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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 361 records · Page 20Linked to original sources

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome.

Total ovarian volumes were measured before the administration of HCG in 42 women undergoing treatment for infertility by in-vitro fertilization (IVF) and embryo transfer and considered to have an exaggerated response to stimulation ( > 20 follicles). Seven women who subsequently developed moderate or severe ovarian hyperstimulation syndrome (OHSS) (n = 7; group 1) were compared with 35 matched controls (five matched controls per case; n = 35; group 2) of similar age, number of follicles and duration of infertility who underwent follicular stimulation, oocyte recovery, in-vitro fertilization and embryo transfer during the same period but did not develop moderate or severe OHSS. The mean age, duration of infertility and total number of follicles were similar but the mean total ovarian volume was significantly higher in the group of women who developed moderate or severe OHSS compared with controls (271.00 +/- 87.00 versus 157.30 +/- 54.20 ml; P < 0.01). We conclude that total ovarian volume measured before HCG administration is higher in women who develop moderate or severe OHSS compared with controls and may therefore be used as an additional parameter in the preventative strategy for the ovarian hyperstimulation syndrome.

Adult↗

Materno-fetal immunoglobulin transfer and passive immunity during the first trimester of human pregnancy.

Passive transfer of immunity from the mother to the first trimester fetus is of particular interest because of the reported high incidence of serious fetal sequelae due to congenital infection. We have examined the relationship between maternal serum, coelomic fluid and amniotic fluid concentrations of immunoglobulin (Ig) and complement. Ig fractions G (IgG), A (IgA), and M (IgM) and complement factors 3 (C3) and 4 (C4) were measured in 34 normal pregnancies between 6 and 12 weeks of gestation. The concentrations of specific antibodies for Toxoplasma gondii, cytomegalovirus (CMV) and rubella were also measured on 21 matched samples from the same study group. IgG and IgA concentrations were detected in all coelomic fluid samples whereas IgG was only measurable in two amniotic fluid samples. IgG and IgA concentrations were respectively 28 and 128 times lower in coelomic fluid than in maternal serum and probably reflect fetal serum concentrations. Significant positive linear correlations were found between gestational age and the coelomic concentrations of IgG (P = 0.001) and IgA (P = 0.014). There was no obvious association between immunoglobulin concentrations in coelomic fluid and maternal serum suggesting increasing active transport across the placenta with advancing gestation. IgM, C3 and C4 were not detected in coelomic or amniotic fluid samples. Specific antibodies were found in 13 out of 63 samples of coelomic fluid and in 32 out of 63 samples of maternal serum. They were found in coelomic fluid only if they were present in maternal serum. These results suggest that maternal IgG and IgA are potentially available to the embryo as early as the 6th week of gestation. The presence in the coelomic fluid of the IgG fraction, both total and infectious agent-specific transferred via the placenta, indicates that they may provide limited protection against congenital infection in the first trimester.

Amniotic Fluid↗

CD44 is expressed throughout pre-implantation human embryo development.

The cell surface glycoprotein CD44 has been demonstrated in a variety of cell types in embryonic and adult tissues. We have established that CD44 is present on human oocytes, cumulus cells, early embryos and pre-hatched blastocysts by indirect immunofluorescence. We have also shown that CD44 is present on 8-11 week placental stroma cells, but not on the trophoblast. These findings demonstrate that CD44 is present throughout preimplantation development, and that down-regulation occurs on the embryonic surface after implantation.

Blastocyst↗

Intra-observer, interobserver, interultrasound transducer and intercycle variation in colour Doppler assessment of uterine artery impedance.

In this study we assessed the variability of measuring uterine artery pulsatility index by colour Doppler ultrasound using different ultrasound transducers (abdominal 3 MHz, abdominal 5 MHz, endovaginal 5 MHz with and without a full bladder). We then assessed the intra-observer coefficient of variation for the different transducers and interobserver variability for two observers using the endovaginal probe. The intercycle variability and effects of a full bladder on uterine artery blood flow were also assessed. The uterine vessels were most easily identified using the endovaginal transducer. The most reproducible results were obtained using the endovaginal probe. The coefficients of variation obtained for the vaginal route were intra-observer 4.1%, interobserver 11.8% and intercycle 16.5%. The blood flow indices were significantly different between the endovaginal and both transabdominal 5 and 3 MHz probes (P = 0.0027 and 0.0005 respectively). There was no significant effect of a full bladder on pulsatility index. This study suggests that transvaginal colour Doppler ultrasound is reproducible and the results obtained from clinical use would be reliable.

Abdomen↗

Detection of sickle gene by coelocentesis in early pregnancy: a new approach to prenatal diagnosis of single gene disorders.

Coelomic fluid, placental tissue and maternal blood were collected at 7-10 weeks gestation from each of 58 women undergoing elective termination of pregnancy for psychological indications. In all samples, a 364 bp fragment of the human beta-globin gene spanning positions -23 to 341 was amplified. The restriction endonuclease Ddel was used to detect the sickle mutation which abolishes its restriction site. beta-Globin DNA was successfully amplified from all samples. In 53 cases a normal maternal beta-globin genotype was detected. In three out of five cases, where the maternal haemoglobin phenotype was HbAS, heterozygosity for the sickle mutation was demonstrated on analysis of coelomic fluid. In the remaining two cases a normal beta-globin genotype was observed. Three further coelomic fluid samples were found to be heterozygous for the sickle mutation. In these instances the maternal haemoglobin phenotype was normal, indicating paternal transmission of the sickle gene. The results of the present study have established that the diagnosis of sickle cell anaemia, and potentially other human single gene disorders, is feasible by coelocentesis.

Amniocentesis↗

Description of circadian rhythm in uterine artery blood flow during the peri-ovulatory period.

Uterine artery blood flow was assessed by transvaginal colour and pulsed Doppler ultrasound prospectively in six women during the peri-ovulatory period. All patients had regular ovulatory menstrual cycles and a mid-luteal serum progesterone consistent with spontaneous ovulation in the preceding cycle. Each patient underwent serial transvaginal ultrasound examination and Doppler assessment of blood flow in the uterine arteries. When the mean follicular diameter was > 16 mm or day -2 from the estimated day of ovulation was reached, patients were scanned at 6 hourly intervals at 0600, 1200, 1800 and 2400 h until follicular rupture. The pulsatility index (PI) and time averaged maximum velocity (TAMX) were calculated as Doppler indices of impedance to blood flow and velocity respectively. A venous blood sample was taken at each visit for subsequent hormonal analysis. The mean uterine artery PI showed a marked daily fluctuation with a nadir occurring most commonly at 0600 h. A comparison between the mean PI values at 0600 and 1800 h showed significantly lower results at 0600 h in both dominant (P < 0.05) and nondominant (P < 0.02) uterine arteries. Furthermore, mean uterine artery TAMX showed daily fluctuations with peak values most commonly occurring at 0600 h with the nadir occurring during the afternoon and late evening. There was no temporal relationship between the fluctuations in PI and changes in luteinizing hormone, follicle stimulating hormone, oestradiol or progesterone concentrations. These observations suggest that there is a circadian rhythm in uterine artery blood flow during the peri-ovulatory period which appears to be independent from the hormonal changes.

Adult↗

Ovarian stromal blood flow in women with polycystic ovaries--a possible new marker for diagnosis?

Blood flow changes in the ovarian stroma of women embarking on in-vitro fertilization treatment were assessed on day 2 or 3 of the menstrual cycle using colour and pulsed Doppler ultrasound. Women were divided into three groups: group 1, 63 women with regular, ovulatory menstrual cycles and normal ovaries on ultrasound scan; group 2, 13 women similar to group 1 but with polycystic ovaries (PCO) on ultrasound scan; and group 3, 12 women with biochemical evidence of previous anovulatory cycles and/or oligomenorrhoea and/or elevated serum luteinizing hormone concentrations (> 10 IU/l) in the early follicular phase together with PCO on ultrasound scan. A subjective assessment of the intensity and quantity of coloured areas in the ovarian stroma appeared to be greater in both groups 2 and 3 compared with group 1. Mean (SEM) ovarian stromal peak systolic blood flow velocity (Vmax) was 16.88 (1.79) and 16.89 (2.36) cm/s in groups 2 and 3 respectively. These velocities were significantly greater than the mean (SEM) ovarian stromal Vmax of group 1; 8.74 (0.68) cm/s (P < 0.001). Mean (SEM) ovarian stromal time averaged maximum velocity (TAMX) was 10.55 (0.91) and 10.89 (1.80) cm/s in groups 2 and 3 respectively, both significantly greater than mean ovarian stromal TAMX of group 1, (P < 0.001). There was no significant difference in pulsatility index (PI) between the three groups. There thus appears to be significantly greater ovarian stromal blood flow velocity in women with polycystic ovaries as detected by colour and pulsed Doppler ultrasound. Increased ovarian stromal blood velocity may be a new parameter to assist in the ultrasound diagnosis of PCO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correlation of p-glycoprotein detection by immunohistochemistry with mdr-1 mRNA levels in osteosarcomas. Pilot study.

All the factors that influence prognosis in patients with osteosarcomas have not been fully determined. One reported predictor of poor outcome is increased multi-drug resistant gene (mdr-1) expression, as measured by reverse transcription and polymerase chain reaction (RT-PCR). We examined whether immunostaining for p-glycoprotein, the protein product of mdr-1, could be used instead of RT-PCR to indicate the presence of the multidrug-resistant phenotype. The sensitivity of the immunostaining was determined using KB cell sublines. For 13 cases of osteosarcoma, samples were immunostained for p-glycoprotein and the levels of mdr-1 expression quantitated with use of RT-PCR. Three osteosarcomas with undetectable levels of mdr-1 expression by RT-PCR were negative immunohistochemically. Ten cases showed mdr-1 expression ranging from approximately 1 to 32 copies of mdr-1 mRNA/cell. Of these cases, five cases contained occasional tumour cells with positive immunostaining. There was no correlation between levels of expression and the presence or number of immunoreactive cells. These results indicate that the presence of p-glycoprotein immunostaining does not reliably correlate with the level of mdr-1 expression. However it may be useful in conjunction with RT-PCR to further define different subgroups of osteosarcomas that may have different prognoses, and this is currently under investigation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Self-assembly in vitro of purified CA-NC proteins from Rous sarcoma virus and human immunodeficiency virus type 1.

The internal structural proteins of retroviruses are proteolytically processed from the Gag polyprotein, which alone is able to assemble into virus-like particles when expressed in cells. All Gag proteins contain domains corresponding to the three structural proteins MA, CA, and NC. We have expressed the CA and NC domains together as a unit in Escherichia coli, both for Rous sarcoma virus (RSV) and for human immunodeficiency virus type 1 (HIV-1). We also expressed a similar HIV-1 protein carrying the C-terminal p6 domain. RSV CA-NC, HIV-1 CA-NC, and HIV-1 CA-NC-p6 were purified in native form by classic methods. After adjustment of the pH and salt concentration, each of these proteins was found to assemble at a low level of efficiency into structures that resembled circular sheets and roughly spherical particles. The presence of RNA dramatically increased the efficiency of assembly, and in this case all three proteins formed hollow, cylindrical particles whose lengths were determined by the size of the RNA. The optimal pH at which assembly occurred was 5.5 for the RSV protein and 8.0 for the HIV-1 proteins. The treatment of the RSV CA-NC cylindrical particles with nonionic detergent, with ribonuclease, or with viral protease caused disassembly. These results suggest that RNA plays an important structural role in the virion and that it may initiate and organize the assembly process. The in vitro system described should facilitate the dissection of assembly pathways in retroviruses.

Amino Acid Sequence↗

Solid malignant neoplasms after childhood irradiation: decrease of the relative risk with time after irradiation.

The pattern of the temporal distribution of solid cancer incidence after irradiation in childhood is not well known, although, its importance in radioprotection is well known. We studied a cohort of 1,055 children from 8 European cancer centres, who received radiotherapy between 1942 and 1985 for a first cancer in childhood. After a mean follow-up of 19 years, 26 children developed a solid second malignant neoplasm (SMN), as compared to 5.6 expected from general population rates. Both the excess relative risk and the excess of absolute risk of solid SMN were higher among children who were younger at time of the irradiation. After reaching a maximum 15 to 20 years after irradiation, the excess relative risk of SMN decreased with time after irradiation, when controlling for age at irradiation and sex. The analysis of the risk of thyroid, brain and breast cancer together, as a function of the dose averaged on these 3 organs lead to similar results.

Adolescent↗

Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues.

We have cloned cDNAs encoding three human alpha-1 adrenergic receptor (AR) subtypes and characterized pharmacological properties of the expressed receptor protein. A number of significant sequence corrections have been identified and compared with previously published data, at both nucleotide and amino acid levels; the most major differences occur for the human alpha-1a/dAR. Pharmacological characterization was performed simultaneously using six cloned alpha-1AR subtypes (human and rat alpha-1a/d, human and hamster alpha-1b, human and bovine alpha-1c) stably expressed in rat-1 fibroblasts at approximately equal receptor concentrations (1-2 pmol/mg of total protein). In general, human alpha-1AR subtypes have similar pharmacology compared to their rat, hamster and bovine homologs, although a few minor species differences important for alpha-1AR classification are noted. In addition, much lower inactivation (approximately 20%) by the alkylating agent chloroethylclonidine is noted in this study compared to previous reports for both human and bovine alpha-1cAR membrane preparations. All six alpha-1AR subtypes couple to phosphoinositide hydrolysis in a pertussis toxin-insensitive manner, including the cloned human alpha-1a/dAR which had not been expressed previously. In spite of significant sequence differences between human alpha-1ARs and their other species counterparts, previously established ligand selectivity remains fairly comparable. In summary, these data represent the first side-by-side comparison of pharmacological properties between species homologs of alpha-1AR subtypes and should facilitate the development of alpha-1AR subtype selective drugs for clinical use.

Amino Acid Sequence↗

Needlestick/sharps injuries and HIV exposure among health care workers. National estimates based on a survey of U.S. hospitals.

Exposure to HIV in the workplace is a major concern for health care workers. The greatest risk for bloodborne pathogen transmission is associated with percutaneous injuries involving hollow-bore needles contaminated with patient blood. Limited data are available about how many sharps injuries (SIs) and needlesticks (NSs) occur in the United States, with estimates ranging from 100,000 to 1 million injuries per year. We conducted a survey of 100 infection control practitioners located at randomly selected U.S. hospitals to assess the number of SIs or NSs occurring during 1990; 65 (65%) responded. The mean number of NS/SIs reported was 45, with a mean of 1.1 known HIV-related NS/SIs. The underreporting rate was estimated to be 18.5%. Assuming that the hospitals provided exact numbers of injuries and were representative of the approximately 5,100 U.S. hospitals, then about 252,000 NS/SIs were reported in U.S. hospitals in 1990 (95% CI = 193,000-312,000). If the under-reporting rate was 33% to 66%, then the point estimate for the total number of NS/SIs ranges from 378,000 to 756,000. Similar extrapolation involving the reported number of NS/SIs contaminated with blood from an HIV-infected patient yields an estimate of 5,610 exposures in 1990 (95% CI = 1,300-8,300). The number of U.S. hospital workers sustaining NS/SIs with potential exposure to HIV appears to be considerable. Efforts to reduce the risk of bloodborne pathogen transmission from NS/SIs are warranted.

Bias↗

Ultrasound features of normal early pregnancy development.

Recent advances in ultrasound imaging have improved the assessment of early pregnancy development. The gestational sac can be detected within the uterine cavity as early as 4 weeks and 3 days after the last menstrual period. High resolution images of early embryos have enabled ultrasound studies of normal brain, abdominal wall or limb development. The definition of standard developmental morphological features may open the possibility of screening for structural defects early in the first trimester of pregnancy.

Crown-Rump Length↗

Use of transvaginal ultrasonography with color Doppler imaging to determine an appropriate treatment regimen for uterine fibroids with a GnRH agonist before surgery: a preliminary study.

The aim was to obtain data that could be used to determine the most appropriate treatment regimen for uterine fibroids with a gonadotropin releasing hormone analog (goserelin) before surgery. Fifteen premenopausal women (aged 27-53 years; mean 40 years) were referred from a gynecological outpatients' clinic. They all had uterine fibroids and were awaiting hysterectomy or myomectomy. All women were scheduled to receive an implant of goserelin (3.6 mg), undergo transvaginal ultrasonography and have a sample of peripheral blood taken at monthly intervals for 6 months. The main outcome measures were fibroid size and indices of blood flow (the pulsatility index and peak systolic velocity) in both uterine arteries and the principal artery supplying the largest fibroid. The concentrations of follicle stimulating hormone, estradiol, luteinizing hormone and progesterone were measured in peripheral plasma. Twelve women (80%) completed 2 months of treatment, but only three (20%) completed the study (due to side-effects of the drug). After 2 months of treatment, the plasma hormone levels were all in the low-normal range; the mean fibroid volume had decreased by 53% and the mean peak systolic blood velocity in the fibroid artery had decreased by 45%. Mean changes in all indices were < 10% over the next 4 months of treatment. Six women (40%) had fibroids with an initial volume of > 100 ml; these tumors showed the largest reduction in size. We conclude that women with a uterine fibroid of > 100 ml are the best candidates for treatment with goserelin (3.6 mg/month) before surgery. Two months' treatment effects a marked reduction in fibroid volume and blood flow and is associated with good compliance.

Journal Article↗

The endometrial cell surface and implantation. Expression of the polymorphic mucin MUC-1 and adhesion molecules during the endometrial cycle.

The cell surface mucin MUC-1 is present in endometrial epithelial cells and their associated apical glycocalyx and is also released into gland lumens as a secretory product. MUC-1 mRNA and core protein are found at low levels in the proliferative phase of the cycle, but their abundance increases after ovulation. Endometrial MUC-1 has been found to carry sialokeratan sulphate chains and these show a dramatically increased abundance in cells and secretions in the post-ovulatory phase of the cycle, reaching a maximum in secretions 6-7 days after the LH peak. The apical epithelium also contains adhesion receptor molecules of the integrin and CD44 families. MUC-1 is large and highly glycosylated and probably extends farther from the cell surface than these 'conventional' glycoprotein receptors. It has the potential to inhibit sterically receptor-mediated cell-cell adhesion. However, it is also possible that MUC-1 displays specific (e.g., glycan) recognition structures for the initial attachment of the blastocyst or that the embryo may create a specialised microenvironment in which to implant.

Cell Adhesion Molecules↗

Reference ranges for fetal venous and atrioventricular blood flow parameters.

This cross-sectional study establishes reference ranges with gestation for Doppler parameters of fetal venous and atrioventricular blood flow. Color flow Doppler was used to examine 143 normal singleton pregnancies at 20-40 weeks' gestation. Flow velocity waveforms were recorded from the ductus venosus, right hepatic vein and inferior vena cava. The waveforms are triphasic, reflecting ventricular systole, early diastole and atrial contraction. Peak velocities for these parameters were measured with pulsed Doppler and a new index, the peak velocity index for veins (PVIV), was calculated. Similarly, time-averaged maximum velocities for the whole cardiac cycle were measured and the pulsatility index for veins (PIV) was calculated. Flow velocity waveforms were also recorded at the level of the atrioventricular valves and the ratios of peak velocities at early diastolic filling (E) and atrial contraction (A) were calculated. Regression analysis was used to define the association of each measured and calculated Doppler parameter with gestational age. Blood flow velocities in the fetal veins and velocities and E/A ratios across the atrioventricular valves increased significantly with gestation, whereas PVIV and PIV decreased. Blood flow velocities were highest in the ductus venosus and lowest in the right hepatic vein, and PVIV and PIV were highest in the hepatic vein and lowest in the ductus venosus. In the ductus venosus, there was always forward flow throughout the heart cycle, whereas in the inferior vena cava and hepatic vein during atrial contraction, flow was away from or towards the heart or there was no flow. Pulsatility of flow velocity waveforms in the venous system is the consequence of changes in pressure difference between the venous system and the heart during the heart cycle. The finding that PVIV and PIV decrease with gestation is consistent with decreasing cardiac afterload and maturation of diastolic ventricular function.

Journal Article↗