Drug use and physical trauma: risk factors for preterm delivery.

OBJECTIVE: The present investigation was undertaken to determine the incidence of alcohol, cocaine, and marijuana use among pregnant patients who suffered any type of physical trauma and to determine if the combination of substance use and physical trauma in pregnancy has extended perinatal implications. METHODS: In this single institution, prospective patient series undertaken over 18 months, all pregnant patients who suffered any type of physical trauma were considered for study. RESULTS: Among 6828 live births over an 18-month period, there were 157 (2.3%) patients who reported physical trauma (insignificant = 153, minor = 2, severe = 2). Consent to screen for the presence of alcohol, marijuana, and cocaine was obtained from 85 (54%) patients with refusal by the remainder. Screening was positive in 11% for one or more substances. The perinatal morbidity and mortality for the 153 patients with insignificant trauma was 50:1000 and 20:1000, respectively, all associated with preterm labor and delivery which occurred in 21% of the patients. None of the four patients with minor or severe trauma either had a positive drug/alcohol screen or any perinatal morbidity or mortality. No maternal mortality occurred. CONCLUSION: An 11% incidence of positive drug screens was encountered in consenting pregnant trauma victims and a 21% incidence of preterm birth was encountered even in this patient population with so-called insignificant trauma.

Trial of labor after cesarean delivery: experience in the non-university level II regional hospital setting.

OBJECTIVE: We sought to determine the extent to which vaginal birth after cesarean delivery was attempted since 1987 or 1988 in a representative sample of three regional level II hospitals in Mississippi. METHODS: The medical record department in each hospital identified all potential study subjects for this retrospective case series. One author abstracted relevant information from each medical record and entered it into a relational data base. RESULTS: Among 18,703 live births, 1574 patients had previous abdominal delivery (8.4%). Trial of labor was undertaken in 286 patients (18%), with an overall successful vaginal delivery rate of 71%. Although success rates for the three level II hospitals were similar (63-81%), utilization rates varied considerably (7-40%). One uterine dehiscence led to hysterectomy; otherwise, there were no serious perinatal complications or differences in measures of maternal morbidity, except for a higher incidence of endomyometritis with failed trial of labor (13 versus 3%). The only consistent differences observed between successful and unsuccessful trials in all groups were length of hospitalization and rate of cervical dilatation in active labor (1.4 versus 0.5 cm/hour). CONCLUSION: Although each regional level II hospital successfully conducted trials of labor in patients with previous cesarean birth, there was considerable variation among sites regarding frequency of utilization, suggesting a strong influence of nonclinical patient-physician factors upon the decision-making process.

Differences in the susceptibility of human blood cell lines to vaccinia virus.

The replication of vaccinia virus in human hematopoietic cell lines was studied, to ascertain whether the cell type and the stage of differentiation can influence the outcome of the infection. Lymphocytic NB104 cells and myelogenous leukemic K562 cells can be productively infected with vaccinia. Whereas NB104 cells were readily lysed, cells from the K562 line stayed persistently infected. Infection of promyelocytic leukemia HL60 cells results in an abortive infection in which the virus is uncoated, does not replicate, remains latent and can be rescued by cocultivation with permissive cells. Upon addition of phorbol esters to HL60 cell cultures, viral replication resumed. These results suggests that, although vaccinia virus replication is almost independent of host-specific functions, the outcome of the infection may depend on the cell type and its stage of differentiation.

Depletion of sodium butyrate from the culture medium of Friend erythroleukemia cells undergoing differentiation.

Friend erythroleukemia cells can be induced to undergo erythroid differentiation by a variety of unrelated compounds. The fact that sodium butyrate causes reversible alterations in growth, morphology, and biochemistry in many cell systems prompted us to reexamine its pattern of induction of differentiation and to compare it to that of dimethyl sulfoxide (DMSO) and hexamethylbisacetamide (HMBA). By the fourth day of induction, a peak in hemoglobin accumulation was reached in the cultures treated with each of these potent inducers. Differences, however, were noted in cultures in which there had been no change of medium for 7 days. Whereas DMSO or HMBA induced cultures reached a stationary stage of growth and maintained a high percentage of benzidine positive cells, butyrate treated cultures resumed active growth and showed a marked decrease in the percentage of benzidine positive cells. However, the actual number of terminally differentiated cells remained relatively constant. The addition of fresh butyrate to 4-day treated cultures prevented the decrease in the percentage of benzidine positive cells. Measurement of [14C]butyrate uptake into the cells showed a decrease in the incorporation of the inducer with time coincident with the decrease in the percentage of benzidine positive cells and of the butyrate in the medium. Incorporation of [3H]thymidine into cells undergoing differentiation for 4 days indicated that butyrate treated cells, but not cells treated with DMSO or HMBA were capable of active DNA synthesis and growth after removal of the inducers. These data suggest that butyrate, a natural fatty acid, is metabolized by the cells and with time its concentration is reduced to a level below that required to stimulate differentiation. Additional evidence to support this notion are the results obtained with conditioned medium (CM) from induced cultures. CM-DMSO and CM-HMBA retained the capacity to induce differentiation whereas CM-butyrate lost its potency with time.

Vaccinia virus DNA sequences in the nucleus of persistently infected Friend erythroleukemia cells.

FL vac cell lines are Friend erythroleukemia cells persistently infected with vaccinia virus. These cells produce attenuated leukemia virus, virulent poxvirus, resist superinfection with vaccinia, and show high levels of spontaneous erythrodifferentiation and decreased tumorigenicity in syngeneic hosts (Pogo, G.T. and Friend, C. (1982) Proc. Natl. Acad. Sci. USA 79, 4805-4809). To determine whether resistance to superinfection was associated with the presence of vaccinia DNA in the nucleus, DNA from cells at different passage levels was hybridized to a vaccinia DNA probe. Vaccinia DNA sequences were detected in the nucleus of cells of lines that were productively infected with vaccinia. No such sequences were detected in productively infected with vaccinia. No such sequences were detected in productively infected L cells nor in persistently infected cell lines that no longer produced infectious particles but were resistant to superinfection. Although no evidence of integration of vaccinia DNA was observed, differences in the restriction patterns were detected at some passage levels. The presence of vaccinia virus DNA sequences in the nucleus apparently did not affect the size of the provirus, the integration pattern or the expression of the leukemia virus.

The functional independence of mands and tacts.

This study demonstrates functional independence in the acquisition of mands and tacts. Some subjects first learned to mand the experimenter's placement of objects with the prepositional phrases "On the left" and "On the right." They were regularly tested for collateral appearance of tacts with these same phrases. Other subjects learned to tact the location of objects with these prepositional phrases and were regularly tested for collateral appearance of mands. All subjects were next trained in the repertoire that had not been trained in the first condition (either tact or mand). After all subjects had learned both to mand and to tact correctly, another assessment of mand-tact independence was undertaken. Mands (tacts) were reversed and testing assessed collateral reversal of tacts (mands). The results demonstrated that tacts and mands, even when incorporating identical response forms, were functionally independent during acquisition. Subsequent modification of one repertoire (by reversal training) produced collateral reversal in three of nine subjects.

Characterization of leukemogenic virus produced by a new line of Friend erythroleukemia virus-transformed cells.

A new cell line designated SQ-A was established from the spleen of a leukemic DBA/2J mouse inoculated with the anemic strain of Friend erythroleukemia virus (FLV-A). The cells are similar in morphology, growth pattern, and tumorigenicity to our prototype erythroleukemia line 5-86 but are more sensitive to the cytotoxic effects of inducers of differentiation. The virus produced by SQ-A cells induces erythroleukemia associated with anemia in adult mice but has little activity when assayed on XC cells. It was characterized to determine what factors influence its leukemogenic potential. As compared to the attenuated virus from cultures of 5-86 and G-2 cells, the subunits of the RNA from the virions of SQ-A cells are the same size, and the amount of reverse transcriptase activity and RNase H present in the purified virions of the three lines are similar. However, differences are observed in levels of endonuclease and protein kinase. Both enzymes are increased in SQ-A virions. The activity of protein kinase in SQ-A virions is about 5 times higher than that in the attenuated virions. The number of polypeptides and their phosphorylation patterns also distinguish the virions of SQ-A. Whereas 5-86 virions contain seven proteins, three of which are phosphorylated in vitro, SQ-A virions contain eight proteins, all of which are phosphorylated. The extra protein in SQ-A virions has a molecular weight of 25,000 and is not glycosylated.

Increased mouse minor hemoglobin during erythroid stress: a model for hemoglobin regulation.

In mice with "diffuse" hemoglobin (Hb), the decrease in the proportion of minor Hb during ontogeny qualitatively resembles the decline observed in human Hb F. Since Hb F reappears during some forms of erythroid stress, we investigated the effect of hematopoietic stress on minor Hb in DBA/2 mice. The stresses were acetlyphenylhydrazine-induced hemolysis, phlebotomy, or infection with Friend erythroleukemia virus. Recovery from anemia was associated with a transient increase in the synthesis of minor Hb similar to the reappearance of Hb F in man. Minor Hb synthesis also increased during the evolution of erythroleukemia induced by both the anemic and the polycythemic strains of virus. Thus, the mouse model can be used to study Hb regulation, since changes in the modulation of minor Hb synthesis occur under conditions which are associated with alterations in Hb F synthesis in humans.

Benign thyroid disease and upper airway obstruction: case presentations, pathophysiology, and management.

Investigations of three cases with large goiters and marked respiratory stridor showed different mechanisms of airflow limitations. This report describes the flow volume loop and Machida fiberoptic tracheoscopy as newer methods for evaluating the larynx and trachea. Indications for tracheotomy in benign thyroid disease are discussed.

Variations in the response of cloned murine friend erythroleukemia cells to different inducers.

Cells of the line 3BM-78 derived from murine bone marrow cells infected in vitro with polycythemic Friend leukemia virus (FLV-P) produce virus with spleen focus-forming activity (SFFV) and can be induced to synthesize hemoglobin. Fifteen clones, isolated from this line, have been analyzed in detail for the effect of different inducing agents (dimethyl-sulfoxide, DMSO; hexamethylene bisacetamide, HMBA; and sodium butyrate, SB) on the synthesis of hemoglobin and virus at the clonal level. All the clones proved to be inducible with one or more of the agents, but the degree of the response depended on the type and concentration of the agent used. In general, the effectiveness of the agent--within the usual range of concentration for induction--both for hemoglobin and for virus synthesis, was in the order HMBA greater than DMSO greater than SB. Reverse transcriptase activity was, however, more easily induced than hemoglobin synthesis in that stimulation was seen at lower concentrations of the same inducing agent. This clonal analysis confirmed that virus and hemoglobin production are regulated independently in these erythroleukemic cells chronically infected with FLV-P.

Induction of differentiation of murine erythroleukemia cells by aminonucleoside of puromycin and inhibition of this induction by purines and purine derivatives.

The effect of the aminonucleoside of puromycin (AMS) on Friend erythroleukemia cells in culture was investigated, because purines and purine analogues are known to act as inducers of differentiation. After treatment with 20-30 micro M AMS for 4 days, the cultures contained between 80 and 90% benzidine-positive cells. Stimulation of hemoglobin synthesis was dose and time dependent. Inosine had no stimulatory activity; however, when it was added to the medium together with AMS, erythroid differentiation was almost completely inhibited. The inhibitory effect of inosine on this potent inducer was also dose and time dependent. No cytotoxicity was observed with either compound, alone or in combination. Inhibition of AMS stimulation of erythroid differentiation was also observed in the presence of inosine monophosphate and poly(inosinic acid). Hypoxanthine had a dual effect. At high concentrations (500 microgram/ml) it acted as an inducer, but when added at low concentrations (20 microgram/ml) together with AMS it inhibited differentiation. These findings suggest there is a link between purine biosynthesis and the event(s) required to trigger differentiation. Agonist-antagonist activity of closely related biological compounds has thus been revealed in the erythroleukemia cells.

Control by stimulus features during fading.

Sixteen children were given four successive circle-size discrimination problems with luminance as the fading stimulus. Children who were first presented with a difficult size discrimination failed to acquire this discrimination. Those who first received an easy discrimination learned the difficult discrimination. At the end of each 10-trial block, two probe stimuli were presented to monitor any shift in control from luminance to size. One probe was the same size as the positive stimulus but of different luminance; the other was the same luminance but of different size. If, in the course of fading, size and luminance both controlled responding, fading was successful. If luminance alone controlled responding until the end of fading, the size discrimination was not established. Dual control, and thus successful fading, resulted when the target stimuli were very discriminable, or when the target stimuli were subtly different provided that previous fading series had first established less subtle discriminations.

A clarification of continuous repertoire development.

The key-peck response of five pigeons was reinforced on a schedule whenever the interval between pecks at two response keys was between 1.0 and 2.33 seconds in the presence of a 2,500-Hertz tone or between 4.66 and 6.0 seconds in the presence of a 1250-Hertz tone. There was no tendency for responses of intermediate duration to occur when test tones of intermediate frequency were presented. This result clarifies a previous finding using a similar procedure but with a visual intensity stimulus dimension.

Observations on cell lines derived from a patient with Hodgkin's disease.

Permanent cell lines have been established from a spleen nodule and lymph node of a male Hodgkin's disease (HD) patient whose father has the same disease. Th in vitro growth pattern morphological and cytogenetic characteristics of these lines maintained continuously for over 2 years are described. The cultures contain a population of mixed cell types that grow in suspension. Between 5 and 10% of the cells have surface immunoglobulins M and D. B-cell alloantigens are also detectable. While the cultures are predominantly lymphoid, some of the large cells, by light and electron microscopy, resemble the Reed-Sternberg and Hodgkin's cells of the original biopsies. Although the cells maintain the human diploid karyotype, they are heterotransplantable in nude mice. After 14 months of culture, chromosome rearrangement and losses, commonly seen in leukemic bone marrow, occurred. Close to 100% of the cells are Epstein-Barr nuclear antigen positive, but they lack Epstein-Barr viral (EBV) capsid antigen and EBV-induced early antigen. Nucleic acid hybridization tests indicated that there were no more than two EBV genome equivalents per cell. Tests with HD sera free of anti-EBV were negative. Electron microscope examination of the cells revealed the presence of intracellular as well as extracellular rare pleomorphic particles ranging from 400 to 1200 A. The nature of these particles, which increased in number after the cultures were treated with halogenated pyrimidines but not with dimethyl sulfoxide, remains questionable. The cultures derived from the mouse-passaged HD cells, however, had reverse transcriptase activity and readily identifiable type C particles which were probably of murine origin. These cultures have some unique features that make them useful in studying the perplexing pathological entity of HD.