Maternal uterine artery Doppler flow velocimetry and the risk of stillbirth

OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine artery Doppler flow velocimetry at 22-24 weeks. METHODS: Data were available from 30,519 unselected women from seven units in the UK who had uterine artery Doppler performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109) was assessed using time to event and logistic regression analysis. Stillbirths were subdivided into placental (due to abruption, preeclampsia, or growth restriction) or unexplained. RESULTS: The risk of placental stillbirth was increased among women with a mean pulsatility index in the top decile (adjusted hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8-10.6) and those with a bilateral notch (adjusted HR 3.9, 95% CI 2.0-7.8). The relationship between a mean pulsatility index in the top decile and the risk of unexplained stillbirth was weaker (adjusted HR 2.5, 95% CI 1.1-5.6) and there was no association with a bilateral notch. Placental stillbirths occurred at earlier gestations than unexplained stillbirths (median [interquartile range] 30 [26-36] compared with 38 [36-40], P<.001). Consequently, being in the top 5% of predicted risk of stillbirth on the basis of the combination of mean pulsatility index and notching was a good predictor (sensitivity, specificity, and positive likelihood ratio) of all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively). CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of stillbirth due to placental causes than unexplained stillbirth. Consequently, abnormal uterine artery Doppler was a good predictor of stillbirth at extreme preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE: II.     

Best Evidence Medical and Health Professional Education (BEME) collaboration: A moving spotlight

Early this year, a Massachusetts Institute of Technology professor of philosophy presented a new theory of time that caught our interest. One of the key concepts that Professor Skow presented is the “moving spotlight” theory. As Skow asserts, the experiences had a year ago or 10 years ago are still just as real, they’re just “inaccessible” because they are now in a different part of spacetime. This was felt to be an elegant notion to inform this ‘spotlight’ piece on BEME (www.bemecollaboration.org).     

Trends in recent systemic lupus erythematosus mortality rates

National death rates from systemic lupus erythematosus (SLE) were calculated for the period 1972 to 1976 according to age, sex, and race and were compared to rates for 1968 to mid-1972. The time trend in the age-adjusted death rates from SLE was also analyzed for the entire period 1968 to 1977. The previously reported variable sex and race ratios persist through the recent period, particularly the greater mortality rates among black women during middle and early adulthood. An overall decline in the adjusted death rates in the younger age groups (1–49 years old) in each race-sex group is seen in the recent period.     

Coupled CH4 production and oxidation support CO2 supersaturation in a tropical flood pulse lake (Tonle Sap Lake,Cambodia)

Carbon dioxide (CO₂) supersaturation in lakes and rivers worldwide is commonly attributed to terrestrial–aquatic transfers of organic and inorganic carbon (C) and subsequent, in situ aerobic respiration. Methane (CH₄) production and oxidation also contribute CO₂ to freshwaters, yet this remains largely unquantified. Flood pulse lakes and rivers in the tropics are hypothesized to receive large inputs of dissolved CO₂ and CH₄ from floodplains characterized by hypoxia and reducing conditions. We measured stable C isotopes of CO₂ and CH₄, aerobic respiration, and CH₄ production and oxidation during two flood stages in Tonle Sap Lake (Cambodia) to determine whether dissolved CO₂ in this tropical flood pulse ecosystem has a methanogenic origin. Mean CO₂ supersaturation of 11,000 ± 9,000 μatm could not be explained by aerobic respiration alone. ¹³C depletion of dissolved CO₂ relative to other sources of organic and inorganic C, together with corresponding ¹³C enrichment of CH₄, suggested extensive CH₄ oxidation. A stable isotope-mixing model shows that the oxidation of ¹³C depleted CH₄ to CO₂ contributes between 47 and 67% of dissolved CO₂ in Tonle Sap Lake. ¹³C depletion of dissolved CO₂ was correlated to independently measured rates of CH₄ production and oxidation within the water column and underlying lake sediments. However, mass balance indicates that most of this CH₄ production and oxidation occurs elsewhere, within inundated soils and other floodplain habitats. Seasonal inundation of floodplains is a common feature of tropical freshwaters, where high reported CO₂ supersaturation and atmospheric emissions may be explained in part by coupled CH₄ production and oxidation.

Globally, most lakes and rivers are supersaturated with dissolved carbon dioxide (CO₂) relative to the atmosphere, highlighting their outsized role in transferring and transforming terrestrial carbon (C) (1–3). Terrestrial–aquatic transfers of C can include CO₂ dissolved in terrestrial ground and surface waters (3–6), dissolved inorganic carbon (DIC) from carbonate weathering (7, 8), or organic C from various sources that is subsequently respired in lakes and rivers (9, 10). Initially, oceanic export was thought to be the only fate for terrestrial–aquatic transfers of C, but a growing body of research on sediment burial of organic C and CO₂ emissions from freshwaters prompted the “active pipe” revision to this initial set of assumptions (11). Although freshwaters are now recognized as focal points for transferring and transforming C on the landscape, most of this research has been conducted within temperate freshwaters (2, 11, 12). Few studies focus on the mechanisms of CO₂ supersaturation in tropical lakes and rivers, with most conducted in just one watershed, the Amazon (4, 13–15).CO₂ supersaturation within tropical freshwaters is likely influenced by their unique flood pulse hydrology. The canonical flood pulse concept hypothesizes that annual flooding of riparian land will lead to organic C mobilization and respiration (16). Partial pressures of CO₂ (pCO₂) have been measured in excess of 44,000 μatm in the Amazon River (13), 16,000 μatm in the Congo River (17), and 12,000 μatm in the Lukulu River (17). Richey et al. (13), Borges et al. (18), and Zuidgeest et al. (17) have each shown that that riverine pCO₂ scales with the amount of land flooded in these watersheds. Yet it was only recently that Abril and Borges (19) proposed the importance of flooded land to the “active pipe.” These authors differentiate uplands that unidirectionally drain water downhill (via ground and surface water) from floodplains that bidirectionally exchange water with lakes and rivers (19). They conceptualize how floodplains combine high hydrologic connectivity, high rates of primary production, and high rates of respiration to transfer relatively large amounts of C to tropical freshwaters (19).Methanogenesis inevitably results on floodplains after dissolved oxygen (O₂) and other electron acceptors for anaerobic respiration such as iron and sulfate are consumed (16, 19). Horizontal gradients in dissolved O₂ and reducing conditions have been observed extending from the center of lakes and rivers through their floodplains in the Mekong (20, 21), Congo (22), Pantanal (23), and Amazon watersheds (4). CH₄ production and oxidation occur along such redox gradients (4, 16, 19, 23). CH₄ is produced by acetate fermentation (Eq. 1) and carbonate reduction (Eq. 2) within freshwaters (24, 25). CH₄ production coupled with aerobic oxidation results in CO₂ (Eq. 3 and ref. 25), yet no studies have quantified the relative contribution of coupled CH₄ production and oxidation to CO₂ supersaturation within tropical freshwaters.CH3COOH→CO2+CH4,[1]CO2+8H++8e−→CH4+2H2O,[2]CH4+2O2→CO2+2H2O.[3]The relative contribution of coupled CH₄ production and oxidation to CO₂ supersaturation within tropical freshwaters can be traced with stable C isotopes of CO₂ and CH₄. Methanogenesis results in CH₄ that is depleted in ¹³C (δ¹³C = −65 to −50‰ from acetate fermentation and −110 to −60‰ from carbonate reduction) compared to other potential sources of organic and inorganic C (δ¹³C = −37 to −7.7‰; see Materials and Methods) (24–26). The oxidation of this ¹³C-depleted CH₄ results in ¹³C-depleted CO₂ (24–26). At the same time, CH₄ oxidation enriches the ¹³C/¹²C of residual CH₄ as bacteria and archaea preferentially oxidize ¹²C-CH₄ (25). This means that the ¹³C/¹²C of CO₂ and CH₄ can serve as powerful tools to determine the source of CO₂ supersaturation within freshwaters.Tonle Sap Lake (TSL) is Southeast Asia’s largest lake and an understudied flood pulse ecosystem that supports a regionally important fishery (21, 22, 27). Each May through October, monsoonal rains and Himalayan snowmelt increase discharge in the Mekong River and cause one of its tributaries, the Tonle Sap River, to reverse course from southeast to northwest (21). During this course reversal, the Tonle Sap River floods TSL. The TSL flood pulse increases lake volume from 1.6 to 60 km³ and inundates 12,000 km² of floodplain for 3 to 6 mo per year (21, 27). Holtgrieve et al. (22) have shown that aerobic respiration is consistently greater than primary production in TSL (i.e., net heterotrophy), with the expectation of consistent CO₂ supersaturation. But, the partial pressures, C isotopic compositions, and ultimately the source of dissolved CO₂ in TSL remain unquantified.To quantify CO₂ supersaturation and its origins in TSL, we measured the partial pressures of CO₂ and CH₄ and compared their C isotopic composition to other potential sources of organic and inorganic C. We carried out these measurements in distinct lake environments during the high-water and falling-water stages of the flood pulse, hypothesizing that CH₄ production and oxidation on the TSL floodplain would support CO₂ supersaturation during the high-water stage. We found that coupled CH₄ production and oxidation account for a nontrivial proportion of the total dissolved CO₂ in all TSL environments and during both flood stages, showing that anaerobic degradation of organic C at aquatic–terrestrial transitions can support CO₂ supersaturation within tropical freshwaters.     

Measuring progress to healing: A challenge and an opportunity

Complete healing is problematic as an endpoint for evaluating interventions for wound healing. The great heterogeneity of wounds makes it difficult to match groups, and this is only possible with multivariate stratification and/or very large numbers of subjects. The substantial time taken for wounds to heal necessitates a very lengthy study. Consequently, high quality randomised controlled trials demonstrating an effect of an intervention to a satisfactory level of statistical significance and with a satisfactory level of generalisability are extremely rare. This study determines that the healing of venous leg ulcers receiving multi‐component compression bandaging follows a linear trajectory over a 4‐week period, as measured by gross area healed, percentage area healed, and advance of the wound margin. The linear trajectories of these surrogates make it possible to identify an acceleration in healing resulting from an intervention, and allows self‐controlled or crossover designs with attendant advantages of statistical power and speed. Of the metrics investigated, wound margin advance was the most linear, and was also independent of initial ulcer size.     

A controlled study of plasma exchange in the treatment of severe rheumatoid arthritis

To learn whether the removal of immune complexes from the circulation by plasma exchange could effect an improvement in disease activity in rheumatoid arthritis (RA) patients, we performed a controlled study of 20 patients with severe progressive disease which had not responded to previous therapy. Ten patients (Group 1) were hospitalized, continued on their regular antiinflammatory medication, and given a graded course of physiotherapy. A further 10 patients (Group 2) received the same treatment as the first group with the addition of a concurrent course of plasmapheresis. Clinical measurement of disease activity after treatment revealed little difference between the two groups with a statistically significant improvement in four measures in Group 1 and in five in Group 2. Laboratory studies suggested that the intensity of plasma exchange was sufficient to remove circulating immune complexes in these patients. Our results confirm that hospitalization in itself is of benefit in the treatment of acute exacerbations of rheumatoid arthritis. The marginal improvement achieved by the addition of plasma exchange in the management of these patients (despite the removal of circulating immune complexes) makes its short-term use of questionable value in the treatment of severe rheumatoid arthritis.     

Benign hepatic cyst in a patient on antiestrogen therapy for metastatic breast cancer

Tamoxifen is a useful agent in the management of metastatic breast cancer. We describe a patient who was treated sucessfully with Tamoxifen but developed a benign but symptomatic hepatic cyst during treatment. Development of a solitary hepatic lesion during Tamoxifen therapy should be thoroughly investigated before treatment is changed. Cancer 50:1882-1883, 1982.     

Associative thinking in schizophrenia: A contextualist approach

Explored the question of whether responses that appeared to be highly pathological on the basis of the word association test did indeed reflect an underlying aberrant associative process or whether the associations actually had a greater degree of meaning than was evident from the test (N = 60). Utilizing contextualist techniques designed by the authors, which were analogous to the word association test but yet measured schizophrenic associative thinking in specific contexts that more closely approximated natural language situations, the quality and purposiveness of the schizophrenics' associations were examined. The word association test technique was judged to be inadequate by itself to account for underlying associative processes involved in schizophrenic associative thought disorder. A majority of responses (70% schizophrenic, 81% nonschizophrenic) judged to be pathological on the basis of the word association test alone became meaningful in the context of a sentence created by the Ss to explain purposively their associations. The schizophrenics' experience of a stimulus word and consequent associations to that word became clearer when placed within an appropriate context (i.e., a sentence), rather than examined as isolated semantic features (as in the word association test).