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Biomedical subjects

J Mather

Publications and source records attributed to J Mather.

At least 19 recordsLinked to original sources
PubMed2000

A preliminary study of sonographic grading of fetal intracardiac echogenic foci: feasibility, reliability and association with aneuploidy.

OBJECTIVES: To prospectively and quantitatively grade intracardiac echogenic focus/foci (ICEF) using sonographic gain reduction and to determine the association of ICEF by grade with fetal aneuploidy. METHODS: Women referred for raised maternal age (> or = 35 years), or > 18 years of age and with a Down syndrome risk > or = 1/270, increased trisomy 18 risk by second trimester serum screen or a prior aneuploid offspring were included in this institutionally approved protocol. Only pregnancies of gestational age between 14 and 24 weeks were included. All women had a targeted ultrasound and were offered fetal chromosome analysis. The classification of ICEF was made from a four-chamber view of the fetal heart. The echo amplitude of the ICEF was compared to that of the thoracic spine and categorized according to the comparative gain setting at which the image of the relevant structure disappeared: Grade O = no ICEF present, Grade 1 = ICEF image lost before thoracic spine when gain was reduced, Grade 2 = ICEF image lost at same gain setting as thoracic spine, Grade 3 = thoracic spine image lost before ICEF. The primary outcome was a prenatally or post-natally detected chromosomal abnormality. RESULTS: A total of 885 eligible women were examined during the 21-month study period. ICEF were seen in 29 (3.3%) fetuses: 24(83%) in the left ventricle and five (17%) in the right ventricle. A chromosome abnormality was identified in 13/671 (1.9%) fetuses without ICEF (Grade 0) and 0/21 (0%) fetuses with Grade 1 ICEF. In contrast, two of five (40%) fetuses with Grade 2 ICEF were aneuploid (P = 0.005). No Grade 3 ICEF were observed. Additional sonographic abnormalities were seen in both aneuploid fetuses with Grade 2 ICEF. Interobserver agreement on ICEF grading was noted in 50/50 (100%) examinations (kappa = 1.0). CONCLUSIONS: Sonographic grading of ICEF is feasible and highly reliable. Grade 2 ICEF, especially when accompanied by additional sonographic markers of a chromosomal abnormality, are associated with aneuploidy significantly more frequently than Grade 1 ICEF.

Adult↗
PubMed2000

Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate.

Randomized trials comparing the aromatase inhibitors, anastrozole and letrozole, to megestrol acetate (MA) in postmenopausal women with advanced breast cancer demonstrated that both agents are better tolerated than MA with comparable efficacy. In addition, one trial revealed that tumor response and time to treatment failure were significantly better with letrozole. Since oncologists are faced with a choice between three agents with at least comparable efficacy but different toxicity profiles and cost, a cost-utility analysis was conducted to quantify these differences and to determine if the new agents are more cost-effective than MA. In the absence of a randomized three-arm trial, a decision model was developed to simulate the most common therapeutic outcomes. The clinical data were obtained from an overview analysis of randomized trials. Total hospital resource consumption was collected from 87 patients with advanced disease that had failed second-line hormonal therapy. Utility estimates were obtained from interviewing a random sample of 25 women from the general public and 25 female health care professionals using the Time Trade-Off technique. The model suggested a similar duration of quality-adjusted progression-free survival between drugs (letrozole 150 days, anastrozole 153 days and MA 146 days). Letrozole had an overall cost of Can$2949 per patient which was comparable to MA at Can$2966 per patient. In contrast, anastrozole was slightly more costly than MA at $Can3149 per patient, respectively. The analysis revealed that letrozole has comparable overall costs relative to MA while providing at least equivalent quality-adjusted progression-free survival. These outcomes were largely related to its higher tumor response rate, which translated to a lower proportion of patients requiring chemotherapy. Anastrozole was slightly more costly than MA and did not demonstrate superiority in quality-adjusted progression-free survival in this palliative setting.

Anastrozole↗
PubMed2000

Fetal intracardiac echogenic foci: current understanding and clinical significance.

The detection of fetal intracardiac echogenic foci (ICEF) by ultrasound was first reported in 1987. Despite many investigations, the relationship of ICEF with congenital heart malformations and chromosomal abnormalities remains unclear. This review describes the current understanding of ICEF based on a literature search from 1980 to the present. ICEF are observed in 0.5 to 20 percent of fetuses, with an overall frequency of 5.6 percent. These small, discrete structures near the papillary muscles and chordae tendinae move in synchrony with the intraventricular valves. They likely represent microcalcification of the papillary muscles. ICEF are most commonly seen in the left ventricle and occasionally in the right ventricle or bilaterally. Intra-atrial or diffuse ICEF are rare. In the chromosomally normal fetus, ICEF are not associated with congenital heart defects. The presence of ICEF in fetuses at high risk for chromosomal abnormalities suggests an increased possibility of aneuploidy, especially if other sonographic markers are noted. A similar association is observed with trisomy 21 in particular. The significance of ICEF in fetuses at low risk for aneuploidy is less clear and represents an area for future research.

Aneuploidy↗
PubMed2000

Efficacy of community-based second trimester genetic ultrasonography in detecting the chromosomally abnormal fetus.

We sought to assess prospectively the efficacy of community-based genetic ultrasonography in detecting chromosomally abnormal fetuses in a high-risk population and determine independent markers of aneuploidy. Patients 18 years old and older who were between 14 and 24 weeks' gestation were included if referred for maternal age greater than 35 years, increased risk of Down syndrome or trisomy 18 by second trimester serum screen, or prior affected offspring. All women had a targeted ultrasonographic examination between April 1997 and June 1999 and were offered fetal chromosomal analysis. Markers of aneuploidy and pregnancy outcomes were recorded prospectively. The primary outcome was prenatally or postnatally detected chromosomal abnormalities. Of the 1030 fetuses seen during the study, 789 had outcome data available and constituted the study group. In this group, 694 (87.9%) ultrasonograms were normal, 73 (9.2%) had one marker present, 17 (2.2%) had two markers present, and 5 (0.6%) had three or more markers present. Fourteen of 17 (82.3%) aneuploid fetuses had an abnormal ultrasonogram (one or more markers present), including 5 of 7 (71.4%) with Down syndrome. Logistic regression showed abnormal four-chamber view, structural anomaly, and intracardiac echogenic focus to be significant aneuploidy markers. The amniocentesis rate was 334 of 1030 (32.4%), and it increased with the number of sonographic markers noted (0 = 29.9%, 1 = 60.2%, 2 = 70.6%, 3 or more = 80%). Genetic ultrasonography is highly effective in identifying chromosomally abnormal fetuses in a community-based practice.

Adolescent↗
PubMed2000

Twin vaginal birth after cesarean.

OBJECTIVE: To determine both success rate and maternal-fetal outcome of vaginal birth after cesarean in twin gestations. METHODS: We identified all women from a single center attempting vaginal birth of twins after cesarean from 1988-98. Twin pairs were excluded for delivery < or = 25 weeks gestation, monoamnionicity, nonvertex twin A, or major anomaly or death of either twin. Cases were matched to the next three consecutive twin gestations attempting vaginal delivery without a prior cesarean. Variables matched were gestational age at delivery (+/- 1 week), presentations of both fetuses, labor onset (spontaneous or induced), and prior vaginal delivery (yes or no). The primary outcome was successful vaginal delivery of both fetuses. Secondary maternal outcomes included chorioamnionitis, hemorrhage requiring transfusion, hysterectomy, uterine rupture, and length of stay. Neonatal outcomes included one and five minute Apgars, NICU admission, and length of NICU stay. RESULTS: Twelve parturients were matched to 36 controls. There were no differences between the groups with respect to maternal demographics, intrapartum variables, fetal genders, birthweights, or chorionicity. Women with a prior cesarean (10/12) delivered both twins vaginally compared to 31/36 parturients without a prior cesarean (P = 1.0). There were no differences between cases and controls with respect to maternal morbidity (1/12 vs 4/36, P = 1.0), or postpartum stay (2.5 +/- 1.0 vs 2.5 +/- 2.3 days, P = .25). Neonatal outcomes were similar by birth order, except that second-born twins of cases had significantly longer NICU stays than controls (22.7 +/- 3.8 vs 10.4 +/- 7.8 days, P = .04). CONCLUSION: Twin trial of labor after cesarean is associated with a high success rate of vaginal delivery but may be associated with a more lengthy NICU stay for the second twin.

Cesarean Section↗
PubMed1999

Receptor binding and biological activity of mammalian expressed sensory and motor neuron-derived factor (SMDF).

Sensory and motor neuron-derived factor (SMDF) is a member of the neuregulin family of proteins. SMDF is structurally characterized by a novel N-terminal domain. Using the signal sequence and N-terminal 28 amino acids (the "epitope") of herpes simplex virus type 1 glycoprotein D (gD), we have expressed SMDF as an epitope-tagged protein (gD-SMDF) in 293 cells, and purified it to > 98% homogeneity on a monoclonal anti-gD column. gD-SMDF stimulates human Schwann cell growth and 3H-thymidine incorporation in MCF-7 and T47D human breast tumor cells in vitro. The biological activity of gD-SMDF is consistent with its ability to compete with 125I-labeled heregulinbeta1 peptide (rHRGbeta1(177-244)) to bind to soluble dimeric ErbB receptor-IgG fusion proteins. gD-SMDF binds with low affinity to homodimeric ErbB3-IgG and ErbB4-IgG but with higher affinity to heterodimeric ErbB2/ErbB3-IgG and ErbB2/ErbB4-IgG. Using a SMDF-IgG(Fc) fusion protein we generated a monoclonal antibody (3G11) which binds SMDF, crossreacts with rHRGbeta1(177-244), and neutralizes the in vitro activities of gD-SMDF and rHRGbeta1(177-244) in human Schwann cells.

Animals↗
PubMed1999

Effectiveness of a writing improvement intervention program on the readability of the research informed consent document.

BACKGROUND: Problems with the comprehensibility of human research informed consent have been documented since the 1970s, and efforts aimed at rewriting consents have not been successful in consistently producing more readable consents. This study employed researched principles of reading comprehension research to create writing intervention program designed to help the research writer produce more comprehensible informed consent documents. The purpose of this study was to determine if this intervention program was effective. METHOD: The key component of the writing improvement intervention packet was a newly formatted consent form that contained annotated instructions for researchers on how to write each section for optimum comprehension. The resulting consent forms were evaluated using a Readability and Processability Form (RPF). The RPF is based on reading research and includes the Fry Scale, which yields an approximate grade reading level. The RPF assigned points to each of the 20 areas of comprehension analysis according to strict scoring criteria, and target scores were established by the authors in consultation with the hospital institutional review board. RESULTS: We evaluated 66 post-intervention informed consents. The mean readability and processability score was 62, resulting in the RPF classification of "good." The established readability and processability target range was good to excellent or 61-100 points; 66% of the forms scored in this range. In our 1995 pre-intervention study, the corresponding score was 12%. The target range for grade reading level was 8th grade: 53% scored in that range as compared with 4% in 1995. A question-by-question analysis of each of the 20 checklist items on the RPF identified important aspects of the consent writing that improved and others that were still weak and needed improvement. CONCLUSIONS: The Hartford Hospital writing improvement intervention program was associated with the production of more comprehensible informed consent documents. Using the intervention materials, investigators from a variety of departments could function independently to produce readable consent forms. This program may help others who wish to assist their research departments in creating consents that are written for optimal reading comprehension.

Cognition↗
PubMed1997

The role of cultured Schwann cell grafts in the repair of gaps within the peripheral nervous system of primates.

With recent advances in cell culture techniques it is possible to isolate human SCs from adult peripheral nerves, expand and purify their number in cell culture, and construct a cellular prosthesis from the cultured cells. The current study was designed to ascertain whether these techniques could be used to repair nonhuman primate nerve injuries. In 12 adult female cynomologous monkeys, the musculocutaneous (msk) nerve was divided and prevented from regenerating and the brachioradialis nerve (brach) was exposed bilaterally (n = 24 nerves) and injured so that a 15-mm gap existed within the nerve. The brach nerves were either repaired with sural nerve autografts (n = 6), guidance channels which contained monkey SCs (120 x 10(6) cells/ml; n = 6), or guidance channels without SCs (n = 6). The remaining brach nerves (n = 6) had either no injury or an injury to the nerve without a repair. Autologous expanded primate SCs were increased in number at least 10-fold over a 2-week period at which time the SC purity exceeded 99.9%. Monkeys in each group, including the control group, regained some degree of elbow flexion after 3 months despite sectioning both the mask nerve and the brach nerve; therefore, we were unable to determine simply on clinical grounds which repair was the most effective in promoting functional recovery. Brach nerves repaired with sural nerve grafts were superior to both the channels which contained SCs and empty channels in regards to the number of myelinated axons proximal, within, and distal to the repair site (P < 0.05). Electrophysiologic results closely paralleled the histologic data with evidence of reinnervation of the brachioradialis muscle based on the compound muscle action potential in both sural nerve graft and monkey SC channel repair groups.

Animals↗
PubMed1996

Testicular germ cell populations in the adult rat after continuous in-vivo testicular infusion of inhibin-A and activin-A.

This study investigated the in-vivo effects of inhibin-A and activin-A on germ cell subpopulations in the adult rat testis. Each animal received a total of 2 micrograms (dose 5 ng/0.5 microliter/h) of activin, inhibin or 0.1% bovine serum albumin (vehicle control) delivered intratesticularly into the left testis via a cannula connected to an abdominal minipump implant. To establish whether the hormones exerted any effect on procarbazine-induced germ cell depletion, a single intraperitoneal dose of this agent was given to a group of the rats 24 h after the start of testicular infusion of activin or inhibin. Rats were killed 14 days later. Inhibin treatment caused a reduction in the number of round spermatids without altering serum FSH levels. In procarbazine-treated rats, infusion of inhibin reduced the number of pachytene spermatocytes and reduced blood FSH levels simultaneously. Infusion of activin had no significant effect on the numbers of germ cells, but reduced the number of dead cells in the seminiferous tubules of procarbazine-treated rats. The data would therefore suggest that the effects of inhibin and activin on the seminiferous epithelium are influenced by the testicular microenvironment, and that they are capable of influencing the growth and survival of germ cells by both FSH- and non FSH-mediated mechanisms. Further experiments are needed to identify the physiological role(s) of inhibin and activin in spermatogenesis.

Activins↗
PubMed1996

Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice.

Activins and inhibins, members of the transforming growth factor-beta superfamily, are involved in diverse physiological and developmental processes. We have previously shown that mice deficient in alpha-inhibin develop gonadal sex cord-stromal tumors at an early age. The tumor development is rapidly followed by a wasting syndrome that includes severe weight loss, hepatocellular necrosis around the central vein, and depletion of the parietal cells in the glandular stomach. The liver histology in inhibin-deficient mice is similar to the pathological effects of short-term treatment of rats and mice with recombinant activin A. Consistent with these findings, we have shown that the gonadal tumors in the inhibin-deficient mice secrete high levels of activins. In addition, Northern blot analysis has localized activin receptor type II (ActRII) to the liver. Based on these studies, we postulated that tumor-produced activins act through ActRII to cause the wasting syndrome in inhibin-deficient mice. To test this hypothesis and determine the significance of elevated levels of activin signaling through ActRII in vivo, we generated compound homozygous mutant mice deficient in both alpha-inhibin and ActRII. Despite the continued development of gonadal sex cord-stromal tumors and elevated serum levels of activin A and B, the compound homozygous mutant mice suffered no unusual weight loss, and the stomachs and livers of the majority of the mice were histologically normal. These results demonstrate that increased levels of activin signaling through ActRII in hepatocytes and the glandular stomach causes the hepatocellular necrosis and depletion of parietal cells in the glandular stomach as well as the severe weight loss in vivo.

Activin Receptors↗
PubMed1994

Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy.

A number of growth factors have been implicated in the development and perpetuation of preretinal fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). The aim of this study was to determine the potential role of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in PDR development. Immunostaining for EGF, TGF-alpha, and EGF-R was compared between normal retina, PDR retina, and PDR preretinal membranes. Weak staining for EGF and EGF-R was observed throughout the neural retina from non-diabetic eyes while weak to moderate staining for TGF-alpha was observed in the ganglion cell layer and the inner and outer nuclear layers. In contrast, intense staining for EGF and TGF-alpha and moderate staining for EGF-R were observed throughout the PDR retina. Immunoreactivity for EGF, TGF-alpha, and EGF-R was seen in the majority of the 11 excised membranes studied and, though variable, was generally greater than that observed in normal retinas. These results suggest an autocrine/paracrine role for EGF, TGF-alpha, and EGF-R in PDR.

Diabetic Retinopathy↗