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Biomedical subjects

E Morandi

Publications and source records attributed to E Morandi.

At least 19 recordsLinked to original sources

Silent brain embolism during transcatheter closure of patent foramen ovale: a transcranial Doppler study.

The aim of this report is to quantify the amount of spontaneous microembolism detected in brain vessels by transcranial Doppler (TCD) during transcatheter closure of right-to-left shunt (RLS). We examined 29 patients who had had a stroke or a transient ischaemic attack (17 females and 12 males; mean age 45+/-15 years). They all underwent TCD monitoring during the procedure and microembolic signals (MES) were recorded. Detection of MES was distributed as follows: during femoral catheterisation in 8 patients (25%), during atrial catheterisation in 5 patients (17%), during transeptal crossing in 14 patients (48%), during left disc opening in 28 patients (96%) and during right disc opening in 7 patients (24%). The highest rates of MES were observed during left disc opening and less during transeptal crossing with an average count of 31 (range 3-135) and 3 (range 1-18) respectively. Brain embolism occurs throughout the procedure after femoral catheterisation for PFO closure. Our results indicate that the majority of MES reached the brain during the opening of the left disc in the left atrium: 28/29 patients exhibited MES with an average of 31 (3-135), thus supporting the notion that gas embolism accounted for the findings.

Adult↗

Does transcatheter closure of patent foramen ovale really "shut the door?" A prospective study with transcranial Doppler.

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) is increasingly being performed and monitored with transthoracic or transesophageal echocardiography, whereas contrast-enhanced transcranial Doppler (ce-TCD), which probably represents the most suitable tool to quantify right-to-left shunt (RLS) in the brain vessels, has been systematically overlooked. Our goal is to prospectively assess efficacy and safety of PFO transcatheter closure using ce-TCD. METHODS: A total of 140 consecutive patients (mean age, 46+/-13 years; male/female ratio, 63/77) with PFO-related large RLS and no other recognized cause of focal cerebral ischemia underwent transcatheter closure. TCD was done preoperatively and 1 month after the procedure in all patients, after 3 months in 120, after 6 months in 112, and after 1 year in 104 patients. RESULTS: Implantation was successful in all patients. During Valsalva strain, a large shunt was still detectable in 31 of 140 (22%), 15 of 120 (13%), 9 of 112 (8%), and 9 of 104 (9%) patients at the 1-, 3-, 6-, and 12-month visits, respectively. Periprocedural and postprocedural complications included atrial fibrillation in 8% and scintillating scotomata in 6% of patients. During the 1-year follow-up period, only 1 transient ischemic attack was recorded in a patient with paroxysmal atrial fibrillation and complete PFO closure. CONCLUSIONS: Transcatheter PFO closure in patients with cryptogenic stroke and large RLS may be less successful than reported previously. TCD appears the ideal tool to follow up the closure process and to identify early, during follow-up, those patients who will be left with a significant shunt. Atrial fibrillation is more common than believed previously and may underlie the occurrence of further cerebrovascular events despite complete PFO closure. Irritative visual phenomena may occur as a consequence of nickel toxicity.

Adult↗

Transcranial Doppler and risk of recurrence in patients with stroke and patent foramen ovale.

The importance of patent foramen ovale (PFO) in stroke of unknown cause remains disputed, as PFO may be present in up to 20% of normal people and in a high proportion of patients with non-vascular disorders. Recent evidence suggests that the amount of right-to-left shunt (RLS) may be the crucial factor for stroke occurrence and relapse. The aim of the study was to assess predictors of recurrence in PFO-related stroke patients with particular emphasis on amount of shunting. Patients less than 61 years old who had been admitted for a PFO-related stroke within the previous 5 years, were re-evaluated on a follow-up visit. The clinical syndrome, residual disability, vascular risk factors and number of relapses as the index event were assessed. RLS sizing was semi-quantitatively performed with saline-enhanced transcranial Doppler (TCD), by assuming a cut-off of more or less 10 bubbles recorded in the cerebral vessels as a criterion to discriminate large versus small shunt, respectively. Thereafter patients were prospectively followed-up for a median time of 23 months. Total follow-up was 61 months. Fifty-nine patients (M/F = 23/36, mean age 43 +/- 13) were studied. Overall there were 23 relapses in 13 patients. The amount of shunting was the only significant independent variable associated with relapse: at the end of the follow-up period the recurrence rate was 0.66 and 8.2% per patient per year in patients with small and large shunt, respectively. This difference was statistically significant (chi2 = 10.39, P = 0.0012; OR 17.05, 95% CI 2.10-755.22). In patients with PFO-related stroke, the amount of RLS as assessed with TCD is the only independent predictor of relapse. PFO sizing is mandatory in patients with PFO.

Female↗

The mechanisms of blood vessel closure in humans by the application of ultrasonic energy.

BACKGROUND: The use of the ultrasonically activated scalpel (UAS) for vessel closure has attained widespread acceptance in many surgical fields. The aim of our study was to investigate the electron microscopic changes to the blood vessels after the application of UAS. METHODS: We collected 10 arterial and 10 venous segments from vessels that had previously been closed by UAS during abdominal operations. The samples were then prepared for ultramicroscopic analysis. Pathological changes in the lumen and the three wall layers of the blood vessel were examined under scanning and transmission electron microscopy. RESULTS: All of the vessel segments showed similar changes: the presence of a blood clot, endothelial cell condensation, coagulative necrosis of the wall, and charring of the vessel at its tip. The edge of the cut vessel were closed by the coagulation bond, which was tied up by collagen fibrils escaped from denaturation. CONCLUSION: When ultrasonic energy is applied to tissues, it changes their structure so as to make a new extracellular matrix.

Cystic Duct↗

Angiogenic effects of suture biomaterials. An experimental study in rats.

Angiogenesis is a limiting step of inflammation and wound healing. Although laboratory tests for the evaluation of the angiogenetic effects of biomaterials are available, no investigations have been performed. In this study we examine the angiogenetic effect of suture biomaterials in the rat mesenteric window model. Absolute controls had laparotomy only, controls had mesenteric window wounding, test groups had the insertion of either a thread of collagen, polyglactin 910, polyglycolic acid salt, silk or of a titanium clip. We considered the percentage area of the mesenteric window covered by neovessels. After 7 days, negligible angiogenesis was found in absolute controls, significant angiogenesis in controls, collagen, polyglactin 910 and polyglycolic acid salt treated rats, without differences between treatments. A significant increase of angiogenesis in comparison to the control group was found in rats treated with silk and titanium. Ultramicroscopy of the neovessels showed specific changes of their architecture in titanium-treated rats. In conclusion, angiogenesis during wound healing is differently influenced by the suture material used. Silk and titanium stimulated angiogenesis in a different way.

Animals↗

Metastatic melanoma of the gallbladder.

A 38-year-old man arrived at our clinic with symptoms and investigation results (U.S. scan and MR) suggestive of acute calculous cholecystitis. He gave a past history of excision of a stage I melanoma of the shoulder. Metastatic disease was suspected following measurement of CA 19.9 levels and the CT scan. The patient underwent laparotomy and cholecystectomy; pathological examination confirmed the presence of a malignant melanoma metastatic lesion of the gallbladder.

Adult↗

The p75(NTR)-induced apoptotic program develops through a ceramide-caspase pathway negatively regulated by nitric oxide.

SK-N-BE neuroblastoma cell clones transfected with p75(NTR) and lacking Trk neurotrophin receptors, previously reported to undergo extensive spontaneous apoptosis and to be protected by nerve growth factor (NGF) (Bunone, G., Mariotti, A., Compagni, A., Morandi, E., and Della Valle, G. (1997) Oncogene 14, 1463-1470), are shown to exhibit (i) increased levels of the pro-apoptotic lipid metabolite ceramide and (ii) high activity of caspases, the proteases of the cell death cascade. In the p75(NTR)-expressing cells, these parameters were partially normalized by prolonged NGF treatment, which, in addition, decreased apoptosis, similar to caspase blockers. Conversely, exogenous ceramide increased caspase activity and apoptosis in both wild-type and p75(NTR)-expressing cells. A new p75(NTR)-expressing clone characterized by low spontaneous apoptosis exhibited high endogenous ceramide and low caspase levels. A marked difference between the apoptotic and resistant clones concerned the very low and high activities of nitric-oxide (NO) synthase, respectively. Protection from apoptosis by NO was confirmed by results with the NO donor S-nitrosoacetylpenicillamine and the NO-trapping agent hemoglobin. We conclude that the p75(NTR) receptor, while free of NGF, triggers a cascade leading to apoptosis; the cascade includes generation of ceramide and increased caspase activity; and the protective role of NO occurs at step(s) in between the latter events.

Apoptosis↗

Prospective study of healing time after hemorrhoidectomy: influence of HIV infection, acquired immunodeficiency syndrome, and anal wound infection.

PURPOSE: Hemorrhoids and rectal diseases are very frequent in HIV-positive patients, especially in those with homosexual habits. This study was designed to compare posthemorrhoidectomy healing time in such patients, and evaluate the role of various factors related to their HIV-positive status. METHODS: The study involved a prospective series of 48 male patients (32 HIV-seropositive and 16 with acquired immunodeficiency syndrome) who underwent hemorrhoidectomy between 1992 and 1996; 20 age-matched and gender-matched seronegative patients were retrospectively identified as controls. Healing times, postoperative complications, and wound infections were recorded, and the delaying effect of CD4+, Karnofsky Index scores, and HIV-ribonucleic acid were evaluated. Between-group differences were analyzed using Cox's model, Student's t-test, chi-squared test, and Fisher's exact probability test. P values of <0.05 were considered statistically significant. RESULTS: Cox's model revealed that HIV positivity and the presence of acquired immunodeficiency syndrome significantly delayed wound healing, which also correlated with the presence of infection. The healing rate in HIV-positive patients was 66 percent after 14 weeks and 100 percent after 32 weeks; the corresponding figures for patients with acquired immunodeficiency syndrome were 0 and 50 percent. All of the controls were healed after 14 weeks (P < 0.01 vs. both the patients with acquired immunodeficiency syndrome and HIV+ patients). Centers for Disease Control and Prevention HIV-positive status (including CD4+ counts) and the performance status proved to be of prognostic value. CONCLUSIONS: Our data suggest that the indications for hemorrhoidectomy in patients with acquired immunodeficiency syndrome need to be considered extremely carefully because of the high incidence of delayed wound healing.

Acquired Immunodeficiency Syndrome↗

Induction of apoptosis by p75 neurotrophin receptor in human neuroblastoma cells.

The low-affinity nerve growth factor receptor p75NTR belongs to a membrane receptor superfamily whose members, in certain cell types, are able to transduce an apoptotic signal. To investigate the effect of p75NTR expression in neuroblastoma cells, we transfected the p75NTR cDNA into SK-N-BE cells, a neuroblastoma cell line that lacks expression of both p75NTR and TrkA. Cell clones expressing elevated levels of p75NTR showed a high degree of cell death by apoptosis, even in serum-supplemented medium. Moreover, the level of apoptosis correlated directly with the expression level of the receptor, indicating that p75NTR could activate the cell death program by itself. Clones expressing p75NTR showed a dramatic increase of cell death when switched into serum-free medium; these cultures rapidly extinguished. This apoptotic effect was greatly inhibited by NGF treatment. Our results support the hypothesis that p75NTR, when it is not bound by NGF, may play a role in neuronal selection during embryonic development and suggest that neuroblastomas may arise from immature neuroblasts that escape programmed cell death. Therefore, the loss of p75NTR expression in developing neural crest cells might be a primary event in the genesis of neuroblastoma.

Apoptosis↗

Noninvasive evaluation of cardiotoxicity of 5-fluorouracil and low doses of folinic acid: a one-year follow-up study.

PURPOSE: To conduct a serial evaluation of the cardiac effects of antineoplastic therapy with 5-fluorouracil (5-FU) and low-dose folinic acid. PATIENTS AND METHODS: Sixteen patients with colon-rectal carcinoma, without cardiac disease, treated with 400 mg/ m2/die of 5-FU and 20 mg/m2/die of folinic acid for five days, once a month, for six months. Parameters evaluated: blood pressure, ECG, two-dimensional and digitized M-mode echocardiograms before and after the first and fifth drug administrations of the first cycle, after the fifth drug administration of the sixth cycle and six months after the treatment. RESULTS: Blood pressure, heart rate, left ventricular (LV) diameter and LV mass index did not change; all of the patients showed a decrease in the peak shortening rate of the LV diameter index of systolic function, and of the peak lengthening rate of the LV diameter and peak thinning rate of LV posterior wall, indexes of diastolic function, with abnormal values in 11 patients at the end of treatment LV wall motion remained normal in all; two patients developed transient T wave inversion without chest pain and with normal cardiac enzymes and myocardial scintigraphy during dypiridamole stress test. Six months after the treatment all indexes of LV systolic and diastolic function had returned within the normal limits and were similar to pre-treatment values. CONCLUSIONS: 5-FU and low-dose folinic acid treatment induced a decrease of LV systolic function and an impairment of diastolic function, that developed without symptoms and were transient and reversible.

Adult↗

Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma.

The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach. A total of ninety-three patients (median age 63 years) were reviewed. The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment. The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated. The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole. Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%). There was no apparent difference in overall survival and event-free survival between patients who received different treatments. In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%). In conclusion the indolent nature of the disease justifies a conservative approach. The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.

Adult↗

hnRNP A1 selectively interacts through its Gly-rich domain with different RNA-binding proteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are abundant nuclear polypeptides, most likely involved in different steps of pre-mRNA processing. Protein A1 (34 kDa), a prominent member of the hnRNP family, seems to act by modulating the RNA secondary structure and by antagonizing some splicing factors (SR proteins) in splice-site selection and exon skipping/inclusion. A role of A1 in the nucleo-cytoplasmic transport of RNA has also been proposed. These activities might depend not only on the RNA-binding properties of the protein but also on specific protein-protein interactions. Here we report that A1 can indeed selectively interact, in vitro, both with itself and with other hnRNP basic "core" proteins. Such selective binding is mediated exclusively by the Gly-rich C-terminal domain, where a novel protein-binding motif constituted by hydrophobic repeats can be envisaged. The same domain is necessary and sufficient to promote specific interaction in vivo, as assayed by the yeast two-hybrid assay. Moreover, an in vitro interaction with some SR proteins was also observed. These observations suggest that diverse and specific protein-protein interactions might contribute to the different functions of the hnRNP A1 protein in mRNA maturation.

Amino Acid Sequence↗

Severe abdominal pain in patients with AIDS: frequency, clinical aspects, causes, and outcome.

BACKGROUND: The exact prevalence of abdominal pain in AIDS patients, as well as the entire spectrum of causative disorders, has not yet been well defined. In addition, the existing data derive almost exclusively from surgical series describing only those patients who have undergone emergency surgical procedures. METHODS: We reviewed our experience with patients presenting with severe abdominal pain from a large series of non-selected consecutive AIDS patients seen at our institution over a period of 4 years. RESULTS: Of 458 patients, 71 (15%) had severe abdominal pain, and its occurrence was associated with a reduced patient survival. Specific diagnoses were made premortem in 42 patients (59%), potential causes of pain were identified at postmortem examination in 23 patients (33%), whereas no specific causes were found in 6 patients (8%). Most of the causative disorders (65%) were AIDS-related, whereas HIV-independent pathologic conditions were found in only 18% of the patients. The predominant site of pain, combined with a few key symptoms, had a high predictive diagnostic value in nearly half of the patients. The indications for emergency laparotomy were limited and substantially similar to those of the non-HIV population. CONCLUSIONS: Severe abdominal pain frequently complicates the course of AIDS, and its occurrence is associated with reduced survival. In most patients it is due to disorders closely associated with the HIV infection. Specific causes of pain may be identified in most of the cases by an appropriate diagnostic evaluation.

AIDS-Related Complex↗

Distal splenorenal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. First stage of a randomized, controlled trial.

In 1984 we started a prospective controlled trial comparing endoscopic sclerotherapy (ES) with the distal splenorenal shunt (DSRS) in the elective treatment of variceal hemorrhage in cirrhotic patients. The study population included 40 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1988. These patients were drawn from a pool of 173 patients who underwent either elective surgery or endoscopic sclerotherapy during this time. Patients were assigned to one of the two groups according to a random-number table: 20 to DSRS and 20 to ES. During the postoperative period, no DSRS patient died, while one ES patient died of uncontrolled hemorrhage. One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS. Four ES patients suffered at least one episode of gastrointestinal bleeding: two from varices and two from esophageal ulcerations. Five ES patients developed transitory dysphagia. Long-term follow-up was complete in all patients. Two-year survival rates for shunt (95%) and ES (90%) groups were similar. One DSRS patient rebled from duodenal ulcer, while three ES patients had recurrent bleeding from esophagogastric sources (two from varices and one from hypertensive gastropathy). One DSRS and two ES patients have evolved a mild chronic encephalopathy; four DSRS and two ES patients suffered at least one episode of acute encephalopathy. Two ES patients had esophageal stenoses, which were successfully dilated. Preliminary data from this trial seem to indicate that DSRS, in a subgroup of patients with good liver function and a correct portal-azygos disconnection, more effectively prevents variceal rebleeding than ES. However no significant difference in the survival of the two treatment groups was noted.

Adult↗

A monoclonal-based, two-site enzyme immunoassay of human insulin.

A procedure is described for the efficient production of insulin-specific monoclonal antibodies, which involves primary and secondary immunization of BALB/c mice in the hind footpads with bovine or porcine insulin and fusion of lymphocytes from popliteal lymph nodes with a P3x63 murine myeloma line. With this protocol, over 200 positive hybrids were obtained from four separate fusions. Dissociation constants of 31 purified monoclonals, cross-reacting with human insulin, were determined by two different methods and ranged between 4 X 10(-10) and 2 X 10(-6) mol/l. 24 monoclonals were biotinylated, paired in all possible combinations and tested by ELISA for their capacity to simultaneously bind to human insulin in a two-site assay. More than 40 monoclonal pairs were found which formed a sandwich with the hormone. The development of a simple and rapid one-step enzyme immunoassay is described, which involves a first monoclonal bound to the wells of a microtiter plate and a second monoclonal conjugated to alkaline phosphatase. With this assay, insulin can be determined in a range between 0.08 and 7.5 ng/ml in 3-4 h.

Alkaline Phosphatase↗