Search PubMed⌕ Search

Biomedical subjects

K Ward

Publications and source records attributed to K Ward.

At least 73 records · Page 4Linked to original sources
PubMed1997

Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction.

OBJECTIVES: The factor V Leiden mutation is the most common genetic predisposition to thrombosis. However, little is known concerning the reproductive outcome of mutation carriers or prenatal expressivity of this thrombogenic mutation. Our purpose was to examine whether this mutation presents phenotypically as miscarriage or idiopathic placental thrombosis. STUDY DESIGN: We performed two studies. First, a case-control comparison to determine whether fetal or maternal carriers of the factor V Leiden mutation are at risk for spontaneous miscarriage was performed, and, second, a cohort study evaluating placental infarction in fetuses carrying this mutation was performed. RESULTS: We found a twofold increase in the factor V Leiden carrier frequency in 12 of 139 (8.6%) abortuses compared with 17 of 403 (4.2%) unselected pregnant women seen in the labor and delivery suite and, even more remarkable, a tenfold increase in the fetal carrier frequency in 10 of 24 (42%) placentas with > 10% placental infarction compared with 7 of 372 (1.9%) placentas with < 10% placental infarction. CONCLUSIONS: These findings suggest a prenatal phenotype and effects of this mutation at the fetoplacental interface. If large prospective studies confirm these findings, then testing for this thrombogenic mutation should be considered in women and placental tissue from spontaneous abortuses and placentas with evidence of placental infarction. In addition to identifying individuals and families at risk for thrombosis, this information may help to improve our understanding of hemostasis and circulatory disturbances at the fetoplacental interface.

Abortion, Spontaneous↗
PubMed1997

A promoter mutation that increases transcription of the tumor necrosis factor-alpha gene is not associated with preterm delivery.

OBJECTIVE: Increased amniotic fluid concentrations of tumor necrosis factor-alpha are observed in women with preterm labor and subsequent preterm birth. We tested whether a mutation in the promoter region of tumor necrosis factor-alpha gene, TNF T2, which increases transcription of the gene, is more frequent in a preterm delivery cohort. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 203 women and 44 fetuses delivered at < 37 weeks of estimated gestational age. The polymerase chain reaction was used to amplify the promoter region of the tumor necrosis factor-alpha gene. The resulting polymerase chain product was subjected to allele-specific enzymatic digestion with Nco I. Fragments were size fractionated on a 3% Metaphor agarose gel stained with ethidium bromide. Results were analyzed with use of a chi 2 contingency table. RESULTS: No statistically significant differences for either the TNF T1 or TNF T2 allele frequencies were found between women or fetuses delivered preterm compared with a control group or previously published allele frequencies. CONCLUSIONS: The frequency of this tumor necrosis factor-alpha promoter mutation, TNF T2, is not increased in either women or fetuses delivered at < 37 weeks' gestation. Basal levels of tumor necrosis factor-alpha are unlikely to affect a woman's risk of preterm delivery. Tumor necrosis factor-alpha variants should not be used as a predictive test for preterm delivery.

Adolescent↗
PubMed1997

The incidence of the factor V Leiden mutation in an obstetric population and its relationship to deep vein thrombosis.

OBJECTIVE: A common missense mutation in the factor V gene, the Leiden mutation, renders factor Va resistant to cleavage inactivation by activated protein C and predisposes patients to thrombotic events. We sought to evaluate the prevalence of the Leiden mutation and the associated thromboembolic events in a community hospital's low-risk obstetric population. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 407 women. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnI 1 for mutation detection. Medical charts were reviewed and patient characteristics, including age, gravidity, parity, obstetric complications, medical complications, and mode of delivery, were recorded. RESULTS: Fourteen of the 407 women carried the factor V Leiden mutation (13 heterozygotes and 1 homozygous mutant) for an allele frequency of 3%, consistent with the published carrier rate. Four of the 14 carriers (28%) had deep venous thrombosis, whereas the frequency of deep venous thrombosis in this obstetric population was <1%. Another patient carrying the mutation had a consumptive coagulopathy of unknown etiology at 20 weeks' gestation, necessitating delivery. CONCLUSIONS: The Leiden mutation is relatively common in the general obstetric population. The high rate of deep venous thrombosis noted in our series suggests the need for genetic testing for this mutation in women with a thrombotic event during pregnancy.

Adult↗
PubMed1997

The factor V Leiden mutation is not a common cause of recurrent miscarriage.

Some investigators suggest that placental thrombosis and infarction can cause recurrent miscarriage. We have shown that the common missense mutation in the factor V gene, the Leiden mutation, which renders factor Va resistant to cleavage inactivation by activated protein C, predisposes to placental thrombosis and spontaneous miscarriage. Our objective was to determine the frequency of the Leiden mutation in a population with well-characterized idiopathic recurrent miscarriage. DNA was extracted from whole blood of 40 couples with a history of idiopathic recurrent miscarriage and 25 couples with a history of proven fertility (seven or more live births). The polymerase chain reaction was used to amplify exon 10 of the factor V gene followed by allele-specific restriction with Mnl1 for mutation detection. Results were analyzed with a chi 2 contingency table. None of the 40 women with idiopathic recurrent miscarriage carried the mutation and only one of their reproductive partners was heterozygous for the mutation. Similarly, none of the control women carried the mutation, and only one of the 25 control male partners was heterozygous for the mutation. In our referral population, the factor V Leiden mutation which predisposes to thrombosis is not a common cause of recurrent miscarriage.

Abortion, Habitual↗
PubMed1997

Gene targeting demonstrates additive detrimental effects of interleukin 1 and tumor necrosis factor during pancreatitis.

BACKGROUND & AIMS: During severe pancreatitis, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are produced in large quantities. The aim of this study was to determine whether either one plays a more dominant role and if their detrimental effects are additive. METHODS: Necrotizing pancreatitis was induced in transgenic (-/-) knockout mice deficient in either IL-1 type 1 receptors, TNF type 1 receptors, or both IL-1 and TNF type 1 receptors. Wild-type mice served as controls. Mortality was assessed for 10 days. Additional animals were killed on days 0, 1, 2, 3, and 4 for determination of pancreatitis severity. RESULTS: All three knockout groups showed decreased amylase and lipase, histological score, serum IL-6, and mortality compared with wild-type groups. Animals devoid of receptors for both cytokines showed improved survival and decreased IL-6 levels compared with those devoid of either IL-1 or TNF receptors individually, yet they failed to show a further decrease in pancreatitis severity. CONCLUSIONS: Preventing the activity of IL-1beta or TNF-alpha has a nearly identical beneficial effect on the severity and mortality of acute pancreatitis. Preventing the activity of both cytokines concurrently has no additional effect on pancreatitis severity but further attenuates the systemic stress response and is associated with an additional but modest decrease in mortality.

Amylases↗
PubMed1997

Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.

Loss-of-function mutations in the G4.5 gene have been shown to cause Barth syndrome (BTHS), an X-linked disorder characterized by cardiac and skeletal myopathy, short stature, and neutropenia. We recently reported a family with a severe X-linked cardiomyopathy described as isolated noncompaction of the left ventricular myocardium (INVM). Other findings associated with BTHS (skeletal myopathy, neutropenia, growth retardation, elevated urinary organic acids, and mitochondrial abnormalities) were either absent or inconsistent. A linkage study of the X chromosome localized INVM to the Xq28 region near the BTHS locus, suggesting that these disorders are allelic. We screened the G4.5 gene for mutations in this family with SSCP and direct sequencing and found a novel glycine-to-arginine substitution at position 197. This position is conserved in a homologous Caenorhabditis elegans protein. We conclude that INVM is a severe allelic variant of BTHS with a specific effect on the heart. This finding provides further structure-function information about the G4.5 gene product and has implications for unexplained cases of severe infantile hypertrophic cardiomyopathy in males.

Abnormalities, Multiple↗
PubMed1997

Assessment of bone status using the contact ultrasound bone analyser.

Broadband ultrasound attenuation (BUA) was measured at the calcaneum in 367 healthy white schoolchildren (193 girls and 174 boys) aged 6-15 years. The mean calcaneal BUA increased with age and was significantly related to age, height, and weight. Measurement of calcaneal BUA may be helpful in the radiation free assessment of childhood disorders associated with increased fracture risk.

Adolescent↗
PubMed1997

Large vestibular aqueduct syndrome: a genetic disease?

OBJECTIVE: Our objective was to determine the familial incidence of large vestibular aqueduct syndrome (LVAS) detected by CT and MR imaging and to propose the genetic inheritance of LVAS. MATERIALS AND METHODS: We retrospectively reviewed cases of LVAS revealed by temporal-bone CT and MR imaging at the University of Utah Health Sciences Center. We interviewed 25 patients with LVAS regarding family history of hearing loss. Any family members with onset of hearing loss before 30 years old also underwent CT and MR imaging. The vestibular aqueduct (on CT scans) or the endolymphatic duct (on MR images) was measured at the midpoint of the distal limb. A measurement greater than 1.5 mm in diameter was considered abnormally large. Diagnosis of LVAS was made if the patient had hearing loss and positive imaging findings. RESULTS: Of the 25 patients, five were found to have familial involvement, resulting in subsequent study of eight additional symptomatic individuals. A total of 33 patients had positive CT or MR imaging findings. Twenty-nine underwent both studies, two underwent CT only, and two underwent MR imaging only. Among the 33 patients with LVAS, 39% familial occurrence was observed (13 patients). In four of the five different families, the involvement occurred among siblings in one generation. In one of the five families, the involvement occurred in two generations, affecting an uncle and a cousin of the patient. CONCLUSION: In patients with LVAS, a significant subgroup had familial involvement. Based on the pedigrees of the familial cases, the pattern was most consistent with autosomal recessive inheritance, although a smaller component of autosomal dominant or multifactorial inheritance may exist.

Deafness↗
PubMed1997

Cauda equina syndrome resulting in late sequela of calcaneal gait and neuropathic heel ulcer.

The case of a 27-year-old female, 5 years after a motor vehicle accident that resulted in spinal cord damage, is reviewed. She progressed well after her accident for 4 years, at which time she developed a neuropathic heel ulceration, aggravated by her calcaneal gait and pregnancy weight gain. The rarity of such a case involving neuropathic ulceration and calcaneal gait after partial deficit of cauda equina function prompted this article.

Adult↗
PubMed1997

Premature rupture of the amniotic membranes diagnosed by placental bed biopsy.

Biopsies of the maternal placental bed are usually made to investigate abnormalities of the uteroplacental vasculature. A placental bed biopsy was taken from a 36-year-old, gravida 4, para 3 woman. She had delivered normally at 39 weeks of gestation, following spontaneous labor, without clinical signs of premature rupture of the membrane. She was discharged without complications of the delivery. The placental bed biopsy showed histologic signs of amniotic rupture. There were desquamated stratified squamous epithelial cells in edema fluid between muscle fibers, surrounded by intense neutrophilic inflammation. Uterine venules contained fibrin clots with squamous epithelial cells. Some veins had plugs of detached, coiled, and occlusive amniotic thrombi. To our knowledge, histologic evidence of amniotic membrane rupture and amniotic fluid thrombosis with local embolization has not been previously reported in a biopsy of the placental bed.

Adult↗
PubMed1996

AIDS. HIV in prison: the importance of prevention.

Although the prison service aims to give inmates the same quality and range of health care services as those received by the general public, the provision of condoms and materials for cleaning shared injecting equipment is not the norm. These relatively inexpensive measures could, however, save many lives.

Condoms↗
PubMed1996

Cytostatic effect of Epstein-Barr virus latent membrane protein-1 analyzed using tetracycline-regulated expression in B cell lines.

Tetracycline-regulated vectors were used to obtain inducible expression in stable transfected B cell lines of two Epstein-Barr virus (EBV) latent genes, LMP1 and EBNA2. The transfected genes were tightly repressed by low, nontoxic concentrations of tetracycline (< or = 1 microgram/ml) and, following removal of tetracycline, were induced to levels comparable to or up to 3x that of EBV-transformed normal lymphoblastoid cell lines. In transfected DG75 cells, induced expression of LMP1, but not of EBNA2, led to the expected upregulation of various cell surface markers, including: CD40, CD54, CD58, and HLA class I.A novel observation was that both LMP1 and EBNA2 independently caused the downregulation of surface IgM, an effect mirrored in EBV-positive Burkitt lymphoma lines undergoing phenotypic drift during the transition from latency I to latency III in which both LMP1 and EBNA2 are upregulated. Most remarkably, induced LMP1 expression almost completely inhibited cell growth for 4 to 5 days, after which the cells recovered a limited proliferative capacity. The cytostatic effect of LMP1 was observed in all three B cell lines studied: DG75, BJAB, and Akata. Further analysis showed that induction of LMP1 coincided with a reduction in the levels of c-myc, and that the cytostatic effect was due to an accumulation of cells at the G2/M phase of the cell cycle. These data suggest a novel function for the LMP1 oncogene in controlling the proliferation of EBV-infected cells by regulating progress through G2/M phase.

Antigens, Surface↗
PubMed1996

Determination of fetal RhD status from uncultured amniocytes.

OBJECTIVE: To determine the accuracy of DNA analysis for fetal RhD status using polymerase chain reaction (PCR) on uncultured amniocytes. METHODS: Three hundred forty-seven amniotic fluid (AF) samples obtained for a variety of clinical indications were tested for fetal RhD status using PCR and primers specific for the genes coding for D and Cc/Ee. Fetal RhD status was confirmed by serologic methods on neonatal cord blood obtained at the time of delivery. RESULTS: In 346 of 347 cases (99.7%), the PCR results of AF were in agreement with the serologic RhD blood type. The single error was in an RhD-negative fetus (misidentified as RhD-positive) whose AF was contaminated with blood from an RhD-positive mother. The likelihood of an erroneous result was 0.3%. CONCLUSION: Polymerase chain reaction-based analysis of fetal RhD status using uncultured amniocytes and established primers appears to be highly accurate.

Amniotic Fluid↗
PubMed1996

The factor V Leiden mutation may predispose women to severe preeclampsia.

OBJECTIVE: A recent study showed that resistance to activated protein C may underlie some cases of severe preeclampsia. A common missense mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C. Our objective was to determine whether this mutation is more prevalent in patients with severe preeclampsia than in normotensive controls. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 158 gravid women meeting criteria of The American College of Obstetricians and Gynecologists for severe preeclampsia and 403 normotensive gravid women. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by allele-specific restriction with Mnl 1 for mutation detection. Results were analyzed with a chi(2) contingency table. RESULTS: No patients were homozygous for the Leiden mutation. Fourteen of 158 women with severe preeclampsia (8.9%) were heterozygous for the Leiden mutation compared with 17 of 403 normotensive gravid controls (4.2%). The difference in frequency between women with severe preeclampsia and normotensive controls was statistically significant, chi(2) 4.686, p = 0.03. CONCLUSIONS: Our data suggest that carriers of the factor V Leiden mutation are at increased risk for severe preeclampsia. Deoxyribonucleic acid analysis for the factor V Leiden mutation could serve as one component of a genetic screening profile for preeclampsia and other adverse pregnancy outcomes. Women who carry this mutation are at increased risk for deep venous thrombosis. Carriers of this common thrombophilic mutation may be identified so that adequate counseling regarding future contraceptive usage and effective thromboembolic prophylaxis during pregnancy and surgical procedures may be offered.

Adult↗