Biomedical subjects

A Papageorgiou

Publications and source records attributed to A Papageorgiou.

At least 37 records · Page 2Linked to original sources

PubMed1998

Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.

In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.

Administration, Inhalation↗

PubMed1998

Developmental regulation of the soluble form of insulin-like growth factor-II/mannose 6-phosphate receptor in human serum and amniotic fluid.

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/MPR) has a specific binding site for IGF-II, a fetal mitogen. In rodents, IGF-II/MPR expression declines dramatically after birth. To see whether such developmental regulation occurs in humans, we studied the ontogeny of the soluble form of IGF-II/MPR in amniotic fluid (AF) and serum. Phosphomannan-affinity purified AF IGF-II/ MPR was a single band of approximately 220 kDa, like the band in serum, and it bound IGF-II with affinity identical to that of the membrane-associated form. By quantitative immunoblot, the soluble IGF-II/MPR in serum and AF was found to undergo developmental regulation that parallels that of the rodent, although it is much less pronounced quantitatively. The highest levels are seen in midgestation, decreasing at term in both serum and AF. In serum, they further decline to one-third of the preterm levels by adulthood. As part of characterizing AF IGF-II binding, we also show that the prominent high-molecular mass IGF-II-binding protein in preterm AF is GPC3, a protein of the glypican family, recently cloned because its mutations predispose to Wilms' tumor. For the first time, we show that IGF-II binding to this protein is saturable, and therefore specific. These findings should promote understanding of the role of IGF-II and its binding proteins in human development.

Amniotic Fluid↗

PubMed1997

Palladium(II) complexes of 2-acetylpyridine N(4)-methyl, N(4)-ethyl and N(4)-phenyl-thiosemicarbazones. Crystal structure of chloro(2-acetylpyridine N(4)-methylthiosemicarbazonato) palladium(II). Synthesis, spectral studies, in vitro and in vivo antitumour activity.

The reactions of 2-acetylpyridine N(4)-methyl, (HAc4Me) N(4)-ethyl (HAc4Et) and N(4)-Phenyl (HAc4Ph) thiosemicarbazone with palladium(II) were studied. The ligands and the palladium(II) complexes have been characterized by spectroscopic techniques. The structure of [Pd(Ac4Me)Cl] has been determined by single-crystal x-ray diffraction. The protonation constants of HAc4Me and HAc4Et, Ka1 and Ka2, were determined by spectrophotometry. The effect of palladium compounds on DNA synthesis of P388 and L1210 cell cultures is also reported. Some of these compounds increased the life span of mice bearing tumors.

Animals↗

PubMed1997

A randomized trial of a program of early postpartum discharge with nurse visitation.

OBJECTIVE: Our purpose was to compare an early postpartum discharge program versus standard postpartum care. STUDY DESIGN: A randomized controlled trial in a 637-bed university hospital included 175 healthy women recruited at 32 to 38 weeks gestation from physicians' offices and sonograms. Experimental intervention consisted of discharge 6 to 36 hours post partum with nursing care available by telephone or at home at 34 to 38 weeks' gestation and at < or = 48 hours and at 3, 5, and 10 days post partum. The control included a postpartum stay of 48 to 72 hours and standard follow-up. RESULTS: At 1 month no significant differences were seen in perceived maternal competence (Experimental-Control = 4.3 points [95% confidence interval-7.7 to 16.3]), infant weight gain (1.2 gm/ day [-2.8 to 5.2]); identification of significant neonatal hyperbilirubinemia (rate ratio 0.50 [0.10 to 2.51]), infant utilization of health services (rate ratio 0.88 [0.45 to 1.73]), or predominant breast-feeding (adjusted odds ratio 1.25 [0.88 to 1.75]). Program participants did have significantly less frequent infant bilirubin testing (rate ratio 0.39 [0.17 to 0.94]). The program also enhanced perceived maternal competence in recent immigrants (26.9 points [2.7 to 51.5]). CONCLUSIONS: Early postpartum discharge coupled with prenatal, postnatal, and home contacts leads to no apparent disadvantage and may yield benefits for some mothers and infants.

Community Health Nursing↗

PubMed1997

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant.

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575-1450 g; gestational age: 26.8 weeks, range: 22-31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean +/- SEM) show that apparent volume of distribution (AVd) was 62.1 +/- 3.9 ml/kg, plasma t1/2 beta was 30.5 +/- 4.2 h, elimination rate constant (Kel) was 0.032 +/- 0.004 h-1, plasma clearance was 2.06 +/- 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 +/- 11.1 mg/l. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 +/- 54.5 mg/l and 113.6 +/- 58.2 mg/l, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 +/- 0.39%, n = 26) compared to adult plasma protein (mean +/- SE = 98.73 +/- 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.

Age Factors↗

PubMed1997

Outcome of small-for-gestational age and appropriate-for-gestational age infants born before 27 weeks of gestation.

OBJECTIVE: To evaluate the consequences of being small-for-gestational age at extremely low gestational age. METHODOLOGY: Comparison of two historical cohorts of small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) infants born between 24 and 26 6/7 weeks of gestation (gestational age estimated by early ultrasound at 16 to 18 weeks). Data were collected retrospectively on 191 successive admissions to the neonatal intensive care unit between January 1, 1983, and December 31, 1992. These included: demographic and maternal information, delivery mode and condition at birth, mortality, neonatal intensive care unit morbidities (respiratory distress syndrome, intraventricular hemorrhage, patent ductus arteriosis [PDA], chronic lung disease [CLD], retinopathy of prematurity [ROP], necrotizing enterocolitis, infection), nutrition, and length of hospitalization. RESULTS: Forty-one (21%) of the 191 infants were classified as SGA. Those with congenital anomalies (10% in the SGA and 2% in the AGA group) were excluded from further analysis. Despite a similar rate of respiratory distress syndrome (50%), the SGA infants had a greater rate of failure of indomethacin treatment for PDA closure (54% vs 32% for AGA), a higher risk for CLD defined as a need for supplementary oxygen at 36 weeks (65% vs 32% for AGA), a more prolonged need for oxygen supplementation and ventilatory support (94 days vs 68 days for AGA and 58 days vs 40 days for AGA, respectively). SGA infants were also at greater risk for developing severe ROP (stage >/=III) (65% vs 12% for AGA). CONCLUSIONS: For infants born before 27 weeks, being small-for-gestational age confers additional risks for severe morbidity, ie, PDA ligation, CLD, and ROP.

Fetal Growth Retardation↗

PubMed1997

Attitudes toward obstetrics training. Residents surveyed at McGill University and University of Montreal.

OBJECTIVE: To determine family medicine residents' attitudes toward family practice training in obstetrics and neonatology before and after implementation of a modified obstetrics curriculum at McGill University (MG). DESIGN: Two-group pretest and posttest. Fifty-seven respondents, 31 at MG, 26 at University of Montreal (UM), were case matched as first-year and second-year residents. SETTING: Departments of Family Medicine at MG and UM. PARTICIPANTS: Family medicine residents at MG and UM. INTERVENTION: A modified obstetrics curriculum was introduced at MG (study group); no modifications were introduced at UM (control group). First- and second-year residents' attitudes toward the adequacy of training were assessed through responses to a questionnaire administered in July 1992 and July 1994. MAIN OUTCOME MEASURES: Changes in response scores before and after implementation of the modified curriculum. RESULTS: Repeated multivariate analysis of variance (MANOVA) showed respondents believed family practice obstetrics training was adequate in general, but that family practitioners were inadequately trained in emergency obstetric skills. Scores for items assessing neonatology skills increased significantly in the MG group after the intervention. CONCLUSIONS: Residents' overall confidence in their obstetrics training did not appear to improve, but this might be due to a time lag between curriculum modification and attitudinal change. McGill residents' confidence in neonatology skills improved significantly after curriculum modification.

Adult↗

PubMed1996

Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants.

OBJECTIVE: To test whether early postnatal (0 to 3 hours) intravenous administration of ibuprofen will prevent patent ductus arteriosus (PDA) in preterm neonates. DESIGN: Prospective sequential controlled trial with three treatment arms. SETTING: Level 3 perinatal-neonatal intensive care nursery. PATIENTS: Thirty-four premature newborn infants born from February to August 1993 with a mean birth weight of 913 g (range, 565 to 1460 g) and gestational age of 26.9 weeks (range, 22.4 to 31.0). INTERVENTION: Infants were consecutively assigned within 3 hours of age to treatment with either one dose of ibuprofen lysine (10 mg/kg intravenously) followed by 5 mg/kg per dose intravenously at 24 and 48 hours of age (n = 12), one dose of ibuprofen lysine (10 mg/kg intravenously; n = 11), or saline (n = 11). OUTCOME VARIABLES: Primary outcome variable was the presence of ductus arteriosus by echocardiography and clinical assessments at 3, 7, and 21 days of life. Secondary outcome variables included presence of intraventricular hemorrhage, renal function, ventilatory and oxygen needs, hematologic changes, gastrointestinal function, time to full enteral feeding, duration of hospitalization, and age at discharge. RESULTS: The three groups of patients were comparable in birth weight, gestational age, antenatal administration of betamethasone, and other perinatal characteristics. Ibuprofen treatment significantly reduced plasma levels of prostaglandins, and the levels remained low for 72 hours in newborns who received three doses of the drug. The incidence of PDA and other variables did not differ between patients who received a single dose of ibuprofen and those given saline. However, compared with the saline-treated newborns, babies who received three doses of ibuprofen had no PDA (0/12 vs 7/11 for saline; P < .02), had lower daily mean airway pressures (mean +/- SD, 5.2 +/- 1.1 cm H2O vs 8.3 +/- 2.8 cm H2O for saline; P < .02) and better oxygenation index (2.6 +/- 0.6 vs 4.7 +/- 1.8 for saline; P < .02) at the end of the first week of life, and required fewer days of ventilation (25 +/- 14 days vs 44 +/- 26 days for saline; P < .03). Babies given three doses of ibuprofen tended to tolerate full oral feedings earlier (35 +/- 19 days vs 56 +/- 34 days for saline; P = .09), had shorter duration of hospitalization (71.2 +/- 22.6 days vs 127.3 +/- 74.7 days for saline; P < .05), and were discharged to home at an earlier postconceptional age (37.8 +/- 2.0 weeks vs 44.8 +/- 9.8 weeks for saline; P < .05). ibuprofen treatment in this phase I trial was not associated with any apparent early neurological, intestinal, renal, hepatic, or hematologic complications. CONCLUSIONS: Administration of three doses of ibuprofen within 3 hours after birth in preterm neonates reduced the incidence of PDA without causing notable early adverse drug reactions in this phase I trial. Early closure of the ductus arteriosus was also associated with better respiratory outcome and earlier discharge from the hospital.

Analysis of Variance↗

PubMed1996

[Noninvasive mucinous cystic pancreas carcinoma with a 16-year course].

A 26-year-old woman was operated on because of a suspected infectious pseudocyst of the pancreas. A large cyst was found on the body of the pancreas. During laparotomy a biopsy specimen was taken from the cystic wall, but no evidence of a tumor was obtained. On the basis of these intraoperative findings, a cystogastrostomy was performed and the patient had an uneventful postoperative course. The patient presented 8 years later with a recurrent cyst and was operated. As there was a suspicion of a cystic neoplasm, total resection of the cyst was performed. Based on the histological findings a noninvasive mucinous cystadenocarcinoma of the pancreas was diagnosed. We believe that from the beginning this cyst was a noninvasive mucinous cystadenocarcinoma. Following the complete resection the clinical course was favorable for 8 more years without evidence of recurrence or metastases.

Adenocarcinoma, Mucinous↗

PubMed1996

A randomized, controlled evaluation of two commercially available human breast milk fortifiers in healthy preterm neonates.

OBJECTIVE: To evaluate the added nutritional value of the two commercially available human breast milk fortifiers: Similac Natural Care (NC) and Enfamil Powder (EP). DESIGN: A randomized controlled evaluation in healthy preterm neonates. SETTING: Neonatal Intensive Care Unit, Royal University Hospital, Saskatoon, Saskatchewan, and Neonatal Intensive Care Unit, Jewish General Hospital, Montreal, Quebec, Canada. SUBJECTS: Healthy preterm infants admitted to and cared for in the aforementioned neonatal intensive care units. INTERVENTIONS: Healthy preterm neonates who were receiving expressed breast milk from their own mothers were supplemented with human milk fortifiers (NC and EP) per manufacturer's recommendations. MAIN OUTCOME MEASURES: Gestational age and birth weight, gender, and race. At entry to and exit from the study, serum concentrations of albumin, protein, calcium, phosphorus, and alkaline phosphatase. The age at which the supplements were added and the number of days the infant remained in the hospital. Daily weight gain, head circumference, length, and height were also measured. STATISTICAL ANALYSES PERFORMED: Student's t test was used to test the differences between the groups and within the groups at entry to and exit from the study. Fisher's exact test was used to determine differences in race, size, and gestational age in each group. When necessary, a chi 2 test was used to analyze the preponderance of either sex in each group. A Wilcoxon rank test was applied to the true exit date to determine whether the bias was comparable in each group. RESULTS: The mean (+/- standard error) gestational age and birth weight were similar in both groups: 30 +/- 0.3 weeks and 1,314 +/- 40 g, respectively, for NC vs 29.6 +/- 0.35 weeks and 1,262 +/- 45 g, respectively, for EP. At entry to the study, values for the NC group (N = 29) were albumin 31 +/- 1.2 g/L, serum protein 48 +/- 1.4 g/L, calcium 2.4 +/- 0.03 mmol/L, phosphorus 1.85 +/- 0.08 mmol/L, alkaline phosphatase 347 +/- 27 IU/L. The values for the EP group (N = 30) were albumin 32 +/- 0.9 g/L, serum protein 49 +/- 1.4 g/L, calcium 2.4 +/- 0.4 mmol/L, phosphorus 1.9 +/- 0.1 mmol/L, alkaline phosphatase 420 +/- 34 IU/L. At the study exit, the values for the NC group were albumin 30 +/- 0.7 g/L, serum protein 45 +/- 0.9 g/L, calcium 2.4 +/- 0.3 mmol/L, phosphorus 1.96 +/- 0.07 mmol/L, and alkaline phosphatase 371 +/- 23 IU/L. The values for the EP group were albumin 32 +/- 1.0 g/L, serum protein 46.0 +/- 1.4 g/L, calcium 2.5 +/- 0.03 mmol/L, serum phosphorus 2.2 +/- 0.1, and alkaline phosphatase 367 +/- 27 IU/L. No significant differences were observed between groups at entry to and exit from the study. However, in the EP group the alkaline phosphatase decreased significantly (P = .02) from entry to exit and calcium increased significantly during the same period compared with the NC group (P = .003). The mean daily weight gain was 33 +/- 0.7 g for the NC group and 31 +/- 1 g for the EP group. The weekly gain in head circumference and body length were also similar in both groups: approximately 1 cm/week. Both groups tolerated the fortifiers well. APPLICATIONS/CONCLUSIONS: These findings suggest that both products provide the additional nutritional support necessary for optimal overall postnatal growth in healthy preterm infants. The differences in calcium and alkaline phosphatase may be due to the differences in vitamin D content in fortifiers 88 IU/100 mL in mixed NC vs 270 IU/100 mL in mixed EP. This observation calls for careful monitoring of calcium and alkaline phosphatase values and possible adjustments of vitamin D intake when fortifiers are used for extended periods.

Alkaline Phosphatase↗

PubMed1996

Childrearing attitudes among parents of very low birth weight and normal birth weight children.

The childrearing attitudes of parents of school-age children born at weights under 1500 g (VLBW) were compared with those of parents of age- and gender-matched children born at full term (NBW) to determine whether there were systematic differences between the two groups and whether parental attitudes were associated with child outcomes. Parents completed a self-report measure of childrearing attitudes and provided information on the child's health since birth. The children were given measures of IQ and self-concept, and their teachers rated their social and academic competence. Neonatal morbidity and subsequent need for hospitalization were unrelated to parental attitudes. Parents of VLBW children reported less use of guilt as a control strategy. They were also less child-centered, particularly if their children had chronic respiratory or ear-nose-throat problems. Greater parental warmth, less control through guilt, and less parental detachment were associated with more socially competent behavior and more positive self-concept in 9-year-old VLBW children.

Adaptation, Psychological↗

PubMed1996

A case of relapsing Kawasaki disease and review of the literature.

A review of the literature was carried out on the occasion of one case of Kawasaki disease in a small infant aged 3 months which relapsed 17 years later. Kawasaki disease is of unknown aetiology and mainly affects children under 5 years of age. It is manifested as a necrotizing vasculitis with aneurysms of the coronary arteries and the proximal medium size arteries. One hundred and fifteen thousand cases have been reported up to the present date, an incidence of 6-11/100,000 children. The evidence of coronary aneurysms range from 20-30%, while peripheral aneurysms are rare. Eighteen cases of peripheral ischemia have been reported in the international literature. The diagnosis is clinical and treatment remains symptomatic (anti-inflammatory and anticoagulant). Thrombolytic and anticoagulant management is applied in acute heart attack, and surgical bypass in chronic ischemia. Reversion of the aneurysms is observed in 60% of the cases, while relapse of the disease is possible years or decades later. Death is due to thrombosis of the coronary or rupture of the coronary or distal aneurysm. For this reason, regular fellow-up of the patients is recommended, according to the guidelines for long-term management of patients with Kawasaki disease.

Adolescent↗

PubMed1996

In vivo binding of the radioiodinated peptide YIGSR on B16 melanoma cells.

It has been reported that metastatic melanoma cell lines selectively bind in vitro with the synthetic laminin pentapeptide tyrosyl-isoleucyl-glycyl-seryl-arginine (YIGSR). The aim of this study was to investigate whether the same peptide can bind on melanoma cells in vivo as well. Iodine-125-labeled YIGSR was administered to B16 melanoma-bearing animals. Microscopic autoradiography of tumor and organ sections taken 24 h after peptide administration showed that the peptide did accumulate on the surface of certain tumor cells. The peptide binding cells were frequent in metastatic sites and tumors grown for 24 days and rare in tumors grown for 10 days. A similarly radiolabeled control pentapeptide (peptide DRLKY) did not bind to any tumor cell. It is suggested that the YIGSR binding tumor cells may represent a distinct melanoma cell population with a high metastatic potential.

Animals↗

PubMed1995

Maternal asthma and idiopathic preterm labor.

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.

Adult↗

PubMed1995

Maternal anthropometry and idiopathic preterm labor.

OBJECTIVE: To assess the etiologic role of maternal short stature, low pre-pregnancy body mass index (BMI), and low rate of gestational weight gain in idiopathic preterm labor. METHODS: We carried out a three-center case-control study of 555 women with idiopathic onset of preterm labor (before 37 completed weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases with early preterm labor (before 34 completed weeks) and cases with recurrent preterm labor (before 37 completed weeks plus a history of prior preterm delivery or second-trimester miscarriage). Controls were matched to cases by race and smoking history. All subjects responded in person to questions about height, pre-pregnancy weight, gestational weight gain, and obstetric and sociodemographic histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight gain demonstrated excellent test-retest reliability, with intra-class correlation coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses, women with a height of 157.5 cm or less had an increased risk of idiopathic preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09-2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI 1.16-2.62). Conditional logistic regression models containing all three anthropometric variables and controlling for parity, marital status, language, age, and education yielded virtually identical point estimates and CIs. CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of gestational weight gain may lead to shortened gestation by increasing the risk of idiopathic preterm labor.

Anthropometry↗

PubMed1995

Comparative study on cytogenetic damage induced by homo-aza-steroidal esters in human lymphocytes.

The effect of P[N,N-bis(2-chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-N-methyl-17 alpha-aza-D-homo-5 alpha-androstan-17-one (compound 3) and 3 beta-hydroxy-17 alpha-aza-D-homo-5 alpha-androstane (compound 2) on sister-chromatid exchange (SCE) frequencies and on human lymphocytes proliferation kinetics was studied. The results are compared with those of the P[N,N-bis(2-chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-17 alpha-aza-D-homo-5 alpha-androstan-17-one (compound 1). All compounds were found to be active in inducing markedly increased SCE rates and cell division delays. A correlation between potency for SCE induction, effectiveness in cell division delay and previously established antitumour activity of these compounds was observed.

Androstanes↗

PubMed1995

Comparative study of SCE induction and cytostatic effects by homo-azasteroidal esters of N,N-bis(2-chloroethyl)aminobenzoic acid in human lymphocytes.

The effect of homo-azasteroidal esters of benzoic acid mustard isomers and the 4-methyl derivatives, which have steroidal lactams as a biological basis, on cytogenetic damage was studied. Twenty compounds were comparatively studied, on a molar basis, as regards their ability to induce sister-chromatid exchanges (SCEs) and cell division delays. A correlation between potency for SCE induction, effectiveness in cell division delay and previously established antitumor activity of these compounds was observed.

Antineoplastic Agents↗

PubMed1995

Inhibition of angiogenesis, tumour growth and metastasis by the NO-releasing vasodilators, isosorbide mononitrate and dinitrate.

1. The effect of the nitric oxide (NO)-producing nitrovasodilators isosorbide mononitrate (ISMN) and isosorbide dinitrate (ISDN) were assessed on (a) the in vivo model of angiogenesis of the chick chorioallantoic membrane (CAM) and (b) on the growth and metastatic properties of the Lewis Lung carcinoma (LLC) in mice. 2. Isosorbide 5-mononitrate (ISMN) and isosorbide dinitrate (ISDN), inhibited angiogenesis in the CAM dose-dependently. ISMN was more potent in inhibiting this process. Both compounds were capable of completely reversing the angiogenic effect of alpha-thrombin. These effects of ISMN and ISDN on angiogenesis were comparable to those previously observed with sodium nitroprusside which generates NO non-enzymatically. 3. Mice, implanted intramuscularly with LLC, received daily i.p. injections of ISMN for 14 days resulting in a significant decrease in the size of the primary tumour and a reduction in the number and size of metastatic foci in the lungs. ISDN had a similar but less pronounced effect than that observed with ISMN. 4. Addition of ISMN or ISDN to cultures of bovine, rabbit and human endothelial cells and to cultures of LLC cells had no effect on their growth characteristics. 5. These results indicate that ISMN and ISDN inhibit angiogenesis and tumor growth and metastasis in an animal tumour model. The possibility should therefore be considered that these nitrovasodilators which are widely used therapeutically and have well characterized pharmacological profiles, may also possess antitumour properties in the clinic.

Animals↗