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Biomedical subjects

D Lorusso

Publications and source records attributed to D Lorusso.

At least 19 recordsLinked to original sources
PubMed2007

Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome).

Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand-to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic reaction associated with certain chemotherapeutic agents. Pegylated liposomal doxorubicin (PLD), a long-circulating formulation of doxorubicin in which doxorubicin hydrochloride is encapsulated within pegylated liposomes, is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome-related Kaposi's sarcoma. The incidence of PPE is increased in patients receiving PLD compared with conventional doxorubicin. In studies that utilized the currently approved dose of PLD (50 mg/m(2) every 4 weeks), approximately 50% of all patients receiving PLD experienced PPE, and approximately 20% experienced grade 3 PPE. The pathophysiology of PPE, as it occurs with any drug with which it is associated, is not well understood. Studies evaluating the development of PPE specifically associated with PLD have not fully elucidated the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors. When PPE develops, clinical interventions with respect to altering PLD administration include dose reduction, less frequent dosing, and ultimately, drug withdrawal with several consequences on treatment efficacy. This article will review the available data regarding the etiology and potential management strategies of PPE associated with PLD.

Antineoplastic Agents↗
PubMed2006

Role of gemcitabine in ovarian cancer treatment.

Newer agents and combinations are needed in order to improve current results in ovarian cancer treatment. Gemcitabine is a novel agent that has shown promising activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogues, Gemcitabine has been combined with Carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Further combination of Gemcitabine and other agents, including paclitaxel, are also feasible and have been actively studied in order to establish the role of Gemcitabine in the management of treated and untreated ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Colonic smooth muscle responses in patients with diverticular disease of the colon: effect of the NK2 receptor antagonist SR48968.

BACKGROUND: Little is known about the pathophysiology of diverticular disease. AIM: To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated. PATIENTS: Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer. METHODS: Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied. RESULTS: Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P < 0.05). Electrically evoked contractions were significantly reduced by atropine in all preparations and were virtually suppressed by combined SR48968 and atropine. Tetrodotoxin suppressed electrically evoked contractions only in patients with colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease. CONCLUSIONS: The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

Aged↗
PubMed2004

Phase II study of pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. May a new treatment schedule improve toxicity profile?

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has shown promising activity in the treatment of recurrent ovarian cancer but skin toxicity remains the dose-limiting toxicity of the drug. The aim of this study was to investigate whether a different treatment schedule may improve the toxicity profile, especially in terms of dermatological and mucosal toxicity. METHODS: It is an open-label phase II study in a population of heavily pretreated ovarian cancer patients. PLD was administered at the dose of 35 mg/m2 q21 until disease progression or unacceptable toxicity. RESULTS: Thirty-seven heavily pretreated (median number of previous chemotherapy regimens 2, range 1-6) ovarian cancer patients were enrolled. All patients received at least two courses of chemotherapy and all were evaluated for response. No one showed complete response, while five partial responses (13.5%), 16 stabilizations of disease (48.6%) and 14 progressions of disease (37.8%) were observed. The median time to response was 12 weeks (range 8-16). The median duration of response was 22.8 weeks (range 4-68), the median duration of stabilization of disease was 17.6 weeks (range 4-28). Palmar plantar erythrodysesthesia (PPE) occurred in 8 patients (21.6%) and was of grade 3 in one patient (2.8%). Grade 1 stomatitis occurred in 3 patients (8.1%). Grade 3-4 neutropenia occurred in only 4 patients (10.8%). CONCLUSIONS: PLD at the dose of 35 mg/m2 q21 seems to translate into an acceptable skin toxicity profile with a response rate comparable to others obtained with a standard schedule.

Adult↗
PubMed2004

Role of pegylated liposomal doxorubicin (PLD) in epithelial ovarian cancer.

Pegylated liposomal doxorubicin (PLD, Caelyx) is an emerging option for patients with recurrent ovarian carcinoma. Several phase II studies showed promising activity of PLD in recurrent ovarian cancer patients with response rate ranging from 16 to 25%. A phase III randomized trial compared PLD 50 mg/m2 day 1 every 4 weeks with Topotecan 1.5 mg/m2 daily for 5 days q 21 in recurrent ovarian cancer patients. No differences in progression free survival and overall survival were documented between treatment arms in the general population but a survival advantage was reported for platinum-sensitive subset. Our experience with PLD in the treatment of ovarian cancer is reported in this review article. Pegylated liposomal doxorubicin is effective as a second line treatment in ovarian cancer patients; comparative data are needed to establish its role in first line therapy.

Antibiotics, Antineoplastic↗
PubMed2003

Phase II study of liposomal doxorubicin and gemcitabine in the salvage treatment of ovarian cancer.

In total, 70 patients were enrolled into this phase II study, to evaluate the activity of the pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) combination in recurrent ovarian cancer patients. PLD, 30 mg m(-2), was administered on day 1 by 60' i.v. infusion, followed by GEM, 1000 mg m(-2), given by 30' i.v. on days 1 and 8; cycles were repeated every 21 days. In all, 67 patients are so far evaluable for response. Seven complete responses (10.4%, 95% CI: 3.1-17.7), 16 partial responses (23.9%, 95% CI: 13.7-34.1), 26 disease stabilisations (38.8%, 95% CI: 27.1-50.5) and 18 progressions (26.9%, 95% CI: 16.3-37.5) have been registered. Within the resistant population (n=36), the response rate was 25% (95% CI: 10.9-39.1). Within the group of platinum-sensitive patients (n=31), the response rate was 45.2% (95% CI: 27.7-62.7). A total of 443 courses are evaluable for toxicity. Grade 3-4 hematological toxicity was registered in 30 patients (42.8%), mainly represented by neutropenia (35.6%); palmar-plantar erythrodysesthesia affected 24 patients (34.2%), but it was of grade 3 in only seven of them (10%).

Adult↗
PubMed2003

Increased farnesyltransferase activity in human colorectal cancer: relationship with clinicopathological features and K-ras mutation.

BACKGROUND: The enzyme farnesyltransferase has emerged as an important target for anti-cancer therapies. Farnesyltransferase inhibitors have been introduced in clinical trials of subjects with colorectal cancer. We investigated Farnesyltransferase activity, beta-subunit Farnesyltransferase protein expression and its mRNA in patients with colorectal cancer and its relationship with clinicopathological features and K-ras mutation. METHODS: Farnesyltransferase activity was determined by Farnesyltransferase [3H] SPA enzyme assay. Beta-subunit Farnesyltransferase protein expression was investigated by Western blotting and its mRNA by reverse transcriptase-polymerase chain reaction. K-ras mutation was detected by polymerase chain reaction amplification and restriction enzyme analysis. Multiple linear regression analysis was used to analyse relationships among age, sex, site of tumour, Dukes' stage, histological differentiation, K-ras mutation and Farnesyltransferase activity in normal mucosa and cancer. RESULTS: The levels of Farnesyltransferase activity and beta-subunit Farnesyltransferase protein expression were significantly higher in cancer than in normal mucosa. Moreover, tumours located on the right side, with mucinous histological differentiation and with K-ras mutation showed higher levels of Farnesyltransferase activity. CONCLUSIONS: Our findings suggest that Farnesyltransferase activity may be a potential marker of tumourigenicity. The differences in Farnesyltransferase activity in relation to histological grading, tumour location and K-ras mutation described here may constitute a starting point for investigating the causes of this variation within the large bowel.

Adenocarcinoma↗
PubMed2003

Persistent dyspepsia after laparoscopic cholecystectomy. The influence of psychological factors.

BACKGROUND: Many patients with gallstone disease continue to report gastrointestinal symptoms after cholecystectomy, but the predictive value of preoperative factors is not well understood. We aimed to investigate whether psychological symptoms can be associated with poor outcome after cholecystectomy in patients with gallstones and dyspepsia. METHODS: A sample of 52 consecutive patients with uncomplicated gallstone disease and dyspepsia (conceived in a broader sense to include symptoms of the whole digestive tract) were assessed for psychological (revised 90-item Hopkins Symptom Checklist) and gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale). One year after laparoscopic cholecystectomy, patients rated their gastrointestinal symptoms and were divided into improved and unimproved on the basis of the change in symptoms. RESULTS: Twenty-one (40.4%) patients did not improve after surgery. Improved and unimproved patients did not differ in terms of sex, age, education or illness duration. Unimproved patients showed significantly higher psychological and dyspeptic symptoms than improved patients before surgery. Logistic regression showed that psychological factors were significantly associated with unimprovement after surgery. CONCLUSIONS: Patients with gallstone disease and dyspeptic symptoms are unlikely to improve 1 year after surgery if they show psychological distress before surgery. Psychological symptoms were strongly associated with poor post-cholecystectomy outcome, thus highlighting the clinical relevance of joint assessment of psychological and gastrointestinal symptoms before surgery.

Adult↗
PubMed2003

Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.

BACKGROUND: A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles. RESULTS: One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups. CONCLUSIONS: We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.

Adult↗
PubMed2001

Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder.

Cholecystokinin is the most important stimulant of postprandial gallbladder contraction, and a regulator of gallbladder fasting tone. The aim of this study was to evaluate the effect of dexloxiglumide on isolated human gallbladder contraction induced by cholecystokinin-octapeptide and to compare this effect to that of lorglumide and amiglumide, two glutaramic acid analogs of dexloxiglumide. The negative logarithms of the antagonist dissociation constant (pK(B)) values were 7.00 +/- 0.14, 6.95 +/- 0.11, and 6.71 +/- 0.10 for lorglumide, dexloxiglumide, and amiglumide, respectively. Dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. A similar effect was obtained both with lorglumide and amiglumide. Moreover, the slopes for the three antagonists did not differ significantly from unity. These data show that the three molecules have a potent antagonistic effect, of a competitive nature, on gallbladder cholecystokinin type 1 receptors. It may be concluded that dexloxiglumide, lorglumide, and amiglumide exhibit a promising therapeutic profile for biliary colic and other gastrointestinal disorders in which CCK1 receptors play important physiological roles.

Cholecystokinin↗
PubMed2001

Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.

24 patients were enrolled into a phase I-II study conducted to determine the maximum tolerated doses of topotecan-gemcitabine in sequential combination and the response rate in platinum/paclitaxel resistant ovarian cancer patients. A total of 83 courses are evaluable, with a median number of three cycles administered per patients (range 2-7). Topotecan was administered on days 1-5 by 30 min i.v. infusion immediately after gemcitabine given by 30 min i.v. on days 1 and 3; cycles were repeated every 28 days. The starting doses were topotecan 0.7 mg/m(2) and gemcitabine 200 mg/m(2). Following dose levels were 08/400; 0.9/600; 0.9/800 for topotecan and gemcitabine, respectively. The maximum tolerated dose (MTD) was reached at dose level 3, the dose-limiting toxicity being represented by febrile neutropenia and thrombocytopenia. After the MTD was reached, granulocyte-colony-stimulating factor was administered in 27% of cycles. Mild and manageable was non hematological toxicity. All patients are so far evaluable for response. Among them 2 complete responses (8.3%; 95% CI: 2.6-19), 1 partial response (4.2%; 95% CI: 3.8-12), 9 no change (37.5%; 95% CI: 18-56.8) and 12 progressions (50%; 95% CI: 30-70) have been registered. Based on these data, there is no evidence that combining topotecan and gemcitabine is better than using either of the two drugs used separately.

Adult↗
PubMed1999

Effect of somatostatin on human gallbladder motility: an in vitro study.

In vivo studies have demonstrated that somatostatin induces human gallbladder relaxation. To determine whether this polypeptide acts directly on the gallbladder muscle, its effect on strips of human gallbladder was studied in vitro. Strips of gallbladder were set up isometrically in an organ bath containing oxygenated Krebs' solution. Dose-response curves to cholecystokinin-octapeptide and carbachol were first established. The ability of somatostatin to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (7.2 x 10(-8) M) and carbachol (3.5 x 10(-6) M) was assessed in 32 strips at 4.3 x 10(-6) M concentration which mimics the plasma concentrations found in patients with somatostatinoma and in 12 additional strips at 4.3 x 10(-8) M concentration. Somatostatin action on the intrinsic innervation by using electrical field stimulation (EFS) (200 mA 5 msec in duration, 30 Hz; 400 mA, 1 msec in duration, 10 Hz) was also evaluated in 39 strips. Somatostatin had no effect on the basal or carbachol-generated tensions. On the contrary, somatostatin (4.3 x 10(-6) M) reduced cholecystokinin-octapeptide-generated tensions by 8% (P < 0.001) and reduced EFS-generated tensions at 30 Hz by 7.7% (P < 0.01) and those at 10 Hz by 41.2% (P < 0.01). All responses to cholecystokinin-octapeptide and carbachol were abolished by dibutyryl-guanosine 3', 5'-cyclic monophosphate (5 x 10(-3) M) and atropine (10(-5) M), respectively (P < 0.0002 and P < 0.0002). All responses to electrical field stimulation were reduced or abolished by tetrodotoxin (2 x 10(-6) M) (P < 0.001 and P < 0.0001, respectively). Our findings show that somatostatin exerts its inhibitory action on the response to cholecystokinin-octapeptide and on the intrinsic innervation of the gallbladder smooth muscle. The probable neurotransmitter is the acetylcholine.

Carbachol↗
PubMed1997

Effects of cholecystectomy on gastric emptying and myoelectrical activity in man.

To investigate the effects of cholecystectomy on gastric motor function, 13 patients with symptomatic gallstones were studied before and 8-12 months after surgery. Twelve healthy subjects entered the study as control group. The cutaneous electrogastrography and ultrasound examination of gastric emptying were simultaneously performed at pre- and post-prandial states. The dominant gastric frequency and its coefficient of variation were not affected by surgery. After cholecystectomy, an increase in normal 3 cpm wave percentage and a decrease in power ratio were found (P < 0.05 and P < 0.01, respectively). Gastric emptying recorded after cholecystectomy was faster than before surgery (306.9 +/- 15.9 min vs 336.9 +/- 11.8 min, respectively; P < 0.05). Such changes were associated with the relief of symptoms, and the comparison between patients and controls showed a normalization of the gastric electrical activity and gastric emptying after surgery. In conclusion, in symptomatic patients, gallstones are associated with motor dysfunctions, and cholecystectomy seems to induce a normalization of gastrointestinal motility.

Adult↗
PubMed1997

[Subcutaneous emphysema during laparoscopy. A case report].

Diagnostic and therapeutic laparoscopy is a safe procedure, which, however, is not without complications. In this article, we report a case of subcutaneous emphysema, as a consequence of pneumoperitoneum, during laparoscopic cholecystectomy. The mechanism for the development of this complication and its management are discussed.

Carbon Dioxide↗
PubMed1997

[Surgical therapy of the peptic ulcer in a hospital specializing in gastroenterology. Effects of therapy with h2 antagonists].

To evaluate how the introduction of H2-receptor antagonists has modified the epidemiology of surgical management of peptic ulcer, we examined data records of patients operated on for gastric or duodenal ulcer in our Institute. Patients were divided into two groups: a) patients operated from 1970 to 1979 and b) patients operated from 1980 to 1992. The comparison between the two groups showed the following variations: decrease in male/female ratio from 8 to 4.4:1 (p = 0.0009); decrease in duodenal/ gastric ulcer ratio from 5 to 3.5:1 (p = 0.02); decrease in elective/emergency surgery ratio from 16 to 6.4:1 (p = 0.00006); increase in mean age of patients undergoing emergency operations from 51 to 58 years (p = 0.05); decrease in elective/emergency surgery ratio for gastric ulcer from 17.5 to 5.3:1 (p = 0.03), above all for the increase in emergency operations for hemorrhage; decrease in the prevalence of operations for refractory duodenal ulcer from 49% to 36% (p = 0.00009). Our findings show that H2-receptor antagonists have greatly modified the epidemiology of surgical treatment of peptic ulcer with a clear decrease in elective surgery for refractory duodenal ulcer in men and an increase in emergency surgery for gastric ulcer.

Adolescent↗
PubMed1996

Gallbladder motility in vitro in men with gallstones following Billroth II gastric resection.

Gastric surgery induces an increased incidence of gallstones. To investigate the changes in gallbladder kinetics after gastric resection, 20 male patients were studied: ten patients undergoing cholecystectomy for gallstones developed after Billroth II gastric resection and ten patients undergoing cholecystectomy for cholelithiasis without previous abdominal surgery. Longitudinal strips from the gallbladder wall were suspended in an organ bath and the isometric tension recorded. Dose-response curves to cholecystokinin-octapeptide and carbachol were obtained. Half the maximal response to cholecysto-kinin-octapeptide was 0.50 +/- 0.11 x 10(-7) M in the first group and 1.36 +/- 0.37 x 10(-7) M in the second group (P < 0.05). The ED50 to carbachol was 24.33 +/- 2.69 x 10(-7) M in the gastrectomy group and 40.39 +/- 5.01 x 10(-7) M in the control group (P < 0.01). There was no significant difference in the maximal contractile response either to cholecystokinin-octa-peptide or carbachol in the two groups. Our study shows an increased gallbladder sensitivity to cholecystokinin-octapeptide and carbachol in patients with gallstones developed after Billroth II gastric resection.

Aged↗