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Biomedical subjects

L Marino

Publications and source records attributed to L Marino.

At least 37 records · Page 2Linked to original sources

Long-term ECG changes in depressed elderly patients treated with nortriptyline. A double-blind, randomized, placebo-controlled evaluation.

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24-111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Age Factors↗

Reduced heat loss following sucrose ingestion in premature and normal human newborns.

To determine the energy savings caused by sucrose taste, we measured heat loss through direct calorimetry for 23 premature and normal term infants who were studied a total of 31 times. Following stabilization in the calorimeter, crying was induced by applying 1 ml cold water to the infant's foot. After 4 min, 0.1 or 0.2 ml sucrose were delivered intraorally through a remote syringe to arrest crying. Crying was accompanied by a 13.2% increase in metabolic rate that was quickly and completely reversed during crying cessation caused by sucrose taste. Heat loss was inversely and linearly related to infant body weight. The implications of these findings for minimizing crying and energy expenditure in normal newborns and especially in ill or small newborns are discussed.

Basal Metabolism↗

Electrically-elicited surface mechanomyogram in myotonic dystrophy.

The surface oscillation of the muscle during electrical stimulation is detectable by an accelerometer as a surface mechanomyogram (MMG). The aim of this study was to evaluate whether MMG properties reflect the mechanical muscle changes induced by myotonic dystrophy (MyD). To this end, the tibialis anterior of seven MyD patients and seven age- and sex-matched controls (C) was supramaximally stimulated at 1 (single twitches), 5, 10, 15, 20 Hz for 3 s at the most proximal motor point. RESULTS SINGLE TWITCHES: The MMG amplitude was 67% less, the duration 37% longer, the electromechanical delay 64% longer, and the spectrum mean frequency, 44% lower in the MyD patients than in controls. REPETITIVE STIMULATION: At each stimulation frequency, the average MMG peak-to-peak was less in the MyD patients than in C. CONCLUSION: The differences between the MMGs of MyD patients and C support the hypothesis that, together with the well-known changes in sarcolemmal excitability, an alteration in electromechanical coupling and a failure in contractile machinery may coexist in MyD.

Biomechanical Phenomena↗

Detection of Mycobacterium ulcerans in environmental samples during an outbreak of ulcerative disease.

Mycobacterium ulcerans is an environmental bacterium which causes chronic skin ulcers. Despite significant epidemiological evidence to suggest that water is the source of infection, the organism has never been identified in the environment. Environmental water samples were collected from a small town in which an outbreak of 29 cases had occurred in a 3-year period. These were examined by mycobacterial culture and PCR amplification. Similar to previous studies, M. ulcerans was not cultured from the water samples. However, five samples were positive for M. ulcerans by PCR. These samples were collected from a swamp and a golf course irrigation system within the outbreak area. This is the first time that M. ulcerans has been demonstrated to be present in the environment and supports the postulated epidemiology of disease due to this organism.

DNA, Bacterial↗

Development of a PCR assay for rapid diagnosis of Mycobacterium ulcerans infection.

The diagnosis of Mycobacterium ulcerans infection is hampered by the slow growth of the bacterium in culture, resulting in a delay of several months before a specific diagnosis can be obtained. In addition, M. ulcerans cannot be isolated from water even when there is convincing epidemiological evidence implicating this as the source of infection. The aim of the present study was to develop a PCR assay to circumvent the problems of delayed diagnosis and insensitivity of standard bacterial culture for M. ulcerans. For the PCR, we isolated an M. ulcerans-specific DNA fragment, 1,109 bp long, which is repeated at least 50 times throughout the genome. Use of this sequence as a target for PCR allowed us to detect as few as 2 molecules of genomic DNA in vitro. The PCR was used to detect M. ulcerans DNA in fresh tissue and paraffin-embedded sections from all seven patients with culture-confirmed cases of infection.

Base Sequence↗

HCV viraemia is more important than genotype as a predictor of response to interferon in Sicily (southern Italy).

BACKGROUND/AIMS: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. METHODS: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. RESULTS: Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score. CONCLUSIONS: Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.

Adult↗

Mental disorder as a Roschian concept: a critique of Wakefield's "harmful dysfunction" analysis.

J. C. Wakefield (1992a, 1992b, 1993) recently proposed that mental disorder is best conceptualized as a "harmful dysfunction," whereby "harm" is a value judgment regarding the undesirability of a condition, and "dysfunction" is the failure of a system to function as designed by natural selection. The authors maintain, however, that (a) many mental functions are not direct evolutionary adaptations, but rather adaptively neutral by-products of adaptations, (b) Wakefield's concept of the evolutionarily designed response neglects the fact that natural selection almost invariably results in substantial variability across individuals, and (c) many consensual disorders represent evolutionarily adaptive reactions to danger or loss. The authors propose that mental disorder is a Roschian concept characterized by instrinsically fuzzy boundaries and that Wakefield's analysis may only prolong scientific debate on a fundamentally nonscientific issue.

Biological Evolution↗

[Incidence and characterization of large-cell anaplastic lymphoma].

PURPOSE: Large cell anaplastic lymphoma (LCAL) is a new entity among large cell lymphoma. Diagnosis is based upon morphology and on positivity to Ki1 antigen. The objectives of this study were: 1) to determine the incidence of LCAL in the patient population seen at the Instituto Roffo between 1981 and 1993; 2) to study the immunological phenotype; 3) to study the association with Epstein-Barr virus and HIV; 4) To study the expression of oncogen bcl-2 and 5) to evaluate tumoral growth factor. MATERIAL AND METHODS: The study was done on 1030 biopsies of nodal and extranodal lymphoproliferative diseases, with Hodgkin and non-Hodgkin lymphoma. Of the 1030 consecutive cases, 67 were selected. They revealed pleomorphic cells with sinusoidal disposition. Biotin and avidin peroxidase techniques were used to identify the following antigens: CD30(Ki 1), CD45RO (UCHL1), CD20(L26), CD45(CL), Epstein Barr virus (VEB), human immunodeficiency virus (HIV), CD15, CD68, PCNA, bcl-2 oncogen, vimentin, membrane epithelial antigen (EMA). Of these cases, only 10 revealed strong positive reaction to CD 30 (Ki1), thus they were considered to fulfill criteria to be classified as LCAL. RESULTS: 1. Incidence of LCAL in the lymphoma population under study was 1%. 2. Phenotype was B in 3 cases, T in 3, and macrophage in 1.3. There was 1 case of positive EBV and 3 positive HIV. 4. Eight of 10 LCAL cases were positive for bcl-2 protein. 5. Tumoral growth factor was 57%. Also, it was noted that most cases were secondary to Hodgkin lymphoma, and a few secondary to polymorphic immunoblastic lymphoma, with negative reaction to CD15 and EMA and positive for Vimentin. CONCLUSIONS: 1. Incidence of LCAL amongst patients with lymphoma is very low. 2. Immunological phenotype is varied. 3. There was no significant association with EBV or HIV. 4. Oncogen bcl-2 was demonstrated in most cases. 5. There was a high percentage of cells in proliferation.

Adolescent↗

Glycine-extended post-translational processing intermediates of gastrin and cholecystokinin in the gut.

Cholecystokinin (CCK) and gastrin are two polypeptide hormones of the gut that share complete structural homology in their carboxyl-terminal pentapeptide. Both peptides are biologically activated from their glycine-extended precursor forms by a carboxyl-terminal alpha-amidation reaction. In the present studies we used region specific antisera to characterize the carboxyl-terminally amidated and glycine-extended forms of gastrin and CCK in mammalian intestine. Multiple amidated molecular forms of gastrin and CCK and their corresponding glycine-extended forms were detected throughout the most of the small bowel. Although, we detected substantial amounts of glycine-extended CCK in the proximal rat duodenum, we detected none of the corresponding amidated molecular forms. In contrast, the proximal duodenum of dog and hog contained both glycine-extended and amidated CCK. These findings suggest that there may be peptide, tissue and species specific differences in expression and activity of the peptide alpha-amidating enzyme.

Amino Acid Sequence↗

Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or corticosteroid treatment.

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo-glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis.

Adult↗

Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study.

OBJECTIVE: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. DESIGN: Two pair-matched case-control studies. SETTING: A referral-based hospital. PATIENTS: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. MEASUREMENTS: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history. MAIN RESULTS: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma. CONCLUSIONS: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender.

Aged↗

Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis.

Hepatitis C virus (HCV) replication was assessed before and during alpha-interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were "responders" and 11 patients "non-responders" to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV-RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5'-noncoding (NC) region were more sensitive than primers from a non-structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, 32%, respectively). Positive strand HCV-RNA titre and positivity rate for the negative strand were similar in responders and non-responders before IFN treatment, as well as anti-c100-3 titre by enzyme-linked immunosorbent assay (ELISA), and anti-5-1-1, anti-c33c, anti-c22 positivity rate by immunoblot assay (RIBA). HCV-RNA positivity by both NC and NS primers was more frequent before IFN among responders. During IFN treatment, serum HCV-RNA was detectable, mostly at low titres, in 1 (NC positive) of the 11 responders and in 9 (4 NS positive and 5 NC positive) of the 11 non-responders. Among the four non-responders who were NS positive during IFN, three were NC positive before IFN. Serum HCV-RNA was always found in our post-transfusion or sporadic anti-HCV positive patients with CH. Viraemia generally decreased during IFN treatment, but no available HCV markers clearly distinguished responders from non-responders before IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antibodies to Mycobacterium paratuberculosis in patients with Crohn's disease.

IgG antibodies against Mycobacterium paratuberculosis protoplasmic antigen were looked for by an enzyme immunosorbent assay in patients with Crohn's disease, Ulcerative colitis, active pulmonary tuberculosis, past pulmonary tuberculosis, and in healthy controls. Serum reactivity for these antibodies was not correlated to PPD skin test positivity without history of mycobacterial disease. A cutoff based on the mean absorbance value of a pool of healthy blood donors was chosen. Positive values were found in 12/24 (50%) patients with active pulmonary tuberculosis and 2/10 (20%) skin-test-positive subjects with past pulmonary tuberculosis as expected, because antigenic sharing is common among different mycobacteria. The control group of blood donors showed borderline positivities in 3/149 cases (2.01%). Positive values were found in 4/108 (3.70%) patients with Crohn's disease and 2/40 (5%) with ulcerative colitis. We conclude that our data do not support a causal relationship between the M. paratuberculosis and Crohn's disease, but occasional patients with inflammatory bowel diseases show unexpected positivities for these mycobacterial antibodies.

Adolescent↗