Hydro-chemical responses at different scales in a rural catchment, UK, and implications for managing the unintended consequences of agriculture.

Diffuse pollutant transfers from agricultural land often constitute the bulk of annual loads in catchments and storm events dominate these fluxes. There remains a lack of understanding of how pollutants move through catchments at different scales. This is critical if the mismatch between the scales used to implement on-farm management strategies, compared to those used for assessment of environmental quality, is to be addressed. The aim of this study was to understand how the mechanisms of pollutant export may change when assessed at different scales and the corresponding implications for on-farm management strategies. A study was conducted within a 41 km2 catchment containing 3 nested sub-catchments, instrumented to monitor discharge and various water quality parameters. Storm data over a 24-month period were analysed and hysteresis (HI) and flushing (FI) indices calculated for two water quality variables that are typically of environmental significance; NO3-N and suspended sediment (SSC). For SSC, increasing spatial scale had little effect on the mechanistic interpretation of mobilisation and the associated on-farm management strategies. At the three smallest scales NO3-N was chemodynamic with the interpretation of dominant mechanisms changing seasonally. At these scales, the same on-farm management strategies would be recommended. However, at the largest scale, NO3-N appeared unaffected by season and chemostatic. This would lead to a potentially very different interpretation and subsequent on-farm measures. The results presented here underscore the benefits of nested monitoring for extracting mechanistic understanding of agricultural impacts on water quality. The application of HI and FI indicates that monitoring at smaller scales is crucial. At large scales, the complexity of the catchment hydrochemical response means that mechanisms become obscured. Smaller catchments more likely represent critical areas within larger catchments where mechanistic understanding can be extracted from water quality monitoring and used to underpin the selection of on-farm mitigation measures.

Diffuse water pollution during recent extreme wet-weather in the UK: Environmental damage costs and insight into the future?

Periods of extreme wet-weather elevate agricultural diffuse water pollutant loads and climate projections for the UK suggest wetter winters. Within this context, we monitored nitrate and suspended sediment loss using a field and landscape scale platform in SW England during the recent extreme wet-weather of 2019-2020. We compared the recent extreme wet-weather period to both the climatic baseline (1981-2010) and projected near- (2041-2060) and far- (2071-2090) future climates, using the 95th percentiles of conventional rainfall indices generated for climate scenarios downscaled by the LARS-WG weather generator from the 19 global climate models in the CMIP5 ensemble for the RCP8.5 emission scenario. Finally, we explored relationships between pollutant loss and the rainfall indices. Grassland field-scale monthly average nitrate losses increased from 0.39-1.07 kg ha-1 (2016-2019) to 0.70-1.35 kg ha-1 (2019-2020), whereas losses from grassland ploughed up for cereals, increased from 0.63-0.83 kg ha-1 to 2.34-4.09 kg ha-1. Nitrate losses at landscape scale increased during the 2019-2020 extreme wet-weather period to 2.04-4.54 kg ha-1. Field-scale grassland monthly average sediment losses increased from 92-116 kg ha-1 (2016-2019) to 281-333 kg ha-1 (2019-2020), whereas corresponding losses from grassland converted to cereal production increased from 63-80 kg ha-1 to 2124-2146 kg ha-1. Landscape scale monthly sediment losses increased from 8-37 kg ha-1 in 2018 to between 15 and 173 kg ha-1 during the 2019-2020 wet-weather period. 2019-2020 was most representative of the forecast 95th percentiles of >1 mm rainfall for near- and far-future climates and this rainfall index was related to monitored sediment, but not nitrate, loss. The elevated suspended sediment loads generated by the extreme wet-weather of 2019-2020 therefore potentially provide some insight into the responses to the projected >1 mm rainfall extremes under future climates at the study location.

Current advisory interventions for grazing ruminant farming cannot close exceedance of modern background sediment loss - Assessment using an instrumented farm platform and modelled scaling out.

Water quality impairment by elevated sediment loss is a pervasive problem for global water resources. Sediment management targets identify exceedance or the sediment loss 'gap' requiring mitigation. In the UK, palaeo-limnological reconstruction of sediment loss during the 100-150 years pre-dating the post-World War II intensification of agriculture, has identified management targets (0.20-0.35 t ha-1 yr-1) representing 'modern background sediment delivery to rivers'. To assess exceedance on land for grazing ruminant farming, an integrated approach combined new mechanistic evidence from a heavily-instrumented experimental farm platform and a scaling out framework of modelled commercial grazing ruminant farms in similar environmental settings. Monitoring (2012-2016) on the instrumented farm platform returned sediment loss ranges of 0.11-0.14 t ha-1 yr-1 and 0.21-0.25 t ha-1 yr-1 on permanent pasture, compared with between 0.19-0.23 t ha-1 yr-1 and 0.43-0.50 t ha-1 yr-1and 0.10-0.13 t ha-1 yr-1and 0.25-0.30 t ha-1 yr-1 on pasture with scheduled plough and reseeds. Excess sediment loss existed on all three farm platform treatments but was more extensive on the two treatments with scheduled plough and reseeds. Excessive sediment loss from land used by grazing ruminant farming more strategically across England, was estimated to be up to >0.2 t ha-1 yr-1. Modelled scenarios of alternative farming futures, based on either increased uptake of interventions typically recommended by visual farm audits, or interventions selected using new mechanistic understanding for sediment loss from the instrumented farm platform, returned minimum sediment loss reductions. On the farm platform these were 2.1 % (up to 0.007 t ha-1 yr-1) and 5.1 % (up to 0.018 t ha-1 yr-1). More strategically, these were up to 2.8 % (0.014 t ha-1 yr-1) and 4.1 % (0.023 t ha-1 yr-1). Conventional on-farm measures will therefore not fully mitigate the sediment loss gap, meaning that more severe land cover change is required.

Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial.

BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/µl. Regardless of alloimmunization status, CCIs < 5000/µl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

Reversal of the net dinitrogen gas flux in coastal marine sediments.

The flux of nitrogen from land and atmosphere to estuaries and the coastal ocean has increased substantially in recent decades. The observed increase in nitrogen loading is caused by population growth, urbanization, expanding water and sewer infrastructure, fossil fuel combustion and synthetic fertilizer consumption. Most of the nitrogen is removed by denitrification in the sediments of estuaries and the continental shelf, leading to a reduction in both cultural eutrophication and nitrogen pollution of the open ocean. Nitrogen fixation, however, is thought to be a negligible process in sub-tidal heterotrophic marine systems. Here we report sediment core data from Narragansett Bay, USA, which demonstrate that heterotrophic marine sediments can switch from being a net sink to being a net source of nitrogen. Mesocosm and core incubation experiments, together with a historic data set of mean annual chlorophyll production, support the idea that a climate-induced decrease in primary production has led to a decrease in organic matter deposition to the benthos and the observed reversal of the net sediment nitrogen flux. Our results suggest that some estuaries may no longer remove nitrogen from the water column. Instead, nitrogen could be exported to the continental shelf and the open ocean and could shift the effect of anthropogenic nitrogen loading beyond the immediate coastal zone.

Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

Objective: The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. Materials and methods: For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. Results: The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1ß, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p < 0.05). Loss of taste was observed in patients with elevated serum IL-8 (p < 0.05). Conclusions: Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age.

BACKGROUND: Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. OBJECTIVE: To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. METHODS: Facial photographs were collected of 250 Chinese women, aged 25-70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. RESULTS: Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans-epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. CONCLUSIONS: We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.

An open and closed case: timing of closure following laparostomy.

INTRODUCTION: Laparostomy is important in the management of patients with intra-abdominal gastrointestinal catastrophe or trauma. It carries significant risk and is resource intensive, both in terms of nursing and surgically. The main goal is to achieve prompt myofascial closure (MFC) in order to minimise morbidity and mortality. Early MFC was initially defined as within 2-3 weeks but there is growing evidence that this should be measured in days. METHODS: Retrospective analysis was undertaken of laparostomy cases between 2016 and 2018 at an acute trust and trauma centre serving a population of 500,000. Indication, duration of open abdomen (OA), number of relook procedures and consultant presence were examined to see whether they affected MFC rates, morbidity and mortality. RESULTS: Overall, 76 laparostomies were performed during the 3-year study period. The most common indication was peritonitis (68.4%). As duration of OA and number of relook procedures increased, the chances of MFC fell significantly. After day 1, MFC rates fell by 20% with each subsequent 24 hours. Leaving the abdomen open primarily at index procedure compared with performing laparostomy following a postoperative complication was associated with significantly higher MFC rates (92.6% vs 68.2%, (p=0.006). The mortality rate was 15.8%. CONCLUSIONS: If the OA is not closed within five days or by the third relook procedure, then achieving MFC is unlikely. Alternative methods should be employed to close the abdomen rather than continuing to take the patient back to theatre for relook laparotomies while increasing the risk of morbidity and mortality. A proactive strategy to forming primary laparostomy at the index procedure has high closure rates.

Rethinking the contribution of drained and undrained grasslands to sediment-related water quality problems.

Grass vegetation has been recommended for use in the prevention and control of soil erosion because of its dense sward characteristics and stabilizing effect on the soil. A general assumption is that grassland environments suffer from minimal soil erosion and therefore present little threat to the water quality of surface waters in terms of sediment and sorbed contaminant pollution. Our data question this assumption, reporting results from one hydrological year of observations on a field-experiment monitoring overland flow, drain flow, fluxes of suspended solids, total phosphorus (TP), and molybdate-reactive phosphorus (<0.45 mum) in response to natural rainfall events. During individual rainfall events, 1-ha grassland lysimeters yield up to 15 kg of suspended solids, with concentrations in runoff waters of up to 400 mg L(-1). These concentrations exceed the water quality standards recommended by the European Freshwater Fisheries Directive (25 mg L(-1)) and the USEPA (80 mg L(-1)) and are beyond those reported to have caused chronic effects on freshwater aquatic organisms. Furthermore, TP concentrations in runoff waters from these field lysimeters exceeded 800 mug L(-1). These concentrations are in excess of those reported to cause eutrophication problems in rivers and lakes and contravene the ecoregional nutrient criteria in all of the USA ecoregions. This paper also examines how subsurface drainage, a common agricultural practice in intensively managed grasslands, influences the hydrology and export of sediment and nutrients from grasslands. This dataset suggests that we need to rethink the conceptual understanding of grasslands as non-erosive landscapes. Failure to acknowledge this will result in the noncompliance of surface waters to water quality standards.

Lessons learned from laparoscopic treatment of gastric and gastroesophageal junction stromal cell tumors.

BACKGROUND: Stromal cell tumors of the gastric and gastroesophageal junction are rare neoplasms that traditionally have been resected for negative margins using an open approach. This study aimed to evaluate the efficacy laparoscopic resection of gastric and gastroesophageal stromal cell tumors and the lessons learned from experience with this method. METHODS: This retrospective review evaluated all patients who underwent laparoscopic resection of gastric or esophageal stromal cell tumors at a tertiary referral center between December 2002 and March 2005. Medical records were reviewed with regard to patient demographics, preoperative evaluation, operative approach, tumor location and pathology, length of operation, complications, and length of hospital stay. RESULTS: A total of 12 consecutive patients with a mean age of 55 +/- 5.9 years were treated. Preoperative endoscopic ultrasound (EUS) was performed for 11 of 12 patients with a diagnostic accuracy of 100%, whereas EUS-guided fine-needle aspiration was performed for 10 of 12 patients with a diagnostic accuracy of 50%. Four patients with symptomatic gastroesophageal junction leiomyomas were treated with enucleation and Nissen fundoplication. Eight patients were treated with laparoscopic wedge resection of gastric lesions. Complete R0 resection was achieved for all the patients undergoing laparoscopic resection. Intraoperative endoscopy was performed for four patients and resulted in shorter operative times. The average operative time for this entire series was 169 +/- 17 min: 199 +/- 24 min for the first six cases and 138 +/- 19 min for the last six cases. The median hospital length of stay was 2 days. One patient with esophageal leiomyoma had persistent dysphagia at the 12-month follow-up assessment. There were no other complications and no deaths in this series of patients. CONCLUSIONS: Laparoscopic resection of gastric and gastroesophageal junction stromal cell tumors may be performed safely with low patient morbidity. This approach can achieve adequate surgical margins and lead to short hospital stays. Improvements in the technique have led to shorter operative times.

Cytokine gene expression in intact anagen rat hair follicles.

Substantial cellular proliferative activity is necessary to produce a mature hair follicle. Therefore, it is likely that cytokines and their receptors play an important controlling role. To provide an understanding of the mechanisms involved during hair growth, we investigated the expression of cytokines in rat anagen hair follicles. A new technique was developed that allowed the rapid isolation of large numbers of intact, viable, anagen, rat pelage hair follicles. Total RNA was isolated from these follicles using an acid-phenol-chloroform extraction and analyzed for cytokine expression. Using the conventional technique of Northern blotting, it was only possible to detect transcripts for transforming growth factor beta (TGF beta) and insulin-like growth factor I (IGFI). Polymerase chain reaction amplification of reverse-transcribed mRNA detected cDNA fragments for TGF beta, IGF I, IGF II, nerve growth factor beta (NGF beta), and interleukin-1 alpha (IL-1 alpha). The amplified products were confirmed by digestion with restriction endonucleases. The proteins themselves for TGF beta and IGF I have been shown to be present within the anagen hair follicle using immunogold antibody labeling. This study has provided the first reported cytokine expression profile of rat anagen hair follicles. It is likely that the analysis of the pattern and timing of expression of these cytokines in the follicle will provide valuable insights into hair growth regulation.

Biological activities of human recombinant interferon alpha/beta targeted by anti-Epstein-Barr virus monoclonal antibodies.

The requirement of high doses of interferon (IFN) during therapy severely restrict its application. Thus a model using an Epstein-Barr virus (EBV) membrane antigen (MA) specific monoclonal antibody (MAb) was developed to assess the feasibility of coupling minimal amounts of IFN to a MAb and specifically delivering the IFN to the target cells. Coupled IFN was first shown to retain fully both its anti-viral and anti-proliferative properties when tested on human tumor cell lines QIMR-WIL (EBV-MA+) and the U-266 (EBV-MA-). A series of in vitro pulsing experiments demonstrated the specific targeting of both the anti-viral and anti-proliferative properties of IFN to the EBV-MA+ QIMR-WIL cells and not EBV-MA- cell lines.

Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity.

BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.

A comparison of several calcium antagonists on uterine, vascular and cardiac muscles from the rat.

An assessment was made of the potencies of nifedipine, gallopamil, diltiazem, cinnarizine and salbutamol as inhibitors of tension development by the uterus and cardiovascular tissues from the term pregnant rat. The rank order of potency was nifedipine greater than gallopamil greater than diltiazem for those preparations on which these compounds were potent, viz. spontaneous and oxytocin-induced tension development of the uterus, spontaneous tension development of hepatic portal vein, potassium chloride (KCl)-induced pressure rises of perfused mesenteric bed and electrically-stimulated (0.5 Hz) ventricular muscle. The rank order of potency of nifedipine, gallopamil and diltiazem was different for those preparations on which they exhibited low potency, viz. noradrenaline-induced pressure rises of perfused mesenteric bed and tension development of aorta. Gallopamil and diltiazem, but not nifedipine, were more potent against tension development by ventricular muscle stimulated at 2.5 Hz than at 0.5 Hz, suggesting that nifedipine interacts at a different site from the other compounds. Cinnarizine was less potent than the other calcium antagonists on the uterus and portal vein, was the second most potent compound against KCl-induced pressure rises of the mesenteric bed and was equipotent against responses to noradrenaline and KCl of the mesenteric bed (unlike the other compounds). This suggests that the site of action of cinnarizine differs from that of the other calcium antagonists. Nifedipine, gallopamil and diltiazem, like salbutamol, exhibited selectivity for inhibition of tension development by the uterus relative to the cardiovascular tissues.

Effects of calcium entry blockers on tension development and calcium influx in rat uterus.

Spontaneous and potassium chloride (KCl)-induced tension development of strips of whole uterus from the day-22 pregnant rat was reduced when the tissues were incubated in a calcium ion (Ca2+)-free medium. Strips of whole uterus, in an initially Ca2+-free medium, responded to the cumulative addition of Ca2+ with graded phasic tension development and associated rapid electrical discharges. The spasms were inhibited by gallopamil (100 nM) and diltiazem (1 microM). Strips of whole uterus in a depolarizing (40 mM K+) medium, which was initially Ca2+-free, responded to the cumulative addition of Ca2+ with graded tonic tension development without associated electrical discharges. These spasms were inhibited by calcium entry blockers with a rank order of potency of nifedipine = gallopamil greater than diltiazem greater than cinnarizine. KCl-induced tension development in endometrium-free uterine strips was antagonized by calcium entry blockers with a rank order of potency of nifedipine greater than gallopamil greater than diltiazem greater than cinnarizine. Ca2+ influx into endometrium-free uterine strips was assessed by means of the 'lanthanum method'. KCl induced a concentration-dependent increase in 45Ca2+ influx which was suppressed or abolished by nifedipine (2.5 nM), gallopamil (100 nM), diltiazem (500 nM) or cinnarizine (5 microM). It is concluded that spontaneous and KCl-induced tension development of rat uterus involves Ca2+ influx from the extracellular medium into the myometrial cell. These results support the hypothesis that nifedipine, gallopamil, diltiazem and cinnarizine inhibit Ca2+- and KCl-induced tension development of rat uterus by reduction of Ca2+ influx.

The spasmogenic action of oxytocin in the rat uterus--comparison with other agonists.

A low concentration (0.2 nM) of oxytocin induced phasic tension development in the isolated uterus of the day-22 pregnant rat. Tonic spasm was also induced by higher concentrations of oxytocin (2 and 20 nM). Spasmogenic responses to bradykinin and potassium chloride (KCl) also contained phasic and tonic components while acetylcholine induced tonic spasm only. The phasic component of the responses to oxytocin and to bradykinin and both components of the response to KCl were inhibited by (+)-cis diltiazem (0.1 and 1 microM). The tonic component of the responses to oxytocin and to bradykinin and the responses to acetylcholine were only reduced by (+)-cis diltiazem at concentrations greater than 10 microM. (-)-cis Diltiazem was less potent than (+)-cis diltiazem as an inhibitor of calcium (Ca2+)-induced spasm in a depolarizing medium and of the phasic spasms induced by oxytocin. The two isomers were of similar potency as inhibitors of oxytocin-induced tonic spasm. Spasmogenic responses to oxytocin, bradykinin, acetylcholine and KCl were decreased when uteri were bathed in media which were Ca2+-free or of low Na+ content. However, there was no correlation between the rank order of sensitivity of the four spasmogens to the changed media and to their inhibition by (+)-cis diltiazem. Oxytocin (0.2 nM) increased the frequency, duration and amplitude of spike activity, measured by extracellular electrical recording, in parallel with enhancement of phasic tension development. With higher concentrations of oxytocin (2 and 20 nM) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)-cis diltiazem (10 microM), oxytocin (0.2, 2 and 20 nM) produced graded tonic spasm without spike activity. Oxytocin (0.2 nM) produced a small increase in 45Ca2+ influx into myometrium as assessed by the 'lanthanum method'. Higher concentrations of oxytocin (2 and 20 nM) did not increase 45Ca2+ influx. It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca2+ influx via voltage-dependent Ca2+ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca2+ influx. All of the spasmogenic response to KCl can be explained by Ca2+ influx through voltage-dependent Ca2+ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.

Myelomeningocele at the sacral level. Long-term outcomes in adults.

We reviewed the long-term outcome of thirty-six patients who had a myelomeningocele at the sacral level and whose average age was twenty-nine years (range, nineteen to fifty-one years). The patients were followed at our institution for an average of ten years (range, one to thirty-three years); however, the medical records from birth on were available for all of the patients. Instead of the expected outcome that function had been maintained in this group of patients, we found a decline in the ability to walk of eleven of the thirty-five patients who had been community ambulators initially. At the time of the most recent follow-up examination, five had become household ambulators, two were non-functional ambulators, and four were non-ambulators. The one patient who initially had been a household ambulator was a non-ambulator at the time of the most recent follow-up examination. A decrease in plantar flexion was found in fourteen patients and a decrease in plantar sensation, in fifteen. Breakdown of the skin and soft-tissue infections on the plantar surface of the metatarsal heads and of the heel were seen in twenty-seven and twenty-three patients, respectively, and were related to the absence of plantar sensation. Fifteen patients had osteomyelitis involving the lower extremity. Eleven patients had had a total of fourteen amputations: five involved one toe or more, four involved one ray or more, two were Syme amputations, and three were below-the-knee amputations. By the most recent follow-up examination, thirty-three patients had had a total of 371 orthopaedic procedures. The procedures included tendinous procedures; osteotomies; soft-tissue releases, transfers, and débridements; amputations; and arthrodeses of the lower extremities or spine.

Elastomeric valves, a new design.

The convex bileaflet valve replaces the flat biflap inflow valve designed by Long Sheng Yu and the tricusp semilunair outflow valve. One reason is easier manufacturing. Convex bileaflet valves are developed for the 11, 20, 40, 70 and 140cc ventricles. Testing included curves (Cardiac Output versus Venous Pressure, Cardiac Output versus Heart rate), flow visualization studies, paint and bloodbag studies. The curves and flow visualization were done by connecting ventricles to one of our standard mock circulations. Paint and bloodbag studies were done by connecting the hearts to a bloodbag, but the bag was filled with water for the paint studies. The curves show high cardiac output, even with pumping at high heart rates (150 BPM+). The flow visualization shows a good stream through the sinus Valsalvae. No stagnating flow is visible. The bloodbag studies which provoke thrombosis show it on the edges of the heart valves, and little in the groove between the valve and the sinus Valsalvae. Heparninzation prevents the thrombosis. Results of our tests were good. The convex bileaflet valve seems to have good future.

[Ischaemia of the lower limbs: anaesthesia and intensive care]. / Anesthésie-réanimation d'un patient en ischémie aiguë des membres inférieurs.

OBJECTIVES: To appreciate the severity of a patient with acute limb ischaemia, to know how to manage these patients during the perioperative period. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: acute limb, ischaemia, prognosis, complications, rhabdomyolysis, hyperkalaemia, compartment syndrome, fasciotomy. DATA SYNTHESIS: Ischaemia of the lower limbs is a medico-surgical emergency. The ischaemia implies a decrease of cellular energetic stocks and an increase in intracellular calcium. During reperfusion, the calcium paradox is exacerbated and ROS formation produces membrane damage. Tissue oedema and a local and general inflammatory syndrome occur. Clinical symptoms of acute ischaemia include pallor, pulselessness, decrease of temperature and pain. Occurrence of neurological symptoms is a sign of severity. Prognosis of patients relates directly to preexisting collateral circulation, aetiology of the occlusion (thrombosis vs embolus), duration of ischaemia, topography of the occlusion (severity of proximal occlusions as the acute aortic occlusion), and co-morbidity (renal failure, heart failure). The temperature of the ischaemic limb, quality of the downstream circulation, extension of the thrombus, arterial pressure and association to a venous thrombosis are other prognostic factors of lower limb ischaemia. The first treatment to be initiated is high doses of heparin. Once the diagnosis is made, the number of preoperative tests will be as small as possible because of the urgency of revascularization. Arteriography will be performed only when really needed and when its realization will not delay revascularization and will not alter the patient's prognosis. Where general anesthesia is required, the choice of anaesthetic agents will be based on their haemodynamic stability. During severe acute limb ischaemia, monitoring of invasive pressure is recommended, as well as regular dosages of potassium, arterial gases and CPK. Preoperatively in case of severe ischaemia, (proximal occlusion lasting more than 6 hours), preventive treatment, including controlled reperfusion with heparinized serum is indicated. Surveillance and prevention of a rhabdomyolysis and renal failure are imperative. Immediately after reperfusion, a dosage of potassium must be performed; moreover that hyperkalaemia is favoured by acidosis or renal failure. Postoperative haemodialysis is performed in case of hyperkalaemia or renal failure. Occurrence of compartment syndrome has to be checked and fasciotomy must be performed in case of a doubt on the microcirculation integrity.