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Biomedical subjects

R Romeo

Publications and source records attributed to R Romeo.

At least 55 records · Page 3Linked to original sources

Synthesis and characterization in solid and solution of trans-dichloro-1-(2', 6'-difluorophenyl)-1H,3H-thiazolo [3,4-a]-benzimidazole(tri-n-propyl-phosphine)-palladium(II)": a palladium(II) complex of a ligand with anti-HIV properties.

The 1-(2',6'-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (L), a highly potent nonnucleoside HIV-1 reverse transcriptase inhibitor, has been reacted with [Pd2Cl4(PPr3n)2] in order to study its coordinating properties towards metal ions. The structure of the synthesized product has been examined in solution by 1H and 13C NMR, and in solid by X-ray analysis. [Pd(PPr3n)(L)Cl2] has a trans structure and L coordinates through imine nitrogen. The loss of anti-HIV properties of L, by complexation, suggests that, unless biological inactivation is simple due to steric reasons, the imine nitrogen atom is an active site of the molecule.

Anti-HIV Agents↗

Inhibition of biliary bicarbonate secretion in ethinyl estradiol-induced cholestasis is not associated with impaired activity of the Cl-/HCO-3 exchanger in the rat.

BACKGROUND/AIMS: Bicarbonate is a major component of bile salt independent bile flow, which is impaired in ethinyl estradiol (EE)-cholestasis. To examine this subject in EE-cholestasis, we studied: 1) basal and glucagon-stimulated biliary bicarbonate secretion both in vivo and in the isolated perfused rat liver (IPRL); 2) H+/HCO-3 transport processes in isolated rat hepatocyte couplets. METHODS: Rats received EE (5 mg.kg b.w.-1) for 5 days. Intracellular pH (pHi) was measured (BCECF-AM) using a single-cell microfluorimetric setup. RESULTS: Bile flow was markedly (p < 0.01) decreased in EE-treated rats. Bicarbonate concentration in bile was decreased (p < 0.01) and bicarbonate secretion was 2.5-fold lower in EE-treated animals than in controls, both in bile-fistula rats [19.5 +/- 5.1 (n = 23) vs 54.2 +/- 5.7 (n = 20) nmol.min-1g liver-1; p < 0.01] and in the IPRL [11 +/- 2 (n = 8) vs 24 +/- 3 (n = 8) nmol.min-1.g liver-1; p < 0.01]. In control IPRL, a bile/perfusate gradient for bicarbonate is maintained, while it is lost in EE-treated IPRL because of the lower bicarbonate concentration in bile. Glucagon stimulated bile flow and bicarbonate secretion to a similar extent in EE-treated and control IPRL (+25% vs +23%). Resting pHi of EE-treated hepatocyte couplets was higher in comparison with controls in KRB [7.25 +/- 0.07 (n = 35) vs 7.20 +/- 0.05 (n = 33); p < 0.02] but similar in Hepes [7.08 +/- 0.07 (n = 24) vs 7.05 +/- 0.06 (n = 26)]. Basal activity of the Cl-/HCO-3 exchanger was similar in EE-treated and control hepatocyte couplets [H+ flux = 2.87 +/- 1.12 (n = 18) vs 3.01 +/- 1.23 mM/min (n = 15)] and was stimulated to a similar extent by glucagon. Na+/HCO3-symport activity was increased in EE-treated hepatocyte couplets (p < 0.05) while the Na+/H+ exchanger was unchanged. CONCLUSIONS: Bicarbonate biliary secretion is markedly impaired during EE-cholestasis in association with a marked decrease of bile salt independent bile flow. However, the Cl-/HCO-3 exchanger and its hormonal regulation are normal, indicating that the lower bicarbonate excretion in EE-cholestasis is not due to a compromised activity of this anion exchanger. Since the bile/perfusate gradient for bicarbonate is dissipated in EE-treated IPRL, the impaired bicarbonate excretion could be caused by a reflux of biliary bicarbonate via leaky tight junctions.

Animals↗

Osmotic drugs in the treatment of cochlear disorders: a clinical and experimental study.

On the grounds of positive results obtained with Meniere's patients, agents such as glycerol and mannitol have been included in the therapeutical protocol of other cochlear disorders presenting with hearing loss either of sudden onset, but not observed at an early stage, or accompanied by tinnitus and aural pressure. Intravenous infusions of either 10% glycerol or 18% mannitol were given to selected patients 3 to 6 times with a time interval of 1 to 3 days. Hearing loss, tinnitus and aural pressure were evaluated as improved, unchanged or worsened. In 33% of the glycerol group and 23.8% of the mannitol group we observed hearing threshold improvement, while aural fullness improved in 45% of the glycerol and 56.2% of the mannitol groups, and tinnitus was only relieved in 13.1% of the glycerol and 5.8% of the mannitol group. A parallel experimental study was carried out on guinea-pigs in order to shed light on the effects of mannitol and glycerol on the inner ear. Cochlear blood flow was measured with a laser Doppler flowmeter at the level of the basal turn of the cochlear lateral wall, both in normal and hydropic guinea-pigs, before and after osmotic intraperitoneal infusion. Basal values in the normal cochlea were much higher than in the hydropic one, and both mannitol and glycerol markedly influenced the local blood flow in the normal cochlea, giving few or no changes in the hydropic one.

Animals↗

[Inhalation of foreign bodies: epidemiological data and clinical considerations in the light of a statistical review of 92 cases].

In the present work 92 patients were studied all of whom had inhaled a foreign body (FB) into one of the tracheobronchial branch. The following factors were evaluated: sex, age, nature of the FB, localization in the respiratory tree, clinical symptoms, radiological findings, time lapse between diagnosis and removal. The peak incidence (61.9%) was in children under 3 years of age with a male-female ratio of 2:1. The most frequently inhaled FBs were of organic nature (31.5%); of these 58.6% were peanuts. The time lapse between inhalation and removal of the FB was as follows: in 20.5% the object was removed within 24 hours; in 66.4% within one week; in 12% in more than a week; and in 1.1% it took more than 8 weeks. In 53.2% of the cases the right bronchial branches were involved while in 28.2% the left side was affected. The most frequent symptoms were coughing (73.9%), wheezing (69.5%), dyspnea (51%) and fever (17.3%). Radiography detected the FB in only 7 cases (8.7%); in the remaining cases only indirect signs of the FB could be found: atelectasia (11.9%), emphysema (19.5%), cardio-mediastinic shift controlateral to the FB (10.8%). As regards complications, only 6 patients showed signs of slight endobronchial bleeding, 2 cases showed a pneumothorax and one other patient required a tracheotomy because of the particular shape of the FB which proved unable to pass backward through the glottis. In all cases the FB was removed using stiff bronchoscopy under either local or general anesthesia. The authors feel that, even if no clinical signs are found and radiography proves negative, one must always consider the possibility of a FB in the tracheal-bronchial branches, particularly in patients within the age range most at risk (under 3 years) and in those having a highly suspicious clinical history. In addition, the authors assert that the use of corticosteroids before and after the bronchoscopy markedly decreases the incidence of post-operative subglottic edema which would require an emergency tracheotomy.

Adult↗

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C.

To compare the long-term effectiveness and tolerability of lymphoblastoid interferon (IFN-alphaN1) and recombinant interferon alfa 2a (IFN-alpha2a) in patients with chronic hepatitis caused by hepatitis C virus (HCV), 234 consecutive patients with HCV-related chronic hepatitis were randomized prospectively to receive titrated doses (starting dose = 6 million units [MU]) of IFN-alpha2a (n = 118) or IFN-alphaN1 (n = 116) for 12 months. HCV RNA was detected by reverse-transcription polymerase chain reaction (RT-PCR), quantified by branched-DNA (bDNA) assay, and genotyped by reverse hybridization assay. Thirty-one patients in the IFN-alpha2a group and 28 in the IFN-alphaN1 group (total, 59 [25%] had normal transaminases and undetectable HCV RNA by RT-PCR after 12 months of therapy, but only 19 in the first group and 20 in the second group (total, 39 [17%]) had biochemical and virological responses 12 months after treatment was discontinued. The two treatment groups differed in terms of prevalence of major drug-related adverse reactions (23% vs. 37%, P = .025). The mean total dose per patient was similar for the two groups, i.e., 502 MU IFN-alpha2a vs. 496 MU IFN-alphaN1, and the cost of each sustained response was $31,800 and $32,440, respectively. By multivariate analysis, pretreatment viremia higher than 0.2 MEq/mL and infection with genotype 1 were independently associated to treatment failure. The outcome of treatment in chronic hepatitis C patients was not improved by the administration of high cumulative doses of lymphoblastoid IFN.

Female↗

Lingual thyroid: value of integrated imaging.

Lingual thyroid is an uncommon cause of oropharyngeal mass, due to a congenital anomaly of thyroidal development and migration: It is defined precisely as the presence of thyroid tissue in the midline of the tongue base between circumvallatae papillae and the epiglottis. We report a case of lingual thyroid in which the integration of clinical data, sonography, color-duplex Doppler, MRI and scintigraphy was determinant in demonstrating the disease. A 22-year-old woman presented with a sensation of foreign body in the throat, dysphonia, dyspnoea and dysphagia; we performed sonography (7.5 MHz linear probe), color Doppler (7 MHz Doppler frequency, PRF 3500 Hz) and MRI (1.5 T, spin-echo T1- and T2-weighted images with administration of Gd-DTPA); a scan with 123I demonstrated a relevant uptake at the base of the tongue, but no uptake at the typical thyroid location. The gland was removed and partially transplanted in the strap muscles of the neck.

Adult↗

Serum erythropoietin and blood lead concentrations.

The aim of the study was to test the hypothesis that high blood lead levels are associated with depressed serum erythropoietin concentrations in workers occupationally exposed to lead. The results in exposed workers and in a control group of unexposed subjects were compared. Blood lead values were < or = 20 micrograms/dl in unexposed subjects and > or = 30 micrograms/dl in exposed subjects. The two groups of exposed workers and the control population were matched for sex and age. Hemoglobin levels were not affected by blood lead values and did not differ significantly between the three groups. The two-tailed, nonparametric Mann-Whitney U-test was used to compare unpaired groups. The Spearman rank correlation test was used to evaluate the dose-effect relationship between Pb and EPO. The analysis of the data indicate that erythropoietin values are significantly lower in exposed subjects than a controls. However no correlation was demonstrated between blood lead concentrations and erythropoietin in any group.

Adult↗

Respiratory disease as a result of talc inhalation.

Three cases of respiratory disease in workers with occupational exposure to talc containing asbestos fibers are reported. Standard chest roentgenographs, high-resolution computed tomography, respiratory function tests, morphologic study of bronchoalveolar lavage fluid (BAL), light microscopic examination, and mineralogical analysis by transmission electron microscopy (TEM) of BAL was performed. All subjects showed bilateral pleural plaques, and in two subjects the study of BAL revealed lymphocytic alveolitis with an increased T4/T8 ratio. Mineralogical analysis of BAL detected asbestos-fiber concentrations of 510, 2039, and 3392 fibers/mL and many asbestos bodies. In one patient, mineralogical analysis of lung tissue was also performed; a concentration of 3,659,000 fibers/g dry tissue was found. Simultaneously, we performed a mineralogical study of 12 commercial talc samples, including those used by the patients during the last phase of their working lives. TEM revealed asbestos fibers in five samples. Two subjects used two of these talc powders. The study presented here confirms the need to perform all relevant clinical tests together with the study of BAL and mineralogical analysis of the materials to which the patients are or were exposed to determine occupational exposure to fibers, including those associated with talc, which are often misidentified.

Air Pollutants, Occupational↗

Lack of association between type of hepatitis C virus, serum load and severity of liver disease.

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.

Adult↗

Discrepancies in osmolal gaps and calculated alcohol concentrations.

OBJECTIVES: To estimate unexplained osmolal gaps (UEOG) during ethanol ingestions after accounting for measured ethanol concentrations and to explore the causes of observed discrepancies. DESIGN AND SPECIMENS: A random convenience sample of serum specimens with a request to perform osmometry for the detection of alcohols was studied. MAIN OUTCOME MEASURES: Serum concentrations of sodium, glucose, urea nitrogen, ethanol, osmolality, and ethanol were measured by two analytic methods to determine calculated osmolalities and osmolal gaps using two commonly used formulas. RESULTS: In 79 serum specimens submitted for osmometry, mean ethanol concentrations were 199 +/- 154 (SD) mg/dL; 15 specimens had no detectable ethanol. After regression of the calculated ethanol concentrations and the measured ethanol concentrations, the Dorwart and Chalmers formula showed a large constant bias of 45.217 +/- 6.414 (SE) mOsm/kg in predicting measured ethanol concentrations. The Smithline and Gardner formula was similarly as precise (r = .9786), but had a much smaller bias of -3.929 +/- 6.623 (SE) mOsm/kg. Actual mean differences between measured and calculated osmolalities (including ethanol osmols) gave an estimate of UEOG seen during ethanol ingestions. Using the less biased formula, the mean UEOG was 1.4 +/- 8.5 mOsm/kg, giving a 95% upper limit of the reference range of 18 mOsm/kg in this population with ethanol ingestions. Three significant outliers were identified and their UEOG could be explained by the presence of mannitol, isopropanol, or possibly a change in the assumed value for fractional water, normally a constant in these formulas for calculated osmolality. Other specific causes of osmolal gap and UEOG are discussed. CONCLUSION: The potential range of osmolal gaps seen during ethanol ingestions after accounting for ethanol is demonstrated to be greater than in previous studies, which have included a lower proportion of ethanol-intoxicated subjects in their study sample.

1-Propanol↗

Evidence of non-A, non-B, non-C infection in chronic hepatitis by polymerase chain reaction testing for hepatitis B and C viruses.

BACKGROUND/AIMS: Although hepatitis C virus is clearly the major cause of non-A, non-B acute and chronic hepatitis, there is a group of patients with histologically documented chronic hepatitis with no serological marker of hepatitis B and C, nor any other risk factors for liver disease. METHODS: We have investigated 17 well-characterized patients with chronic active hepatitis. HBV-DNA and HCV-RNA were tested by polymerase chain reaction in 17 serum samples and in six liver biopsies. RESULTS: Four of the 17 patients had serum HCV-RNA detectable by polymerase chain reaction, while none had HBV-DNA detectable by polymerase chain reaction. Three of the six liver samples gave a positive signal by cyclin A and HLA, and only these were considered for the study. One of the three was HCV-RNA positive, while none was HBV-DNA positive. CONCLUSIONS: Our results, obtained through careful elimination of all known risk factors for liver disease, strongly suggest that non-A, non-B, non-C hepatotropic virus(es) could be involved in some cases of chronic active liver disease.

Adolescent↗

Alpha interferon treatment of chronic hepatitis C.

Hepatitis C virus infection is a common disease with a high propensity to progress towards chronicity. Alpha interferon has been proposed to halt progression of the disease and prevent the development of more severe liver diseases such as cirrhosis and hepatocellular carcinoma. Unfortunately, less than 20% of treated patients show a long-lasting ALT normalization and HCV-RNA negativity. Factors which might be predictive of a long term response to interferon are debated. Univariate analysis of data collected in randomized clinical studies, has shown that IFN dose, age, duration of disease, cirrhosis and early response (primary) to IFN were all predictors of a sustained response to IFN, but with differences in different studies. When data were analyzed by a multivariate analysis, short duration of the disease and absence of cirrhosis were found to predict long-term response to interferon. Finally, many evidences indicate that response rates to therapy may be better in patients with low pretreatment levels of HCV-RNA measured either by polymerase chain reaction (PCR) or the branched-DNA assay (b-DNA).

Chronic Disease↗

Morphologic change in rabbit femoral arteries induced by storage at four degrees Celsius and by subsequent reperfusion.

PURPOSE: Cold-stored arteries function well as microvascular autografts, but little is known of the morphologic changes that occur in them during cold storage or of further changes during reperfusion. METHODS: In part A of the study, rabbit femoral arteries were stored at 4 degrees C for up to 6 months. In part B rabbit femoral arteries were stored at 4 degrees C for up to 6 months, inserted as end-to-end autografts into contralateral femoral arteries, and reperfused for 24 hours. Tissue was examined by histologic study, transmission and scanning electron microscopy, histochemical study, immunohistochemical study, and tissue culture. RESULTS: Cell viability declined gradually at 4 degrees C, so that by 4 weeks no viable cells remained. However, the extracellular framework and elastic lamellae remain intact. If cold-stored arteries are reinserted as autografts for 24 hours, this accelerates breakdown of necrotic cells and reduces the thickness of the medial wall and internal elastic lamina but does not alter the extracellular framework. CONCLUSIONS: Cold storage results in acellular vascular grafts with intact extracellular frameworks. After 24 hours reperfusion there is no major change to the extracellular framework.

Actins↗

Efficacy and tolerance of alpha-2b interferon therapy on HCV infection of hemodialyzed patients.

A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed patients were given a standard alpha-2b interferon regimen (3 megaunits subcutaneously three times weekly, following each hemodialysis) over six months as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N = 3). Thirteen of these 19 had increased levels of aminotransferase at the time of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the polymerase chain reaction and the bDNA test, respectively, at the beginning and at the end of antiviral treatment, and a third time at least six months after the end of therapy (mean follow-up 18 +/- 9 months). HCV genotype was determined in the 15 patients who had detectable HCV RNA before treatment. The biological response (long-term response, relapse or non-response) was defined as usual according to the serum aminotransferase levels during therapy and at least six months after. A post-treatment liver biopsy, allowing comparison with semiquantitative pathological scores, was performed in 14 patients. Only one of the 19 treated patients did not complete therapy because of poor tolerance, while 18 of the 19 fairly tolerated a complete six month course of alpha-2b interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Serum hepatitis C virus (HCV) RNA: a reliable tool for evaluating HCV-related liver disease in anti-HCV-positive blood donors with persistently normal alanine aminotransferase values.

BACKGROUND: The significance of hepatitis C virus (HCV) antibodies in blood donors with persistently normal alanine aminotransferase (ALT) levels requires evaluation. STUDY DESIGN AND METHODS: The serum and the liver were assayed for HCV RNA. Liver histology was analyzed in 14 HCV-positive subjects who had repeatedly normal ALT values over a follow-up period of at least 3 months. RESULTS: HCV RNA was not detected in liver and serum, and liver histology showed minimal changes in more than one-half of the subjects (8/14), even if third-generation recombinant immunoblot assay was positive; this demonstrated that HCV can be eradicated spontaneously. Moderately histopathological liver lesions were usually found in HCV RNA-positive subjects (6/14), but one subject had active disease that required interferon therapy; this shows that chronic hepatitis may be present in HCV-positive individuals despite repeatedly normal transaminase values. HCV genotypes other than 1b (II) were usually identified, and the presence or absence of serum and liver HCV RNA correlated completely in all 14 patients. CONCLUSION: Serum HCV RNA should be assayed in those HCV-positive donors having repeatedly normal transaminase activity; if it is positive, indicating an ongoing HCV infection, a liver biopsy should be performed to measure the degree of the liver disease and determine the appropriate antiviral therapy.

Adult↗

Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial.

The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.

Adolescent↗