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Biomedical subjects

F Mosca

Publications and source records attributed to F Mosca.

At least 37 records · Page 2Linked to original sources

Combined percutaneous and surgical approach to a postnephrectomy arteriovenous fistula.

The case of a patient with long-standing severe heart failure that was ultimately found to be secondary to a large communication between the right renal artery stump and the inferior vena cava is reported. The occurrence of an arteriovenous fistula should be suspected in patients who underwent previous nephrectomy since early diagnosis would avoid relevant cardiac complications and the demise of a patient suffering from a disease that may be corrected surgically or percutaneously. We describe a combined approach that allowed the percutaneous decompression of the inferior vena cava and relief of the volume overload to the heart prior to the surgical ligation of the arteriovenous fistula. This approach should be considered a valuable option for treating long-standing high output postnephrectomy arteriovenous fistulas.

Aged↗

Laparoscopic and hand-assisted laparoscopic live donor nephrectomy.

Renal grafts from living donors represent an important source of organs, particularly for young patients with chronic renal failure. Laparoscopic donor nephrectomy is a relatively new technique, which has the potential to increase the pool of available kidney grafts by removing some disincentives to live donation. The technique used for left kidney donation at our center, the first to introduce laparoscopic live donor nephrectomy in Italy, is described in this report. To further reduce warm ischemia time, the kidney is preloaded inside the extraction bag and 2 staplers are used to transect the renal artery and vein. The spread of the new technique in our country and in the rest of Europe is likely to raise the issue of training in laparoscopic surgery for transplant surgeons.

Creatinine↗

[Prevention of mycotic infections in liver transplant recipients: comparison of two chemoprophylactic protocols].

BACKGROUND: The aim of the study was to compare and evaluate the efficacy of two chemoprophylactic protocols against mycotic infections in a liver transplant recipients population. DESIGN: single-blind, randomized. SETTING: Liver transplant Center of a National Health System teaching hospital. METHODS: Eighty-eight consecutive patients submitted to liver transplantation were enrolled in the study. Immediately before surgery they were randomized to receive sequential treatment with intravenous liposomal amphotericine B + oral itraconazole or intravenous fluconazole + oral itraconazole. Intravenous drugs were administered in the first postoperative week, and oral treatments for the following three weeks. In addition to analyzing the frequency and incidence of colonization, local and disseminated infection of mycotic origin, the causes of death and the possible risk factors for mycotic disease have been examined. RESULTS: Eighty-five patients completed the study. No significative difference was evident in the two groups as regards to single organ and systemic fungal infection rate. Two out of a total of 5 deaths were related to mycotic disease. Pre-transplant fungal colonization, more severe liver disease indicating the transplant procedure and the rejection of the graft were all risk factors for the development of mycotic infection. CONCLUSIONS: The two protocols used in the study showed and equal efficacy in preventing fungal infections in liver transplant recipients.

Adult↗

Thoracoscopic splanchnicectomy for pain relief in unresectable pancreatic cancer.

HYPOTHESIS: Unilateral truncal thoracoscopic splanchnicectomy (TS) provides safe and effective treatment for pain relief in patients with unresectable pancreatic cancer. DESIGN: Before-and-after trial of 24 patients undergoing 25 TS procedures. SETTING: Surgical unit at a university teaching hospital. PATIENTS: A consecutive sample of 24 patients with severe pain due to unresectable (primary or recurrent) pancreatic cancer refractory to drug therapy and with a life expectancy of less than 6 months. INTERVENTION: The key point of the reported operation is intrathoracic carbon dioxide insufflation, which allows a more distal division of the greater splanchnic nerve and a 2-port technique. MAIN OUTCOME MEASURES: Pain and the effect of this symptom on quality of life were assessed before and after TS using a 10-point visual analog pain scale (VAS) and the Nottingham Health Profile questionnaire, respectively. RESULTS: Four TS procedures were technical failures because of pleural adhesions. One patient required a contralateral procedure 12 weeks after TS. Mean (+/- SD) preoperative VAS basal score was 7.4 +/- 1.7. Twenty-four hours after TS, it was reduced to 0.6 +/- 1.0. Significant reduction of VAS scores persisted over the first 3 months after TS (P<.001). Recurrence of pain of low intensity (mean VAS basal score, 4.2) was observed in 8 patients. Significant improvement (P<.001) in each area covered by the Nottingham Health Profile questionnaire was reported at 1 month after TS. CONCLUSION: Thoracoscopic splanchnicectomy offered substantial short-term relief of pain in patients with unresectable pancreatic cancer, and significantly ameliorated the quality of their residual life.

Aged↗

Lymphokine release from human lymphomononuclear cells after co-culture with isolated pancreatic islets: effects of islet species, long-term culture, and monocyte-macrophage cell removal.

This study evaluated the release of Th1 and Th2 cytokines from human lymphomononuclear cells (LMC) in response to purified human (HI) or bovine (BI) islets, and the role of long-term (3-4 weeks) islet culture and removal of monocyte-macrophage cells. The results showed that HI and BI caused a similar increase of the release of gamma interferon (IFN), IL-2 and IL-6 from LMC, whereas BI had a more marked effect than HI on IL-10 release. Culturing the islets had possible positive effects (reduction of IFN and IL-2), but also potentially negative effects (increase of TNF). Removal of monocyte-macrophage cells determined a significant reduction of IL-6, IL-10 and TNF production in response to xeno-islets.

Animals↗

Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid.

OBJECTIVE: The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS: Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 microM. RESULTS: The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 +/- 5.4 nM and 1.5 +/- 0.6 microM (liver), respectively, and 161 + 23 microM and 420 +/- 18 microM (duodenum), respectively. The figures for the liver were significantly lower (P < 0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 +/- 11 microM (liver) and 705 +/- 19 microM (duodenum, P < 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. CONCLUSION: The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

Adrenergic beta-Agonists↗

Mycophenolic acid glucuronidation and its inhibition by non-steroidal anti-inflammatory drugs in human liver and kidney.

OBJECTIVE: The aims of this investigation were to study the glucuronidation of mycophenolic acid (MPA) in human liver and kidney and to search for a compound that inhibits MPA glucuronidation among the non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A sensitive and reproducible radiometric assay was developed to measure the rate of MPA glucuronidation in human liver and kidney microsomes. The assay employed uridine 5'-diphosphate-[U-14C]-glucuronic acid (UDPGA) and MPA-glucuronide was isolated by TLC. The final concentrations of UDPGA and MPA necessary were 1 mM (liver), and MPA concentration was 0.5 mM (kidney). The inhibition of MPA glucuronidation was studied with 18 NSAIDs and tacrolimus. RESULTS: Glucuronosyl transferase activity followed Michaelis-Menten kinetics and the Km (mean +/- SD; mM) was 0.31+/-0.06 (liver; n = 5) and 0.28+/-0.07 (kidney; n = 5; P = 0.555); the Vmax (mean SD; nmol/mg per minute) was 5.2+/-1.4 (liver; n = 5) and 10.5+/-1.2 (kidney; n = 5; P = 0.0005). The MPA glucuronidation rates (mean +/- SD; nmol/min/mg) were 3.3+/-0.9 (liver; n = 10) and 7.8+/-1.5 (kidney; n = 10; P = 0.0002). The rate of MPA glucuronidation ranged between 2.0 and 5.1 nmol/ mg per minute with a 2.5-fold variation (liver) and between 5.7 and 9.8 nmol/mg per minute with a 1.7-fold variation (kidney). The inhibition study was performed in liver and revealed that the percentage of control ranged from 8%+/-3% (niflumic acid) to 119%+/-16% (Ketoralac). The inhibition curves for MPA glucuronidation rate were determined with the four most effective inhibitors: niflumic acid, flufenamic acid, mefenamic acid and diflunisal. Their IC50 estimates (microM) were 8+/-1, 19+/-9, 63+/-8 and 109+/-15, respectively (liver), and 8+/-2, 13+/-2, 49+/-4 and 122+/-18, respectively (kidney). The IC50 estimate for niflumic acid was eightfold lower than the peak plasma levels after a single oral dose of 250 mg of this drug. CONCLUSION: The human liver and kidney are important sites of MPA glucuronidation. MPA glucuronidation was inhibited to various extents by different NSAIDs and the four most effective inhibitors were niflumic acid, flufenamic acid, mefenamic acid and diflunisal. These drugs have similar molecular structures consisting of two aromatic rings bearing a carboxylic group.

Aged↗

Inhibition of human liver phenol sulfotransferase by nonsteroidal anti-inflammatory drugs.

OBJECTIVE: The aim of this investigation was to study the inhibition of 11 nonsteroidal anti-inflammatory drugs (NSAIDs) on the human liver phenol sulfotransferases (HL-PST) and catechol sulfotransferase (HL-CST). METHODS: The activities of HL-PST and HL-CST were measured with 4 microM 4-nitrophenol and 60 microM dopamine (the sulfate acceptors) and 0.4 microM 3'-phosphoadenosine-5'-phosphosulfate [35S] (the sulfate donor). Samples of liver were obtained from five patients, aged 55-79 years, undergoing clinically indicated hepatectomy. The inhibition curves were constructed with at least five concentrations of the inhibitor. RESULTS: With the exception of piroxicam, NSAIDs inhibited HL-PST, and the estimates of the inhibitory concentration for 50% of responses (IC50; microM) were: 0.02 (mefenamic acid), 3.7 (diflunisal), 5.4 (nimesulide), 9.5 (diclofenac), 30 (salicylic acid), 41 (ketoprofen), 74 (indomethacin), 159 (ibuprofen), 245 (ketoralac) and 473 (naproxen). With 4-nitrophenol as the variable substrate, the inhibition of salicylic acid on HL-PST was non-competitive and the Ki and Kies were 18 microM and 21 microM (n = 5; P = 0.548), respectively. HL-CST was less susceptible than HL-PST to inhibition by NSAIDs, with only five drugs inhibiting this enzyme. The IC50 estimates for these drugs (microM) were 76 (mefenamic acid), 79 (diflunisal), 103 (indomethacin), 609 (salicylic acid) and 753 (diclofenac). CONCLUSION: The comparison of the IC50 estimates of HL-PST with the therapeutic plasma concentrations of NSAIDs corrected for the plasma unbound fraction was consistent with the view that mefenamic acid and salicylic acid, when administered at therapeutic doses, should impair the hepatic sulfation of those compounds that are substrates of phenol sulfotransferase.

Aged↗

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Journal Article↗

Genetics of drug response to immunosuppressive treatment and prospects for personalized therapy.

The use of immunosuppressive agents in the treatment of transplant rejection and autoimmune disorders is gaining momentum, with significant improvements of both graft and patient survival. The individual response to drugs, however, is variable and unexpected toxicity, or impaired activity might be seen, as a result of molecular determinants that eventually dictate how the individual will respond to immunosuppressive agents. This review addresses a number of issues related to pharmacogenetics, and discusses how this approach might be used to improve the clinical efficacy and tolerability of therapeutic options for the management of organ transplantation and autoimmune disorders in the next decade.

Autoimmune Diseases↗

Palliative treatment of malignant esophageal stenosis: the role of self-expanding stent endoscopic implantation.

Endoscopic tube implantations were carried out in 40 patients with malignant stenosis of the esophagus and gastric cardia using self-expanding metallic stents. The indications for endoscopic intubation were the advanced stage of the tumor in 27 cases and risk factors that made resection inadvisable in 13 cases. In three patients, it proved impossible to implant a stent endoscopically because we were not able to pass the guide wire through the stenosis, whereas correct stent placement was achieved in 37 cases. Functional results were good in 33 patients, but four patients did not show any improvement of symptoms. Complications occurred in nine patients (24.3%): two bleedings, three neoplastic obstructions, one food obstruction, and three distal dislodgements of the prosthesis were observed, but could be readily corrected. No deaths occurred. The median survival time was 151 days (range 25-545 days). This study suggests that endoscopic placement of metallic self-expanding stents is safe and is to be preferred to plastic stents for easier implantation and lower morbidity.

Aged↗