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Biomedical subjects

A Mele

Publications and source records attributed to A Mele.

At least 145 records · Page 8Linked to original sources

[Autoimmune hemolytic anemia with cold antibodies and hemoglobinuria secondary to EBV infection].

The infection caused by EBV can be followed by immunological complications. One of these is autoimmune hemolytic anemia that up to today has been observed during infective mononucleosis only a few times. The authors describe a patient with this rare complication of the EBV infection and discuss its main clinical, pathogenetic and laboratory aspects, with particular attention to the presence of hemoglobinuria and to the absence of anti-i-antibodies. The disease's evolution was spontaneously favorable. For this reason and for the possible risks secondary to transfusions and to other therapeutical interventions, the authors believe that in autoimmune hemolytic anemia a vigil wait is more opportune before beginning the therapy.

Anemia, Hemolytic, Autoimmune↗

Virology of the hepatitis A epidemic in Italy.

We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-microliters serial serum samples available from 2 patients. Particular care was taken to rule out the possibility of false-positive results during analysis. Results demonstrated PCR amplification of the 3'-region of the VP3 gene in 5 of the 12 implicated lots of factor VIII and in the serial serum samples of both patients. PCR amplification also revealed that the gene sequences detected in patients' sera were identical to the sequences detected in the product they had received. In all, 3 VP3 sequences (found to be 96-99% identical) were amplified. Further characterization of the HAV found in the factor VIII concentrate and the patients' sera was attempted by PCR amplification of the VP1/2A region. Successful amplification of this region was achieved in the serum of only 1 patient and in the concentrate he received. This fourth amplified sequence was identical in both serum and factor VIII concentrate. Attempts to transmit hepatitis A from the contaminated lots to 3 chimpanzees resulted in no signs of infection after 10 months of observation. Based on the Italian experience, persons with severe hemophilia who receive large-pool concentrate are at potential risk for HAV infection and should be vaccinated against HAV or use an alternative to solvent-detergent-prepared concentrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The outbreak of hepatitis A in Italian patients with hemophilia: facts and fancies.

To determine whether an outbreak of hepatitis A that occurred in 52 Italian hemophiliacs was acquired through the infusion of contaminated factor VIII or through environmental enteric transmission, a case-control study of the first 29 infected patients was carried out. Case patients were neither more nor less likely than controls (hemophiliacs without HAV infection) to have traveled to high-risk countries, consumed raw shellfish or had contact with persons with jaundice. The case patients, however, were more likely than controls to have received a factor VIII concentrate treated with solvent-detergent and to have had larger infusions of the concentrate during the presumed HAV incubation period. In the PCR analysis of HAV sequences from implicated lots of factor VIII, HAV sequences were found in 5 of 12 lots of factor VIII implicated in the outbreak. Three different strains of HAV were recovered, suggesting that lots were not contaminated from the same plasmapheresis donor. To obtain molecular evidence that the HAV detected in the factor VIII preparations was responsible for transmission of HAV, serial serum samples from two patients were tested for HAV gene sequences and compared with those of the implicated lots. The genomic sequences of HAV obtained for two matched sets of factor VIII and recipient serum samples were identical within each set, but different for the two sets.

Adolescent↗

Thrombolytic and haemorrhagic effects of bolus doses of tissue-type plasminogen activator and a hybrid plasminogen activator with prolonged plasma half-life (K2tu-PA: CGP 42935).

K2tu-PA is a hybrid plasminogen activator linking the kringle 2 domain of tissue-type plasminogen activator (t-PA) to the catalytic protease domain of single-chain urokinase-type plasminogen activator (scu-PA). K2tu-PA, as t-PA has high affinity for fibrin and is activated by fibrin but has a longer plasma half-life (over 30 min). The aim of this study was to compare the effects of bolus doses of recombinant t-PA (rt-PA) and K2tu-PA, on: 1) lysis of performed thrombi (fibrinolysis), 2) accretion of new fibrin on pre-existing thrombi during fibrinolysis (thrombus growth), 3) thrombolysis as assessed by reduction of thrombus weight and 4) systemic plasma proteolysis and blood loss from a standard wound. A jugular vein thrombosis model and an ear bleeding model were adopted in rabbits. Saline produced 11 +/- 2% fibrinolysis. rt-PA, 0.2 mg/kg, 0.4 mg and 0.8 mg/kg produced 35 +/- 4%, 54 +/- 4% and 78 +/- 6% fibrinolysis, respectively. K2tu-PA, at the same doses, produced 39 +/- 5%, 57 +/- 6% and 83 +/- 6% fibrinolysis, respectively. Thus, no differences in the fibrinolytic activity of rt-PA and K2tu-PA were observed. Injection of saline was followed by an accretion of 56.4 +/- 5.9 micrograms of radioactive new fibrin on the thrombi. The injection of the three increasing doses of rt-PA was followed by an accretion of 54.9 +/- 5.3 micrograms, 49.1 +/- 6.1 micrograms and 47.2 +/- 4.8 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Properties of chimeric (tissue-type/urokinase-type) plasminogen activators obtained by fusion at the plasmin cleavage site.

Two hybrid plasminogen activators (K2tu-PA and FK2tu-PA), linking the kringle 2 domain or the finger plus the kringle 2 domains of tissue-type plasminogen activator (t-PA) to the catalytic domain of single-chain urokinase-type plasminogen activator (scu-PA) were studied. At variance with similar constructs previously reported, they were obtained by fusion of the t-PA and scu-PA derived portions at their plasmin cleavage site (between Arg275 of t-PA and Ile159 of scu-PA), thus eliminating from scu-PA the two peptide bonds (Glu143-Leu144 and Arg156-Phe157) that lead to low molecular weight scu-PA and to thrombin-inactivated tcu-PA. The specific activities of K2tu-PA and FK2tu-PA, as measured by fibrin plate were 2.5 x 10(6) and 1.0 x 10(6) t-PA equivalent units/mg, respectively. Activation of plasminogen by hybrid PAs was stimulated by both CNBr-digested fibrinogen (40- and 80-fold) and Des-A-fibrin monomers (6- and 12-fold). The relatively weak stimulation of chimeric PAs by minimally degraded fibrin monomers was consistent with their reduced fibrin binding capacity. Like scu-PA, the chimeric PAs, in the single-chain form, were insensitive to inhibition, as they retained full activity after prolonged incubation in plasma and did not interact with SDS-reactivated recombinant PAI-1. The concentration producing 50% lysis of blood clots in 3 h was 0.5 microgram/ml for K2tu-PA and 1 microgram/ml for FK2tu-PA, as compared to 0.5 microgram/ml and > 2 micrograms/ml for t-PA and scu-PA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Design↗

Hepatitis B mass immunization of adolescents: a pilot study in a community.

The National Type Specific Hepatitis Surveillance System (SEIEVA) and seroepidemiological studies have shown that in addition to newborns from mothers who are carriers for hepatitis B surface antigen (HBsAg), adolescents are at high risk of acquiring type B hepatitis virus because of increasing importance of the heterosexual transmission of this virus. In order to evaluate logistic problems and acceptance rate of adolescents to mass vaccination against hepatitis B, a pilot study was carried out among all 7th grade children registered in the 9 schools of an hepatitis B endemic area located in the suburbs of Naples. After meetings held by the local health department with school teachers and parents, 1219 out of 1250 (97.5%) invited children received the first dose of hepatitis B vaccine; 1215 and 1209 received, respectively, the second and third doses. Anti-hepatitis B surface antigen (anti-HBs) values were studied in 406 subjects one month after the third dose, and 21 out of 406 (5.2%) had anti-HBs values less than 10 IU/L. We consider 95% of subjects with anti-HBs values greater than 9 IU/L a good achievement for a field vaccination program. The high acceptance rate of vaccination found in our study outlines the importance of active offer of vaccination combined with school involvement.

Adolescent↗

A community survey on maternal and child health services utilization in rural Ethiopia.

A household health interview survey on MCH services utilization was carried out in 22 villages of a rural district of Arsi region, Ethiopia, before the launching of an integrated MCH programme. Coverage of antenatal services was 26%, and 61% of the women who received antenatal care reported having had 3 or more visits. Antenatal care was positively associated with living within 10 km of the Health Centre. Twenty-eight percent of the mothers attended the under-5 clinic and most returned for 3 or more visits. In addition, 99% reported having breast-fed their last child but more than 25% started weaning only after the seventh month of age. Differences in practice of treating diarrhoea according to knowledge of ORS were found. Of the 33% of those with knowledge of ORS, almost 90% reported use of ORS for treating child's diarrhoea, showing a positive attitude towards modern health care. The proportion of women using family planning was 5%, with no difference found between Christians and Muslims. Results on EPI coverage validated data from routine reporting. Integration of MCH services including out-reach activities may increase access and coverage of MCH services.

Adolescent↗

Census in a rural area of Ethiopia: methodology and results.

A census and an ecologic survey were performed in 39 villages of a rural district of Arsi Region, Ethiopia, in difficult field circumstances. Information on age, ethnic group, education and family relationship, as well as data on health facilities and availability of basic services were collected. Supervised students, working in teams, were used as interviewers. Communities were involved through plenary meetings and community health agents participated in the data collection process. A total of 64,714 people in 12,152 households were registered. The repeatability of age assessment was investigated by comparing the results from two villages with data obtained in a pilot study carried out 6 months earlier. The technical error was only 0.80 and 1.67 in the 0-5 and 6-15 age-groups, respectively. Three percent of the total population was under one year, less than previously estimated. This may, in part, be due to the family planning programme in the region. Eighteen percent of the households were headed by females. School attendance was less common among females and in the Oromo ethnic group. The availability of basic services, including safe water and basic sanitation supplies, was very poor in the area.

Adolescent↗

Immunodetection of human atherosclerotic plaque with 125I-labeled monoclonal antifibrin antibodies.

To test the affinity of a new F(ab')2 monoclonal antibody (TRF1) against human fragment D dimer of cross-linked fibrin for atherosclerotic plaques free of detectable thrombi, 6 atherosclerotic segments of carotid and femoral artery, and as a control 5 segments of atherosclerosis-free internal mammary artery, were drawn from 11 male patients undergoing bypass surgery. All segments were carefully washed in order to remove possible endoluminal thrombi, and cut to obtain pairs of intimal fragments of similar weight, containing either plaques (n = 16), or fatty streaks (n = 12), or normal endothelium (n = 20). Each fragment underwent a direct binding test to TRF1, or to a non-specific antibody, both labeled with 125I. The activity in each fragment was measured after 3 h of incubation at 37 degrees C, and after washing the fragments every hour for 3 h. TRF1 binding (as percentage of initial activity) was significantly higher (P < 0.001) in atherosclerotic than in normal fragments (26% +/- 11.5%, vs. 9.2% +/- 3.9% in fatty streaks, and 1.9% +/- 0.6% in normal endothelium), and indirect immunofluorescence confirmed TRF1 uptake within the plaque wall. By contrast, the non-specific antibody did not show any significant binding. These preliminary results demonstrate the high specific affinity of TRF1 for atherosclerotic plaques, probably due to the hemorheologic phenomena that activate platelets and provoke the formation of fragment D dimers of cross-linked fibrin on the plaque surface.

Arteriosclerosis↗

Estimation of early childhood mortality using preceding birth technique in a community-based setting.

The preceding birth technique, an indirect method for estimating early childhood mortality based on ascertaining the survival of previous children, was applied in rural Ethiopia within a system of demographic surveillance. Trained community health workers acted as interviewers and transmission flow of the routine health information system was used for data reporting. Data were collected for a median 12 month period from 39 sampled villages of Ticho district in Arsi region. From 1064 mothers having at least a second birth, the proportion dead of the last birth was 0.138 (95% CI 0.117-0.150), corresponding approximately to the probability of dying between birth and age two. It approximates to an infant mortality rate of about 100 x 1000 live-births. From 974 mothers having at least a higher-order birth, the proportion dead of the second to last birth was 0.203 (95% CI 0.178-0.228), equivalent to the risk of dying between 0 and age 5. In spite of the progressive migration of the surveyed population, the process and the outcome of the study suggest that PBT may well be inserted into a primary health care information system run by trained community health workers.

Birth Order↗

Striatal extracellular dopamine in conscious vs. anesthetized rats: effects of chloral hydrate anesthetic on responses to drugs of different classes.

Many investigations using the microdialysis technique have been performed in anesthetized animals, both in this laboratory and elsewhere. Concern arises with this preparation that the anesthetic may compromise neuronal function, or that it may interact with test drugs affecting neurotransmitter overflow. In addition, in these studies the microdialysis probe typically is introduced into the brain on the day of testing, and data collection commences within an hour or two following probe insertion. It has been suggested that transmitter recovered in the perfusate probably represents leakage due to tissue damage as well as exocytotic release, and may not accurately reflect neuronal responses to the manipulations of interest. Such potential confounds present important implications for the interpretation of data from these studies. The present investigation examined the effects of chloral hydrate anesthetic on (1) basal dopamine (DA) overflow in the anterior striatum, and (2) DA responses to systemically delivered drugs of two different classes known to influence DA activity. Three putative indices of impulse-dependent release were measured: (a) the time course and stability of basal DA overflow over several hours; (b) sodium channel involvement by adding tetrodotoxin (TTX) to the artificial CSF; and (c) calcium channel involvement using magnesium (Mg) in a calcium-free perfusate. Basal DA levels became stable in both conscious and anesthetized preparations by the second hour after probe insertion. Levels of recovered DA overflow in the anterior striata of conscious rats were approximately double those in chloral hydrate-anesthetized rats. Consistent with other findings, this suggests a general depression of CNS function by chloral hydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Thrombolytic activity of two chimeric recombinant plasminogen activators (FK2tu-PA and K2tu-PA) in rabbits.

The aim of this study was to evaluate the thrombolytic activity of two hybrid plasminogen activators (HPAs) in a rabbit jugular vein thrombosis model. In the two HPAs the kringle-2 domain (K2tu-PA) or the finger and the kringle-2 domains (FK2tu-PA) of tissue-type plasminogen activator (t-PA) are linked to the catalytic protease domain of single chain urokinase type plasminogen activator (scu-PA). The two HPAs were compared with rt-PA and scu-PA on a weight/weight basis. K2tu-PA, FK2tu-PA, rt-PA and scu-PA were infused at doses of 0.4, 0.8 and 1.2 mg/kg over 3 h. Saline served as control. Saline produced 11 +/- 2% thrombolysis. The three doses of K2tu-PA led to 38 +/- 4%, 66 +/- 5% and 89 +/- 7% thrombolysis, respectively; the three doses of FK2tu-PA: 18 +/- 3%, 29 +/- 5% and 33 +/- 6%, respectively; the three doses of rt-PA 32 +/- 2%, 49 +/- 3% and 68 +/- 6%, respectively; the three doses of scu-PA 16 +/- 2%, 24 +/- 3% and 32 +/- 4%, respectively. K2tu-PA and rt-PA showed a statistically significant higher thrombolytic activity than FK2tu-PA and scu-PA at the three tested doses (p less than 0.01). The thrombolytic activity of K2tu-PA was significantly higher than rt-PA at the two higher doses (p less than 0.01). Both K2tu-PA and rt-PA produced a statistically significant reduction of fibrinogen, alpha 2-antiplasmin and plasminogen 3 h after the start of the infusions of the two higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changing epidemiology of hepatitis B in Italy: public health implications.

In Italy, a dramatic decline of hepatitis B infection occurred in recent years as a result of nonmedical and medical factors. The national type-specific surveillance system shows that the age of maximum incidence changed from early childhood, when the risk of becoming a chronic carrier after infection is very high, to late adolescence. Data of several seroepidemiologic studies are consistent with this picture, but could not be compared with previous data on similar age groups. In 1981, a seroepidemiologic study on a national sample of 5,005 recruits showed a high prevalence of serologic markers of hepatitis B infection among young adults in Italy. In 1990, the authors replicated that original study on a national sample of 4,993 recruits. The adjusted prevalence of hepatitis B core antibodies among Italian male recruits dropped from 16.8% to 5.8% in 9 years. The authors anticipate a substantial reduction in the rate of production of chronic carriers and the rates of liver cirrhosis and primary liver carcinoma in Italy in the next decades. Vaccination campaigns, especially if combined with nonimmunologic preventive measures, will further reduce the rate of hepatitis B infection in Italy.

Adolescent↗

Chronic cocaine alters limbic extracellular dopamine. Neurochemical basis for addiction.

The extracellular concentration of dopamine in the ventral striatum was measured daily by means of brain microdialysis. Chronic cocaine (10 mg/kg twice daily) altered the dopamine output compared to that in vehicle-injected rats, inducing a pronounced increase in the first 3 days followed by a clear-cut decrease. This reduction in the output of dopamine during chronic cocaine as well as during withdrawal may be neurochemical substrate for the addictive properties of cocaine.

Animals↗

Prevalence of hepatitis C virus antibodies and hepatitis C virus-RNA in an urban population.

Several studies had been carried out on anti-hepatitis C virus (HCV) prevalence in populations with blood exposure risks and in blood donors. New tests are now available which allow the investigation to extend to other parameters such as antibody type and HCV-RNA. In this study the prevalence of anti-HCV c100-3 and the associated epidemiological, clinical, and virological markers were evaluated in subjects from an urban population located in central Italy. In positive cases the time persistence of HCV-RNA and anti-HCV antibody pattern was studied. For this purpose, sera from 1,484 randomly sampled individuals, aged 30-69 years, collected in 1985 and stored at -80 degrees C were retrospectively tested. The prevalence was 0.87% (i.e., 13 anti-HCV c100-3 positive cases). A significant association was observed with raised alanine transaminase (ALT) levels (P less than 0.001). Paired serum samples from 11 out of the 13 subjects collected in 1985 and 1991 were tested by nested polymerase chain reaction (PCR) using primers from the 5' non-coding region and by 4-RIBA. Concordant RIBA patterns between 1985 and 1991 were observed in the majority of positive paired sera (7/9) as well as for HCV-RNA (6/9). HCV-RNA was present in sera simultaneously positive to both types of antibody or to anti-c100-3 or anti-c22 alone. A wide spectrum of viral and antibody patterns in anti-HCV c100-3 positive sera was observed in this urban population and persisted for at least 6 years.

Adult↗

Proton nuclear magnetic resonance spectroscopy studies of the inclusion complex of piroxicam with beta-cyclodextrin.

Proton nuclear magnetic resonance spectroscopy showed that piroxicam sodium salt forms an inclusion complex with beta-cyclodextrin in aqueous solution. The 1:1 stoichiometry of the complex was determined by the continuous variation method. Significant nuclear Overhauser effects were observed between the inner protons of beta-cyclodextrin and protons of both the aromatic rings of piroxicam sodium salt, a result indicating that two isomeric 1:1 complexes must be present in solution within the range of concentrations investigated. The overall association constant was 113 M at 298 K. At concentrations less than 1.0 x 10(-3) M, the complex is completely dissociated.

Chemical Phenomena↗