Short-chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs. OBJECTIVE: The objective of this study was to determine whether short-chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43. METHODS: We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA. RESULTS: Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t-PA expression from two- to tenfolds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43. CONCLUSIONS AND CLINICAL RELEVANCE: Short-chain fatty acids were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.

Chronic airway inflammation provides a unique environment for B cell activation and antibody production.

BACKGROUND: B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways. OBJECTIVE: We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation. METHODS: We analysed B cells from NP or tonsil, or after ILC2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody-secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT-PCR. RESULTS: NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein-Barr virus-induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with tonsil. Antibody production and the frequency of antibody-secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC-mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell-targeted therapies may provide new treatment options for CRSwNP.

Live birth sex ratios and father's geographic origins in Jerusalem, 1964-1976.

OBJECTIVE: To examine whether ancestry influenced sex ratios of offspring in a birth cohort before parental antenatal sex selection influenced offspring sex. METHODS: We measured the sex ratio as the percent of males according to countries of birth of paternal and maternal grandfathers in 91,459 live births from 1964 to 1976 in the Jerusalem Perinatal Study. Confidence limits (CI) were computed based on an expected sex ratio of 1.05, which is 51.4% male. RESULTS: Of all live births recorded, 51.4% were male. Relative to Jewish ancestry (51.4% males), significantly more males (1,761) were born to Muslim ancestry (54.5, 95% CI = 52.1-56.8, P = 0.01). Among the former, sex ratios were not significantly associated with paternal or maternal age, education, or offspring's birth order. Consistent with a preference for male offspring, the sex ratio decreased despite increasing numbers of births over the 13-year period. Sex ratios were not affected by maternal or paternal origins in North Africa or Europe. However, the offspring whose paternal grandfathers were born in Western Asia included fewer males than expected (50.7, 50.1-51.3, P = 0.02), whether the father was born abroad (50.7) or in Israel (50.8). This was observed for descendents of paternal grandfathers born in Lebanon (47.6), Turkey (49.9), Yemen & Aden (50.2), Iraq (50.5), Afghanistan (50.5), Syria (50.6), and Cyprus (50.7); but not for those from India (51.5) or Iran (51.9). The West Asian group showed the strongest decline in sex ratios with increasing paternal family size. CONCLUSIONS: A decreased sex ratio associated with ancestry in Western Asia is consistent with reduced ability to bear sons by a subset of Jewish men in the Jerusalem cohort. Lower sex ratios may be because of pregnancy stress, which may be higher in this subgroup. Alternatively, a degrading Y chromosome haplogroup or other genetic or epigenetic differences on male germ lines could affect birth ratios, such as differential exposure to an environmental agent, dietary differences, or stress. Differential stopping behaviors that favor additional pregnancies following the birth of a daughter might exacerbate these lower sex ratios.

Elevated presence of myeloid dendritic cells in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the mechanism underlying the onset and amplification of this inflammation has not been fully elucidated. Dendritic cells (DCs) are major antigen-presenting cells, central inducers of adaptive immunity and critical regulators of many inflammatory diseases. However, the presence of DCs in CRS, especially in nasal polyps (NPs), has not been extensively studied. OBJECTIVE: The objective of this study was to characterize DC subsets in CRS. METHODS: We used real-time PCR to assess the expression of mRNA for markers of myeloid DCs (mDCs; CD1c), plasmacytoid DCs (pDCs; CD303) and Langerhans cells (LCs; CD1a, CD207) in uncinate tissue (UT) from controls and patients with CRS as well as in NP. We assayed the presence of DCs by immunohistochemistry and flow cytometry. RESULTS: Compared to UT from control subjects (n = 15) and patients with CRS without NP (CRSsNP) (n = 16) and CRSwNP (n = 17), mRNAs for CD1a and CD1c were significantly elevated in NPs (n = 29). In contrast, CD207 mRNA was not elevated in NPs. Immunohistochemistry showed that CD1c(+) cells but not CD303(+) cells were significantly elevated in NPs compared to control subjects or patients with CRSsNP. Flow cytometric analysis showed that CD1a(+) cells in NPs might be a subset of mDC1s and that CD45(+) CD19(-) CD1c(+) CD11c(+) CD141(-) CD303(-) HLA-DR(+) mDC1s and CD45(+) CD19(-) CD11c(+) CD1c(-) CD141(high) HLA-DR(+) mDC2s were significantly elevated in NPs compared to UT from controls and CRSsNP, but CD45(+) CD11c(-) CD303(+) HLA-DR(+) pDCs were only elevated in NPs compared to control UT. CONCLUSION AND CLINICAL RELEVANCE: Myeloid DCs are elevated in CRSwNP, especially in NPs. Myeloid DCs thus may indirectly contribute to the inflammation observed in CRSwNP.

Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the palate lung and nasal epithelium clone (PLUNC) family in patients with CRS. METHODS: Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot, and immunohistochemical analysis. RESULTS: Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or patients with CRS. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of patients with CRS compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in the expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin. CONCLUSIONS: Decreased SPLUNC1 and LPLUNC2 in NPs reflect a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules.

Assessing wave energy effects on biodiversity: the wave hub experience.

Marine renewable energy installations harnessing energy from wind, wave and tidal resources are likely to become a large part of the future energy mix worldwide. The potential to gather energy from waves has recently seen increasing interest, with pilot developments in several nations. Although technology to harness wave energy lags behind that of wind and tidal generation, it has the potential to contribute significantly to energy production. As wave energy technology matures and becomes more widespread, it is likely to result in further transformation of our coastal seas. Such changes are accompanied by uncertainty regarding their impacts on biodiversity. To date, impacts have not been assessed, as wave energy converters have yet to be fully developed. Therefore, there is a pressing need to build a framework of understanding regarding the potential impacts of these technologies, underpinned by methodologies that are transferable and scalable across sites to facilitate formal meta-analysis. We first review the potential positive and negative effects of wave energy generation, and then, with specific reference to our work at the Wave Hub (a wave energy test site in southwest England, UK), we set out the methodological approaches needed to assess possible effects of wave energy on biodiversity. We highlight the need for national and international research clusters to accelerate the implementation of wave energy, within a coherent understanding of potential effects-both positive and negative.

Mussel farming as a nutrient reduction measure in the Baltic Sea: consideration of nutrient biogeochemical cycles.

Nutrient loads from the land to the sea must be reduced to combat coastal eutrophication. It has been suggested that further mitigation efforts are needed in the brackish Baltic Sea to decrease nutrients, especially in eutrophic coastal areas. Mussel farming is a potential measure to remove nutrients directly from the sea. Mussels consume phytoplankton containing nitrogen (N) and phosphorus (P); when the mussels are harvested these nutrients are removed from the aquatic system. However, sedimentation of organic material in faeces and pseudo-faeces below a mussel farm consumes oxygen and can lead to hypoxic or even anoxic sediments causing an increased sediment release of ammonium and phosphate. Moreover, N losses from denitrification can be reduced due to low oxygen and reduced numbers of bioturbating organisms. To reveal if mussel farming is a cost-effective mitigation measure in the Baltic Sea the potential for enhanced sediment nutrient release must be assessed.

Assessment and management of patients with chronic cough by Certified Respiratory Educators: a randomized controlled trial.

BACKGROUND: The value of other health care professionals is increasingly being recognized to compensate for the shortage of physicians in Canada. Chronic cough is one of the most common reasons for consultation with a respirologist. In the present study, a prospective, randomized, controlled study was undertaken to determine whether Certified Respiratory Educators (CREs) could manage screened patients with chronic cough as effectively as respirologists. METHODS: An eight-week, prospective, parallel-design, randomized, controlled trial of the management of chronic cough patients was conducted. Patients were screened to exclude those with potentially life-threatening conditions. The primary outcome was the number of patients whose cough resolved or subjectively improved. RESULTS: A total of 198 patients were randomly assigned, and eight-week data were available on 151 patients. Mean age of the patients was 49.8+/-13.4 years, 70.2% were female and median cough duration was 16 months. The screening process was effective and referral wait times decreased from a median of two months to less than four weeks (P<0.0001). The educators averaged 4.9 contacts per patient compared with 2.7 by the physicians over the eight-week study period (P<0.0001). Most patients had had multiple therapeutic trials before referral. Cough resolved or improved in two-thirds of the patients at eight weeks; however, more patients showed improvement in the educator arm than in the physician arm, P<0.02. Cough-specific quality of life improved similarly in the two study arms at eight weeks (physician arm: 61.5+/-14.1 to 52.6+/-14.4, P<0.0001; CRE arm: 58.1+/-14.9 to 50.0+/-15.8, P=0.0003). CONCLUSIONS: CREs can safely and effectively assess, as well as appropriately treat, screened patients with chronic cough with a resultant reduction in wait times.

Climate-driven ecosystem succession in the Sahara: the past 6000 years.

Desiccation of the Sahara since the middle Holocene has eradicated all but a few natural archives recording its transition from a "green Sahara" to the present hyperarid desert. Our continuous 6000-year paleoenvironmental reconstruction from northern Chad shows progressive drying of the regional terrestrial ecosystem in response to weakening insolation forcing of the African monsoon and abrupt hydrological change in the local aquatic ecosystem controlled by site-specific thresholds. Strong reductions in tropical trees and then Sahelian grassland cover allowed large-scale dust mobilization from 4300 calendar years before the present (cal yr B.P.). Today's desert ecosystem and regional wind regime were established around 2700 cal yr B.P. This gradual rather than abrupt termination of the African Humid Period in the eastern Sahara suggests a relatively weak biogeophysical feedback on climate.

MEAD: an interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat.

This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions.

Treatment of olfactory dysfunction, II: studies with minocycline.

OBJECTIVES/HYPOTHESIS: The treatment of anosmia has changed minimally since the early 1970s, despite dramatic advances in the understanding of the molecular biology of olfaction. Recent studies from the authors' laboratory have suggested that most common causes of clinical olfactory dysfunction, including rhinosinusitis, appear to be associated with increased apoptotic death of olfactory sensory neurons. This appears to result in a decline in the number of functioning mature olfactory sensory neurons, despite the capacity of the olfactory epithelium for regeneration. The current study evaluated the ability of the antibiotic minocycline to inhibit olfactory sensory neuron apoptosis. This drug is known to inhibit apoptosis separate from its anti-infective properties. Olfactory sensory neuron apoptosis was triggered by surgical deafferentation ("bulbectomy"), the standard experimental model. Earlier studies have indicated that bulbectomy and sinusitis invoke similar proteolytic enzyme cascades in olfactory sensory neurons. STUDY DESIGN: Histological analysis of animal olfactory tissue. METHODS: Mice underwent unilateral olfactory bulbectomy to induce apoptotic olfactory sensory neuron death, with and without 45 mg/kg intraperitoneal minocycline given 12 hours before surgery and every 12 hours until death. Mice were killed at 2 and 4 days after bulbectomy and assessed for activation of capsase-3 and olfactory sensory neuron survival by immunohistochemical analysis. RESULTS: Minocycline resulted in partial suppression of cell death at 2 days after surgery when compared with untreated animals. CONCLUSION: Minocycline inhibits olfactory sensory neuron death in the face of a potent pro-apoptotic stimulus. This drug is well tolerated and is currently undergoing human trials for the management of a variety of neurological disorders associated with apoptosis. The current results suggest that minocycline may be efficacious in the management of peripheral olfactory loss as well.

Pathology of the olfactory epithelium: smoking and ethanol exposure.

OBJECTIVE: To investigate the effects of tobacco smoke on the olfactory epithelium. Cigarette smoking has been associated with hyposmia; however, the pathophysiology is poorly understood. The sense of smell is mediated by olfactory sensory neurons (OSNs) exposed to the nasal airway, rendering them vulnerable to environmental injury and death. As a consequence, a baseline level of apoptotic OSN death has been demonstrated even in the absence of obvious disease. Dead OSNs are replaced by the mitosis and maturation of progenitors to maintain sufficient numbers of neurons into adult life. Disruption of this balance has been suggested as a common cause for clinical smell loss. This current study will evaluate the effects of tobacco smoke on the olfactory mucosa, with emphasis on changes in the degree of OSN apoptosis. STUDY DESIGN: A rat model was used to assess the olfactory epithelium after exposure to tobacco smoke. METHODS: Rats were exposed to tobacco smoke alone (for 12 weeks), smoke plus dietary ethanol (for the final 5 weeks), or to neither (control). Immunohistochemical analysis of the olfactory epithelium was performed using an antibody to the active form of caspase-3. Positive staining for this form of the caspase-3 enzyme indicates a cell undergoing apoptotic proteolysis. RESULTS: Control rats demonstrated a low baseline level of caspase-3 activity in the olfactory epithelium. In contrast, tobacco smoke exposure triggered a dramatic increase in the degree of OSN apoptosis that affected all stages of the neuronal lineage. CONCLUSIONS: These results support the following hypothesis: smell loss in smokers is triggered by increased OSN death, which eventually overwhelms the regenerative capacity of the epithelium.

Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction.

OBJECTIVE: The pathology of the olfactory mucosa is poorly understood; however, most cases of hyposmia and anosmia appear to be associated with a decline in the number of functioning mature olfactory sensory neurons (OSNs). Under normal conditions, OSNs undergo apoptotic cell death at a baseline rate likely secondary to their exposed location in the nose. Regeneration of mature OSNs from precursors in the epithelium allows the animal to maintain an adequate number of neurons necessary for olfactory sensation. In many cases of olfactory dysfunction, this balance is apparently disturbed, with a net loss of OSNs. The current study will examine normal and diseased olfactory tissue for the presence of data demonstrating that the preferred mechanism of OSN cell death is apoptotic in both health and disease. The potential therapeutic implications will be discussed. STUDY DESIGN: Histologic analysis of human and animal olfactory tissue. METHODS: Normal and diseased human and animal olfactory mucosa were assessed for immunohistochemical evidence of apoptosis. RESULTS: Increased activity of the apoptotic effector enzyme caspase-3 was demonstrated in diseased olfactory mucosa in comparison with normal controls. CONCLUSION: These results indicate that a common pathway may mediate OSN cell death from a diverse set of pathologic insults including aging, trauma, and sinusitis. Interference with this pathway of cell death is currently the subject of intense pharmacotherapeutic research for the management of stroke and meningitis. These drugs may ultimately prove useful in the treatment of clinical olfactory dysfunction.

Identification of characteristic regions and representative stations: a study of water quality variables in the Kattegat.

Gradients in nutrient distributions and the effects of eutrophication are common features in most coastal marine areas. These structures occur in aquatic systems due to spatial differences in hydrography, nutrient loading and key biogeochemical processes. Two statistical methods, cluster analysis and probability mapping, have been used in the present study to determine characteristics and patterns in water quality variables. Combined, these two methods provide a useful tool to statistically determine spatial homogeneity and representativity of areas and stations. A case study is presented here in which water quality variables (salinity, dissolved inorganic nitrogen, dissolved inorganic phosphorus and chlorophyll) in surface waters of the Kattegat are analysed for the time period 1993-1997. It was found that morphology, the proximity to sources of nutrient loading from land, nutrient uptake and the infrequent water exchange between the Baltic Sea in the south and the Skagerrak in the north all contribute to create distinct regions of water quality. Regions with concentrations significantly different from the overall mean are identified. In addition to identification of regions with similar characteristics, representative stations (as well as not representative stations) for the respective regions were made. This type of information can be used to design new or revise old monitoring programs.

Provider willingness to screen all sexually active adolescents for chlamydia.

OBJECTIVES: To assess differences in provider willingness to screen all sexually active male and female adolescents for chlamydia and to determine whether concerns about cost effectiveness of screening are related to provider willingness to screen for chlamydia. METHODS: All primary care providers in a managed care organisation self administered a survey about screening all sexually active adolescents for chlamydia. RESULTS: Respondents were 217 physicians (MDs) and 121 nurse practitioners (NPs) or physician assistants (PAs). Excluding obstetrician/gynaecologists, more providers were willing to routinely screen adolescent females than males for chlamydia (67% v 49% respectively; p<0.001). Independent predictors of provider willingness to screen both males and females included belief that routine screening is cost effective and being a NP/PA v an MD. Belief that chlamydia screening is easier in females than males independently predicted less willingness to screen males. CONCLUSION: Information that reduces provider concern about the cost effectiveness of screening may increase provider willingness to screen adolescents for chlamydia. Availability of urine based tests may reduce provider beliefs that females are easier to screen than males and increase chlamydia screening in males.

Apoptosis in the aging olfactory epithelium.

OBJECTIVES: Olfactory receptor neurons undergo apoptosis at a baseline rate, probably secondary to environmental damage even in the absence of gross disease. The study demonstrates age-related changes in expression of genes known to regulate apoptosis in the rat olfactory mucosa. These results are compared with gene expression in young rats and rats that have undergone surgical deafferentation of the olfactory receptor neurons. STUDY DESIGN: The olfactory mucosae from three groups of rats were studied: young, normal rats (age, 12 wk); old, normal rats (age, 24 mo); and young rats 9 days after bilateral removal of the olfactory bulb. Bulbectomy is known to produce an initial wave of apoptotic cell death in the population of olfactory neurons. At 9 days after the injury, the olfactory mucosae consist of an enhanced population of regenerating neurons destined to also undergo apoptosis, since their synaptic target (bulb) has been removed. METHODS: Ribonuclease protection assays and histological analysis of the three groups were performed. RESULTS: Ribonuclease protection assay analysis indicates that age induces increases in the expression of pro-apoptotic genes in the olfactory mucosae similar to the increase seen after deafferentation (bulbectomy). Specifically, the expression of procaspase-3 and bax was increased in aged animals and bulbectomized animals when compared with young, normal animals. CONCLUSIONS: Aging induces changes in gene expression in the olfactory mucosae that appear to favor apoptosis, probably associated with increased fragility of olfactory receptor neurons in older animals. These changes may, at least in part, explain the age-related decline in olfactory sensation and loss of olfactory receptor neurons seen in elderly patients.

Adolescent chlamydia testing practices and diagnosed infections in a large managed care organization.

GOAL: To determine chlamydia screening practices and the resulting positive test results for adolescents enrolled in a large nonprofit managed care organization. STUDY DESIGN: The electronic medical records of all 12- to 19-year-olds enrolled in a large nonprofit managed care organization serving a demographically diverse patient population from January 1998 through December 1999 were reviewed retrospectively. RESULTS: Among the 43,205 female and 44,133 male managed care organization members, ages 12 to 19 years in 1998-1999, 7575 adolescents (8.7%) (6914 females [16%] and 661 males [1.5%]) were tested for chlamydia. Among the members tested, chlamydia was diagnosed in 1109 adolescents (14.6%) (983 females [14.2] and 126 males [19.1%]); 761 (68.6%) adolescents were retested for chlamydia; and 182 (16.4%) had repeat positive test results. The median time to diagnosis of a repeat infection was 6 months. CONCLUSIONS: Chlamydia imposes a large disease burden in the private, organized healthcare sector. Managed care organizations can use operational data to enhance chlamydia prevention services by defining testing practices and local disease prevalence.

Efficacy of endoscopic sinus surgery in the management of patients with asthma and chronic sinusitis.

An association between chronic sinusitis and asthma has been noted for many years, although the precise nature of the relationship is poorly understood. Earlier studies, using traditional surgical techniques, have demonstrated subjective improvement in asthmatic complaints. Reports demonstrating improvement following endoscopic sinus surgery for chronic sinusitis are rare. To report our experience with endoscopic sinus surgery and asthmatics, we reviewed the charts of 75 consecutive patients with asthma and chronic sinusitis who underwent endoscopic sinus surgery between 1994 and 1996. Study criteria included the following: chronic sinusitis, one year preoperative and one year postoperative follow-up from endoscopic sinus surgery, and asthma requiring inhaled steroids and oral prednisone for control. Many patients required prednisone bursts for control of asthma. Number of days and total dose of oral prednisone were used as objective measures of asthma control. Number of weeks of antibiotics was used as a relative measure of sinusitis. Fourteen of the 15 patients meeting study criteria decreased their postoperative prednisone requirement by total number of days (preoperative 84 versus postoperative 63 days [p < 0.0001]). Postoperatively, patients required an average of 1300 mg less oral prednisone (p < 0.033). Antibiotic use also decreased, with an average use of antibiotic nine weeks preoperatively versus seven weeks postoperatively (p < 0.045). This study provides corroborative objective evidence that, at least in the short term, endoscopic sinus surgery is efficacious in the management of patients with chronic sinusitis and asthma.

Welfare state and infant mortality.

This article seeks to understand the effects of welfare-state spending on infant mortality rates. Infant mortality was chosen for its importance as a social indicator and its putative sensitivity to state action over a short time span. Country fixed-effects models are used to determine that public health spending does have a significant impact in lowering infant mortality rates, net of other factors, such as economic development, and that this effect is cumulative over a five-year time span. A net effect of health spending is also found, even when controlling for the level of spending in the year after which the outcome is measured (to account for spurious effects or reverse causation). State spending effects infant mortality both through social mechanisms and through medical ones. This article also shows that the impact of state spending may vary by the institutional structure of the welfare state. Finally, this study tests for structural breaks in the relationship between health spending and infant mortality and finds none over this time period.