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Biomedical subjects

B Gonik

Publications and source records attributed to B Gonik.

At least 19 recordsLinked to original sources
PubMed1992

Progesterone and estradiol suppress human mononuclear cell cytotoxicity.

Fetal trophoblast is generally resistant to lysis by cytotoxic cells. We hypothesized that progesterone and estrogens secreted by the trophoblast act at the choriodecidual interface where they are present in high concentrations to provide a local, paracrine immunosuppressive effect on cellular cytotoxicity. Using peripheral blood mononuclear cells as effector cells in a cytotoxicity assay, we evaluated the effects of progesterone, estrone, estradiol and estriol, either alone or in combination, on cellular cytotoxicity. Both progesterone and estradiol suppressed cytotoxicity in a dose-dependent manner. Estrone, estriol, pregnenolone and cholesterol had no effect. A synergistic suppression of cytotoxicity was observed when estrone, estradiol, estriol and progesterone were combined. We speculate that trophoblast production of progesterone and estradiol may be an important local immunosuppressive mechanism contributing to fetal survival.

Cells, Cultured↗
PubMed1992

Why patients fail antibiotic prophylaxis at cesarean delivery: histologic evidence for incipient infection.

A prospective, blinded study was conducted to test the hypothesis that antimicrobial prophylaxis failure after cesarean delivery is associated with incipient infection of the uterus, as determined by histologic evaluation of bacterial invasion and acute inflammatory cell response. One hundred nineteen patients undergoing cesarean delivery and receiving antibiotic prophylaxis were included in this study. At the time of the operation, a hysterotomy biopsy was obtained for hematoxylin and eosin staining. Marked histologic differences were noted in decidual inflammation, myometrial inflammation, and myometrial polymorphonuclear cell invasion in those patients who subsequently developed endometritis (N = 7) compared with subjects without postpartum endometritis. Using two techniques for in situ identification of bacteria within myometrial tissue (acridine orange and fluorescein DNA probe to bacterial ribosomal RNA), all clinically infected parturients demonstrated large numbers of organisms in the myometrial layer of the biopsy specimen, compared with few organisms seen in a matched subset of noninfected controls. These data support the concept that incipient infection at the time of cesarean delivery may limit the effectiveness of antimicrobial prophylaxis. Use of rapid-diagnosis methodologies may allow timely identification of these at-risk patients so that therapeutic antibiotics can be initiated.

Anti-Bacterial Agents↗
PubMed1991

Sexually transmitted viral disease in women.

During the past decade, the incidence of sexually transmitted viral diseases has increased dramatically. In many cases, diagnosis is difficult, consequences are severe, and curative therapy is not available at present. In this article, Drs Peaceman and Gonik review current evidence about sexual transmission of viruses and discuss the latest methods of diagnosis, management, and prevention.

Female↗
PubMed1991

Increased progesterone concentrations are necessary to suppress interleukin-2-activated human mononuclear cell cytotoxicity.

Fetal trophoblast is generally resistant to lysis by cytotoxic cells. Trophoblast progesterone and estrogens may act at the choriodecidual interface, where they are present in high concentrations to provide a local, paracrine immunosuppressive effect on cellular cytotoxicity. However, interleukin activation of these cytotoxic lymphocytes enhances their ability to lyse trophoblast. Recent evidence suggests that immunoactivation occurs in certain aberrant pregnancy conditions, including preeclampsia. Preeclamptic placentas produce more progesterone in vitro than do normal placentas. To study the potential association between progesterone production and immunoactivation, we evaluated the immunomodulatory effect of progesterone on cellular cytotoxicity. Comparisons were made with the use of both normal and interleukin-2-stimulated peripheral blood mononuclear cells as effector cells in a cytotoxicity assay. Progesterone suppressed cytotoxicity in a dose-dependent manner. Interleukin-2 augmented cellular cytotoxicity, and higher concentrations of progesterone were required to attenuate this response. An additive suppression of cytotoxicity was also observed when estrone, estradiol, estriol, and progesterone were combined. We speculate that the higher placental production of progesterone seen in preeclampsia may be a trophoblast compensatory response to immunoactivated maternal effector cells.

Chromium↗
PubMed1991

Natural killer cell cytotoxicity to herpes simplex virus-1-infected cells is not altered by pregnancy.

There is evidence to suggest a decrease in natural killer cell cytotoxicity during pregnancy, but information regarding immune responsiveness to actual infection is limited. An in vitro study was undertaken to examine the effect of herpes simplex virus infection on natural killer cell cytotoxicity with peripheral blood mononuclear cells from pregnant (N = 8) and nonpregnant (N = 5) women. The peripheral blood mononuclear cells were separated by Ficoll-Hypaque centrifugation. Effector cells were incubated with live herpes simplex virus-1, ultraviolet-inactivated herpes simplex virus-1, or media alone for 18 hours at 37 degrees C. K562 target cells were used in a sodium chromate release assay with an effector-to-target cell ratio of 100:1. Baseline natural killer cell values (mean +/- SE) for pregnant patients (13.4% +/- 2.4%) and nonpregnant patients (19.8% +/- 3.7%) were similar. Natural killer cell cytotoxicity was significantly increased by incubation with live virus for both pregnant (37.5% +/- 6.2%) and nonpregnant subjects (49.8% +/- 7.6%). There was no difference in mean values between media and ultraviolet-inactivated herpes simplex virus-1-exposed samples for either group. Results suggest that (1) infection with live virus, but not viral antigen alone, can augment natural killer cell response in vitro and (2) natural killer cell response to herpes simplex virus-1 infection is not altered by pregnancy.

Cytotoxicity, Immunologic↗
PubMed1991

Shoulder dystocia recognition: differences in neonatal risks for injury.

Shoulder dystocia (SD) is an event whose current diagnostic approach is based on subjective criteria alone. Since the risk for immediate neonatal morbidity is critically linked to recognition and appropriate management of this obstetric emergency, we hypothesized that infants having injuries consistent with SD are frequently delivered without the intrapartum identification of this condition. A retrospective analysis of 26,033 vaginal births from January 1979 to April 1987 identified 162 maternal cases in which SD was diagnosed during delivery (incidence, 0.62%). Within this subset of patients, 24 neonates (15%) were identified as having either brachial plexus or fractured clavicle injuries associated with delivery. An additional 60 neonates were identified as having similar injuries immediately following delivery but without obstetric recognition of SD. Therefore 71% of all the injured infants were the product of deliveries without SD recognition. A comparison was made of maternal and neonatal variables for three groups (SD, uninjured; SD, injured; unrecognized SD, injured). The SD, injured group distinguishes itself from the other two groups by significant differences in the degree to which variables previously associated with SD are present. Conversely, both other groups are similar in all parameters except for accepted SD maneuvers utilized. These results support our hypothesis that SD is underreported in the obstetric literature and that unrecognized SD is associated with an increased risk of neonatal injury. Efforts to define objectively the threshold forces associated with neonatal injury and to develop SD teaching models should improve this clinical dilemma.

Adult↗
PubMed1991

Evaluation of phenazopyridine hydrochloride as a tool in the diagnosis of premature rupture of the membranes.

This is a prospective study to determine whether a maternal orally administered azo dye, phenazopyridine hydrochloride, would cross into amniotic fluid, and thus be of potential aid in the diagnosis of rupture of the membranes. Based on anecdotal experience, we hypothesized that this compound would cross the placenta and be excreted in the fetal urine, causing discoloration of the amniotic fluid. Ten patients with uncomplicated pregnancies undergoing elective amniocentesis for obstetric indications received an oral dose of 400 mg of phenazopyridine hydrochloride 4 hours prior to the procedure. Amniotic fluid was also available from five control patients who did not receive phenazopyridine hydrochloride. The typical orange-to-red discoloration of the urine was seen in all study patients, indicating ingestion of the dye. None of the ten patients had evidence of the azo dye in their amniotic fluid by visual inspection or by spectrophotometric absorbance. After the amniotic fluid samples were acidified, the presence of the azo dye was visually demonstrable, and spectrophotometry confirmed measurable concentrations (mean +/- SE: 13.08 +/- 0.72 micrograms/ml). We conclude that although phenazopyridine hydrochloride does cross the placenta into the fetal compartment, its presence causes a visual and spectrophotometric change in the color of amniotic fluid only when the normal basic pH of amniotic fluid is acidified.

Amniotic Fluid↗
PubMed1991

Comparison of two enzyme-linked immunosorbent assays for detection of herpes simplex virus antigen.

Two enzyme-linked immunosorbent assays (ELISAs) for herpes simplex virus (HSV) detection were compared with culture in a prospective, blinded study with 153 patients with suspected recurrent oral or genital HSV. A subset of 15 of these subjects were studied daily until symptom resolution during a single episode of recurrent HSV. Direct-site specimens were collected and either placed in viral transport media (for Ortho ELISA and fresh inoculation into primary rabbit kidney cells) or frozen in ELISA collection media (DuPont). One hundred eighty-six culture-ELISA comparisons were analyzed. On the basis of culture positivity, the DuPont and Ortho ELISAs differed substantially with regard to sensitivity (93 versus 35%) but had similar specificities (95 versus 100%) and positive (85 versus 100%) and negative (98 versus 85%) predictive values. There were seven DuPont ELISA-positive, culture-negative samples which were confirmed positive for HSV by blocking antibody test (revised specificity, 100%; positive predictive value, 100%). Six of these discrepant samples were from previously culture-positive subjects. These results demonstrate that currently available ELISA kits vary substantially as to their sensitivities in detecting HSV antigen from direct-site specimens. In addition, antigen detection, by ELISA technology, is not always synonymous with state of viral infectivity as judged by tissue culture cytopathic effect.

Antigens, Viral↗
PubMed1991

Induction of cytokines in normal placental cells by the human immunodeficiency virus.

Placental cotyledon mononuclear cells (CMC) resemble peripheral blood monocytes/marcophages (MM) with respect to their expression of surface antigens and cellular function. CMC also express the CD4 antigen receptor and are thus susceptible to infection with the human immunodeficiency virus (HIV). When vertical transmission of HIV from mother to fetus occurs, the infection often remains latent until appropriate factors initiate the transcription of virus-specific mRNA. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) which are produced by MM, up-regulate HIV expression in infected cells. The induction of cytokines in MM does not require active infection with HIV since heat-inactivated HIV (iHIV) and envelope gp120 caused cytokine secretion. We studied the ability of CMC from normal placentas to secrete these cytokines following stimulation with endotoxin, iHIV, recombinant GP160 and GAG55, and synthetic p17, HGP-30. Whereas CMC spontaneously secreted low levels of IL-1 beta and TNF-alpha, they constitutively secreted high levels of IL-6. All cytokine levels could be boosted by endotoxin. GP160, iHIV, and HGP-30 failed to augment cytokine levels above baseline. In contrast, GAG55 significantly boosted only TNF-alpha. The relevance of these findings is discussed with respect to the putative roles of cytokines in the immunoregulation of HIV in utero.

Cell Transformation, Viral↗
PubMed1991

Risk factors for shoulder dystocia: an engineering study of clinician-applied forces.

We report on engineering risk factors associated with clinician-applied forces during vaginal delivery of newborns. Specifically, we present and interpret data from a series of experiments using force-sensing devices on 29 randomly selected vaginal births, including two shoulder dystocia deliveries and one birth injury. The results indicate that clinician-applied peak forces are typically about 47 N for routine deliveries, 69 N for difficult deliveries, and 100 N for a shoulder dystocia delivery (P less than .01). The time required to deliver fetal shoulders doubles for nonroutine deliveries (P less than .01). In addition, impulse and rate of application of force distinguish between routine and nonroutine deliveries (P less than .03). We conclude that, if properly perceived, force, force rate, and the duration of force are objective parameters that can be used in recognizing and managing shoulder dystocia and in predicting thresholds for birth injury.

Biophysical Phenomena↗
PubMed1990

Multicenter clinical evaluation of the Du Pont Herpchek HSV ELISA, a new rapid diagnostic test for the direct detection of herpes simplex virus.

A new 4h rapid enzyme-immunoassay for direct detection of herpes simplex virus (HSV) antigen (Du Pont Herpchek) was evaluated with 743 clinical samples collected at obstetrics and gynecology (OB/GYN), sexually transmitted diseases (STD), and ophthalmology clinics. The sensitivity and specificity of Herpchek was 98.0% and 98.4% respectively compared to virus isolation in cell culture. Confirmatory blocking ELISA tests, clinical history and follow up indicate that the true specificity of the test is 100%.

Adult↗
PubMed1990

Immune modulation of natural killer cell cytotoxicity against herpes infected target cells in pregnancy.

Natural killer cell cytotoxicity (NKC) is a nonspecific, primary immunodefense system active against a variety of pathogens, including herpes simplex virus (HSV). Evidence suggests that during pregnancy, NKC is attenuated. The regulatory mechanisms for this immune attenuation have yet to be defined. We examined two cytokines (interleukin-2 [IL-2] and alpha interferon [IFN]) for their ability to alter NKC responsiveness during pregnancy, utilizing an HSV-infected target cell model. Peripheral mononuclear effector cells were isolated from 19 pregnant and 19 nonpregnant subjects by Ficoll-Paque separation. These cells were incubated with IFN, IL-2, or media alone, and analyzed for %NKC by an 18 h chromium release assay. The percentage of NKC was lower using the effector cells from the pregnant subjects as compared to nonpregnant controls. Incubation with either IFN or IL-2 resulted in a significant augmentation of NKC in both the pregnant and nonpregnant derived cells. There were no differences in IL-2 dose requirements or levels of cytotoxicity achieved (43.1 +/- 6.8% vs. 44.4 +/- 6.8%, respectively) between pregnant and nonpregnant derived cells. The IFN-mediated augmentation of NKC was somewhat blunted in pregnancy both in terms of absolute levels of cytotoxicity achieved (26.1 +/- 3.9% vs. 37.2 +/- 4.9%, respectively) and dose response curves generated. These results demonstrate that NKC against HSV infected cells is attenuated during pregnancy and can be immunoregulated with the use of either IFN and IL-2. The restoration of NKC responsiveness with IFN, however, remains incomplete during pregnancy, suggesting that this cytokine's mechanism of action differs from that of IL-2.

Antigens, CD↗
PubMed1989

Prostacyclin release and cytotoxicity of peritoneal cells are inversely related in pregnant and non-pregnant mice infected with herpes simplex virus.

Cytotoxicity of peritoneal cells in a HSV-infected murine model is attenuated in late pregnancy. Prostacyclin (PGI2) is elevated at this time in reproductive tissues and has been implicated in the regulation of the immune response. The purpose of this study was to estimate PGI2 in the peritoneal wash or culture supernatants of peritoneal cells obtained from uninfected and HSV-infected pregnant and virgin mice using a radioimmunoassay for 6-keto-prostaglandin F1 alpha. The peritoneal wash of uninfected pregnant and virgin mice contained high levels of 6-keto-PGF1 alpha, 505 +/- 51 pg/100 microliters, (mean +/- S.E., n = 15), and 200 +/- 19 pg/100 microliters, (n = 30), ad did peritoneal effector and target cell cultures (1,159 +/- 118 pg/100 microliters, n = 6, and 1,057 +/- 207 pg/100 microliters, n = 7), respectively. HSV-infection induced in vitro cytotoxicity and suppressed the release of 6-keto-PGF 1 alpha (r = -0.897, P less than 0.05, n = 18). Its concentration was significantly higher (14-fold, P less than .05) in the peritoneal wash, but not in the cell culture, of pregnant (212 +/- 29 pg/100 microliters, n = 19) as compared to virgin mice (18.5 +/- 3.4 pg/100 microliters, n = 27). The levels of 6-keto-PGF1 alpha were inversely correlated (P less than .05) with the combined effects of HSV-infection and cytotoxicity.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Clinical evaluation of a new herpes simplex virus ELISA: a rapid diagnostic test for herpes simplex virus.

A new sensitive and rapid enzyme-linked immunosorbent assay (ELISA) test (Du Pont HERPCHEK) for the detection of herpes simplex virus (HSV) antigen was evaluated. A total of 563 clinical samples collected from patients attending obstetrics and gynecology and sexually transmitted disease clinics in two geographic locations were tested by ELISA, and the results were compared with virus isolation in cell culture. The sensitivity and specificity of the ELISA were 97.5 and 98.6%, respectively. When a confirmatory blocking ELISA was used to demonstrate the presence of HSV antigen in culture-negative but ELISA-positive samples, the specificity of the assay increased to 100%. The assay is easy to perform and may be used to diagnose HSV infection rapidly without the need for culture confirmation.

Adult↗
PubMed1989

Objective evaluation of the shoulder dystocia phenomenon: effect of maternal pelvic orientation on force reduction.

This report describes the use of maternal pelvic and fetal models, a tactile sensing glove, and a microcomputer data acquisition system to measure fetal shoulder extraction forces. Sixty-nine experiments were carried out in the laboratory setting to simulate vaginal delivery of the aftercoming fetal shoulders. The tests were conducted using a variety of fetal biclavicular diameters (10-13 cm) and maternal pelvic angle positions (McRoberts, 10 degrees; lithotomy, 25 degrees). When comparing lithotomy versus McRoberts positioning, there was a consistent reduction in force needed to extract the fetal shoulders with the latter maneuver. No simulated clavicles were fractured during shoulder delivery until a biclavicular diameter of 12.0 cm was reached. At this point, five of eight clavicles (63%) were fractured at 25 degrees and zero of seven (0%) were fractured at 10 degrees (P less than .025). For all 69 experiments, fetal neck extension readings were consistently lower than the total traction forces recorded by the tactile sensing glove. This suggests that, in addition to the axially oriented fetal neck forces, a component of flexion (lateral force) was also present. As the difficulty of shoulder delivery increased, the impact of these inadvertent flexion forces became most pronounced at the level of the brachial plexus. This is the first study to measure shoulder extraction forces reproducibly using a laboratory model for shoulder dystocia and to describe the pathophysiology of specific neonatal injuries from a force perspective. The results document objectively that McRoberts positioning reduces shoulder extraction forces, brachial plexus stretching, and the incidence of clavicular fracture.

Delivery, Obstetric↗