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Biomedical subjects

G Orlando

Publications and source records attributed to G Orlando.

At least 37 records · Page 2Linked to original sources
PubMed2000

Laparoscopic cholecystectomy and the Peter Pan syndrome.

We report the case of a patient who experienced hemobilia a few weeks after undergoing laparoscopic cholecystectomy (LC). This condition was due to the rupture of a pseudo-aneurysm of the right hepatic artery in the common bile duct, probably caused by a clip erroneously fired during LC on the lateral right wall of the vessel. It also caused the formation of multiple liver abscesses and the onset of sepsis. This life-threatening complication led to melena, fever, epigastric pain, pancreatitis, liver dysfunction, and severe anemia, requiring urgent hospitalization and operation. In the operating theater, the fistula was closed, the liver abscesses drained, and a Kehr tube inserted. Thereafter, the patient's general condition improved, and she is now well. LC is often considered to be the gold standard for the management of symptomatic cholelithiasis. However, recent data have undermined that opinion. The apparent advantages offered by LC in the short term (less pain, speedier recovery, shorter hospital stay, and lower costs) have been overwhelmed by the complications that occur during long-term follow-up. When the late downward trend in the bile duct and the vascular injury rate are taken into consideration, the learning curve is prolonged. Therefore, LC should be regarded as the surgical equivalent of a modern Peter Pan-i.e., it is like a young adult who should make definitive steps toward becoming an adult but does not succeed in doing so. We report the case of a patient who experienced hemobilia a few weeks after undergoing laparoscopic cholecystectomy. Based on the facts in this case, we argue that the endoscopic procedure still needs to be perfected and cannot yet be considered the gold standard for selected cases of gallstone disease.

Biliary Fistula↗
PubMed2000

Binding and preliminary evaluation of 5-hydroxy- and 10-hydroxy-2,3, 12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines as dopamine receptor ligands.

The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10-hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3, 4-ij]isoquinolines were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D(1)-like and D(2)-like subtypes. All compounds showed very low D(1) affinities. This could be ascribed to the absence of a catechol nucleus or of the beta-phenyldopamine pharmacophore. Only the N-methyl-5-hydroxy- (5a), N-methyl-10-hydroxy- (6a), and N-methyl-4-bromo-10-methoxy-2,3, 12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines (26a) bound the D(2) receptors with low affinity, in the same range as dopamine. In compounds 5a and 6a, the 2-(3-hydroxyphenyl)ethylamine moiety does not meet the requirements of the D(2) agonist pharmacophore: namely, the 2-(3-hydroxyphenyl)ethylamine does not reach the trans, fully extended conformation. The three compounds did not interact with recombinant human D(4) receptors, and only 5a showed low affinity for rat recombinant D(3) receptors. Analysis of the influence of Na(+) on [(3)H]spiperone binding showed that 5a displays a potential dopamine D(2) agonist profile, whereas 6a probably has a dopamine D(2) antagonist activity. The D(2) agonist activity of 5a was proved by the effects on prolactin release from primary cultures of rat anterior pituitary cells.

Animals↗
PubMed2000

Atypical endometriosis revisited: clinical and biochemical evaluation of the different forms of superficial implants.

OBJECTIVE: To investigate the activity of different forms of endometriosis implants by clinical and biochemical evaluation. DESIGN: Prospective, blinded study. SETTING: Tertiary-care university hospital. PATIENT(S): Forty-seven infertile patients with minimal or mild endometriosis diagnosed at laparoscopy were included in the clinical investigation. INTERVENTION(S): Patients were submitted to a preoperative evaluation of endometriosis-associated dysmenorrhea by means of a 10-point linear analog scale and to laparoscopic staging of endometriosis following a current classification system. In the biochemical investigation, tissue samples from different endometriosis lesions and control tissues were assessed for prostaglandin (PG) F(2 alpha) production. MAIN OUTCOME MEASURE(S): Evaluation of the correlation between endometriosis-associated dysmenorrhea and the extent of the disease. Evaluation of the production of PGF(2 alpha) by the different tissues sampled. RESULT(S): No positive correlation was present between any of the implant subgroups and the associated dysmenorrhea. White peritoneal implants were associated with milder pain symptoms than black or red lesions. The biologic activity of red and black superficial implants, expressed as the production of PGF(2 alpha), was similar. CONCLUSION(S): No positive correlation was demonstrated between endometriosis-associated dysmenorrhea and the current classification of endometriosis, which includes characterization of the different morphologic aspects of superficial endometriosis implants.

Adult↗
PubMed2000

Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo.

Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene production that may be rapidly extincted by ill-defined silencing mechanisms. In the present article, it is reported that transcriptionally active drugs, retinoic acid (RA) and histone deacetylase inhibitor trichostatin A (TSA), enhance AdV transgene expression in infected cells and tissues. The association of RA and TSA increased more than seven-fold above control the activity of AdVs encoding for LacZ or VEGF165. This effect was, at least in part, mediated by the direct activation of retinoic acid receptors. Finally, administration of RA and TSA alone at days 0 and 5 after infection prolonged transgene production up to 21 days after infection versus 6-8 days in untreated controls. These results indicate that transcriptionally active drugs improve AdV function and may represent a novel strategy to more efficiently design AdVs for gene therapy interventions.

Adenoviridae↗
PubMed1999

A pilot study on the safety and effectiveness of immunosuppression without prednisone after liver transplantation.

BACKGROUND: Corticosteroids are commonly used in the immunosuppression therapy after liver transplantation, yet are associated with considerable side effects. Retrospective studies have shown that corticosteroids can be safely withdrawn from months to years after transplant. We prospectively investigated the effects of early immunosuppression without the use of corticosteroids on graft outcome and transplant complications. METHODS: Forty-five patients undergoing liver transplantation were randomized to receive immunosuppression composed of cyclosporine microemulsion and azathioprine with (n=22) or without prednisone (n=23), in conventional doses. In those patients who received prednisone, this was withdrawn within 3 months after transplant. The median follow-up of survivors was 14 months (range: 6-24). The study end points were to determine graft survival and function, infectious complications, including hepatitis C virus (HCV)-RNA levels in HCV-infected recipients, acute rejection, kidney function, and metabolic complications. RESULTS: Eleven deaths occurred, 6 of which were in the prednisone group. Two-year survival did not differ between patients treated with or without prednisone (70.2% vs. 78.3%, P=0.83), nor did the causes of death. No differences were observed with regard to graft function, renal function, and infectious complications. In the subset of patients who received transplants for HCV-related cirrhosis, the dynamics of virus replication HCV-RNA was faster among those treated with prednisone. The incidence and severity of acute rejection was similar in the two groups. More than 80% of acute rejections in both groups were classified as mild or moderate and underwent spontaneous resolution. Only two patients in each group had severe acute rejection requiring additional treatment with high-dose steroids. Patients receiving prednisone tended to have greater biochemical signs of cholestasis, higher serum cholesterol and glucose levels, and more frequent insulin requirement than those treated without corticosteroids. CONCLUSIONS: Liver transplantation can be performed safely without using corticosteroids in the early postoperative course, and there is no need for routine aggressive steroid treatment of established acute rejections.

Adult↗
PubMed1999

Leptin inhibits norepinephrine and dopamine release from rat hypothalamic neuronal endings.

Noradrenergic and dopaminergic afferents arising from the brain stem to the hypothalamus still play a poorly characterised role in food intake control. We have studied the effect of leptin, an adipocyte-derived hormone which has been implicated in the regulation of feeding behaviour, on [3H]norepinephrine and [3H]dopamine release from perfused hypothalamic neuronal endings (synaptosomes) in vitro. We have found that leptin (0.01-10 nM) does not modify basal, while it inhibits depolarization-induced norepinephrine and dopamine release. We can hypothesize that at least part of the anorectic activity of leptin in the hypothalamus is effected through an inhibition of noradrenergic and dopaminergic firing.

Animals↗
PubMed1999

Leptin stimulates prostaglandin E2 and F2alpha, but not nitric oxide production in neonatal rat hypothalamus.

Leptin, an adipocyte-derived 16 kDa polypeptide hormone, has been found to regulate food intake and thermogenesis by modulating stimulatory and inhibitory pathways in the feeding circuitry of the hypothalamus, among which corticotropin releasing hormone (CRH). Nitric oxide (NO) and prostaglandins have been shown to be involved in both CRH neurosecretion and feeding regulation. We have investigated the role of NO, prostaglandin E2 and prostaglandin F2alpha as mediators of the hypothalamic effects of leptin and their possible involvement in leptin-stimulated CRH secretion. Using primary cultures of neonatal (5- to 6-day-old) rat hypothalamic cells, we confirmed that leptin (0.1-10 nM) stimulates CRH secretion. This effect was not blocked by L-N(G)-nitro-methyl-arginine (L-NAME, 100 microM), a NO-synthase competitive inhibitor; and leptin did not stimulate NO production. Cyclooxygenase inhibition by indomethacin (10 microM) did not modify leptin-induced CRH secretion, while leptin stimulated prostaglandin E2, and prostaglandin F2alpha secretion. In conclusion, leptin-induced hypothalamic CRH secretion is not modulated by NO-synthase- or cyclooxygenase-mediated mechanisms; leptin does not stimulate NO production, but it stimulates prostaglandin E2 and F2alpha production, which could add to the growing list of mediators of leptin signaling in the hypothalamus.

Animals↗
PubMed1998

Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. A randomized, controlled trial.

BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary disease, mechanical ventilation is often needed. The rate of weaning failure is high in these patients, and prolonged mechanical ventilation increases intubation-associated complications. OBJECTIVE: To determine whether noninvasive ventilation improves the outcome of weaning from invasive mechanical ventilation. DESIGN: Multicenter, randomized trial. SETTING: Three respiratory intensive care units. PATIENTS: Intubated patients with chronic obstructive pulmonary disease and acute hypercapnic respiratory failure. INTERVENTION: A T-piece weaning trial was attempted 48 hours after intubation. If this failed, two methods of weaning were compared: 1) extubation and application of noninvasive pressure support ventilation by face mask and 2) invasive pressure support ventilation by an endotracheal tube. MEASUREMENTS: Arterial blood gases, duration of mechanical ventilation, time in the intensive care unit, occurrence of nosocomial pneumonia, and survival at 60 days. RESULTS: At admission, all patients had severe hypercapnic respiratory failure (mean pH, 7.18+/-0.06; mean PaCO2, 94.2+/-24.2 mm Hg), sensory impairment, and similar clinical characteristics. At 60 days, 22 of 25 patients (88%) who were ventilated noninvasively were successfully weaned compared with 17 of 25 patients (68%) who were ventilated invasively. The mean duration of mechanical ventilation was 16.6+/-11.8 days for the invasive ventilation group and 10.2+/-6.8 days for the noninvasive ventilation group (P = 0.021). Among patients who received noninvasive ventilation, the probability of survival and weaning during ventilation was higher (P = 0.002) and time in the intensive care unit was shorter (15.1+/-5.4 days compared with 24.0+/-13.7 days for patients who received invasive ventilation; P = 0.005). Survival rates at 60 days differed (92% for patients who received noninvasive ventilation and 72% for patients who received invasive ventilation; P = 0.009). None of the patients weaned noninvasively developed nosocomial pneumonia, whereas 7 patients weaned invasively did. CONCLUSIONS: Noninvasive pressure support ventilation during weaning reduces weaning time, shortens the time in the intensive care unit, decreases the incidence of nosocomial pneumonia, and improves 60-day survival rates.

Aged↗