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Biomedical subjects

C V Smith

Publications and source records attributed to C V Smith.

At least 91 records · Page 5Linked to original sources
PubMed1994

Vibroacoustic stimulation for risk assessment.

VAS of the human fetus produces a profound alteration of fetal behavior and FHR. Many authors have reported on the success of the technique in improving the efficiency of antepartum FHR testing without altering the predictive reliability of the tests. VAS has other potential advantages in the antepartum assessment of fetal well-being and provocation of fetal activity to improve ultrasonographic anatomic visualization. Experimentally, VAS offers a unique opportunity to assess how the fetus responds to its external environment. The information currently available suggests that exposure of the fetus to VAS is safe in its present clinical applications. Additional investigation is needed to characterize the best frequency, duration, intensity, and choice of stimulus to provide the most consistent responses. The literature to date presents a confusing array of studies that have used different methodologies, making comparisons of studies difficult. It is the opinion of the author that VAS is a safe clinical technique as currently employed.

Acoustic Stimulation↗
PubMed1994

Intravaginal prostaglandin E2 for cervical ripening and initiation of labor. Comparison of a multidose gel and single, controlled-release pessary.

A study was conducted to compare the efficacy and safety of two methods of delivering prostaglandin E2 (PGE2) as a low-dose gel delivered in up to two sequential, 2.5-mg doses and as a single-dose, controlled-release, 10-mg pessary. A cervical change was present in both groups, but a Bishop score > or = 8 occurred in more nulliparous patients in the pessary than in the gel group by 12 hours after dosing. Labor was initiated without oxytocin more frequently in the pessary than gel group for nulliparas and multiparas. Reversal of uterine hyperstimulation was possible by removal of the pessary without tocolytic therapy. The controlled-release PGE2 pessary was more effective in changing the cervix in nulliparas and in initiating labor and offered the advantage of removal when desired.

Administration, Intravaginal↗
PubMed1993

Investigation of possible mechanisms of hepatic swelling and necrosis caused by acetaminophen in mice.

Vascular congestion and liver swelling have long been recognized as features of the hepatotoxic effects of acetaminophen (AAP) in mice and rats and have been proposed as contributing factors to the eventual extent of necrosis produced. Neutrophil accumulation in the hepatic microcirculation has been proposed as being responsible for the blockage of hepatic blood flow and thereby the expansion of the region of damage. We therefore determined in mice the effects of hepatotoxic doses of AAP on the messenger RNA for intercellular adhesion molecule-1 (ICAM-1), which is a critical determinant of neutrophil adhesion, activation and ultimately of neutrophil-mediated tissue injury. Hepatotoxic doses of AAP did not upregulate ICAM-1 messenger RNA. However, doses of bacterial lipopolysaccharide (LPS) did cause a rapid and dramatic increase in ICAM-1 message, which was accompanied by a much greater hepatic accumulation of neutrophils, but which led to only scattered single cell necrosis. In addition, we investigated the effects of pentoxifylline (PTX) on AAP-induced vascular congestion and on hepatic necrosis as evaluated histologically and by measurement of plasma transaminase activities. Although PTX has been shown to increase blood cell deformability and improve vascular perfusion in a number of animal models of restricted blood flow, and is used in humans for the treatment of intermittent claudication, we found no decrease in AAP-induced hepatic swelling or in AAP-induced necrosis in response to PTX. With some dosing regimens, PTX-treated animals proved to be slightly more susceptible to AAP, which may be related to the reported potentiation of the cytotoxicities of a number of alkylating anti-cancer drugs by PTX and other methylxanthines. We conclude from these studies that upregulation of ICAM-1 and subsequent adhesion and vascular plugging by neutrophils are not significant determinants of AAP-induced liver swelling and necrosis and that whatever hemorheological advantages PTX might offer in AAP-induced hepatic damage appear to be overshadowed by effects that potentiate the toxic responses.

Acetaminophen↗
PubMed1993

Hyperoxic lung injury in Fischer-344 and Sprague-Dawley rats in vivo.

Supplemental oxygen remains an important therapy for pulmonary insufficiency, despite the potential adverse effects of hyperoxic exposures. Recently, He et al. reported that hyperoxic ventilation more readily damaged isolated perfused lungs from Fischer-344 rats than from Sprague-Dawley rats (Am. J. Physiol. 259:L451), which correlates with the previously reported strain differences in hepatic responses to diquat-induced oxidant stress in vivo (J. Pharmacol. Exp. Ther. 235:172). We therefore examined the differences in hyperoxic lung injury in Fischer-344 and Sprague-Dawley rats in vivo. Adult male rats were exposed to > 95% O2 and were sacrificed after 24, 48, or 60 h. Control animals were maintained in room air. Dramatically greater increases in pleural effusions and bronchoalveolar lavage protein concentrations in response to hyperoxia were observed in the Fischer-344 rats than in the Sprague-Dawley rats (p < .05 at both 48 and 60 h for both measurements). Additionally, the glutathione concentrations in alveolar lining fluid decreased from 800 microM to 115 microM in Fischer-344 rats after 60 h of > 95% O2, but did not change in Sprague-Dawley rats. We conclude that the greater susceptibility of Fischer-344 than of Sprague-Dawley rats to hyperoxic lung injury in vitro reported previously also is observed in vivo and that this strain difference offers unique opportunities to study mechanisms of hyperoxic lung injury.

Animals↗
PubMed1993

Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice.

Lung injury caused by breathing enriched oxygen continues to be a major problem in clinical medicine. Experimentally, hyperoxic lung injury is characterized by pulmonary edema and associated neutrophil accumulation. Although extensively investigated, the mechanisms for neutrophil accumulation and the role of this accumulation in hyperoxic lung injury remain controversial. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that when increased on endothelium by inflammatory cytokines leads to increased adhesion of neutrophils to the inflamed endothelium and transendothelial migration. The purpose of this study was to examine the role of inflammation in hyperoxia-induced lung injury by investigating ICAM-1 expression in the lungs of mice exposed to > 95% oxygen continuously. Lung tissue from mice exposed to > 95% oxygen was analyzed for ICAM-1 mRNA by slot blot analysis and for ICAM-1 protein expression. We also examined lungs from mice exposed to hyperoxia for up to 96 h by light microscopy to correlate pulmonary inflammation with ICAM-1 expression. We found that mRNA for ICAM-1 increased 56% over baseline after 48 h of exposure to hyperoxia, that ICAM-1 protein increased by more than 5-fold over baseline after 96 h of exposure to hyperoxia, and that lung inflammation and injury were not evident until 96 h of exposure. Our data demonstrate that exposure to hyperoxia causes an increase in ICAM-1 gene transcription and/or mRNA stability in mouse lungs, and that this increase is followed by an increase in ICAM-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Oxidant stress responses in premature infants during exposure to hyperoxia.

To assess oxidant stress responses in newborn infants treated with elevated concentrations of oxygen, we measured plasma concentrations of glutathione (GSH) and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk gestational age. All infants recruited into the study were mechanically ventilated and had catheters placed in their umbilical arteries as part of their normal clinical management. Blood samples were obtained on d 1, 3, and 5 and weekly thereafter or until the catheters were removed. We observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher than the 0.1 to 0.3 microM we find in adults. Interestingly, plasma GSSG concentrations were inversely correlated to the inspired oxygen tensions. This effect appeared to arise from the patient selection criteria whereby, of the infants studied, those breathing the lowest partial pressures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of GSH in the premature infants were substantially, indeed often dramatically, lower than we have observed in adult humans (6 to 10 microM). Finally, we found that in patients with both umbilical arterial and umbilical venous catheters arterial GSSG concentrations were consistently higher than venous concentrations; conversely, arterial GSH concentrations were lower than venous concentrations. The elevated GSSG concentrations we observed in these infants indicate marked oxidant stress responses in prematurely born infants, even in those infants exposed only to room air. The positive arteriovenous gradients of GSSG concentrations across the lungs of these infants suggest that at least some of the increased plasma GSSG originates in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1993

Bone marrow transplantation in miniature swine: IV. Development of myeloablative regimens that allow engraftment across major histocompatibility barriers.

Studies of the myeloablative regimens capable of permitting successful BMT across MHC barriers in miniature swine have been performed. To minimize graft-versus-host disease (GVHD), engraftment was studied in the F1-->P combination (i.e., MHC homozygous ["parental"] swine receiving bone marrow from one-haplotype matched MHC heterozygous ["F1"] donors). Animals given total body irradiation (TBI) up to 1100 cGy, 10 cGy/min, in a single dose failed to engraft. Increasing the dose rate led to unacceptable extramedullary toxicity without improving engraftment. Eleven different fractionated TBI regimens were tested in this F1-->parent model. At all of the dose rates tested, a total dose of less than 1000 cGy was insufficient for engraftment, and a total dose of 1400 cGy led to unacceptable toxicity. Between these extremes, a window was defined in which engraftment could be obtained without unacceptable extramedullary toxicity utilizing 2 equally divided fractions of TBI delivered 24 hr apart. The addition of 50 mg/kg cyclophosphamide i.v. to fractionated TBI (1150 cGy total dose [500 + 650]) also permitted engraftment, with decreased incidence of interstitial pneumonitis as compared to fractionated TBI (1300 cGy total dose [650 x 2]). Both of these regimens were also confirmed to permit engraftment between heterozygous donors and recipients sharing a single common haplotype ("F1-->F1"). The regimen of 1300 cGy (650 x 2) also permitted engraftment in completely MHC mismatched BMT, but with subsequent death from GVHD. These studies of the myeloablative regimens permitting engraftment across defined MHC barriers in miniature swine provide a basis for further studies of allogenic BMT and GVHD in this large animal preclinical model.

Animals↗
PubMed1992

Characterization of a polymorphism of CD4 in miniature swine.

A polymorphism of CD4 in miniature swine has been identified by failure of cells from some animals to react with mAb 74-12-4. The phenotypic, molecular genetic, and functional characteristics of these animals have been defined. Cells from heterozygous animals bear approximately 50% the number of 74-12-4-reactive molecules on their surface as do cells from animals homozygous for the wild type. Animals of both phenotypes demonstrate similar flow cytometric profiles for CD8+ T cells. Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4. CD4 allelism is confirmed by Southern blot analysis, revealing RFLP. Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes. Proliferative responses to PHA and alloantigen stimulation by a full haplotype mismatch or a class II mismatch alone are equivalent for animals of both phenotypes. These data suggest that the allelic form of CD4, designated CD4.2 in contrast to the wild-type CD4.1, is capable of performing normally as an accessory molecule in the generation of immune responses. Furthermore, antixenogeneic responses to C57B10.BR were equivalent, suggesting that both CD4 molecular types may be capable of interacting with xenogeneic class II molecules. Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules.

Animals↗
PubMed1992

Prenatal exposure to phenobarbital and quantifiable alterations in the electroencephalogram of adult rat offspring.

OBJECTIVE: Our purpose was to measure central nervous system insult from prenatal phenobarbital by quantified electroencephalographic evaluation of mature rat offspring. STUDY DESIGN: Twenty-four adult female rats were given phenobarbital as 0, 20, 40, or 60 mg/kg/day subcutaneously between 9 and 10 AM for 28 days before breeding and throughout gestation. The electroencephalograms of 90-day-old offspring were sampled over 24 hours and converted to the power spectra. RESULTS: Female offspring exposed prenatally to 20 mg and males exposed prenatally to 40 mg displayed an increase in delta and a decrease in alpha and middle-beta waveform activities. Females exposed prenatally to 40 mg and males exposed prenatally to 60 mg displayed decreases in delta, theta, alpha, and middle-beta activities. CONCLUSIONS: Prenatal phenobarbital exposure produced dose- and sex-dependent changes in the electroencephalogram of mature offspring consistent with a generalized deficit in the neuronal synchronization mechanisms that are critical for normal sleep and learning.

Animals↗
PubMed1992

Characterization of fetal body movement recorded by the Hewlett-Packard M-1350-A fetal monitor.

OBJECTIVE: The purpose of this study was to evaluate the ability of a commercially available monitor, the Hewlett-Packard M-1350-A fetal monitor, to record and discriminate between various fetal body movements. STUDY DESIGN: Twenty-four patients between 29 and 42 weeks' gestation were monitored over a 20 to 30 minute period simultaneously by the Hewlett-Packard instrument and ultrasonography. RESULTS: All 593 single or clustered fetal movements recorded by the monitor were seen ultrasonographically as being extremity movements that were either isolated or combined with trunk motion. Discriminating between these two types of movements was not possible on the basis of the duration of recorded movements. All adequate fetal heart rate accelerations were attributed to combined trunk and extremity movements. Detection of fetal hiccups was less exact, and recording of fetal hand, mouth, breathing, and rapid eye movements was beyond the sensitivity of the monitor. Signal artifacts were attributable to either motion of the maternal abdomen or Doppler transducer and became less of a problem with experience. CONCLUSION: Fetal extremity movements were recorded with accuracy by this new fetal monitor.

Adult↗
PubMed1992

In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine.

Recent data in mice have shown that early administration of recombinant human interleukin-2 (rIL-2) provides significant protection from lethal graft-versus-host disease. Because of the potential clinical importance of these findings, it will be important to assess the effectiveness of this therapy in a large animal preclinical bone marrow transplantation model. We report here our initial studies of the in vitro and in vivo effects of rIL-2 in miniature swine. In vitro 4-day cultures of pig peripheral blood lymphocytes (PBL) in complete medium containing rIL-2 at 1,000 U/ml resulted in optimal proliferation and generation of lymphokine-activated killer (LAK) cells. A pig-mouse hybridoma cell line was found to be highly sensitive as a LAK cell target. Two naive pigs received 20,000 U/kg and 2 pigs received 100,000 U/kg of rIL-2 intravenously twice a day for 4 days. No clinical symptoms were seen during or after administration at the lower dose while both high dose-treated animals showed generalized erythema from days 2 to 4, and one showed mild diarrhea during this period. The disappearance of IL-2 activity from the serum showed two components: (1) an initial fast component with a half-time of approximately 10 min and (2) a slow component with a half-time of approximately 60 min. LAK cell precursors disappeared from the peripheral circulation by 6 min after rIL-2 administration and began to recover by 6 h in the low dose recipients and only after 12 h in the high dose recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Relation of mild idiopathic polyhydramnios to perinatal outcome.

The relation between clinically obvious polyhydramnios and poor perinatal outcome has been described. Much less is known about mild, unexplained polyhydramnios, which usually is initially suggested by sonographic examination late in gestation. The purpose of the present investigation was to relate mild idiopathic polyhydramnios to perinatal outcome. Mild polyhydramnios was defined sonographically as an amniotic fluid index of 24.1-39.9 during fetal biophysical testing. All subjects had singleton gestations not complicated by conditions known to predispose to polyhydramnios. We diagnosed mild polyhydramnios in 97 of 1177 patients (8.2%) undergoing fetal testing at 26-42 gestational weeks. Premature delivery, intrapartum complications, and neonatal depression were no more frequent in the pregnancies complicated by mild, unexplained polyhydramnios than in a comparable control group with normal fluid volume. The mild polyhydramnios group showed a significantly higher incidence of birth weight greater than 4000 g than did the control group (18.6 versus 8.6%; P less than .05). We conclude that mild idiopathic polyhydramnios in late gestation is relatively common. Except for a higher incidence of large for gestational age fetuses, this condition by itself is not associated with an increased risk of adverse perinatal outcomes.

Female↗
PubMed1992

Successful induction of long-term specific tolerance to fully allogeneic renal allografts in miniature swine.

Major histocompatibility complex class II matching is of overwhelming importance for achieving tolerance to kidney transplants (KTX) in miniature swine. When class II antigens are matched, long-term specific tolerance across complete MHC class I antigen barriers can uniformly be induced by a 12-day perioperative course of cyclosporine. This same regimen is ineffective in fully MHC-mismatched combinations. We hypothesized that initial induction of tolerance to kidney donor class II antigens by bone marrow transplantation might allow tolerance to be induced to a subsequent fully allogeneic KTX in combination with CsA therapy. We report here the results of such fully allogeneic KTX performed in 4 recipients of prior single-haplotype class II-mismatched BMT. All animals received KTX from donors class II matched to the BMT donor and received a 12-day course of intravenous CsA (10 mg/kg/day). All four animals have maintained normal serum creatinine values (less than 2.0 mg/dl) for greater than 200 days posttransplant. Specific hyporesponsiveness to both BMT and KTX donor-type MHC antigens was found in mixed lymphocyte culture and cell-mediated lympholysis assays. Compared with third-party grafts, significantly prolonged survival of BMT donor-specific (P = 0.031) and KTX donor-specific (P = 0.031) skin grafts was observed. These results demonstrate that induction of tolerance to class II antigens by BMT allows a short course of CsA to induce specific tolerance to fully allogeneic renal allografts.

Animals↗
PubMed1992

Induction of specific tolerance to class I-disparate renal allografts in miniature swine with cyclosporine.

Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg----dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (greater than 100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 +/- 0.9 days (P less than 0.0001). The specificity of tolerance was assessed both in vivo with subsequent skin grafts and in vitro by mixed lymphocyte response (MLR) and cell-mediated lymphocytotoxicity (CML). Survival of donor-specific skin grafts was prolonged compared with skin grafts bearing third-party class I antigens (19.5 +/- 2.0 versus 11.5 +/- 2.0 days, n = 4, P less than 0.05). Tolerant recipients had markedly diminished or absent anti-donor MLR and CML responses, but maintained normal reactivity to third party. Four of eight CsA-treated recipients showed detectable levels of anti-donor IgM, while none demonstrated the presence of anti-donor IgG, which was found in all rejecting controls.

Animals↗