α-Lipoic acid blocks the GMCSF induced protease/protease inhibitor spectrum associated with fetal membrane weakening in-vitro.

INTRODUCTION: We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNFα and thrombin induced FM weakening. α-Lipoic-acid (LA) blocks TNFα and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors. METHODS: FM fragments were cultured±LA and then±GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors. RESULTS: GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1). LA inhibited GMCSF-induced FM weakening and all enzymatic changes. Untreated weaker versus stronger regions of fresh FM showed comparable differences in proteases and protease inhibitor patterns to GMCSF-stimulated versus controls. CONCLUSION: LA blocks GMCSF-induced human FM weakening and associated protease increases and inhibitor decreases. The GMCSF-induced spectrum of protease/protease-inhibitor changes is similar to that in the natural weak FM fragments. In concert with previously reported GMCSF-induced changes in MMPs & TIMPs, these other protease and protease-inhibitor changes presumably facilitate FM weakening and rupture. LA blocks these GMCSF effects and therefore may be a useful agent to prevent PPROM.

Differential expression of fibulin family proteins in the para-cervical weak zone and other areas of human fetal membranes.

OBJECTIVE: Human fetal membranes (FM) at term have been shown to contain a weak zone in the region overlying the cervix which exhibits characteristics of increased collagen remodeling and apoptosis. It has been hypothesized that the FM rupture initiation site is within this weak zone. Although the FM weak zone has been partially characterized, it is unclear what structural differences in the extracellular matrix result in its decreased rupture strength. A screen for differentially expressed proteins in the amnion of the weak zone versus other FM areas demonstrated that fibulin 1 was decreased. We investigated potential regional differences in all fibulin protein family members. METHODS: FM fibulins were localized by immunohistochemistry. Detected fibulins were screened by Western blot for differences in abundance in the amnion of the weak zone versus non-weak zone FM regions. Amnion epithelial and mesenchymal cells were also screened for fibulin production. RESULTS: Fibulins 1 and 5 were detected in the cytoplasm of and in a pericellular pattern surrounding all FM cells, and in a dense extracellular pattern in the amniotic compact zone. Fibulin 3 was detected within the cytoplasm of amnion epithelial and chorion trophoblast cells. Fibulins 2 and 4 were not detected. Fibulins 1, 3 and 5 demonstrated decreased abundance of 33%, 63% and 58% (all P<0.01) in amnion of the weak zone relative to other FM regions. Amnion cells produced all three detected fibulins. Furthermore, TNF inhibited amnion cell fibulin production in a dose dependent manner. CONCLUSION: Fibulins 1, 3 and 5 were localized coincident with major microfibrillar networks in amnion. Each showed decreased abundance in the amnion component of the FM weak zone. Amnion epithelial and mesenchymal cells produced all three fibulins and their abundance was inhibited by TNF. We speculate that the amnion microfibrillar layer undergoes significant remodeling with the development of the FM weak zone.

Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction.

BACKGROUND: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. HYPOTHESIS: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. ANIMALS: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. METHODS: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA. RESULTS: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7-1.8) and venous (1.3, 1.2-1.7) plasma and in BALF (0.3, 0.2-0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21-50) were greater in affected horses during clinical exacerbation compared with remission (P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.

The effects of Strongylus vulgaris parasitism on eosinophil distribution and accumulation in equine large intestinal mucosa.

REASONS FOR PERFORMING STUDY: Eosinophilic granulocytes have been associated with parasite or immune-mediated diseases, but their functions in other disease processes remain unclear. Cause and timing of eosinophil migration into the equine gastrointestinal mucosa are also unknown. OBJECTIVE: To determine the effects of intestinal parasitism on eosinophils in equine large intestinal mucosa. METHODS: Large intestinal mucosal samples were collected from horses and ponies (n = 16) from the general veterinary hospital population, ponies (n = 3) raised in a parasite-free environment, ponies experimentally infected with 500 infective Strongylus vulgaris larvae and treated with a proprietary anthelmintic drug (n = 14), and a similar group of ponies (n = 7) that received no anthelmintic treatment. Total eosinophil counts and eosinophil distribution in the mucosa were determined by histological examination. A mixed model analysis was performed and appropriate Bonferroni adjusted P values used for each family of comparisons. P<0.05 was considered significant. RESULTS: There was no difference in large intestinal mucosal eosinophil counts and eosinophil distribution between ponies infected with S. vulgaris and those raised in a parasite-free environment. Experimental infection with S. vulgaris, with or without subsequent anthelmintic treatment, did not change eosinophil counts, and counts were similar to those for horses from the general population. CONCLUSIONS: Migration of eosinophils to the equine large intestinal mucosa appears to be independent of exposure to parasites. Large intestinal mucosal eosinophils may have more functions in addition to their role in defence against parasites.

The physiology of fetal membrane rupture: insight gained from the determination of physical properties.

Premature rupture of the fetal membranes is a major cause of preterm birth and its associated infant morbidity and mortality. Recently, it has become clear that rupture of the fetal membranes, term or preterm, is not merely the result of the stretch and shear forces of uterine contractions, but is, in significant part, the consequence of a programmed weakening process. Work in the rat model has demonstrated that collagen remodeling, with activation of matrix metalloproteinases (MMPs), and apoptosis increase markedly in the amnion at end-gestation, suggesting that these processes are involved in fetal membrane weakening. We have developed fetal membrane strength testing equipment and a systematic tissue sampling methodology that has allowed us to demonstrate that term, non-labored, fetal membranes have a zone of weakness overlying the cervix, which contains biochemical markers of both collagen remodeling and apoptosis. These findings provide strong support for the concept of programmed fetal membrane weakening prior to labor. Our model has also been used to establish the physical properties of individual fetal membrane components (amnion, chorion), determine the sequence of events during the fetal membrane rupture process, and demonstrate that treatment of fetal membranes with TNF or IL-1beta, in vitro, induces weakness and the identical biochemical markers of collagen remodeling and apoptosis seen in the physiological weak zone. The ability to simultaneously correlate macroscopic physical properties with histological and biochemical fetal membrane characteristics, presents a unique perspective on the physiology of fetal membrane rupture.

A pilot study of methyl chloride emissions from tropical woodrot fungi.

Flux chamber measurements made in a rainforest provide evidence that methyl chloride is emitted from rotting wood. However, its net flux was found to be into the soil, probably due to competing production and consumption processes within the soil. Evidence was found for a regional source, possibly vegetation, since its concentration above the canopy was substantially greater than reported average equatorial values.

Oxytocin activates the inositol-phospholipid-protein kinase-C system and stimulates prostaglandin production in human amnion cells.

It has been postulated that fetal hormonal signals act upon amnion to trigger labor via prostaglandin (PG) production. Human amnion epithelial cell cultures were established to test the effects of potential activators of the inositol phospholipid-protein kinase-C effector system on intracellular inositol phosphate turnover, intracellular free calcium ([ Ca2+]i), and PGE2 production. Oxytocin provoked 3-, 2.5-, and 4-fold increases in inositol triphosphate, inositol bisphosphate, and inositol monophosphate, respectively. [Ca2+]i, measured with the fluorescent dye fura-2, was stimulated by oxytocin and vasopressin (oxytocin greater than vasopressin) in a dose-dependent manner. The [Ca2+]i transient produced by oxytocin reached a peak in 15 sec, followed by a slow return to baseline over 10 min. Preincubation with phorbol 12-myristate-13 acetate (PMA) markedly blunted the oxytocin-induced transient. No [Ca2+]i transient was seen with leukotrienes, PG, serotonin, angiotensin, or alpha- or beta-adrenergic agents. PGE2 production increased 30- to 50-fold with phospholipase-C and PMA, and 10-fold with the calcium ionophore A23187. Oxytocin and vasopressin produced 10- and 3-fold PGE2 increases, respectively. Increased PGE2 production induced by PMA, oxytocin, and A23187 was first seen after 8 hr of incubation and reached maximal levels at 24 h. Minimal PGE2 stimulation occurred with agents that produced no [Ca2+]i transient. Direct activators of the inositol phospholipid-protein kinase-C system in human amnion induce large increases in PGE2 in human amnion cells. Oxytocin and vasopressin are hormonal activators of this system in these cells, as demonstrated by their effects on inositol phosphate turnover and [Ca2+]i. These hormones also increase PGE2 production and may influence labor by stimulating PGE2 production in amnion through the inositol phospholipid-protein kinase-C system.

Adenosine triphosphate activates the phospholipase-C cascade system in human amnion cells without increasing prostaglandin production.

Human amnion is hypothesized to be a target tissue for hormone messages from the fetus regarding labor. We have previously demonstrated prostaglandin E2 (PGE2) release in amnion after treatment with phorbol and oxytocin, but other potential agonists of the inositol phospholipid/protein kinase-C system have not been investigated. The effects of extracellular ATP on cytosolic calcium concentration [( Ca2+])i) inositol phosphate (IP) accumulation, and PGE2 production were studied in cultured human amnion cells. Intracellular free calcium [Ca2+]i was measured using the fluorescent dye fura-2. Addition of 0.01-30 microM ATP resulted in a [Ca2+]i transient which peaked within 15 sec and returned to baseline over 10 min. UTP (1 microM) was more effective than ATP (1 microM); [Ca2+]i levels rose from 233 to 2880 nM (UTP) and 2320 nM (ATP). A reduced effect was observed with other nucleotides in a rank order of agonist potency of ITP greater than CTP greater than ADP greater than GTP greater than TTP. No effect was seen with AMP, cAMP, or adenosine. This is consistent with P2 purinoceptors, as described in other tissues. ATP (100 microM) also dramatically increased IP accumulation. Inositol triphosphate, inositol bisphosphate, and inositol monophosphate were increased 7-, 9-, and 16-fold respectively. The agonist potency order of other nucleotides for IP accumulation was the same as that of [Ca2+]i. Pharmacological concentrations of ATP (1 mM) were required to increase PGE2 production. Many other nucleotides were equally effective at this concentration. ATP activates the phospholipase-C system in human amnion, as demonstrated by the increase in [Ca2+]i and inositol phosphates. The physiological significance of purinergic stimulation of this tissue remains unclear.

Protein kinase-C activation is required for oxytocin-induced prostaglandin production in human amnion cells.

In previous work we reported that oxytocin activates phospholipase-C (PLC) and increases prostaglandin E2 (PGE2) release in amnion. Whether either of the consequences of activation of PLC by oxytocin, activation of protein kinase-C (PKC) or increases in intracellular calcium, directly results in the production of PGE2 is unknown. Phorbol esters (PMA) and epidermal growth factor (EGF) are also known to increase PGE2 release from amnion. In some tissues these agents are capable of activating the PLC postreceptor cascade system. This study was undertaken primarily to explore the mechanism of oxytocin-induced PGE2 production in amnion and secondarily to determine whether common aspects of PGE2 production by oxytocin, PMA, and EGF include activation of PLC or subsequent steps in this cascade followed by new mRNA/protein production. Involvement of PLC was assessed by inositol phosphate (IP1) turnover. IP1 turnover was increased by oxytocin (2.99 +/- 0.31-fold; P less than 0.01), but not by EGF or PMA. PMA inhibited oxytocin-provoked IP1 turnover (P less than 0.05). PKC involvement was initially evaluated with two PKC inhibitors, H7 and staurosporine. Each inhibited PGE2 production by oxytocin as well as that by PMA and EGF in a dose-dependent fashion. With H7, the IC50 for all agents was 5 microM; the IC50 for staurosporine was 2 nM for PMA and oxytocin and 5 nM for EGF. Agonist-induced PGE2 production was also assessed in cells in which PKC activity had been tachyphylaxed with a high concentration of PMA (400 ng/mL for 48 h). In such cells oxytocin and PMA no longer stimulated (P less than 0.001) PGE2 production, but EGF-stimulated PGE2 production was only slightly reduced. PKC involvement is, thus, implicated for oxytocin and PMA. Other enzymes that are inhibited by H7 and staurosporine are implicated in the production of PGE2 caused by EGF. Although tachyphylaxed cells produced no PGE2 with oxytocin, oxytocin increased intracellular calcium to levels higher than those seen in control cells (435 +/- 102 vs. 286 +/- 1.2) Actinomycin-D (P less than 0.001) and cycloheximide (P less than 0.05) inhibited PGE2 production caused by oxytocin, PMA, and EGF. PGE2 production by oxytocin in human amnion cells proceeds by activation of PKC, followed by new protein and mRNA production. Further, in cells without PKC, oxytocin-induced calcium transients do not increase PGE2. The ability of EGF to stimulate PGE2 in cells with no PKC activity also establishes that PKC activation is not a common intracellular step in the induction of PGE2 production by all agents.

Multi-state investigation of the actual disinfection/sterilization of endoscopes in health care facilities.

PURPOSE: The purpose of this investigation was to observe and assess the actual disinfection or sterilization of endoscopes in health care facilities. MATERIALS AND METHODS: A total of 22 hospitals and four ambulatory care centers in three states were studied. Facility protocols were reviewed, interviews conducted with relevant personnel, actual disinfection or sterilization procedures observed, and biologic tests performed to determine and assess disinfection/sterilization procedures. RESULTS: Fundamental errors observed during the course of the investigation included respective failures to time the period of disinfection, to clean all channels, to flush all channels with disinfectant, to fully immerse the endoscope in the disinfectant solution, and to use a disinfectant. At 78% of the facilities, failure to sterilize all biopsy forceps was observed. A total of 23.9% of the bacterial cultures from the internal channels of 71 gastrointestinal endoscopes grew 100,000 colonies or more of bacteria. These cultures were obtained after the completion of all disinfection/sterilization procedures and the device was deemed ready for use in the next patient. CONCLUSIONS: These data indicate that actual disinfection/sterilization procedures for endoscopes are not always optimal, and high-level disinfection of gastrointestinal endoscopes is not always achieved.

The adenylate cyclase system and prostaglandin production in human decidua parietalis.

We studied the beta-adrenergic system in the human decidua and its effect on prostaglandin E2 and F2a release from dispersed decidual cells in culture. Beta-adrenergic receptors in decidual membranes were partially characterized using (+)[125I]HYP. Specific binding was demonstrated with maximum binding capacity (Bmax) of 70 +/- 10.6 fmol/mg and an affinity (KD) of 20.85 +/- 1.86 pmol. cAMP dependent phosphoproteins in decidual cytosol were also identified. Two phosphoproteins of M(r) 42,000 and 22,000 were seen in all preparations. Three others (M(r) 39,000, 23,000 and 21,000) were identified in only some of the preparations. Phosphoproteins of similar M(r) to those seen in cytosol prepared from decidual homogenates were also identified in cytosol of cultured decidual cells. Phosphorylation of the 42,000 M(r) and 22,000 M(r) proteins was maximal (3.04 +/- 0.35-fold and 5.7 +/- 0.68-fold) with 10(-6) M cAMP. Cultured decidual cells produced prostaglandin E2 and F2a which increased in a dose-dependent manner in response to dbcAMP, forskolin or isoproterenol. The decidua contains an intact beta-adrenergic system that, when activated, is capable of phosphorylating specific proteins and modulating prostaglandin release.

Physiological apoptotic agents have different effects upon human amnion epithelial and mesenchymal cells.

Foetal membrane rupture is thought to follow from gene-controlled tissue remodelling and apoptosis. We reported previously that staurosporine, cycloheximide, actinomycin D, as well as more physiological apoptotic agents (lactosylceramide, 15d-PGJ(2)) increase prostaglandin release in parallel with induction of apoptosis in WISH and amnion epithelial cells. Also, inhibition of prostaglandin release by cyclooxygenase inhibitors or PKA activators is accompanied by a parallel decrease in apoptosis. We hypothesize that amnion prostaglandin metabolism is linked with apoptosis in amnion epithelial cells and thus to membrane rupture. Amnion mesenchymal cells are also critical for membrane integrity. Their susceptibility to apoptotic agents is unknown and is the subject of this report. In amnion epithelial cells, lactosylceramide (125 microM) induced 6.5-fold, 20-fold increases in PGE(2) and NMP production (apoptosis), respectively. Conversely, in mesenchymal cells, lactosylceramide doses up to 200 microM had no effect on PGE(2) or NMP release. In both cell types, incubation with 15d-PGJ(2) (5-100 microM) demonstrated dose and time dependent increases in PGE(2) and NMP. PKA activators inhibited 15d-PGJ(2) induced PGE(2) release and apoptotis in epithelial cells, but not in mesenchymal cells, however. Major amnion cell types have different sensitivities to physiological apoptotic agents. Prostaglandin release occurs coincident with apoptosis in both amnion epithelial and mesenchymal cells.

Hydrogen peroxide induced apoptosis in amnion-derived WISH cells is not inhibited by vitamin C.

Increased reactive oxygen species (ROS) have been identified as a potential cause of remodelling and apoptotic change in fetal membrane. Vitamin C has been suggested as a therapeutic agent to prevent ROS induced chorio-amnion apoptosis. The purpose of this study was to determine whether hydrogen peroxide (HP), a ROS, initiates apoptosis in the WISH cell model and whether vitamin C would inhibit HP induced apoptosis. HP induced apoptosis in WISH cells; as assessed by cytochrome-c release from mitochondria, Poly-(ADP-ribose)-Polymerase (PARP) cleavage, nuclear matrix protein (NMP) release and DNA fragmentation analysis. HP induced dose dependent release of cytochrome-c, PARP cleavage, NMP release, and DNA fragmentation. HP also increased PGE(2)release in parallel with apoptosis in WISH cells, in a manner similar to that reported with other apoptotic agents. Vitamin C pre-incubation caused cytochrome-c release earlier, and at lower HP doses, than HP alone. It had no effect on HP induced PARP cleavage, but enhanced DNA fragmentation, and induced NMP release on its own. Vitamin C partially suppressed dose dependent HP induced PGE(2)release. We conclude that HP causes apoptosis in WISH cells and vitamin C pre-incubation does not inhibit, and may accelerate and exacerbate, HP induced apoptosis.

Vitamin C exacerbates hydrogen peroxide induced apoptosis and concomitant PGE2 release in amnion epithelial and mesenchymal cells, and in intact amnion.

This study was undertaken to investigate the effect of hydrogen peroxide (HP), a reactive oxygen species, and vitamin C, an antioxidant, on apoptosis and prostaglandin (PGE(2)) release in human amnion epithelial and mesenchymal cells, and intact amnion. Amnion cells and explants were incubated with and without HP and vitamin C. Cytoproliferation assay for viability, DNA fragmentation and PARP cleavage for apoptosis, EIA for PGE(2), and western blots for cyclooxygenases (COX) were performed. In amnion cells and explants, HP (0-5 mm) induced dose dependent apoptosis as per DNA fragmentation and PARP cleavage. HP (0-0.5 mm) also induced PGE(2)release concomitant with apoptosis in both cell types. In amnion explants, HP (0-10 mm) induced COX-2 protein and PGE(2)release concomitant with apoptosis. Vitamin C (0.01-10 mm), alone, enhanced epithelial but inhibited mesenchymal cell viability. It induced PGE(2)release in amnion explants. Vitamin C (1 mm) failed to inhibit HP induced apoptosis, but instead exacerbated it in epithelial and mesenchymal cells, and amnion explants. Vitamin C (0-10 mm) enhanced HP induced PGE(2)in mesenchymal cells. HP induces concomitant apoptosis and PGE(2)release in amnion epithelial and mesenchymal cells, and in intact amnion explants. HP induced apoptosis is not inhibited but enhanced by vitamin C.

Consent forms--how, or whether, they should be used.

If written consent forms are to be used--their use normally is not mandatory--care should be taken that their use is proper and, hence, beneficial. To be of benefit to the physician, the consent forms must help him in meeting his duty to inform the patient or in protecting him from a patient's claim that his was not an informed consent (or both). Consent forms are of no benefit to the physician or the patient if they are worded poorly or put to poor use. Suggestions are provided to help the physician in considering his or her use of written consent forms.

Occupational hazards to health care workers: diverse, ill-defined, and not fully appreciated.

Health care workers are challenged by an imposing group of occupational hazards. These hazards include exposure to ionizing radiation, stress, injury, infectious agents, and chemicals. The magnitude and diversity of these hazards are not fully appreciated. The acquired immunodeficiency syndrome epidemic has created additional occupational hazards and has focused attention on the problem of occupational hazards to health care workers. Concern over the nosocomial transmission of the human immunodeficiency virus has contributed to efforts to implement universal infection control precautions and to decrease needlestick injuries. Health care organizations and providers, who have prompted health and safety campaigns for the general public, should not overlook the dangers associated with the health care setting.

Glove use by health care workers: results of a tristate investigation.

The Center for Devices and Radiological Health, in collaboration with the state health departments of Iowa, Maryland, and Massachusetts, conducted a multi-state, multi-institutional investigation of glove use by health care workers (HCWs). Twenty-two hospitals and four ambulatory care centers were included in the investigation. All 26 health care facilities were found to have adopted universal precautions policies for glove use by HCWs, per Centers for Disease Control guidelines. Four hundred five observations were made of HCWs performing procedures that may involve contact with patient body fluids, particularly blood. The prevalence of glove use during selected procedures was as follows: arterial blood gas procedures, 92.3%; intravenous line initiation/maintenance, 77.6%; and phlebotomy, 70.6%. Glove use during phlebotomy (p less than 0.001) and intravenous line procedures (p less than 0.05) was significantly lower in the state with a prevalence of the acquired immunodeficiency syndrome (AIDS) below the national average than in the states with a higher AIDS prevalence. The investigation suggests that health care facilities have responded to the Centers for Disease Control and Occupational Safety and Health Administration campaign to adopt universal precaution policies for glove use by HCWs. Actual glove use by HCWs appears to be substantial but not universal. Glove use by HCWs is significantly related to statewide AIDS prevalence.

The role of the veterinarian in hurricanes and other natural disasters.

Hurricanes create a multiplicity of complicated problems and hazards ranging from outbreaks of infectious disease to animal control problems precipitated by destruction of property. A multidisciplinary response is required to solve such problems. The pool of knowledge derived from various professionals interacting with multiple levels of government agencies (federal, state, and local) will provide the expertise needed. Because the veterinarian is trained to deal with disease involving populations of animals (e.g., herds or flocks) as well as individuals, and because of his/her intensive clinical training, the veterinarian is uniquely qualified to deal with the disaster situation. The veterinarian possesses extensive knowledge in disease and disease processes and has the capability of disease and injury management in affected populations, which qualifies him/her for an essential role, with unlimited potential as a member of any disaster relief team. There is considerable potential for veterinarians to play a role in responding to natural disasters. The areas of disease control, animal care, animal control, protection of the food supply, disinfection/sterilization, and planning are all areas where veterinarians can take an active part. Inclusion of the veterinarian in the process of planning for and responding to natural disasters will yield significant public health benefits.

The relationship of birth weight and intrauterine diagnostic ultrasound exposure.

Imaging with ultrasound is common in obstetric practice. Several laboratory animal studies have shown retardation in fetal growth after experimental ultrasound exposure. This investigation was conducted to determine whether human fetuses exposed to diagnostic ultrasound (sonography) have a greater risk of growth retardation than fetuses not so exposed. This retrospective cohort study compares the birth weights of 1598 exposed and 944 unexposed single live births at the Johns Hopkins Hospital in Baltimore, Maryland during calendar year 1981. Confounding variables, defined as those associated with both exposure status and birth weight outcome, were included in multivariable analysis. Both exposure to more than one ultrasound procedure and first exposure during the third trimester were associated with a reduction in birth weight. However, the most consistent effect associated with birth weight appeared to be the indication for an ultrasound examination. The relationship of ultrasound exposure and reduced birth weight appeared to be due to shared common risk factors, which lead to both exposure and a reduction in birth weight.