Colorectal cancer screening: results of a 5-year program in asymptomatic subjects at increased risk.

BACKGROUND AND AIMS: The province of Ferrara has one of the highest incidences of colorectal cancer (CRC) in Italy. In January 2000, we set up a colonoscopy screening program focussing on first-degree relatives of CRC patients. We now report the results 5 years after the beginning of the project. SCREENEES AND METHODS: In October 1999, we started a campaign stressing the usefulness of colonoscopy for the first-degree relatives of CRC patients. Subjects included in the screening program were aged between 45 and 75 years with at least one first-degree relative affected by CRC. They were invited to an interview where a physician suggested colonoscopy as a screening option. RESULTS: In 5 years, 776 subjects were interviewed and 733 (94.4%) agreed to an endoscopic examination (M/F:375/401; mean age 55 years): 562 colonoscopies were performed. Adenomas and cancers were found in 122 (21.7%) and 12 (2.1%) subjects, respectively. Histological examination in 181 persons with lesions (32.8%) showed (most serious lesion quoted) 47 hyperplastic polyps (26% of all lesions), 2 serrated adenomas (1.1%), 68 tubular adenomas (48%), 24 tubulovillous adenomas (13.3%), 9 adenomas with high grade dysplasia (5%) and 12 adenocarcinomas (6.6%). The majority of the cancers were at an early stage (8 Dukes A and 3 Dukes B). Sedation was used in only 42 colonoscopies (7.5%). CONCLUSIONS: A colonoscopy-based screening in this selected high-risk population is feasible. Even without sedation subjects readily agreed to the endoscopic procedure. We identified a significant number of advanced neoplasms and cancers at an early stage suggesting that this could be a useful tool in early identification of CRC.

Evaluation of a new rapid immunoassay for the detection of Helicobacter pylori in faeces: a prospective pilot study.

BACKGROUND: Detection of Helicobacter pylori antigen in faeces is a valid method to diagnose H. pylori infection. Presently available stool tests are performed in the laboratory, and diagnostic report is delayed. AIM: To evaluate a new rapid stool test in a pre-treatment setting and to compare it with a validated laboratory stool test. METHODS: A total of 105 patients underwent gastroscopy with brush cytology, and biopsies for histology and rapid urease test, to assess H. pylori presence. Helicobacter pylori-status was considered positive if at least two tests were positive; negative if all tests were negative; indeterminate if one test was positive and two negative. Stool specimens were tested using either a rapid immunoassay kit (ImmunoCard STAT) or a laboratory enzyme immunoassay kit (Hp StAR). RESULTS: Sixty patients were infected with H. pylori, 44 non-infected, one indeterminate. The sensitivity and specificity of ImmunoCard STAT were 85 and 93%; those of Hp StAR were 88 and 100% (not significant). CONCLUSIONS: ImmunoCard STAT seems a reliable method for detecting H. pylori in untreated patients. It could replace laboratory stool tests, as it is easy and can be performed quickly. These characteristics might be a breakthrough for diagnosing H. pylori in the doctor's office.

Massive bleeding in an adult patient suffering from Meckel's diverticulum.

The case of a 22-year-old male who bled from a Meckel's diverticulum is described. The diagnosis was achieved after 99mTechnetium pertechnetate scintigraphy. With the administration of somatostatin very clear images were obtained. The histological examination confirmed the presence of ectopic gastric mucosa. The literature, over the last 10 years, has been reviewed to identify factors associated with bleeding in adults. Ectopic gastric mucosa is the most important factor predicting bleeding. The diagnostic approach to bleeding Meckel's diverticulum and the improvement in the quality of 99mTechnetium pertechnetate scintigraphy, following administration of somatostatin, is discussed.

Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients.

BACKGROUND: The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested. AIM: To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer. METHODS: In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. H. pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4-6 weeks after the end of treatment, confirmed 4 weeks later by 13C-urea breath test. RESULTS: Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2-97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7-93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%). CONCLUSIONS: One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.

Surface lysine residues modulate the collisional transfer of fatty acid from adipocyte fatty acid binding protein to membranes.

The transfer of unesterified fatty acids (FA) from adipocyte fatty acid binding protein (A-FABP) to phospholipid membranes is proposed to occur via a collisional mechanism involving transient ionic and hydrophobic interactions [Wootan & Storch (1994) J. Biol. Chem. 269, 10517-10523]. In particular, it was suggested that membrane acidic phospholipids might specifically interact with basic residues on the surface of A-FABP. Here we addressed whether lysine residues on the surface of the protein are involved in this collisional transfer mechanism. Recombinant A-FABP was acetylated to neutralize all positively charged surface lysine residues. Protein fluorescence, CD spectra, and chemical denaturant data indicate that acetylation did not substantially alter the conformational integrity of the protein, and nearly identical affinities were obtained for binding of the fluorescently labeled FA [12-(9-anthroyloxy)oleate] to native and acetylated protein. Transfer of 2-(9-anthroyloxy)palmitate (2AP) from acetylated A-FABP to small unilamellar vesicles (SUV) was 35-fold slower than from native protein. In addition, whereas the 2AP transfer rate from native A-FABP was directly dependent on SUV concentration, 2AP transfer from acetylated protein was independent on the concentration of acceptor membranes. Factors which alter aqueous-phase solubility of FA, such as ionic strength and acyl chain length and saturation, affected the AOFA transfer rate from acetylated but not native A-FABP. Finally, an increase in the negative charge density of the acceptor SUV resulted in a marked increase in the rate of transfer from native A-FABP but did not increase the rate from acetylated A-FABP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term cyclic and periodic omeprazole in the prevention of recurrences of duodenal ulcer]. / Omeprazolo long-term a cicli e a domanda nella prevenzione delle recidive dell'ulcera duodenale.

The aim of this study was to establish if the discontinuous assumption of omeprazole was effective to reduce the recurrence of duodenal ulcer disease as the cyclic periodical assumptions of the same drug. Consequently two different posologies, after duodenal ulcer recovery, were compared, both based on omeprazole. In the first trial 20 mg/die were administrated for the first 15 days of every month, for 1 year. In the second, the same dose were administrated for 15 days only when symptoms occurred. It was not utilised a comparison with placebo or other drugs. Symptomatic score and recurrence rate were evaluated by means of EGDS after 6 months and 1 year. In some patients were also controlled the gastrinemia. Both trials were effective in the prevention of duodenal ulcer relapse, without increasing gastrinemia. Nevertheless patients assuming omeprazole only when symptomatic, showed a greater symptomatic score. Concluding, the assumption of omeprazole only when symptoms occur is effective in the prevention of relapse but require a close relation between patients and the medical team.

Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1.

Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.

Specific uptake of retinol-binding protein by variant F9 cell lines.

Serum retinol-binding protein (RBP) specifically binds to and is internalized by F9 embryonal carcinoma cells. Monolayers of F9 cells were differentiated into a primitive endoderm stage by addition of retinoic acid. Fluorescein-derivatized or radiolabeled RBP associated with F9 cell monolayers at 37 degrees C in a time- and concentration-dependent manner. Competition by simultaneous incubation with excess unlabeled RBP indicated that this association was specific and saturable; the apparent dissociation constant was 200-300 nM using either tracer. At 37 degrees C, over 80% of the cell-associated RBP was internalized, and only a small fraction was bound to the cell surface; fluorescence microscopy indicated that internalized RBP was in small vesicles within the cytoplasm. Internalized RBP was subsequently degraded and released from the cell in an acid-soluble form. Parental F9 cells were heterogeneous in their ability to associate with RBP. Random subcloning identified natural variant F9 cell lines which did, or did not, express this biological activity upon retinoic acid-induced differentiation. The clonal nature of the capacity for RBP uptake suggests that this specific internalization is a heritable trait. Together, these observations provide strong evidence that RBP uptake occurs by a receptor-mediated process in F9 cells. The cycle of RBP internalization and degradation by F9 cells bearing specific RBP receptors may provide a regulable mechanism for the cellular accumulation of serum retinol.

Cloning, sequencing and chromosomal assignment of a gene from Saccharomyces cerevisiae which is negatively regulated by glucose and positively by lipids.

We report the molecular cloning, nucleotide (nt) sequence and chromosomal assignment of the Saccharomyces cerevisiae gene GLP1. This gene encoded a 15-kDa protein that was synthesized at a low level during growth on glucose and was induced ninefold upon glucose deprivation. When glucose withdrawal was accompanied by the addition of fatty acids the induction was enhanced an additional two- to threefold. The GLP1 gene product was identified as a soluble protein and purified using a combination of gel permeation and ion exchange chromatography. Using oligodeoxyribonucleotides as hybridization probes we have isolated the GLP1 gene and sequenced the single, long open reading frame which is 351 nt in length and is not interrupted by introns. The GLP1 gene directed the transcription of a 700-nt mRNA in response to glucose deprivation. The accumulation of the mRNA was further enhanced twofold by the addition of oleate. We have localized the GLP1 gene to S. cerevisiae chromosome VI.

Primary CNS lymphoma in AIDS. A clinical and pathological case report.

A case is reported of a primary central nervous system lymphoma in a heterosexual patient affected by acquired immunodeficiency syndrome. Because of the rarity and the aggressive diagnostic procedures, pre-mortem diagnosis is seldom established. This radiosensitive tumor, however, often contains monoclonal immunoglobulin productive cells and shows, at CT-scan, a multicentric arrangement. On this basis, a careful analysis of the cerebrospinal fluid and CT-scan may offer a possible mean of earlier diagnosis and improve the survival of these patients.

Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA.

Human adipocyte lipid-binding protein (H-ALBP) was purified from normal subcutaneous adipose tissue to greater than 98% homogeneity, utilizing a combination of acid fractionation, gel filtration, covalent chromatography on activated thiol-Sepharose 4B, and anion-exchange chromatography. Human ALBP comprised about 1% of total cytosolic protein in human adipose tissue, had a relative molecular mass of about 15 kDa, and existed as a monomer in solution. The amino terminus of H-ALBP was blocked to sequencing. When a liposome ligand delivery assay was used, H-ALBP saturably bound oleic acid with about 1 mol of ligand bound per mole of protein. Additionally, H-ALBP saturably bound retinoic acid as determined by the quenching of intrinsic tryptophan fluorescence. A full-length H-ALBP cDNA has been cloned; the sequence predicts a 649-base mRNA comprised of a 62-base 5'-noncoding region containing an 18S ribosome-binding site, a single 396-base open-reading frame, and a 191-base 3'-noncoding region. Comparative sequence analysis indicated that the 132 amino acid H-ALBP is a member of a multigene family of intracellular lipid-binding proteins and contains the consensus substrate phosphorylation sequence for tyrosyl kinases.

Purification of murine adipocyte lipid-binding protein. Characterization as a fatty acid- and retinoic acid-binding protein.

An adipose-specific protein has been purified from murine 3T3-L1 adipocytes to greater than 98% homogeneity. A purification procedure was developed utilizing a combination of gel filtration, cation exchange chromatography, and covalent chromatography on activated-thiol Sepharose 4B. The protein exists as a single polypeptide with a molecular weight of about 15,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein contains 2 mol of reduced sulfhydryl groups per mol of protein and an amino terminus blocked to sequencing. Automated Edman degradation of trypsin and CNBr-derived peptides has verified that the purified protein is that predicted by the mRNA (Bernlohr, D. A., Angus, C. W., Lane, M. D., Bolanowski, M. A., and Kelly, T. J. Jr. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5468-5472). Based on sequence analysis, the 15-kDa adipocyte protein is considered to be a member of a family of tissue-specific, cytosolic lipid-binding proteins. Utilizing a liposome assay, the purified protein binds both oleic acid and retinoic acid saturably with approximately 1 mol of ligand bound per mol of protein. Dissociation constants determined from Scatchard analysis were 3 and 50 microM, respectively. This report represents the first demonstration of a member of this family of structurally related proteins that is capable of binding both fatty acid and retinoic acid. Hence, we propose the name adipocyte lipid-binding protein, or ALBP.

An in vitro model to study bacterial invasion of periodontal tissues.

In periodontal disease, the abilities of bacteria to adhere to and degrade in vivo basement membranes should be considered as two of the rate-limiting steps for the potential active or passive invasion of gingival connective tissues. To study these mechanisms in greater detail, we used the PF HR-9 basement-membrane-like matrix to establish an in vitro model of bacterial invasion and degradation. Three gram-negative anaerobic periodontopathic organisms, Bacteroides gingivalis, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans, bound in considerably higher numbers to the HR-9 matrix than did 6 strains of gram-positive facultative organisms typically associated with periodontal health. In a further experiment with B. gingivalis, the organism rapidly degraded Type IV collagen, the major macromolecular component constituting the HR-9 matrix. Streptococcus mitis, the nonperiodontopathic bacterium tested, did not degrade this model matrix. This study provides evidence that B. gingivalis, a periodontopathic bacterium, is able to adhere to and degrade basement membranes, whereas nonperiodontopathic organisms appear not to share in these abilities.

Sex differences in adults' spatial and verbal memory span.

Spatial span (Corsi's block-tapping test) and verbal span (Wechsler Digits Forward test) were measured in 300 medical students (150 males and 150 females). Significant differences pointing to a better performance of males were found on both spatial span (p less than 0.001) and verbal span (p less than 0.05).