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Biomedical subjects

D Donati

Publications and source records attributed to D Donati.

At least 127 records · Page 7Linked to original sources

Lonidamine in advanced colorectal cancer: a phase II study of the Italian Oncology Group for Clinical Research (GOIRC).

Twenty-one patients with metastatic colorectal adenocarcinoma, all previously treated with chemotherapy for metastatic disease, were treated with lonidamine (LDN). The major toxicity encountered was muscular (myalgias in 48%) and gastro-intestinal (nausea and/or vomiting in 52%). Other toxicities included abdominal pain, somnolence, fever, arthralgia and ototoxicity. In the 14 patients evaluable for response we observed no complete or partial remission, 8 stable disease and 6 progressive disease. LND has no clinically worthwhile activity against colorectal carcinoma refractory to conventional chemotherapy.

Adenocarcinoma↗

The release of interleukin-1-like activity by macrophages in two models of immunological inflammation in the rat.

Interleukin-1 (IL-1) is a putative mediator of inflammation released by activated macrophages in vitro. The IL-1 release by rat macrophages collected either from exudates in pertussis-induced air pouches or from the peritoneum during adjuvant arthritis has been investigated. In air pouch inflammation LPS-stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at day 6 after challenge. This enhanced IL-1 release parallels the extent of mononuclear cell migration in the inflammatory lesion. In adjuvant arthritis LPS-stimulated macrophages collected from sensitized animals release more IL-1 than cells from control rats at days 16 and 23 after adjuvant injection. The secondary inflammation in arthritic rats was statistically significant at days 16 to 28. These results indicate that during immunological inflammation macrophages either from the inflamed area or from a non-inflamed region release more IL-1 than control cells. This release parallels the extent of the inflammation and may be important in its pathogenesis.

Air↗

Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research.

Despite treatment, emesis remains a major problem with cisplatin (CDDP) chemotherapy. Reasons for variability in antiemetic response among patients and in subsequent cycles are largely unknown and toxicity is sometimes severe. We have, therefore, carried out a multicenter, double-blind randomized trial comparing a combination of high-dose metoclopramide (MTC) (1 mg/kg x 4) and methylprednisolone (P) (treatment A) with a shorter but higher single-dose schedule of metoclopramide (3 mg/kg x 2) combined with dexamethasone (DEX) and diphenhydramine (DIP) to prevent extrapyramidal reactions (treatment B). Three hundred sixty-seven consecutive patients treated with various chemotherapy combinations containing CDDP were studied. Complete protection from vomiting/nausea was, at first cycle, 72.5%/79.5% with treatment B and 55.8%/65.1% with treatment A, a statistically significant difference (P less than .002/P less than .005). In subsequent cycles, protection from emesis significantly decreased with no difference between the two treatments. Multifactorial analysis shows that women, younger patients, outpatients, and patients who experienced emesis in previous cycles were at higher risk of suffering nausea and/or vomiting. Both regimens were well tolerated, but patients treated with treatment B had significantly less extrapyramidal reactions (1.7%/6.1%, P = .053). Treatment B is preferred due to its greater efficacy and lower incidence of extrapyramidal reactions. Trials on antiemetic therapy should take into account the important variables able to influence the efficacy of treatment. There is still a need for improving prevention of emesis in CDDP-treated patients.

Age Factors↗

Arachidonic acid lipoxygenation may be involved in interleukin-1 induction of prostaglandin biosynthesis.

The induction of prostaglandin (PG) biosynthesis by human recombinant interleukin-1 beta (hrIL-1 beta) has been investigated using rat-isolated stomach strip preparations. hrIL-1 beta (30 and 120 pM) increased CaCl2 responses in a dose-dependent manner with both concentrations significantly potentiating maximum contraction (62.4 +/- 5.1 and 184.2 +/- 36.9%, respectively). This enhancement was characterized further using inhibitors of arachidonic acid metabolism, mRNA and protein synthesis as well as a selective leukotriene (LT) D4 antagonist. Indomethacin (5.6 microM) reduced CaCl2 contractions in the presence of hrIL-1 beta (30 pM) such that only a small residual response was evident, this being reduced further by NDGA (20 microM). Contrastingly, nordihydljroguaiaretic acid reduced only the enhancement of response due to hrIL-1 beta. These findings, supported by parallel radio-immunoassay of PGE2 in the bathing medium after drug treatments suggest strongly that the augmentation of contraction by hrIL-1 beta is due mainly to increased production of PGs. Furthermore, this enhancement is inhibited in a dose-dependent manner by the LTD4 antagonist FPL55712. Additionally, using actinomycin-D and cycloheximide we demonstrated that the hrIL-1 beta induced potentiation is dependent upon mRNA and protein biosynthesis as both compounds substantially reduced responses in the presence of the interleukin. These results provide possible evidence that hrIL-1 beta induced PG production is mediated by a lipoxygenase product, most likely LTD4, which in turn could be important for the induction of de novo protein synthesis.

Animals↗

Controlled trial of thymopentin in hemodialysis patients who fail to respond to hepatitis B vaccination.

Uremic patients are at high risk of hepatitis B virus (HBV) infection and, despite the availability and efficacy of hepatitis B vaccine, a high rate of non responders has been reported. Forty uremic patients undergoing maintenance hemodialysis who failed to produce any measurable anti-HBs antibody response after 4 administrations of 5 micrograms of Hevac B Pasteur vaccine were admitted to a randomized controlled clinical trial. Group A (14 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals and 12 doses of 50 mg s.c. of thymopentin on alternate days between the first and the second vaccination. Group B (11 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals. Group C (15 patients) received 3 doses of 10 micrograms s.c. each of vaccine at monthly intervals. Immunization rates were 86% in group A (on both 1-month and 6-month checks), 36% on the 1-month and 27% on the 6-month check in group B, 53% on the 1-month and 47% on the 6-month check in group C. Anti-HBs antibody titers were similar in group A and C but notably lower in group B. Thymopentin seems as useful therapeutical tool for non responder patients. As it promotes T cell maturation and responsiveness, which are impaired in uremia, it could play a major part in the management of uremic immunodeficiency.

Clinical Trials as Topic↗

Fractures of the lower end of the humerus in the adult.

The authors report their experience in the treatment of 34 fractures of the lower end of the humerus treated surgically over the last 6 years. The fractures are divided into four types in assessing the functional results; open and closed; those involving and not involving the joint. Satisfactory clinical results were obtained in 22 of the 34 cases (64%). Complications were directly related either to the severity of the lesion (comminuted and open fractures) and/or inadequate surgical technique.

Adolescent↗

Natural history and treatment of uremia secondary to Fabry's disease: an European experience.

Fabry's disease, a very unusual cause of end-stage renal disease, is actually included in the contraindications to renal transplantation. The few published studies, based on very few patients, report a high rate of life-threatening complications, mostly infectious, following kidney transplant in these patients. We have evaluated retrospectively 12 uremic patients in renal function replacement treatment for Fabry's disease. In transplanted patients (n = 8; whole observation period 241 months), no lethal complication was ever recorded. Fever and acroparesthesias ameliorated. Cardio- and cerebrovascular complications did not progress. Although no increase in serum enzymatic activity was measured, renal transplantation provided an alternative route by excretion of an amount of the metabolic product (ceramide-trihexoside). When undergoing maintenance hemodialysis (whole observation period 291 months), 3 deaths and several cardiac and cerebral complications occurred. Angiokeratomas, fever and pains were unmodified. These data disagree with what has been previously stated. The transplanted patients' survival shifts towards the all-time rate and a satisfying rehabilitation is provided. Fabry's disease should not be considered a high-risk disease; and patients suffering from it should decidedly enter a regular transplantation program.

Adolescent↗

Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

We designed a multicenter, double-blind randomized study to determine the safety and antiemetic effectiveness of intravenous (IV) methylprednisolone (P) combined with high-dose IV metoclopramide (MTC) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy. One hundred eighty-five patients were evaluable for treatment efficacy. MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes (P = .001 and P = .0008, respectively) and the maximal intensity of nausea (P = .0124 with a score system; P = .0155 with a linear analogue scale) and length of nausea (P = .0056). The subgroup with a major incidence of nausea and vomiting was women, especially young women, outpatients, and those treated with higher doses of cisplatin. Side effects were low and equally distributed between the two treatment groups. We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy.

Adult↗

Biliary calculi caused by hemobilia.

Formation of biliary calculi caused by hemobilia is rare. Including the two cases reported here, there are only a total of four in the literature. The characteristics of these calculi in vitro, on computerized tomographic scan, and cholecystography are described. The condition for the occurrence seems to be that blood clots remain in the gallbladder sufficiently long (about 6 months) to become encrusted with bile constituents. Patients with hemobilia with clots in the gallbladder should be observed for this complication.

Adolescent↗

[Systemic and nonsystemic causes of pathological mandibular fractures].

The problem of pathological fractures of the lower jaw with particular reference to their aetiology is examined in the light of personal experience. Odontogenic and hematogenic osteomyelitis, primary and metastatic tumours, degenerative lesions, traumas, inclusions of the teeth and the whole apparatus are discussed individually.

Fractures, Spontaneous↗

[Hand-Schüller-Christian syndrome arising in the mandible. A case report].

The history of Letterer-Siwe, Hand-Schüller-Christian disease, and eosinophilic granuloma of the bone, and the evolution of the concept of grouping them together under the common term of histiocytosis X are presented. The characteristics of the disease, with particular emphasis on oral manifestations, are reviewed. The therapy for the disease is briefly outlined. One case of Hand-Schüller-Christian syndrome is presented. The discussion is focused on the problem of chemotherapy in disseminated forms.

Adult↗

[Splenic rupture: conservative treatment with sonographic control of its course].

The spleen is the abdominal organ most frequently damaged in blunt abdominal trauma. Because of the high incidence of fatal sepsis after splenectomy, conservative treatment is getting increasingly important. Besides CT and radionuclide scanning, sonography has become an increasingly important tool in diagnosis and follow-up.

Adolescent↗

Antiemetic activity of two different high doses of metoclopramide in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

High-dose metoclopramide has been proposed as an effective antiemetic agent in patients treated with cisplatin. Its optimal dosage schedule, however, has not yet been completely defined. We report the results of a multicenter, double-blind, randomized clinical trial where the efficacy and safety of two fixed high-dose regimens of metoclopramide (60 and 120 mg, respectively) have been tested in 112 patients receiving cisplatin treatment. No statistically significant difference has been found between the two groups. In patients treated with cisplatin at doses greater than 100 mg/m2, the higher dose regimen seems more efficacious, but this result should be confirmed in a larger group of patients. Treatment was generally well-tolerated. However, a consistent percentage of patients (about 60%) still present with vomiting, and this makes further investigation necessary.

Adult↗