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Biomedical subjects

G Orlando

Publications and source records attributed to G Orlando.

At least 19 recordsLinked to original sources
PubMed2005

Amantadine monotherapy is ineffective in the treatment of hepatitis C virus recurrence in the post-liver transplantation setting.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection is universal after liver transplantation (LT), yet no effective therapy is available. Amantadine (Am) is currently under evaluation. The aim of this study was to assess the safety and the effectiveness of Am monotherapy in LT patients with HCV recurrence. METHODS: Twelve patients who underwent transplantation 1-4 years earlier were included when there was detectable serum HCV-RNA and histological signs of liver damage with evidence of progressive hepatic fibrosis. Basal Ishak's scores were 2.1 +/- 1.3 and 5.1 +/- 2.7, respectively. Exclusion criteria were histological cirrhosis and comorbidities. All patients were receiving cyclosporine, with or without azathioprine. Amantadine was given orally (200 mg/d) for 3 months. RESULTS: Eight (67%) patients completed a 3-month treatment course without dose adjustments. Am was reduced to 100 mg/d in 3 cases and withdrawn in 1 due to side effects, namely, insomnia (n = 7; 58%), tremor (n = 4; 33%), headache (n = 2; 17%), asthenia (n = 2; 17%), and dermatitis, diarrhea, and increased creatinine (each n = 1; 8%). Serum HCV-RNA levels decreased in 3 patients, increased in 3, and remained unchanged in the others. Alanine aminotransferase (ALT) remained abnormal in all cases. Liver function test results did not improve. CONCLUSIONS: Short-term Am monotherapy was ineffective to treat post-LT HCV relapse and was associated with significant side effects.

Amantadine↗
PubMed2002

Synthesis and biological evaluation of a novel pyroglutamyl-modified TRH analogue.

The TRH analogue 3, incorporating the (S)-isothiazolidine-1,1-dioxide-3-carboxylic acid (1) moiety in place of the native L-pyroglutamic acid (pGlu) residue, has been synthesized and fully characterized by 1H and 13C NMR. The effects of replacing pGlu with its sulphonamido counterpart on biological activity have been investigated. This peptide, which is significantly stabilized towards hydrolysis by pyroglutamyl peptidase type I (PP I, EC 3.4.19.3), has shown to maintain in vitro prolactin-releasing activity.

Animals↗
PubMed2001

Effects of cocaine- and amphetamine-regulated transcript peptide, leptin and orexins on hypothalamic serotonin release.

We have studied the effects of cocaine- and amphetamine-regulated transcript (CART) peptide-(55-102), leptin, orexin-A and orexin-B on basal and depolarization (K(+) 15 mM)-induced serotonin (5-hydroxytryptamine, 5-HT) release from rat hypothalamic neuronal endings (synaptosomes) in vitro. We have found that leptin and CART peptide-(55-102) have no effect on 5-HT release, while orexin-A and orexin-B inhibit depolarization-stimulated serotonin release. We can conclude that leptin and CART peptide-(55-102), which play a physiological role as feeding inhibitors, do not acutely affect 5-HT release from hypothalamic synaptosomes; on the other hand, feeding induced by orexin-A and orexin-B could be partially explained by decreased 5-HT release.

Animals↗
PubMed2001

Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients.

BACKGROUND: Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intra- and postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. METHODS: Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. RESULTS: The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P=0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P<0.02). At electron microscopy, an overt endothelial damage (cytoplasmic vacuolization, cell leakage, and destruction with exposure of hepatocytes to the sinusoidal lumen) was invariably found in control grafts, both at reperfusion and at day 7 after transplant. These features were significantly ameliorated by TUDCA (P<0.001). Several ultrastructural cytoplasmic abnormalities of hepatocytes were seen. Among these, damage to mitochondria matrix and crystae was significantly reduced in TUDCA-treated versus control grafts (P<0.01). Mild to severe damage of bile canaliculi was a constant feature in control biopsies, with dilatation of canalicular lumen and loss of microvilli. Both these abnormalities were markedly ameliorated (P<0.001 by TUDCA). The best preservation was observed when TUDCA was given through both routes. CONCLUSIONS: The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied.

Adenosine↗
PubMed2001

Chromatin-derived acidic peptides modulate catecholamine release in the hypothalamus.

We have studied the neuromodulatory effects of three synthetic peptides, structurally related to chromatin-derived acidic peptides (ACPs): ACP-1 (Asp-Asp-Ser-Asp-Glu-Glu-Asn), corresponding to the C-terminal fragment of the largest subunit of eukaryotic RNA polymerase II; a more lipophilic derivative, ACP-2 (Ala-Ile-Ser-Pro-Asp-Asp-Ser-Asp-Glu-Glu-Asn); and its phosphorylated form ACP-3 (Ala-Ile-Ser-Pro-Asp-Asp-Ser(P)-Asp-Glu-Glu-Asn). Rat hypothalamic synaptosomes, loaded with [(3)H]norepinephrine or [(3)H]dopamine, were perfused with the above peptides, both basally and during a depolarizing stimulus. We have found: ACP-1 inhibited both dopamine and norepinephrine release; ACP-2 inhibited dopamine release, without affecting norepinephrine release; ACP-3 was almost ineffective, except for a weak dopamine inhibiting effect only at a higher concentration.

Animals↗
PubMed2001

Synthesis and preliminary pharmacological evaluation of 5-hydroxy- and 5,6-dihydroxy-1,2,3,7,12,12a-hexahydrobenzo[5,6]cyclohepta[1,2,3-ij]isoquinoline derivatives as dopamine receptor ligands.

A series of 5-hydroxy- and 5,6-dihydroxy-1,2,3,7,12,12a-hexahydrobenzo[5,6]cyclohepta[1,2,3-ij]isoquinoline derivatives (5a--e and 6a--e) were synthesized as conformationally rigid analogues of 1-benzyltetrahydroisoquinoline and evaluated for their affinity at D(1) and D(2) dopamine receptors. All compounds showed lower D(1) and D(2) affinities than dopamine. The 5-hydroxy-1-methyl-2,3,12,12a-hexahydrobenzo[5,6]cyclohepta[1,2,3-ij]isoquinoline 5a and the 5,6-dihydroxy analogue 6a showed D(2) agonist activity. This was proved by their effects on prolactin release from primary cultures of rat anterior pituitary cells. Molecular modeling studies showed that the geometric parameters (namely the distances from meta and para hydroxyl oxygens to the nitrogen and the height of nitrogen from the hydroxylated phenyl ring plane) of the dopaminergic pharmacophore embedded in our compounds have lower values in comparison with those observed in D(1) and D(2) selective ligands.

Animals↗
PubMed2001

Lunotriquetral arthrodesis using cancellous bone graft.

Previous reports of lunotriquetral arthrodesis suggest relatively low rates of primary fusion without the use of permanent fixation and/or prolonged immobilization. We performed 26 lunotriquetral arthrodeses in 24 patients with a technique using cancellous bone graft to fill a biconcave space created in the adjoining bones with parallel K-wire fixation. The indications included symptomatic lunotriquetral instability and degenerative arthritis. All patients received conservative treatment before surgery. Primary fusion was achieved in all wrists in an average of 50 days. Postoperative wrist flexion/extension averaged 77%/80% of unaffected sides. Radial/ulnar deviation averaged 95%/91% of unaffected sides. Pain relief was good or very good in 83%. Eight-eight percent returned to the workforce. This study shows reliable, effective results with a technique that adheres to the principles of intercarpal arthrodesis and avoids permanent internal fixation.

Adolescent↗
PubMed2001

Combined free tissue transfer and infrainguinal bypass graft: an alternative to major amputation in selected patients.

OBJECTIVES: The purpose of this study was to document outcome and adverse prognostic factors in patients requiring combined free tissue transfer and distal bypass grafting for otherwise nonreconstructible infrainguinal arterial occlusive disease and advanced tissue necrosis. METHODS: Between July 1990 and November 1999, 65 patients, all of whom would have required at least below-knee amputation, underwent free tissue transfer in conjunction with infrainguinal bypass grafting at the University of Rochester. Preoperative variables were assessed for their influence on outcome with chi(2) and outcome with life-table analysis with Cox proportionate hazard testing. RESULTS: Free tissue transfer was performed synchronously with arterial reconstruction with autologous vein in 49 patients and after a previous functioning venous bypass graft in 16 patients. The 30-day mortality rate was 5%, and major complications occurred in another 16% of patients. Flap location, weight-bearing status, preexisting osteomyelitis, and the timing of bypass grafting relative to flap construction had no effect on outcome. All five free flap failures occurred within the first 30 days. All other flaps subsequently survived, even in seven patients whose bypass grafts thrombosed. Five-year limb salvage and patient survival rates were 57% and 60%, respectively, and 65% of patients regained meaningful ambulation. The combination of diabetes and dialysis-dependent renal failure was the strongest predictor of overall limb loss (P <.005; relative risk = 4.0), and diabetes alone was the strongest predictor of death (P <.02; relative risk = 5.2). CONCLUSION: Free tissue transfer combined with infrainguinal bypass grafting in selected patients is safe and effective. The combination of diabetes and chronic renal insufficiency, particularly the need for dialysis, is a powerful predictor of failure and should be considered a strong contraindication for this procedure.

Amputation, Surgical↗
PubMed2000

Cocaine- and amphetamine-regulated transcript peptide-(55-102) and thyrotropin releasing hormone inhibit hypothalamic dopamine release.

Cocaine- and amphetamine-regulated transcript (CART) peptide-(55-102) and thyrotropin releasing hormone (TRH) play an anorectic role in the hypothalamus. Catecholamines are also involved in appetite control and we have previously found that leptin, an adipocyte-derived anorectic hormone, inhibits hypothalamic norepinephrine and dopamine release. We have studied the effect of CART peptide-(55-102) and TRH on basal and depolarization (K+ 15 mM)-induced norepinephrine and dopamine release from rat hypothalamic neuronal endings (synaptosomes) in vitro. We have found that basal catecholamine release was not modified; both CART peptide-(55-102) and TRH, the former with a higher sensitivity, dose-dependently inhibited depolarization-induced dopamine release, and did not affect the stimulated norepinephrine release. Considering the role played by dopamine in the central mechanisms of reward, these findings suggest that the inhibition of dopamine release could underlie the decreased appetitive behaviour induced by CART peptide-(55-102) and TRH.

Animals↗
PubMed2000

Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain.

It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165+30 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 17+/-6 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization.

Chest Pain↗
PubMed2000

A possible prolactin-related adverse effect of certain antineoplastic anthracyclines.

Nonhormonal antineoplastic therapy can affect the endocrine system with consequent effects on the growth of hormone-sensitive tumors. Amongst anthracycline antibiotics, we have found daunorubicin and epirubicin able to acutely stimulate prolactin (PRL) secretion both in vivo, in the rat, and in vitro, from rat anterior pituitary cell cultures. Despite a similar structure, doxorubicin showed no such activity. Considering the possible role of PRL in breast cancer cell proliferation, the effects of certain anthracyclines might be viewed as an adverse drug reaction involving the anterior pituitary gland.

Animals↗
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↗