An insight into an intriguing oxidative biotransformation pathway of 5-O-caffeoylquinic acid by a gut bacterium.

Microbiota is known to play a pivotal role in generating bioavailable and bioactive low-molecular-weight metabolites from dietary polyphenols. 5-O-caffeoylquinic acid (5-CQA), one of the main polyphenols found in human diet, was submitted to a resting cell biotransformation study using three gut bacteria species Lactobacillus reuteri, Bacteroides fragilis and Bifidobacterium longum. These bacteria were selected according to their belonging to the main phyla found in human gut microbiota. Our study highlighted the ability of only one of the strains studied, L. reuteri, to bioconverse 5-CQA into various metabolites due to the expression of the cinnamoyl esterase enzyme as the first step. Interestingly, one known natural compound, esculetin, was described for the first time as a 5-CQA-derived metabolite after conversion by a gut bacterium, the other metabolites had already been reported. This evidence highlighted an interesting oxidative pathway occurring in vivo by intestinal microbiota leading to esculetin. This molecule was also identified after electrochemical and enzymatic oxidations of caffeic acid. The oxidation capacity of L. reuteri led to less diverse metabolites in comparison to those obtained either electrochemically and enzymatically where dimers and trimers were reported. Thus, esculetin may have interesting and benefical biological effects on gut microbiota, which should be further evaluated. Novel synbiotics could be formulated from the association of L. reuteri with 5-CQA.

What the acute physician needs to know about Anti-NMDA receptor encephalitis: two case presentations.

These case reports look at two patients with anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis presenting to the same acute medical unit within a month of each other. The following covers the characteristic signs, symptoms and timeline associated with this condition and discusses whether we should be sending CSF for anti-NMDAr antibody testing more readily.

Youth diet quality and hazard of mood disorder in adolescence and adulthood among an Australian cohort.

BACKGROUND: Prospective studies on youth diet and mood disorders outcomes are limited. We examined if youth diet quality was associated with mood disorder onset over a 25-year follow-up period. METHODS: In 1985, Australian participants (aged 10-15 years) completed a 24-hour food record. A validated 100-point Dietary Guidelines Index (DGI) assessed diet quality. In 2009-11, 1005 participants (aged 33-41 years) completed the lifetime Composite International Diagnostic Interview for age of first DSM-IV defined mood disorder (depression or dysthymia). Cox proportional hazards regression estimated hazard of mood disorder during the 25-year follow-up according to baseline DGI score. Sensitivity analyses censored the study at 5, 10, and 15 years after baseline and used log binomial regression to estimate relative risk (RR). Covariates included baseline negative affect, BMI, academic performance, smoking, breakfast eating, physical activity, and socioeconomic status. RESULTS: The mean(SD) youth DGI score was 45.0(11.5). A 10-point higher DGI was not associated with hazard of mood disorder onset over the 25-year follow-up (Hazard Ratio (HR):1.00; 95% Confidence Interval (CI):0.89-1.13). The only indication that higher DGI might be associated with lower risk of mood disorder was within the first 5 years after baseline and this was not statistically significant (RR=0.85; 95% CI:0.60-1.18). LIMITATIONS: Loss-to-follow-up. A single 24-hour food record may not represent usual diet. CONCLUSION: Youth diet did not predict mood disorders in adulthood. The suggestions of a lower risk of mood disorder during late adolescence highlights that further prospective studies are needed.

An eating pattern characterised by skipped or delayed breakfast is associated with mood disorders among an Australian adult cohort.

BACKGROUND: Meal timing may influence food choices, neurobiology and psychological states. Our exploratory study examined if time-of-day eating patterns were associated with mood disorders among adults. METHODS: During 2004-2006 (age 26-36 years) and 2009-2011 (follow-up, age 31-41 years), N = 1304 participants reported 24-h food and beverage intake. Time-of-day eating patterns were derived by principal components analysis. At follow-up, the Composite International Diagnostic Interview measured lifetime mood disorder. Log binomial and adjacent categories log-link regression were used to examine bidirectional associations between eating patterns and mood disorder. Covariates included sex, age, marital status, social support, education, work schedule, body mass index and smoking. RESULTS: Three patterns were derived at each time-point: Grazing (intake spread across the day), Traditional (highest intakes reflected breakfast, lunch and dinner), and Late (skipped/delayed breakfast with higher evening intakes). Compared to those in the lowest third of the respective pattern at baseline and follow-up, during the 5-year follow-up, those in the highest third of the Late pattern at both time-points had a higher prevalence of mood disorder [prevalence ratio (PR) = 2.04; 95% confidence interval (CI) 1.20-3.48], and those in the highest third of the Traditional pattern at both time-points had a lower prevalence of first onset mood disorder (PR = 0.31; 95% CI 0.11-0.87). Participants who experienced a mood disorder during follow-up had a 1.07 higher relative risk of being in a higher Late pattern score category at follow-up than those without mood disorder (95% CI 1.00-1.14). CONCLUSIONS: Non-traditional eating patterns, particularly skipped or delayed breakfast, may be associated with mood disorders.

Bi-directional associations between healthy lifestyles and mood disorders in young adults: The Childhood Determinants of Adult Health Study.

BACKGROUND: Healthy lifestyles prevent cardiovascular disease and are increasingly recognized in relation to mental health but longitudinal studies are limited. We examined bi-directional associations between mood disorders and healthy lifestyles in a cohort followed for 5 years. METHOD: Participants were aged 26-36 years at baseline (2004-2006) and 31-41 years at follow-up (2009-2011). At follow-up, lifetime mood disorders (depression or dysthymia) were retrospectively diagnosed with the Composite International Diagnostic Interview. A five-item lifestyle score (comprising body mass index, non-smoking, alcohol consumption, leisure time physical activity and healthy diet) was measured at both time points. Linear and log multinomial regression determined if mood disorder before baseline predicted changes in lifestyle (n = 1041). Log binomial regression estimated whether lifestyle at baseline predicted new episodes of mood disorder (n = 1233). Covariates included age, sex, socio-economic position, parental and marital status, social support, major life events, cardiovascular disease history, and self-rated physical and mental health. RESULTS: A history of mood disorder before baseline predicted unfavourable trajectories of lifestyle over follow-up, including somewhat lower risk of improvement [relative risk (RR) 0.76, 95% confidence interval (CI) 0.56-1.03] and greater risk of worsening (RR 1.46, 95% CI 0.99-2.15) of lifestyle independent of confounding factors. Higher lifestyle scores at baseline were associated with a 22% (RR 0.76, 95% CI 0.61-0.95) reduced risk of first episodes of mood disorder, independent of confounding factors. CONCLUSIONS: Healthy lifestyles and mood disorders are closely related. Our results suggest that healthy lifestyles may not only reduce cardiovascular disease but also promote mental health.

The association between quitting smoking and weight gain: a systematic review and meta-analysis of prospective cohort studies.

This systematic review and meta-analysis aimed to quantify weight gain after smoking cessation and the difference in weight gain between quitters and continuing smokers. Five electronic databases were searched before January 2015. Population-based prospective cohort studies were included if they recorded the weight change of adult smokers from baseline (before smoking cessation) to follow-up (at least 3 months after cessation). Thirty-five cohort studies were identified, including 63,403 quitters and 388,432 continuing smokers. The mean weight gain was 4.10 kg (95% confidence interval [CI]: 2.69, 5.51) and body mass index (BMI) gain was 1.14 kg m(-2) (95% CI: 0.50, 1.79) among quitters. Compared with continuing smoking, quitting smoking was significantly associated with absolute weight (adjusted mean difference [MD]: 2.61 kg; 95% CI: 1.61, 3.60) and BMI gain (adjusted MD: 0.63 kg m(-2) ; 95% CI: 0.46, 0.80). Subgroup analyses using geographic region found that the difference in weight gain was considerably greater in studies from North America than from Asia. Follow-up length was identified as a source of heterogeneity, such that studies with longer follow-up showed greater difference in weight gain. Effective strategies are needed to encourage smokers to quit irrespective of potential weight gain and to help quitters avoid excess weight gain.

[The simultaneous appearance of three uncommon tumours]. / Synchrones Auftreten dreier seltener Tumoren.

A 70-year-old woman presented with nasal obstruction and pain projecting onto the left cheek. The face seemed asymmetric including exophthalmus on the right side. Nasal endoscopic inspection revealed a sarcomatous tumor located on the middle turbinate. The CT showed that the tumor filled the left maxillary sinus completely and had eroded the maxillary bone. In addition, a round, sharply defined intraorbital neoplasm on the right side was identified in the contrast-enhanced MRI. Histological examination of the extirpated intraorbital tumour showed a neurilemmoma. A tissue biopsy of the intranasal tumour falsely suggested an intestinal adenocarcinoma. Multiple neoplasms suspicious of disseminated lung metastases were detected in the CT of the thorax. One round lesion removed by thoracoscopy revealed a carcinoid. The intranasal tumour was excised completely and the histology proved beyond doubt an inverted papilloma.

[Bacillus Calmette-Guerin maintenance treatment in non-invasive bladder tumors: 1 year follow-up results of multicenter URO-BCG-4 trial]. / Traitement d'entretien par BCG-thérapie des tumeurs de vessie n'infiltrant pas le muscle (TVNIM): résultats à un an de l'étude multicentrique URO-BCG-4.

INTRODUCTION: Intravesical instillations of BCG remains the gold standard for intermediate and high risk NMIBC management. Maintenance treatment is recommended, however, the frequency of side effects responsible for the discontinuation of maintenance therapy over four out of five patients before the third year suggest a reduction or even spacing instillations. The objective of the study URO-BCG-4 was the evaluation of a new maintenance schedule by intravesical instillations of BCG combined reduced dose (third dose) and a decrease number of instillations per cycle (two or three). MATERIAL AND METHODS: Multicenter study of the French Association Oncologic Committee (12 university hospital centers), randomized, prospective, comparing reference diagram of BCG maintenance therapy one third of usual dose (group I) to a regimen combining third dose and decrease the number of instillations per cycle (two instead of three) (group II). We present the preliminary results at 1year of this Program of Clinical Research (CHU Rouen Promoter 2003-081). RESULTS: The rate of recurrence was respectively 9 and 7% (P=0.678) in groups I and II. The rate of tumor progression are 3 and 2.8% in groups I and II (P=1). Tolerance of intravesical instillations of BCG scored according to the WHO classification (Geneva 1979) was similar in the two groups. CONCLUSION: The decrease in the BCG dose (third dose) and the changes in the number and rate of instillations did not alter free tumor recurrence survival. The toxicity of intravesical instillations of BCG was identical in both groups. The use of the WHO classification has shown its limitations in the study of side effects of BCG as too complex and often not exhaustive. The rate of increase muscle was comparable in the two groups; however, a larger clinical experience is required.

Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women.

BACKGROUND: Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741). METHODS: Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N=65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N=50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration. RESULTS: Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated. CONCLUSION: A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.

The waved with open eyelids (woe) locus is a hypomorphic mouse mutation in Adam17.

The waved with open eyes (woe) locus is a spontaneous recessive mouse mutation that exhibits wavy fur, eyelids open at birth, and enlarged heart and esophagus. In this study, we confirmed the previously identified woe phenotypes and additionally identified anterior eye segment defects, absence of the meibomian glands, and defects in the semilunar cardiac valves. Positional cloning identified a C794T substitution in the Adam17 gene that ablates a putative exonic splicing enhancer (ESE) sequence in exon 7 resulting in aberrant Adam17 splicing. The predominant woe transcript, Adam17(Delta)(exon7), lacks exon 7 resulting in an in-frame deletion of 90 bp and a putative Adam17(Delta252-281) protein lacking residues 252-281 from the metalloprotease domain. Western blot analysis in woe identified only the precursor form of Adam17(Delta252-281) protein. Absence of cleavage of the prodomain renders Adam17(Delta252-281) functionally inactive; however, constitutive and stimulated shedding of Adam17 substrates was detected in woe at significantly reduced levels. This residual Adam17 shedding activity in woe most likely originates from full-length Adam17(T265M) encoded by the Adam17(C794T) transcript identified expressed at severely reduced levels. These results show that even small amounts of functional Adam17 allow woe mice to survive into adulthood. In contrast to Adam17(-/-) mice that die at birth, the viability of woe mice provides an excellent opportunity for studying the role of Adam17 throughout postnatal development and homeostasis.

Sex differences in presentation, severity, and management of stroke in a population-based study.

OBJECTIVES: Women may have poorer outcomes after stroke than men because of differences in their acute management. We examined sex differences in presentation, severity, in-hospital treatment, and early mortality in a cohort of first-ever-in-a-lifetime stroke patients. METHODS: Data were collected from May 1, 1996, to April 30, 1999, in the North East Melbourne Stroke Incidence Study. Stroke symptoms, prestroke medical history, in-hospital investigations, admission and discharge medications, initial stroke severity, and 28-day mortality were recorded. Multivariable regression was used to estimate sex differences in treatment, investigations, and 28-day mortality. RESULTS: A total of 1,316 patients were included. Women were older (mean age 76 +/- 0.6 vs 72 +/- 0.6, p < 0.01), had more severe strokes (median NIH Stroke Scale score 6 vs 5, p < 0.01), and more likely to experience loss of consciousness (31% vs 23%, p = 0.003) and incontinence (22% vs 11%, p = 0.01) than men. Women were less often on lipid-lowering therapy on admission. Echocardiography and carotid investigations were less frequently performed in women due to greater age and stroke severity. Women had greater 28-day mortality (32% vs 21%, p < 0.001) and stroke severity (44% vs 36%, p = 0.01) than men, but adjustment for age, comorbidities, and stroke severity (for mortality only) completely attenuated these associations. CONCLUSION: Sex differences seen in this study were mostly explained by women's older age, greater comorbidity, and stroke severity. The reasons for differences according to age may need further examination.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

[Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence]. / Localisation sous-rétinienne inaugurale d'une rechute de leucémie aiguë myéloblastique (LAM5).

BACKGROUND: Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. CASE REPORT: A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. DISCUSSION: Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

Female genital warts: global trends and treatments.

The increasing incidence of human papillomavirus (HPV) infection and HPV-associated conditions such as genital warts in women is a global concern. Genital warts are a clinical manifestation of HPV types 6 and 11, and are estimated to affect 1% of sexually active adults aged between 15 and 49. HPV infection is also strongly associated with cervical cancer, and is prevalent in as many as 99% of cases. The psychological stress of having genital warts is often greater than the morbidity of the disease, and therefore successful treatment is crucial. Current treatments are patient-applied and provider-administered therapies. Imiquimod 5% cream, a patient-applied therapy, is an efficacious treatment with tolerable side-effects and a low recurrence rate, and has the potential to be an effective strategy for the management of genital warts.

Efficacy of the internal mammary artery in combined aortic valve replacement-coronary artery bypass grafting.

BACKGROUND: While internal mammary artery (IMA) use predicts improved survival after coronary bypass grafting (CABG), it remains unknown whether patients undergoing concomitant aortic valve replacement (AVR) realize a similar benefit. METHODS: All patients at a single teaching institution, undergoing combined AVR-CABG, which included a graft to the left anterior descending coronary artery (LAD) from 1984 to 1994 (n = 227) were examined retrospectively. RESULTS: Patients receiving an IMA graft (yesIMA, n = 135) and patients receiving only saphenous vein grafts (nonIMA, n = 92) were not different in their presenting symptoms, or in their incidence of preoperative risk factors. The patients with IMA were more likely to be male, have a later year of operation, be younger, and have a greater body surface. Morbidity was not different between groups. IMA use did not affect 30-day mortality. Long-term actuarial survival was greater in the group with IMA (63% +/- 7% vs 42% +/- 6% at 5 years, p < 0.01). A multivariate Cox proportional hazards model demonstrated that use of an IMA graft improved survival, while recent myocardial infarction, diabetes, earlier year of operation, and lower ejection fraction diminished long-term survival. The relative risk of IMA grafting was 0.570. CONCLUSIONS: Within the limits of a retrospective analysis, patients in a modern era of cardiac operation, who undergo combined AVR-CABG, do not suffer increased morbidity from IMA use, and may realize a survival benefit from use of the IMA as a conduit for bypass of the LAD coronary artery.

The downregulation of CD4 and MHC-I by primate lentiviruses: a paradigm for the modulation of cell surface receptors.

The human and simian immunodeficiency viruses (HIV and SIV) downregulate the cell surface expression of CD4, their primary receptor, and of class I histocompatibility complex (MHC-I), a critical mediator of immune recognition. While the first of these effects seems important to preserve viral infectivity, the second likely promotes immune evasion. Three HIV-1 proteins, Nef, Env and Vpu, contribute to downregulate CD4, Env forms a complex with CD4 in the endoplasmic reticulum, thereby retaining the receptor in this compartment. Nef and Vpu, on the other hand, act as connectors between CD4 and specific intracellular trafficking pathways, targeting the receptor for degradation in the lysosome and the proteasome, respectively. Some of the downstream partners of the viral proteins in these events have been identified, and include the adaptor complex of clathrin-coated pits, the beta subunit of COP-I coatomer, and the ubiquitin pathway-related h-beta TrCP protein. HIV-induced MHC-I downregulation, mostly the effect of Nef, also reflects a redistribution of this receptor, with its accumulation in the Golgi. The modalities of this process, however, are as yet imperfectly understood. New evidence indicates that the mechanisms employed by primate lentiviruses to downmodulate CD4 and MHC-I are also exploited by a number of cellular regulatory processes.

Epsilon-aminocaproic acid administration and stroke following coronary artery bypass graft surgery.

BACKGROUND: Epsilon-aminocaproic acid is routinely used to reduce bleeding during cardiac surgery. Anecdotal reports of thrombotic complications have led to speculation regarding this drug's safety. We investigated the association between epsilon-aminocaproic acid administration and postoperative stroke. METHODS: Six thousand two hundred ninety-eight patients undergoing isolated coronary artery bypass graft surgery between 1989 and 1995 were studied. Data was obtained from the Duke Cardiovascular Database as well as from an automated intraoperative anesthesia record keeper. Patients identified as having postoperative stroke were reviewed and confirmed by a board certified neurologist blinded to epsilon-aminocaproic acid administration. RESULTS: Postoperative stroke occurred in 97 patients (1.5%). Three thousand one hundred thirty-five (49.8%) patients received epsilon-aminocaproic acid. Increased age was associated with a higher incidence of postoperative stroke (p = 0.0001). In contrast, there was no significant difference (p = 0.7370) in the incidence of stroke between use of epsilon-aminocaproic acid (1.3%) and nonuse (1.7%). Multivariable logistic regression found no significant effect of epsilon-aminocaproic acid use on stroke after accounting for age, date of surgery, and history of diabetes. CONCLUSIONS: This series suggests that epsilon-aminocaproic acid administration does not increase the risk of postoperative stroke.

Ambulatory management of multiple gestation.

Ambulatory management of multiple gestation requires careful and continuing care by the obstetrician. The initial evaluation should include a comprehensive history, including use of fertility enhancing drugs and ART, family history, social history; a general physical examination, including a pelvic examination; laboratory evaluation, including complete blood cell count, dipstick urinalysis for protein and glucose, urine culture, blood type, Rh factor and irregular blood antibody determination, serology for rubella, syphilis, hepatitis B surface antigen and varicella (if there is no history). A Papanicolaou smear should be done at the time of the pelvic examination, as should evaluation for bacterial vaginosis. Ultrasound assessment of placentation should be done at 14 weeks' gestation, but vaginal or perineal ultrasound of cervical length should be done at the initial visit. Other testing procedures should include repeat ultrasound evaluation for fetal growth every 4 weeks in a dichorionic placentation and every 3 weeks if monochorionic placentation is present. Triple screen MSAFP at 16-18 weeks' gestation and blood sugar screening at 22-26 weeks should be performed. After the first trimester, the patient should schedule physician visits every 2 weeks or less. Routine medications should include one prenatal vitamin per day, additional folic acid supplementation of 1.0 mg per fetus, supplemental iron preparation, and additional calcium to equal 1500 mg/day. The use of low-dose aspirin to prevent preeclampsia in twin gestations has not been adequately studied. Continuing vigilance by the knowledgeable obstetrician should occur. Multiple gestations should not be cared for by non-physician providers or by family physicians. Referral to a maternal-fetal medicine unit is recommended.

Umbilical cord blood interleukin-6 levels and neonatal morbidity.

OBJECTIVE: To study umbilical cord interleukin-6 levels and the occurrence of neonatal sepsis, congenital pneumonia, necrotizing enterocolitis, and grade II-IV intraventricular hemorrhage. METHODS: Umbilical cord blood was collected from 133 preterm newborns. The study population was divided according to the presence or absence of neonatal complications. Interleukin-6 levels and clinical characteristics were compared by univariate and multivariate analyses. RESULTS: Sixteen neonates had adverse outcomes, and 117 were unaffected. The median interleukin-6 level was significantly higher in affected than in unaffected infants (145 pg/mL versus 0 pg/mL, P = .002). Elevated interleukin-6 levels were associated independently with neonatal morbidity in multiple logistic regression modeling that included gestational age, birth weight, and antenatal steroid exposure. CONCLUSION: Umbilical cord blood interleukin-6 levels are elevated in neonates who subsequently develop sepsis, congenital pneumonia, necrotizing enterocolitis, or grade II-IV intraventricular hemorrhage.