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Biomedical subjects

R Romagnoli

Publications and source records attributed to R Romagnoli.

At least 55 records · Page 3Linked to original sources

Coronally advanced flap for the treatment of buccal gingival recessions with and without enamel matrix derivative. A split-mouth study.

BACKGROUND: The coronally advanced flap (CAF) is a predictable method for achieving root coverage in buccal gingival recessions. The use of enamel matrix derivative (EMD) has already been tested in treating intrabony defects. No clinical comparative study has been published evaluating the CAF in combination with EMD in treating buccal gingival recessions. METHODS: This split-mouth study was performed to assess the efficacy of EMD to improve the results of a root coverage procedure. Fourteen pairs of Miller Class I and II bilateral comparable defects were selected in 12 patients. In each patient, one site was randomly assigned to the test group and the contralateral site to the control group. The treatment consisted of a CAF procedure with (test) or without (control) EMD. Gingival recession (REC), clinical attachment level (CAL), probing depth (PD), and extension of keratinized tissue (KT) were recorded at baseline and 6 months postsurgery. RESULTS: The average initial REC was 3.71 mm (SD +/- 1.68) for the test group, and 3.50 mm (SD +/- 1.56) for the control group. The 2 groups were statistically homogeneous. The mean root coverage was 3.36 mm (SD +/- 1.55), corresponding to a value of 91.2% for the test group, and 2.71 mm (SD +/- 1.20), equal to 80.9% for the control group. The differences between the 2 groups were not statistically significant. The mean CAL gain was 3.57 mm (SD +/- 1.55) for the test group and 2.79 mm (SD +/- 1.19) for the control group. No changes of PD and KT were found. CONCLUSIONS: This study suggests that EMD does not seem to significantly improve the clinical outcomes of gingival recession treated by means of CAF, even though the test group showed slightly better results in terms of root coverage and CAL. Further studies with a larger number of teeth and higher statistical power are needed to support this conclusion.

Adult↗

DNA sequence-recognizing properties of minor groove alkylating agents. Effects of the replacement of N-methylpyrrole by an N-methylimidazole on tallimustine and its own homologue.

The linkage of an heterocycle, like N-methylimidazole, to minor DNA groove binders containing two or three pyrroles lead to a new class of oligopeptides with reduced antitumor activity both in vitro and in vivo if compared to tallimustine (CAS 115308-98-0) and its tetrapyrrole homologue 9. In the present paper is reported the correlation between the cytoxicity of tallimustine and its derivatives 9-11 with their ability to inhibit polymerase chain reaction (PCR) amplification of oestrogen receptor and Ha-ras gene sequences, containing A + T rich and G + C rich regions, respectively. Tallimustine and its tetrapyrrole homologue 9 were found to have higher sequence selectivity for the human oestrogen receptor (ER) gene with respect to the relative imidazole-containing analogues.

Animals↗

[(3)H]MRE 3008F20: a novel antagonist radioligand for the pharmacological and biochemical characterization of human A(3) adenosine receptors.

The lack of a radiolabeled selective A(3) adenosine receptor antagonist is a major drawback for an adequate characterization of this receptor subtype. This paper describes the pharmacological and biochemical characterization of the tritiated form of a new potent A(3) adenosine receptor antagonist, the pyrazolo triazolo pyrimidine derivative [(3)H]5N-(4-methoxyphenylcarbamoyl)amino-8-propyl-2-(2-furyl )pyrazolo [4,3-e] -1,2,4- triazolo[1,5-c]pyrimidine ([(3)H]MRE 3008F20). [(3)H]MRE 3008F20 bound specifically to the human adenosine A(3) receptor expressed in CHO cells (hA(3)CHO), and saturation analysis revealed a single high affinity binding site, K(D) = 0.80 +/- 0.06 nM, with a B(max) = 300 +/- 33 fmol/mg protein. This new ligand displayed high selectivity (1294-, 165-, and 2471-fold) in binding assay to human A(3) versus A(1), A(2A), and A(2B) receptors, respectively, and binds to the rat A(3) receptors with a K(i) > 10 microM. The pharmacological profile of [(3)H]MRE 3008F20 binding to hA(3)CHO cells was evaluated using known adenosine receptor agonists and antagonists with a rank order of potency consistent with that typically found for interactions with the A(3) adenosine receptors. In the adenylyl cyclase assay the same compounds exhibited a rank order of potency identical with that observed in binding experiments. Thermodynamic data indicated that [(3)H]MRE 3008F20 binding to hA(3)CHO is entropy- and enthalpy-driven in agreement with the typical behavior of other adenosine antagonists to A(1) and A(2A) receptors. These results show that [(3)H]MRE 3008F20 is the first antagonist radioligand with high affinity and selectivity for the human A(3) adenosine receptor and may be used to investigate the physiopathological role of A(3) adenosine receptors.

Adenosine↗

[Hepatic arterial vascular anatomy and its variants].

PURPOSE: We investigated the frequency of anatomical variants of the hepatic artery, which can influence interventional angiographic procedures. MATERIAL AND METHODS: We reviewed 150 consecutive angiograms performed for the treatment of primary (112) or metastatic (38) liver tumors and evaluated the frequency of anatomical variants of the hepatic artery based on the classification proposed by Michels in 1955, which describes 10 variants. The so-called typical anatomy, which is in fact only found in 55% of cases, is indicated as type I. RESULTS: The typical anatomy (type I variant) was seen in 78 patients (52%) and variants were seen in the other 72 (48%). We found 15 type II variants (10%), 23 type III (15.5%), 1 type IV and 1 type V (0.6%), 3 type VI (2%), 1 type VII (0.6%) and finally 6 type IX (4%). There were no type VIII or X variants, but in 22 patients (14.7%) vascular anatomy did not fit Michaels' classification. DISCUSSION AND CONCLUSIONS: In our series the typical hepatic artery anatomy was found in 52%, which is in agreement with Michels' findings, while the frequency of the individual anatomical variants differed. Not all of the variants reported by Michels were seen in our series and we found 22 patients with different variants. Disagreement might be due to the fact that Michels' was an autoptic series while our patients were cancer patients only and thus variability could be at least partly accounted for by neoplastic neovascularization. We believe that thourough knowledge of the anatomical variants of the hepatic artery is fundamental to angiographic practice, in particular for interventional procedures, because such variants can influence the choice of vascular technique and of materials.

Angiography↗

Synthesis, in vitro antiproliferative activity, and DNA-binding properties of hybrid molecules containing pyrrolo[2,1-c][1, 4]benzodiazepine and minor-groove-binding oligopyrrole carriers.

The synthesis, biological activity, and DNA-binding properties of a series of four hybrids prepared by combining polypyrrole minor groove binders and pyrrolo[2,1-c][1,4]benzodiazepine (PBD) 13, related to the naturally occurring anthramycin (3) and DC-81 (4), have been described, and structure-activity relationships have been discussed. These hybrids 22-25 contain from one to four pyrrole units, respectively. To investigate sequence selectivity and stability of drug/DNA complexes, DNase I footprinting and arrested polymerase chain reaction (PCR) were performed on human c-myc oncogene, estrogen receptor gene, and human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) gene sequences. The antiproliferative activity of the hybrids has been tested in vitro on human myeloid leukemia K562 and T-lymphoid Jurkat cell lines and compared to antiproliferative effects of the natural product distamycin A 1, its tetrapyrrole homologue 17, DC 81 (4), and the PBD methyl ester 12. The results obtained demonstrate that the hybrids 22-25 exhibit different DNA-binding activity with respect to both distamycin A 1 and PBD 12. In addition, a direct relationship was found between number of pyrrole rings present in the hybrids 22-25 and stability of drug/DNA complexes. With respect to antiproliferative effects, it was found that the increase in the length of the polypyrrole backbone leads to an increase of in vitro antiproliferative effects, i.e., the hybrid 25 containing the four pyrroles is more active than 22, 23, and 24 both against K562 and Jurkat cell lines.

Antineoplastic Agents↗

Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: a further validation of the relationship between chemical solvolytic stability and cytotoxicity.

The chemical resolution, using N-tosyl-L-proline as a chiral auxiliary, of a racemate of the pyrazole analog (+/-)-N-Boc-CPzI of the left hand segment (CPI) of the antitumor agent CC-1065, and the cytotoxic evaluation of both enantiomers are described. The reported results further validate the direct relationship between chemical solvolytic stability of the cyclopropane ring and cytotoxicity proposed by Boger and coworkers.

Animals↗

Characterization of toad liver glutathione transferase.

The major form of glutathione transferase from the toad liver previously designed as Bufo bufo liver GST-7.6 (A. Aceto, B. Dragani, T. Bucciarelli, P. Sacchetta, F. Martini, S. Angelucci, F. Amicarelli, M. Miranda and C. Di Ilio, Biochem. J. 289 (1993) 417-422) has been characterized. According to its partial amino acid sequence, the toad enzyme may be included in the pi class GST and named bbGST P2-2. However, bbGST P2-2 appears to be immunologically, structurally and kinetically distinct from any other members of pi family, including bbGST P1-1, suggesting that it may constitute a subset of pi class GST. The data support the hypothesis that the transition from aquatic to terrestrial life causes a switch of the GST amphibian pattern promoting the expression of a GST form (bbGST P2-2) able to counteract, with higher efficiency, the toxic effects of reactive metabolites of oxidative metabolism and those of hydrophobic xenobiotics.

Amino Acid Sequence↗

Novel benzoyl nitrogen mustard derivatives of pyrazole analogues of distamycin A: synthesis and antileukemic activity.

The design and synthesis of novel benzoic acid mustard (BAM) derivatives of distamycin A bearing one or more pyrazole rings replacing the pyrrole rings of the latter are described. In vitro and in vivo activities against L1210 leukemia are reported and discussed. Some of these compounds show an activity profile comparable to tallimustine 1. All the compounds bearing the pyrazole ring close to the BAM moiety show reduced cytotoxicity in comparison to derivatives characterized by the BAM linked to a pyrrole: the same effect has not been observed when occurring at the amidine terminus of the oligopeptidic frame.

Animals↗

Identification of families with hereditary breast and ovarian cancer for clinical and mammographic surveillance: the Modena Study Group proposal.

Hereditary factors play a fundamental role in the pathogenesis of breast cancer (BC). Approximately 15-20% of all BCs have been reported to show familial clustering. In spite of the recent demonstration and chromosomal localization of BC predisposing genes, clinical clues and careful inspection of pedigree still remain major instruments in HBC diagnosis. The aim of the present study was to develop minimum operational criteria for the selection of family groups at high risk of developing BC. Following a stepwise procedure, families were stratified into four clusters with increasing probability of genetic involvement. So far, 317 BC-prone families have been identified and distributed in the four groups, and 151 high risk women underwent our clinical and mammographic surveillance program. Among these, after a mean follow-up of 24 months, six BCs and one OC were diagnosed (one BC and one OC occurred in the same woman) and one 'interval' BC was observed. Since the prevalence rate so far detected is dramatically higher than that seen at the first round of Italian population-screening programs, our preliminary data support the usefulness of the proposed procedure in selecting high risk individuals.

Adult↗

1H-pyrazolo[2,3-d][1,2,4]triazine-3,7-diones as a new class of human leukocyte elastase inhibitors.

A novel series of 1H-2-phenyl-substituted-pyrazolo[2,3-d][1,2,4]triazine-3,7-diones (3a-g) as potential inhibitors of Human Leukocyte Elastase (HLE) are reported, the acyl-pyrazole being probably involved in the inhibition mechanism of the serino-protease enzymes. The most potent inhibitor both in vivo and in vitro was 2-o-methoxyphenyl-5-methyl-6-nitro-pyrazolo[2,3-d][1,2,4]triazine-3,7-di one (3e), which significantly suppressed the HLE-induced pulmonary injury in rats when administered orally (100 mg/kg, 3 h prior to HLE administration.

Animals↗

Duodenogastric reflux of bile in health: the normal range.

Duodenogastric reflux (DGR) is suspected to be an aetiological factor in the pathogenesis of foregut disease. The 'Bilitec' bile probe allows continuous detection of bilirubin, based on spectrophotochemical properties. We aimed to describe duodenogastric bile reflux in healthy, normal volunteers in a Western European population, as a basis for the future study of DGR in disease. An international multicentre study was established. DGR was measured using 24 h ambulatory bile and pH monitoring in the proximal stomach, in 43 normal volunteers from the third to the seventh decades. Subjects adhered to a standard protocol. The total test period, supine and upright components, were analysed. The 90th percentile values for absorbance thresholds of 0.14, 0.25, 0.3, 0.4 and 0.5 were 40.5%, 20.9%, 19.6%, 11.6% and 4.6% of the total time respectively. There was a wide range of absorbance within each threshold. Supine DGR was greater than upright, and associated with an alkaline tide. The upright phase was further subdivided into upright fasting, prandial and post prandial phases, and ranges for these periods are also described. No relationship between age, weight, or body mass index and duodenogastric reflux was seen. The results of this study form a range which allows further investigation into the contribution of duodenogastric bile reflux in the pathogenesis of foregut disease.

Adult↗

Erythromycin enhances early postoperative contractility of the denervated whole stomach as an esophageal substitute.

OBJECTIVE: To determine whether early postoperative administration of erythromycin accelerates the spontaneous motor recovery process after elevation of the denervated whole stomach up to the neck. SUMMARY BACKGROUND DATA: Spontaneous motor recovery after gastric denervation is a slow process that progressively takes place over years. METHODS: Erythromycin was administered as follows: continuous intravenous (i.v.) perfusion until postoperative day 10 in ten whole stomach (WS) patients at a dose of either 1 g (n = 5) or 2 g (n = 5) per day; oral intake at a dose of 1 g/day during 1.5 to 8 months after surgery in 11 WS patients, followed in 7 of them by discontinuation of the drug during 2 to 4 weeks. Gastric motility was assessed with intraluminal perfused catheters in these 21 patients, in 23 WS patients not receiving erythromycin, and in 11 healthy volunteers. A motility index was established by dividing the sum of the areas under the curves of >9 mmHg contractions by the time of recording. RESULTS: The motility index after IV or oral administration of erythromycin at and after surgery was significantly higher than that without erythromycin (i.v., 1 g: p = 0.0090; i.v., 2 g: p = 0.0090; oral, 1 g: p = 0.0017). It was similar to that in healthy volunteers (i.v., 1 g: p = 0.2818; oral, 1 g: p = 0.7179) and to that in WS patients with >3 years of follow-up who never received erythromycin (i.v., 1 g: p = 0.2206; oral, 1 g: p = 0.8326). The motility index after discontinuation of the drug was similar or superior to that recorded under medication in four patients who did not experience any modification of their alimentary comfort, whereas it dropped dramatically parallel to deterioration of the alimentary comfort in three patients. CONCLUSIONS: Early postoperative contractility of the denervated whole stomach pulled up to the neck under either i.v. or oral erythromycin is similar to that recovered spontaneously beyond 3 years of follow-up. In some patients, this booster effect persists after discontinuation of the drug.

Adolescent↗

Gastric symptoms and duodenogastric reflux in patients referred for gastroesophageal reflux symptoms and endoscopic esophagitis.

BACKGROUND: The role of excessive duodenogastric reflux (DRG) in the genesis of gastric symptoms in patients primarily referred for both gastroesophageal reflux (GER) symptoms and esophagitis is poorly understood. METHODS: The study is based on the clinical, endoscopic, histologic, and 24-hour gastric data from the Bilitec optoelectronic device (Prodotec, Florence, Italy, licensed by Synectics Medical, Stockholm, Sweden) from 49 patients having both typical GER symptoms and gastric symptoms suggestive of excessive DGR (i.e., epigastric pain, nausea, or bilious vomiting) in the absence of previous esophageal or gastric surgery (group 1). Helicobacter pylori organisms were searched for on antral biopsy specimens with use of the Giemsa method. The percentages of total, upright, and supine time during which absorbance exceeded various thresholds through all the working range of the Bilitec device were calculated. Bilitec data from group 1 were compared with those from 16 patients with endoscopic esophagitis and GER symptoms only (group 2) and 25 healthy subjects (group 3). RESULTS: The prevalence of an abnormal Bilitec test result in group 1 increased from 27% (13/49) at the 0.25 absorbance threshold to 36% (18/49) at thresholds ranging from 0.40 to 0.60 and to 41% (20/49) when multiple thresholds ranging from 0.25 to 0.60 were considered. In group 2 one patient had an abnormal Bilitec test result at the 0.25 to 0.30 threshold, whereas the other 15 patients had a normal test result. H pylori antral infection was present in 14 group 1 patients. None of these had an abnormal Bilitec test result, whereas the test was positive in 40% of the H pylori-negative patients without endoscopic gastritis and in 70% of H pylori-negative patients with endoscopic gastritis (P = .001). CONCLUSIONS: Twenty-four-hour intragastric bile monitoring provides the clinician with unequivocal evidence of excessive DGR in 41% of patients with an intact stomach having endoscopic esophagitis, GER symptoms, and gastric symptoms suggestive of DGR. The most dependable data are obtained when absorbance thresholds higher than 0.40 are considered. H pylori antral infection and excessive DGR at 24-hour intragastric bile monitoring are mutually exclusive.

Adolescent↗

PNU 157977: a new potent antitumour agent exhibiting low in vivo toxicity in mice injected with L1210 leukaemia cells.

The design, synthesis, in vitro and in vivo activity against L1210 murine leukaemia of the dibromo nitrogen mustard derivative of 2, called PNU 157977, is described and the structure-activity relationship discussed. This dibromo derivative is almost two orders of magnitude more cytotoxic than the dichloro counterpart having the same oligopeptidic chain (IC50 2.7 ng/ml versus 225 ng/ml), and it showed in vivo an increased survival time which is 5- and 3-fold longer than that of tallimustine and 2 (and T/C 750 versus 133 and 213) respectively. Moreover PNU 157977 shows activity against the M5076 solid tumour markedly inferior to that of the closely analogous 2. Footprinting experiments conducted using the oestrogen receptor PCR probe as the footprinting target molecule show that PNU 157977 possesses a different sequence-specific alkylation and greater cleavage activity than either 2 or tallimustine.

Animals↗

[Effect of immobilization after treatment of mandibular fractures].

BACKGROUND AND AIM: The aim of this study was to assess whether the duration of intermaxillary block in patients with non-condylar mandibular fractures can interfere with restored mandibular function and whether there is a statistically significant correlation between the duration of joint immobilisation and the onset of temporo-mandibular joint pathologies. METHODS: A clinical evaluation was made of 40 patients treated for non-condylar mandibular fractures during the period 1991-1992. The patients were subdivided into two groups depending on the type of treatment and the duration of the intermaxillary block. Group A included patients treated with intermaxillary block alone lasting more than 25 days. Group B included patients treated surgically with intrafocal osteosynthesis with immobilisation lasting less than 15 days. RESULTS: The follow-up of results (3.7 years) showed a maximum mean aperture in Group A of 45.1 mm compared to 50.1 mm in Group B. The mean score for mandibular clinical dysfunction in patients in Group A was 5.0 points (SD +/- 4.75), whereas it was 0.7 points (SD +/- 1.45) in patients in Group B. This difference between the two groups was statistically significant (p < 0.01). CONCLUSIONS: The results of this study suggest that jaw immobilisation in mandibular fractures may be potentially damaging for the temporo-mandibular joint, sometimes leading to painful dysfunctional syndromes. For this reason, even in the case of mandibular fractures without decomposition, the authors feel that it is advisable to avoid long periods of immobilisation in patients with a positive history of mandibular dysfunction.

Fracture Fixation↗

[Magnetic resonance with endorectal coil in the local staging of prostatic carcinoma. Comparison with histologic macrosections in 40 cases].

PURPOSE: Endorectal coil MRI is widely used in the diagnostic workup of prostate cancer, but diagnostic accuracy rates reported in the literature are quite variable. We report our personal experience with endorectal coil MRI in the local staging of prostate carcinoma. MATERIAL AND METHODS: Forty consecutive patients with histologically proved prostate carcinoma were examined with endorectal coil MRI at high field strength (1.5 T). All patients underwent a sagittal T1-weighted SE location sequence (TR 400, TE 20), an axial T1-weighted SE (TR 400, TE 20), two axial T2-weighted FSE sequences (TR 3000, TE 102, ETL 8) with and without fat suppression, and a coronal T2-weighted FSE sequence (TR 3000, TE 102, ETL 8); an axial Fast Multiplanar Spoiled Gradient Recalled (FMSPGR) dynamic sequence after Gd-DTPA injection was also performed in 18 patients. MR staging of local tumor spread was done according to the current literature criteria. All patients were submitted to radical prostatectomy, and histologic macrosections on the same plane as MR images were obtained from surgical specimens. MR and histologic staging were compared to assess MR accuracy in detecting capsular infiltration, seminal vesicles and apex involvement. The diagnostic yield of Gd-DTPA was also investigated. RESULTS: MRI correctly staged 31 of 40 cases (77.5%). MR accuracy was 80% in detecting capsular infiltration (85.7% sensitivity and 73.6% specificity), 90% in seminal vesicle involvement (91.6% sensitivity, 89.2% specificity) and 72.5% in apex involvement (79.1% sensitivity, 62.5% specificity). Dynamic studies with Gd-DTPA did not improve staging accuracy in any case. DISCUSSION AND CONCLUSIONS: In agreement with most of the current literature, MRI showed moderate overall accuracy in the local staging of prostate carcinoma. Particularly, MRI had good accuracy in detecting seminal vesicle involvement but moderate sensitivity and specificity in demonstrating capsular infiltration and apex involvement. Due to its high cost, MRI should not be routinely used in prostate cancer staging but should be reserved to the patients whose clinical and serological data suggest extraprostatic tumor spread, whose preoperative demonstration could avoid noncurative surgery.

Aged↗

[Cine magnetic resonance with dobutamine following a myocardial infarct].

PURPOSE: Dobutamine cine MRI is a new diagnostic imaging technique in the pretreatment (revascularization) assessment of myocardial infarction patients. We report the results of a comparative study of the diagnostic yield of dobutamine cine MRI with that of stress echocardiography in the assessment of viable myocardium. We also propose a new method for analysis of cine MR images, employing digital subtraction, aimed at decreasing subjectivity in the quantitative assessment of myocardial wall thickening. MATERIAL AND METHODS: Twenty-six patients (21 men and 5 women) with a history of myocardial infarction who were scheduled for revascularization were submitted to stress echocardiography and dobutamine cine MRI to evaluate contractile recovery of the segments considered akinetic or hypokinetic at baseline echocardiography. Dobutamine was administered in growing doses (5, 10, 15 gamma/kg/min). We considered 16 segments of the left ventricle in each patient. We performed a quantitative analysis of systolic wall thickening on individual cine MR frames both by manual measurements and by digital subtraction. RESULTS: In the 416 segments studied, we found 307 normokinetic, 64 scarred and 45 viable segments with stress echocardiography, versus 302 normokinetic, 83 scarred and 31 viable segments with dobutamine MRI. Wall thickening analysis on Cine MR images showed 268 normal, 68 scarred and 80 viable segments, versus 274 normal, 58 scarred and 84 viable segments with digital subtraction. Three months after revascularization 15 patients were examined to check contractile recovery of the segments considered as viable. Echocardiography had 79% sensitivity and 97% specificity, while cine MRI had 96% and 86%, respectively. Quantitative assessment of systolic wall thickening by cine MRI and digital subtraction had 96% sensitivity and 91% specificity, with no statistically significant differences between the two techniques. In patients with anteroseptal wall myocardial infarction stress echocardiography had 75% sensitivity and 97% specificity. In the subgroup of 13 patients with diaphragmatic or inferior wall infarction echocardiography sensitivity dropped to 68%, versus 96% of cine MRI, but its specificity was higher, namely 97 versus 86%. CONCLUSIONS: In anteroseptal infarction, echocardiography permits to distinguish viable myocardium and scarred myocardial tissue with good sensitivity and specificity, but cine MRI performs better. In inferolateral or diaphragmatic infarction, cine MRI has much higher sensitivity than stress echocardiography and thus makes the technique of choice to evaluate viable myocardium in these sites. The digital subtraction technique is as accurate as manual measurements, but reduces the error rate and permits quicker evaluation, particularly in subendocardial thickening.

Adult↗