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Biomedical subjects

D Donati

Publications and source records attributed to D Donati.

At least 37 records · Page 2Linked to original sources

Comparison between midline incision and limited right skin crease incision for right-sided colonic cancers.

We compared the postoperative recovery parameters between patients undergoing curative surgery for right-sided colonic carcinoma using a limited skin crease incision and a traditional midline incision. A retrospective study was carried out analyzing clinical records and histopathological reports for all patients operated in one colorectal surgical unit for cancer of the right colon over a 2-year period. Palliative procedures were excluded. We analyzed demographic details, operative data (length of incision and time of operation), recovery parameters (time to parenteral analgesia, time to first oral fluid intake, time to first solid meal, time to discharge) and oncological parameters (lymph node harvest and resection margins). A total of 123 patients were analyzed, 61 with a midline incision and 62 with a skin crease incision. Demographic and tumour data (number of lymph nodes resected and resection margins) as well as postoperative complications were similar between the two groups. Wound length was significantly longer in the midline incision group (median, 20 cm vs. 10 cm; p<0.0005), as was the duration of surgery (median, 60 min vs. 45 min; p0.0005). With regard to postoperative recovery, the skin crease incision group had a significantly quicker return of bowel function ( p<0.0005), shorter time to oral fluid ( p<0.001) and solid food ( p<0.0005) intake, and shorter hospital stay ( p<0.0005) than the midline incision group. There was no statistically significant difference between the two groups concerning postoperative narcotic requirements. In conclusion, the limited skin crease approach for right colon cancer resection is technically feasible and safe. It can achieve the same standards of tumour resection and clearance as the vertical midline approach while reducing postoperative recovery.

Adenocarcinoma↗

Neoadjuvant chemotherapy for Ewing's tumour of bone: recent experience at the Rizzoli Orthopaedic Institute.

The results achieved in 157 patients with non-metastatic Ewing's sarcoma of the bone treated at a single institution between 1991 and 1997 according to a new protocol (REN-3) are reported. Induction chemotherapy consisted of two cycles of 'VAC': vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of 'VIAc': V, ifosfamide (I), actinomycin (Ac). After local treatment, patients received three more cycles of VAC, two of VIAc, three cycles of I plus etoposide (E) and two cycles with V, C and Ac. Local treatment was surgery in 53% of patients, surgery+radiotherapy in 25% and radiotherapy only in 22%. With a follow-up ranging between 4 and 10 years (mean: 7 years), 110 patients (70%) remained continuously event-free, 2 patients died of toxicity and 45 patients relapsed: 33 due to metastases and 12 due to local recurrence always associated with metastases. The 5-year event-free survival (EFS) and overall survival (OS) were 71.0 and 76.5% respectively. These results are significantly better that the ones achieved in our previous three studies in which a three-drug VAC regimen (REA-1), and 4-drug VACAc regimen (REA-2 and REN-1) was used, and in our most recent study (REN-2) which was based on a six-drug regimen as in the present study, but where I and Ac were used only after the local treatment. However, since REN-3 surgery was used in a significantly larger number of patients, we cannot say whether the better outcome of this study was due to the use of a six-drug regimen with an early delivery of ifosfamide and actinomycin, or to the wider use of surgery as local treatment or both.

Adolescent↗

Quality of life and length of survival in advanced cancer patients on home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) in patients with advanced cancer is controversial because survival is usually short and there are no data regarding the quality of life (QoL). METHODS: Sixty-nine advanced cancer patients enrolled in a program of HPN in six different Italian centers were prospectively studied as regards nutritional status (body weight, serum albumin, serum transferrin and total lymphocyte count), length of survival and QoL through the Rotterdam Symptom Checklist questionnaire. These variables were collected at the start of HPN and then at monthly intervals. All these patients were severely malnourished, almost aphagic and beyond any possibility of cure. RESULTS: Nutritional indices maintained stable until death. Median survival was 4 months (range 1-14) and about one-third of patients survived more than 7 months. QoL parameters remained stable till 2-3 months before death. CONCLUSIONS: HPN may benefit a limited percentage of patients who may survive longer than the time allowed by a condition of starvation and depletion. Provided that these patients survive longer than 3 months, there is some evidence that QoL remains stable for some months and acceptable for the patients.

Adult↗

Allograft arthrodesis treatment of bone tumors: a two-center study.

The current study consists of an outcome review of a consecutive series of 92 patients with knee arthrodesis using an allograft, done for malignant or aggressive tumors in two centers on different continents during a period of 18 years (mean followup, 5 +/- 4 years). The data were compiled by creating a computerized file using the information provided by both centers. Seventy-five of the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the remaining 10 (11%) had benign disease, mostly giant cell tumor or revision procedures for failed allograft or total joint replacement. Seventy-two patients (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16 years; 51 were males and 41 were females. Tumor complications were a major problem for patients in the series. Thirty-four percent of the patients died, 47% had metastases develop, and 9% had a local recurrence. Allograft complications included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of 44%. Repeat surgery was required for more than 50% of the patients with 26 requiring one additional operation, 11 requiring two, and 10 requiring three or more operations. Nineteen of the patients required an amputation (20%), only four of which were for recurrent tumor. When these data were compared with data for a control series of 880 patients with allografts other than allograft arthrodeses, the complications were greater and the outcome less successful, suggesting that other approaches should be considered unless there are special indications for this procedure.

Adult↗

High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study.

With the intention of starting an international protocol between Italy and Scandinavia on neoadjuvant treatment of extremity osteosarcoma using the four active drugs at maximum doses (doxorubicin 75 mg/m2 pre-operatively, and 90 mg/m2 post-operatively, cisplatin 120 mg/m2, methotrexate 12 g/m2, and ifosfamide 15 g/m2), a single center (the Rizzoli institute) performed a pilot study to closely monitor toxicity, safety, and tumor necrosis. Only 7 patients (10%) had a reduced number of the scheduled cycles. A total of 1,050 of the expected 1,076 cycles (98%) were administered. Delays and dose reduction were minimal, leading to a mean received dose intensity of 89%. Limb salvage surgery was performed in 59 cases (87%), with 6 amputations and 3 rotation plasties. Chemotherapy-induced necrosis higher than 95% was observed in 38 patients (56%). Eleven patients had total necrosis (16%). At a median follow-up of 60 months (range 50-65 months), 53 patients (73%) were continuously disease-free. Six of the relapsed patients were rescued with further treatments leading to an overall survival of 87%. Hematological toxicity was remarkable despite the use of G-CSF and hospitalization due to febrile neutropenia occurred in 25 patients (37%). Platelet transfusions were required in 77 of the 194 episodes of grade 4 thrombocytopenia, but no case of major bleeding was observed. Red blood cell transfusions were necessary in all patients (in 15 cases perioperatively only). Non-hematological toxicity comprised grade 1-2 nephrotoxicity in 3 cases, CNS toxicity in 2 cases, and dilata- tive cardiopathy leading to heart transplantation in 1 case. In conclusion, the pilot study was feasible in the vast majority of cases with toxicity not superior to that of the previous protocols where chemotherapy was given in lower doses. The rate of limb salvage procedures, event-free survival and overall survival seemed to be higher than in previous protocols. On the basis of this study, in March 1997 the Italian and Scandinavian Sarcoma Groups started a new protocol for osteosarcoma of the extremities.

Adolescent↗

[Management of obese patients: surgical therapy].

At present, the management of obesity includes integration of therapeutic strategies such as diet, physical training, behaviour therapy and pharmacologic therapy. An increased number of selected patients with morbid obesity, where medical therapy was ineffective, have been surgically treated in the last years due to less invasive surgical techniques, such as laparoscopic surgery. Main operations include gastroplasty, adjustable gastric banding, gastric bypass, bilio-pancreatic diversion. A less invasive procedure is intragastric balloon, i.e. a temporary device which is removed after few months. Surgery shows efficacy to induce weight loss and duration in time. All obese patients can't be treated by the same operation. Available surgical techniques are different and have to be chosen in each case according to the patient's clinical conditions.

English Abstract↗

Human CD38 and its ligand CD31 define a unique lamina propria T lymphocyte signaling pathway.

CD38, a nonlineage-restricted surface glycoprotein, is an ecto-enzyme (ADP ribosyl cyclase/cADPR hydrolase/EC 3.2.2.6) that regulates cytoplasmic Ca2+ and cell-cell interactions. The molecule also delivers trans-membrane signals, despite a structural ineptitude to the scope. To reconcile these issues in a unitarian model, we compared the effects of CD38 signaling in circulating and residential T lymphocytes, the latter represented by those colonizing the intestinal lamina propria. Results are as follows: 1) LP T cells express an enzymatically active form of CD38, characterized by a modified ratio between cyclase and hydrolase functions; 2) LP T cells do not mobilize Ca2+ upon CD38 ligation, as seen in PB T cells (this condition is due to a lack in activation of PLC- g, constantly observed in PB T lymphocytes); 3) The early steps of CD38 signaling involve activation of lck, syk, and LAT; 4) Late events include synthesis and release of IL-2, IL-4, IL-5, IL-10, IFN-g and GM-CSF; 5) The uniqueness of the CD38 pathway in LP T cells is not caused by impaired interactions with the CD31 ligand. The differences observed concern the signaling machinery that CD38 exploits for its own use and not the interplay with its ligand.

ADP-ribosyl Cyclase↗

Biofeedback avoids surgery in patients with slow-transit constipation: report of four cases.

Biofeedback is established treatment for intractable constipation in patients with an element of pelvic floor dysfunction. In those with intractable slow-transit constipation and normal pelvic floor function, colectomy is usually recommended. We report four patients with isolated slow-transit constipation who benefited from biofeedback and avoided surgery. All four patients were extensively investigated for pelvic floor dysfunction before undergoing a standard biofeedback course of four outpatient sessions. All improved in terms of bowel frequency, laxative use, bloating, straining, and lifestyle. Improvement has been maintained for a median of nine (range, 5-12) months without the requirement for further treatment. Biofeedback represents a safe and inexpensive treatment for these patients and may avoid surgery in a significant proportion.

Adult↗

A new alternative synthesis of 5-cyanophthalide, a versatile intermediate in the preparation of the antidepressant drug citalopram.

An alternative versatile synthesis of 5-cyanophthalide, a key synthetic intermediate in the preparation of the antidepressant drug Citalopram, is presented. The synthesis reported here allows the preparation of this important intermediate in three steps, avoiding the manipulation of environmentally detrimental cyanides.

Antidepressive Agents, Second-Generation↗

Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists.

After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia.

Animals↗

Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol.

From January 1993 to March 1995, 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol. 133 patients had localised disease, while 29 had metastases at diagnosis. These last patients were simultaneously operated upon for their primary and metastatic lesions. Chemotherapy consisted preoperatively of two cycles of high dose methotrexate (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned drugs used as single agents. The mean follow-up of all patients was 6.5 years (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event-free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients with localised disease, and 17 and 24% for patients with metastases at diagnosis. These results did not differ from those achieved in our previous study (IOR/OS-3) in which IFO was used only postoperatively in poor responders.

Adolescent↗

3-Hydroxy-(4H)-benzopyran-4-ones as potential iron chelating agents in vivo.

Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalised from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, post-ischaemic reperfusion, etc.). In order to be used for therapeutical purposes in vivo, a reliable iron chelator should be capable of preventing the undesired effects that follow the electrochemical activation of iron (see below). Bearing in mind the molecular structure of some flavonols that are able to chelate iron, we synthesised a new oral iron-chelator, 2-methyl-3-hydroxy-4H-benzopyran-4-one (MCOH). We demonstrate that MCOH chelates iron in a 2:1 ratio showing a stability constant of approximately 10(10). MCOH is able to cross cell membranes (erythrocytes, ascite tumour cells) in both directions. Following intraperitoneal administration to rats, it is quickly taken up by the liver and excreted in the urine within 24h. A similar behaviour has been documented after oral administration. We propose that MCOH may represent the prototype of a new class of iron chelating agents to be developed for iron-removal therapy in vivo with the goal of preventing tissue damage caused by the iron redox cycle.

Administration, Oral↗

Latent class analysis of DSM-IV schizotypal personality disorder criteria in psychiatric patients.

The aim of the study was to evaluate the latent structure of DSM-IV schizotypal personality disorder (SPD) diagnostic criteria. The sample consisted of 564 consecutively admitted inpatients and outpatients. Exploratory latent class analysis identified a four-class model as the best fitting model for DSM-IV SPD criteria. The first of the SPD latent classes was mainly characterized by odd thinking, inappropriate affect, and interpersonal features; the second class by cognitive/perceptual difficulties; the third class by paranoid features; and the fourth class by absence of SPD features. The conditional probability pattern of the fourclass solution could be safely replicated across confounder strata. Unlike previous findings, oddness, aloofness, and social withdrawal, rather than positive symptoms, best characterized SPD even in clinical samples.

Adult↗

Histologic response of high-grade nonmetastatic osteosarcoma of the extremity to chemotherapy,.

In 510 patients with osteosarcoma of the extremity treated at the authors' institute between March 1983 and June 1995 with different regimens of neoadjuvant chemotherapy, factors that influenced the histologic response were investigated. The rate of total necrosis was not related to the patients' gender, age, site, size of tumor, serum of alkaline phosphatase values, or route of cisplatin administration. The histologic response significantly and independently correlated with the number of drugs administered before surgery and with the histologic subtype of the tumor. According to the number of drugs used, the percentage of total necrosis was 31% for a four-drug regimen, 18% for a three-drug regimen, and only 1.5% for a two-drug regimen. According to the histologic type, the rates of total necrosis were 41% for telangiectatic tumors, 36% for fibroblastic tumors, 15% for osteoblastic tumors, and 3% for chondroblastic tumors. The authors concluded that in neoadjuvant therapy of osteosarcoma, the histologic response to preoperative treatment, which correlates with prognosis, depends on the effectiveness of the chemotherapy regimen and on some features intrinsically inherent to the tumor. These data should be considered when selecting the type of treatment (adjuvant or neoadjuvant) and the combinations of drugs to be used in preoperative treatment of patients with osteosarcoma.

Adolescent↗