Biomedical subjects
R Holmes
Publications and source records attributed to R Holmes.
Evaluating the impact of workstation usage on radiology report times in the initial 6 months following installation.
Picture archiving and communications systems (PACS) workstations are reported to improve workflow by making studies immediately available for review upon their completion. This study tested the hypothesis that a workstation would decrease the time from completion of a study to dictation of results (report time). A four-monitor, 2K x 2K workstation (Imation Cemax-Icon, Fremont, CA), was installed in a body imaging computed tomography (CT) reading room. Use of the workstation by the staff radiologists was voluntary. Images were also printed on film and films continued to be hung at the routine hanging times. To evaluate the workstation's maximum impact, data were collected for report times for studies completed during the routine day shift of the staff radiologist (Monday to Friday, 8 AM to 5 PM). Data were collected before workstation installation (August 1997 to November 1997) and for the subsequent 6 months. Histograms of the number of studies (743 v 103) versus report time (mean, 11.7 v 7.4 hours) showed a bimodal distribution, with peaks at approximately 6 and 24 hours, both before (8/97-11/97) and after (6/98) the workstation's installation. However, the number of studies dictated greater than 60 hours (25.2% v 20.4%) and the percentage of studies in the second peak (16 to 48 hours; 4.4% v 0%) both decreased. In conclusion, the workstation decreased the mean (11.7 v 7.4 hours) and standard deviation (19.8 v 9.1 hours) for report times. This was due to a decrease in both the number of cases dictated the day following their completion and the number of outliers (markedly delayed dictations). The decrease in outliers is probably due to a decrease in the number of "lost" film-based studies.
Small for gestational age is not a diagnosis.
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An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses.
Insulin-like growth factors (IGFs) and their receptors in the fetus are essential for growth and postnatal survival but the role of maternal IGFs is less well understood. Animal and in vitro evidence suggests that maternal IGF-I may have important effects on placental function. Recent work in humans suggests that although there is no relationship between maternal serum IGF-I and normal fetal growth, levels are low in pregnancies complicated by fetal growth restriction due to placental dysfunction. A prospective and observational study was undertaken of the distribution and concentration of placental type I IGF receptors (IGF-IR) in women with small for gestational age (n=26) or appropriately grown (n=14) fetuses. Women were scanned biweekly from 24 weeks to delivery and cases (birthweight <5th centile) were assigned to two groups: 'fetal growth restriction' (FGR; umbilical artery pulsatility index [UAPI] > +2 s.d.; n=16) and 'normal small for gestational age' (SGA; normal UAPI, growth velocity and amniotic fluid; n=10). Immunohistochemistry of the IGF-IR was performed on formol saline-fixed placental biopsies obtained at delivery. In control pregnancies IGF-IR were present in villous endothelium and stroma, trophoblast and decidua and their distribution and density were unchanged in both SGA and FGR pregnancies. We hypothesize that a therapeutic elevation of maternal IGF-I in FGR pregnancy might lead to enhanced placental function and so fetal growth. Our findings of normal localization and density of placental IGF-IR in FGR encourage us to extend our work to look at the effects of maternal IGF-I on the transport of glucose and amino acids.
Human corneal and lens aldehyde dehydrogenases. Localization and function(s) of ocular ALDH1 and ALDH3 isozymes.
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NH2-terminally truncated HER-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer.
We identified an NH2-terminally truncated HER-2/neu product of M(r) 95,000 with in vitro kinase activity by Western blotting and immunoprecipitations using domain-specific antibodies. p95 levels correlated with the extracellular domain (ECD) shed from different cells under varied conditions. Both ECD and p95 were at approximately 20-fold lower levels in SKOV3 ovarian carcinoma cells, as compared to BT474 breast carcinoma cells. Both were stimulated by treatment of cells with the phorbol ester tumor promoter phorbol 12-myristate 13-acetate and the lysosomotrophic agent chloroquine. The hydroxamate inhibitor of metalloproteases, TAPI, suppressed both p95 and ECD in a dose-dependent fashion, with maximal inhibition at < or = 10 microM in BT474 cells. Cancer tissues were analyzed by Western blotting and scored for p95HER-2/neu and for p185HER-2/neu expression. Breast and ovarian cancer tissues were both found to express p95HER-2/neu in addition to p185HER-2/neu. Of 161 breast cancer tissues, 22.4% expressed p95, 21.7% overexpressed p185, and 14.3% were p95 positive and overexpressed p185. A higher proportion of node-positive patients (23 of 78) than node-negative patients (9 of 63) expressed p95 in all tumors combined (P = 0.032). In the group that overexpressed p185, those that contained p95 were associated with node-positive patients (15 of 21), whereas those that were p95 negative were associated with node-negative patients (8 of 11; P = 0.017). Neither p95- nor p185-rich patients significantly correlated with tumor size or with hormone receptor status in this study. Our findings show that breast cancers, which express the HER-2/neu oncogene, are heterogeneous with respect to HER-2/neu protein products. p95HER-2/neu appears to distinguish tumors that have metastasized to the lymph nodes from those in node-negative patients.
Prognosis following prenatal diagnosis of heart malformations.
Our objective was to document the prognosis of cases with fetal heart malformations (FHM). Forty-two fetuses assessed both in a regional fetal medicine and paediatric cardiology unit were classified prenatally into isolated FHM or those associated with extra-cardiac structural or karyotypic anomalies (ECA) and this classification was not changed subsequently (analogous to an intention to treat analysis). The end points studied included chromosomal abnormality, pregnancy outcome and follow-up at one year of age. FHM were isolated in 16 (38%) and associated with ECA in 26 (62%) of cases. The karyotypic abnormality rate was 8/42 (19%) overall and 8/26 (31%) in ECA cases. The pregnancy outcome included termination of pregnancy in 19 (45%), intrauterine death of two (5%) and live birth in 21 (50%). 12/16 (75%) of isolated FHM cases were live born compared with 9/26 (35%) of ECA cases (P < 0.03). Of the isolated FHM live born babies, 8/12 (67%) were alive at the end of the first year and seven of these were growing normally and did not require cardiac medication. However, a considerable proportion of their first year was spent in hospital (median 8%, interquartile range 5-10). Only one of nine ECA live born cases was alive but with poor growth and dependence on cardiac drugs at one year. These data confirm previous findings in prenatal diagnosis series that the prognosis for FHM is worse than that reported in studies of congenital heart disease at birth and is strongly dependent upon the presence of ECA. In their absence, outcome is better than previously published. Counselling must take place only after full fetal medicine assessment and should be based upon prenatal data.
Clinical outcome of patients undergoing multivessel coronary stent implantation.
OBJECTIVES: To evaluate the outcome of patients undergoing multivessel coronary stent implantation. BACKGROUND: Percutaneous transluminal coronary angioplasty has been shown to be an effective treatment for multivessel coronary artery disease, although the need for repeat revascularization continues to be a limitation. Intracoronary stent placement has been shown to reduce the need for subsequent revascularization. METHODS: Seventy-seven patients without prior coronary artery bypass grafting (CABG) undergoing multivessel coronary revascularization in which stents were placed in all treated segments over a 5 year period at our institution were identified. Clinical and angiographic characteristics and outcomes were analyzed. RESULTS: One hundred and eighty-eight coronary lesions were successfully treated (2.1+/-0.3 treated vessels/patient, 2.4+/-0.6 treated lesions/patient) using 2.8+/-1.2 stents/patient (range 2-9) and 1.4+/-0.8 stents/vessel (range 1-6). Procedural success rate [angiographic success without in-hospital death, Q-wave myocardial infarction (Q-wave MI) or CABG] was achieved in 76 of 77 patients (98.7%). Anatomically complete revascularization was achieved in 46 (59.7%) patients. Modified ACC/AHA Type B2 and C lesions comprised 75.5% of the 188 lesions. The left anterior descending artery was treated in 57 (74.0%) patients. The indication for stent placement was dissection or threatened/abrupt closure in 54 segments (28.8%). In-hospital events included death in one patient (1.3%); no patient suffered a Q-wave MI or required CABG. Stent occlusion occurred in two (2.6%) patients, and repeat percutaneous intervention of the target vessel was also required in these two patients. Any of these adverse events occurred in three (3.9%) patients. No further events occurred after hospital discharge in the 30 days after the procedure. Of hospital survivors (n=76), adverse events at 6 months included death in two patients (2.6%), MI in two (2.6%), CABG in six (7.9%); nine (11.8%) patients underwent repeat percutaneous intervention and 15 (19.7%) underwent any revascularization. CONCLUSIONS: Multivessel coronary stent placement is associated with an excellent procedural success rate despite a high rate of adverse lesion characteristics, and a low rate of death or MI during follow-up. The need for further revascularization compares favorably with published rates with multivessel PTCA and single stent implantation for discrete de novo lesions.
Expansion and division of conjoined twins.
Omphalopagus conjoined twins were born by cesarean section after their 24-year-old gravida 2, para 1 mother went into labor at 35 weeks' gestation. Initial studies included roentenograms, an upper gastrointestinal study, small bowel follow-through, and computerized tomography with intravenous contrast from neck through pelvis. Results of these studies showed that the twins had very little shared vasculature, but did share a pericardium and liver parenchyma. The infants were allowed to gain weight and grow. After 3 weeks, tissue expanders were placed subcutaneously and were rapidly expanded in 2 weeks. The infants were then separated. An Argon Beam Coagulator was used to aid the separation of the liver. The abdominal fascia was closed primarily on each infant, and the skin easily closed without tension. During the first 36 hours of the postoperative course, both infants required significant ventilatory support including inhaled nitric oxide. After this period, the ventilatory support decreased dramatically and rapidly. The infants were discharged 9 days after their surgical separation. Conjoined omphalopagus twins, the use of tissue expanders and the Argon Beam Coagulator, and the postoperative course are discussed.
A stepwise approach to evaluation of undernutrition and failure to thrive.
The primary care physician is key to evaluating children who are undernourished or failing to thrive. The comprehensive stepwise approach to evaluation is simple and effective. Positive outcomes can be expected.
Serial transvaginal ultrasonography following McDonald cerclage and repeat suture insertion.
The aim of this study was to explore the hypothesis that serial transvaginal ultrasonography identifies early evidence of suture failure and that repeat cerclage delays delivery. We undertook a review of our policy of transvaginal ultrasonographic cervical surveillance after McDonald cerclage and of repeat suture insertion if persistent cervical effacement developed. Data from 26 pregnancies in 26 women are analyzed. The women had had a total of 57 mid-trimester miscarriages with a median of 2 (1-6) mid-trimester losses per woman. Twelve (46%) of the 26 women developed cervical changes at scan and underwent repeat cerclage. All 14 women who had a single suture inserted progressed to live births but 1 of the 13 women who had repeat cerclage had a mid-trimester miscarriage (p>0.05). The median gestation at delivery for the women who had repeat cerclage was 35 (22-39) weeks compared with 38 (36-40) weeks for those who had a single suture (p>0.05). The median interval from the detection of cervical changes at scan to delivery was 13 (4-19) weeks. Serial transvaginal ultrasonography after cervical cerclage identifies a group of women who are more likely to deliver preterm, and provides an opportunity for intervention (repeat cerclage) which appears to delay delivery by an average of 7 weeks.
Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth.
A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.
Acquired immunodeficiency syndrome in Alabama: special concerns for black women.
BACKGROUND: Among AIDS case reports from rural and small town areas of the United States, rates are higher in the South than in any other part of the country. METHODS: For this study, we analyzed AIDS surveillance statistics from the state of Alabama for trends, distributions, and populations affected. We aggregated Alabama AIDS surveillance data in 5-year intervals--1981 to 1985, 1986 to 1990, 1991 to 1995--and made comparisons based on geographic area of residence of people diagnosed with AIDS. RESULTS: Of the 3,558 cases of AIDS reported in Alabama in the period 1981 to 1995, 86% were men and 14% were women. Among women, 69.7% were black and 29.1% were white. Among men, 48.4% were black and 50.9% were white. We compared these figures with 1995 Alabama population estimates of 26.2% black, 73.7% white, and < 1% another race. The rates for black women and white women increased 170-fold and 23-fold, respectively, from the 1981 to 1985 period to the 1991 to 1995 period. For the same periods, case rates for black men and white men increased more than 80-fold and 50-fold, respectively. Black women showed a rise per 100,000 population-from 0.3 (1981 to 1985) in both northern and southern Alabama to 37 in northern Alabama and 64 in southern Alabama (1991 to 1995). CONCLUSIONS: Black women are at disproportionately high risk, particularly in the southern counties of Alabama. HIV is increasingly prevalent in rural and small town communities in Alabama and is more often transmitted heterosexually than it has been previously.
Development and validation of a discriminative quality of life questionnaire for osteoporosis (the OPTQoL).
We report the development and validation of an osteoporosis-targeted quality of life questionnaire to measure the impact of the disease in the general population. From multiple focus groups with women with osteoporosis, healthy women at risk for osteoporosis, spouses and relatives of women with osteoporosis, and health care providers, we identified over 300 potential items related to the disease. A lengthy questionnaire incorporated these items and was administered to a second large study cohort of 222 women with clinical osteoporosis (history of fracture, significant height loss, and/or kyphosis); 101 women with known low bone mineral density levels that would categorize them as osteoporotic but who had not yet shown obvious physical manifestations of the disease; and 142 women with other conditions (such as arthritis, cancer, depression) expected to also have an impact on quality of life. Final items from among the original 300 were chosen for their demonstrated relationship with osteoporosis as measured by clinical manifestations and low bone density and with quality of life measured by a standard generic questionnaire, the SF-36. The final questionnaire contains 26 scored items in three domains-physical activity, adaptations, and fears- and six nonscored questions relating to osteoporotic changes and diagnosis. This instrument is unique among osteoporosis-targeted questionnaires in that it attempts to measure the total impact of the disease on quality of life within a population at a single point in time.
Human corneal and lens aldehyde dehydrogenases. Purification and properties of human lens ALDH1 and differential expression as major soluble proteins in human lens (ALDH1) and cornea (ALDH3).
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Deep inelastic scattering of polarized electrons by polarized 3He and the study of the neutron spin structure.
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Long-term dual perfusion of isolated human placental lobules with improved oxygenation for infectious diseases research.
An improved method for long-term perfusion of the isolated human term placental lobule has been developed to investigate the maternofetal transfer of infectious agents, in particular the human immunodeficiency virus (HIV). The purpose of this paper is to describe those modifications that allow for substantially prolonged perfusions in in a biohazard environment. The method described has been adapted from previous models. The perfusion apparatus has been modified for use within a biohazard hood, and, intravenous bags contain the medium for circulation of perfusates in closed circuits. A Mera Silox-S 0.3 membrane oxygenator delivers more oxygen to the tissue, and, Electromedic Cardioplegia heat exchangers warm the perfusate prior to oxygenation. Viability criteria (glucose consumption, lactate production, de novo production of human placental lactogen (hPL), volume loss, flow, temperature, pressure, oxygen transfer, carbon dioxide production, absence of IgM transfer and light and electron microscopy) demonstrate that the placental tissue remains in a functional state throughout the perfusion. Oxygen and glucose consumption are both stable over time; lactate levels remain constant; and hPL continues to be produced. These significant modifications of the perfusion system have permitted the investigators to increase the duration of perfusion to 48 h while preserving normal metabolic function of ultrastructurally intact tissue as demonstrated by ultra structural observations. This perfusion model device provides biohazard precautions and may be applied to other studies of placental physiology.
Induction of RANTES expression by astrocytes and astrocytoma cell lines.
The cellular infiltrate found during the acute phase of multiple sclerosis (MS) consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during the inflammatory response. We examined the ability of human astrocytoma cell lines, as well as primary human and rat astrocytes, to generate a specific member of the intercrine/chemokine family of cytokines, RANTES, when exposed to TNF-alpha, IL-1 beta and IFN-gamma. Astrocytoma cells as well as primary astrocytes produced RANTES upon incubation with TNF-alpha or IL-1 beta. IFN-gamma alone did not induce RANTES production by astrocytes, but it potentiated the effects of either TNF-alpha or IL-1 beta. Induction of RANTES by TNF-alpha was mediated by the p55 receptor since a specific anti-p55 antiserum mimicked the effect of TNF-alpha. These results indicate that human astrocytes are capable of generating a cell-specific chemokine that can account for the inflammatory cellular infiltrate observed during the acute phase of MS, in a process that is regulated by cytokines.