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Biomedical subjects

F Russo

Publications and source records attributed to F Russo.

At least 55 records · Page 3Linked to original sources

Rare presentation of carcinosarcoma arising in bladder diverticulum.

An 87-year-old man presented with hematuria and dysuria. An endoscopic examination revealed a bladder mucosa which was almost entirely occupied by diverticula. On the left lateral wall of the bladder there was a huge diverticulum which contained a 12 cm mass extending beyond the bladder wall in the extraperitoneal tissues. Upon histological examination the mass proved to be a carcinosarcoma which was composed by a squamous carcinoma and a sarcoma resembling a malignant fibrous histiocytoma. The two components, i.e. carcinomatous and sarcomatous, were separated by a sharp collision border and no intermingling was ever noted. The epithelial component showed immunoreactivity for cytokeratin and EMA, while the mesenchymal component was diffusely reactive for vimentin, alpha-1-antitrypsin and lysozime. Both components were reactive for galectin-3, whereas S100, desmin and smooth muscle actin were negative. This is the fourth reported case of carcinosarcoma originating in a bladder diverticulum.

Aged↗

High potent and selective arylpiperazine derivatives as ligands for the 5-HT1A receptor.

This paper reports the synthesis and affinities on the 5-HT1A versus the alpha1A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16-24. Arylpiperazines 16-23 show affinities values in the nanomolar range for the 5-HT1A receptor. The compound 16 is highly potent (Ki 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (Ki 9.40 and 5.06 nM, selectivity 207 and 73, respectively).

Animals↗

Design, synthesis and binding properties of novel and selective 5-HT(3) and 5-HT(4) receptor ligands.

This work reports the synthesis and the binding tests on the 5-HT(3) and 5-HT(4) receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The compound with higher affinity and selectivity for the 5-HT(3) over the 5-HT(4) receptor was the 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one 28 (5-HT(3) K(i)=3.92 nM, 5-HT(4) not active), the compound with higher affinity and selectivity for the 5-HT(4) over the 5-HT(3) receptor was the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester 41 (5-HT(4) K(i)=81.3 nM, 5-HT(3) not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.

Animals↗

Epidermal growth factor and 17beta-estradiol effects on proliferation of a human gastric cancer cell line (AGS).

BACKGROUND: Recent evidence suggests that both estrogens and growth factors play an important role in the growth of gastrointestinal tumors. The expression of estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the gastrointestinal tract might therefore result in functional cross-talk between estrogens and EGF. The aim of the present study was to evaluate in vitro the effects of 17beta-estradiol and EGF administration on cell proliferation of a human gastric adenocarcinoma cell line (AGS) and investigate whether any interaction of these compounds may play a role in regulating gastric cancer cell proliferation. METHODS: Estrogen and EGFRs were detected by enzyme immunoassay. Cell proliferation was assessed with the MTT test. RESULTS: Exposure of AGS cells to increasing concentrations of 17beta-estradiol showed an anti-proliferative action at concentrations of 2 microM or higher. The addition of increasing concentrations of EGF stimulated cell growth, with a maximal response at 50 ng/ml EGF. The effect of increasing 17beta-estradiol concentrations combined with 50 ng/ml EGF was to increase cell growth at the lower estradiol concentrations. At the highest estradiol concentration the EGF proliferative effect was suppressed, and a decrease in proliferation rates occurred. Moreover, a significant negative correlation was found between 17beta-estradiol concentrations and EGFR expression. CONCLUSIONS: These findings suggest that growth of cultured gastric cancer cells (AGS) might be modulated by sex steroid hormones through interaction with EGF.

Adenocarcinoma↗

Inhibition of neutral endopeptidase potentiates the effects of atrial natriuretic peptide on acute cyclosporin-induced nephrotoxicity.

BACKGROUND: The use of cyclosporin A (CyA) is limited by its significant nephrotoxicity. Atrial natriuretic peptide (ANP) has been shown to ameliorate the reduction in glomerular filtration rate (GFR) induced by CyA, but its effect is transient. One explanation may be the rapid breakdown of this hormone by neutral endopeptidase (NEP) which is highly active in the kidney. In the present study, we examined the effect of the NEP inhibitor thiorphan on the acute fall in GFR induced by CyA. METHODS: After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg.kg(-1), i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 microg.kg(-1) i.v. as bolus and a maintenance infusion of 1 microg. kg(-1).min(-1)); (3) thiorphan alone (5 mg.kg(-1) i.v. as bolus and a maintenance infusion of 0.5 mg.kg(-1). min(-1)); (4) ANP plus thiorphan (as in 2 and 3), and (5) an infusion of 0.9% saline, increased from 1.2 to 3 ml.h(-1). The GFR was measured as the clearance of (3)H-methoxyinulin (ml.min(-1).100 g(-1) body weight). RESULTS: The data show: (1) the GFR fell from 1.06 +/- 0.15 to 0.59 +/- 0.09 ml.min(-1).100 g(-1) (p < 0.01) 60 min after CyA and remained depressed for at least 2 h; (2) ANP caused a marked initial rise in GFR from 0.49 +/- 0.07 to 1.23 +/- 0.18 ml.min(-1).100 g(-1) (p < 0.005 vs. CyA) which declined rapidly to the value seen after CyA injection alone, despite continuing ANP infusion; (3) thiorphan caused a modest, but significant increase in GFR within 15 min from 0.48 +/- 0.04 to 0.69 +/- 0.10 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which was sustained during infusion and for at least 30 min after stopping infusion; (4) ANP plus thiorphan produced a marked increase in GFR from 0.58 +/- 0.09 to 1.39 +/- 0.44 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which then decreased, but remained above the post-CyA injection value, until infusion of both drugs ended; (5) more than doubling the saline infusion rate per se had no significant effect on the GFR response to CyA. The blood pressure decreased significantly during ANP infusion, but more so when combined with thiorphan. CONCLUSION: These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance, and prolong, the vasodilator and diuretic effects of ANP.

Acute Disease↗

Antibiotic drug prescription in respiratory tract infections: a pharmacoepidemiological survey among general practitioners in a region of Italy.

Data concerning patients undergoing antibiotic treatment for upper (URTI) or lower (LRTI) respiratory tract infections were collected from 23 General Practitioners (GPs) in the Campania Region of Italy from November 15, 1997 to March 15, 1998. The objectives of the study were: a) to assess the occurrence of URTIs and LRTIs; b) to document the factors that influence GPs' choice of therapy; c) to correlate antibiotic choice with duration and outcome of treatment; d) to assess the incidence of unwanted effects. 2198 questionnaires were collected. Patients were +/-43.9 of age. URTIs were diagnosed in 65.4% and 34.6% LRTIs. The mean duration of antibiotic treatment was 4.5 days in URTIs and 5.6 days in LRTIs. The choice of antibiotic treatment was influenced by clinical assessment of infections (67.1%). The most commonly used antibiotic categories in URTIs were macrolides (39.3%), penicillins (27.4%) and cephalosporins (23.8%) whereas for LRTIs mainly cephalosporins (63.8%), penicillins (9.2%) and fluoroquinolones (7.4%) were used. Adverse events were experienced by 3.9% of patients.

Adolescent↗

Placement of peritoneal dialysis catheter by percutaneous method with the Veress needle.

In our center, a total of 451 peritoneal dialysis catheters were implanted in 424 uremic patients from 1986 to 1999. All catheters were implanted by the percutaneous method of Di Paolo. From 1986 to May 1997 (period A), we inserted 389 catheters using the Weston-Roberts catheter armed with a metallic sharp mandrel for the first access to the peritoneal cavity. After May 1997 (period B), we implanted 62 peritoneal dialysis catheters, replacing the metallic sharp mandrel with the Veress needle to arm the Weston-Roberts catheter. The aim of this retrospective study was to determine the incidence of early complications (within 2 weeks) and to compare the incidence between the two groups (period A versus period B). The results suggest that the incidence of perforation of abdominal organs is lower, but not significantly so, when the Veress needle is used.

Catheterization↗

[Functional heart murmur and echocardiography: a solved problem?].

BACKGROUND: Is it really vanished the need for echocardiography in the differential diagnosis of functional pediatric murmurs? METHODS: To this aim 260 children (132 males, 128 females; age range 1-84 months) were examined with auscultatory cardiac murmur. All children underwent a clinical and instrumental evaluation (ECG and echocardiography) from two pediatric cardiologists with independent assessment. RESULTS: Two hundred and ten patients (Group A) were evaluated clinically with functional murmur, 45 patients (Group B) with pathological murmur, 5 patients (Group C) with uncertain pathology. ECG showed changes in 1 Group B patient. Echocardiography showed pathology in 15 Group A patients (6 patients with patent foramen ovale, 5 patients with interatrial defect, 2 patients with bicuspid aortic valve, 1 patient with mitral insufficiency, 1 patient with restrictive cardiomyopathy). Pathology was excluded in 3 Group B patients, and in 2 Group C patients. In our clinical analysis echocardiography showed sensitivity 75%, specificity 97%, positive predictive value 90%, and negative predictive value 92%. CONCLUSIONS: In our experience we suggest to perform echocardiographic examination in children with functional murmur for complete assessment.

Child↗

Whipple's disease. Description of a case and survey of the literature.

A case of Whipple's disease (WD) personally observed is described. A 28-year-old male was admitted to hospital for evaluation of weakness, intermittent fever and weight loss arisen since a month. On clinical investigation, he complained of vomit and diarrhea since three months. He had neither familial and personal past history of gastrointestinal diseases, nor any other important diseases. He denied use of drugs. Physical examination was negative. Laboratory findings showed anemia, low blood lymphocytes, low serum iron and total iron binding capacity, low total serum protein and low serum albumin and high level of ESR. Stool were negative for parasites and occult blood. Cultures of blood and urine were negative. Stool fat assay was > 7 g/24 h and D-xylose test showed a two-hour serum concentration < 25 mg/dl. Abdominal TC showed lumbo-aortic and mesenteric enlarged lymph nodes. An upper video endoscopy showed a duodenal lymphangectasia. Histological examination showed villar atrophy with massive infiltration of large PAS-positive diastase-resistant foamy cells. Ziehl-Nielsen staining was negative. WD was diagnosed and patient underwent therapy based on cotrimoxazole. This report emphasizes the difficulty to diagnose WD correctly, because of its rareness and clinical polymorphism. Recently, studies have identified a bacillus, Tropheryma whippelii, associated with WD, so that, in the next future, the diagnosis of WD will be faster and more accurate. Finally, it is important to administer antibiotics which can cross the blood brain barrier for at least one year, in order to prevent neurological relapse, often lethal.

Journal Article↗

Severe paronychia due to zidovudine-induced neutropenia in a neonate.

We describe the case of an HIV-perinatally exposed child who was treated with zidovudine prophylaxis for reduction of perinatal transmission. At 4 weeks of age, he developed severe paronychia of the great toes as a result of Candida albicans and Escherichia coli. At that time, laboratory tests showed anemia and neutropenia. Zidovudine-related hematologic toxicity resolved after completion of the prophylactic regimen and the infant became HIV-antibody negative (seroreverter) at 8 months of age. Paronychia resolved after treatment with oral fluconazole and topical antiseptics but the soft tissue of the nailfold was penetrated by the edge of the nail plate, resulting in the formation of a cutaneous bridge over the nail that resolved by spontaneous necrosis. To our knowledge, this rare complication has not previously been described in an HIV-perinatally exposed child treated with zidovudine.

Anti-HIV Agents↗

Chronic lymphocytic leukaemia and neuroendocrine cancer.

We report a unique association between neuroendocrine cancer and chronic lymphocytic leukaemia (CLL) in a 63-year-old man. Neuroendocrine cancer was resistant to various conventional treatments and following locoregional progression we treated the patient with hypoxic pelvic perfusion of cisplatin 100 mg/m2 plus mitomycin 40 mg/m2, using the stopflow method, for three cycles: a dramatic and surprising reduction of > 75% in the evaluable lesions was observed. The cumulative effect of treatment produced a complete response from CLL. At cytogenetic examination the neuroendocrine cells were diploid, whereas CLL cells showed trisomy 12. Moreover, deletion of the short arm of chromosome 3 was found in both neoplastic populations. Whether the abnormality seen on chromosome 3 in the two diseases represents a critical event is not known.

Chromosome Deletion↗

Inhibitory effect of 17beta-estradiol on growth and the polyamine metabolism of a human gastric carcinoma cell line (HGC-27).

BACKGROUND: Estrogens may, by means of their receptors, modulate the growth of several tumors including gastrointestinal neoplasms. This control may occur through interaction with other molecules such as polyamines. An inverse relation between polyamine levels and the estrogen receptorial content has previously been demonstrated in vivo in human gastric carcinoma. The aim of the present study was to evaluate the effects of 17beta-Estradiol administration on the in vitro cell proliferation rates and the polyamine metabolism of an estrogen receptor-positive human gastric cancer cell line (HGC-27). METHODS: Estrogen receptors were detected with enzyme immunoassay. Cell proliferation was assessed by means of [3H]-thymidine incorporation and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. The polyamine content was evaluated with high-performance liquid chromatography and the ornithine decarboxylase activity with a radiometric technique. RESULTS: Exposure of HGC-27 cells to increasing concentrations of 17beta-Estradiol showed that an antiproliferative action became evident at concentrations of 8 microM or higher. At such concentrations, ornithine decarboxylase (ODC) activity was also significantly reduced, as were all polyamine levels, compared with the untreated control. These findings suggest that one of the mechanisms underlying 17beta-Estradiol inhibition of HGC-27 cell proliferation is a decrease in ODC activity and, hence, in polyamine production.

Cell Division↗

Detection of Helicobacter pylori cagA gene by polymerase chain reaction in faecal samples.

OBJECTIVE: The polymerase chain reaction (PCR) has been extensively and successfully used to detect Helicobacter pylori in gastric juice and gastric biopsies. In contrast, the results obtained using faeces as biological samples for PCR are rather conflicting. This may be due to the presence of faecal inhibitory compounds (polysaccharides) which can inhibit the amplification reaction. The aim of this study was to characterize the H. pylori genotype in faecal samples by using specific primers for the cagA gene. To overcome the problem of contamination by polysaccharides, we used a filter-based extraction technique already applied in a previous study. METHODS: Antral and body biopsies were obtained from 30 symptomatic patients undergoing upper endoscopy. PCR was used to detect the presence of H. pylori organisms in faecal samples by using primers selected for the urease gene A. In addition, H. pylori organisms were characterized both in faecal samples and paraffin-embedded biopsies by PCR with specific primers for the cagA gene. RESULTS: All patients showed a positive CLO test (rapid urease test) and evidence of H. pylori by Warthin-Starry stain. PCR detected the urease A gene in the faecal samples of all patients. The cagA gene was detected in the faecal and biopsy samples of 18 subjects (60%). Duodenal ulcer and/or antral erosions were observed in 15 of the 18 cagA-positive patients (83.3%) and in five of the 12 cagA-negative patients (41.7%). Endoscopic features of normal mucosa or gastritis were observed in three cagA-positive patients (16.7%) and in seven cagA-negative patients (56.3%). cagA-positive status was found to be significantly related to the endoscopic features of duodenal ulceration and/or antral erosions. CONCLUSIONS: Our findings prove that faeces are suitable samples for the detection of cagA status. Moreover, they confirm the existence of a significant relationship between cagA-positive status and duodenal ulcer and/or antral erosions.

Adult↗

Combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) anf erythropoietin (EPO) for the treatment of advanced non-responsive chronic lymphocytic leukemia.

We report the use of a colony-stimulating granulocyte-macrophage factor (GM/CSF) and erythropoietin (EPO) combination as salvage treatment in four heavily-pretreated patients with refractory/ recurrent B-CLL. Induction therapy was subcutaneous GM-CSF 2.5 microg/ kg, and EPO, 150 units/kg both daily for the first 14 d. Maintenance therapy was GM-CSF on days 1, 3 and 5 and Epo on days 2, 4 and 6 at the same doses with weekly recycling. All the patients responded favourably. A significant reduction of lymphocytosis, lymphoadenomegaly, and organomegaly was obtained within one month of therapy. The number of infections and transfusional requirement decreased dramatically. The hemoglobin increased to over 11 g/dl in 3 out of 4 patients. With a median follow-up of 11 months (range 5-13) we observed 4 partial responses (NCI/IWCLL) and only one progression after a 10-month partial response. This combination regimen seems very active, safe and easy to administer. It may represent a promising therapeutical option in heavily pretreated patients. Further clinical and biological studies on a larger cohort of patients are needed to confirm these preliminary data, to clarify the hypothetical interactions between these cytokines and B-CLL cell proliferation pathways, and to establish if this therapy may have an impact on survival.

Administration, Cutaneous↗

Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects.

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).

Adult↗

Helicobacter pylori infection and host cell responses.

It is well known that Helicobacter pylori is able to colonize the gastric mucosa, causing a chronic and persistent infection with complications, such as peptic ulcer and gastric cancer. This review places emphasis on some epidemiological aspects of Helicobacter pylori infection and its mode of transmission. At the same time, invasive and non-invasive methods of diagnosis of Helicobacter pylori infection are illustrated. More space is devoted to the host response following invasion of the stomach. In this respect, the role played by different growth factors and polyamines in the course of Helicobacter pylori disease is discussed also in relation to the result of eradicating treatment. On the other hand, an accurate description of the host immune responses against Helicobacter pylori organism and/or their components (e.g. lipopolysaccharides) is reported. Finally, since Helicobacter pylori has been classified as a class I carcinogen, current researches are focussed on the Helicobacter pylori-induced carcinogenesis.

Animals↗