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Biomedical subjects

M Greenwald

Publications and source records attributed to M Greenwald.

At least 37 records · Page 2Linked to original sources
PubMed1996

Nicotine and cotinine in maternal and neonatal hair as markers of gestational smoking.

OBJECTIVE: To determine the extent of fetal exposure to cigarette smoke, which cannot be clearly extrapolated from maternal reports, the authors measured concentrations of nicotine and cotinine in maternal and neonatal hair and corroborated these measures with maternal history and measures of pregnancy outcome. DESIGN: Prospective study of 94 mother-infant pairs. SETTING: Newborn nurseries of two hospitals in Toronto. PARTICIPANTS: 93 mothers, including active smokers, passive smokers and nonsmokers, and their newborns (including one set of twins). INTERVENTIONS: Hair collected from mothers and neonates shortly after birth was analysed by radio-immunoassay. MAIN OUTCOME MEASURES: Maternal data on demographic variables, obstetric history, diseases, drugs taken and smoking; infant data on demographic variables and birth indicators (gestational age, method of delivery, weight, head circumference, length, presence of meconium, need for resuscitation, need for special care and congenital malformations); hair concentrations of nicotine and cotinine. RESULTS: Neonates of active smokers had more adverse outcomes than other infants, including lower birth weight, smaller head circumference, shorter length and more perinatal complications. The difference was statistically significant. Amounts of cotinine extracted from mothers' and infants' hair showed significant differences among active smokers, passive smokers and non-smokers. When other people in the household and the mother smoked, neonatal hair concentrations of nicotine and cotinine in the infants were threefold higher than those in the infants of mothers who were the only smokers in their households. CONCLUSIONS: Hair concentrations of nicotine and cotinine are a powerful biological marker of the extent of intrauterine exposure to tobacco smoke.

Adolescent↗
PubMed1995

Steroid hormone effects on the proliferation of human ovarian surface epithelium in vitro.

OBJECTIVE: The histologically bland-appearing epithelium of the human ovary is responsible for approximately 90% of ovarian cancers. Capitalizing on our ability to propagate this tissue in vitro, we have begun to characterize the steroid hormone responsiveness of the human ovarian surface epithelium. STUDY DESIGN: Primary cultures of the human ovarian surface epithelium are characterized as normal epithelium on the basis of morphologic features, normal karyotype, and immunohistochemistry demonstrating AE1/AE3 cytokeratin positivity and factor VIII negativity. Estrogen and progestin receptors were quantitatively analyzed with a standard receptor-ligand binding assay. Cellular proliferation in response to 1 x 10(-7) mol/L 17 beta-estradiol, progesterone, dihydrotestosterone, and dexamethasone were assessed by means of cell counts and a tetrazolium-based colorimetric assay. RESULTS: Scatchard analyses identified 8.8 x 10(3) estrogen receptors per cell in the premenopausal human ovarian surface epithelium cells, whereas the postmenopausal cells were negative for estrogen receptors. A total of 3.2 to 13.0 x 10(3) progestin receptors per cell was identified, with variable progestin receptor expression in the postmenopausal cells. No significant effect on cell growth could be demonstrated as a result of any of the steroid hormones investigated under the study conditions. CONCLUSIONS: Expression of estrogen and progestin receptors in human ovarian surface epithelium cells may be related to menopausal status. Steroid hormones, however, did not influence cell proliferation under these experimental conditions.

Cell Division↗
PubMed1995

Optic pathway tumors in children: the effect of neurofibromatosis type 1 on clinical manifestations and natural history.

OBJECTIVE: To distinguish the clinical manifestations and natural history of optic pathway tumors (OPT) associated with neurofibromatosis type 1 (NF-1 OPT) from that of OPT not associated with NF-1 (non-NF-1 OPT). METHODS: Two groups of children with OPT were compared: (1) 17 children with NF-1 OPT who were followed prospectively, and (2) 19 children with non-NF-1 OPT who were identified retrospectively by a review of medical records. RESULTS: Precocious puberty was a common initial sign in the children with NF-1 OPT (5/17), and was not found in any patients without NF-1. In contrast, children with non-NF-1 OPT had symptoms attributable to increased intracranial pressure (12/19 and nystagmus (5/19); these symptoms were not found in any patient with NF-1. Decreased visual acuity at the time of diagnosis was common in both groups. There was no significant difference between the children with NF-1 OPT and those with non-NF-1 OPT as to age at diagnosis or sex distribution. Optic nerve involvement was more common in NF-1 (p < 0.001). Both isolated and bilateral optic nerve tumors were found exclusively in children with NF-1, whereas chiasmal (p = 0.016) and optic tract involvement (p = 0.001) were more common in those with non-NF-1 OPT. Radiographic evidence of hydrocephalus was found in none of the children with NF-1 OPT compared with 79% of the non-NF-1 OPT group. Progressive disease was seen in 12% of patients with NF-1 OPT compared with 63% of those with non-NF-1 OPT. CONCLUSIONS: Differences exist between NF-1 OPT and non-NF-1 OPT both at the time of diagnosis and during follow-up. Optic pathway tumors caused by NF-1 and non-NF-1 OPT have different biologic properties that distinguish both their initial clinical manifestations and their natural history.

Astrocytoma↗
PubMed1994

The tyrosine kinase activity of the C-erbB-2 gene product (p185) is required for growth inhibition by anti-p185 antibodies but not for the cytotoxicity of an anti-p185-ricin-A chain immunotoxin.

Our previous studies have demonstrated that 7 of 10 IgG antibodies against distinct epitopes on the extracellular domain of the c-erbB-2 gene product (p185) inhibit the anchorage-independent growth of SKBr3 human breast-cancer cells that overexpress this transmembrane tyrosine kinase growth-factor receptor. Two of 7 growth-inhibitory antibodies also block the binding and function of the gp30 and p75 c-erbB-2 ligands. In this report we have studied phosphorylation of p185 and different intracellular substrates after binding of antibodies that do or do not inhibit tumor-cell growth. A correlation has been found between antibodies that inhibit growth and the intensity of tyrosine phosphorylation of p185. At late intervals, serine phosphorylation of at least 3 intracellular substrates is increased preferentially by growth-inhibitory antibodies. To test the importance of p185 kinase activity more critically, NIH3T3 cells were transfected with an expression vector containing the full-length human c-erbB-2 gene (cell line 17313), c-erbB-2 with deletion of the kinase region from codons 751-979 (cell line 9309) or c-erbB-2 with deletion of most of the intracellular domain from codons 684-1255 (cell line 9310). Unconjugated antibodies inhibited anchorage-independent growth of 17313 cells as well as SKBr3 cells, but did not inhibit growth of either 9309 or 9310 cells. In contrast, the cytotoxic effect of anti-p185-ricin A chain (RTA) conjugates was comparable for 17313, 9309 and 9310. The tyrosine-kinase activity of p185 is required for growth inhibition mediated by unconjugated anti-p185 antibodies, but not for the cytotoxic activity of anti-p185-RTA immunotoxins.

3T3 Cells↗
PubMed1994

Hair concentrations of nicotine and cotinine in women and their newborn infants.

BACKGROUND: To date, no biological markers have been identified that can predict the extent of fetal exposure to the toxic constituents of cigarette smoke. A variety of xenobiotic agents have been shown to accumulate in growing hair. PATIENTS AND METHODS: We measured maternal and neonatal hair concentrations of nicotine and cotinine in 94 mother-infant pairs. Mothers who were active smokers, nonsmokers, and passive smokers and their infants were included. RESULTS: Mothers who were active smokers (n = 36) had mean (SEM) hair concentrations of 19.2 (4.9) ng/mg for nicotine and 6.3 (4.0) ng/mg for cotinine, significantly higher than concentrations in nonsmokers (n = 35) (1.2 [0.4] ng/mg for nicotine and 0.3 [0.06] ng/mg for cotinine, P < .0001). Infants of smokers had mean hair concentrations of 2.4 (0.9) ng/mg for nicotine (range, 0 to 27.3 ng/mg) and 2.8 (0.8) ng/mg for cotinine (range, 0 to 12.2 ng/mg), significantly higher than concentrations in infants of nonsmokers (0.4 [0.09] ng/mg for nicotine and 0.26 [0.04] ng/mg for cotinine, P < .01). Mothers with passive smoke exposure and their infants (n = 23) had significantly higher hair concentrations of nicotine (3.2 [0.8] ng/mg for mothers and 0.28 [0.05] ng/mg for infants) and cotinine (0.9 [0.3] ng/mg for mothers and 0.6 [0.15] ng/mg for infants) than nonsmoking mothers and their infants (P < .01). There was a significant correlation between maternal and neonatal hair concentrations of nicotine (r = .49, P < .001) or cotinine (r = .85, P = .0001). CONCLUSIONS: This is the first biochemical evidence that infants of passive smokers are at risk of measurable exposure to cigarette smoke. Hair accumulation of cigarette smoke constituents reflects long-term systemic exposure to these toxins and therefore may be well correlated with perinatal risks.

Adult↗
PubMed1994

Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study.

To assess the natural history of optic pathway tumors (OPT) in children with neurofibromatosis type 1 (NF-1), from January 1985 through May 1993 we performed a prospective, longitudinal study of OPT in an unselected population of children with NF-1. Of 227 children with NF-1 seen in a specialty clinic, 176 (77%) underwent neuroimaging. Children in whom tumors were identified were followed closely by both repeated neuroimaging and ophthalmologic examinations to detect tumor growth or visual deterioration. Thirty-three children (19%) were found to have OPT at a median age of 4.2 years. The median age of children who had ophthalmologic complaints was significantly lower than that of children who had no such complaints (1.9 vs 5.3 years; p < 0.001). Although eight tumors were discovered because of ophthalmologic complaints or evidence of precocious puberty, 25 children (76%) were free of symptoms at the time of diagnosis. Twenty-one children (64%) had normal ophthalmologic findings at diagnosis; six children, all with chiasmal tumors, had previously unrecognized decreased visual acuity. Only three children (9%) had evidence of either tumor growth or deteriorating vision after diagnosis; the median duration of neuroimaging follow-up was 2.4 years (range, 0.2 to 7.2 years) and of ophthalmologic examinations 3.4 years (range, 0.2 to 8.1 years). All symptomatic OPT were diagnosed before 6 years of age. We conclude that OPT rarely progress during the next few years in children with NF-1 once the OPT have been discovered. The utility of screening neuroimaging for OPT in symptom-free children with NF-1 appears very limited.

Adolescent↗
PubMed1994

Prevalence of fetal exposure to cocaine in Toronto, 1990-1991.

There has been an increasing use of cocaine in North America among women of reproductive age. The potential effects of cocaine on the fetus have raised serious concerns about the health of large numbers of children exposed in utero to the drug. Using neonatal hair and urine tests for benzoylegconine (BE), we quantified the incidence of fetal exposure to cocaine among 600 babies born in 3 nurseries in Toronto from 1990-91. A total of 37 babies (6.25%) tested positive for cocaine exposure by either hair test, urine test, or both. The hair test detected 33 cases and failed to identify 4 babies who had low urine concentrations of BE. The urine test failed to identify 76% of the cases. In downtown Toronto, the overall rate of fetal exposure to cocaine was 12.5% (25/200), significantly higher than in the 2 suburban nurseries (3%; 12/400). Babies are born with hair which has grown during the last trimester of pregnancy; hence, our analysis identifies women who have used cocaine long after they became aware of pregnancy. Our figures translate to more than 5,000 babies annually in the greater Toronto area who are cared for postnatally by mothers regularly using cocaine. Because history and urine testing during delivery fail to identify the majority of these cases, most of these children are not likely to receive the appropriate medical and social services and follow-up.

Adolescent↗
PubMed1993

Polysymptomatic syndromes and autonomic reactivity to nonfood stressors in individuals with self-reported adverse food reactions.

This study compared symptom reports and cardiovascular reactivity of a group of 24 individuals recruited from the community who reported a cognitive or emotional symptom caused by at least one food (food-sensitivity reporters, FSR) vs those of 15 controls (C) without a history of food, chemical, drug, or inhalant sensitivities. The main findings were: 1) FSR indicated sensitivities not only to foods, but also to environmental chemicals, drugs, and natural inhalants, as well as significantly more symptoms than C in multiple systems; 2) more FSR than C noted recent state depression and anxiety, as well as higher trait anxiety on the Bendig form of the Taylor Manifest Anxiety Scale; 3) however, on multiple regression analysis, not only depression, but also the number of sensitivities (foods, chemicals, drugs, inhalants), accounted for part of the variance in total number of symptoms (38 and 17%, respectively), whereas none of the affective measures accounted for any of the variance in total number of sensitivities over all subjects; 4) after controlling for depression and anxiety, FSR still showed a trend toward poorer performance on a timed mental arithmetic task (p = 0.16); and 5) FSR and C showed opposite patterns of heart rate change to two different stressful tasks (mental arithmetic and isometric exercise) (group by task interaction, p < 0.05). The data are discussed in terms of a time-dependent sensitization (TDS) process that predicts a cross-sensitizing and cross-reactive role for xenobiotic agents (e.g., foods, chemicals, drugs, and inhalants) and for salient psychological stress in the expression of psychophysiological dysfunctions of FSR. As in other chronically ill populations, negative affect in food-sensitive individuals may explain greater symptom reporting, but not necessarily account for the illness itself. For either a food or a psychological stimulus to begin to elicit sensitized responses, e.g., marked physiological differences from C, FSR may require multiple, intermittent exposures spaced over 5-28 days rather than on only 1 day.

Adult↗
PubMed1993

Are current pediatric dose recommendations for intravenous theophylline appropriate?

Theophylline, a first-line antiasthma drug, is often associated with severe toxicity even when taken in the recommended schedule. Theophylline toxicity has been associated with upper respiratory tract infections (URTI) due to reduced total-body clearance of theophylline. Some researchers believe this inhibition stems from a direct effect of viruses, but others postulate it is a result of the fever. We examined whether current theophylline dose recommendations are appropriate for children with acute asthma with a concurrent URTI. We also wished to elucidate whether the viral infection or the fever inhibits theophylline clearance. A total of 2254 medical records of asthmatic children admitted to The Hospital for Sick Children in Toronto were reviewed between 1987 and 1990. Clearance rate was calculated as the ratio between the infused dose rate and measured steady-state concentrations. Subsequently, these clearance rates were used to calculate steady-state concentrations that would be achieved by the recommended dose rates of theophylline. Reduced theophylline clearance was associated with the presence of URTI (p = 0.029) but not fever. Age correlated significantly with theophylline clearance (p = 0.027). If these children were to receive the recommended intravenous dose rate of theophylline, two-thirds of them would achieve steady-state serum concentrations above 15 mg/L, and one-third would achieve concentrations above 20 mg/L. Reevaluation of the present recommended theophylline dose rate is needed, as the majority of children requiring intravenous theophylline have a concurrent URTI with compromised total-body clearance. A correction factor of 60% is recommended to adjust the dose rate during an URTI. If utilized by prescribing physicians, it may reduce theophylline toxicity during an URTI episode.

Adolescent↗
PubMed1993

Infant death in San Francisco 1989-1990.

This paper examines all of the unexplained and violent deaths of children less than one year of age in the City and County of San Francisco during the years 1989-1990. A total of 62 cases were collected and analyzed retrospectively. Among the cases we examined, 34 deaths were determined as SIDS, while seven were moded as accidents and two as homicides. The deaths were examined with respect to the following parameters: sex, race, age, height and weight, cause and manner of death, significant autopsy and microscopic findings; circumstances of death including place, the person discovering or reporting the death, the presence of siblings or previous child death in the family and previous illness in the same child. A particular stress is given to the definition and diagnosis of SIDS, according to the international literature, and to the criteria adopted to distinguish SIDS cases from accidents and homicides. A review of both the American and European literature shows that most articles do not include comparisons of data from both the autopsy and the scene. Additionally there is little standardization in the investigation and the extent of postmortem examinations performed. An international standardization of these methods appears necessary and the use of protocols to assure complete investigation and postmortem examination will allow more intensive evaluation of data. Here we give a brief presentation of the necropsy protocol for Sudden Unexpected Infant Death recently written and approved by the California Department of Health Services and used in the Chief Medical Examiner's Office in San Francisco.

Age Factors↗
PubMed1992

Accumulation of cocaine in maternal and fetal hair; the dose response curve.

Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolites for example Benzoylecgonine (BZ), have been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the clinically used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation.

Animals↗