasms. We subjected the promoter regions of two genes residing at 11p, namely the tumour-suppressor gene WT1 (Wilms' tumour gene) (11p13) and the calcitonin gene (11p15.5), to methylation analysis in human sporadic colorectal cancer using genomic sequencing. Both genes showed significant hypermethylation of CpG sites within their promoter regions in adenomas and carcinomas compared with normal colonic mucosa. Although the WT1 promoter region was significantly hypermethylated, two CpG sites located in Sp1 motifs were unmethylated in the majority of cases (68-74% of carcinomas). The expression of WT1 gene, as revealed by in situ hybridization, showed no differences between normal colonic mucosa and malignant carcinoma. Together with earlier observations, our present results support the view that the short arm of human chromosome 11 is subjected to widespread regional hypermethylation in various human malignancies.

Adenoma↗

p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Adult↗

Determination of trace level impurities in uranium compounds by ICP-AES after organic extraction.

The determination was studied of Al, B, Be, Cd, Ca, Co, Cu, Mg, Mn, Mo, Pb, Si, Sn, V, Cr, Ni, and Fe as trace level impurities in uranium compounds by ICP-AES after extraction of uranium with three different mixtures of di-(2-ethyl-hexyl) phosphate (D2EHP) and tri-(2-ethyl-hexyl)-phosphate (T2EHP) in solvents like toluene, carbon tetrachloride, hexane and cyclohexane. The study was carried out in presence of different concentrations of HCl and HNO(3). A single extraction with D2EHP in cyclohexane using nitric acid as matrix was sufficient to reduce the U(3)O(8) concentration from 100 g/l to 100 microg/ml. The ICP-AES instrumentation applied, allowed the determination of metal concentrations ten-times lower than those usually found in nuclear grade U(3)O(8). To check the efficiency of the extraction and the accuracy of the proposed method, Certified Reference Materials were used in the dissolution and extraction steps. The method described can be used for the determination of trace metals in nuclear grade U(3)O(8).

Journal Article↗

Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration.

A retrospective analysis of 321 gastric cancer patients was made to assess the prognostic value of TNM classification, tumour differentiation, Laurén classification, proliferative rate, inflammatory reaction and tumour invasion in vascular or neural structures of the gastric wall. The TNM classification showed the strongest correlation with survival in univariate and multivariate analyses (P < 0.0001). The invasion in lymphatic or vascular system and Laurén classification were also independent prognosticators in multivariate analysis (P < 0.05). In univariate analysis, the WHO-grade, the size and the location of the tumour and perinueral invasion were significant prognostic factors (P < 0.01), as were the infiltration of lymphocytes and plasma cells in the tumour (P < 0.05). On the other hand, the mitotic indices reflecting the proliferative activity of the tumour cells showed no significant correlation with the prognosis. The results indicate that the prognostic power of the TNM classification can be further increased by assessment of the above special histological features in gastric cancer.

Adult↗

Retroperitoneal fibrosis with antineutrophil cytoplasmic antibodies.

A middle aged man showed retroperitoneal fibrosis with signs of vasculitis verified by biopsy of the retroperitoneal mass. Antineutrophil cytoplasmic antibodies (ANCA) with cytoplasmic staining pattern (cANCA) were strongly positive, although there were no clinical or histological signs of Wegener's granulomatosis. No cases of cANCA associated retroperitoneal fibrosis have been described except in connection with Wegener's granulomatosis. ANCA have been found to associate with any inflammatory disorders. This observation may broaden the clinical spectrum of cANCA positive vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗

Enterococcus faecium strains with vanA-mediated high-level glycopeptide resistance isolated from animal foodstuffs and fecal samples of humans in the community.

The occurrence and the further spread of high-level glycopeptide-resistant, vanA-positive Enterococcus faecium strains outside of hospitals have been investigated. We could isolate such bacteria directly from thawing liquids of commercially produced frozen poultry (chickens, turkeys; no further data on previous feeding with avoparcin were available). In 5 of 13 samples of raw minced meat of pigs originating from 13 different butcher's shops, glycopeptide-resistant E. faecium (VanA type) could be detected after overnight broth cultivation of these samples. No glycopeptide-resistant enterococci could be isolated from meat samples of chickens that were fed without avoparcin. VanA type E. faecium strains were also identified in 12 fecal samples recovered from 100 nonhospitalized humans in the rural area of Saxony-Anhalt federal county. These results suggest a possible role of the food chain in the spread of glycopeptide-resistant E. faecium. Molecular typing (macrorestriction and multilocus enzyme analysis) reveal a wide dissemination of the vanA gene among strains of different ecological origins.

Animals↗

Effect of water activity and temperature on growth and fumonisin B1 and B2 production by Fusarium proliferatum and F. moniliforme on maize grain.

The effect of different water activities (aw, 0.968, 0.956, 0.944, 0.925) and temperature (25 degrees C and 30 degrees C) on colonization and production of fumonisin B1 (FB1) and B2 (FB2) on sterile layers of maize by Fusarium proliferatum and F. moniliforme isolates was determined over periods of 6 weeks. Generally, both F. moniliforme and F. proliferatum grew faster with increasing aw and best at 30 degrees C. All three isolates produced more FB1 than FB2 regardless of aw or temperature. Very little FB1 and FB2 were produced at 0.925 aw, with maximum produced at 0.956 and 0.968 aw at both temperatures tested. Most FB1 and FB2 were produced by F. moniliforme (25N), followed by F. proliferatum isolates (73N and 131N). At all aw levels and both temperatures there was an increase in FB1 and FB2 concentration with time. Statistical analyses of aw, temperature, time, two- and three-way interactions showed some significant differences between isolates and FB1 and FB2 production.

Fumonisins↗

Comparison of classic and quantitative prognostic factors in hormone receptor-positive and hormone receptor-negative female breast cancer.

The prognostic variables of 281 women with breast carcinoma (followed up for more than 8 years) were studied using Cox's analysis. Clinical and histologic features, nuclear morphometric variables, and mitotic indices were analyzed separately in progesterone receptor-negative (PR-) and -positive tumors (PR+). In PR- tumors, axillary lymph node status (p = 0.0025) and tumor size (p = 0.03) were predictors of survival in the univariate analysis. Tumor size (p < 0.0001), axillary lymph node status (p = 0.0006), the volume-corrected mitotic index (M/V index) (p = 0.0023), and the mitotic activity index (MAI) (p = 0.0067) were found to be related to survival according to univariate analysis of PR+ tumors. In PR- tumors, axillary lymph node status (p = 0.002), year of treatment (p = 0.017), and circumscription of the tumor margin (p = 0.02) had independent predictive value. In PR+ tumors, tumor size (p < 0.001), the MAI (p = 0.001), and axillary lymph node status (p = 0.04) predicted survival independently in Cox's analysis. In PR- tumors, histologic type (p = 0.008) was an independent predictor of recurrence-free survival, whereas in PR+ tumors, the M/V index (p < 0.001), tumor size (p = 0.007), and the standard deviation of the nuclear perimeter (p = 0.026) were independently related to recurrence-free survival. The results indicated that mitotic indices and nuclear morphometric variables are of limited value in predicting patient survival in breast carcinomas that are hormone receptor negative. Thus, a separate analysis is advocated for hormone receptor-positive and -negative tumors when the predictive value of quantitative measurements and histologic variables is tested in patients with breast cancer.

Aged↗