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Biomedical subjects

M Mancuso

Publications and source records attributed to M Mancuso.

At least 55 records · Page 3Linked to original sources

Fungal infections in lung transplantation. Incidence, risk factors and prognostic significance.

BACKGROUND AND AIM OF THE WORK: Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival. METHODS: 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant. RESULTS: The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08). CONCLUSIONS: 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.

Adolescent↗

Attitudes of primary care physicians toward cancer-prevention trials: a focus group analysis.

PURPOSE: Recruitment of low-income and minority women to cancer-prevention trials requires a joint effort from specialists and primary care providers. We sought to assess primary care providers' attitudes toward participating in cancer-prevention trial recruitment. PROCEDURES: We conducted a focus group with seven Boston-based primary care providers serving low-income and minority women. Providers discussed knowledge, attitudes, and beliefs regarding their role in recruitment to prevention trials. FINDINGS: A qualitative analysis of the focus group transcript revealed nine categories. Three categories related specifically to the primary care physician: 1) the dual role physicians play as advocates for both patient and research; 2) threats to maintaining the primary care relationship; and 3) general philosophy toward prevention. An additional six categories could be subdivided as they apply to the primary care physician, the patient, and the community: 4) trust/commitment; 5) benefits of the research; 6) access to the research; 7) knowledge and recall of the research; 8) influences of media coverage about the research; and 9) cultural sensitivity. CONCLUSIONS: Investigators conducting cancer-prevention trials must address the concerns of primary care physicians to optimize recruitment of subjects- especially low-income and minority women-into trials.

Attitude of Health Personnel↗

Cytogenetic damage in peripheral lymphocytes of mitochondrial disease patients.

Recent studies indicate an important role of endogenous oxidative stress in the onset and/or in the progression of mitochondrial encephalomyopathies. In particular, the increased production of radical species caused by altered mitochondrial functionality could affect both mitochondrial and nuclear DNA integrity. We performed the micronucleus assay coupled with fluorescence in situ hybridization (FISH) to detect chromosome damage in peripheral blood lymphocytes in a group of patients affected by different forms of mitochondrial encephalomyopathies. Moreover the comet assay has been carried out to detect primary and oxidative damage in the nuclear DNA. Our results show a significant presence of both DNA and chromosome damage in patients compared to a matched group of controls. A reduction in DNA alterations is also observed in patients after treatment with coenzyme-Q10.

Adult↗

Potential involvement of ubiquinone in myotonic dystrophy pathophysiology: new diagnostic approaches for new rationale therapeutics.

An impairment of mitochondrial function may contribute to the pathophysiology of myotonic dystrophy (MyD). Coenzyme Q10 (CoQ10) deficiency has been previously observed, even if in a restricted sample of patients. The aim of this investigation was to obtain more information about coenzyme Q10 and its relationships to the aerobic metabolism in a group of MyD patients. Serum CoQ10 appeared significantly reduced with respect to normal controls: 0.93 +/- 0.22 vs. 1.58 +/- 0.28 micrograms/ml (p < 0.05). Moreover, the results demonstrated an inverse tendency between CoQ10 levels and the CTG expansion degree. Basal blood lactate levels were significantly higher than controls (p < 0.05). A borderline inverse correlation between CoQ10 and lactate, corresponding to lactate threshold, was found. These data suggest a possible role of CoQ10 in the pathogenesis of MyD, which may be mediated by mechanisms of cellular damage common to the oxidative pathway. Therapeutic strategies may be devised by virtue of this rationale.

Coenzymes↗

Abnormal levels of human mitochondrial transcription factor A in skeletal muscle in mitochondrial encephalomyopathies.

Human mitochondrial transcription factor A (hmtTFA or Tfam), a 25-kDa protein encoded by a nuclear gene located on chromosome 10q21, is involved in the control of replication and transcription of mtDNA. To better understand the complex relationship between h-mtTFA and mitochondrial function, we assessed by western blot the levels of h-mtTFA in skeletal muscle from 7 patients affected by mitochondrial diseases (MD) caused by different mtDNA mutations. We related these results to exercise lactate production as well as to the pathologic features of the underlying myopathy. h-mtTFA levels were significantly inversely related to blood lactate and the percent of RRF, borderline to cox negative fibers. Our results indicate that hmtTFA may be involved in the cascade of events which determine functional impairment of MD.

Adult↗

Evidence favouring the gastro-oral route in the transmission of Helicobacter pylori infection in children.

OBJECTIVE: Several studies support the view that Helicobacter pylori is acquired in early life and within families. However, the exact route of transmission remains unknown. Given that H. pylori colonizes only the human gastric mucosa, the hypothesis that history of vomiting in siblings may be a relevant risk factor was tested in a paediatric setting. METHODS: One hundred urban children (age range 0.8-16.6 years, median 9), 44% with evidence of active H. pylori infection, were recruited. A structured questionnaire dealing with socio-economic issues was completed. Vomiting siblings and siblings of vomiting index children were screened for H. pylori by means of (13)C-urea breath test. Serum samples from index children were assayed for immunoglobulin G to hepatitis A (HAV) and Epstein-Barr virus (EBV) in order to check for faecal-oral and oral-oral exposure, respectively. RESULTS: Vomiting siblings of H. pylori-infected index children and siblings of H. pylori-infected vomiting index children had a high rate of active H. pylori infection (60 and 67%, respectively). History of vomiting in siblings was positively associated with active H. pylori infection in the index children (multivariate odds ratio 2.4, 95% confidence interval 1.3-4.3). Seropositivity for HAV and EBV was found in 1 and 68 index children, respectively. The agreement between active H. pylori infection and EBV seropositivity was not significant (kappa = 0.26). CONCLUSIONS: History of vomiting in siblings is an independent risk factor for H. pylori. Nowadays, transmission of H. pylori in urban children may involve the gastro-oral route more than the faecal-oral or oral-oral pathways.

Adolescent↗

Epidemiology of dystrophinopathies in North-West Tuscany: a molecular genetics-based revisitation.

A molecular genetics-based epidemiological investigation was carried out in 1997 in the territory of North-West Tuscany, central Italy, to calculate incidence and prevalence rates of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Results were compared with a previous epidemiological study conducted in the same area in 1981, in the pre-dystrophin era. Routine adoption of methods of molecular diagnosis determined an increase in prevalence of BMD from 1.06 x 10(-5) to 2.42 x 10(-5) inhabitants, while cumulative incidence of DMD was markedly decreased from 23.12 x 10(-5) during the period 1965-1976 to 10.71 x 10(-5) male live births during the period 1977 1994. The combined reduction of DMD/BMD diagnostic error rate and familial recurrence could explain these results, providing the bases for a consistent redefinition of dystrophinopathy carrier frequency in the area considered.

Dystrophin↗

Circulating thrombopoietin levels in neonates with infection.

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.

C-Reactive Protein↗

Helicobacter pylori infection in children with celiac disease: prevalence and clinicopathologic features.

BACKGROUND: Celiac disease is frequently associated with chronic gastritis. Helicobacter pylori is the main etiologic agent of chronic gastritis. The aim of this study was to assess the prevalence of H. pylori, the related symptoms, and the endoscopic and histologic gastric features in children with celiac disease. METHODS: Eight-one (24 boys, 57 girls; age range: 1.4-17.7 years, median 6.8) children with celiac disease were studied. All children had a blood sample taken. In a subgroup of 30 children who underwent endoscopy, three gastric biopsy specimens were taken for histology (hematoxylin and eosin, Giemsa, immunohistochemistry) and urease quick test. Symptom complaints were recorded. Age- and sex-matched (one case, one control) children without celiac disease were used for comparison. Serum H. pylori IgG were measured by means of a locally validated commercial enzyme-linked immunoassay. RESULTS: Overall, 15 of 81 (18.5%) children with celiac disease and 14 of 81 (17.3%) control children were positive for H. pylori. The percentage of H. pylori positivity was similar in children with untreated and treated celiac disease. Recurrent abdominal pain was the only symptom that helped to distinguish between H. pylori-positive and H. pylori-negative children. However, symptoms disappeared in patients with celiac disease after gluten withdrawal, irrespective of H. pylori status. All endoscopic (erythema, nodularity) and histologic (superficial-, interstitial-, lymphocytic-gastritis, activity, lymphoid follicles) findings did not differ between celiac and nonceliac H. pylori-positive children. CONCLUSIONS: Prevalence and clinical expressivity of H. pylori infection is not increased in children with celiac disease. The clinicopathologic pattern of the infection is not specifically influenced in this condition.

Abdominal Pain↗

Testing for serum IgG antibodies to Helicobacter pylori cytotoxin-associated protein detects children with higher grades of gastric inflammation.

BACKGROUND: Little information is available about the relationships between Helicobacter pylori cytotoxin-associated protein (CagA) and clinicopathologic features in children. The purpose of this study was to test whether determining serum IgG antibodies to CagA is a useful tool for detecting more severe disease. METHODS: One hundred twenty-seven consecutive children (age range, 0.75-17.8 years; median, 9.4 years) referred for gastroscopy were included in the study. Antral and corpus biopsies were taken for gastric histology and H. pylori detection. Major symptoms and endoscopic findings were recorded. A serum sample was drawn from each child and assayed for IgG antibodies CagA by a commercial enzyme-linked immunosorbent assay. RESULTS: Sixty-three (50%) children had no evidence of H. pylori infection, 28 (22%) were H. pylori positive/CagA positive, and 36 (28%) were H. pylori positive/CagA negative. There were no differences in clinical diagnosis and occurrence of any predominant symptom according to H. pylori and CagA status. Findings of antral nodularity were more frequent (p = 0.003) in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children. The gastritis score was significantly higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children (5.7 +/- 1.9 vs. 3.8 +/- 1.6, respectively; p = 0.0003), either in the antral (p = 0.0002) or in the corpus (p = 0.001) mucosa. Inflammation (p = 0.0001) and activity (p = 0.0001) scores were both higher in H. pylori-positive/CagA-positive children than in H. pylori-positive/CagA-negative children, but the H. pylori density score was not significantly different (p = NS). In no case was normal gastric mucosa found in H. pylori-positive/ CagA-positive children. Lymphocytic gastritis (p = 0.0008) and lymphoid follicles (p = 0.000003) were a more frequent finding in H. pylori-positive children than in H. pylori negative children, irrespective of CagA status. CONCLUSION: Testing for serum IgG to CagA detects higher grades of gastric inflammation among children with H. pylori infection. It may be useful in targeting H. pylori-positive/ CagA-positive children for antimicrobial therapy while reducing the need for endoscopy and gastric biopsy.

Adolescent↗

The seagull wing self retaining prosthesis in the surgical treatment of pectus excavatum.

BACKGROUND: Between June 1958 and June 1996 we operated many patients affected by pectus excavatum with an original surgical technique. In this study we evaluated the durability of the results. METHODS EXPERIMENTAL DESIGN: Retrospective study with a mean follow-up time of 15.8 years/pt, and 60% complete. SETTING: private and institutional practice. PATIENTS OR PARTICIPANTS: 357 patients (253 males and 104 females, mean age = 18.2+/-5.1 years) affected by pectus excavatum. The grade of PE (Chin classification) was I in 76 patients, II in 165 and III in the remaining 116. Most of the patients required operation for aesthetic reasons only (339 patients; 95%). INTERVENTION: the surgical technique consisted of a double transversal sternotomy at the level of the lowest and highest part of the depression associated with a longitudinal sternotomy. A wedge resection of the ribs was then performed and the sternum was fixed using an original stainless steel strut prosthesis moulded into a seagull wing. The strut was removed 12 months postimplantation. RESULTS: There were no operative deaths. Four patients (1.2%) had sternal wound infection, which was successfully treated. From the aesthetic point of view, the postoperative results were excellent in 262 patients (73.4%), good in 82 (22.9%) and poor in 13 (3.6%). All subjective symptoms, when present, disappeared after surgery. CONCLUSIONS: The seagull wing prosthesis appears to be safe, easy to implant and to remove, and comfortable for the patient. This technique has shown good long-term results independently of type of deformity and patient age.

Adolescent↗

The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression.

Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population of patients who were treated with buprenorphine the day before for relieving postoperative pain. However, due to the high variability of opioid responsiveness, buprenorphine was effective in some patients and poorly effective in some others. Similarly, buprenorphine produced respiratory depression with a large variability, ranging from mild depression to no effect. We found that the placebo analgesic response depended on the buprenorphine analgesic effectiveness of the previous day. Analogously, we found that a placebo respiratory depressant response was more pronounced in those patients with a respiratory depressant response to buprenorphine on the day before, irrespective of the analgesic effectiveness. These specific effects suggest that (1) the placebo effect is experience-dependent; (2) the mechanisms underlying placebo analgesia and placebo respiratory depression are independent from each other and, by considering the role of endogenous opioids in placebo analgesia, might involve different subpopulations of opioid receptors.

Analgesia↗

Hyporesponsiveness to intradermal administration of hepatitis B vaccine in insulin dependent diabetes mellitus.

The immune response to intradermal or intramuscular hepatitis B vaccine in 18 children with insulin dependent diabetes mellitus (IDDM) compared with 24 healthy children was studied. Patients were divided into responders, hyporesponders, and non-responders according to their antihepatitis B serum concentrations after hepatitis B vaccination. We also studied HLA class II antigen distribution and did delayed type hypersensitivity (DTH) tests on children with IDDM and controls. No difference in the immune response (antihepatitis B surface antigen antibody titres) was found with intramuscular administration, whereas with intradermal administration a statistically lower immune response (p < 0.001) was observed in children with IDDM v controls. This hyporesponsiveness cannot be attributed to HLA class II antigen distribution because their frequency was the same in both groups of children with IDDM. It is suggested that the poor immune response to intradermal hepatitis B vaccine may be due to impaired macrophage activity resulting in failure of antigen presentation, which may be of importance in the immune dysfunction in children with IDDM. This hypothesis is suggested by a significantly lower score on a DTH test to a battery of antigens in the IDDM group when compared with controls. It is therefore suggested that when the hepatitis B vaccination is offered to children with IDDM it may be preferable to give it intramuscularly.

Adolescent↗

[Intravascular treatment of iliac aneurysms].

INTRODUCTION: We investigated the feasibility of the intravascular treatment of iliac aneurysms in patients at high perioperative risk. MATERIAL AND METHODS: January, 1996, to December, 1997, seven iliac aneurysms in 5 patients were treated using endovascular procedures. The patients were 4 men and 1 woman whose mean age was 70 years (range: 61-74 years). Four of 7 aneurysms were in the common iliac artery (2 true aneurysms and 2 anastomotic aneurysms after aortoiliac bypass) and 3 were true internal iliac artery aneurysms. Preoperative CT and arteriography were performed in all cases to define the vascular morphology of the aneurysm, including its exact diameter and length. All procedures were performed in the operating room by a team of vascular radiologists and vascular surgeons, using a portable digital RX system (Philips BV29). The femoral approach was always used, which was percutaneous under local anesthesia in 4 cases and surgical under epidural anesthesia in the other 3 cases, according to the patient's general condition and to common femoral artery morphology. Six endovascular Passager grafts were positioned in the common iliac artery using over-the-wire techniques; platinum coil embolization of the aneurysmatic internal iliac artery had been performed in 2 cases. Coil embolization of the hypogastric artery aneurysm was the only treatment in 1 case. Bilateral aneurysms were treated separately, at intervals of no less than 3 months. RESULTS: Immediate aneurysm exclusion was obtained in all cases, as confirmed at 2-20 months' follow-up in 6 cases. A displaced prosthesis needed reoperation in 1 case. No complications were observed during or early after the procedures, which were always well tolerated by the patients. DISCUSSION: The endovascular treatment of iliac aneurysms is a relatively recent procedure and thus only short- and mid-run results are currently available, which appear satisfactory in 85% of the world's literature cases. Prosthesis displacement and intimal hyperplasia are reported as the main causes of failure. Lacking long-term results, we reserve this method to selected cases. Shorter hospitalization is another advantage. CONCLUSIONS: This little invasive procedure appears suitable for high-risk patients and in the aneurysmatic complications metachronous to surgical bypass.

Aged↗