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B Holm

Publications and source records attributed to B Holm.

At least 37 records · Page 2Linked to original sources
PubMed1998

Interleukin-1alpha, interleukin-6 and interleukin-8 in cervico/vaginal secretion for screening of preterm birth in twin gestation.

BACKGROUND: The purpose was to determine the prognostic value of interleukin (IL) 1-alpha, IL-6 and IL-8 in cervico/vaginal secretion for preterm birth (<37 weeks of gestation) in twin pregnancies. METHODS: The study included screening of 121 women with twin pregnancies with sampling at 24, 26, 28, 30, 32 and 34 weeks of gestation. IL-1alpha, IL-6 and IL-8 was analyzed with ELISA immunoassays. The detection limit was 30 pg/mL for IL-1 and IL-8 and 40 pg/mL for IL-6. Vaginal fluid was smeared and dried for later evaluation of bacterial vaginosis (presence of clue cells). RESULTS: Spontaneous preterm birth occurred in 36 women and 65 women were delivered at term. IL-8 was significantly higher (p=0.03) in samples from women delivered preterm (median 3.72 ng/g mucus, range <0.07-220.00) compared with samples from women delivered at term (median 3.03 ng/g mucus, range <0.08-378.60). At 28 weeks of gestation, IL-8 (cut off 1.75 ng/g mucus) was associated with preterm delivery (relative risk 2.2, CI 95% 1.1-4.5) with a sensitivity, specificity, positive and negative predictive value of 78.8, 45.8, 44.8 and 79.4%, respectively. The levels of IL-1alpha and IL-6 were not significantly associated with preterm birth. Bacterial vaginosis was found in 47/541 (8.7%) samples analyzed. The levels of IL-1alpha and IL-8 were significantly higher in samples positive for bacterial vaginosis than in negative samples (p<0.0001 and p<0.01, respectively). There was no significant association between the level of IL-6 and bacterial vaginosis. CONCLUSIONS: IL-8, but not IL-1alpha and IL-6, was associated with preterm delivery but the relationship was too weak to be of predictive value for preterm birth in twin pregnancies. IL-1alpha and IL-8, but not IL-6, were associated with bacterial vaginosis.

Adult↗
PubMed1997

In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin.

The acquisition of drug-resistant tumour cells is the main problem in the medical treatment of a range of malignant diseases. In recent years, three new classes of anti-cancer agents, each with a novel mechanism of action, have been brought forward to clinical trials. These are the topoisomerase I (topo I) poisons topotecan and irinotecan, which are both camptothecin derivatives, the taxane tubulin stabilizers taxol and taxotere and, finally, the antimetabolite gemcitabin, which is active in solid tumours. The process of optimizing their use in a combination with established agents is very complex, with numerous possible drug and schedule regimens. We describe here how a broad panel of drug-resistant small-cell lung cancer (SCLC) cell lines can be used as a model of tumour heterogeneity to aid in the selection of non-cross-resistant regimens. We have selected low-fold (3-10x) drug-resistant sublines from a classic (NCI-H69) and a variant (OC-NYH) SCLC cell line. The resistant cell lines include two sublines with different phenotypes towards alkylating agents (H69/BCNU and NYH/CIS), two sublines with different phenotypes against topo I poisons (NYH/CAM and NYH/TPT) and three multidrug resistant (MDR) sublines (H69/DAU, NYH/VM, and H69/VP) with combinations of mdr1 and MRP overexpression as well as topoisomerase II (topo II) down-regulation or mutation. Sensitivity to 20 established and new agents was measured in a standardized clonogenic assay. Resistance was highly drug specific. Thus, none of the cell lines was resistant to all drugs. In fact, all resistant cell lines exhibited patterns of collateral sensitivity to various different classes of drugs. The most intriguing pattern was collateral sensitivity to gemcitabin in two cell lines and to ara-C in five drug-resistant cell lines, i.e. in all lines except the lines resistant to topo I poisons. Next, all sensitivity patterns in the nine cell lines were compared by correlation analysis. A high correlation coefficient (CC) for a given pair of compounds indicates a similar pattern in response in the set of cell lines. Such data corroborate the view that there is cross-resistance among the drugs. A numerically low coefficient indicates that the two drugs are acting in different ways, suggesting a lack of cross-resistance between the drugs, and a negative correlation coefficient implies that two drugs exhibit collateral sensitivity. The most negative CCs (%) to the new drug leads were: taxotere-carmustine (BCNU) (-75), taxol-cisplatin (-58), ara-C-taxol (-25), gemcitabin-doxorubicin (-32), camptotecin-VM26 (-41) and topotecan-VP16 (-17). The most negative correlations to the clinically important agent VP-16 were: cisplatin (-70); BCNU (-68); camptothecin (-38); bleomycin (-33), gemcitabin (-32); ara-C (-21); topotecan (-17); melphalan (-3); and to the other main drug in SCLC treatment cisplatin were: doxorubicin (-70); VP-16 (-70); VM-26 (-69); mAMSA (-64); taxotere (-58); taxol (-58). Taxol and taxotere were highly correlated (cross-resistant) to VP-16 (0.76 and 0.81 respectively) and inversely correlated to cisplatin (both -0.58). Similarly, camptothecin and topotecan were correlated to cisplatin but inversely correlated to VP-16 and other topo II poisons. From the sensitivity data, we conclude that collateral sensitivity and lack of cross-resistance favours a cisplatin-taxane or topo I-topo II poison combination, whereas patterns of cross-resistance suggest that epipodophyllotoxin-taxane or topo I poison-cisplatin combinations may be disadvantageous.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Expression and signal transduction of T-cell antigen receptor (TCR)/CD3 complexes on fresh or in vitro expanded T lymphocytes from patients with Hodgkin's and non-Hodgkin's lymphomas.

T-cell responses against soluble antigens, alloantigens and mitogens are frequently diminished in patients with certain types of cancer. In the present study, the authors investigated possible mechanisms for the partial T-cell immunodeficiency in patients with Hodgkin's or non-Hodgkin's lymphomas. It was found that T-cells from lymphoma patients had significantly reduced proliferative responses to EBV-transformed B-cell lines and to anti-TCR/CD3 MoAb; a 30-50% reduction of cells expressing membrane T-cell receptor (TCR) complexes; and a significantly reduced signal transduction function. Long-term in vitro culture conditions were developed to expand T cells in TCR/CD3-dependent or TCR/CD3-independent manners. With such methods, it was found that the decreased T-cell responses in patients with Hodgkin's and non-Hodgkin's lymphomas appeared to be an intrinsic T-cell defect (not at the antigen presenting cell level), and the T-cell responses could be recovered after only a few days in culture. Thus, it is suggested that the T-cell response-defect in Hodgkin or non-Hodgkin lymphoma patients is a reversible phenomenon, dependent on the patient's tumour-bearing environment.

B-Lymphocytes↗
PubMed1997

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. CONCLUSIONS: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Adult↗
PubMed1996

Coexistence of Th1- and Th2-type cytokine profiles in anti-CD2 monoclonal antibody-induced tolerance.

Anti-CD2 monoclonal antibody OX34 has been shown to suppress immunity in rodents in vitro and in vivo. To evaluate the effects of OX34 on vascularized allografts, Lewis (RT1(1)) hearts were transplanted heterotopically into Wistar Furth (RT1(u)) rats. A single 5 mg/kg intraperitoneal dose of OX34 administered at transplantation induced indefinite graft survival (mean survival time >140.3+/-12.3 vs. 12.7+/-0.7 control, P=0.001). The mixed lymphocyte response was partially inhibited at 60 days after transplant, returning to normal at 100 days. Donor-specific tolerance was confirmed by acceptance of second donor (>100 days, n=2) and rejection of third-party (mean survival time: 7.5+/-0.5 days, n=2) hearts. Immunohistochemical staining of allograft tissue from tolerant animals demonstrated abundant CD2+, CD4+, and CD8+ graft-infiltrating cells. To elucidate further the nature of these cells, we compared the expression of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma mRNA in allografted tissue from tolerant, acutely rejecting (AR), isografted, and naive animals using nonisotopic in situ hybridization. A significant increase in IL-2, IL-4, IL-10, and IFN-gamma mRNA was observed in graft-infiltrating cells of both tolerant and AR animals. IL-10 mRNA expression 4 days after transplant was significantly elevated in the OX34-treated compared to AR recipients. These data demonstrate that a single dose of OX34 at engraftment induces tolerance to vascularized allografts. Expression of both T helper 1 and T helper 2 cytokine mRNA profiles (IL-2/IFN-gamma and IL-4/ IL-10, respectively) are up-regulated locally in graft-infiltrating cells of AR and tolerant animal allografts.

Animals↗
PubMed1996

[Deep venous thrombosis in intravenous drug addicts].

Long-lasting intravenous drug abuse causes sclerosis of the superficial venous system. Many drug abusers thus choose to inject into the major veins of the groin or neck. Such practice may, among various other complications, cause deep venous thrombosis. We describe four patients with venous thrombophlebitis localised at the ileo-femoral junction. All patients were intravenous drug abusers, who for many years had injected various drugs into the groin. Two patients suffered a relapse after the treatment was discontinued. One patient had nonfatal pulmonary embolism. All four patients were treated with low-molecular-weight heparin. Three patients were later treated with warfarin, but, owing to bad compliance, this treatment had to be discontinued quite soon in two cases. We conclude that the management of deep venous thrombosis can be difficult in intravenous drug abusers. This is due mainly to poor venous access, the risk of transmitting blood-borne viruses to health personnel, asocial behaviour, and poor compliance. For most patients, we advocate administration of low-molecular-weight heparin for at least three months. Supporting treatment with metadone should be considered in selected cases.

Adult↗
PubMed1996

Mechanisms of tolerance to rat heart allografts using posttransplant TLI. Changes in cytokine expression.

Lewis rats were rendered tolerant to ACI heart allografts using a regimen of posttransplant total lymphoid irradiation (TLI), rabbit antithymocyte or antilymphocyte globulin (RATG or RALG), and a single donor blood transfusion. All three treatment modalities were required to induce tolerance. The mechanism of the maintenance of tolerance was investigated by comparing the secretion of cytokines in the MLR, and the expression of cytokine mRNA in the allografts of tolerant and nontolerant Lewis rats. Although, the 3H-thymidine incorporation and secretion of IL-2 was frequently comparable in the MLR from tolerant and nontolerant rats, the secretion of IFN-gamma was markedly reduced in the tolerant rats. This was reflected in a markedly reduced frequency of cells expressing IFN-gamma mRNA in the allografts of tolerant as compared with nontolerant hosts. The frequency of cells expressing IL-2 and IL-10 mRNA was also reduced, but no significant difference was observed for cells with IL-4 mRNA. Spleen cells from nontolerant rats rapidly rejected ACI allografts in irradiated adoptive hosts, but spleen cells from tolerant rats did not. Evaluation of the cytokine mRNA expression at early and late time points in the allografts of adoptive hosts showed a pattern similar to that of the primary hosts. Thus, the tolerant state was associated with a maintenance or elevation of IL-4 expression and a marked reduction of IFN-gamma expression. Previous reports have shown that TLI alone induced this shift in the early recovery phase after irradiation.

Animals↗
PubMed1996

Cardia allograft unresponsiveness using a posttransplant strategy : characterization of the graft infiltrate.

We evaluated a combined posttransplant strategy using antilymphocyte serum (ALS) at time of engraftment followed by low dose total lymphoid irradiation (TLI) and donor bone marrow cell (BMC) inoculation administered either intrathymically (IT) or intravenously (IV) in the vigorously rejecting strain combination DA into Lew recipients. Allograft survival was significantly prolonged with administration of ALS in combination with TLI and IT (105 +/- 28.6 days) or IV (106.8 +/- 28.6 days) BMC compared to administration of ALS combined with either TLI (17.8 +/- 0.4 days) or BMC (9.0 +/- 0.0 days), or TLI combined with BMC (1 1.5 +/- 0.5 days) (P < 0.000 1, experimental vs control animals). There was no difference in survival between those animals who underwent IT or IV BMC inoculation. Third-party (WF) BMC inoculation did not significantly prolong allograft survival (10.0 +/- 1.0 days). A mild to moderate cellular infiltrate was present in allograft tissue after 100 days. To further characterize these cells, cytokine mRNA expression in allograft tissue (> 100 days posttransplant) was evaluated using nonisotopic in situ hybridization. A similar cytokine profile was demonstrated in allograft tissue compared to naive and isograft tissue, except for a slight increase in IL-2 (P < 0.02, control vs IV BMC; P = NS, other groups). In summary, unresponsiveness was induced in a high-responder strain combination using a combined posttransplant strategy of ALS, TLI, and donor antigen either IT or IV. The cytokine profile of the graft infiltrating cells was similar to that of normal tissue. Unresponsiveness may be the result of functional inactivation of these cells.

Animals↗
PubMed1996

Effects of water and ambient air temperatures on human diving bradycardia.

Upon apnoeic face immersion, humans develop a diving response resembling that found in diving mammals. There have been contradictory reports regarding the influence of water temperature on the magnitude of the resulting bradycardia. This study examined the influence of both water and ambient air temperatures on human diving bradycardia. A group of 23 volunteers performed three series of apnoeic episodes after 60 min exposure to air at temperatures of 10, 20 or 30 degrees C. Oral and skin temperatures were measured during this exposure and during the subsequent test on 5 subjects. At 20 degrees C air temperature oral and skin temperatures were measured on 10 subjects. Heart rate (HR) was recorded for the 23 subjects during apnoea in air and apnoea with the face immersed in water of 10, 20 or 30 degrees C, at each air temperature. We found that both air and water temperatures had significant effects on immersion bradycardia, but in opposite directions. Face immersion in cold water after exposure to a high ambient air temperature induced the most pronounced bradycardia. We further observed that exposure to different ambient air temperatures resulted in different patterns of HR response to water temperature. The range in which the response was positively correlated to water temperature differed at 30 degrees C ambient air from that at 10 and 20 degrees C ambient air. We concluded from these studies that human bradycardia resulting from apnoeic face immersion is inversely proportional to water temperature within a range which is determined by the ambient air temperature. Thus, the interval in which the response to cold stimulation varies with temperature, would appear to be determined by the ambient temperature before stimulation.

Adult↗
PubMed1996

ICRF-187 rescue in etoposide treatment in vivo. A model targeting high-dose topoisomerase II poisons to CNS tumors.

The catalytic cycle of topoisomerase II is the target of some of the most successful antitumor agents used today, e.g. etoposide (VP-16), in the treatment of testicular cancer and small-cell lung cancer. The cell kill mediated by topoisomerase II poisons can be antagonized by distinct drug types. Thus, we have demonstrated etoposide antagonism with the type-II anthracycline aclarubicin, the antimalarial drug chloroquine, and the cardioprotective agent ICRF-187. In other setups, combinations of agonist and antagonists have led to high-dose regimens for counteracting drug resistance. Thus, the exploitation of folinic acid rescue for methotrexate toxicity and the use of mesna to protect against cyclophosphamide toxicity have enabled the use of high-dose methotrexate and cyclophosphamide protocols. Using a similar approach, we have studied possible ways to apply antagonists to topoisomerase II poisons. NDF1-hybrid female mice were treated with the various drugs and drug combinations. Lethality (LD10 and LD50 values) was computed by use of the maximum-likelihood method, and the antitumor effect of the drugs was compared in mice inoculated i.p. with either L1210 cells or Ehrlich ascites tumor cells. In addition, the compounds were tested on L1210 cells inoculated intracranially. The toxicity of the various drugs was evaluated by weight and leukocyte counts. ICRF-187 rescues healthy mice from lethal doses of topoisomerase II poisons. In mice the ICRF-187 LD10 was 500 mg/kg. Within a wide non-toxic dose range (50-250 mg/kg) of ICRF-187 we found protection against m-AMSA and etoposide lethality. Thus, the LD10 of etoposide increased from 34 mg/kg for the single agent to 122 mg/kg for its combination with ICRF-187, corresponding to a 3.6-fold etoposide dose escalation. In contrast, ICRF-187 did not protect against lethal doses of the non-topoisomerase II-directed drug paclitaxel. We further investigated the anti-tumor effect of equitoxic schedules in mice inoculated i.p. with L1210 or Ehrlich ascites tumor cells. The L1210-bearing mice appeared to obtain a larger increase in life span from the etoposide and ICRF-187 combination as compared with etoposide alone, whereas this was not the case in mice inoculated with Ehrlich ascites tumor cells. As the hydrophilic ICRF-187 is not expected to cross the blood-brain barrier, in contrast to the lipophilic etoposide, we investigated the effect of the drug combination in mice inoculated intracranially with L1210 cells. We obtained a significant increase in life span in mice treated with ICRF-187 + etoposide as compared with mice treated with an equitoxic dose of etoposide alone. Thus, there appear to be potential routes by which one can benefit from this antagonism. ICRF-187 is a powerful nontoxic protector against the lethality of the topoisomerase II-directed drugs etoposide and m-AMSA in vivo. A brain tumor model demonstrates the superiority of high-dose etoposide treatment with ICRF-187 protection as compared with etoposide treatment alone. This implies that tumors in the brain can be reached by cytotoxic drug doses and that normal tissues can be protected due to differences in drug transport across the blood-brain barrier. ICRF-187 is therefore a promising lead compound for the development of schedules using high-dose topoisomerase II poisons in the treatment of brain tumors and metastases.

Amsacrine↗
PubMed1996

Tracheal ligation does not correct the surfactant deficiency associated with congenital diaphragmatic hernia.

INTRODUCTION: Experimental tracheal ligation (CDH + TL) has been shown to reverse the profound lung hypoplasia associated with congenital diaphragmatic hernia (CDH) and to normalize gas exchange. The aim of this study was to determine whether this experimental therapy would correct the surfactant deficiency present in the fetal lamb model of CDH. METHODS: The CDH lamb model was created at 80 days' gestation, and tracheal ligation was performed at 110 days. At term, the lambs were delivered and were ventilated for 30 minutes. The lambs were killed, a pressure-volume curve performed, and the lungs lavaged to measure total phospholipid content. Finally, type II pneumocytes were isolated, and surfactant synthesis was assessed by the incorporation of tritiated choline into phosphatidylcholine. RESULTS: CDH + TL resulted in a lung significantly larger than that of CDH alone. The lungs of the former also had better oxygenation and ventilation. However, lung compliance was reduced compared with controls. Total alveolar phospholipid was dramatically lower, with a decrease in the proportion of phosphatidylcholine present. Surfactant synthesis by the isolated type II pneumocyte was significantly impaired. CONCLUSION: Occlusion of the fetal trachea produces a lung comparable in size to a normal control lung. However, broncheoalveolar lavage analysis shows a marked reduction in total phospholipid, with a decrease in surfactant synthesis by the type II pneumocyte. The normalization of gas exchange reported for this animal model may be only a transient phenomenon. Further studies are required to assess the impact of this surfactant deficiency on long-term lung function.

Animals↗
PubMed1995

Tolerance induced by direct inoculation of donor antigen into the thymus in low and high responder rodents.

A novel approach to tolerance induction in rats was recently described where donor antigen is inoculated directly into the thymus along with a brief period of immunosuppression in a pretransplant strategy. To develop a strategy that has more clinical appeal, we evaluated the timing of donor antigen inoculation in relation to allografting, the use of frozen bone marrow as the antigen, and the dose response of purified T cells as the antigen in a low responder heterotopic heart allograft combination. Additionally, the success of this pretransplant strategy in different low and high responder strain combinations was defined. In tolerant low responder animals we evaluated in vitro and in vivo cellular immunity. Tolerant host strain naive CD8+ T cell responses to donor and third party stimulators were compared to determine if tolerance is related to the strength of the response of the T cell subsets to donor antigen. Frozen bone marrow can induce tolerance in a low responder combination. Additionally, the dose of purified T cells necessary for tolerance induction was 5 x 10(5) cells. The pretransplant strategy was successful in two low responder strain combinations, Lewis into Wistar Furth and Lewis into DA, but unsuccessful in all high responder strain combinations evaluated. Low responder animals unresponsive to donor heart allografts demonstrate intact cell-mediated immunity and donor-specific tolerance in vivo by rejecting third party but not second donor strain hearts. The in vitro responses of tolerant animals demonstrated donor-specific suppression of the MHC class II response but an intact (normal) response to third party stimulators by proliferation assays and IFN-gamma production, suggesting suppression at the CD4+ T cell subset level.

Animals↗
PubMed1995

A comparison of spontaneous versus induced tolerance in an experimental model of rat hepatic allograft transplantation.

In some rodent haplotype combinations, spontaneous tolerance (ST) develops after orthotopic liver transplantation (OLT) without any immunosuppression [e.g., Lewis (Lew, RT1) into Wistar Furth (WF, RT1u)] whereas in other combinations vigorous, progressive rejection rapidly leads to the death of the recipients. We (and others) have induced tolerance (IT) in a rejecting strain combination [Dark Agouti (DA, RT1a) into Lew] by intrathymic inoculation of donor bone marrow cells and 1 cc of antilymphocyte serum (ALS) 7-14 days prior to OLT. We hypothesized that cellular immunity in the two groups of animals was similar. We first compared survival in each group of animals and found that there was no difference in the number of animals surviving > 100 days (8/11 vs 16/17, ST vs IT, respectively, P = 0.11). Liver function studies were similar in these animals at 2 and 4 weeks after OLT and comparable to syngeneic Lew into Lew OLT animals, but significantly lower than in the rejecting DA into Lew combination treated with only ALS. Animals that were unresponsive to their allografts demonstrated donor-specific tolerance by the acceptance of donor strain (n = 4, ST and IT) and rejection of third party (n = 1 and n = 2, ST and IT groups, respectively) heterotopic heart allografts. One-way mixed lymphocyte cultures (MLC) of peripheral blood lymphocytes against donor and third party antigen were suppressed to donor and third party stimulators versus the MLC of unmanipulated animals. Naive host strain responder lymph node cells and purified T cells demonstrated strong proliferative responses to donor strain antigen in both the ST and IT animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.

OBJECTIVE: To determine the efficacy of partial liquid ventilation (PLV) by means of a medical-grade perfluorochemical liquid, perflubron (LiquiVent), in premature lambs with respiratory distress syndrome (RDS). Further, to determine the compatibility of perflubron with exogenous surfactant both in vitro and in vivo during PLV. DESIGN: Prospective, randomized, controlled study, with in vitro open comparison. SUBJECTS: Twenty-two premature lambs with RDS. INTERVENTIONS: In vitro assays were conducted on three exogenous surfactants before and after combination with perflubron. We studied four groups of lambs, which received one of the following treatment strategies: conventional mechanical ventilation (CMV); surfactant (Exosurf) plus CMV; PLV; or surfactant plus PLV. MEASUREMENTS AND MAIN RESULTS: In vitro surface tension, measured for three exogenous surfactants, was unchanged in each animal after exposure to perflubron. Lung mechanics and arterial blood gases were serially measured. All animals treated with PLV survived the 5 hours of experiment without complication; several animals treated with CMV died. During CMV, all animals had marked hypoxemia and hypercapnia. During PLV, arterial oxygen tension increased sixfold to sevenfold within minutes of initiation, and this increase was sustained; arterial carbon dioxide tension decreased to within the normal range. Compliance increased fourfold to fivefold during PLV compared with CMV. Tidal volumes were increased during PLV, with lower mean airway pressure. Resistance was similar for both CMV and PLV; there was no difference with surfactant treatment. CONCLUSIONS: We conclude that PLV with perflubron improves lung mechanics and gas exchange in premature lambs with RDS, that PLV is compatible with exogenous surfactant therapy, and that, as a treatment for RDS in this model, PLV is superior to the surfactant studied.

Animals↗