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Biomedical subjects

P Dotto

Publications and source records attributed to P Dotto.

At least 19 recordsLinked to original sources

Interpretation of expression-profiling results obtained from different platforms and tissue sources: examples using prostate cancer data.

The analysis of expression signatures is a powerful tool for the classification of cancer and other tissue samples. Several protocols and platforms are available on the market, and these lead to both confirmatory and complementary results. We review the main processing techniques for cross-platform comparisons and the different tissue sources for cancer profiling. Some examples and the cross-interpretation of bibliographic data related to prostate cancer are also presented.

Data Collection↗

[A multicentre trial of the diagnostic value and cost of electrocardiography in symptoms suggesting arrhythmia with a new event recorder with transtelephonic transmission].

Events recorders are used for electrocardiographic documentation of symptoms of arrhythmia too sporadic and short lasting to be recorded by 24 hour Holter monitoring. However, there are no French studies comparing the value and cost of event recorders with conventional diagnostic methods. Recently, a new telediagnostic device has become available in France leading to an assessment of the technique. The aim of this study was to determine the value of this event recorder and the cost of diagnostic ECG in the assessment of presumed arrhythmic symptoms such as palpitations or rare tachycardia (<3 episodes per week) of short duration, compared with conventional techniques. Fifty-eight patients with these criteria were randomised, 30 to Survcard (Group I) and 28 to conventional diagnostic methods (Group II). The patients were comparable with respect to age, sex distribution, type of symptoms and associated cardiac disease. The ECG diagnosis of the symptoms was established in 20 cases (66.6%) of patients in Group I in 17 +/- 16 days, and in 14 cases (50.0%) of Group II in 23 +/- 28 days. The difference between the two groups was not statistically significant. The cost of a positive diagnosis for Group I (Survcard) varied from 0 to 228.47 Euro with an average of 71.22 +/- 117.02 Euro. The cost of positive diagnosis in Group II varied from 76.80 to 2340.41 Euro with an average of 480.39 +/- 797.41 Euro. In conclusion, this study showed that the percentage of patients with a positive diagnosis was comparable in the two groups but that the cost was 6 times higher in the group investigated by conventional methods than in the Survcard group because of more costly medical intervention.

Arrhythmias, Cardiac↗

[New systems of mapping and navigation in electrophysiology].

The indications of radiofrequency ablation of arrhythmias have considerably increased since the introduction of the technique in the early 1990s. Interventional rhythmologists now treat arrhythmias which are more and more complex by their mechanism. This requires accurate representation of the ablation catheter position and the integration of spatial and temporal data to identify the arrhythmogenic substrate. The systems of mapping and navigation developed over the last ten years are important tools for interventional rhythmologists. They are very useful for the identification of complex arrhythmogenic substrates which require "individualised" ablations in specific cases. The aim of this article is to review different systems of mapping, and/or navigation currently on the market and their principal characteristics without entering into the details of their use in interventional electrophysiology.

Arrhythmias, Cardiac↗

Correlation between electrogram morphology and standard criteria to validate bidirectional cavotricuspid block in common atrial flutter ablation.

AIM: Assessment of a bidirectional conduction block within the cavotricuspid isthmus (CTI) is critical during radiofrequency (RF) atrial flutter (AF) ablation. We investigated the use of bipolar atrial electrogram (BAE) morphology as an additional criterion identifying CTI block and tested it against two recognized criteria: differential pacing and reversal of the right atrial depolarization sequence during coronary sinus (CS) pacing. METHODS AND RESULTS: An RF ablation procedure was performed during 600 ms CS pacing in 100 consecutive patients with a common AF. BAE recorded along the CTI were continuously monitored. CTI conduction block was achieved by RF ablation in all patients and a clear change in BAE polarity in the Electrogram recorded by the dipoles located on the CTI and immediately lateral to the intended line of block (RS to QR pattern) associated with a confirmed CTI conduction block was observed in all cases. BAE morphology changes predicted bidirectional CTI conduction blocks with a 100% positive and a 100% negative predictive value. At a mean follow-up of 33 +/- 11 months, there was a 5% AF recurrence rate. CONCLUSIONS: Our study suggests that morphological changes in BAE recorded at sites lateral and adjacent to the target line of block may be used as a unique and robust criterion to validate CTI conduction block during AF ablation procedure.

Atrial Flutter↗

What is the 'true' function of skin?

Conventional textbook wisdom portrays the skin as an organ that literally enwraps whatever each of us stands for as a more or less functional, individual member of the mammalian species, and has it that the skin primarily establishes, controls and transmits contacts with the external world. In addition, the skin has long been recognized to protect the organism from deleterious environmental impacts (physical, chemical,microbiological), and is well-known as crucial for the maintenance of temperature, electrolyte and fluid balance. Now, ever more studies are being published that show the skin to also operate as a huge and highly active biofactory for the synthesis,processing and/or metabolism of an astounding range of e.g. structural proteins, glycans, lipids and signaling molecules. Increasingly, it becomes appreciated that the skin, furthermore, is an integral component of the immune, nervous and endocrine systems, with numerous lines of cross-talk between these systems established intracutaneously (e.g. Ann NY Acad Sci Vol 885, 1999; Endocrine Rev 21:457-487, 2000; Physiol Rev 80:980-1020, 2001; Exp Dermatol 10: 349-367, 2001). All these emerging cutaneous functions beyond the classical image of the skin as a barrier and sensory organ are immediately relevant for many of the quandaries that clinical dermatology, dermatopathology, and dermatopharmacology are still struggling with to-date, and offer the practising dermatologist attractive new targets for therapeutic intervention. Yet, many of these skin functions are not even mentioned in dermatology textbooks and await systematic therapeutic targeting. Following a suggestion by Enno Christophers, the current 'Controversies' feature brings together an unusually diverse council of biologists and clinicians, who share their thought-provoking views with the readers and allow us to peek into the future of research in cutaneous biology, not the least by reminding us of the -- often ignored -- evolutionary and embryonal origins of our favorite organ. Hopefully, this unique discussion feature will foster an understanding of the 'true' skin functions that is both more comprehensive and more profound than conventional teaching on this topic, and will stimulate more than 'skin-deep' reflections on the full range of skin functions.

Aging↗

The keratinocyte growth-differentiation switch.

Growth/differentiation control of normal epithelial cells has been relatively understudied, because of the complexities involved in their cultivation and characterization. The present review is focused on progress in this area using the mouse primary keratinocyte system. This system reproduces under well defined culture conditions the switch between epithelial cell growth and differentiation which occurs in vivo, and enables the study of cells derived from wild type mice as well as mice with specific genetic alterations.

Animals↗

Growth regulatory proteins that repress differentiation markers in melanocytes also downregulate the transcription factor microphthalmia.

Expression of basic fibroblast growth factor cDNA or dominantly acting oncogenes, e.g., E1A, in immortalized mouse melanocytes leads to autonomous growth in vitro, depigmentation, and in the case of the oncogenes, tumorigenesis. Because downregulation of pigmentation is a common event in human metastatic melanoma cells grown in culture, we determined the molecular basis of depigmentation in a mouse melanocyte model system. We tested the effect of E1A mutants deficient in their ability to neutralize several regulatory proteins and determined changes in melanogenic gene expression. We identified Microphthalmia as the affected, downregulated transcription factor in melanocytes rendered amelanotic by E1A, basic fibroblast growth factor, or the oncogenes ras or neu, and in an amelanotic cell variant of Cloudman S91 mouse melanoma. Against expectations, sequestration of p300, a transcriptional adaptor that mediates responses to cyclic adenosine monophosphate, was not required for the full transforming effects of E1A. Our results suggest that in addition to controlling tyrosinase (albino locus) and tyrosinase-related protein 1 (TR-P1/gp75/brown locus), both known to possess the DNA consensus site for binding the Microphthalmia protein, this transcription factor also controls other melanocyte-specific genes such as pink-eyed dilution and Pmel 17 (silver), but not tyrosinase-related protein 2 (slaty locus). Furthermore, these findings show that microphthalmia is downregulated not only by experimentally introduced dominantly acting oncogenes but also by the aberrant expression of basic fibroblast growth factor and by spontaneous tumorigenic transformation.

Animals↗

Pepsin concentration in gastroduodenal biopsy homogenates in chronic ulcer disease.

A modification of Berstad's spectrophotometric method was tested and proved capable of detecting pepsin concentrations in mucosal perendoscopic biopsy homogenates. The relationship between this parameter and pepsin in gastric juice and pepsinogen group I in serum and in biopsy homogenates was analyzed. From the biochemical point of view, the assay was found sufficiently accurate. Mucosal pepsinogen group I, but not mucosal pepsin, concentration was found higher in gastric and duodenal ulcer patients than in controls. Patients with corpus-fundic gastric ulcer showed significantly lower mucosal pepsin and mucosal pepsinogen group (PG) I. Aging and smoking did not influence either parameter but male duodenal ulcer subjects presented higher mucosal pepsinogen group I concentration. The lack of any relationship between serum and mucosal PG I and between pepsin in gastric juice and in mucosa raises a question, at least in methodological terms, about the validity of using serum pepsinogen group I and pepsin as indicators of peptic output.

Adult↗

Markers of slow-healing peptic ulcer in the elderly. A study on 1,052 ranitidine-treated patients.

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P = 0.002) and persisting ulcer symptoms (P = 0.0001); indicators of slow-healing DU were ulcer size (P = 0.0001), persisting ulcer symptoms (P = 0.0001), alcohol (P = 0.0003), and NSAID (P = 0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P = 0.0352).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Gastric bicarbonate secretion in high-relapsing, smoking duodenal ulcer patients.

Gastric bicarbonate secretion has been evaluated by Feldman's method in 48 duodenal-ulcer patients. The relationship between smoking, clinical ulcer outcome (healing and recurrence) and bicarbonate secretion has been analysed. Heavy smokers secreted higher bicarbonate ions than did non-smokers. High-relapsing patients produced lower bicarbonate output. These preliminary data suggest that an impaired gastric bicarbonate secretion is associated with smoking, a well-known ulcer-associated factor; further-more, it may single out high-relapsing duodenal ulcer patients.

Adult↗

Helicobacter pylori infection, cigarette smoking and alcohol consumption. A histological and clinical study on 286 subjects.

UNLABELLED: Helicobacter pylori (Hp) is connected with active/chronic gastritis, gastric gastric and duodenal ulcer. It is not known whether exogenous factors are involved in Hp infection. The aim of this prospective study, performed on 286 consecutive subjects undergoing upper gastrointestinal endoscopy, was to evaluate the influence of smoking and alcohol consumption on Hp infection. For each patient the following parameters were taken into account: sex, age, smoking (no, < 10, > 10 cig/day) and alcohol (no, < 40, > 40 g ethanol/day) intake, antiulcer therapy (no, H2-blockers, omeprazole, sucralfate), presence of gastric or duodenal ulcer (DU). At least two biopsies from both the antrum and the corpus were obtained for histological examination; the gastritis was classified and scored according to the Sydney system. STATISTICS: chi-squared test (corrected), Fisher's exact test. RESULTS: 43 pts had Hp (27M, 16F; age 57.8 yrs, range 23-91), 47 Hp ++ (25M, 22F; age 61.1, range 19-86), 81 Hp + (48H, 33F; age 56, range 16-84), 115 Hp- (75M, 40F; age 57.8, range 19-84). Hp infection was found to be significantly correlated with presence of ulcer symptoms, gastritis, lymphoid follicles and, among DU patients, with active DU. The other parameters considered did not influence Hp infection. In conclusion smoking habits and alcohol consumption do not affect Hp infection of the stomach.

Adolescent↗

[Alcohol-dependent mast cell activation in ulcer].

Numerous studies have shown that alcohol causes both acute and chronic damage to gastroduodenal mucosa. The methods of damage differ however, and experimental studies in animals have shown that the degranulation of mast cells in gastric mucosa causes acute hemorrhagic lesions after the consumption of alcohol. It is not known whether this mechanism also operates in man. The aim of the present study was therefore to evaluate whether there is a correlation between mast-cell activation, determined by assaying tryptase levels in gastric mucosa, and the consumption of alcohol in patients with ulcerative diseases. Thirty-one patients with cicatrized ulcerative lesions (13 gastric ulcers, 18 duodenal ulcers) were included in the study. Biopsies at the level of the gastric fundus and antrum and the duodenal bulb were performed in all patients to determine tryptase levels. Biopsy material was frozen and subsequently homogenized; the enzyme was assayed in the supernatant using a radioimmunometric method. The mean daily alcohol consumption was calculated in clinical terms for each patient over the past 5 years and patients were subdivided into non-drinkers and moderate (< 60 g alcohol/day) and excessive (> 60 g alcohol/day) drinkers. It was found that tryptase concentrations were higher in the fundus compared to the gastric antrum and duodenal bulb, irrespective of alcohol consumption both in patients with gastric ulcer and duodenal ulcer. The importance of mast cells in provoking alcohol-dependent damage was studied at a gastric level. Alcohol leads to their degranulation and therefore contributes to the formation of gastric lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Esaprazole effect on acid, peptic and alkaline secretion in duodenal ulcer patients.

To study the effect of Esaprazole, a new antiulcer drug, on acid, peptic and alkaline secretion a modified gastric acid test was performed in 18 duodenal ulcer patients. Pentagastrin was administered as bolus 30' and 75' after the beginning of the test, followed by Esaprazole 300 mg i.v. at 90'. Gastric juice was collected every 15' for determination of: total volume, volume of non parietal secretion, acid, bicarbonate and pepsin output. Serum pepsinogen group I was determined by radioimmunoassay. Esaprazole had a significant inhibitory effect on the total volume of gastric secretion and on volume of non parietal secretion. Pepsin output and serum pepsinogen group I were not affected by Esaprazole, while bicarbonate secretion was reduced. Antiulcer activity of Esaprazole seems to be due to the reduction of total volume of gastric secretion.

Adult↗

Individualized treatment of duodenal ulcer disease. A pilot study.

UNLABELLED: A substantial number of duodenal ulcer (DU) patients relapse despite maintenance treatment with antisecretory drugs. The influence of certain risk factors and the heterogeneity of the disease could explain such behavior. The present prospective, open study compares the one-year clinical outcome (with upper GI endoscopy at the beginning of the study, at 6 and 12 months, and at every symptomatic relapse) of four groups of DU subjects, consecutively recruited from December 1987 to December 1988, separated in accordance with whether or not a bleeding DU episode had previously occurred, and whether or not an evaluation of gastric acid secretion had been made. Thus, Group I (17 patients; 12 males, 5 females) included heavy smokers and/or gastric acid hypersecretors; Group II (13 patients; 12 males, 1 female) non- or light smokers non-hypersecretors; Group III (34 patients; 22 males, 12 females) subjects with unknown gastric acid secretion; Group IV (33 patients; 30 males, 3 females) previously bleeding DU patients. All patients, except those in Group II (who were left untreated), were given ranitidine 150 mg at bedtime. The outcome of Groups I+II was compared with that of Group III (considered as "standard therapy") and Group IV patients, the latter presumably with a low risk of relapse because of the low prevalence of smokers. STATISTICS: Chi-square test, Fisher's exact test, analysis of variance and the logrank test. During the year of follow-up, 27/97 patients withdrew from the study, while 18 had a DU relapse (remission rates 82.1% +/- 7.4% in Groups I+II, 70.5% +/- 8.4% in Group III, 87.5% +/- 5.9% in Group IV).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The natural history of duodenal ulcer disease.

With a view to describing the natural history of duodenal ulcer, currently linked with powerful and widely used drugs, we retrospectively reviewed all patients followed-up at our unit between 1978 and 1989. All DU subjects with at least 5 years of clinical-endoscopic follow-up were admitted to the study. Concomitant gastric ulcer, previous gastrointestinal surgery and treatment other than with H2-blockers (where necessary) were considered exclusion criteria. Forty-four patients (35 males, 9 females, mean age 44.5) proved eligible for this study. At monthly intervals in the patients' history of ulcer disease (starting from a baseline month 0 when ulcer symptoms first appeared), we compared all cases in which the duration of disease coincided, i.e. for each month of the clinical course of the ulcer there was a certain number of patients at the same point in time; patients' histories coincided variously over a period ranging from 0 to 15 years. We considered endoscopically-diagnosed relapses (both symptomatic and asymptomatic) and hemorrhages as marker events for the activity of DU disease. A year-by-year duodenal ulcer activity rate was obtained for both treated and untreated subjects, as follows: No. of events/mean No. of patients followed-up per month x 100. Fisher's exact test and multivariate analysis (stepwise logistic regression) were used to investigate risk factors of poor outcome. We found that the years between the 1st and 5th and between the 10th and 15th from the onset of duodenal ulcer disease had higher peaks of activity, mostly in untreated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗