Interventions at caesarean section for reducing the risk of aspiration pneumonitis.

BACKGROUND: Various interventions are used as prophylaxis for aspiration pneumonitis in obstetric anaesthesia. This review, based on a Cochrane systematic review currently being updated, examines whether interventions given before caesarean section reduce the risk of aspiration pneumonitis. METHODS: Twenty-two studies, involving 2658 women providing data in a usable format for meta-analysis were identified. RESULTS: Compared to no treatment or placebo, there was a significant reduction in the risk of intra-gastric pH <2.5 with antacids (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.09-0.32), H2 antagonists (RR 0.09, 95% CI 0.05-0.18) and proton-pump antagonists (RR 0.26, 95% CI 0.14-0.46). H2 antagonists were associated with a reduced risk of intra-gastric pH <2.5 when compared with proton-pump antagonists (RR 0.39, 95% CI 0.16-0.97), but compared with antacids the findings were unclear. Combined use of antacids plus H2 antagonists was associated with a significant reduction in the risk of intra-gastric pH <2.5 when compared with placebo (RR 0.02, 95% CI 0.00-0.15) or compared with antacids alone (RR 0.12, 95% CI 0.02-0.92). CONCLUSION: The quality of evidence was weak and may not reflect a reduction in the risk of aspiration pneumonitis since none of the studies assessed substantive clinical outcomes or potential adverse effects. Further work is required to validate the suitability of surrogate markers of pH and gastric volume for clinical outcomes in the context of aspiration pneumonitis.

The power of hope: being a doctor is more than relying solely on the numbers.

AIMS: To ascertain whether a physician's positive or negative attitude significantly impacts the quality of life of ophthalmic patients. METHODS: A standardised, validated, time trade-off, utility instrument was administered to consecutive vitreoretinal patients by interview to assess the quality of life associated with their current ocular health state (baseline scenario). Each was then given a scenario for the exact same health state with the same long-term prognosis in which their doctor emphasised the possible negative consequences (bad-news scenario) and one for the same health state in which their doctor emphasised the positive consequences (good-news scenario). RESULTS: Among the 247 patients enrolled were 140 women (57%) and 107 men (43%) with a mean age of 66 years and a mean educational level of 13.8 years after kindergarten. The mean baseline utility for 247 patients was 0.87 (SD = 0.19; 95% CI 0.84 to 0.89). The mean bad-news scenario utility was 0.80 (SD = 0.22, 95% CI 0.78 to 0.83), a 70% diminution in quality of life compared with the mean baseline utility (p = 0.0009). The mean good-news scenario utility was 0.89 (SD = 0.18, 95% CI 0.86 to 0.91), an insignificant difference compared with the mean baseline utility (p = 0.26). CONCLUSION: Ocular patients had a considerably poorer quality of life when their physician emphasised the possible negative consequences associated with their eye disease(s), as opposed to a more positive approach. While at times necessary, a negative emphasis approach can theoretically result in a considerable loss of life's value.

The effect of comorbidities upon ocular and systemic health-related quality of life.

AIM: The purpose of the study was to assess whether, and to what degree, comorbidities affect patient quality of life. METHODS: A cross-sectional, quality-of-life study of 170 consecutive vitreoretinal patients compared the utility associated with a participant's primary (most incapacitating) disease and the utility associated with a grouping of all of the participants' diseases. The ocular diseases present included diabetic retinopathy (44%), macular degeneration (30%), lattice degeneration/retinal tear (14%), retinal vascular obstruction (5%), uveitis, macular oedema, macular pucker (5%) and others (2%). Participants underwent interviewer-administered, time trade-off utility questions for each disease, then for a compilation of all diseases. Their primary disease was defined by the lowest utility reported for a single disease, while other health conditions were considered comorbidities. A two-tailed, paired t test was used to compare the means of the primary disease utilities and compilation utilities. The study was powered to have a 90% chance of detecting an 8% difference in mean utility between the two utility groups RESULTS: The mean lowest utility for the most disabling single health condition (primary disease) was 0.82 (SD 0.22; 95% CI 0.79 to 0.85. The mean utility for the grouping together of all diseases was 0.80 (SD 0.24, 95% CI 0.76 to 0.84). No significant difference was found between the mean utilities of the two groups (p = 0.56). CONCLUSIONS: The overall health-related quality of life of a patient in an ophthalmic population with serious diseases appears to be primarily determined by the single disease that most adversely affects the individual's quality of life. This conclusion has significant implications in clinical care and when considering the use of comorbidities in cost-utility analyses.

Giving women their own case notes to carry during pregnancy.

BACKGROUND: In many countries women are given their own case notes to carry during pregnancy so as to increase their sense of control and satisfaction with their care. OBJECTIVES: To evaluate the effects of giving women their own case notes to carry during pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (January 2004). SELECTION CRITERIA: Randomised controlled trials of women given their own case notes to carry during pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria and assessed study quality. One reviewer extracted data from the included studies using a standard form (checked by second reviewer). We assessed estimates of effect using relative risk with 95% confidence intervals. MAIN RESULTS: Three trials were included (n = 675 women). Women carrying their own notes were more likely to feel in control (relative risk (RR) 1.56, 95% confidence interval (CI) 1.18 to 2.06). Women's satisfaction: one trial reported more women in the case notes group (66/95) were satisfied with their care than the control group (58/102) (RR 1.22, 95% CI 0.99 to 1.52); two trials reported no difference in women's satisfaction (one trial provided no data and one trial used a 17 point satisfaction scale). More women in the case notes group wanted to carry their own notes in a subsequent pregnancy (RR 1.79, 95% CI 1.43 to 2.24). Overall, the pooled estimate of the two trials (n = 347) that reported on the risk of notes lost or left at home was not significant (RR 0.38, 95% CI 0.04 to 3.84). There was no difference for health related behaviours (cigarette smoking and breastfeeding), analgesia needs during labour, miscarriage, stillbirth and neonatal deaths. More women in the case notes group had operative deliveries (RR 1.83, 95% CI 1.08 to 3.12). REVIEWERS' CONCLUSIONS: The three trials are small, and not all of them reported on all outcomes. The results suggest that there are both potential benefits (increased maternal control and satisfaction during pregnancy, increased availability of antenatal records during hospital attendance) and harms (more operative deliveries). Importantly, all of the trials report that more women in the case notes group would prefer to hold their antenatal records in another pregnancy. There is insufficient evidence on health related behaviours (smoking and breastfeeding) and clinical outcomes. It is important to emphasise that this review shows a lack of evidence of benefit rather than evidence of no benefit.

Management of incomplete abortion in South African public hospitals.

OBJECTIVE: To describe the current management of incomplete abortion in South African public hospitals and to discuss the extent to which management is clinically appropriate. DESIGN: A multicentre, prospective descriptive study. SETTING: South African public hospitals that manage gynaecological emergencies. SAMPLE: Hospitals were selected using a stratified random sampling method. All women who presented to the above sampled hospitals with incomplete abortion during the three week data collection period in 2000 were included. METHODS: A data collection sheet was completed at the time of discharge for each woman admitted with a diagnosis of incomplete, complete, missed or inevitable abortion during the study period. Information gathered included demographic data, clinical signs and symptoms at admission, medical management, surgical management, anaestetic management, use of blood products and antibiotics and complications. Three clinical severity categories were used for the purpose of data analysis and interpretation. MAIN OUTCOME MEASURES: Detail of medical management, detail of surgical management, use of blood products and antibiotics, methods of analgesia and anaesthesia used, and use of abortifacients. RESULTS: There is a trend towards low cost technology such as the use of manual vacuum aspiration and sedation anaesthesia; however, this is mainly limited to the better resourced tertiary hospitals linked to academic units. The use of antibiotics and blood products has decreased but much of the use is inappropriate. The use of abortifacients does include some use of misoprostol but merely as an adjunct to surgical evacuation. CONCLUSIONS: The management of incomplete abortion remains a problem in South Africa, a low income country that is still managing a common clinical problem with costly interventions. The evidence of a trend towards low cost technology is promising, albeit limited to tertiary centres. This study has given us information as how to best address this problem. More training in low cost methods is needed, targeting in particular the district and regional hospitals, and reinforced by skills training focussed mainly on undergraduates and midwife post-abortion care programmes.

Hydroboration. 97. Synthesis of new exceptional chloroborane--Lewis base adducts for hydroboration. Dioxane--monochloroborane as a superior reagent for the selective hydroboration of terminal alkenes.

Several less volatile oxygen-containing Lewis bases, such as tert-butyl methyl ether, dioxane, anisole, ethyl acetate, beta-chloroethyl ether, and monoglyme, were examined as prospective mono- and dichloroborane carriers. Dioxane, ethyl acetate, and beta-chloroethyl ether form relatively stable boron trichloride adducts, but the boron trichloride adduct of monoglyme is not very stable and must be used immediately. On the other hand, tert-butyl methyl ether and anisole fail to form stable boron trichloride adducts and the corresponding ether-cleaved products are obtained. Among the selected oxygen-containing Lewis bases, only dioxane forms stable and reactive mono- and dichloroborane adducts. Monoglyme and beta-chloroethyl ether give stable dichloroborane adducts requiring excess of diborane. Convenient methods for the preparation of mono- and dichloroborane adducts of dioxane from dioxane-BCl(3) and NaBH(4) in the presence of catalytic amounts of tri- or tetraglyme were developed. The dioxane--monochloroborane adduct hydroborates representative olefins cleanly and rapidly. The corresponding alcohols were obtained in quantitative yields after oxidation. Also, the hydroboration of several terminal olefins with dioxane--monochloroborane were highly regioselective and the primary alcohols were obtained almost exclusively (>99.5%), after oxidation. Accordingly, dioxane-monochloroborane should serve as a reagent of choice for such hydroborations. The dioxane--dichloroborane adduct showed remarkable selectivity toward 2-substituted terminal olefins, such as 2-methyl-1-butene and beta-pinene, when compared to simple terminal and hindered olefins, giving a unique tool for selective hydroborations. Dichloroborane adducts of monoglyme and beta-chloroethyl ether also showed high reactivity, even at room temperature, toward simple unhindered olefins. However, hydroboration of hindered olefins is slow and requires either higher temperatures or the addition of 1 equiv of boron trichloride to liberate free dichloroborane, as in the case of the previously known dichloroborane adducts of methyl sulfide and diethyl ether.

Molecular addition compounds. 18. Borane adducts with hydroxydialkyl sulfide borates for hydroboration. New, essentially odorless, water-soluble sulfide borane acceptors for hydroboration.

Hydroxydialkyl sulfides of general formula RS(CH2CH2)nH (R = Et, t-Bu, i-Am; n = 1-3) and thiodiethanol monomethyl ether (9) have been synthesized and used as borane carriers. The compounds 3 and 6 (R = Et, n = 2, 3), 7 (R = t-Bu, n = 3), and 9 are completely miscible with water and exhibit only very mild odor. The sulfides were transformed into the corresponding borates by treatment either with boric acid or with diborane. The borates complex 3 mol of borane per 1 mol of borate to give highly reactive, stable, liquid adducts, hydroborating 1-octene in 15 min at room temperature. The adducts derived from water soluble sulfides 3 and 9, selected for the hydroboration of more hindered olefins, reacted readily with (-)-beta-pinene, 1-methylcyclohexene, and 2,3-dimethyl-2-butene. The carrier borates liberated from the adducts during hydroboration are readily hydrolyzed to give 3 and 9, which can be washed off with water from trialkylboranes or oxidation products. Consequently, hydroxydialkyl sulfides 3 and 9 are the first completely water-soluble sulfide borane carriers that can be washed off in the workup of hydroboration products. The adducts derived from 3 and 9 are new, highly promising reagents suitable for large scale hydroborations and reductions.

Efficient intramolecular asymmetric reductions of alpha-, beta-, and gamma-keto acids with diisopinocampheylborane.

[figure: see text] alpha-, beta-, and gamma-Keto acids are reduced with diisopinocampheylborane at room temperature to the corresponding hydroxy acids with predictable stereochemistry in very high ee. The gamma-hydroxy acids produced were conveniently cyclized to the corresponding lactones. This provides a simple synthesis of 4-hexanolide, a component of the pheromone secreted by the female dermestid beetle Trogoderma glabrum.

Dexmedetomidine: a novel sedative-analgesic agent.

Since the first report of clonidine, an alpha2-adrenoceptor agonist, the indications for this class of drugs have continued to expand. In December 1999, dexmedetomidine was approved as the most recent agent in this group and was introduced into clinical practice as a short-term sedative (<24 hours). Alpha2-adrenoceptor agonists have several beneficial actions during the perioperative period. They decrease sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; reduce anesthetic and opioid requirements; and cause sedation and analgesia. They allow psychomotoric function to be preserved while letting the patient rest comfortably. With this combination of effects, alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and adjuvant treatment of perioperative myocardial ischemia. Furthermore, their role in pain management and regional anesthesia is expanding. Side effects consist of mild to moderate cardiovascular depression, with slight decreases in blood pressure and heart rate. The development of new, more selective alpha2-adrenoceptor agonists with improved side effect profiles may provide a new concept for the administration of perioperative anesthesia and analgesia. This review aims to give background information to improve understanding of the properties and applications of the novel alpha2-adrenoceptor agonist, dexmedetomidine.

Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam.

BACKGROUND: The intraerythrocytic parasite Plasmodium falciparum induces the life-threatening neurologic syndrome of cerebral malaria (CM) from within cerebral blood vessels, without entering the brain parenchyma. OBJECTIVES: 1) To assess the use of CSF as an indicator of specific pathologic processes occurring in the brain during CM; 2) to compare this with other neurologic and infectious diseases to understand the distinct pathogenic features of CM; 3) to test the hypothesis that CM involves a specific functional breakdown of the blood-brain barrier (BBB). METHODS: 1) Radial immunodiffusion assays to detect albumin and IgG in matched plasma and CSF samples as indicators of BBB integrity and intrathecal IgG production; and 2) ELISA for soluble intracellular adhesion molecule-1 and sE-selectin, the cytokines tumor necrosis factor-alpha and transforming growth factor-beta1, and the matrix metalloproteinase MMP-9, to detect cellular activation and inflammatory responses within the brain. RESULTS: Albumin and IgG indices implied only minimal degree of BBB breakdown in a few cases of CM, with most remaining within the normal range. In contrast, cryptococcal, tubercular, and acute bacterial meningitis produced detectable changes in the composition of the CSF and evidence of BBB breakdown. CONCLUSIONS: CM appears to involve only subtle functional changes in BBB integrity with minimal intraparenchymal inflammatory responses compared with other neurologic infections. This focuses attention on local events within and around the cerebral microvasculature in CM, rather than indicating widespread parenchymal disease.

Improved procedures for the generation of diborane from sodium borohydride and boron trifluoride.

Improved procedures for the generation of diborane by the reaction of NaBH4 in triglyme or tetraglyme with the BF3 adducts of di-n-butyl ether, tert-butyl methyl ether, monoglyme, dioxane, and tetrahydropyran were developed. In these systems, generation of diborane requires 2-4 h at 25 degrees C (faster reactions take place at 50 degrees C). The byproduct NaBF4 precipitates from the reaction mixture at 25 degrees C as the reaction proceeds. The high-boiling glyme can be conveniently separated from the lower boiling carrier ethers by simple distillation of the latter. On the other hand, diborane was generated very slowly or not generated using the addition of each of six boron trifluoride-etherates (di-n-butyl ether, tert-butyl methyl ether, tetrahydrofuran, tetrahydropyran, dioxane, and monoglyme) to suspensions of sodium borohydride in the corresponding ether. However, diborane was generated rapidly and quantitatively by the addition of NaBH4 in triglyme (or tetraglyme) to the BF3 adduct of triglyme (or tetraglyme) at room temperature. No solid precipitation occurs during the reaction, making it convenient for large-scale applications. The pure solvent triglyme (or tetraglyme) can be easily recovered and recycled by either crystallizing or precipitating NaBF4 from the generation flask. New procedures for the generation of diborane were also developed by the reaction of NaBF4 with NaBH4 in triglyme (or tetraglyme) in the presence of Lewis acids such as AlCl3 and BCl3.

Cost-effectiveness of treatment for threshold retinopathy of prematurity.

OBJECTIVE: Retinopathy of prematurity (ROP) is a leading cause of adverse visual outcomes in premature infants. Both laser photocoagulation and cryotherapy have been demonstrated in clinical trials to be efficacious in reducing the incidence of visual loss occurring secondary to threshold ROP. Visual data recently have become available concerning the long-term clinical efficacy of both treatments, as have data concerning the utility value of visual states in general. Accordingly, we undertook an analysis to ascertain the cost-effectiveness of laser photocoagulation and cryotherapy in the treatment of threshold ROP. DESIGN: A computer simulation economic model is presented to evaluate the cost-effectiveness of cryotherapy and laser photocoagulation therapy, compared with the natural course of the disease, for treating premature infants with threshold ROP. The model applies long-term visual data from previous clinical trials, utility analysis, decision analysis, and economic principles, such as present value analysis, to account for the time value of money to arrive at a cost per quality-adjusted life-year (QALY) gained. OUTCOME MEASURES: Cost per QALY gained from laser therapy and cryotherapy. RESULTS: Laser photocoagulation therapy for threshold ROP costs $678 1998 US dollars (at a 3% discount rate to account for the time value of money) for each QALY gained from treatment. Cryotherapy for the same disease costs $1801 per QALY at a similar discount rate. CONCLUSIONS: From the point of view of cost-effectiveness, laser therapy seems to have an advantage over cryotherapy for the treatment of threshold ROP.

The influence of plasma proteins on the distribution of leucocytes within the brain parenchyma in a murine model of stroke.

Inflammatory responses are thought to play an important role in the exacerbation of neuronal loss following stroke. Leucocyte recruitment following cerebral ischaemia has been demonstrated in experimental animals, and procedures which reduce the entry of leucocytes into the brain reduce neuronal loss and improve aspects of functional recovery in these models. In this study we investigate whether leakage of plasma proteins into the central nervous system (CNS) following ischaemia influences leucocyte adhesion within the parenchyma. Using an in vitro adhesion assay, we demonstrate that the addition of exogenous serum proteins increases macrophage adhesion to CNS tissue. Following permanent middle cerebral artery occlusion (MCAO) in mice, plasma proteins leak into the apparently healthy cortex surrounding the infarcted area. We show that there is increased macrophage adhesion to sections in the border region where endogenous plasma proteins are present within the parenchyma. Using immunohistochemistry, we co-localize plasma protein distribution within the tissue with leucocyte recruitment following MCAO. We show that monocytes, not neutrophils, infiltrate the lesion border where plasma proteins are present in the parenchyma. This distribution is compatible with their contributing to neuropathology, whereas neutrophils are found in clusters in the lesion core. We conclude that leakage of plasma proteins into the brain could influence leucocyte adhesion within the parenchyma. Recruited monocytes may exacerbate neuropathology in situations such as permanent cerebral ischaemia, where disruption of the blood-brain barrier occurs.

Differential adhesion of macrophages to white and grey matter in an in vitro assay.

Microglia, the resident macrophages of the brain, are monocytic cells whose phenotype is determined during development by the unique environment of the central nervous system (CNS). They are quiescent cells when compared with other tissue macrophages, and this downregulation may have important consequences for inflammatory and immune responses in the brain. In the search for features of the brain environment which might exert an influence on microglial behaviour, we have concentrated on the possible role of adhesion molecules. We have developed a robust and reproducible in vitro adhesion assay to look at the interaction between macrophages and brain tissue. We describe here the characterisation of this assay. By injecting agents into the brain in vivo, we were able to study the effect of perturbations in the resident cell population on the adhesion of macrophages to brain tissue in vitro. This provided strong evidence that RAW 264 cells adhere to neurones in preference to other CNS cell types in this assay, and this was confirmed by adhesion assays performed on monolayers of individual cell types. We hypothesise from these results that macrophages interact with CNS neurones in vivo via adhesion molecules, enabling them to sense and respond rapidly to pathology in the brain.

Patient perceptions of quality-of-life associated with bilateral visual loss.

PURPOSE: To ascertain whether patients with unilateral visual loss to a specific level are able to approximate the degree of impairment of quality-of-life experienced by patients with bilateral visual loss to the same level. METHODS: One hundred thirty-three study group patients with (1) visual loss to 20/40 or worse in at least one eye, and (2) a marked difference between the visual acuities in their two eyes, were polled using the time tradeoff method of utility value measurement. All patients were asked to assume that the visual acuity in both of their eyes was as poor as the visual acuity in their worst seeing eye. These utility values were then compared to those obtained from a control group of 173 patients with known utility values who had similar bilateral visual loss. Both the study and control groups were stratified into 4 levels of visual loss (20/40 to 20/50, 20/60 to 20/100, 20/200 to 20/400, and counting fingers to light perception). RESULTS: Mean utility values for the study group ranged from 0.47 to 0.71. Patients with unilateral visual loss, given the assumption of bilateral visual loss to the same degree, routinely demonstrated no significant difference in utility preferences as compared to patients with true bilateral visual loss to the same level. CONCLUSIONS: Patients with unilateral visual loss can very accurately estimate the degree of impairment of quality-of-life that would result if visual loss to a similar degree occurred in the remaining eye with better vision.

The blood-brain barrier and the inflammatory response.

The environment of the brain is controlled by a sophisticated endothelial barrier that prevents the free entry of solutes from the blood. It is commonly assumed that this blood-brain barrier (BBB) also prevents the entry of leukocytes into the central nervous system. However, recent evidence in animal models shows that this is not the case, and leukocytes can cross an intact BBB during health and disease. Indeed, in many neurological diseases, including Alzheimer's disease, prion diseases and AIDS-related dementia, leukocytes enter the brain parenchyma without concomitant BBB breakdown. Current research is concentrating on factors that control the integrity of the BBB and the mechanisms that leukocytes use to enter the brain.

Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system.

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.

Biomechanical and clinical performance of a new synthetic monofilament absorbable suture.

The clinical and mechanical performance of a new, monofilament, synthetic absorbable suture (Biosyn) was evaluated and compared to that of a braided synthetic absorbable suture (Vicryl). The monofilament synthetic absorbable suture was significantly stronger than the braided synthetic absorbable suture over the 4 weeks of implantation. In addition, the monofilament suture potentiated less bacterial infection than did the braided suture. The handling characteristics of the monofilament suture were superior to the braided suture because the monofilament suture required fewer throws to achieve knot security, encountered lower drag forces in fascia and colon, and had a greater double-wrapped first-throw knot security. Evaluated independently in clinical settings, the monofilament sutures were found to have excellent strength, first-throw hold, knot security, passage through tissue, knot repositioning, and ease of handling.