PubMed Health⌕ Search

Biomedical subjects

Raffaele Manna

Publications and source records attributed to Raffaele Manna.

18 recordsLinked to original sources

Fecal calprotectin in first-degree relatives of patients with ulcerative colitis.

OBJECTIVES: The pathogenesis of inflammatory bowel disease seems to depend on the combination of genetic and environmental factors. To evaluate genetic susceptibility, one approach is to search for specific markers in apparently unaffected family members of patients. Our aim was to evaluate fecal calprotectin concentrations (FCCs) in first-degree relatives of patients with ulcerative colitis (UC). PATIENTS: Fifty-five patients with UC and 167 healthy first-degree relatives were recruited; 38 of the patients' spouses were also enrolled. One hundred fifty healthy subjects participated as the control group. METHODS: FCCs were determined by ELISA. FCCs were compared among the groups by Kruskal-Wallis analysis of variance (ANOVA) test followed by Mann-Whitney U test. RESULTS: Significantly greater FCCs were found in first-degree relatives of patients with UC (76.0 [34.7-129.6] microg/g) as compared with controls (31.6 [17.0-45.0]) (P < 0.0001). Fecal calprotectin levels in patients with UC (256.0 [153.0-356.0] microg/g) were significantly higher as compared with first-degree relatives, spouses (43.8 [18.6-89.0] microg/g), and controls (P < 0.0001 for all comparisons). FCC of relatives was significantly higher than FCC of spouses (P = 0.01). FCC of spouses had a significantly higher FCC with respect to controls (P = 0.01). CONCLUSIONS: First-degree relatives of patients with UC had greater FCC values and could have a subclinical intestinal inflammation. It needs to be clarified if this finding is the consequence of genetic predisposition, of environmental factors, or the interaction of both, and if relatives with high FCC have a greater risk of developing the disease.

Adult↗

Management and treatment of lactose malabsorption.

Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous beta-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.

Adaptation, Physiological↗

Wegener's granulomatosis: a challenging disease for otorhinolaryngologists.

Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its aspecific presenting symptoms. Detection of serum circulating antineutrophil cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to identify WG at an early stage and to implement stage-adapted therapy. c-ANCA levels may also help to evaluate the response to medical therapy. Recently, the quality of life of WG patients has been improved by administering cotrimoxazole in order to prevent infections and recurrent diseases during the remission period.WG is of special significance to the otorhinolaryngologist because it is often initially limited to the upper respiratory tract before becoming systemic. The aim of this paper was to describe a series of WG patients and underline the difficulties involved in diagnosing and treating this challenging disease. This was a prospective study in 23 consecutive patients with head and neck manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means of both c-ANCAs detection using indirect immunofluorescence and histology in biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2 mg/kg/day) and glucocorticoids (prednisone; 1 mg/kg/day). If an improvement or toxic events occurred, CYC was discontinued and methotrexate was started. If, during remission of the disease, low serum c-ANCAs levels were detected, CYC was suspended and cotrimoxazole (1 g/day) was introduced. Serum c-ANCAs detection was positive for all patients. Biopsy was diagnostic from the beginning in 19/23 cases. The six patients with limited WG did not show a progression to systemic disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas 19/23 patients were alive with good control of relapses.

Anti-Inflammatory Agents↗

Circulating levels of cyclosporin A in inflammatory bowel disease: relationships with lymphocyte inhibition and the age of patients.

OBJECTIVE: To determine in the same blood sample the concentrations of cyclosporin A (CsA) and the degree of CsA-induced lymphocyte inhibition; to establish a relationship between these parameters; and to investigate the factor(s) influencing such a putative relationship. METHODS: Ten patients with a diagnosis of Crohn's disease (n=7) or ulcerative colitis (n=3) were enrolled in the study. The patients, who had never been immunosuppressed, were treated with microemulsion CsA twice daily by the oral route; at steady-state, blood samples were collected 0, 0.5, 1, 2, 3, 5, 7 and 12 h after the morning dose. CsA blood levels were measured by means of radioimmunoassay. The percentages of lymphocytes during the S-phase were assessed by flow-cytometry on the same blood specimens, only for samples collected at 0 h and 2 h. RESULTS: An inverse relationship emerged between CsA blood concentrations and the percentage of lymphocytes during the S-phase: the latter was maximal before the beginning of treatment and minimal in association with peak CsA levels. Furthermore, a highly significant correlation was found between trough CsA levels and the age of the patient, since the percentage of inhibited lymphocytes increases with age.

Administration, Oral↗

FMF revisited.

Explore the source record for details and available documents.

Eastern Orthodoxy↗

Systemic inflammatory diseases and silicone breast prostheses: report of a case of adult still disease and review of the literature.

There has been a debate about the possibility of a link between silicone breast implants and the onset of systemic connective tissue diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) and other inflammatory pathologies, such as silicone implant associated syndrome and adult Still disease. We report a case of adult Still disease in a patient with a silicone gel breast implant. The disease regressed with steroidal treatment, and the patient is now no longer steroid-dependent, although the implant is still in place.

Adult↗

Non-life-threatening sepsis: report of two cases.

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

Adenocarcinoma↗

Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

OBJECTIVE: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS. METHODS: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes. RESULTS: Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants. CONCLUSION: The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.

Antigens, CD↗

Familial Mediterranean fever is no longer a rare disease in Italy.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, characterised by short, recurrent attacks of fever with abdominal, chest or joint pain and erysipelas-like erythema. It is an ethnically restricted genetic disease, found commonly among Mediterranean populations, as well as Armenians, Turks, Arabs and Jews. Traditionally, Italians have been considered little affected by FMF, despite the geographical position of Italy (northern Mediterranean basin) and the migratory changes in its population. The objective was to characterise the demographic, clinical and genetic features of FMF in Italy. Patients of Italian origin were recruited from those referred to Italian-French medical centres for FUO (Fever of Unknown Origin) or 'surgical' emergencies; clinical history, genealogy and physical examination were recorded; all other possible infectious, neoplastic, auto-immune and metabolic diseases were excluded. Mutational analysis of the gene responsible for FMF (MEFV on 16p13.3) was performed, after which geno-phenotypical correlations were established. Italian FMF patients, 40 women and 31 men, aged from 3 to 75 years, have shown all the clinical manifestations indicative of FMF described in the literature, but with a lower incidence of amyloidosis. The genetic tests have been contributive in 42% of cases. The frequency of each different mutation has been similar to that found in a series of 'endemic' countries. The geno-phenotypical correlations have suggested the existence of genetic and/or environmental modifier-factors. Among Italians FMF seems to be more frequent than was believed in the past. The data presented are consistent with their geographical location and their history.

Adolescent↗

Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss. STUDY DESIGN: A prospective study in patients with sudden sensorineural hearing loss. METHODS: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies. RESULTS: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P =.0004). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P =.0020). CONCLUSIONS: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments.

Adolescent↗

Autoimmunity in sudden sensorineural hearing loss: possible role of anti-endothelial cell autoantibodies.

In order to verify whether anti-endothelial cell autoantibodies (AECAs) can be used as serological markers of inner ear vasculitis in sudden sensorineural hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated. All patients underwent a routine general physical examination and extensive audiovestibular, microbiological and immunological investigations. Fourteen normal subjects without a history of HL, autoimmune or metabolic disease served as controls. Detection of AECAs was performed using an indirect immunofluorescence technique. AECA-positive patients were treated with methylprednisone, while AECA-negative patients were treated with a combined regimen of steroids, plasma expander and aspirin. The average hearing recovery for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after treatment and every 3 months thereafter; median follow-up was 12 months (range 9-18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were AECA-positive and thus differed significantly from the normal population in whom only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was associated with being AECA-positive in 8/11 cases. During follow-up, 25/32 patients improved their hearing and 17 of these patients were AECA-negative. The seven cases without hearing improvement were all AECA-positive. In patients with SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may represent a serological marker of vasculitis even if they are not inner ear-specific and even if they represent an epi-phenomenon rather than the only cause of SSHL.

Adolescent↗

[Probiotics: history, definition, requirements and possible therapeutic applications].

The ingestion of probiotics is associated with various beneficial effects on human health and modifies the physiological homeostasis of the intestinal flora. Probiotics are microorganisms with some particular characteristics: human origin, safety in human use, bile and acid resistance, survival in the intestine, at least temporary colonization of the human gut, adhesion to the mucosa and bacteriocine production. Thanks to these characteristics, probiotics block the invasion of human intestinal cells by the enteroinvasive bacteria. Furthermore, they should be able to stimulate and modulate the intestinal immune response, and to protect and stabilize the mucosal barrier. Finally, the efficacy of probiotics should be evident and documented with valid studies. All their properties should be maintained during processing and storage. Probiotics are usually used to protect the host from pathogens. With regard to this, they are useful in the prevention of antibiotic and traveler's diarrhea and they may play a role in the management of gastric Helicobacter pylori infection. Furthermore, their efficacy in the treatment of infectious diarrhea, in inflammatory bowel diseases, in pouchitis and in food allergy has been shown. Probiotics can improve the symptoms of irritable bowel syndrome and of lactose malabsorption. Finally, it has been suggested that such microorganisms may play a role in the prevention of carcinogenesis and of tumor growth.

Adult↗

[Familial Mediterranean fever: an ancient hereditary disease].

Familial Mediterranean fever (FMF) is an autosomal recessive disorder that mainly affects people living around the Mediterranean sea (i.e. Turks, Armenians, Arabs and Jews), but cases of FMF are now being increasingly diagnosed in every country of the world (including Italy). Described for the first time in 1945, it has recently become more relevant, after the discovery of the responsible gene, the MEFV gene which encodes a 781-aminoacid protein called pyrin that seems to play a role in the regulation of the inflammatory process. As the prototype of an emerging group of disorders fated to become more and more popular--the hereditary auto-inflammatory disorders--FMF is an under-diagnosed cause of fever of unknown origin. Fever is the main but not the only symptom; sterile serosites are the most common associated features. The classical clinical picture is being continuously enriched. Geno-phenotype correlations and interval-free symptoms are the new clinical insights, while fundamentally important studies attempt to enlighten its obscure pathogenesis. In spite of the introduction of alternative treatments, colchicine is still the only suitable drug for the prevention of acute episodes and the development of amyloidosis.

Algorithms↗

[Functional dyspepsia: definition, classification, clinical and therapeutic management].

Dyspepsia is a very common syndrome characterized by pain and/or discomfort of the upper abdomen. Sometimes, an organic disease causes this syndrome (organic dyspepsia); more frequently, there are no known diseases (functional dyspepsia). These latter conditions are identified by exclusion. The pathogenesis of this syndrome is yet to be clarified. Currently, functional dyspepsia is classified in ulcer-like dyspepsia, dysmotility-like dyspepsia and nonspecific dyspepsia, in which symptoms do not clearly fit into any of the above categories. The current guidelines for the management of "uninvestigated dyspepsia" suggest testing for Helicobacter pylori infection and relative treatment if positive. A gastroscopy should be performed in case of persistence of symptoms to discriminate between the organic and functional forms. In the latter, to optimize patient management, it is necessary to find the exact subgroup. Antacids, H2-receptor antagonists and proton pump inhibitors have been demonstrated to be useful in ulcer-like dyspepsia. Prokinetic agents are more effective in the dysmotility-like dyspepsia. Further studies will be necessary to confirm the efficacy of emerging therapeutic strategies.

Adult↗