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Biomedical subjects

A Gabriele

Publications and source records attributed to A Gabriele.

At least 37 records · Page 2Linked to original sources
PubMed1997

Intense neoadjuvant chemotherapy with cisplatin and epirubicin for advanced or bulky cervical and vaginal adenocarcinoma.

Twenty-two consecutive patients with bulky or locally advanced cervical or vaginal adenocarcinoma were treated with a neoadjuvant chemotherapy regimen consisting of nine weekly courses of cisplatin (50 mg/m2) and three courses of epirubicin (70 mg/m2) at Weeks 1, 4, and 7, followed by radical hysterectomy. Salvage radiotherapy was administered to inoperable patients, whereas postoperative treatment with irradiation or further chemotherapy was given to those with detection of risk factors at surgery. Three patients (14%) did not complete the planned courses of chemotherapy (one refused after the first administration, one had severe myelotoxicity, and one had severe nephrotoxicity). Twenty-one subjects received at least four courses of treatment and were therefore evaluable for response. We observed 4 clinically complete and 10 partial responses, accounting for an objective response rate of 67%. Eighteen subjects (82%) underwent surgery without serious complications. No histopathologic complete response was observed. The response rate is in the lower range observed with other regimens for squamous cell carcinoma. Although feasible, this regimen implies a significant risk of myelotoxicity. This enhanced toxicity may be justified only if balanced by long-term survival.

Adenocarcinoma↗
PubMed1997

Cisplatin-, epirubicin- and paclitaxel-containing chemotherapy in uterine adenocarcinoma.

PURPOSE: To evaluate the toxic effects and antitumour activity of a multidrug regimen with cisplatin, epirubicin and paclitaxel (CEP) as initial therapy in patients with uterine adenocarcinoma. PATIENTS AND METHODS: Forty-nine patients with histologically-confirmed diagnoses of locally advanced, recurrent or metastatic cervical or endometrial adenocarcinoma entered the study. Treatment consisted of epirubicin (E) given at 70 mg/m2 followed by paclitaxel (P) (175 mg/m2 over three hours) and cisplatin (C) (50 mg/m2), repeated every three weeks. Eligibility criteria also included age < or = 75 years, no previous chemotherapy, no previous radiotherapy to the tumour parameters, bidimensionally-measurable lesions, no previous or ongoing cardiac disease, and renal and liver function within normal limits. Complete blood cell counts were repeated weekly, and tumor response was assessed every three cycles. A maximum of eight courses was administered in responding patients. RESULTS: From January 1996 to January 1997, 30 patients with endometrial adenocarcinoma and 19 with cervical adenocarcinoma entered the study, for a total of 213 cycles of treatment. In patients with endometrial carcinoma the overall clinical and pathological response rates were 73% (95% CI, range 54%-88%) and 35% (95% CI, range 16%-57%) respectively; in patients with locally advanced cervical carcinoma the overall clinical and pathological response rates were 64% and 62%. WHO grade 3-4 neutropenia occurred in 61% of the patients, with one possible toxic death. Retreatment had to be delayed for at least one week because of persisting neutropenia in 34% of the patients. Mild peripheral neuropathy and stomatitis were observed in 46% and 23% of the patients. One patient presented acute congestive heart failure after the third cycle of treatment. CONCLUSION: The high antitumour activity and the good tolerability of CEP suggest that this regimen should be prospectively compared to standard combinations as initial treatment of advanced endometrial carcinoma.

Adenocarcinoma↗
PubMed1997

Treatment of fallopian tube carcinoma with cyclophosphamide, adriamycin, and cisplatin.

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.

Adult↗
PubMed1997

Modification of 35% carbon dioxide hypersensitivity across one week of treatment with clomipramine and fluvoxamine: a double-blind, randomized, placebo-controlled study.

The effects of short treatments (7 days) with clomipramine and fluvoxamine on the reactivity to inhalations of 35% CO2/65% O2 were compared in 39 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, randomized, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting treatment), 3, and 7. Patients on placebo did not report any significant changes in their reactivity to 35% CO2 across the three sessions, whereas patients on clomipramine and fluvoxamine reported a significant attenuation of the reactivity on day 7. These results indicate that treatments with clomipramine and fluvoxamine decrease hypersensitivity to 35% CO2 after a few days, suggesting a relevant role of the modulation of CO2 sensitivity by the serotonergic system in antipanic properties of these compounds.

Adult↗
PubMed1997

Second-look laparotomy in the management of fallopian tube carcinoma.

OBJECTIVE: To evaluate the role of second-look laparotomy following platinum-based combination chemotherapy in patients with fallopian tube carcinoma. METHODS: A retrospective chart review was conducted on 21 patients with tubal carcinoma who underwent second-look laparotomy following cytoreductive surgery and platinum-based combination chemotherapy. RESULTS: Thirteen patients (62%) were found to be free of disease at second-look operation. Neither stage nor grade were predictive of findings at second-look procedure. The absence of gross residual disease following primary surgery was the only predictor of disease-free status at second-look laparotomy (p < 0.01). With a mean follow-up of 49 months among the survivors, four (31%) of the patients with negative second-look laparotomy have had a recurrence. The median survival following a positive second-look laparotomy was 18 months (range 5-42 months). CONCLUSION: Second-look laparotomy provides useful prognostic information in patients with tubal carcinoma. The high rate of recurrent disease after negative second-look laparotomy, and the lack of an effective second-line treatment in patients with persistent disease, represent major criticisms of this procedure.

Adult↗
PubMed1996

Primary carcinoma of the fallopian tube. A retrospective analysis of 47 patients.

BACKGROUND: Fallopian tube carcinoma is a rare disease, and few data about prognostic factors are available in the literature. PATIENTS AND METHODS: The medical charts of 47 patients with primary carcinoma of the fallopian tube treated at our institution between 1982 and 1994 were reviewed. Age, stage, histologic grade, residual disease after surgery, peritoneal cytology and lymph-node involvement were evaluated for their prognostic impact in a univariate analysis. RESULTS: The mean age of the patients was 57.5 years and 19 of them (40%) had early-stage disease. Poorly differentiated tumors were diagnosed in 64% of the patients. Eleven of 20 patients (55%) submitted to surgical evaluation of lymph nodes had retroperitoneal involvement. Thirty-three patients received CAP chemotherapy following surgery, and the overall clinical response rate was 80%. Sixteen patients (34%) had recurrences within 8 to 50 months from diagnosis. Twenty patients (42.6%) are alive without disease, one patient is alive with tumor, and 26 patients (55.3%) died of the disease. The median survival for the group as a whole was 44 months, and the actuarial 5-year survival was 29%. In univariate analysis stage (I + II vs. III + IV), grade (G1 + G2 vs. G3) residual disease after surgery (less than 2 cm vs. greater than 2 cm). peritoneal cytology (negative vs. positive) and lymph-node metastases were all factors significantly affecting survival. CONCLUSIONS: Aggressive cytoreductive surgery followed by platin-based chemotherapy offer the possibility of long-term control of primary tubal carcinoma.

Adult↗
PubMed1996

Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer.

OBJECTIVE: To evaluate the antitumour activity of paclitaxel in patients with endometrial cancer pretreated with cisplatin, doxorubicin and cyclophosphamide (PAC). MATERIALS AND METHODS: Eligible patients had complete initial surgery, expected survival > or = 3 months, performance status < or = 1, measurable or evaluable disease. Paclitaxel was given over three hours at the dose of 175 mg/m2, repeated every 3 weeks. Tumour response was first evaluated after 3 cycles. A maximum of 10 cycles was given in responders. RESULTS: 19 patients entered the study and a total of 105 cycles were administered. Complete and partial responses were achieved in 2 and 5 patients, respectively, for an overall response rate of 37% (95% CI: 16%-62%). The response rate in patients refractory to platinum was 22%. One patient is alive without evidence of disease 16 months after the start of treatment. The most common side effects were mild to moderate myalgia and peripheral neuropathy, which occurred in 31% and 47% of patients, respectively. In only 1 patient treatment had to be discontinued because of severe myalgia. CONCLUSION: Paclitaxel is active in patients with endometrial cancer pretreated with PAC. Further studies with paclitaxel incorporated in the initial treatment for advanced disease are warranted.

Adult↗
PubMed1996

Brain metastases from a primary carcinoma of the fallopian tube.

Central nervous system involvement by gynecological tumors is considered an uncommon event. Among 47 patients registered for tubal carcinoma in our institution between 1982 and 1994, 3 (6.4%) developed brain metastases. The median age at the time of the diagnosis of central nervous system metastases was 61 years. The median interval between diagnosis of tubal cancer and documentation of brain involvement was 37 months. All deposits were diagnosed as contrast-enhancing, space-occupying lesions on computed tomography scans. Two patients had cerebral metastases, 1 had cerebellar involvement. The central nervous system was the only site of recurrent disease in 1 patient 37 months after diagnosis of tubal carcinoma. The median survival from diagnosis of brain metastases was 1 month. Attention should be paid to the possibility of distant metastases associated with tubal carcinoma in order to treat these patients promptly.

Adenocarcinoma↗
PubMed1996

Chromatin defects in normal and malformed human ejaculated and epididymal spermatozoa: a cytochemical ultrastructural study.

Cytochemical defects in chromatin were examined by transmission electron microscopy (TEM) after the staining by alcoholic phosphotungstic acid (PTA) of normal and malformed ejaculated spermatozoa from 35 male partners of infertile couples, and in six sperm samples retrieved from the caput epididymidis of men affected by obstructive azoospermia. PTA staining was also analysed in normal ejaculates of fertile men after incubation of the washed spermatozoa with dithiothreitol (DTT) to reduce disulfides to thiols, or with DTT followed by iodoacetamide, a blocking agent for thiol groups. PTA stained 63 (27-100)% of malformed heads and 25 (10-100)% of normal sperm heads (median (range) n = 35; P = 0.0001, Wilcoxon matched pairs test). The percentage of normal heads stained by PTA was negatively correlated with the percentage of heads of normal form, with condensed chromatin and a normal acrosome (Spearman r = 0.75; P = 0.0001), and positively correlated with the percentage of malformed heads after conventional TEM analysis (Spearman r 0.60; P = 0.0001). Staining with PTA in normal heads was not correlated with the presence of non-condensed chromatin in otherwise normal sperm heads evaluated by conventional TEM analysis. In spermatozoa recovered from the caput epididymidis, 15% of normal heads were stained with PTA, significantly fewer than in ejaculated sperm samples (P = 0.014). The reduction of disulfides to thiols was associated with PTA staining of all normal heads, and this was prevented by incubation with iodoacetamide. We conclude that PTA staining of the nuclei of human ejaculated spermatozoa may indicate a defect of chromatin condensation, owing to an excess of free thiol groups. The lower percentage of normal epididymal sperm heads that stained with PTA in cases of obstructive azoospermia compared with ejaculated sperm may be related to an overoxidation of thils owing to the ageing of spermatozoa.

Chromatin↗
PubMed1996

Molecular diagnosis of p53 mutations in gastric carcinoma by touch preparation.

Thirty-one tumor samples from selected cases of gastric carcinoma were analyzed for mutations of the p53 tumor suppressor gene. Template DNA was prepared according to the touch preparation procedure, which allowed us to isolate clusters of neoplastic cells out of a stromal cellular background to be used as a template in the amplification of target exons of the p53 locus. In our present study, by polymerase chain reaction/single strand conformation polymorphism analysis we give evidence of p53 mutations occurring in the DNA-binding core domain of the protein (exons 5 through 9), which are clustered in stages III and IV of the disease (six mutations out of seventeen samples; 35%). No p53 mutations were detected in fourteen gastric cancer samples at I and II stages. Beside the use of conventional molecular scanning procedures, our study proposes the application of the touch preparation method to increase the detection of genetic alterations in human solid tumors.

Base Sequence↗
PubMed1996

[Brain metastases in patients with malignant ovarian epithelial tumors].

From September 1983 to September 1994, 23 patients with Central Nervous System (CNS) metastases from ovarian carcinoma were observed in our institution. The mean age at the time of CNS metastases diagnosis was 59 years, the mean interval between diagnosis of ovarian carcinoma and documentation of the CNS involvement was 35 months. All the patients presented neurological symptoms. One patient had meningeal carcinomatosis; 22 presented parenchymal lesions. Nine patients had a single CNS lesion and 13 had multiple metastatic sites. CNS was the only site of disease in 9 patients, while 8 had concomitant extraperitoneal dissemination. Four patients received hormonal treatment with a mean survival (MS) of 3 months; 14 received radiotherapy alone (MS 5.5 months), 5 underwent surgical resection of solitary lesion followed by radiotherapy (MS 17 months). Number of CNS lesions, extent of the disease at time of CNS metastases and the treatment were the factors which significantly affected survival. The prognosis of these patients appears poor, however, early diagnosis followed by multimodal treatment may result in significant palliation an improve overall survival in a selected group of patients.

Adult↗
PubMed1995

Hypersensitivity to inhalation of carbon dioxide and panic attacks.

Thirteen healthy subjects with infrequent panic attacks and without agoraphobia who did not meet DSM-III-R criteria for panic disorder, 43 patients with panic disorder, and 43 healthy control subjects who never experienced panic attacks underwent one vital capacity inhalation of 35% CO2. Healthy subjects with infrequent panic attacks reacted similarly to patients with panic disorder and more strongly than healthy subjects who never experienced panic attacks. The results suggest that (a) subjects with sporadic unexpected panic attacks and patients with panic disorder belong to the same spectrum of vulnerability and (b) CO2 hypersensitivity might be a trait marker of panic attacks rather than of a clinical diagnosis of panic disorder.

Administration, Inhalation↗
PubMed1995

HIV infection and invasive cervical carcinoma in an Italian population: the need for closer screening programmes in seropositive patients.

OBJECTIVE: To evaluate in an Italian population the prevalence, characteristics at first diagnosis and outcome of HIV-seropositive individuals with cervical carcinoma referred to a tertiary-care institution. DESIGN: A retrospective evaluation of all patients referred for invasive cervical carcinoma from 1991 to 1994. SETTING: The departments of obstetrics and gynaecology, and radiotherapy at San Gerardo Hospital, University of Milan, Italy. PATIENTS: A total of 340 women were treated over a 3-year period (186 aged < 50 years). Six patients were found to be HIV-seropositive. INTERVENTIONS: Seropositive patients were treated according to current institutional protocols, irrespective of HIV status. Four underwent radiotherapy and two radical hysterectomy as primary treatment. RESULTS: Although five HIV-seropositive patients were known to be infected 13-81 months before diagnosis of cervical cancer, none had received a PAP smear in the last year and only one in the last 2 years. HIV patients were younger than general population (P = 0.02), with a significant history of intravenous drug use (P = 0.000001) and with more advanced disease (P = 0.04). Two HIV-positive patients also received polychemotherapy (one adjuvant and one salvage treatment) and both completed the planned treatment. Within 24 months two patients had died of cancer and one of AIDS; one is alive with AIDS and cancer and two are free of disease. CONCLUSIONS: This study confirms that in a southern European population, HIV-seropositive women present to tertiary-care institutions with more advanced disease and have a poorer prognosis than the general population. Strict screening programs for cervical dysplasia and cancer are warranted for HIV-seropositive patients.

Adult↗
PubMed1995

Age at onset of panic disorder: influence of familial liability to the disease and of childhood separation anxiety disorder.

OBJECTIVE: The authors investigated the relation of age at onset of panic disorder to liability to panic disorder and agoraphobia. METHOD: Two hundred thirty-one outpatients with panic disorder were compared with 131 surgical outpatients on demographic variables and familial risk of psychiatric disorders. The distribution of patients' ages at onset of panic disorder and several covariates were entered in a stepwise survival analysis. RESULTS: The patients with panic disorder had a significantly higher rate of childhood separation anxiety disorder and higher familial risks of panic disorder/panic disorder with agoraphobia and alcoholism. A family history of panic disorder with agoraphobia and the presence of childhood separation anxiety disorder influenced age at onset of panic disorder. CONCLUSIONS: Age at onset of panic disorder may reflect genetic penetrance, and separation anxiety disorder may be an individual predictor of earlier onset of panic disorder.

Adult↗
PubMed1994

Sperm-zona pellucida binding of human sperm is correlated with the immunocytochemical presence of proacrosin and acrosin in the sperm heads but not with the proteolytic activity of acrosin.

OBJECTIVE: To determine whether the sperm-zona pellucida (ZP) binding is related to the presence of immunoreactivity for proacrosin and acrosin and/or to the proteolytic activity of acrosin. SETTING: The Andrology Clinic, University of L'Aquila, Italy. PATIENTS: Thirty-five infertile couples and 15 men of proven fertility. INTERVENTIONS: Salt-stored unfertilized oocytes after IVF were inseminated with a mixture of equal numbers of test and fertile donor sperm after swim-up selection, respectively labeled with fluorescein or rhodamine. Total acrosin activity, the percent of sperm immunostained for proacrosin and acrosin, and the percent of sperm with oval heads were evaluated in fresh semen and after swim-up selection. MAIN OUTCOME MEASURES: Three zonae were used for each patient and sperm-ZP binding ratio (ZP ratio) was calculated as the total number of test sperm bound to ZP divided by the total number of control sperm bound to ZP. The ZP ratio was compared with the percent of live sperm immunostained for proacrosin and acrosin, with total acrosin activity and with the percent of sperm with oval heads after swim-up selection. RESULTS: The sperm-ZP binding ratio was correlated positively with the percent of sperm immunostained for proacrosin and acrosin and with the percent of sperm with oval heads, but not with acrosin activity. Ejaculates with immunostaining for proacrosin and acrosin > or = 55% of sperm (the mean value of infertile couples) and acrosin activity < 24 muIU/10(6) sperm (the mean value of infertile couples) (n = 8) had a ZP ratio > or = 0.5, whereas ejaculates with low immunostaining for proacrosin and low acrosin activity (n = 12) had a ZP ratio < 0.5. The difference between the ZP ratio of the two groups was highly significant. CONCLUSIONS: The ZP binding is related to the immunocytochemical presence of proacrosin and acrosin but not to the proteolytic activity of acrosin in human sperm, suggesting that egg recognition and proteolytic activity are independent functions of proacrosin and acrosin.

Acrosin↗