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Biomedical subjects

N Santoro

Publications and source records attributed to N Santoro.

At least 91 records · Page 5Linked to original sources

Pulsatile gonadotropin-releasing hormone therapy for ovulatory disorders.

Pulsatile GnRH remains a physiologic method of inducing ovulation that is effective and safer than other parenteral preparations. Its lower rate of acceptance in the United States stands in curious contrast to its widespread usage in other countries as a second-line (postclomiphene) technique of choice for ovulation induction. In a high-technology era such as ours, women who may benefit from pulsatile GnRH therapy should not be forgotten. By far the most favorable results are obtained in women with primary or secondary hypothalamic amenorrhea. In such women, pregnancy rates appear comparable to those achieved with exogenous gonadotropins with a much lower risk of multiple pregnancy and ovarian hyperstimulation. These positive aspects, combined with the decreased need for clinical monitoring and the increased sense of control imparted to the patient, lead to the conclusion that women with uncomplicated hypothalamic-pituitary disorders are the ideal patient group to consider for therapy. The application of pulsatile GnRH therapy to other groups of women relies on limited data. By all means, women with polycystic ovarian syndrome who have not ovulated or conceived after other forms of treatment should be considered because reasonable pregnancy salvage can be obtained. We have noted a first-cycle successful pregnancy after failure of exogenous gonadotropins, with or without a superimposed GnRH agonist, and even in vitro fertilization with multiple embryo transfers. Before such invasive, high-technology procedures are entertained, it would appear prudent to consider this simple alternative in women with an overactive hypothalamic-pituitary axis, as seen in polycystic ovarian syndrome. Other ovulatory defects also may be amenable to treatment with pulsatile GnRH, but their practical usefulness will await further clinical study.

Ambulatory Care↗

Total rectal resection, colo-endoanal anastomosis and colic reservoir for cancer of the lower third of the rectum.

The treatment of low rectal cancer is still a widely debated topic in surgical oncology. From March 1990 to August 1991, 18 patients with tumors sited in the lower third of the rectum underwent a total rectal resection extended to the ano-rectal junction. As restorative procedure, a colic J-shaped pouch and a handsewn pouch-endoanal anastomosis was adopted. All the lesions were less than 8 cm from the anal verge; in 94.5% the distal tumor margin was located within 6.5 cm of the cutaneous edge. Histological clearance of the rectum cut edge was documented in all cases. Only one patient (Dukes C) relapsed four months later at the para-anastomotic level. No mortality or major complications related to surgical procedure were found. In 13 patients perfect continence was achieved and in 12 cases less than two bowel movements a day were recorded. No one complained of severe sexual dysfunction. All patients are still alive. The follow up ranged from 6 to 22 months (median: 12). This experience together with data obtained from last years' literature indicate that a conservative surgical procedure, as total rectal resection and colo-anal anastomosis, can be considered a feasible and radical option for treatment of low rectal cancer.

Adult↗

The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP).

A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6-12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.

Antigens, CD↗

Gonadotropin and inhibin concentrations in early pregnancy in women with and without corpora lutea.

We compared serum concentrations of immunoreactive inhibin, hCG, and FSH in normal women with those of two groups of women lacking endogenous luteal function. Twelve functionally agonadal, hypergonadotropic women with premature ovarian failure were given replacement ovarian steroids. Donor oocytes were fertilized in vitro with the husband's semen, and embryos were transferred into these women. A second group of 12 women were normogonadotropic but anovulatory, had undergone previously unsuccessful in vitro fertilization, and possessed cryopreserved embryos. These women were suppressed with a GnRH agonist before sex hormone replacement. Serum samples collected at weeks 2, 3, 4-6, 8-10, and 12-14 of pregnancy were measured for FSH, hCG, and immunoreactive inhibin. Data were compared with concentrations in normally ovulating women with well-established dates of conception. Sex steroid replacement hormone levels did not differ between the ovarian-failure and agonist-suppressed women and approximated that of normal cycles until pregnancy; thereafter, estradiol and progesterone levels remained higher than normal. Despite excessive steroid replacement, FSH remained higher in women with ovarian failure than in agonist-suppressed or normal women. On immunoassay, inhibin failed to show an early rise at 4-6 weeks of pregnancy in either group of aluteal women (0.52 +/- 0.05 ng/mL), whereas normal women demonstrated 0.9 +/- 0.05 ng/mL inhibin in their sera (P less than .001). By 8-10 weeks of pregnancy, women with ovarian failure demonstrated inhibin concentrations identical to those of normal women (1.2 +/- 0.1 and 1.2 +/- 0.15 ng/mL, respectively), whereas agonist-suppressed women lagged behind (0.7 +/- 0.1 ng/mL) (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Malignancies in children with human immunodeficiency virus type 1 infection. The Italian Multicenter Study on Human Immunodeficiency Virus Infection in Children.

Cancer has been closely associated with human immunodeficiency virus (HIV) infection but this is less frequent in children. Non-Hodgkin's lymphomas represent the most frequently reported single tumor. The authors report seven cases of malignant tumors resulting from the analysis of all (n = 1321) children enrolled in the Italian Register for HIV Infection in Children. Tumors were distributed as follows: non-Hodgkin's B-cell lymphoma (four cases); and Kaposi's sarcoma, hepatoblastoma, acute B-cell lymphoblastic leukemia (one case each). Hepatoblastoma had never been previously reported in HIV-infected children. Also in the current series, non-Hodgkin's B-cell lymphoma is the most frequent single tumor. Five of the seven cancers belonged to the B-cell line. All but one of the seven children have died. Specific chemotherapy was provided in three cases, with some clinical improvement. The treatment of malignancies in HIV-infected children is hampered by increased risk of opportunistic infections often fatal even in children with apparent remission from the tumor.

Burkitt Lymphoma↗

[Nuclear magnetic resonance and iron overload in thalassemia].

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.

Adolescent↗

Unbalanced coagulation-fibrinolysis potential during L-asparaginase therapy in children with acute lymphoblastic leukaemia.

Treatment of acute lymphoblastic leukaemia (ALL) with L-asparaginase (L-asp) may be associated with thrombotic complications, but the pathogenetic mechanisms of thrombus formation and persistence remain unclear. We studied the procoagulant activity (PCA) of peripheral blood mononuclear cells and some components of the plasma fibrinolytic system in 10 children with ALL undergoing remission induction therapy which includes L-asp. Mononuclear cells obtained 14 days after starting L-asp treatment generated significantly higher amounts of PCA (identified as tissue factor) than cells isolated before the first dose of L-asp and 7 days after the cessation of L-asp administration (p less than 0.01). Augmented PCA coincided with an increase in the plasma D-dimer. The plasma levels of type 1 plasminogen activator inhibitor were found significantly elevated during L-asp therapy (p less than 0.05), whereas plasminogen levels were markedly decreased (p less than 0.05). These findings suggest that, during the course of L-asp treatment, the coagulation-fibrinolysis balance is shifted towards promotion of fibrin formation and deposition. Although it remains to be conclusively established whether L-asp per se or the concurrent administration of multiple chemotherapeutic agents is responsible for these changes, the latter could contribute to the thrombotic complications associated with remission induction therapy for ALL.

Asparaginase↗

Efficacy and safety of intravenous pulsatile gonadotropin-releasing hormone: Lutrepulse for injection.

A multicenter trial was undertaken to assess the ability of pulsatile gonadotropin-releasing hormone to restore physiologic ovulatory function in women with diminished or absent pulsatile gonadotropin-releasing hormone secretion. In 109 women with primary and secondary hypothalamic amenorrhea, pulsatile gonadotropin-releasing hormone (Lutrepulse [gonadorelin acetate] for Injection) was extremely effective, resulting in ovulation in 91% and 96% of patients, respectively. Overall complications of intravenous line placement ranged from 0% to 11% (mean = 7%). A 12% incidence of multiple pregnancy was noted, and a single case of ovarian hyperstimulation was reported in a woman who also received clomiphene citrate. Pulsatile gonadotropin-releasing hormone treatment appears to be of at least comparable efficacy to human menopausal gonadotropins, with the added benefit of reduced overall risks for the patient with hypothalamic amenorrhea.

Adult↗

Pregnancy after an unsuccessful oocyte donation cycle.

Clearly, to provide adequate counseling to women with POF, information is critically needed concerning the background incidence of spontaneous improvement in ovarian function as well as carefully designed, controlled studies to evaluate the efficacy of presumed therapeutic intervention. The case presented herein underscores our lack of adequate information about this common reproductive disorder.

Adult↗

Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone.

Pulsatile GnRH therapy has yet to achieve widespread acceptance as an alternative to exogenous gonadotropin therapy in women with hypothalamic amenorrhea and complete GnRH deficiency. However, when a physiologically based replacement regimen of pulsatile GnRH is used, a high rate of ovulation and conception can be anticipated in patients with complete GnRH deficiency and hypothalamic amenorrhea. Women with polycystic ovarian syndrome may also benefit from pulsatile GnRH, although rates of ovulation are lower. Pretreatment with a GnRH agonist may improve these rates considerably, but experience is limited. Whether an iv or sc route of administration is chosen, a simplified clinical monitoring protocol can be created which requires a minimum of patient monitoring while assuring maximum safety. Seventy five nanograms per kg appears to be a reasonable initiating dose, with subsequent increases in those who do not respond. The frequency of GnRH administration is best based on the GnRH pulse frequency in normal women. However, further information is needed to determine whether such a variable frequency is clearly superior to a fixed frequency regimen. When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion. Most importantly, and as opposed to exogenous gonadotropin therapy, pulsatile GnRH can be administered by most physicians in the office setting without the necessity of on-line E2 monitoring. This feature will enable more patients to receive treatment by their local physicians, whereas exogenous gonadotropin therapy should be administered by appropriately equipped referral centers. In the future, further studies will be required to determine which other categories of patients might benefit from pulsatile GnRH.

Adult↗

In vitro protein production by the human endometrium.

Protein secretion by the human endometrium was studied in vitro in medium after incubation of tissue minces (n = 10) or glands isolated by collagenase digestion (n = 4) from tissues obtained at the time of curettage from normal women. Samples were incubated in a serum-free medium for 24 h at 38 degrees C in the presence of radiolabeled methionine. Dialyzed medium from each sample was subjected to two-dimensional gel separation, and detected by protein staining. Although 5 of the 27 proteins were considered to be present in the labeling experiments by only one of the three observers, there was agreement about the presence of the 22 others. In addition, the observers categorized the proteins into three groups for purposes of analysis: a) those associated with the follicular phase of the cycle; b) those associated with the luteal phase; and c) those not cycle-related. One protein triplet, labeled #27, showed a significant relation to the luteal phase (p less than 0.01). A complete lack of similarity between the pattern of labeled proteins obtained from the medium and labeled proteins obtained from lysates of cells incubated in the same experiments makes it unlikely that cellular lysis, as opposed to secretion, contributed to the pattern of proteins studied in these experiments.

Culture Techniques↗

[Monosomy 5 (-5), deletion of the long arm of chromosome 6 (6q) and acquisition of a chromosome 21 (+21) in a boy with acute leukemia at high-risk].

The chromosomal abnormality 6q-, associated with acute lymphatic leukemia, is often found both in T cell form and in non T non B cell forms. The absence of chromosome -5, frequently associated with acute non-lymphatic leukemia of the adult, has been rarely found in the acute non-lymphatic leukemia of the child. Trisomy of chromosome 21 is the most associated with acute non-lymphatic leukemia of the adult, has been rarely found in the acute non-lymphatic leukemia of the child. Trisomy of chromosome 21 is the most frequent alteration found in children and adult with acute lymphatic leukemia. In a child (aged 7) affected by acute lymphatic leukemia the karyotype analysis showed simultaneously the presence of the 3 above mentioned abnormalities. It will be important to evaluate later on how the association of monosomy 5 with the deletion of chromosome's 6 long arm and with an acquired chromosome 21, the last two being indexes of a favourable prognosis, can influence the clinical course of the disease.

Child↗

Alterations of the hypothalamic GnRH interpulse interval sequence over the normal menstrual cycle.

Luteinizing hormone (LH) is released in a pulsatile fashion from the anterior pituitary in response to hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Previous autocorrelation analysis of the sequence of interpulse intervals of LH secretion in normal men has supported the hypothesis that the underlying hypothalamic mechanism of GnRH secretion governing episodic LH release is a renewal process, indicating that hypothalamic "memory," if present, does not extend back further in time than the preceding secretory pulse. A similar analysis of pulsatile LH secretion was undertaken in 45 studies of normal women, obtained throughout the menstrual cycle. Analysis of these studies revealed a process consistent with renewal throughout the follicular and early luteal phases. However, this relationship appears to break down in the mid-to-late luteal phase, indicating that alternative feedback pathways provide an overriding influence on the underlying renewal process of hypothalamic GnRH secretion. Pulsatile progesterone secretion by the corpus luteum, which first emerges at this stage of the menstrual cycle, may be the agent responsible for this feedback.

Female↗

Characterization of bromoethanesulfonate-resistant mutants of Methanococcus voltae: evidence of a coenzyme M transport system.

Mutants of Methanococcus voltae were isolated that were resistant to the coenzyme M (CoM; 2-mercaptoethanesulfonic acid) analog 2-bromoethanesulfonic acid (BES). The mutants displayed a reduced ability to accumulate [35S]BES relative to the sensitive parental strain. BES inhibited methane production from CH3-S-CoM in cell extracts prepared from wild-type sensitive or resistant strains. BES uptake required the presence of both CO2 and H2 and was inhibited by N-ethylmaleimide and several reagents that are known to disrupt energy metabolism. The mutants showed normal uptake of isoleucine and were not cross-resistant to either azaserine or 5-methyltryptophan and, thus, were neither defective in general energy-dependent substrate transport nor envelope permeability. Both HS-CoM and CH3-S-CoM prevented the uptake of BES and protected cells from inhibition by it. We propose that M. voltae has an energy-dependent, carrier-mediated uptake system for HS-CoM and CH3-S-CoM which can also mediate uptake of BES.

Alkanesulfonates↗