Search PubMed⌕ Search

Biomedical subjects

J A McGregor

Publications and source records attributed to J A McGregor.

At least 19 recordsLinked to original sources

Molecular evidence for the role of a ferric reductase in iron transport.

Duodenal cytochrome b (Dcytb) is a haem protein similar to the cytochrome b561 protein family. Dcytb is highly expressed in duodenal brush-border membrane and is implicated in dietary iron absorption by reducing dietary ferric iron to the ferrous form for transport via Nramp2/DCT1 (divalent-cation transporter 1)/DMT1 (divalent metal-transporter 1). The protein is expressed in other tissues and may account for ferric reductase activity at other sites in the body.

Biological Transport↗

Efficacy of clindamycin vaginal ovule (3-day treatment) vs. clindamycin vaginal cream (7-day treatment) in bacterial vaginosis.

OBJECTIVE: To compare the efficacy and safety of a 3-day regimen of clindamycin vaginal ovules with a 7-day regimen of clindamycin vaginal cream for the treatment of bacterial vaginosis (BV). METHODS: Women with a clinical diagnosis of BV were treated with a 3-day course of clindamycin ovules or a 7-day course of clindamycin cream administered intravaginally. Three hundred and eighty-four patients received study drug and were included in the evaluable patient population (ovule group, n = 204; cream group, n = 180). Assessments included pelvic examination and diagnostic testing. Primary efficacy endpoints were a resolution of two of three diagnostic criteria at the first follow-up visit and three of three diagnostic criteria at the second. RESULTS: Cure rates in the evaluable patient population were similar between treatment groups: 53.7% (109/204) for the ovule group and 47.8% (85/180) for the cream group (p = 0.2471, 95% CI -4.1-16.0%). The most commonly reported medical event, vulvovaginal pruritus, had similar incidence in both treatment groups. CONCLUSIONS: A 3-day course of clindamycin vaginal ovules is as effective and well-tolerated as a 7-day course of clindamycin vaginal cream in the treatment of BV.

Administration, Intravaginal↗

Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

Adult↗

Bacterial vaginosis in pregnancy.

Bacterial vaginosis is a clinical condition caused by replacement of the normal hydrogen peroxide producing Lactobacillus sp. in the vagina with high concentrations of characteristic sets of aerobic and anaerobic bacteria. Bacterial vaginosis is the most prevalent cause of vaginal discharge or malodor, although 50 percent of women who meet the criteria for this condition are asymptomatic. Bacterial vaginosis is reported in 10 to 41 percent of women, and new evidence has shown association with maternal and fetal morbidity. Studies have shown that spontaneous abortion, preterm labor, premature birth, preterm premature rupture of the membranes, amniotic fluid infection, postpartum endometritis, and postcesarean wound infections are increased because of infection with bacterial vaginosis during pregnancy. Clinical trials demonstrated important reductions in many of these adverse events with appropriate screening and antimicrobial treatment protocols. New low-cost, diagnostic, point-of-care screening tools are available for rapid screening of patients, affording the physician the opportunity to potentially make a dramatic clinical and cost impact in preventing preterm birth and the costly sequelae of prematurity. Practicing physicians need to be aware of current guidelines for screening and treating pregnant patients for bacterial vaginosis. The authors recommend that all pregnant women be screened and treated with the Centers for Disease Control and Prevention (CDC-P) recommended oral regimens early in pregnancy. Each treated women should be evaluated for "test of cure" 1 month after treatment. Mothers likely to benefit from "screen and treat" approaches include 1) those with the highest concentrations of genital anaerobes and mycoplasmas, 2) women with prior preterm birth or who have low body mass (BMI < 19.8 kg/m2), 3) those with evidence of endometritis before pregnancy, and 4) those who are treated with oral agents effective for both presumed intrauterine mycoplasmas and other bacterial vaginosis flora (i.e., oral clindamycin or erythromycin and metronidazole).

Female↗

Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy.

OBJECTIVE: To compare the efficacy and safety of 0.75% metronidazole vaginal gel with oral metronidazole for the treatment of bacterial vaginosis (BV). STUDY DESIGN: Nonpregnant women with BV were enrolled in a multicenter, randomized, investigator-blind treatment trial. Patients were randomly assigned to either 0.75% metronidazole vaginal gel (5 g twice daily for five days) or oral metronidazole (500 mg twice daily for seven days). Follow-up visits occurred approximately two and five weeks after initiation of therapy. RESULTS: BV was clinically eliminated at the first follow-up visit in 83.7% (36/43, 95% CI 72.3-95.1%) of the intravaginal group and 85.1% (40/47, 95% CI 74.6-95.6%) of the oral group. At the final visit, BV was eliminated in 70.7% (29/41, 95% CI 56.3-85.1%) of the intravaginal group and 71.1% (32/45, 95% CI 57.4-84.8%) of the oral group. Significantly more patients in the oral treatment group (51.8%) reported gastrointestinal complaints as compared to the intravaginal treatment group (32.7%, P = .04). CONCLUSION: The efficacy of 0.75% metronidazole vaginal gel twice daily for five days in treating BV was similar to that of standard oral metronidazole treatment and was associated with fewer gastrointestinal complaints.

Administration, Intravaginal↗

Accuracy of salivary estriol testing compared to traditional risk factor assessment in predicting preterm birth.

OBJECTIVE: The objective was to compare the predictive accuracy (percentage of correct vs incorrect predictions) of salivary estriol levels (SalEst; Biex, Inc, Dublin, Calif) with that of the modified Creasy score for predicting preterm labor followed by preterm delivery. STUDY DESIGN: A triple-blinded prospective trial was conducted at 8 US centers. RESULTS: Among 601 evaluable patients, serial salivary estriol testing correctly predicted the appropriate outcome 91% of the time and the Creasy scoring method correctly predicted the appropriate outcome 75% of the time (McNemar test P <. 001). Among subjects with Creasy scores >/=10 (high-risk group, n = 152), use of salivary estriol testing correctly predicted the end point 87% of the time, compared with only 7.2% correctly predicted by modified Creasy scoring (McNemar test P <.001). CONCLUSION: Salivary estriol assessment was more accurate in predicting outcome than was modified Creasy scoring.

Estriol↗

Diurnal variation in saliva estriol level during pregnancy: a pilot study.

OBJECTIVE: The object of the study was to characterize daily values and patterns of salivary estriol levels during normal pregnancy at mid to late gestation. STUDY DESIGN: We measured salivary estriol levels in a clinical research center setting with an established enzyme-linked immunosorbent assay. Fourteen pregnant women (24-36 weeks' gestation) submitted unstimulated saliva samples hourly from 10:00 am until 10:00 pm and at midnight and 2:00, 4:00, 6:00, and 8:00 am. RESULTS: Each subject demonstrated greater salivary estriol levels at night (10:00 pm-6:00 am) than in the daytime (8:00 am-9:00 pm, P <.001). Salivary estriol levels consistently increased at 10:00 pm, peaked at 4:00 am, and returned to daytime levels between 6:00 and 7:00 am. Salivary estriol concentrations were stable during daylight hours. CONCLUSIONS: (1) There was a dramatic diurnal variation in salivary estriol levels (nadir during daylight with nighttime apogee). (2) Diurnal patterns and salivary estriol levels were consistent in each of 14 subjects evaluated in the latter half of pregnancy. Samples for baseline measurements of salivary estriol level should be obtained during daylight hours (8:00 am-8:00 pm).

Adolescent↗

A central theory of preterm and term labor: putative role for corticotropin-releasing hormone.

Near the end of human pregnancy the concentration of placental corticotropin-releasing hormone in maternal blood rises exponentially. The rate of elevation of corticotropin-releasing hormone and its duration through time have been linked to the time of onset of labor. Paradoxically, although glucocorticoids are known to inhibit corticotropin-releasing hormone production within the hypothalamic-pituitary-adrenal axis, cortisol actually increases corticotropin-releasing hormone levels in several areas outside the hypothalamus, including the placenta. Placental corticotropin-releasing hormone may be an important component of a system that controls the normal maturation of the fetus and signals the initiation of labor. Abnormal elevations in corticotropin-releasing hormone, which may be a hormonal response to stressors arising in either the mother, placenta, or fetus, may prove to participate in the premature onset of parturition.

Corticotropin-Releasing Hormone↗

Gestational bleeding, bacterial vaginosis, and common reproductive tract infections: risk for preterm birth and benefit of treatment.

OBJECTIVE: To examine associations between bacterial vaginosis and other prevalent lower genital tract infections and clinically recognized first-trimester bleeding; possible independent and joint effects of gestational bleeding and bacterial vaginosis or other prevalent infections on preterm birth and premature rupture of membranes; and effects of antimicrobial treatment on reducing risks of preterm birth among these women. METHODS: A secondary analysis was conducted of 1100 pregnant women enrolled in a prospective observational study that examined the effects of standardized diagnosis and treatment of lower genital tract infections to prevent preterm birth. RESULTS: Sixty percent of women with first-trimester bleeding had one or more study infections detected at the initial examination. First-trimester bleeding was associated independently with the presence of bacterial vaginosis (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0, 2.3), Trichomonas vaginalis (OR 2.3, 95% CI 1.3, 4.2), and Chlamydia trachomatis (OR 2.7, 95% CI 1.4, 5.1). Preterm birth was increased among women with first-trimester bleeding and bacterial vaginosis (relative risk [RR] 4.4, 95% CI 2.0, 9.5) and bacterial vaginosis and T vaginalis (RR 3.0, 95% CI 1.0, 8.8). Systemic antimicrobial treatment reduced the rate of preterm birth among women with bacterial vaginosis without first-trimester bleeding (RR 0.37, 95% CI 0.16, 0.88). Treatment of women with both first-trimester bleeding and bacterial vaginosis reduced preterm birth (RR 0.52, 95% CI 0.18, 1.55), but not significantly. CONCLUSION: First-trimester bleeding was increased among women with bacterial vaginosis, T vaginalis, C trachomatis, and combinations of these infections. Women with bacterial vaginosis who also experienced first-trimester bleeding were at heightened risk for preterm birth. Treatment of studied infections reduced significantly the risks of preterm birth among women without first-trimester bleeding.

Adolescent↗

Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: role of interleukin 1beta.

A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. Using this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated intracervically using a micro-endoscope, at a time corresponding to 70% of average gestation. Intracervical injection of lipopolysaccharide (LPS) or Escherichia coli reliably induced premature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 36 h after inoculation. No losses were observed in mice inoculated with saline. Pregnancy loss was associated with increased uterine tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL-1beta-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss. This model using direct intracervical bacterial or LPS inoculation is useful for studying preterm pregnancy loss in genetically altered mice in order to develop novel interventions for infection-associated preterm labor.

Animals↗

Chronic plasma cell endometritis in hysterectomy specimens of HIV-infected women: a retrospective analysis.

OBJECTIVE: Abnormal uterine bleeding is a common and troublesome problem in human immunodeficiency virus (HIV)-infected women. We sought to evaluate endometrial pathology among HIV-infected women requiring hysterectomy to explore if endometritis may be common among these patients. METHODS: We performed a retrospective analysis of uterine pathology specimens obtained from HIV-infected and control patients requiring hysterectomy in two urban hospitals between 1988 and 1997 matched for age, surgical indication, and history of gonadotropin-releasing hormone (GnRH) use. Cases were evaluated for the presence of plasma cells and assigned a grade between 0 and 3. RESULTS: Indications included cervical dysplasia (4), carcinoma in situ (2), abnormal uterine bleeding (3), and adnexal mass (3). Some degree of abnormal uterine bleeding occurred in all cases. Plasma cell endometritis was twice as common in HIV-infected women compared to HIV-negative specimens (11/11 versus 11/22) (P < 0.05). Plasma cell endometritis was also of a higher grade in specimens from HIV-infected women than in controls (P = 0.001). CONCLUSION: Chronic endometritis was common and of a higher grade among HIV-infected women requiring hysterectomy in our series. Diagnosis and treatment of endometritis should be considered in HIV-infected women with uterine bleeding and/or tenderness. We speculate that antiretroviral and/or antimicrobial treatment for endometritis may effectively treat endometritis and eliminate the need for surgery in some HIV-infected women. We suggest that consideration and treatment of endometritis in HIV-1 infected women being evaluated for possible hysterectomy has the potential to reduce costs and morbidity for patients and providers who may be exposed during surgical procedures.

Adult↗

Assessment of office-based care of sexually transmitted diseases and vaginitis and antibiotic decision-making by obstetrician-gynecologists.

OBJECTIVE: Survey office-based obstetric-gynecologic practitioners regarding their knowledge of infectious disease care and antibiotic use. METHODS: A survey questionnaire of multiple-choice questions was mailed to Fellows of the American College of Obstetricians and Gynecologists about clinical entities for which recommendations have undergone recent changes or about which there was a lack of consensus in a prior similar survey (Gibbs RS, McGregor JA, Mead PB, et al.: Obstet Gynecol 83:631-636, 1994). RESULTS: Respondents indicated that oral metronidazole was their most frequent choice to treat bacterial vaginosis. Ampicillin (57%) was used more often than penicillin (39%) for intrapartum group B streptococcus prophylaxis. Azithromycin was preferred (61%) over erythromycin-base (38%) for chlamydia treatment during pregnancy. There were several modes of practice that deviated from accepted care: 27% and 29% did not screen for chlamydia and gonorrhea, respectively, in pregnancy; 17% used cultures for Gardnerella vaginalis to diagnose bacterial vaginosis; 25% considered quinolones to be safe in pregnancy; 93% felt metronidazole should never be used in pregnancy; and the majority (66%) would send a patient treated successfully for pelvic cellulitis home with an oral antibiotic. CONCLUSION: Respondents' infectious disease knowledge and practices in obstetrics and gynecology is appropriate in treating sexually transmitted diseases, bacterial vaginosis, and group B streptococcus. Numerous deficiencies still exist in screening for sexually transmitted diseases in pregnancy and diagnosing bacterial vaginosis, as well as in the choice of antibiotics to use or avoid for certain infections.

Adult↗

Telomerase expression in normal epithelium, reactive atypia, squamous dysplasia, and squamous cell carcinoma of the uterine cervix.

Telomerase activity has been detected in a broad range of human malignant neoplasms, and its expression may represent an essential step in the malignant transformation of tissues; however, the expression of telomerase in premalignant lesions remains relatively unexplored. We tested tissue sections of cervical squamous cell carcinomas and squamous intraepithelial lesions, samples of benign reactive atypia, and normal cervical mucosa from hysterectomy and cone biopsy specimens for the expression of telomerase. Mirror-image sections from each sample were paraffin embedded and processed for histologic analysis. The test samples of cervical tissue were crushed under liquid nitrogen, and telomerase activity was determined by the telomeric repeat amplification protocol. Telomerase activity was detected in 18 of 18 cases (100%) of invasive squamous cell carcinoma. Twenty-five of 26 samples (96%) of high-grade squamous intraepithelial lesion also tested positively for telomerase activity, including 10 of 10 samples of moderate dysplasia, 12 of 13 samples of severe dysplasia, and 3 of 3 samples of carcinoma in situ. Telomerase activity was detected in 14 of 25 samples (56%) of low-grade squamous intraepithelial lesion and in 10 of 18 samples (56%) of reactive atypia but was detected in only 9 of 50 samples (18%) of histologically normal cervical mucosa. These results suggest that telomerase expression may be a marker of premalignant and malignant squamous cell lesions of the uterine cervix, although it is also expressed in a high proportion of cases of reactive atypia.

Carcinoma, Squamous Cell↗

A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.

BACKGROUND: Trichomonas vaginalis is a common sexually transmitted pathogen. In the United States, oral metronidazole is the only officially sanctioned treatment option. OBJECTIVE: This study was undertaken to compare the efficacy and safety of 0.75% metronidazole vaginal gel with that of oral metronidazole for the treatment of trichomonal vaginitis. STUDY DESIGN: Women with trichomoniasis were enrolled in this randomized, open-label pilot study of 0.75% metronidazole vaginal gel twice daily for 7 days compared with 7 days of generic oral metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits 5 to 7 days and 21 to 28 days after the last dose of medication. RESULTS: Using culture for test of cure, trichomonal infection was eliminated in all 15 women treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal metronidazole. Adverse events were similar, except that there were more taste-related adverse events in the oral metronidazole group. Significant reductions in genitourinary symptoms were seen in both the oral and intravaginal groups. CONCLUSION: This study has shown that 0.75% metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. Future studies may define a role for metronidazole gel for symptomatic relief in patients intolerant of oral medication or as adjunctive treatment with oral metronidazole for the management of patients infected with metronidazole-resistant strains of T. vaginalis.

Administration, Intravaginal↗

First antenatal visits and metronidazole.

OBJECTIVE: We evaluated the timing of initial antenatal visits to better characterize possible use of metronidazole or other antimicrobials for common reproductive tract infections in early pregnancy. STUDY DESIGN: We determined timing of initial antenatal evaluation in five busy and representative Denver, Colorado, practice settings (most recent 50 patients). RESULTS: Most women were evaluated after completion of 9 weeks of pregnancy. Women seen in private settings received the initial visit earlier than did women in publicly supported clinics. CONCLUSION: Pregnant women with a common reproductive tract infection and bacterial vaginosis can be "screened and treated" at the initial antenatal examination.

Female↗