[Cocaine in pregnancy: a second Contergan?].
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Biomedical subjects
Publications and source records attributed to C Schaefer.
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The 25-yr. follow-up study of the self-concepts of a highly creative group of 10 adolescent girls showed both stability and change. In mid-life the group continued to describe themselves as both creative and intelligent; however, they also changed in that they now regard themselves as having a greater social interest.
There is a growing number of drugs with lung toxicity, and radiologists are increasingly confronted with nonspecific patterns of possibly drug-induced lung disease. The present article reviews clinical symptoms, pathological findings and radiographic features associated with drugs causing lung disease. Roentgen-morphological categorization is based on the predominant pattern and distinguishes five groups of drugs that cause interstitial opacities, air space consolidation, mixed interstitial and consolidating opacities, pulmonary edema and alterations associated with pulmonary vessels. Clinical, pathological and radiological findings are nonspecific in the majority of cases, and clinicians and radiologists can only hope to assess the probability of drug-induced lung disease by correlating radiographic and clinical data. Useful clinical data include respiratory symptoms, results of respiratory function tests, dose and schedule of drug administration, and information concerning concomitant or previous administration of drugs or radiation therapy. Useful radiographic data include the distribution of densities seen on the chest radiograph, the presence or absence of thoracic adenopathy and pleural effusion. Drug-induced lung disease frequently simulates disseminated opportunistic infections (particularly pneumocystis carinii) and must be differentiated from these because the treatment is completely different. Since early recognition and withdrawal of the noxious agent constitute the best treatment for drug-induced disease, the physician's alertness to drug toxicity is most important.
Indirect evidence for the presence of intrinsic factor in amniotic fluid has been provided recently, using either a radioisotope binding assay or a radioimmunoassay. We have determined the unsaturated cobalamin binding capacity and the physicochemical properties of the 3 cobalamin binding proteins in 59 amniotic fluids using radioisotope binding assay, gel filtration and isoelectrofocussing. A good correlation with gestational age was found for the total unsaturated Cbl binding capacity (r = 0.735) and for the concentration of unsaturated haptocorrin (r = 0.746), but not for the concentration of unsaturated intrinsic factor (r = 0.003). When their binding capacities were expressed as a percentage of the total unsaturated Cbl binding capacity, the percentage of intrinsic factor, transcobalamin II and transcobalamin III (the less acidic fraction of haptocorrin) decreased and the percentage of haptocorrin increased in function of gestational age. The physicochemical properties of intrinsic factor in amniotic fluid were close to those in gastric juice: the molecular mass was estimated to 49,200 +/- 4,900 Da (n = 24) in Sephacryl S 300 gel filtration, the cobalamin-protein complex was resolved in 2-6 isoproteins isoelectric at a pH range of 4.6-5.8 and with a mean isoelectric point of 5.18 +/- 0.16 (n = 5) in isoelectrofocusing and it crossreacted with anti-intrinsic factor autoantibodies (from a Biermer anaemia serum). Amniotic fluid collected at 13 wk of gestational age was found to contain intrinsic factor and haptocorrin with less acidic isoproteins than those usually observed in gastric juice and serum. This could indicate that sialic acid is less involved in the composition of the carbohydrate core of cobalamin binding glycoproteins in this period of the gestational age than later on and that cobalamin binding proteins have mainly a foetal origin.
The complex of DnaA protein with its 9 bp consensus binding site, the dnaA box 5'-TT(A/T)T(A/C)CA(A/C)A, blocks transcribing RNA polymerase. In a model system, the rate of transcription was monitored distal to the dnaA box 5'-TTTTCCACA by the expression of a reporter gene. DnaA-dependent transcription termination occurred irrespective of whether the dnaA box region was or was not translated. Only the dnaA box orientation 5'-TTTTCCACA on the non-coding strand, but not the reverse orientation, was active in termination. This suggests that DnaA protein contacts only one strand of the DNA duplex. Oligonucleotide-directed mutation of a dnaA box present within the dnaA coding region resulted in increased expression of dnaA. This demonstrates that DnaA protein-directed transcription termination is an element of the autoregulation of the dnaA gene.
The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.
From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease.
The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-alpha-sensitive rat tumor (DS-carcinosarcoma) was investigated. DS-carcinosarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Tumor blood flow (TBF) was measured with the krypton-85 clearance technique. Treatment with either tumor necrosis factor-alpha (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3 degrees C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-alpha injection and lasted for at least 4 h. The application of local hyperthermia (T greater than 42 degrees C) 3 h after rhTNF-alpha administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-alpha (0.2 and 1.0 mg/kg i.v.) combined with hyperthermia (43.3 and 44.3 degrees C, 40 min, starting 3 h after rhTNF-alpha injection) were given every third day from the fifth to the 20th day after tumor implantation. Monotherapies retarded tumor growth in a dose-dependent manner. Combined treatment was superior to either monotherapy leading to local tumor control in 40-50% of the animals treated. It is concluded that local hyperthermia can enhance the efficacy of rhTNF-alpha treatment by further reducing tumor perfusion.
Effects of Recombinant Human Tumor Necrosis Factor-alpha on Malignant Tumors in vivo/Pathophysiological fundamentals for clinical oncology. The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha; 6.6.10(6) U/mg protein) on growth, metabolism and perfusion of isotransplanted rat tumors (DS-carcinosarcomas) was investigated. Tumor growth was stimulated at low TNF doses (1 and 10 micrograms/kg), and significantly retarded at higher TNF dose levels (0.1 and 1.0 mg/kg). Growth changes were paralleled by variations in perfusion and metabolism. A reduced tumor blood flow enhanced the efficacy of a subsequent heat treatment. From these results, important implications for the clinical use of rhTNF-alpha are obvious (e.g., possible growth stimulation, timing of a combination therapy with other tumor treatment modalities).
The function of DnaA protein as a replisome organizer in the initiation of DNA replication is reviewed. A model is presented showing the construction of two basic types of DnaA-dependent replication origin. New data demonstrate that the dnaA box-DnaA protein complex is a transcription terminator. Only one orientation of the dnaA box results in termination of transcription. Mutation of the dnaA box within the dnaA reading frame shows that DnaA-mediated transcription termination has a role in the autoregulation of the dnaA gene.
Genes clockwise of oriC, the Escherichia coli replication origin (oriC-mioC-asnC), show anticlockwise transcription. The intergenic region between mioC and asnC contains both a terminator and a consensus DnaA-protein-binding site (dnaA box). We analysed termination in this region using galK expression to monitor for transcription. About 50% of the asnC transcripts were not terminated, and about 25% terminated at the asnC terminator. We found that the DnaA protein/dnaA box complex acts as a terminator of transcription for about 25% of the transcripts. Its efficiency could be increased by raising the level of DnaA protein, or it could be inactivated by deletion in the dnaA box or by thermal denaturation of the DnaA protein.
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The effect of human recombinant interleukin 1 beta (rIL 1 beta) on human neutrophils was examined. rIL 1 beta, even at concentrations of 100 ng/ml (100 half-maximal T cell stimulating U/ml) did not change significantly the intracellular free calcium concentration, [Ca++]i, whereas the control stimulus, fmet-leu-phe, significantly elevated [Ca++]i. rIL 1 beta also failed to stimulate production of superoxide, degranulation of lysosomal enzymes, phagocytosis of bacterial particles, chemotaxis, or chemokinesis of human neutrophils. This is substantial evidence that superphysiologic concentrations of interleukin 1 have no direct effect on [Ca++]i, as well as on functional responses of neutrophils.
A population of 968 pregnant Navajo women was followed in a prospective study conducted from 1980 to 1983 at the Indian Health Service Hospitals in Gallup and Crownpoint, New Mexico. The purpose of the study was to examine social and cultural influences on obstetric and neonatal complications. The extent of traditional cultural practices and the availability of social support were ascertained in structured interviews completed during each woman's first prenatal visit. In a subsample of women, the occurrence of stressful life events was also measured during a final prenatal visit in the third trimester of pregnancy. Controlling for a variety of conventional risk factors and other potential confounders, traditional women sustained complications at a rate greater than twice that of the least traditional, most acculturated women (approximate relative risk = 2.1; p = 0.001). Social support and life events were modestly associated with maternal complications (approximate relative risk = 0.7, 0.8, respectively; p = 0.07), with poorer outcomes found among those with low social support and low numbers of life events. It is proposed that the relationship of maternal complications to all three sociocultural variables--traditionality, social support, and life events--may reflect the influences of social isolation on the course and outcomes of pregnancy.
Chlamydia trachomatis is known to cause infant pneumonitis and conjunctivitis and is a suspected cause of otitis media and gastroenteritis. To identify infections associated with exposure to C trachomatis, infant illnesses were studied through a "blinded" review of medical records of 244 infants born to women cultured antenatally for cervical C trachomatis, 25% of whom had C trachomatis-positive cultures. Compared with unexposed infants, infants exposed to C trachomatis had twice the rate of both pneumonitis and recurrent otitis media in the first six months. Infants who were exposed to C trachomatis and who had pneumonitis had higher subsequent rates of gastroenteritis than either unexposed infants or exposed infants without pneumonitis. These results suggest that appreciable outpatient infant morbidity may be associated with maternal infection with C trachomatis, and that it may either cause or promote the occurrence of early, recurrent otitis media and gastroenteritis.
Past work suggests that stressful life changes and the availability of social support exert opposing effects on the health of adolescent mothers and their infants. We have developed a theoretical perspective in which the effects of both stressful and protective social factors are viewed as acting on health through their capacity to either undermine or sustain an individual's sense of permanence and continuity in life experience. To examine this hypothesis, a population of 89 unmarried, pregnant adolescents were studied to ascertain psychosocial influences on maternal and infant health outcomes. This paper reports a cross-sectional analysis of perinatal complications and psychological well-being as they relate to a variety of psychosocial variables, including stressful life events, social network support and a questionnaire measure of the sense of permanence. Multivariate analyses indicate that while life events and social support had effects in the expected directions, the sense of permanence constituted an important, additional factor in the effects of social experience on pregnancy outcomes.
This study was designed to determine whether normal, full-term, exclusively breast-fed infants develop iron deficiency anemia, as defined by hemoglobin or red blood cell indices more than two standard deviations below the age-specific mean, or depletion of iron stores, as defined by an abnormally low serum ferritin level. Thirty-three breast-fed infants were followed from birth to 6 months. Maternal blood and cord blood at delivery, and venous blood from the infants at 2, 4, and 6 months were analyzed for anemia as defined above. At 6 months of age, the mean hemoglobin concentration of these infants was slightly higher than the normal mean; four of 33 infants (12%) had a mean corpuscular volume greater than 2 SD below the reported normal mean; and two of 33 infants (6%) had a serum ferritin level less than 12 ng protein/ml. These data suggest that the infant who is exclusively breast-fed for the first 6 months of life is not at high risk for the development of iron deficiency anemia or the depletion of iron stores during that time.
A number of recent studies have reported reduced growth velocity among breast-fed infants, as compared with standard growth curves. Contradictions between these and previous studies of breast-feeding have been difficult to resolve because of methodological problems, particularly supplementation of breast-feeding with other nutrients. In the present study, 33 term infants, exclusively breast-fed for six months, showed significantly slower rates of growth compared with data from the National Center for Health Statistics (NCHS). Between birth and 6 months of age, these infants lost an average of 20 percentiles in weight for age and 30 percentiles in length in relation to the NCHS population. We discuss these findings in terms of the appropriateness of the NCHS data as standards and the adequacy of exclusive breast-feeding for providing optimum growth through 6 months of age.