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J Fortney

Publications and source records attributed to J Fortney.

35 records · Page 2Linked to original sources

Disruption of bone marrow stromal cell function by etoposide.

Long-term deficits in hematopoietic reconstitution following aggressive chemotherapeutic regimens used before transplantation may be a result, in part, of damage to the bone marrow microenvironment. Disruption of the hematopoietic microenvironment is indicated by delays in functional recovery of the immune system in spite of delivery of healthy peripheral blood or bone marrow progenitor cells. Cultures of primary human bone marrow stromal cells and a cloned murine stromal cell line, S10, were evaluated for functional changes following in vitro exposure to the chemotherapeutic agent, etoposide (VP-16). Stromal cells had reduced capacity to support lymphoid or myeloid cell proliferation following chemotherapy treatment. A consistent reduction of vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stromal cells also followed VP-16 exposure. These observations indicate that functional disruption of the bone marrow microenvironment by chemotherapeutic regimens must be considered when attempting to optimize patient recovery from hematopoietic transplantation.

Antineoplastic Agents, Phytogenic↗

Outcomes of newborns with gastroschisis: the effects of mode of delivery, site of delivery, and interval from birth to surgery.

OBJECTIVE: Our purpose was to determine the impact of delivery site, delivery mode, and delivery-to-surgery interval on outcomes for neonates diagnosed with gastroschisis. STUDY DESIGN: Data were obtained retrospectively by chart review on 56 newborns diagnosed with gastroschisis. Outcome measures examined included primary closure, days to enteral feeding, days in intensive care, total length of stay, and hospital charges. RESULTS: Inborn infants experienced fewer days to enteral feeding (p < 0.01)., shorter total lengths of hospital stay (p < 0.01), and lower hospital charges (p < 0.01). Newborns delivered by cesarean section tended to have longer lengths of stay (p = 0.07), greater hospital charges (p = 0.06), and significantly longer lengths of stay in intensive care (p = 0.05). Shorter intervals from delivery to surgery were observed for inborn neonates (p < 0.01) and for those delivered by cesarean section (p < 0.05). No relationships between hours from delivery to surgery and neonatal outcomes were observed. CONCLUSIONS: Delivery at a regional center is associated with improved outcomes, whereas cesarean deliveries were associated with worse outcomes. We observed no salutary effect related to the interval between delivery and initial surgical repair.

Abdominal Muscles↗

Correlation of end-tidal CO2 to cerebral perfusion during CPR.

STUDY OBJECTIVE: A number of studies have demonstrated a correlation between end-tidal carbon dioxide (ETCO2), cardiac output, and return of spontaneous circulation in experimental animals and in patients undergoing closed-chest CPR. Our study attempted to correlate ETCO2 to cerebral blood flow during cardiac arrest. DESIGN: Sixteen piglets were anesthetized, intubated, and instrumented for cerebral blood flow studies. An ultrasonic flow probe was placed on both internal carotid arteries for continuous flow measurements. The animal was fibrillated, and closed-chest CPR was begun. Continuous ETCO2 measurements were obtained and compared with simultaneous internal carotid, cardiac output, and cerebral blood flow measurements. MEASUREMENTS AND MAIN RESULTS: Correlations between ETCO2 and carotid and cerebral blood flow were determined using Pearson's method. The correlation between ETCO2 and total internal carotid flow was .58 (P = .01, Bonferroni's adjusted P = .30). Correlation between ETCO2 and cerebral blood flow was .64 (P = .01, Bonferroni's adjusted P = .09). A partial correlation coefficient for ETCO2 versus cardiac output was .70, whereas it was only .30 for ETCO2 versus cerebral blood flow. CONCLUSION: Partial correlation coefficients suggest that ETCO2 correlates with cerebral blood flow when changes in cerebral blood flow parallel changes in cardiac output.

Animals↗

Shifting the financial burden: the VA ambulatory care discharge policy.

The Department of Veterans Affairs is a primary source of health care services for many of the nation's uninsured and underinsured. Changes in congressionally mandated eligibility criteria and limited increases in appropriations have forced the Department to adopt a policy of discharging chronic but stable outpatients who have been treated for non-service-connected health conditions. Survey data from one VA medical center suggest that many, but not all, of those discharged: 1) have either Medicare or private insurance coverage; 2) have not sought or found alternative physician services in their local communities; 3) have discontinued taking previously prescribed medications; 4) report worsened health status since discharge; and, 5) have been hospitalized. In general, discharged patients from the lowest income group report the greatest financial access barriers. Preliminary analyses of the discharge policy suggest the potential for decreased access to needed medical services due to financial factors and cost-shifting from the VA to patients and other federal, state and local payers and providers.

Chronic Disease↗

Health, growth and sexual development of teenagers exposed in utero to medroxyprogesterone acetate.

General health, growth and sexual development were evaluated in 74 teenage boys and 98 girls who had been exposed to medroxyprogesterone acetate (MPA) in utero, and 385 boys and 448 girls not exposed. In this 17-year prospective study, the ascertainment of the end points was 'double blind' in that neither the interviewer nor the subject was aware of our interest in MPA. On average, girls exposed to MPA reported reaching the menarche 4 months earlier than the comparison group. This difference disappeared, however, in a multiple regression analysis taking into account social class, the mother's age at menarche and height of the girl's mother and father. Boys exposed to MPA reported their growth spurt to have occurred an average of 6 months earlier and voices to have broken 5 months earlier than unexposed boys. Again, the differences between them and the comparison group disappeared after controlling for confounding variables. There were no significant differences between the MPA-exposed and comparison groups in a wide variety of indices of health reported by the teenagers' mothers. These findings are consistent with the hypothesis that intrauterine exposure to MPA, in the doses used for pregnancy maintenance or for contraception, poses no threat to the long-term health and development of the progeny.

Adolescent↗

Promoter-specific trans activation and repression by human cytomegalovirus immediate-early proteins involves common and unique protein domains.

trans activation of promoters by viral regulatory proteins provides a useful tool to study coordinate control of gene expression. Immediate-early (IE) regions 1 and 2 of human cytomegalovirus (CMV) code for a series of proteins that originate from differentially spliced mRNAs. These IE proteins are proposed to regulate the temporal expression of the viral genome. To examine the structure and function of the IE proteins, we used linker insertion mutagenesis of the IE gene region as well as cDNA expression vector cloning of the abundant IE mRNAs. We showed that IE1 and IE2 proteins of CMV exhibit promoter-specific differences in their modes of action by either trans activating early and IE promoters or repressing the major IE promoter (MIEP). Transient cotransfection experiments with permissive human cells revealed a synergistic interaction between the 72- and the 86-kilodalton (kDa) IE proteins in trans activating an early promoter. In addition, transfection studies revealed that the 72-kDa protein was capable of trans activating the MIEP. In contrast, the 86-kDa protein specifically repressed the MIEP and this repression was suppressed by the 72-kDa protein. Furthermore, observations based on the primary sequence structure revealed a modular arrangement of putative regulatory motifs that could either potentiate or repress gene expression. These modular domains are either shared or unique among the IE proteins. From these data, we propose a model for IE protein function in the coordinate control of CMV gene expression.

Base Sequence↗

Obstetric deaths in Menoufia Governorate, Egypt.

A survey of all registered deaths which occurred during 1981-1983 in women of reproductive age was carried out in Menoufia Governorate, Egypt. Surviving family members were interviewed by trained social workers, and information was collected on symptoms of the disease that led to death. The completed questionnaires were reviewed by a panel of local physicians and a cause of death was assigned by the panel. Maternal mortality was a leading cause of death, second only to heart disease. There were 190 maternal deaths per 100,000 livebirths and 45 maternal deaths per 100,000 married women aged between 15 and 49 years. Most of the maternal deaths (63%) were due to direct obstetric causes of which haemorrhage was the main cause. Another 27% of the maternal deaths were due to indirect obstetric causes of which rheumatic heart disease was the main cause.

Abortion, Spontaneous↗

Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region.

Expression of RNA and protein from the human cytomegalovirus immediate-early (IE) gene region (map units 0.732 to 0.751) was analyzed at early and late times after infection. The level of RNA present at late times (48 to 72 h after infection) was significantly higher than that present at IE times (5 h after infection). The profile of IE RNA in the cytoplasm of infected cells was different from that previously reported on polysomes (R. M. Stenberg, P. R. Witte, and M. F. Stinski, J. Virol. 56:665-675, 1985). The data indicate that the 1.95-kilobase (kb) major IE region 1 mRNA, which codes for the 72-kilodalton (kDa) protein, and the 1.7-kb IE region 2 (IE2) spliced mRNA, which codes for the IE2 55-kDa protein, may be preferentially associated with polysomes. However, the IE2 2.2-kb unspliced mRNA, which codes for an 86-kDa protein, may be preferentially excluded. This RNA was abundant in the cytoplasm under IE conditions but was not present on polysomes in significant quantities. This indicates that IE gene products may be involved in translational control of cytomegalovirus RNA. At late times, new transcription takes place within region 2. A 1.5-kb RNA is transcribed from a late promoter in region 2 that apparently does not function in cells infected with DNA-negative mutant ts66. These results demonstrate that the IE gene region is transcribed throughout infection and that multiple levels of regulation exist.

Antigens, Viral↗

Toxic shock syndrome.

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Contraceptive Devices, Female↗

A study of abortion in countries where abortions are legally restricted.

In countries where induced abortion is permitted, national family planning programs are able to combine pre- and postconceptive fertility control methods to maximize success in achieving personally desired fertility levels and nationally desired growth levels. The proscription against induced abortion tends to produce criminal abortions and consequent morbidity and mortality which, in some countries, are often recognized as a national health problem. The International Fertility Research Program has undertaken this study of incomplete, inevitable, threatened and septic abortion cases, using a standard data collection instrument, to facilitate comparisons across institutions and countries. The data gather since 1971 in nine Asian, African and Middle Eastern hospitals includes 7,331 cases. Policies of the participating institutions with respect to what constitutes a therapeutic abortion affected the proportions of spontaneous abortions and of abortions induced outside the hospital and inside the hospital. Women treated for induced abortion tended to be of higher parity and more likely to have attained their desired family size than patients treated for spontaneous abortions. Morbidity rates were quite low for patients treated in centers where vacuum aspiration was mainly used, particularly in contrast to the morbidity rates for patients treated in centers where dilatation and curettage was used exclusively. High mortality rates in patients admitted with sepsis confirm the need not only for improvement of clinical procedures but also for reconsideration of the legal issues since many patients admitted with sepsis can be assumed to have had abortions induced.

Abortion, Illegal↗

Breech presentations in a sample of Colombian hospitals.

All the breech presentations that occurred in a large sample of data on obstetric deliveries from a random sample of urban hospitals in Colombia are examined. The 463 breeches are analyzed by age and parity of the mother, type of breech presentation (frank or footling) and type of delivery (vaginal or abdominal). The data suggest that abdominal delivery reduces perinatal mortality although cell values are too small to adequately control for birth weight.

Adolescent↗

Etoposide differentially affects bone marrow and dermal derived endothelial cells.

Chemotherapy alteration of the bone marrow microenvironment has the potential to influence hematopoietic recovery following transplantation. To discern the effect of specific drugs on components of the complex marrow microenvironment, in vitro models have significant utility. In the current study we sought to determine whether dermal (HMEC-1) and marrow derived endothelial cells (BMEC-1) respond differently to identical chemotherapy exposure. BMEC-1 cells were consistently more sensitive to etoposide exposure than HMEC-1 cells, measured as reduced viability. BMEC-1 also had reduced focal adhesion kinase (FAK) and VCAM-1 protein expression following chemotherapy, in contrast to dermal derived endothelial cells in which neither protein was influenced dramatically by etoposide. The two endothelial cell lines had markedly different levels of baseline VE-Cadherin protein, which was modestly altered by treatment. These data indicate that marrow derived endothelial cells have disruption of specific proteins following chemotherapy that may influence their ability to facilitate hematopoietic cell entry or egress from the marrow. In addition, these observations suggest that while BMEC-1 and HMEC-1 share a variety of characteristics, they differ significantly in their response to stress and should be incorporated into specific models with this consideration.

Animals↗