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Biomedical subjects

A R Scialli

Publications and source records attributed to A R Scialli.

At least 19 recordsLinked to original sources
PubMed1995

GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group.

OBJECTIVE: To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas. METHODS: This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel-group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater. RESULTS: Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group. CONCLUSION: Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterine-myoma volume, and in alleviating bleeding and other leiomyoma-related symptoms.

Adult↗
PubMed1995

Sustained benefits of leuprolide acetate with or without subsequent medroxyprogesterone acetate in the nonsurgical management of leiomyomata uteri.

OBJECTIVE: To determine the effectiveness of leuprolide acetate (LA) followed by medroxyprogesterone acetate (MPA) in the treatment of abnormal uterine bleeding attributed to leiomyomata uteri. DESIGN: Randomized, double-blinded, controlled clinical trial. SETTING: Human volunteers in an academic research environment. PATIENTS: Premenopausal women with abnormal uterine bleeding attributed to leiomyomata uteri. INTERVENTIONS: Subjects received 6 months of LA after which they were randomized to receive MPA or placebo. MAIN OUTCOME MEASURES: Control of bleeding as assessed by menstrual calendar and self-report; hematologic parameters (hemoglobin and ferritin); uterine size by ultrasonography. RESULTS: More than three quarters of subjects became amenorrheic on LA. The proportion of subjects with improvement in the bleeding abnormality after therapy was not different in the group receiving MPA compared with placebo; however, women who received MPA were less likely to be anemic after therapy than women receiving placebo. Among the women assigned to placebo, 55% experienced an improvement in bleeding compared with pre-GnRH agonist therapy that persisted after discontinuation of LA. There was a high dropout rate (51%), largely associated with failure of the regimens to control bleeding symptoms. CONCLUSIONS: Approximately one half of women with abnormal bleeding attributed to leiomyomata uteri have sustained symptomatic improvement after 6 months of therapy with LA even when only placebo therapy is given, although MPA decreases the incidence of anemia. Leuprolide acetate with or without subsequent progestin may be useful as a component of nonsurgical management of these tumors, with monitoring of hematologic status. The interpretability of these data is limited by the high rate of therapy discontinuation in women with abnormal bleeding of the severity studied here.

Adult↗
PubMed1995

Embryotoxicity of free and liposome-encapsulated taxol in the chick.

Taxol, an inhibitor of microtubule disaggregation, is used in the therapy of breast, ovarian, and other human malignancies. The toxicity of taxol administration is due in part to the polyoxyethylated castor oil (Cremaphor) vehicle in which it is administered; taxol embryotoxicity appears also to be partially attributable to vehicle toxicity. Liposome encapsulation is a novel vehicle for drug administration. The administration of taxol encapsulated in liposomes was evaluated in the chick embryo. Albumen injections of taxol doses up to 30 micrograms/egg were used to characterize dose-response curves for free and liposome-encapsulated taxol, compared to liposome-only and saline-injected control eggs. Sixty percent embryotoxicity (death or malformation) occurred with taxol doses of 1.5 micrograms/egg. A 20-fold higher dose was necessary to produce the same degree of toxicity with liposome-encapsulated taxol. Curve-fitting equations were used to estimate median effective doses (ED50s) and slope functions of the dose response curves. The ED50 for taxol was more than an order of magnitude lower than that for liposome-encapsulated taxol. Estimated slope functions for the two dosage forms of taxol were the same, suggesting similar mechanisms of toxicity. The toxicity of liposomes alone was low.

Abnormalities, Drug-Induced↗
PubMed1994

Taxol and embryonic development in the chick.

Taxol, an inhibitor of microtubule disassembly, is currently under investigation in the therapy of several human cancers. The current investigation was undertaken to characterize potential taxol developmental toxicity in chicks. On one of days 1-4 of incubation, taxol was administered in dimethylsulfoxide (DMSO) or olive oil in a range of doses, the highest of which produced a high incidence of early embryo death. Production of gross structural malformations was sporadic and occurred in vehicle-treated as well as taxol-treated embryos. A more common manifestation of taxol toxicity was a syndrome of visceral abnormalities, including regression of the vitelline circulation, dilatation of the atria, and hemorrhage in the left side of the head and thorax, often with decreased eye pigmentation. Regardless of the day of treatment, this syndrome occurred at 4.5-5 days. To investigate the possibility that taxol induced its effect through disruption of angiogenesis in the vitelline circulation, filters soaked in taxol were applied to the margin of the germ disc. No inhibition of vessel development was demonstrated. We conclude that taxol decreases the viability of embryos and that this impairment of survival precludes the development of birth defects. Solvent toxicity is an important confounder in the investigation of taxol embryotoxicity.

Abnormalities, Drug-Induced↗
PubMed1994

D-mannitol, a specific hydroxyl free radical scavenger, reduces the developmental toxicity of hydroxyurea in rabbits.

Hydroxyurea (HU) is a potent mammalian teratogen. Within 2-4 hours after maternal injection, HU causes 1) a rapid episode of embryonic cell death and 2) profound inhibition of embryonic DNA synthesis. A variety of antioxidants delays the onset of embryonic cell death and reduces the incidence of birth defects. Antioxidants do not block the inhibition of DNA synthesis, indicating that early embryonic cell death is not caused by inhibited DNA synthesis. We have suggested that some HU molecules may react within the embryo to produce H2O2 and subsequent free radicals, including the very reactive hydroxyl free radical. The free radicals could cause the early cell death; antioxidants are believed to terminate the aberrant free radical reactions resulting in lessened developmental toxicity. To investigate whether hydroxyl free radicals cause the early episode of cell death, pregnant New Zealand white rabbits were injected subcutaneously on gestational day 12 with a teratogenic dose of HU (650 mg/kg) in the presence or absence of 550 mg/kg of D-mannitol (Man), a specific scavenger of hydroxyl free radicals. Osmotic control rabbits received HU plus 550 mg/kg of xylose (Xyl, a nonactive aldose). At term, the teratologic effects of HU were ameliorated by Man as evidenced by decreased incidences of the expected limb malformations. Xyl exerted no demonstrable effect on HU teratogenesis. Histological examination of limb buds at 3-8 hours after maternal injection, showed that Man delayed the onset of HU-induced cell death by as much as 4 hours. Xyl had no effect. That Man acts within the embryo was shown by performing intracoelomic injections on alternate implantation sites with Man, Xyl, or saline followed by subcutaneous injection of the pregnant doe with HU. Embryos were harvested 3-8 hours later. Limb buds from saline- and Xyl-injected embryos exhibited the typical pattern of widespread HU-induced cell death at 3-4 hours, whereas Man-injected embryos did not exhibit cell death until 5-8 hours. These results are consistent with those reported for antioxidant-mediated amelioration of HU-induced developmental toxicity and with the hypothesis that hydroxyl free radicals are the proximate reactive species in HU-induced early embryonic cell death.

Animals↗
PubMed1994

Data availability in reproductive and developmental toxicology.

OBJECTIVE: To characterize the availability of reproductive and developmental toxicology information in the literature and the extent to which such information could produce alarm. METHODS: REPROTOX, a computerized data base, was evaluated as a surrogate for the available literature on reproductive and developmental toxicology. A review of 2528 summaries was performed and information in the summaries evaluated as nonreassuring or reassuring. RESULTS: Information on reproductive or developmental effects was available for about half of the summaries. Availability of information was greatest for pharmaceuticals (75% of summaries contained information) and was lowest for nonpesticide chemicals (36% of summaries contained information). Summaries contained nonreassuring information about two-thirds of the time. Information based on human data was variably available according to type of agent, ranging from a low of 5% of pesticide summaries to 88% of vitamin summaries. CONCLUSIONS: Counseling efforts depend on a literature base in which information is missing half the time and in which animal data may be the only available source of information. Information is available more often for pharmaceuticals than for other classes of agents.

Abnormalities, Drug-Induced↗
PubMed1993

Leuprolide acetate and bone mineral density measured by quantitative digitized radiography.

Quantitative digitized radiography uses low-energy photons to measure bone density with precision not available in older techniques. Using this method, lumbar spine density was evaluated in 12 women before and after 6 months of therapy with LA. A 2.9% decrement in mean bone density was documented. The reproducibility of quantitative digitized radiography suggests that this small degree of bone mineral loss is a real phenomenon and not an artifact of measurement. The clinical significance of this degree of bone mineral loss has yet to be established.

Adolescent↗
PubMed1992

Salmonella sepsis and second-trimester pregnancy loss.

Salmonella can produce bacteremia and disseminated disease, including infection of the intrauterine contents and fetal death. Published experience with salmonella infection in pregnancy has involved typhoid; however, nontyphoid gastroenteritis may also produce sepsis and fetal loss. We present a case of second-trimester fetal death associated with group C1 salmonella sepsis. The literature suggests that early diagnosis and treatment of salmonella infection during gestation is associated with a good pregnancy outcome. We recommend that pregnant women with diarrheal illnesses be evaluated by stool culture for salmonella infection.

Adult↗
PubMed1992

Advances in reproductive toxicology.

Research in reproductive toxicology has relied on several animal models as well as on the more difficult-to-perform human studies. In animals, ovarian toxicity is being investigated in more detail, with investigation of characteristics of reversibility. Epidemiology studies using time-to-pregnancy techniques have been useful in identifying potential at-risk populations for further study. Male toxicology research has concentrated on defining normal sperm parameters in experimental animals and in men, particularly when those parameters are evaluated by computer-assisted techniques.

Animals↗
PubMed1990

Perfluorocarbon-based medium for culture of the early chick embryo heart.

In an attempt to prolong the survival of the explanted early chick embryo heart, hearts at stages 10 to 28 were cultured in supplemented Dulbecco's modified Eagle's medium with or without the perfluorocarbon, perfluorotributylamine. The perfluorocarbon was added to the standard culture medium in a 50:50 (vol/vol) mixture. Explants were evaluated daily and were harvested for light microscopy after 2 to 10 d in culture. The tubular shape of the explants was generally maintained for 2 d in culture, after which the hearts became dilated or spherical. Beating was noted in some of the explants on Day 2 in culture but not thereafter. Microscopic evaluation showed patchy areas of necrosis in all explants by Day 3, although large areas of viable epithelioid cells were documented as long as 7 d after explanation. Stage 16 to 18 hearts cultured in the presence of perfluorocarbon were more likely to maintain tubular architecture on microscopy than hearts cultured in standard medium. Hearts cultured from later stages showed no improvement in appearance with the presence of perfluorocarbon and there was a suggestion of increased necrosis in later-stage explants cultured with perfluorocarbon for 4 d. Further modification of the culture system will be required to prolong explant survival and development beyond 2 d.

Animals↗