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Biomedical subjects

M Curzio

Publications and source records attributed to M Curzio.

At least 19 recordsLinked to original sources

Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a diagnostic and therapeutic challenge.

Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary infections are the first cause of death. We report on a patient with CTCL who, after more than 10 years of aggressive antineoplastic treatments, showed extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were inconclusive for an infectious process, and the patient was still asymptomatic. The diagnosis of mycobacteriosis was made on the microbiologic exam of bronchoalveolar lavage. Specific treatment was started with contemporary dosage reduction of chemotherapy. After six months of antibiotic treatment the pulmonary lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic regimen was started obtaining control of CTCL, without aggravation of the pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls encountered when pulmonary mycobacteriosis complicates the course and treatment of CTCL.

Adult↗

Quality assurance and colonoscopy.

BACKGROUND AND STUDY AIMS: Little is known concerning the usefulness and feasibility of quality assurance programs in gastrointestinal departments. The aim of this study was to identify the indicators of quality in colonoscopy, to check their use in clinical practice, and to identify their threshold values. MATERIALS AND METHODS: A prospective study was performed in four endoscopic units. In the first phase, a questionnaire was used to identify the indicators that were considered important and easy to record; in the second phase, the selected items were prospectively recorded. RESULTS: Data from 603 colonoscopies were evaluated. The selected indicators were: rate of cecal intubation, rate of examinations with normal findings, rates of complications, appropriateness of indications, use of a washing machine for disinfection, duration of the disinfection procedure, rate of procedures repeated due to poor colon cleansing, rate of operative procedures, length of waiting time, rate of procedures performed for follow-up of known disease, experience of the operator, and rate of procedures performed with the patient under conscious sedation. A striking difference emerged between the technical standards at three centers, which were fairly good, and the standard at the fourth center, which was less satisfactory. The length of the waiting time was high in all centers, as well as the rate of examinations conducted with an inappropriate indication. The rate of procedures performed under conscious sedation varied widely between the centers. CONCLUSIONS: The study of the indicators of quality of colonoscopy is feasible and easy to perform in clinical practice, and can be useful for quality assurance programs.

Adolescent↗

[Topical beclomethasone dipropionate (BDP) in intestinal inflammatory diseases: the results of a multicentre trial].

The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.

English Abstract↗

Are we correctly using the inhibitors of gastric acid secretion and cytoprotective drugs? Results of a multicentre study.

AIM: To evaluate indications and frequency of prescriptions of pH-modifying and cytoprotective drugs in hospital departments. DESIGN OF THE STUDY: Multicentre cohort transverse relevation. MATERIALS AND METHODS: On a randomly selected day the clinical charts of 3685 inpatients were reviewed by a gastroenterologist and data were collected concerning the drug used, its dosage and indications for the prescription. RESULTS: 26.8% of hospitalized patients were under treatment on the day of the study. Ranitidine was the most frequently prescribed (73.9%). The purpose of treatment was cure of acute disease or symptoms in 27% of cases and prevention of peptic damage in 73%. Fear of development of stress mucosal lesions (28%) and therapy with other drugs (56%) motivated prophylactic treatment in the majority of cases. The examination of clinical charts failed to demonstrate any need for treatment in 51.4% of the patients. Disparities in the frequency of prescription between different departments and hospitals were found. CONCLUSION: Criteria used for prescription of drugs for peptic diseases in hospitalized patients should be strictly monitored to avoid excessive and unmotivated use also in general practice.

Acute Disease↗

Evidences of 4-hydroxynonenal involvement in modulation of phagocyte activities.

The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emission of PMA-stimulated human PMN. These observations have been confirmed by electron-spin resonance (ESR) analysis. HNE, according to other stimuli, induced PMN phosphoinositide-specific phospholipase C (PL-C). All these results considered together suggest the conclusion that HNE represents an interesting endogenous molecule that plays a role as an inflammatory mediator involved a) in the recruitment of phagocytic cells at the inflamed area, and b) in the modulation of respiratory burst and of nitric oxide (NO) production.

Aldehydes↗

Binding of the lipid peroxidation product 4-hydroxynonenal to human polymorphonuclear leukocytes.

4-Hydroxynonenal (HNE) is produced during peroxidation of polyunsaturated fatty acids. It exerts a chemokinetic effect on human polymorphonuclear leukocytes (PMN). Investigations of this mechanism were performed. The results indicate that [3H]-HNE binding to PMN results both in non-specific bonds to the numerous SH groups of the cells and in binding to a saturable, reversible and specific HNE site. Scatchard analysis revealed that this is a single site with an apparent affinity constant of 319 nM and a density of 1.57 pmol (10(6))-1 cells. This specific binding site may be involved in the chemokinetic effect of HNE.

Aldehydes↗

Biphasic diurnal periodicity in bleeding from peptic ulcer.

OBJECTIVE: To evaluate if there was periodicity in the manifestations of gastrointestinal bleeding (hematemesis and melena). METHOD: This is a multicenter prospective study carried out in the Endoscopy Units of eight hospitals. At the time of the emergency endoscopy, the following data were collected: age, sex, endoscopic diagnosis, solar hour of the first hematemesis (vomiting of bright red or tarry black material) and of the first melena (black or bloody soft stools), and any drugs taken during the week before the bleeding episode, regardless of the dose. RESULTS: 806 patients were studied. Bleeding was from peptic ulcer in 405 patients (50%), from esophageal varices in 197 (24%), and from other sources in the remainder. Analysis using single cosinor statistics showed a nonrandom distribution in bleeding from peptic ulcer, whether presenting first with hematemesis (p = 0.02) or melena (p = 0.03). There were two peaks at 6:45 AM and 6:45 PM for hematemesis and at 7:25 AM and 7:25 PM for melena, representing a biphasic diurnal (ultradian) rhythm. CONCLUSIONS: This study shows that bleeding due to peptic ulcer has a biphasic diurnal periodicity. This has potential importance for the pathogenesis of bleeding, for the management of gastrointestinal hemorrhage and the administration of drugs known to cause peptic ulcer bleeding.

Adolescent↗

Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study. The Gruppo di Studio per le Malattie Infiammatorie Intestinali (IBD Study Group).

To assess the familial aggregation of inflammatory bowel disease (IBD) in Italy, the family pedigrees of 411 patients with ulcerative colitis (UC) and 241 patients with Crohn's disease (CD) seen at 14 participating hospitals were studied. Sufficient information was obtained on 97% of 3752 first-degree relatives, 80% of 8869 second-degree relatives, and 74% of 5791 cousins. Thirty-six propositi (5.52%) had a total of 44 affected relatives (16 CD, 28 UC). The prevalence of IBD was higher in first- than in second-degree relatives and cousins (791, 112, and 163 in 100,000, respectively). A strong intrafamilial disease concordance was observed, with 26 cases of UC and 6 of CD among relatives of UC patients and 10 cases of CD and 2 of UC among relatives of CD patients. The prevalence of UC among first-degree relatives of UC patients and that of CD among first-degree relatives of CD patients was 680 and 531 in 100,000, respectively. In conclusion, there is a high degree of familial aggregation for IBD in Italy, with a strong intrafamilial disease concordance.

Adolescent↗

Gastrin (G) cells are the cellular site of the gastric thyrotropin-releasing hormone in human fetuses and newborns. A chromatographic, radioimmunological, and immunocytochemical study.

In this study we analyzed the ontogeny and location of gastric TRH in human fetuses, preterm and term newborns, and adults. TRH immunoreactive cells were found in the antrum towards the bottom of developing glands and double immunostaining demonstrated that this neuropeptide is coexpressed with gastrin in the same cell (G-cell). In the youngest fetuses studied (12 weeks) G cells were few and contained both gastrin and TRH. They increased in number during development and were most abundant between 26 and 36 weeks of gestation. These morphological data correlated with total immunoreactive TRH content extracted from the whole stomachs of six fetuses and two preterm infants. On the contrary G cells containing both hormones were decreased in the newborn at term and not identified in the adult whereas those containing only gastrin were numerous in both. The TRH extracted was indistinguishable from synthetic TRH using chromatographic, radioimmunologic, and enzymatic criteria. As has already been reported, TRH was found in insulin-containing cells of the islets of Langerhans in the pancreas of our fetuses and newborns. These cells presented a similar development pattern to the gastric G cells.

Adult↗

Experimental studies on the mechanism of action of 4-hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils.

The effects of 4-hydroxy-2,3-trans-nonenal (HNE) and nonanal on the activity of phosphoinositide-specific phospholipase C of rat neutrophils have been studied in parallel with their action on neutrophil oriented migration. Concentrations of HNE ranging from 10(-7) to 10(-5) M significantly stimulated the oriented migration of rat polymorphonuclear leukocytes. HNE stimulated both the basal and GTP gamma S-induced phospholipase C activity when used at concentrations between 10(-8) and 10(-6) M. Nonanal was devoid both of chemotactic activity and of any action on phospholipase C activity. The effect of GTP gamma S on the stimulation of phospholipase C induced by HNE was higher when the lowest dose of the aldehyde was used; the finding of an additive effect between 10(-8) M HNE and 2 x 10(-5) M GTP gamma S suggests that the two compounds may share a final common pathway of action. These results suggest that the chemotactic activity of HNE might be mediated, like that of other more well-known chemoattractants, by the stimulation of phosphoinositide-specific phospholipase C.

Aldehydes↗

Morphology and pathogenesis of endocrine hyperplasias, precarcinoid lesions, and carcinoids arising in chronic atrophic gastritis.

The spectrum of endocrine cell changes occurring in 80 cases of body-fundus chronic atrophic gastritis (CAG), mostly type A or multifocal, including various types of hyperplasia, precarcinoid lesions (20 cases), and neoplasia (carcinoid, 24 cases) have been analyzed histologically, histochemically, and ultrastructurally. Changes associated with gland atrophy, pyloric- or intestinal-type metaplasia, regenerative hyperplasia, and hypergastrinemia have been identified and their neoplastic potential evaluated in the light of their proliferative capacity (bromodeoxyuridine incorporation) and clinicopathologic behavior. A close link between disseminated precarcinoid lesions of non-tumor mucosa and multiple carcinoids (carcinoidosis) arising in hypergastrinemic type-A CAG is suggested. Hyperplastic changes, including endocrine cell clusters, seem to have no or only minimal neoplastic potential.

Carcinoid Tumor↗

Influence of 4-hydroxynonenal on chemiluminescence production by unstimulated and opsonized zymosan-stimulated human neutrophils.

The lipid peroxidation product 4-hydroxy-2, 3-trans-nonenal (HNE) has a spectrum of biological effects on different cell types depending on the concentrations tested. In particular micromolar HNE concentrations stimulate neutrophil migration and polarization whereas higher doses inhibit. In our experimental conditions, fMet-Leu-Phe (fMLP) increased CL production of both unstimulated and zymosan-stimulated neutrophils, whereas cell stimulation with low HNE concentrations as well as zymosan addition to HNE incubated cells did not enhance light emission. In contrast 10(-4) M HNE reduced CL emission by unstimulated cells nearly to background values, completely depressed CL production by zymosan-stimulated cells and reduced phagocytosis. Cysteine was found to be able to counteract the HNE effect by about 70 per cent. The possibility that this aldehyde could exert its inhibitory effect through the alkylation of NADPH-oxidase SH-groups is postulated. Moreover, our present data on differences observed between fMLP and HNE indicate a different chemotactic mechanism induced by these two classes of compounds and lead to the conclusion that the local functional features of the attracted cells may be different.

Aldehydes↗

Identification of the endocrine cells detected by the monoclonal antibody HISL-19 in human tissues.

The human endocrine cells reacting with the monoclonal antibody HISL-19 were identified with hormone antisera of proven specificity using a double immunostaining procedure. The epitope for HISL-19 was found in all types of pituitary cells except ACTH cells, in thyroid C cells, in all types of adrenal medullary and pancreatic islet cells and in somatostatin and pancreatic polypeptide cells of the gastrointestinal mucosa. No staining was found in parathyroid cells and in most gastrointestinal endocrine cells. Either paranuclear focal accumulation or diffuse cytoplasmic distribution of immunoreactive material were found. The spectrum of HISL-19 immunoreactive cells was found to be only in part complementary to that of cells immunoreactive for chromogranin A. Thus, it is concluded that the monoclonal antibody HISL-19 is a useful addition to other immunohistochemical markers for the detection of cells showing neuroendocrine features.

Adrenal Medulla↗

Interaction between neutrophils and 4-hydroxyalkenals and consequences on neutrophil motility.

The lipid peroxidation product 4-hydroxynonenal (HNE) and homologous aldehydes have been found to possess chemotactic activity for rat neutrophil leukocytes in the micromolar to picomolar range, depending on the compound. Such an activity is displayed only in the presence of albumin. The mechanisms by which aldehydes could interact with neutrophils are discussed. It is proposed that albumin acts as a carrier for the aldehyde and releases them to a neutrophil receptor. At concentrations around 10(-4) M, 4-hydroxyalkenals have been found to exert toxic effects on a number of cells, including a strong depression of neutrophil motility. Finally, HNE has been found at chemotactic concentrations in the inflammatory site. The possibility that HNE is involved in the neutrophil influx into the inflammatory site is considered.

Aldehydes↗

Nizatidine in the short-term treatment of duodenal ulcer--an Italian Multicenter Study.

One hundred and seventy three patients suffering from duodenal ulcer, were selected for a double-blind, controlled and randomized parallel multicenter study, with interval endoscopic examinations. This study was undertaken to compare the efficacy and safety of nizatidine administered at a single dose (300 mg "nocte") versus ranitidine (300 mg "nocte") in the treatment of acute duodenal ulcer. One hundred and sixty five patients were found to meet every admission criterion and completed the study (86 on nizatidine and 79 on ranitidine). On admission to the study, both groups were seen to have been correctly selected and epidemiologically well-distributed as to history of duodenal ulcer, previous treatments and pre-study symptoms. The ulcer was considered healed when complete re-epithelialization had occurred in areas of ulcerated mucosa. Healing rates of duodenal ulcer proved to be globally similar in the two groups, both in the 4th week (nizatidine, 78%; ranitidine, 78%) and in the 8th week (nizatidine, 91%; ranitidine, 95%). After four weeks of treatment, 67% of the patients treated with nizatidine no longer had any symptoms, while 87% patients no longer suffered from day pain, and 91% had no nocturnal pain. As a result, intake of antacids quickly decreased during the first four weeks. A similar response was observed in the group receiving ranitidine. After administration at a single dose of 300 mg in the evening, nizatidine proved to be at least as effective and safe as 300 mg of ranitidine administered in the same way, with respect both to ulcer healing and symptom response.

Adult↗

Chemotactic activity of aldehydes. Structural requirements. Role in inflammatory process.

The lipid peroxidation product 4-hydroxy-2,3-transnonenal (HNE) and its homologous compounds were found to induce a high significant stimulation of rat neutrophil oriented migration and morphological polarization at concentrations within a pico-micromolar range. These effects are weak with respect to the potent chemoattractant formyl-peptides. The structural requirements for the chemotactic activity of aldehydes were studied and the trans C-C double bond was found to be the essential requirement. The problem of the mechanism by which alpha, beta-unsaturated aldehydes interact with neutrophils is unsolved. With regard to this point, some hypotheses are discussed. The possibility that chemotactic unsaturated aldehydes are present in vivo in the inflammatory site at a concentration at which they are chemotactic in vitro was studied. Rat pleural exudates collected 1,2,3,4 hours after a pleurisy induction were analyzed and HNE was detected both in the supernatant of exudate and in cells. Its concentration in the liquid part of the exudate increased with time, in parallel with an increase in the number of cells in the exudate. It is reasonable that this aldehyde might be formed as a consequence of lipid peroxidation reactions concomitant to the phlogistic process. The hypothesis is proposed that HNE could participate in the neutrophil recruitment in the inflammatory area.

Aldehydes↗

Possible role of aldehydic lipid peroxidation products as chemoattractants.

Previous studies showed that the lipid peroxidation product 4-hydroxy-trans-2-nonenal (HNE) stimulates the rat neutrophil oriented migration in vitro within a micromolar range. Its effect is weak with respect to other known chemoattractants, but highly significant on the basis of a two-way analysis of variance. Other hydroxyalkenals were found to be chemotactic within a pico-micromolar range, and their chemotactic power was not correlated to their lipophilicity. The structural requirements for the chemotactic activity of the hydroxyalkenals were studied by testing the influence of alkanals and 2-alkenals on oriented migration. Alkanals are lacking both the trans double-bond and the hydroxy group, while 2-alkenals are lacking only the hydroxy group. The 2-alkenals (2-octenal, 2-nonenal) were found to be chemotactic, whereas alkanals (hexanal, octanal, nonanal) were ineffective. Therefore the chemotactic activity of the aliphatic aldehydes is dependent on the -C = C-CHO part of their molecule. The possibility that unsaturated aliphatic aldehydes are present in an inflammatory site at a concentration at which they are chemotactic in vitro was also investigated. Carbonyls in pleural exudates were analysed at different times after a pleurisy induction and HNE was detected both in the cells and in the cell-free supernant of the exudate at increasing concentrations during the 4 hours of the experiment. The exact source of HNE is unknown, but since HNE has been identified among the degradation products of peroxidized lipids it is likely that this aldehyde is formed consequent on lipid peroxidation reactions which occur at the phlogistic site. The possibility that HNE is involved, at least in part, in the recruitment of neutrophils in the inflammatory area is suggested.

Aldehydes↗