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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 55 records · Page 3Linked to original sources

Emergence of further serotypes of multiple drug-resistant Streptococcus pneumoniae in Queensland.

We describe 27 cases of multiple drug-resistant pneumococcal infection in Queensland children (7 cases) and adults (20 cases), between February 1995 and October 1996. Seven patients had invasive disease. Serotypes were those commonly associated with paediatric infections and included types 19F (15 strains), 14 (6), 23F (4), 6A (1) and 19A (1). No rifampicin or vancomycin resistance was encountered. However, pneumococci fully resistant to cotrimoxazole, erythromycin and tetracycline were isolated from 25 of 27 cases (93%). Strains with high level resistance to penicillin and chloramphenicol were also recovered from 16 (59%) and 19 (70%) patients respectively. Twelve of 16 penicillin-resistant isolates showed intermediate resistance to ceftriaxone and two strains were fully resistant to this antibiotic. Clones of types 19F and 14 pneumococci, each with two distinctive resistance patterns, appear to be established in south-east Queensland.

Adult↗

Persistence in muscle of an adenoviral vector that lacks all viral genes.

Genetic correction of inherited muscle diseases, such as Duchenne muscular dystrophy, will require long term expression of the recombinant protein following gene transfer. We have shown previously that a new adenoviral vector that lacks all viral genes expressed both full-length dystrophin and beta-galactosidase in mdx (dystrophin-deficient) mouse muscle. We observed a significant histologic improvement of vector-transduced mdx muscle before the eventual loss of vector-encoded transgene expression. In this study, we investigated whether an immunological response against vector-encoded beta-galactosidase contributed to the loss of vector expression and affected vector persistence in muscle. Intramuscular vector injection in control normal mice resulted in an early and complete loss of beta-galactosidase expression accompanied by predominantly CD4+ and CD8+ lymphocytic infiltration and a significant loss of vector DNA. In contrast, intramuscular vector injection in lacZ transgenic mice resulted in persistent expression of beta-galactosidase for at least 84 days with no evidence of inflammation or significant loss of vector DNA. Our studies demonstrate that, in the absence of an immune response induced by beta-galactosidase expression, an adenoviral vector lacking all viral genes is stably maintained in muscle.

Adenoviridae↗

Limitations of nls beta-galactosidase as a marker for studying myogenic lineage or the efficacy of myoblast transfer.

BACKGROUND: Nuclear localizing beta-galactosidase (nls beta-gal) is used as a marker for studying myoblast cell lineage and for evaluating myoblast survival after myoblast transfer, a procedure with potential use for gene complementation for muscular dystrophy. Usefulness of this construct depends on the establishment of the extent to which nls beta-gal or its mRNA may be translocated from the nucleus that encodes it to other non-coding myonuclei in hybrid myofibers and the ease with which the encoding and non-coding myonuclei can be distinguished. Previous in vitro studies (Ralston and Hall 1989. Science, 244:1066-1068) have suggested limited translocation of the fusion protein. We re-examined the extent to which nls beta-gal is translocated in hybrid myofibers, both in vitro and in vivo, and evaluated the extent to which one can rely on histochemistry to distinguish encoding from non-coding nuclei in these myofibers. METHODS: Myotubes formed in co-cultures of a myoblast line (MM14 cells), stably transfected with a construct consisting of a nls beta-gal under the control of the myosin light chain 3F promoter and 3' enhancer (3FlacZ10 cells), and [3H]-thymidine-labeled parental MM14 cells (plated at ratios of 1:6 or 1:20, respectively) were reacted with X-gal. After autoradiography, the distance over which nls beta-gal was translocated in hybrid myotubes was determined. In vivo translocation of nls beta-gal was evaluated by injecting [3H]-thymidine-labeled 3FlacZ10 myoblasts into the regenerating extensor digitorum longus muscle of immunosuppressed normal and mdx (dystrophin deficient) mice. Sections stained with X-gal and subjected to autoradiography permitted determination of the extent of nls beta-gal translocation in hybrid myofibers. RESULTS: In vitro: All nuclei in > 92% of hybrid myotubes showed evidence of nls beta-gal after exposure to X-gal, suggesting extensive translocation. Within hybrid myotubes, MM14-derived myonuclei approximately 350 microns from a 3FlacZ10-derived myonucleus showed evidence of nls beta-gal. In vivo: Similar translocation of nls beta-gal was observed in vivo. One week after myoblast transfer, donor-derived myonuclei were distinguishable from host-derived myonuclei containing nls beta-gal by the greater accumulation of reaction product in donor myonuclei after X-gal staining. However, 2 weeks after injection, host myonuclei often contained a significant amount of nls beta-gal, and accumulation of reaction product could not be used as the criterion for identification of donor myonuclei. CONCLUSIONS: Translocation of nls beta-gal (or its mRNA) is significantly greater than previously reported (Ralston and Hall 1989), resulting in large numbers of nls beta-gal positive non-coding myonuclei in hybrid myofibers. One week after myoblast transfer, distinguishing between nls beta-gal encoding and non-coding myonuclei in hybrid myofibers after X-gal staining of sectioned muscle is feasible; however, by 2 weeks, nls beta-gal increases in host myonuclei, making identification of donor-derived myonuclei problematic. Translocation of nls beta-gal to non-coding myonuclei in hybrid myofibers must be considered when nls beta-gal is used for studies of myogenic lineage or the efficacy of myoblast transfer therapy, particularly if long-term survival of hybrid myotubes is required.

Animals↗

Fibre type-specific and nerve-dependent regulation of myosin light chain 1 slow promoter in regenerating muscle.

The regulation of a slow muscle gene, the myosin light chain 1 slow/ventricular gene, has been studied by in vivo transfection into regenerating rat skeletal muscle. Constructs containing portions of the myosin light chain 1 slow/ventricular promoter linked to reporter genes were injected into fast and slow muscles 3 days after muscle injury by bupivacaine injection, and reporter gene activity was analysed after 10 days. We report that a sequence in the 5' flanking region of the myosin light chain 1 slow/ventricular gene is able to direct slow muscle-specific regulation of reporter genes, and that the expression of the transgene, like that of the corresponding endogenous gene, is dependent on intact nerve. This study validates the use of regenerating muscle as a model for studying muscle gene regulation and is the first demonstration of a myosin gene promoter regulated by nerve activity.

Animals↗

Adolescents, sexual behaviour and HIV-1 in rural Rakai district, Uganda.

OBJECTIVES: To describe the epidemiology of HIV-1 infection among adolescents aged 13-19 years, in rural Rakai district, Uganda. STUDY DESIGN: Baseline survey and 2-year follow-up (1990-1992) of adolescents in a population-based, open rural cohort. METHODS: Annual enumeration and behavioral/serological survey of all consenting adolescents aged 13-19 years at recruitment, residing in 31 randomly selected community clusters. RESULTS: At baseline, of 909 adolescents present in study clusters, 824 (90.6%) provided interview data and serological samples. No adolescents aged 13-14 years were HIV-infected. Among those aged 15-19 years, 1.8% of men and 19.0% of women were HIV-positive. Among young women aged 15-19 years in marital/consensual union, 21.3% were HIV-positive; this rate did not differ significantly from the 29.1% prevalence in those reporting non-permanent relationships; prevalence was significantly lower in women reporting no current relationship (4.3%). After multivariate adjustment, female sex, age 17-19 years, residence in trading centers/trading villages and a history of sexually transmitted disease symptoms remained significantly associated with HIV infection. Seventy-nine per cent of adolescents provided a follow-up serological sample. No young men aged 13-14 years seroconverted during the study; in young women aged 13-14 years, HIV seroincidence was 0.6 per 100 person-years (PY) of observation. Among young men aged 15-19 years, there were 1.1 +/- 0.6 seroconversions per 100 PY of observation prior to age 21 years; among women 15-19 years, the incidence rate was 3.9 +/- 1.0 per 100 PY of observation prior to age 21 years. The mortality rate among HIV-positive adolescents aged 15-19 years, at 3.9 per 100 PY of observation, was 13-fold higher than that among the HIV-uninfected. By 1992, knowledge of sexual transmission was almost universal, the proportions reporting multiple partners had decreased and condom use had increased over baseline. CONCLUSIONS: Adolescents, and young women in particular, are vulnerable to HIV infection. Despite reported behavioral changes, HIV incidence rates remain substantial, and there is a need for innovative HIV preventive measures.

Adolescent↗

Localization of beta-D-galactosidase activity in semithin epon sections of embryonic tissues using differential interference contrast optics.

In the present study we describe a method for the histochemical demonstration of beta-D-galactosidase activity on tissue sections processed for light microscopy at high resolution. 5-Bromo-indolyl-beta-D-galactopyranoside (Bluo-Gal) was utilized as an indigogenic method for the demonstration of Escherichia coli beta-D-galactosidase reporter gene activity whose expression was studied in a transgenic line where the enzyme, with a nuclear localization signal (nlacZ), is under the transcriptional control of a striated muscle-specific promoter. At the light-microscopic level, by using Differential Interference Contrast (DIC) optics, the reaction product was detected as precipitates in the form of fine birefringent crystals. These were located around and inside the nuclei of beta-gal-expressing cells. This simple method allows an easy and rapid identification of few or even one labeled cell(s) within large microscopic fields (whole embryos) and the labeled cell(s) can be evaluated both morphologically and quantitatively.

Animals↗

Absence of MEF2 binding to the A/T-rich element in the muscle creatine kinase (MCK) enhancer correlates with lack of early expression of the MCK gene in embryonic mammalian muscle.

During skeletal muscle development, different types of muscle fibers are generated, which express different combinations of muscle-specific gene products. For example, the muscle creatine kinase gene (MCK) is highly expressed in fetal but not embryonic myotubes. We performed transient transfections of CAT reporter constructs, driven by the MCK promoter with variable lengths of 5'-flanking sequence, into primary cultures of embryonic and fetal muscle cells. Reporter activity was observed in fetal but not embryonic muscle cells. We assayed the ability of nuclear extracts prepared from embryonic and fetal muscle and C2C12 myotubes to bind specific regulatory elements in the MCK enhancer. The profile of DNA/protein complexes resulting from electrophoretic mobility shift assays was qualitatively the same with all extracts used when the oligonucleotide probes represented the MCK-E-box, MHox site, CArG-box, and AP2 site. In contrast, no binding activity to the MEF2 site was observed with embryonic nuclear extract. Interestingly, MEF2 mRNAs and proteins were detected in both fetal and embryonic muscle, with the exception of the MEF2D1b isoform, which is restricted to fetal muscle. Furthermore, we found that protein phosphatase inhibitors included in the preparation of embryonic nuclear extracts or added to the medium of transfected embryonic myotubes can restore MEF2 DNA binding activity, as well as reporter activity driven by the MCK promoter and partial transcriptional activation of the endogenous MCK gene. We propose that phosphorylation of MEF2 regulates its activity and represents an important aspect of the mechanism controlling stage-specific transcription during skeletal myogenesis.

Alkaline Phosphatase↗

Pectin and methyl cellulose do not affect intestinal function in patients after ileal pouch-anal anastomosis.

OBJECTIVES: Although ileal pouch-anal anastomosis is the procedure of choice for most patients with ulcerative colitis or familial adenomatous polyposis, most patients have problems with stool frequency and/or consistency. Although most clinicians recommend fiber supplementation for these patients, we could find no studies that prove the efficacy of this practice. The first purpose of this study was to document the effect of fiber supplementation on intestinal function in patients after ileal pouch-anal anastomosis. Because pectin, a soluble fiber supplement, has been reported to slow gastric and intestinal transit, we also hypothesized that pectin would be a superior fiber supplement in these patients. The second purpose, therefore, was to determine whether the effects of pectin on intestinal transit would result in decreased stool frequency in patients with an ileal pouch. METHODS: Thirteen patients who had undergone ileal pouch-anal anastomosis for ulcerative colitis were entered into a 9-wk crossover study. The protocol consisted of three 2-wk study periods, each of which was preceded by a 1-wk washout period. During the three study periods patients supplemented their diets, in random order, with Citrucel, 1 tablespoon twice daily; pectin, 1 tablespoon twice daily; or no supplement. Patients maintained detailed dietary and bowel function diaries. RESULTS: The effects (mean +/- SE) of Citrucel and pectin supplementation are summarized in Table 1. There was no significant effect of either supplement on stool frequency, pouch function, bloating, or stool consistency. In addition, there were no differences in continence. CONCLUSIONS: We found no evidence to support the common practice of fiber supplementation in patients with an ileal pouch. Furthermore, this study did not find that stool frequency decreased during supplementation with pectin. We conclude that there is little role for fiber supplementation in patients with an ileal pouch.

Adult↗

Infection and transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) in Aedes aegypti (Diptera: Culicidae): effect of preinfection sugar meals and postinfection blood meals.

Frequency of sugar feeding and blood feeding can have an impact on the infection by and transmission of malaria parasites. Data presented here indicate that frequent blood feeding has a deleterious effect on infection by malaria parasites in Aedes aegypti. In addition, mosquitoes that do not blood feed, but instead feed on sugar alone after an infected blood meal, have a higher rate of parasite transmission than mosquitoes fed additional blood meals.

Aedes↗

Isolation and sequence analysis of the cDNA encoding delta 1-pyrroline-5-carboxylate reductase from Zalerion arboricola.

A cDNA encoding delta 1-pyrroline-5-carboxylate reductase (P5CR) was isolated from the pneumocandin (Pmo)-producing fungus, Zalerion arboricola (Za), by complementation of a P5CR-deficient mutant (pro3) of Saccharomyces cerevisiae (Sc). The cloned cDNA was placed under control of the Sc galactokinase (GAL1) promoter and restored P5CR activity to the pro3 mutant. Sequence analysis revealed that the Za P5CR-encoding cDNA encodes an approx. 35 kDa protein with substantial amino acid (aa) identity to P5CR from another filamentous fungus, Neurospora crassa (Nc). Za P5CR exhibits a moderate degree of aa identity to P5CR from plants, bacteria, human and Sc. This is the first gene to be isolated from Za.

Amino Acid Sequence↗

Differential release of prostaglandins by organ cultures of human fetal trachea and lung.

Human fetal lung at 16-19 weeks gestation has a partially differentiated epithelium, and in organ culture, distal airsacs dilate and the epithelium autodifferentiates to type I and II pneumatocytes, processes regulated by endogenous prostaglandin PGE2. Human fetal trachea, at the same gestation, has a terminally differentiated mucociliary epithelium but after 4-6 d in organ culture, develops squamous metaplasia. Tracheal cultures restricted to 3 d have normal phase-contrast and light microscopy appearances and immunohistochemical reactivities (epithelium: cytokeratin 7,8,18; glutathione S-transferase pi-isozyme; epithelial membrane antigen and mesenchyme; desmin; vimentin). In human fetal trachea organ cultures, the predominant prostaglandins released are 6-keto-PGF1 alpha, PGF2 alpha, and PGE2, a pattern similar to that previously described for human adult trachea and lung. In fetal lung cultures, 13,14-dihydro-15-keto-PGF2 alpha is the major prostaglandin released with lesser amounts of 13,14-dihydro-15-keto-PFG2 alpha,PGF2 alpha,PGE2, and 6-keto-PGF1 alpha. Human fetal lung in vitro has the competence to self-differentiate, as early as 12 weeks gestation and presence of high levels in fetal lung of the inactive metabolite 13,14-dihydro-15-keto-PGE2 relative to PGE2 suggests that active prostaglandin catabolism may be one of the mechanisms to retard this stage of maturation in vivo by limiting PGE2 availability. Surprisingly, the profile of prostaglandins released from fetal lung organ culture does not change to that of a mature lung with terminal differentiation of the epithelium, and this may indicate differences in the expression of key prostaglandin-metabolizing enzymes in developing human fetal lung in culture and with in utero ontogeny.

Animals↗

Differing patterns of mechanical response to direct fetal hormone treatment.

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Airway Resistance↗

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

Angioplasty, Balloon, Coronary↗

Inhaled nitric oxide in cardiac failure: vascular versus ventricular effects.

Inhaled nitric oxide (INO) is a powerful and selective pulmonary vasodilator in pulmonary hypertension, including that related to cardiac disease. Recently, NO was shown to have a direct negative inotropic action on the myocardium, but whether INO can impair left ventricular (LV) function is not known. We administered INO during right heart catheterisation in 10 subjects with LV failure and secondary pulmonary hypertension. INO was delivered for 10 min at concentrations of 10, 20, and 40 ppm in spontaneous respiration. Average age was 49.9 years (range 19-59 years), and mean LV ejection fraction EF (LVEF) was 19.9% (range 15-27%). INO produced an average decrease in pulmonary vascular resistance (PVR) of 40% as compared with baseline (p < 0.0001) with no significant change in systemic vascular resistance (SVR). There was no significant difference in the haemodynamic response to the three doses of INO. The large decrease in PVR was due mainly to an increase in pulmonary capillary wedge pressure (PCWP). Cardiac index (CI) rose in 7 patients and was unchanged in 2. One patient had a marked increase in PAWP and a marked decrease in CI during administration of INO, which rapidly reversed after discontinuation of INO. This study demonstrates that the administration of INO to patients with impaired cardiac reserve may result in marked increase in ventricular preload with little benefit to pulmonary pressures. In view of the known in vitro effects of NO and the marked haemodynamic changes demonstrated in response to INO in this study, caution should be exercised when using INO in this population.

Administration, Inhalation↗

An animal model for human melanoma.

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

Animals↗

Isolation of a gene involved in 1,3-beta-glucan synthesis in Aspergillus nidulans and purification of the corresponding protein.

Saccharomyces cerevisiae has two highly homologous genes, FKS1 and FKS2, which encode interchangeable putative catalytic subunits of 1,3-beta-glucan synthase (GS), an enzyme that synthesizes an essential polymer of the fungal cell wall. To determine if GS in Aspergillus species is similar, an FKS homolog, fksA, was cloned from Aspergillus nidulans by cross-hybridization, and the corresponding protein was purified. Sequence analysis revealed a 5,716-nucleotide coding region interrupted by two 56-bp introns. The fksA gene encodes a predicted peptide of 229 kDa, FksAp, that shows a remarkable degree of conservation in size, charge, amino acid identity, and predicted membrane topology with the S. cerevisiae FKS proteins (Fksps). FksAp exhibits 64 and 65% identity to Fks1p and Fks2p, respectively, and 79% similarity. Hydropathy analysis of FksAp suggests an integral membrane protein with 16 transmembrane helices that coincide with the transmembrane helices of the Saccharomyces Fksps. The sizes of the nontransmembrane domains are strikingly similar to those of Fks1p. The region of FksAp most homologous to the Saccharomyces FKS polypeptides is a large hydrophilic domain of 578 amino acids that is predicted to be cytoplasmic. This domain is 86% identical to the corresponding region of Fks1p and is a good candidate for the location of the catalytic site. Antibodies raised against a peptide derived from the FksAp sequence recognize a protein of approximately 200 kDa in crude membranes and detergent-solubilized active extracts. This protein is enriched approximately 300-fold in GS purified by product entrapment. Purified anti-FksAp immunoglobulin G immunodepletes nearly all of the GS activity in crude or purified extracts when Staphylococcus aureus cells are used to precipitate the antibodies, although it does not inhibit enzymatic activity when added to extracts. The purified GS is inhibited by echinocandins with a sensitivity equal to that displayed by whole cells. Thus, the product of fksA is important for the activity of highly purified preparations of GS, either as the catalytic subunit itself or as an associated copurifying subunit that mediates susceptibility of enzymatic activity to echinocandin inhibition.

Amino Acid Sequence↗

Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs.

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.

Adrenal Cortex Hormones↗