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Biomedical subjects

P C Leppert

Publications and source records attributed to P C Leppert.

At least 19 recordsLinked to original sources

Learning from the community about barriers to health care.

One of the major challenges facing obstetrician-gynecologists, especially those serving populations that are diverse in culture and circumstances, is to identify and address the barriers that keep women from seeking timely preventive and prenatal health care. The Department of Obstetrics and Gynecology at Rochester General Hospital held a community focus groups to learn more about women's attitudes toward health care. In addition to economic issues, such as lack of insurance and an inability to pay, the organizers found that many of the factors that prevent or discourage women from seeking health care involve issues of communication and understanding. Many women wanted what they perceived to be additional services. In reality, many of the things desired involved changes in doctor-patient interactions rather than the addition of any new service, and could be addressed with relative ease and minimal cost. Providing staff members with training in cultural sensitivity and encouraging them to develop a real awareness of patient circumstances are first steps that can lead to better communication between provider and patient and to the development of mutual trust. Other factors, such as the fear of incarceration or of losing one's children if health care is sought, present more serious challenges. Providers of care to high-risk, impoverished populations need to develop strong links to mental health, substance abuse, and family preservation services that allow them to intervene with troubled women and their families with services that are alternatives to incarceration and punitive actions.

Attitude to Health

Anatomy and physiology of cervical ripening.

The uterine cervix is a unique organ composed predominately of the extracellular matrix proteins, collagen, elastin, and glycosaminoglycans. During pregnancy and labor, this organ is metabolically active, which is rare in adult tissue. The metabolism is under reproductive hormonal control and is more complex than previously appreciated. Smooth muscle cells, which comprise 10-15% of cervical tissue, undergo programmed cell death and play a role in cervical softening. Apoptosis is a genetically timed event and could explain the species-specific length of gestation. Further research in the next several years will reveal more completely the exciting process of cervical ripening. Only when this phenomenon is understood will rational therapy for preterm labor and post-term pregnancy with an unripe cervix be available. Specific defects in cervical ripening will then be diagnosed and treated. For example, if apoptosis is shown to play an important role in the process of cervical ripening, it could be inhibited. Conversely, it could be induced in the unripe cervix. If we would look for it, we would find that it is probably occurring today in the clinical use of cervical ripening agents. The most important contributor to cervical softening, however, is a rearrangement and realignment of the collagen, elastin, and smooth muscle cells, which occurs due to mechanical forces and to a rearrangement of the collagen that occurs as the content of glycosaminoglycans varies in the cervix with time. One form of dermatan sulfate, decorin, may help to separate the collagen fibrils and then open them up. This rearrangement also involves fiber shortening below the critical length for tensile strength, allowing for extensibility of the cervix. Because of its orientation in the cervix, elastin contributes to the ratchet-like mechanism of dilatation. Finally, the cervix undergoes change in two phases--softening, which involves collagen realignment, and dilatation. The proteolytic enzymes in the cervix degrade cross-linked, newly synthesized collagen, and they help activate other enzymes in a cascade. However, the predominate anatomic and physiologic change in ripening is the rearrangement of collagen.

Animals

Collagen changes in rat cervix in pregnancy--polarized light microscopic and electron microscopic studies.

The structural arrangement of collagen fibers in cervical ripening was studied in normal pregnant rats by picrosirius red staining and polarized light microscopy. The macromolecular arrangement of collagen fibers in the cervices of nonpregnant controls and in firm and rigid cervices of rats in early pregnancy (1-10 days of gestation) were optically anisotropic and had birefringence and a positive sign of elongation when examined by polarized light microscopy. The findings indicated that the structure of these collagen fibers was assembled from well-packed parallel collagen molecules. The direction of fibrous formation was arranged with regularity. In contrast, most of the collagen fibers in the soft cervices were optically isotropic. The fibers were fragmented and had a structure with discontinuous birefringence. Disarray and disorientation of the collagen fibers was found in the soft cervices. These collagen fibers changed their direction of formation. The disorganization of these collagen fibers might have a major impact on weakening the tensile strength of the cervix. Thus, we conclude that the processes of rearrangement of collagen fibers might be an important process in the cervical ripening. Electron microscopic studies suggest that in the focal hydrolytic processes of collagen and other matrix components degradation by lysosomal and phagosomal vesicles were associated with atrophic smooth muscle cells and fibroblasts of the cervices. Hydrolases released from lysosomes from these apoptotic cells may presumably be one of the processes in the remodeling of collagen structure.

Animals

Apoptosis in the cervix of pregnant rats in association with cervical softening.

Cervical ripening in gestation occurs spontaneously in a timely but species-specific fashion as if it were genetically programmed. This study shows that the numbers of dying smooth muscle cells in the cervix increased along with cervical softening in pregnant rats from day 12 of gestation to day 21. The morphological characteristics of the chromatin cleavage in apoptosis are identified. Internucleosomal DNA fragments in the DNA preparations as well as the ladder pattern of double-stranded DNA observed on gel electrophoresis are observed. The deletion and decrease of the cell population in the cervices was demonstrated by a decrease of total DNA in these tissues. The interesting possibility is raised that programmed smooth muscle cell death in the cervix may be involved in the processes of the cervical ripening.

Animals

Three-dimensional structures of uterine elastic fibers: scanning electron microscopic studies.

We report findings that demonstrate for the first time that the structure of the elastic fibers of the uterus and cervix are characteristic to these tissues. Elastic fibers of the uterine corpus and cervix were studied by scanning electron microscopy (SEM). Elastic tissues were prepared from non-pregnant human uteri and pregnant rat uteri by three different methods: extraction from the tissue homogenates, in situ digestion by autoclaving of sliced tissue, and in situ formic acid digestion of sliced tissue. In addition, in situ formic acid digestion of the glutaraldehyde-fixed uterine wall of pregnant rats was done. Under SEM, the uterine elastic fibers revealed two distinct structures--fibrils and thin sheets of elastic membranes. Isolated fibers and membranes ranged in thickness from 0.1 to 0.4 micron which is thinner than aortic elastic lamellae (1-2.5 microns in thickness). These thin sheets of elastic membranes and elastic fibrils probably allow the uterus to maintain its elasticity without exerting excess pressure on the growing fetus. Formic acid digestion of fixed uterine walls of pregnant rats preserved the structural organization of elastic tissues near in vivo conditions. In these tissues, the fibers were arranged in a honeycomb structure made up largely of membranes, although sparse fibrils were present. These elastic, membranous sheets were arranged parallel to the plane of the uterine surface and interconnected with the threads of the membranes or fibrils. In the rat uterine wall, at least 12 parallel layers of elastic sheets were present. In contrast, at low magnification, the elastic tissues in the non-pregnant human uterus had no specific architectural arrangement and exhibited a sponge-like structure. Elastic fibers of the cervix were also made up of membranes and fibrils, and these fibers were organized into fishnet-like structures. These cervical membranes had fenestrations and pits with a diameter of 3-5 microns. In these studies, the concentrations of insoluble elastin in human uteri were found to be 1.38 and 1.32-1.41% of dry-defatted tissues for uterine body and cervix, respectively. The concentrations of total collagen were 38.8 and 64.3-72.4% of dry-defatted tissues for uterine body and cervix, respectively.

Adult

Effects of epidural analgesia: some questions and answers.

The effects of epidural analgesia on first labors have been studied by Thorp and colleagues. One study has been published and is the subject of a question-and-answer discussion, presented here. In this study 711 consecutive nulliparous women at term, with spontaneous onset of labor and cephalic presentation, were divided into one group (n = 447) who received epidural analgesia in labor and another group (n = 264) who received narcotics or no analgesia. The frequency of cesarean section for dystocia was significantly greater (p less than 0.005) in the epidural group (10.3%) than in the nonepidural group (3.8%), even after selection bias was corrected and the variables of maternal age and race; gestational age; cervical dilatation on admission; use, duration, and maximum infusion rate of oxytocin; labor duration; presence of meconium; and birth weight were controlled. For both groups the frequency of cesarean section for fetal distress was similar (p less than 0.20), and the frequency of low Apgar scores at 5 minutes and cord blood gas values showed no significant differences. The authors concluded that "epidural analgesia in labor may increase the incidence of cesarean section for dystocia in nulliparous women".

Analgesia, Epidural

Human recombinant interleukin-1 alpha increases elastase-like enzyme in human uterine cervical fibroblasts.

Production of the elastase-like enzyme, Suc-(Ala)3-p-nitroanilide hydrolase, was examined in human uterine cervical fibroblasts. The metallo-dependent enzyme is present in both media and cellular fractions. Human recombinant interleukin-1 alpha stimulated cells to produce and secrete this elastase-like enzyme. These results suggest that modulation of this enzyme activity by interleukin-1 may play a significant role in the ripening and dilation of the cervix, because elastin is a component of the uterine cervix and its peptides are known to be chemotactic for leukocytes.

Cells, Cultured

Decreased elastic fibers and desmosine content in incompetent cervix.

Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation that represents abnormal functioning. It may serve as a model to elucidate normal function. Because the incompetent cervix results in painless opening of this organ without uterine contraction before term gestation, it is considered one of the causes of midtrimester spontaneous abortion, habitual spontaneous abortion, and early preterm labor. Untreated, it leads to rapid expulsion and often death of the fetus. We used light microscopy to compare decreased elastic fibers in incompetent cervices with those of normal nonpregnant and pregnant cervices. Morphologic analysis of this difference was extended to biochemical quantification of elastin content in one patient with cervical incompetence. The decrease in elastin suggests that one function of cervical elastin may be to maintain a closed and undilated cervix throughout gestation. There may be a relationship between changes in cross-linked elastin and the incompetent cervix; further studies are therefore indicated.

Amino Acids

Orientation of elastic fibers in the human cervix.

We have determined the microanatomy of the cervix in relation to elastic fibers by serial dissection of human cervix in three tissue planes: cross, sagittal, and frontal sections. Analysis suggests that elastin is localized to specific regions of the uterine cervix and not dispersed throughout the connective tissue stroma. By Musto stain the majority of elastic fibers are noted to be oriented from the external os to the periphery and from there in a band upward toward the internal os where they become sparse in the area of the cervix with the greatest amount of smooth muscle just below the internal os. Elastic fibers were noted to be sparsely distributed in the cervical stroma.

Cervix Uteri

Neonatal alloimmune thrombocytopenic purpura: a case report.

We report a case of a sibling pair with neonatal alloimmune thrombocytopenic purpura. Serial antepartum platelet alloantibody quantitation by an enzyme-linked immunoabsorbent assay revealed rising antibody titers during advancing gestation. We discuss the implications of this finding in the antepartum diagnosis of neonatal alloimmune thrombocytopenic purpura, a rare, but frequently fatal disorder.

Adult

Pregnancy outcomes among adolescent and older women receiving comprehensive prenatal care.

This study compares three birth outcomes, gestational age, birthweight, and type of delivery, among adolescent and older mothers. Data were collected from 911 women who attended a comprehensive prenatal-care program in a large urban teaching hospital. Women aged 13-19 years were at increased risk for low-birth-weight babies (less than 2500 g) and for preterm infants of fewer than 38 weeks gestation, even with antenatal care, ethnicity, and other factors controlled. Results of bivariate analyses suggested that women aged 20-36 years are more likely than adolescent mothers to have a cesarean section; however, multivariate analyses suggested that maternal age was not an important factor in relation to type of delivery. Thus, even with similar comprehensive care, pregnant adolescents were at an increased risk of some adverse outcomes. However, the amount of antenatal care is a more important predictor of pregnancy outcome than is maternal age.

Adolescent

Neonatal alloimmune thrombocytopenic purpura.

We reviewed 58 literature reports of neonatal alloimmune thrombocytopenic purpura (NAITP). The mortality rate was 9%. The total incidence of suspected intracranial hemorrhage was 28%. We reviewed 17 sibship cases for the relation of birth order to treatment and outcome. Among firstborn affected infants (n = 17) the mortality rate and incidence of central nervous system sequelae were 24 and 47%, respectively, compared to rates of 5 and 15%, respectively, in their younger affected siblings (n = 20). The improved outcome in the latter group appeared to be related to more frequent cesarean section delivery and more frequent and earlier use of corticosteroids and maternal platelet transfusions in the neonate. Sensitive assays of maternal platelet alloantibody are now available, but they lack specificity for NAITP affecting the current gestation. There are two reports in which sensitive assays revealed rising titers of maternal platelet alloantibody during advancing gestation. We propose further study to determine if this is specific for the antepartum diagnosis of NAITP.

Adrenal Cortex Hormones

Cesarean section deliveries among adolescent mothers enrolled in a comprehensive prenatal care program.

A comparison was made of the incidences of cesarean section deliveries between mothers 18 years of age or younger and those 19 to 21 years of age, all of whom were enrolled in a comprehensive program of prenatal care. Also compared were the indications for surgical delivery between the two groups. The rate of cesarean section deliveries was 8.7% among mothers 18 years of age or younger, compared to 14.5% among mothers 19 to 21 years of age. The general-ward cesarean section rate at the same hospital was 19.4%. Since maternal height and weight, and infant's birth weight may affect the diagnosis of cephalopelvic disproportion, these parameters were also evaluated. However, these did not differ significantly between mothers 18 years of age or younger and those 19 to 21 years of age or between vaginal and surgical births in mothers 18 years of age or younger. Thus, cephalopelvic disproportion did not contribute importantly to the cesarean section rate.

Adolescent

The tendency to IUGR in preterm infants born to young women enrolled in a comprehensive prenatal program.

Low-birthweight infants born to young women in an urban poor and multiethnic community who attended an intensive comprehensive prenatal program were studied. Of the 801 young women followed, 69 (8.6%) delivered infants weighing less than or equal to 2500 gm. Despite comprehensive care, there was a high prevalence of maternal anemia though other obstetric factors were not significantly increased. Of the 69 low-birthweight infants, 82.6% were below the 50th percentile for weight. There was a tendency toward intrauterine growth retardation (IUGR) among preterm infants which was pronounced after 33 weeks gestation. Further studies are needed to determine what developmental insult could arrest growth and lead in some instances to preterm birth and in others to IUGR.

Adolescent

Spontaneous regression of fetal ascites in utero in an adolescent.

Fetal ascites has been documented by ultrasound to progressively disappear prior to birth. This report describes a case in a nineteen-year-old in which fetal ascites was documented in the midtrimester of pregnancy and in which subsequent regression was shown by ultrasound. Although nonimmune fetal hydrops commonly has a poor prognosis, it is possible to adopt an observant attitude while a carefully evaluating for an etiology of fetal ascites.

Adult