A new direction for tackling phosphorus inefficiency in the UK food system.

The UK food system is reliant on imported phosphorus (P) to meet food production demand, though inefficient use and poor stewardship means P is currently accumulating in agricultural soils, wasted or lost with detrimental impacts on aquatic environments. This study presents the results of a detailed P Substance Flow Analysis for the UK food system in 2018, developed in collaboration with industry and government, with the key objective of highlighting priority areas for system interventions to improve the sustainability and resilience of P use in the UK food system. In 2018 the UK food system imported 174.6 Gg P, producing food and exportable commodities containing 74.3 Gg P, a P efficiency of only 43%. Three key system hotspots for P inefficiency were identified: Agricultural soil surplus and accumulation (89.2 Gg P), loss to aquatic environments (26.2 Gg P), and waste disposal to landfill and construction (21.8 Gg P). Greatest soil P accumulation occurred in grassland agriculture (85% of total accumulation), driven by loadings of livestock manures. Waste water treatment (12.5 Gg P) and agriculture (8.38 Gg P) account for most P lost to water, and incineration ashes from food system waste (20.3 Gg P) accounted for nearly all P lost to landfill and construction. New strategies and policy to improve the handling and recovery of P from manures, biosolids and food system waste are therefore necessary to improve system P efficiency and reduce P accumulation and losses, though critically, only if they effectively replace imported mineral P fertilisers.

Phosphorus stocks and flows in an intensive livestock dominated food system.

Current use and management of phosphorus (P) in our food systems is considered unsustainable and considerable improvements in the efficiency of P use are required to mitigate the environmental impact of poor P stewardship. The inherent low P use efficiency of food production from animals means food systems dominated by livestock agriculture can pose unique challenges for improving P management. This paper presents the results of a substance flow analysis for P in the Northern Ireland (NI) food system for the year 2017 as a case study for examining P stewardship in a livestock dominated agricultural system. Imported livestock feed was by far the largest flow of P into the NI food system in 2017 (11,700 t ± 1300 t) and P from livestock excreta the largest internal flow of P (20,400 ± 1900t). The P contained in livestock slurries and manures alone that were returned to agricultural land exceeded total crop and grass P requirement by 20% and were the largest contributor to an annual excess soil P accumulation of 8.5 ± 1.4 kg ha-1. This current livestock driven P surplus also limits the opportunities for P circularity and reuse from other sectors within the food system, e.g. wastewater biosolids and products from food processing waste. Management of livestock P demand (livestock numbers, feed P content) or technological advancements that facilitate the processing and subsequent export of slurries and manures are therefore needed.

The Promise, Practice, and State of Planning Tools to Assess Site Vulnerability to Runoff Phosphorus Loss.

Over the past 20 yr, there has been a proliferation of phosphorus (P) site assessment tools for nutrient management planning, particularly in the United States. The 19 papers that make up this special section on P site assessment include decision support tools ranging from the P Index to fate-and-transport models to weather-forecast-based risk calculators. All require objective evaluation to ensure that they are effective in achieving intended benefits to protecting water quality. In the United States, efforts have been underway to compare, evaluate, and advance an array of P site assessment tools. Efforts to corroborate their performance using water quality monitoring data confirms previously documented discrepancies between different P site assessment tools but also highlights a surprisingly strong performance of many versions of the P Index as a predictor of water quality. At the same time, fate-and-transport models, often considered to be superior in their prediction of hydrology and water quality due to their complexity, reveal limitations when applied to site assessment. Indeed, one consistent theme from recent experience is the need to calibrate highly parameterized models. As P site assessment evolves, so too do routines representing important aspects of P cycling and transport. New classes of P site assessment tools are an opportunity to move P site assessment from general, strategic goals to web-based tools supporting daily, operational decisions.

Phosphorus losses from low-emission slurry spreading techniques.

Low emission slurry spreading techniques are known to improve nitrogen use efficiency, but their impact on phosphorus (P) losses in surface runoff has received little attention. The current study was designed to examine the effect of slurry spreading technique on P losses in runoff. Twelve treatments were examined on 0.5- m by 1.0-m plots in a nominal 2 × 6 factorial design experiment. Treatments comprised grass swards at two different stages of growth, a stubble and a 4-wk regrowth, and six different slurry application treatments: control (no slurry), and slurry applied to simulate splash-plate, injection (across and down slope), and trailing shoe (across and down slope) spreading. Slurry was applied by hand (40 m ha). Rainfall simulations (40 mm h) were conducted at 2, 9, and 28 d post-slurry application. When slurry was applied to the stubble, dissolved reactive P (DRP) concentrations in runoff at Day 2 were 47 and 37% lower ( < 0.05) from the injection and trailing shoe treatments compared with the splash-plate treatment. Similarly, at Day 2, TP concentrations in runoff from the injection treatments were 27% lower ( < 0.05) than the splash-plate treatment. In contrast, application technique had no effect ( 0.05) on P concentrations in runoff following slurry application to the regrowth treatment. Phosphorus concentrations in runoff were unaffected by direction of slurry spreading (across or down) at both applications. Our results indicate that trailing shoe and injection techniques offer the potential to reduce DRP concentrations in runoff during the period immediately after slurry application.

Dynamics of critical source areas: does connectivity explain chemistry?

Critical source area approaches to catchment management are increasingly being recognised as effective tools to mitigate sediment and nutrient transfers. These approaches often assume hydrological connectivity as a driver for environmental risk, however this assumption has rarely been tested. Using high resolution monitoring, 14 rainfall events of contrasting intensity were examined in detail for spatial and temporal dynamics of overland flow generation at a hydrologically isolated grassland hillslope in Co. Down, Northern Ireland. Interactions between overland flow connectivity and nutrient transfers were studied to test the critical source area hypothesis. While total and soluble phosphorus loads were found to be representative of the size of the overland flow contributing area (P=<0.05), the dynamics of concentrations throughout storm hydrographs were found to be complex and storm dependant. Near linear relationships were observed between the contributing area and total overland flow volumes (R(2)=0.86). Export coefficients (kg ha(-1)) calculated using plot size were found to under estimate annual losses of total phosphorus by a factor of 17, when compared to those calculated using the contributing area. This study shows that current critical source area definitions for implementing mitigation measures may be overlooking the importance of storm characteristics in determining nutrient transfers and hence may be insufficient in determining catchment scale risk.

Approaches to the implementation of the Water Framework Directive: targeting mitigation measures at critical source areas of diffuse phosphorus in Irish catchments.

The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs' value as undisturbed reference condition ecosystems.

Sex hormone status may modulate rate of expansion of proximal femur diameter in older women alongside other skeletal regulators.

CONTEXT: Little is known of associations between hip geometry and skeletal regulators. This is important because geometry is a determinant of both hip function and resistance to fracture. OBJECTIVE: We aimed to determine the effects of sex hormone status and other candidate regulators on hip geometry and strength. SUBJECTS AND METHODS: A random sample of 351 women aged 67-79 had two to four hip dual-energy x-ray absorptiometry scans performed over 8 yr of follow-up. Hip structural analysis software was used to measure subperiosteal diameter (PD) and the distance from the center of mass to the lateral cortical margin (d-lat) on three 5-mm-thick cross-sectional regions: narrow neck, intertrochanter, and shaft. Section modulus (Z), bone mineral density (grams per centimeter squared), and an index of bone mineral content (cross-sectional area) were calculated as estimators of bone strength. Serum analytes measured at baseline included SHBG, estradiol, PTH, creatinine, albumin, vitamin D metabolites, and glutamate- and gamma-carboxyglutamate-osteocalcin (OC). A linear mixed model was used to model associations with predictor variables, including testing whether the predictors significantly modified the effect of aging. RESULTS: Aging was associated with increasing PD and d-lat, and higher baseline SHBG significantly modified this effect, in the case of PD, increasing the rates of change at the narrow neck region by 19% for SHBG level 2 sd higher than population mean (P = 0.026). Higher baseline creatinine was independently associated with faster increases in PD and d-lat with aging (P < 0.041). Z declined faster with aging if baseline PTH was higher, and higher albumin had a contrary effect. Z was positively associated with free estradiol and inversely associated with SHBG and glutamate-OC. CONCLUSION: These results show large effects of SHBG on the regulation of proximal femur expansion and bending resistance, probably acting as a surrogate for low bioavailable estrogen. Potentially important effects for fracture resistance in old age were also revealed for PTH, markers related to renal function and the nutritional markers albumin and undercarboxylated OC.

Impact of flow path length and flow rate on phosphorus loss in simulated overland flow from a humic gleysol grassland soil.

In this overland flow simulation experiment, the relationships between flow path length, flow rate and the concentration of different P fractions were investigated. Overland flow was simulated using a 3 mx0.12 m laboratory flume. To remove the impact of rainfall on P lost in overland flow, simulated rainfall was not used during these experiments. Instead overland flow was generated by pumping water into the flume at the surface of the grass sod. The experimental setup allowed for the variation in flow path length and flow rate between and during experimental runs. The results demonstrated that an increase in flow path length caused an increase in Total Dissolved P (TDP), Dissolved Reactive P (DRP) and Total Reactive P (TRP) concentration in overland flow (p<0.01) while an increase in flow rate resulted in a decrease in the concentration of these P fractions in overland flow due to dilution (p<0.01). Total P (TP), Particulate P (PP) and Dissolved Organic P were not affected by the variables tested during this study. When flow path length was increased in conjunction with flow rate, there was an increase in TDP, DRP, and TRP concentrations despite the impact of greater dilution. The results indicate that variations in flow path length during a rainfall event may play a role in determining the concentration of dissolved P fractions in overland flow at field scale.

N-Acetyltransferase 2 polymorphisms, cigarette smoking and alcohol consumption, and oral squamous cell cancer risk.

The risk of squamous cell cancers of the oral cavity (OSCC) is strongly related to the use of tobacco and alcohol. N-Acetyl transferases 1 and 2 (NAT2) metabolize aryl- and heterocyclic amines that are present in tobacco smoke. NAT2 slow acetylator phenotype or genotype is related to reduced ability to detoxify these xenobiotics that are carcinogenic in tissues in which smoking-related cancers develop (e.g. bladder). We studied the association between the deduced NAT2 acetylator phenotypes and OSCC risk in a population-based study of 341 cases and 552 controls. In-person interviews provided information on tobacco use and alcohol consumption. Nucleotide substitutions at position 191, 341, 590, 803 and 857 were determined by a combination of oligonucleotide ligation assays and PCR/RFLP assays. There was no overall association between acetylator status with OSCC risk; the odds ratios for slow and intermediate acetylators, as compared with the rapid acetylators, were 1.2 (95% CI 0.7-2.2) and 1.1 (95% CI 0.6-2.0), respectively. The percent increase in risk of OSCC per pack-year cigarette smoking was similar among slow acetylators (3.0%, 95% CI 2.1-4.0) and the combined intermediate and rapid acetylators (3.5%, 95% CI 2.4-5.0). In contrast, the risk of OSCC per weekly alcoholic drink was stronger among the combined rapid and intermediate acetylators (3.3%, 95% CI 1.8-4.9) compared with slow acetylators (1.6%, 95% CI 0.6-2.7) (interaction P = 0.055). These data raise the possibility that NAT2 may be involved in the activation of one or more pro-carcinogens associated with alcohol consumption.

Oral squamous cell cancer risk in relation to alcohol consumption and alcohol dehydrogenase-3 genotypes.

Heavy alcohol consumption, particularly in combination with cigarette smoking, increases the risk of oral squamous cell carcinoma (OSCC). Alcohol dehydrogenase 3 (ADH3) converts ethanol to acetaldehyde, which is a suspected oral carcinogen. The ADH3*1 allele is associated with increased conversion of ethanol to acetaldehyde, but whether the risk of OSCC is increased among ADH3*1 carriers, or whether the risk of OSCC attributable to alcohol consumption is modified by ADH3 genotype is unclear from previous studies. We examined the association between ADH3 genotypes, alcohol consumption, and OSCC risk in a population-based study of 333 cases and 541 controls from the state of Washington. The distribution of ADH3 genotypes was similar among cases and controls: ADH3*1/*1: 32.7% cases, 36.5% controls; ADH3*1/*2: 49.0% cases, 43.1% controls: ADH3*2/*2: 18.3% cases, 20.3% controls. The age-, sex-, and race-adjusted odds ratios (OR), relative to ADH3*2/*2 carriers, were as follows: ADH*1/*1: OR, 1.0 [95% confidence interval (CI) = 0.7, 1.5]; and ADH3*1/*2: OR, 1.3 (95% CI = 1.0, 1.8). We modeled the risk of OSCC associated with alcohol consumption as modified by ADH3 genotype adjusting for age, sex, race, and cigarette smoking. Among ADH3*2 homozygotes, the risk of OSCC increased 5.3% (2.1-8.5%) with each additional alcoholic drink/week, compared with 2.5% (1.5-2.6%) and 1.2% (0.0-2.4%) among persons carrying the ADH3*1/*2 and ADH3*1/*1 genotypes, respectively. These data suggest that the ADH3*2 allele confers increased susceptibility to the effect of alcohol on OSCC risk in our population.

Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma.

BACKGROUND: Obesity has been shown to affect breast carcinoma prognosis, with the heaviest women having a higher mortality due to breast carcinoma. Few studies have focused on premenopausal women or the correlation of body mass index (BMI) to tumor characteristics related to prognosis. METHODS: The authors conducted a population-based follow-up study for mortality of 1177 women younger than 45 years of age who had invasive ductal breast carcinoma diagnosed from 1983 through 1992. Histologic slides and/or tumor tissue were collected for pathologic review, immunohistochemistry assays, and bivariate flow cytometric analysis. RESULTS: Women with breast carcinoma who were in the highest quartile of BMI were 2.5 times as likely (95% confidence interval [CI], 1.6-3.9) to die of their disease within 5 years of diagnosis compared with women in the lowest quartile of BMI. The tumors of the women in the highest quartile of BMI were more likely to be estrogen receptor negative (odds ratio [OR], 1.5; 95% CI, 1.0-2.2) and to have a high S-phase fraction (OR, 1.9; 95% CI, 1.2-3.1), high histologic grade (OR, 1.7; 95% CI, 1.0-2.9), high mitotic cell count (OR, 2.0; 95% CI, 1.2-3.1), and large tumor size (2 to < 5 cm: OR, 2.3; 95% CI, 1.5-3.1; or > or = 5 cm: OR, 2.7; 95% CI, 1.5-4.8) compared with the tumors of women whose BMI was in the first quartile. Relative to the large tumors (> or = 2 cm) in women in the lowest BMI quartile, the large tumors in women in the highest BMI quartile were more likely to express markers of high proliferation, indicating they may have grown faster than similar size tumors of the thinnest women. In a multivariate analysis including the tumor characteristics, obesity, as measured by being in the highest quartile of BMI, remained an independent prognostic factor for mortality (hazard ratio, 1.7; 95% CI, 1.0-2.9; P < 0.05. CONCLUSIONS: Our study results indicated that being in the highest quartile of BMI was a strong predictor of mortality in women with breast carcinoma diagnosed at a young age. The tumors of the heavy women were larger and more likely to have markers of high cellular proliferation than those of thinner women.

Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history.

BACKGROUND: An increased incidence of breast carcinoma has been reported among relatives of individuals who are affected with the rare recessive disorder, ataxia-telangiectasia (A-T), and who are heterozygous for mutations in the ataxia-telangiectasia mutated (ATM) gene. However, most studies of breast carcinoma cases from the general population have failed to find a higher incidence of ATM mutations in cases when compared with controls. METHODS: Genomic DNA samples from 258 individuals were screened for mutations of all types in each of the 62 coding exons of the ATM gene; 142 of these were from breast carcinoma cases with a first-degree family history or early age at diagnosis, 35 were from cases selected for the presence of either known disease-related mutations (n = 25) or missense alterations of unknown consequences (n = 10) in BRCA1 or BRCA2, and 81 were from matched controls. RESULTS: A total of 12 individuals with ATM mutations were identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI, 3.9-13.4%) and 1 among 81 controls (1.2%; 95% CI, 0.0-6.7%) (P = 0.06). All mutations detected were of the missense type; none were predicted to truncate the ATM protein. Among cases, mutations were found exclusively in patients with a family history of breast carcinoma (12.1%; 95% CI, 6.2-20.6%) (P = 0.02). Similar frequencies of ATM mutations were found in 35 additional cases selected for the presence of BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS: ATM mutations, specifically missense mutations, are more common in breast carcinoma cases selected for first-degree family history and early age at diagnosis.

Tracheal resection and reanastomosis in the neonatal period.

BACKGROUND/PURPOSE: Severe congenital tracheal stenosis is rare. Most of these can be managed conservatively before elective repair. Focal tracheal stenosis has been treated with resection of the involved trachea and primary reanastomosis in older infants. The authors found no reports of repair of this lesion in neonates. Two patients are presented with severe respiratory failure on the first day of life that required extracorporeal life support (ECLS) who underwent successful tracheal resection and reanastomosis (TRR) during the first week of life. METHODS: A retrospective review was conducted. RESULTS: Both babies had severe pulmonary hypertension and carbon dioxide retention despite maximal therapy and were placed on ECLS shortly after transfer. One had an isolated stenosis of the upper trachea, and the other had agenesis of the right lung, esophageal atresia with tracheoesophageal fistula, and a tracheal stenosis at the end of a short trachea with a long, narrow left bronchus. Both underwent diagnostic studies and had surgical repair while on ECLS at day 3 and 7 of life without bleeding complications. They were weaned off ECLS 1 and 8 days after surgery. One patient was extubated and did well. The other was extubated transiently, but required a tracheostomy because of left mainstem bronchomalacia. Both are alive and well at 18 and 38 months of age, with no narrowing of the repairs. CONCLUSION: In the setting of severe respiratory failure requiring ECLS support, TRR can be performed safely and successfully in the neonate with focal tracheal stenosis.

Evaluation of suspected appendicitis in children using limited helical CT and colonic contrast material.

OBJECTIVE: Colonic contrast material evaluation of suspected appendicitis in pediatric patients is technically more challenging than in adults because less intraabdominal fat is present. To determine the accuracy and feasibility of focused CT for pediatric patients, we carried out this retrospective investigation. MATERIALS AND METHODS: Between November 1995 and July 1999, 199 pediatric patients (1-18 years old; mean age, 12 years) were examined with focused CT in the emergency division for suspected appendicitis. The findings on CT were compared with the findings at surgery, pathology, and clinical follow-up. RESULTS: There were 64 true-positive CT scans, two false-negative, 128 true-negative, one false-positive, and four indeterminate. Seventy-four patients underwent appendectomy, with a negative appendectomy rate of 9%. One hundred twenty-five patients without appendicitis were treated nonoperatively. The true-positive rate was 32%, true-negative rate was 64%, sensitivity was 97%, specificity was 99%, positive predictive value was 98%, negative predictive value was 98%, and overall accuracy was 96%. Pediatric patients tolerated the procedure well. Colonic contrast material saved time and provided improved identification of the cecum and appendix. In 62 patients without appendicitis, focused CT provided alternative diagnoses. CONCLUSION: Focused CT appears to be nearly as accurate in pediatric patients as in adults. Focused CT provided alternative diagnoses in 48% of the patients for whom CT findings were negative for appendicitis.

Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer.

The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well-established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin-releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well-tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical-pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.

Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia.

BACKGROUND/PURPOSE: Recurrent pulmonary hypertension in the neonatal population is an unusual event with dire consequences. Pulmonary hypertension seen in association with pulmonary hypoplasia may be refractory to conventional medical management. The effect of the calcium channel antagonist diltiazem was studied in five patients with severe pulmonary hypertension. METHODS: A retrospective review of the hospital records was performed to determine the efficacy of diltiazem for refractory pulmonary hypertension. All five patients experienced and did not respond to maximal conventional therapy, which included inhaled nitric oxide, intravenous nitrates, and extracorporeal membrane oxygenation (ECMO). Right ventricular pressures were determined by transthoracic echocardiograms and were used to document improvement in the pressure gradients. Statistical analyses were performed using a paired Student's ttest. A P value of less than .05 was considered significant. RESULTS: Diltiazem significantly reduced the right ventricular systolic pressure (RVSP) from 82 +/- 8.4 mm Hg to 58.4 +/- 7 mm Hg (P = .008). Two patients died; one had a large ventricular septal defect, and the other suffered multisystem organ failure secondary to sepsis. The surviving patients were weaned off diltiazem and did not experience recurrent pulmonary hypertension. CONCLUSIONS: In cases of pulmonary hypoplasia with recurrent pulmonary hypertension, diltiazem may be considered as a therapy. A multicenter prospective trial is advocated.

Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure.

HYPOTHESIS: Extracorporeal membrane oxygenation (ECMO) is effective in nonneonatal acute respiratory failure under certain circumstances. DESIGN: Retrospective medical record review. SETTING: The intensive care unit of a tertiary care hospital. PATIENTS: Thirty-four nonneonatal patients (mean age, 22 years; range, 8 days to 56 years), with ratios of the PaO2 to the fraction of inspired oxygen persistently below 70, who were treated with ECMO after maximal ventilator therapy had failed (mean time of ventilator therapy, 6.9 days; range, 1-41 days). The mean ECMO duration was 304 hours (range, 56-934 hours). Patients were grouped into 7 categories based on their diagnosis: sepsis or sepsis syndrome (n = 3), bacterial or fungal pneumonia (n = 10), viral pneumonia (n = 5), trauma or burn (n = 2), inhalation injury without burn (n = 1), immunocompromised state (due to transplantation or chemotherapy) (n = 8), and acute respiratory failure of unknown origin (n = 5). MAIN OUTCOME MEASURE: Survival to hospital discharge following ECMO therapy. RESULTS: Overall survival was 53% (18 patients). All 6 patients (100%) with viral pneumonias or isolated inhalation injuries survived. Of 13 patients with bacterial pneumonia, sepsis, or sepsis syndrome not complicated by multiorgan failure, 10 (77%) survived. In contrast, all but 1 of the immunocompromised patients died. Survival in patients who were intubated for less than 9 days before ECMO was 64%, whereas survival fell precipitously to 22% for patients who experienced mechanical ventilation for 9 or more days before the implementation of ECMO. Finally, the proportion of patients who died while receiving ECMO therapy was greater when the ECMO duration exceeded 300 hours (62% vs. 38%; P<.05). CONCLUSIONS: Nonneonatal survival with ECMO therapy is strongly dependent on the diagnosis. Pre-ECMO intubation for less than 9 days had little effect on survival. Survival rates decreased when the length of time of receiving ECMO exceeded 300 hours.

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection.

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.

Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia.

PURPOSE: Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. METHODS: Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed. RESULTS: The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters. CONCLUSIONS: (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.

Risk factors for the recurrence of premature rupture of the membranes.

Premature rupture of the amniotic membranes (PROM) occurs in up to 20% of all births. Although many studies have examined risk factors for PROM and, in particular, preterm PROM (PPROM, if less than 37 weeks' gestation), the aetiology of PROM recurrence has not been examined as closely. This study investigated factors that may increase the risk of PROM among women who have already experienced one PROM birth. Maternally linked Washington State birth certificates from 1984 to 1993 identified 208 women with consecutive PROM births. Controls were a random sample (n = 848) of women who had one birth on record complicated by PROM, but whose subsequent birth was not. Among women with a prior term PROM, increased risk for PROM recurrence (term PROM or PPROM) was associated with an intervening fetal death at less than 20 weeks' gestation (OR = 2.4, 1.3-4.5) and with parity of two or more (OR = 2.0, 1.3-3.4). None of the factors assessed significantly increased the risk of recurrence of PROM (term PROM or PPROM) among women with a prior PPROM. Other potential risk factors for PROM recurrence were evaluated within the two PROM groups (PPROM or term PROM at first birth) by stratifying among the cases according to gestational length at subsequent birth.