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Biomedical subjects

N Santoro

Publications and source records attributed to N Santoro.

At least 109 records · Page 6Linked to original sources
PubMed1986

Cytochrome b and FAD content in polymorphonuclear leucocytes in a family with X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD), an immunodeficiency syndrome characterized by extreme susceptibility to bacterial infections, is due to a defect of the respiratory burst in human phagocytes. NADPH oxidase, the enzyme that catalyzes the reduction of oxygen and the release of oxidative radicals, was studied in polymorphonuclear leucocytes (PMNs) in a family affected by an x-linked inheritance form at high penetrance of the disease. The contents of cytochrome b, suggested as the terminal component of the oxidase electron transport chain, and FAD, the hypothetical proximal component of the chain, were determined in patients and in carriers. Cytochrome b showed the typical behaviour of x-linked CGD: total absence in patients, intermediate values in carriers. FAD content evaluated on plasma membranes was less decreased than cytochrome b. Carriers also showed a decrease of this flavoprotein. Cytochrome b and FAD contents were compared to NBT test and superoxide production: a clear correlation was observed for the cytochrome b, but FAD plasma membrane evaluation could also be an interesting tool for the metabolic characterization of the disease in patients and in carriers.

Adult↗
PubMed1986

Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone.

Hypogonadotropic hypogonadism (HH) is a clinical syndrome occurring in both sexes which has long puzzled clinicians due to the apparent paradox of nonfunctioning gonads in the face of normal or only slightly lowered levels of circulating gonadotropins. Using frequent sampling of gonadotropin levels as an index of hypothalamic GnRH secretion, we have examined the hypothesis that this group of disorders represents a spectrum of abnormal patterns of the pulsatile release of endogenous GnRH. After a broad, normative data base was established in both men and women for purposes of comparison, it appears that quantifiable abnormalities of GnRH secretion are discernible in both males and females with HH. These abnormalities include a total absence of GnRH secretion, defects of the amplitude and frequency of its secretion, and altered bioactivity of the gonadotropins released. In addition, physiological regimens of hypothalamic replacement therapy with exogenous GnRH, which are fashioned to mimic the normal frequency of endogenous GnRH secretion, result in complete normalization of reproductive function and fertility in hypogonadotropic subjects of both sexes. Thus, the heterogeneous nature of HH, as well as its favorable clinical and biochemical responses to GnRH, suggest that the basic defect in this family of disorders involves a partial or complete inability to synthesize and/or release GnRH from the hypothalamus in a manner compatible with physiological reproductive function. Conversely, these findings imply that maintenance of a physiological amplitude and frequency of endogenous GnRH secretion appear to be essential for normal reproductive function.

Adolescent↗
PubMed1986

Intravenous administration of pulsatile gonadotropin-releasing hormone in hypothalamic amenorrhea: effects of dosage.

Eighteen women with well characterized hypothalamic amenorrhea underwent 30 cycles of pulsatile GnRH treatment in an effort to examine the role of GnRH dosage in pituitary and ovarian responses. GnRH was administered iv at 2 doses (25 and 100 ng/kg bolus) at a physiological range of frequencies (90 and 60 min) in the follicular phase of the induced cycles. After demonstration of ovulation by ultrasound and clinical parameters, the frequency of GnRH administration was progressively slowed from every 60 min to every 90 min and then to every 240 min to mimic the slowing of endogenous LH secretion that occurs during the luteal phase in normal women. The results of these induced cycles were compared to those of 62 ovulatory cycles from normal women. Overall clinical and biochemical results revealed the following. Patients receiving doses of 25 ng/kg GnRH successfully ovulated only 80% of the time, with recruitment of a single dominant follicle. Two of 5 patients became pregnant. Peak estradiol levels were significantly lower than normal [261 +/- 33 (+/- SE) vs. 342 +/- 11 pg/ml, respectively; P less than 0.02]. Integrated luteal phase progesterone production was also significantly reduced in the 25 ng/kg group compared to normal (78 +/- 17 vs. 145 +/- 8 ng/ml/entire luteal phase, respectively; P less than 0.02). All women receiving bolus doses of 100 ng/kg GnRH ovulated; maturation of multiple follicles occurred in 5 of 20 cycles, and 6 of 7 women conceived. Peak estradiol values were significantly higher than those in either normal women or the 25 ng/kg group (478 +/- 48 pg/ml; P less than 0.02 for both), with integrated luteal phase progesterone levels significantly higher than those in patients receiving the 25 ng/kg dose (196 +/- 25 ng/ml/luteal phase; P less than 0.02). This study demonstrates that ovulation and fertility can be achieved with a physiological frequency regimen of pulsatile GnRH administration using bolus doses of both 25 and 100 ng/kg in women with hypothalamic amenorrhea; the 25 ng/kg dose of GnRH may represent a threshold of stimulation of the pituitary-ovarian axis and recreates cycles with an inadequate luteal phase; and a 100 ng/kg dose of GnRH may well cause a supraphysiological stimulation of the pituitary-gonadal axis.

Amenorrhea↗
PubMed1986

Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle.

To characterize the spectrum of pulsatile gonadotropin secretion during the course of the normal menstrual cycle, we studied normal women during 51 ovulatory cycles. Plasma gonadotropin concentrations were measured at 10-min intervals for 20-24 h during the early, mid-, and late follicular phases and the early, mid-, and late luteal phases. LH data series were analyzed using 2 different computer-assisted algorithms for pulse detection. The LH interpulse interval decreased during the follicular phase (FP) from 94 +/- 4 (+/- SEM) min in the early FP (EFP) to 71 +/- 4 min by the late FP (LFP; P less than 0.001). The estimation of LH pulse frequency in the EFP was significantly affected by slowing of episodic LH secretion during sleep. In the luteal phase (LP), the LH interpulse interval progressively increased from 103 +/- 8 min in the early LP (ELP) to 216 +/- 39 min by the late LP (LLP; P less than 0.001). Sleep-associated slowing of episodic LH secretion also occurred in the ELP. The mean LH pulse amplitude in the EFP (6.5 +/- 0.4 mIU/ml) decreased significantly by the midfollicular phase (MFP; 5.1 +/- 0.8 mIU/ml; P less than 0.05) and increased once again by the LFP (7.2 +/- 1.2 mIU/ml). LH pulse amplitude was highest in the ELP (14.9 +/- 1.7 mIU/ml), decreased by the midluteal phase (MLP) to 12.2 +/- 2.0 mIU/ml, and declined further by the LLP to 7.6 +/- 1.1 mIU/ml (P less than 0.001 vs. ELP). FSH secretion was significantly (P less than 0.05) correlated with LH secretion at time lags of 0-10 min in 82% of the studies. These results indicate the following. 1) In the EFP and ELP, the frequency of gonadotropin pulsations is reduced at night in association with sleep. 2) The frequency of LH secretion increases from the EFP to MFP and LFP. 3) LH pulse amplitude decreases in the MFP, suggesting enhanced negative feedback of estrogen on the hypothalamic-pituitary axis and/or a decrease in GnRH secretion at this stage. 4) A progressive reduction of LH pulse frequency and amplitude occurs during the LP which is correlated with the duration of exposure of the hypothalamic-pituitary axis to progesterone. 5) A close relationship exists between secretion of LH and FSH, suggesting a common stimulatory factor for both gonadotropins.

Adolescent↗
PubMed1986

Gonadotropin-releasing hormone (GnRH) physiology in men and women.

The combined approach used in studies of GnRH secretion provided a complimentary array of techniques with which to establish the program of amplitude (dose) and frequency of GnRH secretion in the physiologic state. Normative data in men and women were useful in formulating frequency estimates, which could then be applied to the task of replacement of GnRH in deficient (IHH) individuals. Comparison of the results of therapy with these 'ablation-replacement' models then allowed to arrive closer to the true amplitude or dose of exogenous GnRH required to duplicate the physiologic ideal. In addition to providing insight into the neuroendocrine control of reproduction, these applications provided treatment of various reproductive disorders in men and women. Further expansion of the efforts into other potential defects of endogenous GnRH secretion will ultimately uncover those disorders amenable to therapy.

Adolescent↗
PubMed1985

Acute and chronic hepatitis in childhood leukemia: a multicentric study from the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).

The incidence of acute and chronic liver damage and its relation to hepatitis B virus (HBV) infection was evaluated in 164 consecutive children with acute leukemia seen in ten Italian hemato-pediatric units. Thirteen out of 164 children (7.9%) had acute hepatitis (AH) during treatment, while 8/90 (8.8%) showed an acute exacerbation of liver damage within 6 months after therapy withdrawal. Seven of the 13 children with AH while on therapy were HBsAg positive. In 12/13 cases, liver disease progressed to chronicity. Five of eight children who developed AH after completion of treatment were HBsAg positive. Eighty-nine patients (54.2%) developed biochemical evidence of chronic hepatitis during therapy; 48/89 were followed after cessation of treatment and 33 of them showed persisting evidence of liver cell necrosis. Thirty-three out of 133 children (24.8%) tested for serum HBsAg were found positive: 26 (78.7%) of them developed chronic hepatitis. Sixty-four out of 133 patients were evaluated after cessation of treatment: Chronic hepatitis persisted in 16/22 HBsAg-positive (72.7%) and in 17/42 HBsAg-negative (40.4%) children during follow-up. The outcome of these liver diseases after treatment withdrawal did not differ significantly in relation to HBV serology, suggesting that viral rather than toxic agents were responsible for liver damage also in most HBsAg-negative patients. The high incidence of chronic HBV infection in children with leukemia found in this multicentric study could suggest a need for active immunization with HBV vaccine, but the efficacy of such approach in this clinical setting is still to be validated.

Acute Disease↗
PubMedDate not supplied

Postnatal development of prekallikrein (Fletcher factor) in man.

The aim of the present study was to determine the concentration of plasma prekallikrein in healthy infants during the first year of life. Prekallikrein levels evaluated by a chromogenic substrate assay were low in the first 15 days of life and increased progressively from the third week of life, reaching normal adult values after the third month of life. The low levels of prekallikrein during the neonatal age reflect the impaired ability of liver cells to synthesize proteins.

Adult↗
PubMedDate not supplied

Engineered liposomes and virosomes for delivery of macromolecules.

In order to utilize virosomes or proteoliposomes for the delivery of drugs or macromolecules to specific pathologic target cells we elaborated a system to shuttle drugs to solid tissue (liver) as well as to the macrophages, a crucial cellular compartment of the immune system. Using virosomes prepared from the P3HR1 strain of Epstein-Barr virus, we demonstrated that these particles fused with human hepatocarcinoma cell line Li7A and therefore might be used as drug vectors. Furthermore, we report that proteoliposomes prepared by reconstituting in a cocktail of phosphatidylserine-phosphatidylcholine the anion transporter band 3 protein markedly increased the phagocytic activity of macrophages in culture. This could represent a new device to be used as a drug delivery system to enhance specific macrophagic functions.

Anion Exchange Protein 1, Erythrocyte↗
PubMedDate not supplied

Attempts to use liposomes and RBC ghosts as vectors in drug and antisense therapy of virus infection.

Selective targeting of drugs or oligonucleotide for the treatment of viral diseases or cancer is the objective of new strategies that pursue therapy optimization and reduction of toxicity. In this work we report two protocols based on encapsulation of anti-human immunodeficiency virus drugs within targeted liposomes or erythrocytes. Both have been shown to be effective for the specific delivery of drugs or oligonucleotide in the treatment of viral infection.

Adenine↗
PubMedDate not supplied

Research on the mechanisms of premature ovarian failure.

As many as 5% of women may experience menopause at or before age 45 (POF). Four causes are known for POF: (1) Genetic. Clear-cut X chromosome deletions, particularly those in the critical region, result in truncation of reproductive lifespan. Creation of a central genetic data bank for women with POF may assist in defining the genetic contribution to this condition. (2) Autoimmune. POF coexists with virtually all of the permutations of the autoimmune polyglandular failure syndromes, most often in linkage with antithyroid and antiadrenal antibodies. (3) Iatrogenic. Iatrogenic POF results from repeated ovarian surgeries, or from the underlying disease that led to the surgery. (4) Environmental. Environmental toxicants are difficult to pinpoint, but evidence suggests that galactose consumption is linked to early menopause. We investigated the possibility that POF represented premature endocrine aging that was generalized, rather than specifically targeted to the ovary. Detailed investigation of the gonadotropin-releasing hormone-luteinizing hormone system, the somatotrophic axis, the adrenal glucocorticoid and androgen axes, and the prolactin axis have led us to conclude that women with POF are not prematurely aged in any endocrine system other than the ovary. Basic research on how the ovary interacts with the immune system, particularly in the early stages of oogenesis, how the oocyte and follicle interact in fetal life, and how follicles might be protected from damage in the case of immune self-attack are all fruitful avenues of clinically applicable work that may lead to treatments for this most vexing reproductive disorder.

Adult↗
PubMedDate not supplied

An electronic menstrual cycle calendar: comparison of data quality with a paper version.

OBJECTIVES: This pilot study compared a prototype electronic menstrual calendar on a handheld computer with a paper calendar for data quality and participants' perceptions. DESIGN: Twenty-three women completed identical information about menstrual bleeding and symptoms using paper and electronic calendars for 1 month each. RESULTS: Use of the paper calendar resulted in more missing data than the electronic calendar for bleeding characteristics (13% vs. 4%) and symptoms (35% vs. 4%). The electronic calendar's ability to log data entries revealed retrospective entry for 61% of the data. Total data entry and cleaning time was reduced by 81% with the electronic calendar. Overall, participants preferred the electronic (70%) to the paper (22%) calendar. CONCLUSIONS: Data quality with conventional paper calendars may be poorer than recognized. The data-logging feature, unique to the electronic calendar, is critical for assessing data quality. Electronic menstrual calendars can be useful data collection tools for research in women's health.

Computers↗
PubMedDate not supplied

The lived experience of premature ovarian failure.

OBJECTIVE: To describe the lived experience of women who have been diagnosed with idiopathic premature ovarian failure (POF). DESIGN: Phenomenology was used to achieve the purpose. Women were asked to share their experiences in living with premature ovarian failure during an approximately 1-hour interview. The interviews were tape-recorded, transcribed, and analyzed for emergent themes. SETTING: Interviews were conducted in the participants' homes and in a conference room in a hospital. PARTICIPANTS: The six participants were drawn from a multicultural sample of women with idiopathic POF. RESULTS: The women in this study expressed anger at their health care providers for their perceived lack of quality care they had experienced and at the insurance industry for its lack of reimbursement for fertility interventions; they expressed depression and sadness at the prospective outcome of the diagnosis, mixed emotions regarding their significant others, and sadness and resignation about their menopausal symptoms. CONCLUSIONS: Health care providers who create an environment in which women and their significant others will feel supported in asking questions, be assured that their concerns are taken seriously, and be provided with the physical and emotional resources they need can help these women to continue to build and live their lives.

Adaptation, Psychological↗
PubMedDate not supplied

Italian guidelines for the management of infectious complications in pediatric oncology: empirical antimicrobial therapy of febrile neutropenia.

The Italian Association for Paediatric Haematology and Oncology prepared a guideline document aimed at unifying and rationalising as much as possible the management of febrile neutropenia in children with cancer, because of the potential impact of these procedures on hospital costs and on the development of antibiotic resistance. Before starting anti-infective therapy, at least 2 blood cultures, a throat swab, urine-culture, and cultures from any suspected infected site, should be performed. Routine chest X-rays at onset of febrile neutropenia are probably not necessary, in absence of respiratory signs. At the present time, the safer option probably remains the combination of a beta-lactam and an aminoglycoside, and treating febrile neutropenia outside of hospital should be considered an investigational approach. The choice of the most appropriated regimen for each institution should be based also on the local bacteriological statistics and patterns of bacterial resistance. Antibiotic toxicity and cost should be other important factors. Every subsequent addition or substitution of antibiotics should be based on objective signs of clinical deterioration. The only accepted empirical modification is empirical antifungal therapy, while the empirical addition of a glycopeptide antibiotic cannot be recommended.

Anti-Bacterial Agents↗
PubMedDate not supplied

Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent epithelial ovarian cancer: a phase II clinical study.

AIMS AND BACKGROUND: The optimal salvage therapy for recurrent ovarian carcinoma has not been clearly established. Response to second-line chemotherapy is low, with a short median survival (8.8-15 months). We investigated the effect of an aggressive approach consisting of surgery followed by intraperitoneal drug delivery and local hyperthermia. PATIENTS AND METHODS: In a phase II clinical study, 27 patients with advanced/recurrent ovarian carcinoma were treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Median patient age was 53 years (range, 30-67) and mean follow-up was 17.4 months (range, 0.3-36.0). Patients had been surgically staged and heavily pretreated with cisplatin-based, taxol-based or taxol/platinum-containing regimens. Nineteen (70%) patients were cytoreduced to minimal residual disease <2.5 mm. The intraperitoneal hyperthermic perfusion was performed with the closed abdomen technique, using a preheated polysaline perfusate containing cisplatin (25 mg/m2/L) + mitomycin C (3.3 mg/m2/L) through a heart-lung pump (mean flow of 700 mL/min) for 60 min in the hyperthermic phase (42.5 degrees C). RESULTS: Two-year overall survival was 55%. Median times to overall progression and local progression were 16 months and 21.8 months, respectively. Variables that affected the overall survival or time to progression were as follows: residual disease (P = 0.00025), patient age (P = 0.04), and lag time between diagnosis and cytoreductive surgery + intraperitoneal hyperthermic perfusion (P = 0.04). Treatment-related morbidity, mortality and acute toxicity (grade II-III) rates were 11%, 4% and 11%, respectively. Eight (89%) of 9 patients had ascites resolution. CONCLUSION: Our results suggest that cytoreductive surgery + intraperitoneal hyperthermic perfusion is a well-tolerated, feasible and promising alternative in the management of selected patients with recurrent ovarian cancer, but further randomized controlled studies are needed in order to confirm our findings.

Adult↗
PubMedDate not supplied

Isolated pelvic perfusion for the treatment of unresectable primary or recurrent rectal cancer.

Between May 1990 and December 1995, 16 patients with primary or recurrent unresectable rectal cancer were treated by isolated pelvic perfusion. All patients had been previously treated and were considered unsuitable for surgery or further systemic chemotherapy or radiotherapy. The treatment was based on a perfusion lasting 90 min at 40.5 C degrees with 5-fluorouracil, mitomycin-C and mitoxantrone. Whenever technically feasible (10 cases), continuous intraarterial chemotherapy (through a Medtronic device with a catheter in the inferior mesenteric artery) was administered postoperatively. Two complete responses and 2 partial responses were observed; 8 other patients showed stable disease. One patient did not show any response. Finally, 3 patients for various reasons were not assessable. All patients experienced immediate relief of pain. No major side effects directly related to isolated pelvic perfusion were recorded; a transitory bone marrow depletion was observed in all cases. In conclusion, isolated pelvic perfusion is useful in inoperable disease of the pelvis by reliably relieving pain and thereby improving the patients quality of life.

Adult↗
PubMedDate not supplied

Treatment of recurrent sarcoma of the extremities by isolated limb perfusion using tumor necrosis factor alpha and melphalan.

BACKGROUND: 24-60% of patients with soft tissue sarcoma shows local recurrences after treatment of the primary tumor. The event is associated with a high incidence of macroscopic or microscopic metastases and a poor survival. Our goal is to preserve a patient's functional limb by treating such cases with isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rHu TNF-alpha) and melphalan, which have demonstrated a potent antitumor activity in vivo and in vitro studies. METHODS: During the period November 1991 to November 1995, 10 patients with unresectable recurrent soft tissue sarcoma of the limb were treated by ILP at intermediate hyperthermia (40-40.5 degrees C) with rHu TNF-alpha and melphalan. Two patients also received recombinant interferon gamma (rIFN-gamma) before and during ILP. We used a range of 2-4 mg for rHu TNF-alpha and 50-100 mg of melphalan. rIFN-gamma was administered on days -2 and -1 (15 x 10(6) IU) subcutaneously and the same dose was injected in the arterial line during ILP. RESULTS: No perioperative surgical complication was observed. Local toxicity was moderate (grade I or II); general toxicity was observed in 6 patients (2 grade I and 4 grade III). Complete response was obtained in 7 cases; 2 patients had a partial response and finally 1 was a nonresponder and showed local progression, which required surgical amputation. Tumor necrosis (observed in 5 cases) was maximal in 4 patients (80-100%) and absent in the patient who had local progression. CONCLUSIONS: The results we obtained with the treatment of soft tissue sarcoma confirm the efficacy of ILP as a limb-sparing methodology for unresectable recurrences. Furthermore, rHu TNF-alpha and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.

Adult↗
PubMedDate not supplied

Peritoneal carcinomatosis: feature of dissemination. A review.

Peritoneal carcinomatosis is a common event that develops in the natural history of many neoplastic diseases, representing a major problem encountered in cancer, management. Peritoneal seedings are often associated with neoplastic ascites resulting in a source of significant discomfort to the patient. Considered in the past as a terminal condition, peritoneal carcinomatosis was approached during the last two decades as a curable disease. The introduction of cytoreductive surgery or peritonectomy in the treatment of peritoneal neoplastic diseases drastically changed the natural history of peritoneal carcinomatosis. Another technique that showed an important impact on disease control is intraperitoneal hyperthermic perfusion, one of the most fascinating treatments of peritoneal carcinomatosis that results in an impressive increase in overall survival and quality of life in treated patients with low morbidity. This review illustrates the modality of dissemination of peritoneal carcinomatosis in relation to the primary tumor site and grade of malignancy. Peritoneal carcinomatosis is a term used to define an advanced stage of many abdominal neoplastic diseases that differ in biologic aggressiveness and prognosis. The different presentation of peritoneal carcinomatosis in relation to a different primary tumor and different grade of malignancy strongly influences the potentially therapeutic radical approaches using new and advanced modalities like cytoreductive surgery and intraperitoneal hyperthermic perfusion.

Chemotherapy, Cancer, Regional Perfusion↗