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Biomedical subjects

M A Warren

Publications and source records attributed to M A Warren.

At least 37 records · Page 2Linked to original sources
PubMed1995

A time course study of capacitation and the acrosome reaction in human spermatozoa using a revised chlortetracycline pattern classification.

OBJECTIVE: To study the time course of capacitation, spontaneous, and A23187-induced acrosome reaction of human spermatozoa during 8 hours incubation in vitro using the chlortetracycline (CTC) assay with a revised fluorescent pattern classification. DESIGN: Fertile donor spermatozoa were isolated by direct swim-up and incubated in Earle's balanced salt solution for up to 8 hours. At hourly intervals, spermatozoa were stained with CTC before and after the addition of A23187 to induce the acrosome reaction. SETTING: The University Clinic, Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Donors participating in the Donor Insemination Program. MAIN OUTCOME MEASURES: Eight fluorescent patterns identified by the CTC assay and acrosome-reacted spermatozoa detected by indirect immunofluorescence using 18.6 monoclonal antibody. RESULTS: Using a statistical model defined by analysis of deviance allowed rationalization of the CTC pattern classification by grouping together patterns that showed a similar and significant change over time. In addition, spontaneous and A23187-induced acrosome-reacted spermatozoa identified by the CTC assay were shown to be correlated significantly to those identified by indirect immunofluorescence. CONCLUSION: The CTC assay using a revised pattern classification offers a more precise description of human spermatozoa capacitation in vitro. Also, CTC-identified acrosome reaction (both spontaneous and A23187 induced) was confirmed independently by indirect immunofluorescence.

Acrosome↗
PubMed1995

Effects of growth hormone on intestinal morphology of genetically dwarf rats.

Three groups of Lewis rat were studied: dwarf rats, genetically deficient in growth hormone; rehabilitated dwarf rats treated with exogenous growth hormone (GH); and normal wild-type rats. The small intestine of each animal was removed and simple random transverse sections were taken from the proximal and distal regions. The profile areas of villi, crypt and muscle were estimated by point count analysis and combined with intestinal length measurements to obtain absolute volumes. Villus and primary mucosal surface areas were estimated from intersection counts and linear measurements were made of epithelial cell height. Distally, villous volume and surface area were reduced by 42% and 39%, respectively, in the dwarfs compared with controls. These features were significantly smaller (P < 0.01) in dwarfs distally than proximally. Crypt volume and epithelial cell height were decreased equally in both proximal and distal regions of the intestine of dwarf rats. Following GH administration both features increased, crypt volume overshooting control values. These results indicate that GH deficiency has a subtle effect on intestinal morphology and that the intestine is more sensitive distally than proximally. Reconstitution with GH is capable of reversing many of these changes.

Animals↗
PubMed1995

Varicella during pregnancy. Maternal and fetal effects.

To determine the characteristics of maternal varicella at our institution, we reviewed all cases of primary varicella in pregnancy. Using a perinatal database that summarizes all obstetric admissions, we reviewed the medical records of women with varicella infections during pregnancy. Over a 5 1/2-year period, 31 pregnancies were affected by varicella infection among 11,753 deliveries. The mean age of those patients was 19.6 years, significantly different from our overall population of 25.3 years (P < .05). The racial composition of 35% Hispanic, 35% white, and 29% African American was different from that of our general population of 55% white, 38% African American, and 6% Hispanic (P = .023). The mean gestational age of the eruption of vesicles was 25 weeks. Of the 31 women, 7 had preterm labor within a week of their varicella, 3 delivered prematurely, and 3 infants had a birth weight of less than 2,700 grams. Respiratory symptoms developed in 6 women, and pneumonia developed in 4, 2 of whom required ventilatory support, 1 for 5 days, the other for 49 days. Eight women received acyclovir during gestation, and none suffered sequelae. In all, 6 infants had lesions and anomalies noted at birth, 5 possibly associated with varicella. Varicella infection is associated with a greater-than-expected level of both maternal and fetal morbidity. The fetal disease may occur due to maternal infection at any gestation and is most likely a spectrum of complications. The maternal disease appears to be worse in the latter half of pregnancy. Programs of prevention through vaccination must account for a possibly decreased level of immunity in different populations.

Acyclovir↗
PubMed1994

Morphology of the human endometrium in the peri-implantation period.

Although the histology and ultrastructure of the human endometrium are well documented, it is clear that morphometry can reveal subtle changes in cellular biology, especially when combined with suitable sampling and dating of the specimen. These changes reflect functional events, such as protein secretion, which may be studied using the endometrial flushing technique. Although it is likely that further insights into the basic cell physiology of the reproductive tract will result from the use of appropriate in vitro models, the role of endometrial biopsy for clinical monitoring remains essential.

Cells, Cultured↗
PubMed1994

Endometrial differentiation in the peri-implantation phase of women with recurrent miscarriage: a morphological and immunohistochemical study.

OBJECTIVES: To study endometrial differentiation in the peri-implantation phase of women with recurrent miscarriage and to compare the results with endometrium of normal fertile women. DESIGN: A prospective study of endometrial specimens precisely timed from the LH surge, using traditional histologic dating (Noyes' criteria), quantitative histologic measurement (morphometric analysis), and immunohistochemical techniques. RESULTS: Fifteen of 25 (60%) subjects in the recurrent miscarriage group had retarded endometrial development in the peri-implantation period as monitored by morphometry. The recurrent miscarriage group showed reduced levels of four mucin-related secretory epitopes, and greater reductions were associated with morphological retardation. Normal differentiation was observed in all of the 14 subjects in the control group. CONCLUSIONS: Women with idiopathic recurrent pregnancy loss may be divided into two distinct subgroups on the basis of their endometrial response in the peri-implantation period. Precisely timed endometrial biopsy should be incorporated in the investigation of recurrent miscarriage.

Abortion, Habitual↗
PubMed1994

Placental protein 14 in cycles with normal and retarded endometrial differentiation.

The purpose of this study was to investigate whether endometrium with retarded development differs, functionally, from endometrium with normal 'in-phase' development. Precisely timed endometrial biopsies were obtained from 24 women suffering from unexplained infertility at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Frozen sections were labelled with an anti-placental protein (PP) 14 monoclonal antibody using an avidin-biotin peroxidase technique and semi-quantification of endometrial PP14 was performed using a Quantimet 970 image analyser. Serum PP14 and saliva progesterone were measured for each patient. Data were analysed using one- and two-way analysis of variance. Normal and retarded endometrium were identified in 16 (group I) and eight (group II) women respectively. Both groups demonstrated a significant increase of the area of precipitate measured for PP14 from day LH + 4 to LH + 13. However, two-way analysis of variance showed that endometrial PP14 was significantly (P < 0.05) lower in the retarded endometrium group at LH + 10 and LH + 13. Serum PP14 was also significantly lower (P < 0.01) in women with retarded endometrial development at LH + 13. Women with normal endometrial development had a significantly higher (P < 0.05) concentration of cumulative saliva progesterone from LH + 3 to LH + 5. This study indicates that there are functional differences between normal and retarded endometrium. These differences may adversely affect uterine receptivity during implantation and the early placentation stage.

Adult↗
PubMed1994

The artificial cycle as an effective treatment of persistently retarded endometrium in the luteal phase.

The objective of this study was to examine the results of two hormonal treatment modalities on subjects who had persistently abnormal endometrial development in the luteal phase. A prospective study design was used to investigate 14 women who had persistently retarded endometrium associated with infertility (n = 11) or recurrent miscarriage (n = 3). Treatment A consisted of progesterone supplementation in the form of i.m. progesterone at a daily dose of 25-50 mg starting on day luteinizing hormone (LH) + 1 for 14 days. Treatment B consisted of artificial cycles produced after down-regulation of the hypothalamic-pituitary-ovarian axis with Goserelin (3.6 mg s.c.) followed by the administration of a standard hormone replacement therapy. Endometrial biopsy was taken on day 19 of the artificial cycle or days LH + 5 to +7 in the progesterone supplementation cycle. A histological study was made of the endometrial specimens by standard dating criteria and morphometry. The artificial cycle resulted in normal development in all subjects (n = 11), whereas progesterone supplementation restored normal endometrial development in only seven of 11 (64%) subjects. We conclude that persistently retarded endometrium could be treated more effectively with the artificial cycle than with progesterone supplementation.

Abortion, Habitual↗
PubMed1994

Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects.

The purpose of this study was to investigate whether the endometrium of women with unexplained infertility differs in some immunological aspects from the endometrium of normal fertile women. Endometrial biopsies were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II) at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. A panel of 11 monoclonal antibodies was employed to characterize the leukocyte subsets in frozen sections. Semi-quantification was performed with a Quantimet 970 image analyser. Data were analysed using one- and two-way analysis of variance. Compared with fertile controls, women with unexplained infertility had significantly lower numbers of CD8+ (T suppressor/cytotoxic) cells at each post-LH date. In contrast, the number of CD4+ (T helper/inducer) cells was significantly higher in group II. Throughout the luteal phase, infertile women had fewer CD56+ cells than normal fertile controls. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter with the cycle stage but the mean nuclear diameter and axial ratio decreased from LH+7 to LH+13. The differences observed in endometrial leukocytic subpopulations between fertile and infertile women may contribute to unexplained infertility probably by affecting the embryonic maternal dialogue during the implantation and early placentation period.

ADP-ribosyl Cyclase↗
PubMed1994

The effects of undernutrition on connectivity in the cerebellar cortex of adult rats.

The effects of a 30 d period of undernutrition, followed in some animals by nutritional rehabilitation, on neuronal connectivity in adult rat cerebellum were investigated using the disector method. There was no significant difference between well fed (719 +/- 74, mean +/- S.E.) and undernourished (709 +/- 53) synapse-to-neuron ratios in 134-d-old rat cerebellar cortex, nor was there a significant difference in synapse-to-neuron ratios between control animals (941 +/- 71) and previously undernourished rats (813 +/- 42) at 175 d of age. However, the age-related changes were significant (P < 0.05) in the controls, but not in the experimental group. It may be that the period of undernutrition caused subtle changes in the rehabilitating group which reduced the capacity for growth seen in well fed, matched control animals.

Animals↗
PubMed1993

The correlation of placental protein 14 concentrations in uterine flushing and endometrial morphology in the peri-implantation period.

The relationship between the concentrations of placental protein 14 (PP14) in uterine flushing and the endometrial morphology in the mid-luteal phase was assessed in a prospectively designed study involving the precise timing of all samples by the luteinizing hormone (LH) surge. A total of 29 regularly cycling women with unexplained infertility or recurrent miscarriage were studied. To flush the uterine cavity, 10 ml of physiological saline solution was used immediately prior to sampling of an endometrial specimen for morphological study, in the mid-luteal phase. PP14 concentrations were measured by radioimmunoassay in uterine flushings and plasma samples; the endometrium was assessed by the use of histological dating criteria and morphometric techniques. PP14 levels in uterine flushings were correlated with endometrial dating and volume fraction measurement of the glands. They were consistently below the sensitivity of the assay with histological dating of < day LH +5, or when the glandular lumen occupied < 20% of the gland. In contrast, PP14 concentrations in plasma were not related to histological dating or morphometric analyses, and did not differ in patients with normal endometrial development (20.8 ng/ml) and in those with retarded endometrial development (22.5 ng/ml). The presence of detectable concentrations of PP14 in uterine flushing was significantly associated with normal histological dating. Uterine flushing may therefore provide a reliable, non-invasive alternative to endometrial biopsy in the evaluation of endometrial function in the peri-implantation period.

Adult↗
PubMed1993

Is the measurement of oestradiol/progesterone ratios in the peri-implantation period of any value in predicting endometrial development?

To examine the value of the measurement of oestradiol/progesterone ratios in the peri-implantation period, three different types of cycle were studied; natural cycles (n = 13), cycles treated with anti-oestrogens (n = 19), and artificial cycles (n = 41) produced by six different hormone replacement regimens. Normal endometrial development was found to occur across a wide range of oestradiol/progesterone ratios. There was no significant correlation between the oestradiol/progesterone ratios and results of endometrial dating. The results suggest that oestradiol/progesterone ratios are of limited value in predicting endometrial development at the time of implantation.

Embryo Implantation↗
PubMed1993

The fine structure of the human endometrial glandular epithelium in cases of unexplained infertility: a morphometric study.

In the present study attempts have been made to express in quantitative terms the fine structure of the endometrial glandular epithelium in well-timed biopsies from fertile women during the early luteal phase. Biopsies from women with unexplained infertility have also been examined. Certain abnormalities of glandular maturation were found in these women. The nuclear channel system was not present at day luteinizing hormone (LH) + 4 in the infertile group while at LH + 6 there were more cells containing this feature than seen in the fertile group. There also seem to be abnormalities associated with intracellular deposits of glycogen-rich material and mitochondrial elaboration in the infertile women. Changes in the secretory apparatus and rough endoplasmic reticulum were observed. The evidence from the present study suggests that the endometria in the examined group of infertile women is responsive to steroidal stimulation. This response however, may be delayed or inadequate.

Cell Nucleus↗
PubMed1993

Is endometrial development in the peri-implantation period influenced by high concentrations of luteinizing hormone in the follicular phase?

A retrospective study was designed to examine the relationship between luteinizing hormone (LH) concentrations in the follicular phase and endometrial development in the luteal phase of natural and artificial cycles. Two types of cycle were studied: natural cycles (n = 51) in subjects with unexplained infertility were divided into two subgroups, depending on whether LH measurements in the late follicular phase were based on urine (n = 24) or plasma (n = 27) samples; and artificial cycles (n = 17), produced by the administration of a standard hormone replacement therapy, in two subgroups of women, those with premature ovarian failure (n = 10) in whom plasma LH concentrations were high, and those with unexplained infertility (n = 7) who had their hypothalamic pituitary-ovarian axis down-regulated and in whom plasma LH concentrations were low. The correlation between plasma or urine concentrations of LH in the follicular phase and the results of endometrial biopsy obtained in the luteal phase was calculated. In natural cycles, LH concentrations were similar in those with normal or retarded endometrium, and there was no significant correlation between high LH concentration and retarded endometrial development. In artificial cycles, endometrial development was not different between those with low LH concentrations (down-regulated by Zoladex) and those with high LH concentrations (premature ovarian failure). Endometrial development in the peri-implantation period does not appear to be influenced by LH concentration in the follicular phase. The reported association between high LH concentration and poor reproductive performance cannot therefore be explained by abnormal implantation consequent upon retarded endometrial development.

Adult↗
PubMed1993

A study of endometrial morphology in women who failed to conceive in a donor insemination programme.

OBJECTIVE: To examine the morphology of endometrium in women who failed to conceive after nine or more cycles of donor insemination treatment. DESIGN: Prospective study. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Two groups: twenty-six infertile women and a control group of eight fertile women. INTERVENTION: Endometrial biopsy specimens were obtained in the mid-luteal phase, timed precisely by the luteinising hormone surge. MAIN OUTCOME MEASURE: Morphological study of endometrial biopsy specimens by the use of traditional dating criteria and established morphometric techniques. RESULTS: Twelve biopsy specimens (42%) were found to be retarded. In addition, morphometric analysis revealed significant differences in the glandular component of the endometrium between the infertile and fertile groups. CONCLUSION: Endometrial defect leading to implantation failure may be an important underlying cause of failure to conceive after repeated attempts at donor insemination. The endometrium should be investigated in this group of women, and further attempts at donor insemination treatment should be offered only in conjunction with attempts to restore the normality of the endometrium.

Adult↗
PubMed1992

Recovery of artificially inseminated spermatozoa from the fallopian tubes of a woman undergoing total abdominal hysterectomy.

Investigation of the process of sperm transport within the human female reproductive tract must involve the recovery of spermatozoa from the oviducts of women post-coitum or insemination. This case report describes the insemination of a 40-year-old woman with her partner's semen and the subsequent recovery of spermatozoa from her Fallopian tubes, removed at hysterectomy, 2 days post-ovulation. The number of spermatozoa present within the tubes and their location was ascertained using a flushing technique and scanning electron microscopy (SEM). The total number of spermatozoa present within the flushed tube was calculated to be 142, whilst the total number of spermatozoa calculated to be present within the scanned tube was 673. The proportional distribution of spermatozoa within the tubes was virtually identical by the two techniques used. The largest population of spermatozoa resided within the ampulla (66.1% SEM, 68.3% flush), and the smallest population resided within the intramural region (14.9% SEM, 13.4% flush).

Adult↗
PubMed1992

A prospective, randomised, cross-over study comparing the effects of clomiphene citrate and cyclofenil on endometrial morphology in the luteal phase of normal, fertile women.

OBJECTIVE: To examine the effect of two anti-oestrogens, clomiphene citrate and cyclofenil, on endometrial morphology in the luteal phase. DESIGN: A prospective, randomised, cross-over study. SETTING: Jessop Hospital for Women, Sheffield, UK. SUBJECTS: 10 women who were previously fertile and regularly cycling. INTERVENTION: The administration of clomiphene citrate or cyclofenil in the treatment cycles. A LH timed endometrial biopsy was taken on day LH + 6. MAIN OUTCOME MEASURES: Histological dating and morphometric analysis of the endometrial sample. RESULTS: Only one out of 10 subjects had abnormal endometrium. There was no difference in the results between cycles treated with clomiphene citrate and cyclofenil. CONCLUSIONS: Clomiphene citrate or cyclofenil does not have a major adverse effect on endometrial morphology in the luteal phase of normal fertile subjects. The possible adverse effects of anti-oestrogens on endometrium may have been previously overestimated.

Adult↗
PubMed1992

Endometrial responses in artificial cycles: a prospective, randomized study comparing three different progesterone dosages.

OBJECTIVE: To examine the endometrial response to three different regimens of progesterone. DESIGN: A prospective, randomized study. SETTING: The Jessop Hospital for Women, Sheffield. SUBJECTS: 14 women with premature ovarian failure divided into two equal groups. INTERVENTIONS: Three different regimens of hormone replacement therapy containing standard, high and low progesterone dosages. One group received the standard regimen in one cycle and high dosage regimen in another cycle. The second group received the standard regimen in one cycle and low dosage regimen in another cycle. The order of the two dosage regimens was randomized by lottery. MAIN OUTCOME MEASURES: Ultrasonographic measurement of endometrial thickness and morphological study of endometrial biopsy specimens taken on day 19 of the cycle using the traditional dating criteria and morphometric techniques. RESULTS: Compared with standard regimen cycles, the endometrial response in cycles treated with the low dosage regimen showed significant retardation of overall endometrial development and changes in a number of morphometric measurements. The response of endometrial glands to the high dosage regimen was similar to that of the standard regimen, although the stromal cell diameter was increased. CONCLUSIONS: In women receiving hormone replacement therapy normal endometrial development depends on an adequate dosage of progesterone, but increased dosage above our standard regimen does not produce any further change in the glandular component of the endometrium.

Adult↗