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Biomedical subjects

David Segal

Publications and source records attributed to David Segal.

16 recordsLinked to original sources

Idiopathic spontaneous hemoperitoneum during pregnancy.

We present a case of a 24-year old, otherwise healthy, primigravida that was admitted at term with severe abdominal pain, hemoperitoneum, hypovolemic shock and severe fetal bradycardia. There was no history of abdominal trauma. Due to suspected fetal distress and placental abruption an emergency cesarean section was performed. Careful exploration of the abdominal cavity, uterus and placenta did not reveal the origin of hemorrhage, placental abruption was ruled out. Idiopathic spontaneous hemoperitoneum is a rare and life threatening condition. The origin of the hemorrhage often remains obscure, even after a thorough workup. To the best of our knowledge, this is the first case of idiopathic spontaneous hemoperitoneum reported in a pregnant patient at term. A review of the literature was undertaken.

Adult↗

Identification of novel genes expressed during rhabdomyosarcoma differentiation using cDNA microarrays.

Rhabdomyosarcomas (RMS) are highly aggressive tumors that are thought to arise as a consequence of the regulatory disruption of the growth and differentiation of skeletal muscle progenitor cells. Normal myogenesis is characterized by the expression of the myogenic regulatory factor gene family but, despite their expression in RMS, these tumor cells fail to complete the latter stages of myogenesis. The RMS cell line RD-A was treated with 12-O-tetradecanoylphorbol-13-acetate to induce differentiation and cultured for 10 days. RNA was extracted on days 1, 3, 6, 8 and 10. A human skeletal muscle cDNA microarray was developed and used to analyze the global gene expression of RMS tumors over the time-course of differentiation. As a comparison, the genes identified were subsequently examined during the differentiated primary human skeletal muscle cultures. Prothymosin alpha (PTMA), and translocase of inner mitochondrial membrane 10 (Tim10), two genes not previously implicated in RMS, showed reduced expression during differentiation. Marked differences in the expression of PTMA and Tim10 were observed during the differentiation of human primary skeletal muscle cells. These results identify several new genes with potential roles in the myogenic arrest present in rhabdomyosarcoma. PTMA expression in RMS biopsy samples might prove to be an effective diagnostic marker for this disease.

Adult↗

Association of nausea and vomiting in pregnancy with lower body mass index.

OBJECTIVE: To assess the effect of body mass index (BMI) on the tendency of pregnant women to vomit and on their general condition during pregnancy. STUDY DESIGN: We included patients in this study who presented to our gynecological emergency room and clinic during their first trimester of pregnancy. All women completed a questionnaire assessing obstetrical and physical characteristics, including gravidity, parity, gestational age, height and weight for BMI calculation. Women were requested to report the number of vomiting episodes per day and their general condition using a 1 to 10 scale (1-good, 10-bad). Patients were allocated to either a low-frequency group (0-1 vomiting episodes per day) or to a high-frequency group (2 and more vomiting episodes per day). RESULTS: Sixty-one consecutive women were included in the study. The low frequency group consisted of 35 women and the high frequency group included the remaining 26 women. The BMI was significantly lower in the high frequency group as compared to the low frequency group (21.8 +/- 3.5 versus 24.4 +/- 4.7, respectively; P <0.05). Patients in the high frequency group also reported a worse general condition than those in the low frequency group (7.6 +/- 2.2 versus 3.5 +/- 2.1, respectively; P <0.05). CONCLUSION: Patients with higher frequency of vomiting episodes during the first trimester of pregnancy tend to have a lower BMI score and a worse general condition than patients with low frequency of vomiting episodes.

Adult↗

Transfer of insulin lispro across the human placenta.

Our in vitro perfusion study confirms the result of the Boskovic et al., that insulin lispo is not crossing the human placental membranes at low concentrations. In our study maternal steady state concentration reached 48 +/- microU in the maternal artery and 28 +/- 1 microU in the maternal vein, while in the fetal site insulin lispo was not detected. However, the concentration of insulin lispo in placental tissue was 1836 +/- 220 microU.

Female↗

Identification of genes differentially regulated by the P210 BCR/ABL1 fusion oncogene using cDNA microarrays.

OBJECTIVE: The t(9;22) translocation is associated with more than 95% of cases of chronic myeloid leukemia. The resulting fusion of the BCR and ABL1 loci produces the constitutively active BCR/ABL1 tyrosine kinase. A wide range of signal transduction molecules are activated by BCR/ABL1, including MYC, PI-3 kinase, and different STAT molecules. In contrast, relatively few genes are known to be regulated by BCR/ABL1 at the level of transcription. MATERIALS AND METHODS: In an effort to better understand the transcriptional program activated by BCR/ABL1, we used cDNA microarrays to evaluate the relative expression of approximately 6450 human genes in U937 myelomonocytic cells expressing P210 BCR/ABL1 via a tetracycline-inducible promoter. RESULTS: We confirmed the previously reported up-regulation of the PIM1 and JUN oncogenes by BCR/ABL1. In addition, we identified 59 more genes up-regulated by BCR/ABL1. Interestingly, roughly one third of these were genes previously reported to be interferon (IFN)-responsive, including the OAS1, IFIT1, IFI16, ISGF3G, and STAT1 genes. An additional seven BCR/ABL1-regulated genes were found to be IFN-responsive in U937 cells. The expression profile also included genes encoding transcription factors, kinases, and signal transduction molecules, as well as genes regulating cell growth, differentiation, apoptosis, and cell adhesion, features previously suggested to be affected by BCR/ABL1. CONCLUSION: These observations shed novel insight into the mechanism of BCR/ABL1 action and provide a range of targets for further investigation.

Fusion Proteins, bcr-abl↗

Extrusion of fetus into the abdominal cavity following complete rupture of uterus: a case report.

A gravida 10 para 9, after one Cesarean section (CS) followed by four vaginal deliveries was admitted at term without uterine contractions complaining of abdominal pain. The type of uterine scar was unknown. Severe bradycardia was observed at admission and an emergency Cesarean section was performed. A complete uterine rupture was revealed, the fetus in intact membranes and placenta were found in the abdominal cavity.

Abdomen↗

[Anticoagulation in pregnant women with prosthetic heart valve--a new approach for therapy].

The treatment of women in childbearing age with a mechanical heart valve is a challenge for the medical staff. Warfarin (Coumadin) is considered to be a safe and effective anticoagulant for patients with prosthetic heart valves. However, treatment during pregnancy poses many difficulties, especially during the first trimester, due to its ability to cross the placenta and its associated fetotoxicity. Treatment with heparin during the first trimester decreases the rate of embryopathy, but increases maternal morbidity and mortality. Warfarin therapy throughout pregnancy, which is common mainly in Europe, carries low rates of maternal complications and roughly six percent of embryopathy. Several studies compared warfarin treatment throughout pregnancy versus treatment with heparin during the first trimester. The relationship between daily warfarin doses and the rate of embryopathy was recently investigated. We report two cases of pregnant women with mechanical heart valves who were treated with heparin during the first trimester. Both underwent an emergency replacement of the prosthetic valve during the eighth week of pregnancy. In this article, we review the literature regarding anticoagulation therapy in pregnant women with prosthetic heart valves; the comparison between treatment with warfarin throughout pregnancy and heparin in the first trimester; and the relation of daily warfarin doses with the rate of embryopathy. The two case reports demonstrate the common approach for therapy and the danger within it. In the discussion we present a new approach for treating pregnant women with prosthetic valve and guidelines for the medical staff.

Adult↗

Revision total knee arthroplasty.

BACKGROUND: Revision total knee arthroplasties are performed with increasing frequency due to the increasing numbers of primary arthroplasties. OBJECTIVES: To retrospectively analyze 71 patients who underwent 78 revision total knee arthroplasties during the years 1991 to 1999 METHODS: We evaluated the revised knees using the Knee Society Clinical Rating System after an average follow-up period of 3 years and 9 months (2-10 years). The indications for revision included pain and instability, deep infection of the joint, complaints linked to the patella, or post-trauma to the operated knee. RESULTS: The average knee score (evaluation of the knee joint itself) calculated after the revision was 74.5. The results on the knee score were excellent (> 85) in 48% of patients and poor (< 60) in 22%. The functional results (patient's ability to walk and climb stairs) were only 48.3. CONCLUSION: Although the revision of total knee replacements is known to be problematic, most patients show good results on knee examination, and reasonable functional results given the factors involved.

Aged↗

A custom-built insulin resistance gene chip.

OBJECTIVES/AIM: Microarray (gene chip) technology offers a powerful new tool for analyzing the expression of large numbers of genes in many experimental samples. The aim of this study was to design, construct, and use a gene chip to measure the expression levels of key genes in metabolic pathways related to insulin resistance. METHODS: We selected genes that were implicated in the development of insulin resistance, including genes involved in insulin signaling; glucose uptake, oxidation, and storage; fat uptake, oxidation, and storage; cytoskeletal components; and transcription factors. The key regulatory genes in the pathways were identified, along with other recently identified candidate genes such as calpain-10. A total of 242 selected genes (including 32 internal control elements) were sequence-verified, purified, and arrayed on aldehyde-coated slides. RESULTS: Where more than 1 clone containing the gene of interest was available, we chose those containing the genes in the 5' orientation and an insert size of around 1.5 kb. Of the 262 clones purchased, 56 (21%) were found to contain sequences other than those expected. In addition, 2 (1%) did not grow under standard conditions and were assumed to be nonviable. In these cases, alternate clones containing the gene of interest were chosen as described above. The current version of the Insulin Resistance Gene Chip contains 210 genes of interest, plus 48 control elements. A full list of the genes is available at http://www.hbs.deakin.edu.au/mru/research/gene_chip_tech/genechip_three.htm/. CONCLUSIONS: The human Insulin Resistance Gene Chip that we have constructed will be a very useful tool for investigating variation in the expression of genes relevant to insulin resistance under various experimental conditions. Initially, the gene chip will be used in studies such as exercise interventions, fasting, euglycemic-hyperinsulinemic clamps, and administration of antidiabetic agents.

Base Sequence↗

New approaches to gene discovery with animal models of obesity and diabetes.

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes.

Animals↗

Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.

BACKGROUND: The treatment of open fractures of the tibial shaft is often complicated by delayed union and nonunion. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention. METHODS: In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively. RESULTS: Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010). CONCLUSIONS: The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.

Adolescent↗

Central and peripheral mechanisms in chronic tension-type headache.

The second exteroceptive suppression of masseter muscle activity (ES2) and tenderness in pericranial muscles were evaluated in 112 young adults who met IHS criteria in the following diagnostic classifications: 31 chronic tension headache, 31 episodic tension headache, 33 migraine without aura and 17 migraine with aura. An additional 31 subjects served as controls. Pericranial muscle tenderness better distinguished diagnostic subgroups and better distinguished recurrent headache sufferers from controls than did masseter ES2. Chronic tension headache sufferers exhibited the highest pericranial muscle tenderness, and controls exhibited the lowest tenderness (P < 0.01). All chronic tension headache sufferers exhibited muscle tenderness in at least one of the pericranial muscles evaluated, while tenderness was exhibited by 52% of controls. The association between pericranial muscle tenderness and chronic tension headache was independent of the intensity, frequency, or chronicity of headaches. Our findings raise the possibility that pericranial muscle tenderness is present early in the development of tension headache, while ES2 suppression only emerges later in the evolution of the disorder.

Adult↗

Effect of OB/GYN residents' fatigue and training level on the accuracy of fetal weight estimation.

OBJECTIVE: To determine the effect of Ob/Gyn residents' fatigue and training level on the accuracy of their clinical and ultrasonographical estimation of fetal weight (EFW). METHODS: In this study, clinical and ultrasonographical EFWs were performed by various residents. Actual birth weight, gravidity, parity, gestational age, body mass index, presence or absence of diabetes and hypertensive diseases, presentation and amniotic fluid index were recorded. All EFWs were divided into 3 groups according to the hour they were performed. All residents were divided into 4 groups according to their training level. The accuracy of EFW as compared with actual birth weight was then analyzed according to the shift and to the residents' seniority by using the ANOVA test. Multivariate analysis was performed to evaluate the factors that significantly and independently affected the weight evaluation. RESULTS: Statistically significant differences were found between the clinical EFW and the birth weight among the working shifts for birth weights of 2,500 g and more (p = 0.032 and p = 0.035). For clinical EFW, night shifts were the most inaccurate (9.27, 8.05 and 9.78% of error for day, evening and night shift, respectively; p = 0.03). The accuracy of ultrasonographical EFW was not affected by the residents' fatigue level. The residents' training level did not alter the accuracy of either clinical or sonographical EFW. The accuracy of clinical EFW was affected independently by the work shift (p = 0.01), whereas no factor was found to independently effect the accuracy of ultrasonographic EFW. CONCLUSIONS: Ob/Gyn residents' fatigue affects the accuracy of clinical but not ultrasonographical EFWs. Residents' training level does not alter either the clinical or sonographical EFW.

Analysis of Variance↗