Dairy heifers have an earlier increase in serum pregnancy-specific protein B compared with lactating dairy cows. Is this an indicator of earlier conceptus attachment?

This study was designed to use within-individual daily increases in circulating pregnancy-specific protein B (PSPB) to determine time to increase in serum PSPB in nulliparous heifers and multiparous dairy cows following artificial insemination (AI). Weekly cohorts of lactating Holstein cows (n = 56) averaging 122 ± 7 d in milk at AI and nulliparous Holstein heifers (n = 23) averaging 16 ± 0.24 mo old at AI were used in this study. Lactating cows received AI to either Ovsynch (n = 38) or at ~12 h following observed standing estrus (n = 18). All heifers were inseminated ~12 h after observed standing estrus. Blood samples for measurement of PSPB were collected daily from d 15 through d 35 postovulation. Nulliparous heifers had increases in serum PSPB earlier compared with both primiparous and multiparous cows. Day of increase in serum PSPB was defined as the day serum PSPB optical density levels initially increased ≥10% from baseline and continued to increase from baseline of ≥10% the following 2 d. Average PSPB were greater in pregnant heifers compared pregnant cows from d 23 through 29. Early lactation nonpregnant cows maintained greater average optical density of serum PSPB from 15 to 35 d postovulation compared with nonpregnant heifers (n = 38). In summary, fertility differences in heifers versus lactating cows may be due to the differences in timing of increases in serum PSPB. This appears to be one of the first publications that used daily PSPB sampling to investigate possible differences in fertility in heifers versus lactating cows.

The effect of a double dose of cloprostenol sodium on luteal blood flow and pregnancy rates per artificial insemination in lactating dairy cows.

Inadequate luteolysis in fertility programs is a problem for lactating dairy cows treated with a single dose of PGF2α. The proportion of cows with complete luteolysis can be increased by administering 2 doses of PGF2α 24 h apart. This study hypothesized that a double dose of cloprostenol sodium (1.0 mg) could take the place of 2 doses 24 h apart due to its enhanced half-life. Cows were allocated to receive 1 of 3 treatments: negative controls: 0.5 mg of cloprostenol sodium (single; n = 337); positive controls: two 0.5-mg doses of cloprostenol sodium 24 h apart (two/24; n = 313); and treated: 1.0 mg of cloprostenol sodium (double; n = 298) at the final PGF2α of Double-Ovsynch. Cows received artificial insemination (AI) 16 h after final GnRH of Double-Ovsynch. Pregnancy diagnosis was determined at 24, 34, 62, and 184 d post-AI. Pregnancy loss was categorized in the following periods: between 24 to 34, 34 to 62, and 62 to 184 d post-AI. Ultrasonography (B-mode and color Doppler) was used to assess luteal function pre- and posttreatment with various doses of cloprostenol sodium. Luteal volume and luteal blood flow (LBF) from d 7 and 14 corpora lutea were determined before treatment (d -1), and 2 and 4 d after treatment. No evidence was observed of an effect of treatment on pregnancy rates per AI at 24, 34, or 62 d post-AI. No effect was observed of treatment on pregnancy losses occurring between d 24 and 34, 34, and 62, and between 62 and 184 d post-AI. However, third-plus parity cows treated with the single treatment had greater pregnancy loss compared with two/24 and double between d 24 and 34 post-AI. Third-plus parity cows that received the double treatment had lower LBF 2 and 4 d after treatment compared with cows treated with single. Amount of LBF present 4 d after treatment was not a predictor of pregnancy or pregnancy loss. A double dose (1.0 mg) of cloprostenol sodium may be a feasible alternative for fertility programs based on nondifferent outcomes to the two/24 treatment, lower pregnancy losses, and reduced LBF disappearance following treatment in third-plus parity cows in comparison with the single treatment.

Complexation reduces nickel toxicity to purple sea urchin embryos (Strongylocentrotus purpuratus), a test of biotic ligand principles in seawater.

The potential for Ni toxicity in seawater is of concern because of mining and processing activities in coastal regions. Determining Ni speciation is vital to understanding and predicting Ni toxicity and for bioavailability-based nickel risk assessment. The goal of this study was to characterize the complexation of Ni in relation to toxicity using embryological development of purple sea urchin (S. purpuratus). It was predicted that free ion [Ni2+] would be a better predictor of toxicity than total dissolved Ni concentrations (NiD). Synthetic ligands with known logKf values (Ethylenediaminetetraacetic acid (EDTA), Nitrilotriacetic acid (NTA), tryptophan (TRP), glutamic acid (GA), histidine (HD), and citric acid (CA)) were used to test the assumptions of the biotic ligand model (BLM) for Ni in seawater. [NiD] was measured by graphite furnace atomic absorption spectroscopy (GFAAS) and Ni2+ was first quantified using the ion-exchange technique (IET) and then concentrations were measured by GFAAS; [Ni2+] was also estimated using aquatic geochemistry modelling software (Visual Minteq). The mean EC50 values for [NiD] in unmodified artificial seawater control was 3.6 µM (95% CI 3.0-4.5) [211 µg/L 95% CI 176-264] and the addition of ligands provided protection, up to 6.5-fold higher [NiD] EC50 for EDTA. Compared to the control, measured EC50 values based on total dissolved nickel were higher in the presence of ligands. As predicted by BLM theory, [Ni2+] was a better predictor of Ni toxicity with 17% variability in EDTA and CA media while there was 72% variability in the prediction of Ni toxicity with total dissolved Ni. The results of this research provide support for the application of BLM- based prediction models for estimating Ni impacts in seawater.

Short communication: Blood samples before and after embryonic attachment accurately determine non-pregnant lactating dairy cows at 24 d post-artificial insemination using a commercially available assay for pregnancy-specific protein B.

Early pregnancy diagnosis is critical to reproductive success on dairy farms. Reproductive success depends on cows becoming pregnant before 130 d in milk and then maintaining that pregnancy. The earlier non-pregnant cows are identified, the sooner they can be reinseminated, thus reducing days to pregnancy. Assays for pregnancy-specific protein B (PSPB) and pregnancy-associated glycoproteins can be used to diagnose pregnancy >28 d post-artificial insemination (AI) in lactating cows. The objective of this study was to determine whether percentage change in serum levels of PSPB within cow from d 17 to 24 can be used to identify non-pregnant cows using a commercially available assay. This study was performed on a large commercial dairy. Blood samples were taken at d 17 and 24 post-AI. The d 17 sample served as a baseline based on previous data. Cows with a 10% increase in serum PSPB levels from d 17 to 24 were considered pregnant. Lactating dairy cows (n = 206; 39% primiparous and 61% multiparous) were synchronized using G6G-Ovsynch. The PSPB diagnosis was compared with the herd veterinarian's diagnosis via ultrasound on d 34. The sensitivity for a 10% cutoff as a non-pregnant diagnosis was 100%, and the specificity was 93.58%. The positive predictive value was 93.27%, and the negative predictive value was 100%. Low PSPB levels at d 24 were predictive of early pregnancy loss by 60 d post-AI. To our knowledge no other method can diagnose non-pregnancy with 100% accuracy and predict pregnancy loss earlier than 24 d post-AI. Using comparative PSPB samples at d 17 and 24 post-AI provides an accurate non-pregnancy diagnosis earlier than any other pregnancy diagnosing method.

The high-fertility cycle: How timely pregnancies in one lactation may lead to less body condition loss, fewer health issues, greater fertility, and reduced early pregnancy losses in the next lactation.

Body condition loss during early lactation varies among cows in the herd and is associated with future health and reproductive outcomes. The objective of this study was to gain a greater understanding of the relationship between previous calving interval and body condition change during the first 30 d in milk (DIM) and their relationship to subsequent fertility and health variables and sex ratio at birth. Dry cows and heifers (n = 851) from a single farm entered the study approximately 25 d before the due date. They were evaluated and given a body condition score on a 1-to-5 scale with 0.1-point increments weekly until parturition. Body condition score was assessed within 1 wk of parturition and then again 27 to 33 DIM. Previous calving interval, gestation length, periparturient health events (giving birth to twins, dystocia, retained placentas, ketosis, metritis, and displaced abomasum), sire net merit ($), and milk data were used for each cow as recorded in PCDART (Dairy Records Management Systems, Raleigh, NC) by the herd managers. Longer previous calving intervals were related to greater body condition at parturition and body condition loss during the first 30 DIM. A 75% greater proportion of cows with a calving-to-pregnancy interval shorter than 130 d maintained or gained body condition during the first 30 DIM compared with cows with calving-to-pregnancy intervals longer than 130 d. Multiparous cows that maintained or gained body condition (n = 144) had greater pregnancies per AI following first service compared with cows that lost body condition (n = 577) during the first 30 DIM when health events were considered or removed. When cows with health events were considered, multiparous cows that maintained or gained body condition had a greater percentage pregnant by 130 DIM compared with cows that lost body condition (67 vs. 55%; n = 522). Cows that lost body condition during the first 30 DIM regardless of health events experienced greater pregnancy loss (n = 224) between 35 and 60 d after first AI (0.0 vs. 6.7%) compared with cows that maintained or gained body condition (n = 69) during that period. Based on data in this study from a single herd, maintaining a cycle of pregnancy before 130 DIM may reduce the amount of body condition lost after the next parturition, enhance subsequent pregnancies per AI, and reduce the possibility of early pregnancy loss. We refer to this phenomenon as the high-fertility cycle.

PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.

Essentials Phosphoinositide 3-kinase and MAPK pathways crosstalk via PDK1. PDK1 is required for adenosine diphosphate-induced platelet activation and thromboxane generation. PDK1 regulates RAF proto-oncogene Ser/Thr kinase (Raf1) activation in the MAPK pathway. Genetic ablation of PDK1 protects against platelet-dependent thrombosis in vivo. SUMMARY: Background Platelets are dynamic effector cells with functions that span hemostatic, thrombotic and inflammatory continua. Phosphoinositide-dependent protein kinase 1 (PDK1) regulates protease-activated receptor 4-induced platelet activation and thrombus formation through glycogen synthase kinase3ß. However, whether PDK1 also signals through the ADP receptor and its functional importance in vivo remain unknown. Objective To establish the mechanism of PDK1 in ADP-induced platelet activation and thrombosis. Methods We assessed the role of PDK1 on 2MeSADP-induced platelet activation by measuring aggregation, thromboxane generation and phosphorylation events in the presence of BX-795, which inhibits PDK1, or by using platelet-specific PDK1 knockout mice and performing western blot analysis. PDK1 function in thrombus formation was assessed with an in vivo pulmonary embolism model. Results PDK1 inhibition with BX-795 reduced 2-methylthio-ADP (2MeSADP)-induced aggregation of human and murine platelets by abolishing thromboxane generation. Similar results were observed in pdk1-/- mice. PDK1 was also necessary for the phosphorylation of mitogen-activated protein kinase kinase 1/2 (MEK1/2), extracellular signal-regulated kinase 1/2, and cytosolic phospholipase A2, indicating that PDK1 regulates an upstream kinase in the mitogen-activated protein kinase (MAPK) pathway. We next determined that this upstream kinase is Raf-1, a serine/threonine kinase that is necessary for the phosphorylation of MEK1/2, as pharmacological inhibition and genetic ablation of PDK1 were sufficient to prevent Raf1 phosphorylation. Furthermore, in vivo inhibition or genetic ablation of PDK1 protected mice from collagen/epinephrine-induced pulmonary embolism. Conclusion PDK1 governs thromboxane generation and thrombosis in platelets that are stimulated with 2MeSADP by regulating activation of the MAPK pathway.

The effect of prior bisphosphonate therapy on the subsequent therapeutic effects of strontium ranelate over 2 years.

UNLABELLED: Many osteoporotic women prescribed strontium ranelate have previously received bisphosphonates. Prior bisphosphonate use blunted the spinal bone mineral density (BMD) response for 6 months. Hip BMD was blunted to a degree for 2 years, although there was an overall increase in hip BMD in contrast to the heel where BMD did not increase. INTRODUCTION: Many osteoporotic women commenced on strontium ranelate have already received treatment with bisphosphonates. This study investigates whether prior bisphosphonate use impairs the subsequent therapeutic response to strontium ranelate. METHODS: Women were recruited who were either bisphosphonate naïve or currently receiving a bisphosphonate. All women received strontium ranelate and were followed up for 2 years. RESULTS: One hundred and twenty women were recruited. After 2 years, the bisphosphonate-naïve group had significant BMD increases of 8.9%, 6.0% and 6.4% at the spine, hip and heel, respectively. In the prior bisphosphonate group, BMD increased significantly at the spine (4.0%) and hip (2.5%) but not at the heel. At all time points at all sites, the BMD increase was greater in the bisphosphonate-naïve group. BMD at the spine did not increase during the first 6 months in the prior bisphosphonate group but then increased in parallel with the bisphosphonate-naïve group. In contrast, the difference between the two groups in hip BMD continued to increase throughout the 2 years. P1NP was suppressed in the prior bisphosphonate group for the first 6 months. CONCLUSIONS: After bisphosphonate exposure, the BMD response to strontium ranelate is blunted for only 6 months at the spine. At the hip, a degree of blunting was observed over 2 years, although there was an overall increase in hip BMD in contrast to the heel where no increase in BMD was observed.

The safety and efficacy of vertebroplasty using Cortoss cement in a newly established vertebroplasty service.

Vertebroplasty provides an effective means of treating painful vertebral lesions although the majority of the literature relates to vertebroplasty using PMMA cement. The purpose of this study is to assess the safety and efficacy of vertebroplasty using Cortoss, a recently developed bis-GMA resin. Our newly established vertebroplasty service exclusively uses Cortoss cement and has a patient database which is updated on a regular basis using the medical records. To date, there are 34 patients on this database, mean age 66, in whom a vertebroplasty has been performed on 42 vertebral lesions with a mean of 2.2 ml of Cortoss injected into each lesion. The mean duration of follow up was 9.5 months. Eighty-two per cent of patients reported an improvement in their symptoms, while 79% required less analgesia post vertebroplasty. A total of 88.2% experienced no significant complications. In 38% there was an asymptomatic leakage of Cortoss. Four patients (11.8%) experienced significant complications: one asymptomatic PE, one episode of transient radicular leg pain, one generalized rash and one patient suffered retropulsion of the Cortoss due to further vertebral malignancy. Cortoss vertebroplasty provides comparable efficacy and safety to the published literature for PMMA.

Routine versus targeted vertebral fracture assessment for the detection of vertebral fractures.

UNLABELLED: Fracture risk is underestimated in women with unknown vertebral fractures. Using VFA, we compared two screening methods: targeted (6,388 women) and routine (2,176 women). Routine screening detected fractures in 20%. Targeted screening only required 5% attending for DXA to undergo VFA but only detected 9.6% of women with fractures. INTRODUCTION: BMD alone underestimates fracture risk in women with unknown vertebral fractures. We report the results of routine vertebral fracture assessment (VFA) screening and compare with targeted screening. METHOD: Our centre initially targeted VFA at women with reasons to suspect a vertebral fracture. Later we changed to routine VFA screening for all women over 65. We retrospectively compare each screening method's ability to detect vertebral fractures. RESULTS: Six thousand three hundred and eighty-eight women over 65 underwent DXA during the period of targeted VFA and 2,176 during routine VFA. Routine VFA detected 420 (20.0%) women with fracture. Most vertebral fractures (56.2%) occurred in women with osteopenia. Routine VFA would be expected to alter the management of 1 in 6 osteopenic women. Targeted VFA was performed in 332 (5.2%) women detecting 122 (1.9%) women with fractures. It was estimated that targeted VFA only detected 9.6% of women with a vertebral fracture. Targeted VFA failed to detect fractures in 18.1% of the population attending for DXA and in 29% of those with osteoporosis. CONCLUSION: Routine VFA detects vertebral fractures in 20% of women over 65. Targeted VFA greatly reduces the number of VFAs performed but only detects a minority of the women with vertebral fractures.

Cost effectiveness of the Expert Patients Programme (EPP) for patients with chronic conditions.

OBJECTIVE: To assess the cost effectiveness of the Expert Patients Programme (EPP) intervention compared to a treatment as usual alternative. DESIGN: Two-arm pragmatic randomised controlled trial design with waiting list control. SETTING: Community settings in England. PATIENTS: Patients with a wide range of self-defined long-term conditions. INTERVENTION: The EPP based on the US chronic disease self management program (CDSMP), a lay-led self-care group involving six weekly sessions to teach self-care support skills. MAIN OUTCOME MEASURES: Costs estimated over a 6-month period from a societal perspective. Health outcomes estimated in terms of quality adjusted life years (QALYs) generated by patients' response to the EQ5D at baseline and 6-month follow-up. RESULTS: The intervention group is associated with better patient outcomes, at slightly lower cost. Specifically, the intervention group has a 0.020 QALY gain compared with the control group, and a reduced cost of around 27 pounds per patient. The intervention would therefore be considered dominant. While the QALYs gained are small in absolute terms, an additional 0.02 QALY is equivalent to an extra one week of perfect health per year. When the value of a QALY is 20,000 pounds the EPP has a probability of 94% of being cost effective. Indeed, for all plausible values of willingness-to-pay for a QALY the EPP group is more likely to be cost effective than the control group. CONCLUSIONS: The EPP intervention evaluated in this trial is very likely to provide a cost effective alternative to usual care in people with long-term conditions.

Contribution of chlorophyll fluorescence to the apparent vegetation reflectance.

Current strategies for monitoring the physiologic status of terrestrial vegetation rely on remote sensing reflectance data, which provide estimates of vigor based primarily on chlorophyll content. Chlorophyll fluorescence (ChlF) measurements offer a non-destructive alternative and a more direct approach for diagnosis of vegetation stress before a significant reduction in chlorophyll content has occurred. Thus, technology based on ChlF may allow more accurate carbon sequestration estimates and earlier stress detection than is possible when using reflectance data alone. However, the observed apparent vegetation reflectance (Ra) in reality includes contributions from both the reflected and fluoresced radiation. The aim of this study is to determine the relative contributions of reflectance and ChlF fractions to Ra in the red to near-infrared region (650-800 nm) of the spectrum. The practical objectives of the study are to: 1) evaluate the relationship between ChlF and reflectance at the foliar level for corn, soybean and maple; and 2) for corn, determine if the relationship established for healthy vegetation changes under nitrogen (N) deficiency. To obtain generally applicable results, experimental measurements were conducted on unrelated crop and tree species (corn, soybean and maple) under controlled conditions and a gradient of inorganic N fertilization levels. Optical reflectance spectra and actively induced ChlF emissions were collected on the same foliar samples, in conjunction with measurements of photosynthetic function, pigment levels, and carbon (C) and N content. The spectral trends were examined for similarities. On average, 10-20% of Ra at 685 nm was actually due to ChlF. The spectral trends in steady state and maximum fluorescence varied significantly, with steady state fluorescence (especially red, 685 nm) showing higher ability for species and treatment separation. The relative contribution of ChlF to Ra varied significantly among species, with maple emitting much higher fluorescence amounts, as compared to corn and soybean. Steady state fluorescence from individual red and far-red emission bands (F685 and F740, respectively) and their ratio consistently enabled species separation. For corn, the relative ChlF fraction increased in concert with the nutrient stress levels from <2% for non-stressed foliage to >7% for severely N deficient plants. Steady state ChlF at 685 nm provided optimal N treatment separation. This study confirms the trends in the steady state red/far-red ratio (F685s/F740s) associated with N deficiency and vegetation stress, previously established using active single narrow band excitation.

Blurred vision due to psychosocial difficulties: a case series.

PURPOSE: The association between psychological difficulties and accommodative insufficiency in children and young adults has been previously reported. The authors give their experiences with such cases and address the research and service developments required to deal with these problems. METHODS: When no other organic pathology was found in full ophthalmological assessment, and where insufficient improvement in accommodation was found in orthoptic treatment, the patients were referred to liaison psychiatry or to adult or child psychotherapy services for assessment. RESULTS AND CONCLUSIONS: Some cases of accommodative insufficiency referred for ophthalmological assessment were found to have psychosocial difficulties, which played a role in the development of the complaint. For patients and clinicians, it is hard to understand how there can be a psychosomatic translation between personal difficulties and ocular symptoms. The authors use the concept of alexithymia to recognise that some people cannot describe their emotions in words and can only express them physically. The joint management of these cases by both psychiatry and ophthalmology has been valued by the patients.

Reductions in cardiovascular risk in association with population screening: a 10-year longitudinal study.

BACKGROUND: This study was carried out in order to examine changes in cardiovascular risk associated with a population-based screening programme. METHOD: Cardiovascular disease (CVD) risk factor data from a representative sample of residents aged between 45 and 55 years who attended screening a total of three times over a 10-year period were chosen for analysis (n=4113). Cohorts were defined as either 'high risk' or 'normal risk' at baseline for risk factors including blood pressure, body mass index (BMI), cholesterol, smoking and alcohol intake. Mean changes were observed for both groups over three screening episodes, and results were stratified by gender. RESULTS: For the high-risk cohorts (after controlling for age and regression to the mean effects), there were significant decreases in all risk factors, except BMI. Conversely, the observed changes in the normal risk cohorts indicated significant increases in risk factors over the 10-year period. After adjusting for age, the pattern in the normal risk cohorts fluctuated and there were some decreases in risk, but they were not as large as the decreases in risk for the high-risk cohorts. CONCLUSIONS: Population screening for CVD is an effective strategy for identifying and reducing risk in high-risk individuals. These results have significant implications for the role of screening in preventing and controlling cardiovascular disease.

The effects of short-term hormone replacement therapy on long-term bone mineral density.

INTRODUCTION: Short-term hormone replacement therapy (HRT) relieves menopausal symptoms and increases bone mineral density (BMD), but bone loss reoccurs upon discontinuation. This study assesses whether short-term HRT provides long-term BMD benefits. METHOD: This was a prospective study of women aged 50-54 years followed up for 9 years. Women were categorized into three groups according to the treatment they received: No-HRT (n = 340), Short-term HRT (2-4 years, n = 60), and Long-term HRT (9 years, n = 187). RESULTS: BMD increased significantly at the hip (2.4%, p < 0.001) and spine (8.0%, p < 0.001) over 9 years in the Long-term HRT group. Women without treatment lost BMD at the hip (-4.2%, p < 0.001) and spine (-3.5%, p < 0.001). Women in the Short-term HRT group had no significant loss of BMD at the hip (-1.6%, p = 0.08) or spine (-1.4%, p = 0.18) over 9 years. BMD in the Short-term HRT group was significantly higher at 9 years than in the No-HRT group at both spine (difference 0.023 g/cm(2), p = 0.048) and hip (difference 0.016 g/cm(2), p = 0.042). CONCLUSION: After 9 years, women who had taken short-term HRT had no significant loss of BMD and were better off in terms of BMD than those left untreated. Short-term HRT in the early postmenopausal period provides long-term BMD benefits.

Assessment of vegetation stress using reflectance or fluorescence measurements.

Current methods for large-scale vegetation monitoring rely on multispectral remote sensing, which has serious limitation for the detection of vegetation stress. To contribute to the establishment of a generalized spectral approach for vegetation stress detection, this study compares the ability of high-spectral-resolution reflectance (R) and fluorescence (F) foliar measurements to detect vegetation changes associated with common environmental factors affecting plant growth and productivity. To obtain a spectral dataset from a broad range of species and stress conditions, plant material from three experiments was examined, including (i) corn, nitrogen (N) deficiency/excess; (ii) soybean, elevated carbon dioxide, and ozone levels; and (iii) red maple, augmented ultraviolet irradiation. Fluorescence and R spectra (400-800 nm) were measured on the same foliar samples in conjunction with photosynthetic pigments, carbon, and N content. For separation of a wide range of treatment levels, hyperspectral (5-10 nm) R indices were superior compared with F or broadband R indices, with the derivative parameters providing optimal results. For the detection of changes in vegetation physiology, hyperspectral indices can provide a significant improvement over broadband indices. The relationship of treatment levels to R was linear, whereas that to F was curvilinear. Using reflectance measurements, it was not possible to identify the unstressed vegetation condition, which was accomplished in all three experiments using F indices. Large-scale monitoring of vegetation condition and the detection of vegetation stress could be improved by using hyperspectral R and F information, a possible strategy for future remote sensing missions.

Priority issues for hospital boards.

Governing a hospital or healthcare system is a difficult and demanding job. If done properly, the organization can operate well. If the board is inept or incompetent, the organization will suffer. In this article I discuss those functions of board governance that I think are among the most important, along with some recommendations for implementing them.

Cervical screening and health inequality in England in the 1990s.

STUDY OBJECTIVE: s: To examine changing inequality in the coverage of cervical screening and its relation to organisational aspects of primary care and to inequality in cervical cancer incidence and mortality. DESIGN: Retrospective time trends analysis (1991-2001) of screening coverage and cervical cancer incidence and mortality in England. SETTING: The 99 district health authorities in England, as defined by 1999 boundaries were used to create a time series of incidence and mortality rates from cervical cancer per 100 000 population. A subset of 60 district health authorities were used to construct a time series of screening coverage data and GP and practice characteristics. Health authorities were categorised into one of three "deprivation" groups using the Townsend Deprivation Index. PARTICIPANTS: Women aged <35 and 35-64 were selected from health authority populations as the main focus of the study. RESULTS: Cervical cancer screening coverage was consistently higher in affluent areas from 1991-9 but ratio rates of inequality between affluent and deprived health authorities narrowed over time. The increase in coverage in deprived areas was most closely associated with an increase in the number of practice nurses. Cervical cancer incidence and mortality rates were consistently higher in deprived health authorities, but inequality decreased. Screening coverage and cervical cancer rates were highly negatively correlated in deprived health authorities. CONCLUSION: A primary health care intervention such as an organised programme of cervical screening can contribute to reducing inequality in population health.

The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer.

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Breath carbon monoxide as an indication of smoking habit.

STUDY OBJECTIVE: To assess whether the breath carbon monoxide (CO) concentration can be used to determine a patient's smoking habits in a respiratory outpatient clinic. DESIGN: To provide a normal range for smokers and nonsmokers, 41 outpatients and 24 healthy subjects were questioned on their smoking habits and asked to provide two breaths into a CO monitor (EC50 Smokerlyser; Bedfont Instruments; Kent, UK). In a subsequent single-blind study, 51 different outpatients were not told of the purpose of the study and were assessed by extensive questionnaire, spirometry, and Smokerlyser estimation. SETTING: The Chest Clinic and Pulmonary Medicine Department at the Northern General Hospital, Sheffield, UK. PARTICIPANTS: Phase 1 involved 41 outpatients attending the Chest Clinic and 24 nonoutpatient colleagues. In phase 2, an additional 51 different outpatients were studied. MEASUREMENTS AND RESULTS: The mean (SD) breath CO levels were 17.4 (11.6) parts per million (ppm) for smokers and 1.8 (1.3) ppm for nonsmokers (p < 0.001). A level of 6 ppm was taken as the cutoff, as this gave a selectivity of 96% and a sensitivity of 94% for outpatients. Of the 51 study patients, 5 admitted to smoking in the administered questionnaire. Eight denied smoking but had a mean breath CO > 6 ppm (7.5 to 42 ppm). Of these, three admitted to smoking after being explained the implication of the reading. CONCLUSIONS: Breath CO concentration provides an easy, noninvasive, and immediate way of assessing a patient's smoking status. A reading > 6 ppm strongly suggests that an outpatient is a smoker.