Does epidural analgesia influence the mode of delivery in primiparae managed actively? A preliminary study of 1250 women

We studied 1250 primiparous women with a singleton pregnancy, gestational age at delivery of 37-42 weeks, with a single live fetus, vertex presentation whose first and second stages of labour were managed according to strict criteria for the active management of labour. 568 (45%) received epidural analgesia (bupivacaine 0.25%) during labour, and the other 682 (55%) received either Entonox, pethidine or no analgesia. The spontaneous vaginal delivery rate in the epidural group was 67% (95% confidence interval [CI] 63-71%), lower than that in the non-epidural group (87%, 95% CI 84-90%). All instrumental delivery rates were higher in the epidural group. However, the rotational forceps rate in the epidural group (2.5%, 95% CI 1.4-4.1%) was only marginally higher than in the non-epidural group (0.9%, 95% CI 0.3-1.9%). Women who were induced were more likely to request an epidural (56%: 95% CI 50-61%) than those with spontaneous onset of labour (41%: 95% CI 38-45%). Whether labour was spontaneous or induced, a higher proportion of women who received epidural required oxytocin augmentation. The effects of combinations of epidural analgesia, the need for oxytocin augmentation and induction of labour on mode of delivery were additive. This preliminary study suggests that a high rate of spontaneous vaginal delivery can be achieved with epidural analgesia when labour is actively managed.     

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.      

Timely Hepatitis C RNA Testing and Treatment in the Era of Direct-Acting Antiviral Therapy among People with Hepatitis C in New South Wales,Australia

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Sustained stoichiometric imbalance and its ecological consequences in a large oligotrophic lake

Considerable attention is given to absolute nutrient levels in lakes, rivers, and oceans, but less is paid to their relative concentrations, their nitrogen:phosphorus (N:P) stoichiometry, and the consequences of imbalanced stoichiometry. Here, we report 38 y of nutrient dynamics in Flathead Lake, a large oligotrophic lake in Montana, and its inflows. While nutrient levels were low, the lake had sustained high total N: total P ratios (TN:TP: 60 to 90:1 molar) throughout the observation period. N and P loading to the lake as well as loading N:P ratios varied considerably among years but showed no systematic long-term trend. Surprisingly, TN:TP ratios in river inflows were consistently lower than in the lake, suggesting that forms of P in riverine loading are removed preferentially to N. In-lake processes, such as differential sedimentation of P relative to N or accumulation of fixed N in excess of denitrification, likely also operate to maintain the lake’s high TN:TP ratios. Regardless of causes, the lake’s stoichiometric imbalance is manifested in P limitation of phytoplankton growth during early and midsummer, resulting in high C:P and N:P ratios in suspended particulate matter that propagate P limitation to zooplankton. Finally, the lake’s imbalanced N:P stoichiometry appears to raise the potential for aerobic methane production via metabolism of phosphonate compounds by P-limited microbes. These data highlight the importance of not only absolute N and P levels in aquatic ecosystems, but also their stoichiometric balance, and they call attention to potential management implications of high N:P ratios.

The emergence of the Anthropocene era has been marked by major changes in all of Earth’s major biogeochemical cycles (1). For example, fluxes of carbon (C) (as CO₂) to the atmosphere have increased by ∼14% during the last 120 y largely due to fossil fuel combustion. Fluxes of nitrogen (N) into the biosphere have increased by at least 100% due to application of the Haber-Bosch reaction for fertilizer production, land use change favoring N-fixing legumes, and conversion of atmospheric N₂ to available forms (NO_x) by high temperature combustion of petroleum and fossil gas (2). Finally, large-scale mining of phosphorus (P)-rich geological deposits for production of fertilizers has amplified rates of P cycling in the biosphere by ∼400% (1). Each of these perturbations has biophysical and ecological impacts at differing time and space scales. For C, its accumulation in the atmosphere has altered Earth’s radiative balance, warming the planet and perturbing precipitation patterns globally. Amplified inputs of reactive N to the Earth system enter the hydrosphere and, thus, potentially lead to overenrichment of lakes, rivers, and coastal oceans across broad regions. Amplifications of P inputs often impair water quality at watershed and local scales (3), stimulating phytoplankton production and contributing, along with N, to harmful algal blooms, fish kills, and “dead zones” (4, 5). These differential amplifications and their contrasting spatial scales indicate that ecosystems are experiencing not only absolute changes in biogeochemical cycling, but also perturbations in the relative inputs and outputs of biologically important elements (6). Studies of elemental coupling and uncoupling in ecosystems are not yet widespread, but emerging work has shown how C, N, and P are differentially processed as they pass through watersheds (7).The potential for differential alteration in supplies of N and P to aquatic ecosystems suggests that understanding the nutrient status of a water body requires knowledge of not only absolute supplies of limiting nutrients, but also their relative proportions (i.e., their N:P stoichiometry). This work has been facilitated in recent years by the emergence of the theory of ecological stoichiometry (8). For example, seminal work by Redfield (9) found that N:P ratios in marine organic matter were tightly constrained around 16:1 (molar, here and throughout), a value that may represent the central tendency for the N:P ratio of phytoplankton undergoing balanced growth in which major pools of N (protein) and P (RNA) are produced at the same rate (10). In lakes, N:P ratios show much wider variation—around a value of ∼30—perhaps reflecting the biogeochemical connections of lakes to terrestrial systems where N:P ratios have a similar value and range of variation (11). Nevertheless, this classic “Redfield ratio” of 16:1 can be thought of as representing a balanced nutrient supply for primary producers in pelagic ecosystems. When the ratios of N and P supplied deviate from this balanced ratio, primary limitation of growth by N (when N:P is low) or by P (when N:P is high) can occur. For example, phytoplankton growth in lakes with imbalanced total N: total P (TN:TP) ratios that exceed 30:1 is generally P limited (12). Disproportionate inputs of N relative to P from atmospheric deposition can increase lake TN:TP ratios and shift lake phytoplankton from N to P limitation (13), inducing P limitation in zooplankton (14). Imbalanced N:P ratios in nutrient supplies can also shift the competitive advantage among phytoplankton and enhance production of potentially toxic compounds during harmful algal blooms. For example, skewed supplies of N relative to P can increase production of N-rich secondary compounds by phytoplankton, while disproportionate inputs of P relative to N can induce production of C-based toxins (15). High N:P ratios can also enhance proliferation of fungal parasites of phytoplankton (16).Imbalanced N:P ratios can impact aquatic ecosystems in other ways. For example, they can alter the functioning of food webs. In particular, shifts in nutrient supply regimes that enhance P limitation can impede energy flow in trophic interactions because biomass of P-limited primary producers is of low quality for animals due to its low P content (8). Ecosystem shifts to high N:P ratios and more prevalent P limitation can also impact the cycling of the greenhouse-active gas methane (CH₄) because phosphate limitation can result in production of methane under aerobic conditions in both marine and freshwater phytoplankton and bacteria (17, 18). Both chemoheterotrophic and photoautotrophic bacteria (e.g., Pseudomonas, SAR11, Trichodesmium, Synechococcus) can metabolize organic P compounds, called phosphonates, to acquire P. Microbial cleavage of one type of phosphonate, methylphosphonic acid (MPn), to acquire P results in formation of methane (17). While it is likely that anaerobic methane production due to oxygen depletion in response to P-driven eutrophication is the dominant process connecting P to methane dynamics, the significance of aerobic phosphonate metabolism to global methane cycles remains to be assessed. However, contributions are potentially large, given the prevalence of P limitation in both freshwater and marine ecosystems. In light of emerging trends that suggest overall increases in ecosystem N:P ratios due to human impacts (6), these trophic and biogeochemical impacts of stoichiometric imbalance show that it is critical to consider not only absolute levels of nutrients, but also their stoichiometry. In particular, high N:P ratios can accentuate P limitation, causing a suite of ecological impacts that, currently, are poorly described.In this paper, we illustrate the utility of stoichiometric approaches by combining analyses of long-term records of nutrient supply and dynamics, together with contemporary experiments, to examine how imbalances in N:P stoichiometry (e.g., strong divergence from classic Redfield proportions) influence plankton ecology and biogeochemistry across multiple scales in Flathead Lake, a large lake in western Montana. The lake is itself relatively unperturbed by human impacts and, thus, maintains low overall nutrient levels. However, the strong stoichiometric imbalance that we describe makes Flathead Lake appropriate for assessing ecosystem consequences of what appear to be general trends of increasing N:P ratios in global ecosystems (6). Numerous limnological properties of the lake and its inflow rivers have been monitored continuously for several decades, including concentrations of various forms of N and P. Thus, these time-series data allow us not only to assess long-term variability or stability in the stoichiometry of N and P in the lake and its river inflows over decadal time scales, but also to connect its stoichiometry with potential consequences for nutrient limitation, food web dynamics, and biogeochemical cycling under low-nutrient conditions.     

Lipid peroxidation induced by N-acetylcysteine in isolated rat hepatocytes

In isolated rat hepatocytes N-acetylcysteine induces an increase of lipid peroxidation, as evaluated by the malondialdehyde production and diene conjugation. Lipid peroxidation did not result in increased cell mortality. Antioxidants and free radicals scavengers completely protect toward lipid peroxidation induced by N-acetylcysteine.     

Spiral CT angiography and surgical correlations in the evaluation of intracranial aneurysms

We investigated the accuracy of spiral computed tomography angiography (CTA) in the detection and study of intracranial aneurysms by comparing CTA with selective angiograms and surgical findings. Twenty-six patients (9 men and 17 women; mean age 53.1 ± 1.8 years) with suspected intracranial aneurysms were submitted to CTA (1- to 2-mm slices, pitch 1:1, 24 s, RI = 1) after a conventional CT examination showing subarachnoid hemorrhage (SAH) in 19 cases and during neuroradiological investigations performed for other reasons in 7 cases. One hundred twenty to 150 ml iodate contrast agent (0.3–0.4 gI/ml) were injected intravenously at 5 ml/s rate and with 12- to 25-s delay calculated with a preliminary test bolus. Three-dimensional shaded surface display (3D SSD) and maximum intensity projection (MIP) reconstructions were obtained from axial images. Then, within 48 h, all patients were submitted to digital subtraction angiography (DSA), with separate assessment of CTA and DSA findings. Twenty-two aneurysms shown by CTA were confirmed at DSA and surgery (true positives), whereas the vascular lesion was not confirmed at DSA in 2 cases (false positives). The presence of intracranial aneurysms was excluded at both CTA and subsequent DSA in 7 cases (true negatives) and there were no false negatives; sensitivity was 100 %, specificity 77.8 %, and diagnostic accuracy 93.5 %. Computed tomography angiography aneurysm location was confirmed at surgery in all cases, with very high accuracy in assessing the presence of an aneurysm neck (100 %). Computed tomography angiography accurately depicted the aneurysm shape in 20 of 22 cases, but failed to depict its multilobed nature in 2 cases. The mean aneurysm diameter calculated at CTA was 0.99 ± 0.12 cm vs 1.09 ± 0.11 cm at surgery (p < 0.01). The present results suggest that the high sensitivity of CTA, if confirmed by further studies, might help in avoiding having to resort to arteriography after negative CTA in SAH patients. Received 15 July 1997; Revision received 30 September 1997; Accepted 5 November 1997