Major obstetric haemorrhage of 2000 ml or greater: a clinical audit.

Haemorrhage remains a leading cause of maternal death. We conducted an audit to identify strategies to improve the management at our local NHS Trust. A data collection form was based on our local guideline. A coded database search was conducted for all deliveries where the estimated blood loss was ≥2000 ml (from June 1 2015 to December 31 2015), returning 68 search results (13.7/1000 births). Fifty-six records were included. Poor compliance (<75%) was seen in some key areas including the major obstetric haemorrhage (MOH) call activation (52%), the presence of an anaesthetic consultant (63%) and tranexamic acid administration (46%). Thirty out of 56 cases (54%) were acutely transfused. Women, who were not transfused acutely, appeared to be more likely to need a secondary transfusion if no MOH call had been activated (9/27 (33%) versus 3/29 (10%), p = .052). A key area for improvement was the activation of MOH calls. Following this audit, we adjusted our guideline to make it more clinically useful and staff training sessions were held, including simulation training. Impact statement What is already known on this subject? A postpartum haemorrhage (PPH) is an obstetric emergency. A structured approach is important to optimise the care of the mothers during this dangerous time, and has been shown to reduce the transfusion requirements. However, clinical practice may not adhere to the guideline recommendations. What the results of this study add? With the objective evidence of increased rates of PPH ≥2000 ml at our institution, our work identifying the flaws in management was a critical component of the work to improve the outcomes. This study gives impetus to find innovative ways to improve adherence to guidelines, and inspired an update of our local guideline to improve the applicability and utility. This project suggests a new marker for the adequacy of an acute management (a requirement for secondary blood transfusion without having received an acute transfusion), and raises questions about what constitutes optimum PPH management. What the implications are of these findings for clinical practice and/or further research? The primary and secondary transfusion data raised new questions to investigate in the future: does the involvement of consultants and the escalation of care via the instigation of major haemorrhage protocols improve decision-making and patient outcomes? Does the necessity for a secondary transfusion indicate a suboptimal acute care?

Complex traits analysis of chicken growth using targeted genetical genomics.

Dissecting the genetic control of complex trait variation remains very challenging, despite many advances in technology. The aim of this study was to use a major growth quantitative trait locus (QTL) in chickens mapped to chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a variant of the genetical genomics approach to investigate genome-wide gene expression differences between two contrasting genotypes of a marked QTL. This targeted approach allows the direct quantification of the link between the genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics studies. Four differentially expressed genes were localized under the region of the QTL. One of these genes is a potential positional candidate gene (AADAT) that affects lysine and tryptophan metabolism and has alternative splicing variants between the two genotypes. In addition, the lysine and glycolysis metabolism pathways were significantly enriched for differentially expressed genes across the genome. The targeted approach provided a complementary route to fine mapping of QTL by characterizing the local and the global downstream effects of the QTL and thus generating further hypotheses about the action of that QTL.

Changes in plasma gonadotrophins, 17ß-oestradiol, progesterone, prolactin, thyroxine and triiodothyronine concentrations in female Japanese quail (Coturnix coturnix japonica) of a heavy body weight line during photo-induced ovarian growth and regression.

1. Simultaneous changes of the width of the cloacal opening and plasma luteinising hormone (LH), follicle stimulating hormone (FSH), 17ß-oestradiol, progesterone, prolactin, thyroxine (T(4)) and triiodothyronine (T(3)) during photo-induced ovarian growth and regression were measured in commercially bred Japanese quail from a heavy body weight line. 2. Somatically mature female Japanese quail were transferred from short days (light:dark 8L:16D) at 10°C to long days (16L:8D) at 20°C, and sexually mature female Japanese quail were transferred from long to short days. All variables were measured at transfer and every five days thereafter (except for a measurement at 12 instead of 10 d) for 35 d. 3. Transfer from short to long days caused significant increases in LH, FSH, 17ß-oestradiol, ovary weights and oviduct weights after five days, and in the cloacal opening after 12 d. T(3) decreased after five days, whereas no significant changes were observed in T(4) concentrations. Progesterone and prolactin both decreased after 25 long days. 4. The transfer of quail from long to short days caused significant decreases in LH, FSH, 17ß-oestradiol, progesterone, prolactin, ovary and oviduct weights after 12 d and an increase in T(3). There was no significant change in T(4) concentrations. The cloacal opening decreased after 25 short days. 5. These results are the first to show simultaneous changes in gonadotrophins, sex steroids, thyroid hormones and prolactin during photo-induced gonadal growth and regression in female Japanese quail.

The fallacy of the two-minute acid phosphatase cut off.

Research was carried out to determine whether the likelihood of obtaining a positive Acid Phosphatase (AP) test result is affected by the make and type of paper used. Also, we aimed to investigate the frequency of AP positive reactions occurring after 2min using a series of known semen dilutions and to determine whether spermatozoa transfer onto the paper during the act of AP screening. In this research, most brands of paper tested were able to detect a 1 in 40 semen dilution within 2min. Leaving AP test papers for longer will allow the detection of greater dilutions of semen and as the amount of ejaculation is not reliably known in most casework situations and levels of AP activity can vary in different men, this will increase the seminal detection rate in sexual offence allegations.

Changes in plasma gonadotrophins, testosterone, prolactin, thyroxine and triiodothyronine concentrations in male Japanese quail (Coturnix coturnix japonica) of a heavy body weight line during photo-induced testicular growth and regression.

1. Simultaneous changes of cloacal gland area (CGA) and plasma luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone (T), prolactin (PRL), thyroxine (T(4)) and triiodothyronine (T(3)) during photo-induced testicular growth and regression were measured in commercially bred Japanese quail from a heavy body weight line. 2. Somatically mature male Japanese quail were transferred from short days (light:dark 8L:16D) at 10°C, to long days (16L:8D) at 20°C; and sexually mature male Japanese quail were transferred from long to short days. All variables were measured at transfer and every 5 d thereafter for 35 d. 3. Transfer from short to long days caused significant increases in LH, FSH, T and testis weight (TW) after 5 d, and in CGA after 10 d. T(3) decreased after 5 d, whereas T(4) increased significantly after 25 long days and PRL did not undergo any consistent change. The testicular growth rate was k = 0·1146. 4. Transferring quail from long to short days caused significant decreases in LH and FSH after 5 d, and decreases in T, TW and CGA after 10 d. T(4) decreased after 5 d whilst T(3) increased significantly by day 15. PRL decreased significantly after 10 d then rose before declining again. The testicular regression rate was k = 0·0582. 5. The rates of photo-induced testicular development and regression in a strain of large Japanese quail did not differ from rates reported for other strains of quail. CGA was a better indicator of TW than plasma T concentrations during growth and regression. The role of PRL in photo-induced reproductive cycles in male Japanese quail remains to be determined. 6. The photoperiod-induced changes in gonad size and hormone concentrations, together provide valuable information that can be used in future studies of the endocrinology and neuroendocrinology of photoperiodism in birds.

Interstellar cloud material: contribution to planetary atmospheres.

A statistical analysis of the properties of dense interstellar clouds indicates that the solar system has encountered at least a dozen clouds of sufficient density to cause planets to accumulate nonnegligible amounts of some isotopes. The effect is most pronounced for neon. This mechanism could be responsible for much of the neon in Earth's atmosphere. For Mars, the predicted amount of neon added by cloud encounters greatly exceeds the present abundance.

New hypotheses on the function of the avian shell gland derived from microarray analysis comparing tissue from juvenile and sexually mature hens.

Activation of the shell gland region of the avian oviduct is mediated by ovarian steroids. To understand more extensively how shell glands are maintained and function, we have compared gene expression in the shell glands from juvenile and laying hens using a chicken cDNA microarray. Average expression profiles of juvenile and sexually mature shell glands were compared resulting in the identification of 266 differentially regulated genes. Reverse transcription quantitative polymerase chain reaction confirmed expression differences. The differentially expressed genes included several with known involvement in shell gland function, including ion transport and shell matrix proteins. There were also many unpredicted differentially expressed genes, and for some we propose hypotheses for their functions. These include those encoding (a) osteoprotegerin, a decoy death receptor for receptor activator of nuclear factor NFkB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), that in the shell gland, may prevent apoptosis and/or may have an endocrine effect by preventing RANKL's action on bone osteoclasts that mobilize stored calcium; (b) prostatic acid phosphatase (ACPP) and prostate stem cell antigen (PSCA) that could play a role in sperm physiology within the shell gland; (c) urea transporter (SLC14A2) that could provide a novel anti-microbial defence; (d) bactericidal/permeability-increasing protein-like 2 (BPIL2), and other potential anti-microbials that have not previously been documented in the chicken. These new hypotheses, if borne out experimentally, will lead to a greater understanding of shell gland function including the processes involved in eggshell formation and anti-microbial activity.

Colorectal tubulovillous adenomas identified on fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography scans.

OBJECTIVE: The aim of this retrospective study was to assess the significance of incidental focal colonic lesions on fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) scans in patients undergoing staging for noncolorectal cancer. METHOD: Of the 110 patients in our PET/CT database, 10 were found to have abnormally high uptake of tracer in their large bowel. RESULTS: Seven patients who underwent further endoscopic evaluation of these abnormalities had intermediate to high-risk adenomatous polyps. CONCLUSION: Benign colonic polyps produce high-intensity focal FDG uptake in large bowel. Endoscopic evaluation is recommended before curative resectional surgery of the presenting cancer where appropriate.

Timely closure of loop ileostomy following anterior resection for rectal cancer.

The implications of constructing a temporary ileostomy as part of the primary surgery for some rectal cancers must not be underestimated and many patients are particularly keen to have their stoma closed as early as possible. Currently, there are no set protocols in place which determine when this should take place, meaning that stoma reversal can be extremely variable between hospitals in the UK. We have created a policy to give patients a provisional date for ileostomy closure at discharge from primary surgery, which takes into account any necessary adjuvant treatment. We compared time to closure of ileostomy between two adjacent centres that share common stoma-care and oncology teams to see what benefit this policy provides. Patients were recruited over a 2-year period from 2005 to 2007 from two adjacent centres. Centre 1 had a policy to provide patients with a provisional date for closure of their ileostomy. The notes were studied retrospectively to determine time to closure of the ileostomy and reasons for any delays in closure. A total of 107 patients fulfilled the inclusion criteria, of which 83 patients (72%) had their stomas closed. Thirty patients had their stomas closed within 12 weeks (37%) - more than 67% (23/34) in centre 1 against 15% (7/48) in centre 2. At 1 year, all patients in centre 1 had their ileostomy closed, while 10% (5/48) were still waiting in centre 2. The mean time to closure was 13.47 and 25.25 weeks for centres 1 and 2 respectively -P-value < 0.0001. Offering patients a date for ileostomy closure at discharge from their primary resection results in the majority of stomas being closed within 12 weeks. For those patients who are to undergo adjuvant chemotherapy, we aim to perform this surgery in between the second and third cycles of treatment.

A description of the origins, design and performance of the TRAITS-SGP Atlantic salmon Salmo salar L. cDNA microarray.

The origins, design, fabrication and performance of an Atlantic salmon microarray are described. The microarray comprises 16 950 Atlantic salmon-derived cDNA features, printed in duplicate and mostly sourced from pre-existing expressed sequence tag (EST) collections [SALGENE and salmon genome project (SGP)] but also supplemented with cDNAs from suppression subtractive hybridization libraries and candidate genes involved in immune response, protein catabolism, lipid metabolism and the parr-smolt transformation. A preliminary analysis of a dietary lipid experiment identified a number of genes known to be involved in lipid metabolism. Significant fold change differences (as low as 1.2x) were apparent from the microarray analysis and were confirmed by quantitative real-time polymerase chain reaction analysis. The study also highlighted the potential for obtaining artefactual expression patterns as a result of cross-hybridization of similar transcripts. Examination of the robustness and sensitivity of the experimental design employed demonstrated the greater importance of biological replication over technical (dye flip) replication for identification of a limited number of key genes in the studied system. The TRAITS (TRanscriptome Analysis of Important Traits of Salmon)-salmon genome project microarray has been proven, in a number of studies, to be a powerful tool for the study of key traits of Atlantic salmon biology. It is now available for use by researchers in the wider scientific community.

Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray.

Interferons (IFNs) are cytokines that have proinflammatory, antiviral, and immunomodulatory effects and play a central role during a host response to pathogens. The IFN family contains both type I and type II molecules. While there are a number of type I IFNs, there is only one type II IFN. Recently both type I and type II IFN genes have been cloned in salmonid fish and recombinant proteins produced showing IFN activity. We have stimulated an Atlantic salmon cell line (SHK-1) with both type I and type II recombinant salmonid IFNs and analyzed the transcriptional response by microarray analysis. Cells were exposed to recombinant IFNs for 6 or 24 h or left unexposed as controls. RNA was hybridized to an Atlantic salmon cDNA microarray (salmon 17K feature TRAITS/SGP array) in order to assess differential gene expression in response to IFN exposure. For IFN I and II, 47 and 72 genes were stimulated, respectively; most genes were stimulated by a single IFN type, but some were affected by both IFNs, indicating coregulation of the IFN response in fish. Real-time PCR analysis was employed to confirm the microarray results for selected differentially expressed genes in both a cell line and primary leukocyte cultures.

Comparison of portal and peripheral blood levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens in patients with colorectal and pancreatic cancer.

Synchronous serum specimens from the systemic and portal circulations of 43 patients with gastrointestinal cancer were assayed for levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens. The number of patients having a mean ratio of portal to systemic levels greater than 1 and the observed quantity of tumor-associated antigens were significant for carcinoembryonic antigen and CA 125 only in patients with colorectal cancer. No correlations were noted with the surgical stage of disease or with high or low (normal) levels of the three tumor-associated antigens. These findings suggest that peripheral concentrations of these antigens are in equilibrium with shedding from tumors and that hepatic clearance of a single pass does not significantly alter peripheral concentrations.

Pituitary prolactin messenger ribonucleic acid levels in incubating and laying hens: effects of manipulating plasma levels of vasoactive intestinal polypeptide.

Pituitary PRL messenger RNA levels in hens, measured by dot-blot hybridization, correlated directly with concentrations of plasma PRL, being 3-fold higher in incubating than in laying birds. Nest deprivation of incubating hens for 24 h caused a rapid decrease in both plasma PRL and pituitary PRL mRNA, which remained depressed thereafter. A single injection of vasoactive intestinal polypeptide (VIP) in laying hens resulted in an increase (P less than 0.05) in pituitary PRL mRNA whereas passive immunoneutralization of VIP in incubating hens resulted in a decrease (P less than 0.001) in pituitary PRL mRNA. The rapid decrease in pituitary PRL mRNA after nest deprivation or passive immunoneutralization of VIP was associated with a significant increase in pituitary PRL content, presumably a consequence of the decreased PRL secretion. In situ hybridization showed PRL mRNA to be localized in the cephalic lobe of the anterior pituitary gland in which most PRL cells, identified immunocytochemically, were found. Northern blotting studies showed that the pituitary gland contains a single 860 base(s) mature PRL mRNA transcript irrespective of physiological state or VIP manipulation. Both in situ and Northern hybridization studies confirmed that the amount of pituitary PRL mRNA was related directly to the concentration of plasma PRL. These observations are consistent with the view that in incubating hens hypothalamic VIP, in addition to acting as a PRL releasing hormone, also plays a major role in the regulation of the amount of PRL mRNA in the anterior pituitary gland.

Sites of gene expression for vasoactive intestinal polypeptide throughout the brain of the chick (Gallus domesticus).

The peptide neurotransmitter vasoactive intestinal polypeptide (VIP) has several important functions in vertebrates, particularly, influencing the neuroendocrine and autonomic nervous systems both in developing and in adult animals. To document potential brain areas that might play significant functional roles, the distribution of VIP mRNA was examined throughout the entire chick brain by using in situ hybridization histochemistry (ISHH). In addition, a VIP binding-site study was completed that focused on the lateral septal organ (LSO), a circumventricular organ of potential significance in avian species. The areas where VIP message was found included the olfactory bulbs, posterior hippocampus, parahippocampal area, hyperstriatum, archistriatum/nucleus (n.) taenia (amygdala), medial part of the LSO, organum vasculosum of the lamina terminalis, medial preoptic region, bed n. of the pallial commissure, anterior hypothalamic (hypo.) n., lateral hypo. area (most extensive and dense message), periventricular hypo. n., lateral to the paraventricular n., ventromedial hypo. n., stratum cellulare externum, inferior hypo. n., infundibular hypo. n., median eminence, three layers within the stratum griseum et fibrosum superficiale, area ventralis of Tsai, n. tegmenti pedunculopontinus pars compacta (substantia nigra), intercollicular n., central gray, locus ceruleus, parabrachial n., ventrolateral medulla, reticular pontine area, in and about the n. vestibularis descendens. When compared with immunocytochemistry that detected the presence of the peptide product VIP, more areas of the brain were found to contain perikarya expressing VIP by using ISHH, particularly in the telencephalon and the mesencephalon. VIP binding sites were found in the lateral portion of the LSO where the blood-brain barrier is not fully developed. Hence, the LSO was found to contain neural elements that synthesize as well as bind VIP. VIP appears to be a useful peptide for defining major components of the visceral forebrain system in birds.

Expression of biologically active recombinant-derived chicken prolactin in Escherichia coli.

The putative chicken prolactin (chPRL) cDNA clone PRL101 was manipulated in vitro and cloned into the Escherichia coli expression vector pKK2332 to produce a plasmid coding for recombinant-derived mature chPRL (R-chPRL). Expression of this manipulated cDNA sequence in E. coli resulted in the production of a 23 kDa protein which cross-reacted with specific chPRL antisera in Western blots. The partially purified protein stimulated ring dove crop sac mucosa to proliferate in a PRL bioassay, demonstrating that the R-chPRL was biologically active. R-chPRL was expressed at a level of approximately 1.5% of total cell protein.

Evidence for alternative splicing of the chicken vasoactive intestinal polypeptide gene transcript.

Two forms of chicken vasoactive intestinal polypeptide (VIP) mRNA have been identified by reverse transcription (RT)-PCR and RNase protection assay. The shorter form of chicken VIP mRNA encodes a protein that does not contain an analogue of rat peptide histidine isoleucine (PHI) 1-27 or human peptide histidine methionine 1-27. The larger form encodes both VIP and a chicken analogue of PHI 1-27 in the same protein product. Three VIP cDNAs isolated from a chicken hypothalamic cDNA library were derived from the shorter mRNA. Sequence analysis of the longest clone identified an open reading frame that codes for a 165 amino acid preproVIP protein and contains two polyadenylation signals. In situ hybridisation with an oligonucleotide probe from the VIP cDNA sequence showed that VIP-encoding mRNA occurs in cells in the basal hypothalamus, an area of the brain known to contain VIP neurosecretory neurones. RT-PCR of total RNA from liver, kidney, gut, pancreas, pituitary, cerebellum, forebrain and hypothalamus, using primers derived from the VIP cDNA sequence, showed that the shorter form of VIP mRNA is present in all of these tissues. The sequence of the longer form of VIP mRNA was obtained by sequencing a portion of the VIP gene from genomic DNA. This revealed a potential exon that was not represented in the VIP cDNA clones analysed. RT-PCR with primers from this sequence showed that it was expressed in the gut and hypothalamus. RNase protection assays confirmed the presence of the two forms of mRNA in gut and hypothalamus. The relative proportions of the two mRNA forms were: 97.8% VIP only, 2.2% PHI/VIP in the hypothalamus and 98.5% VIP only, 1.5% PHI/VIP in the gut. In conclusion, chicken VIP mRNA is alternatively spliced. The shortest form, which encodes a preproprotein containing only the VIP peptide, is the most abundant. The longer form of chicken VIP mRNA encodes a preproprotein containing sequences for both VIP and a chicken form of PHI.

Sex differences in the LH responses to chicken LHRH-I and -II in the domestic fowl.

Maximal incremental changes in plasma LH were compared in adult hens and cockerels after i.v. injection of chicken (c) LHRH-I (pGlu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Gln8-Pro9-Gly10-N H2) or cLHRH-II (pGlu1-His2-Trp3-Ser4-His5-Gly6-Trp7-Tyr8-Pro9-G ly10-NH2). The LH response to cLHRH-I and -II was more rapid and greater in cockerels than in hens. The potencies of the two decapeptides were the same in cockerels but different in hens. Relative to cLHRH-I, the potency of cLHRH-II was 0.91 (0.6-1.2; 95% confidence limits) in cockerels and 36.5 (16.8-128.6) in hens. The greater potency of cLHRH-II relative to cLHRH-I in the hen than in the cockerel could not be accounted for by sex differences in the half-lives of the decapeptides in the peripheral circulation. The half-lives of both decapeptides in hens and cockerels ranged between 2.42 and 3.77 min. It is concluded that the interaction between LHRH-I and -II and the gonadotrophs is sexually differentiated in the domestic fowl. A new homologous radioimmunoassay was established for cLH. As in other chicken LH radioimmunoassays, there was evidence of cross-reactivity with TSH.

The role of hypothalamic vasoactive intestinal polypeptide in the maintenance of prolactin secretion in incubating bantam hens: observations using passive immunization, radioimmunoassay and immunohistochemistry.

The role of chicken vasoactive intestinal polypeptide (cVIP) as a prolactin-releasing factor was investigated in incubating bantam hens. Specific antibodies were raised against cVIP (anti-cVIP) for passive immunization studies, to develop a radioimmunoassay and to localize VIP neurones immunohistochemically in the hypothalamus. The concentration of plasma prolactin decreased after i.v. injection of anti-cVIP: this low concentration being maintained by daily injection of anti-cVIP. Incubating hens injected daily with anti-cVIP deserted their nests after 4.5 +/- 0.6 days and returned to lay after 20 +/- 1 days. This disruption of incubation behaviour with anti-cVIP was prevented by concomitant, twice daily, injections of 30 IU ovine prolactin. The concentration of plasma LH was not immediately affected after injection of anti-cVIP but increased when the hens deserted their nests. The amount of cVIP, measured by radioimmunoassay, was significantly higher in the median eminence (P less than 0.01) and medial basal hypothalamus (P = 0.05) in incubating than in laying hens. No differences were seen in the amounts of cVIP in the preoptic hypothalamus or in a part of the forebrain including the nucleus accumbens, between laying and incubating hens. Morphological observations were made on immunohistochemically identified cVIP cell bodies in the medial basal hypothalamus. These showed that cVIP cell number, cell area and density of immunoreactive product were significantly (P less than 0.05) greater in incubating than in laying hens. Further, the density of cVIP reaction product in the anterior median eminence was also significantly (P less than 0.01) greater in incubating than in laying hens.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological roles of chicken LHRH-I and -II in the control of gonadotrophin release in the domestic chicken.

The physiological roles of chicken LHRH-I and -II (cLHRH-I and -II) in the regulation of gonadotrophin release were investigated in the domestic chicken. Measurements of the neuropeptides, using specific radioimmunoassays, in brain sections cut in three planes or in grossly dissected brain areas, showed that cLHRH-II occurs in low amounts throughout the brain whereas cLHRH-I is most abundant in the diencephalon. Within the diencephalon, the largest amount of cLHRH-I occurred in the median eminence of the hypothalamus. The amount of cLHRH-I in the median eminence was higher (P less than 0.05) in laying than in out-of-lay hens. No cLHRH-II was detected in the median eminence in either reproductive state. The amount of cLHRH-I in the hypothalamus was increased (P less than 0.05) in cockerels at the onset of puberty and in somatically immature birds after castration. There were no correlated changes in the amounts of hypothalamic cLHRH-II measured in the same experimental samples. Active immunization of laying hens against cLHRH-I but not against cLHRH-II resulted in the complete regression of the reproductive system and a depression in the concentration of plasma LH. These observations, taken together, suggest that gonadotrophin secretion in the hen is more likely to be directly regulated by cLHRH-I than by cLHRH-II.

Effects of inhaled alpha-emitting actinides on mouse alveolar macrophages.

The effects of inhaled alpha-emitting actinides on the alveolar macrophage (AM) population of the rodent lung are reviewed and, in particular, of the effects of 239PuO2 on murine AM. The effects discussed include changes the AM pool size, macrophage diameter, mobility, phagocytic competence, and enzyme content. Finally, similarities in the dose-response relationships for the induction of nuclear aberrations by alpha emitters and in the induction of lung tumors by the same materials are noted.