The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD

OBJECTIVE: In a naturalistic follow-up of adult bipolar patients, the authors examined the contributions of demographic, phenomenological, and clinical variables, including antidepressant use, to prospectively observed mood episode frequency. METHOD: For 1,742 bipolar I and II patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), episodes of mood disorders were evaluated for up to 1 year of treatment. RESULTS: At entry, 32% of the patients met the DSM-IV criteria for rapid cycling in the prestudy year. Of the 1,742 patients, 551 (32%) did not complete 1 year of treatment. Among the 1,191 patients remaining, those with prior rapid cycling (N=356) were more likely to have further recurrences, although not necessarily more than four episodes per year. At the end of 12 months, only 5% (N=58) of the patients could be classified as rapid cyclers; 34% (N=409) had no further mood episodes, 34% (N=402) experienced one episode, and 27% (N=322) had two or three episodes. Patients who entered the study with earlier illness onset and greater severity were more likely to have one or more episodes in the prospective study year. Antidepressant use during follow-up was associated with more frequent mood episodes. CONCLUSIONS: While DSM-IV rapid cycling was prospectively observed in only a small percentage of patients, the majority of these patients had continued recurrences at lower but clinically significant rates. This suggests that cycling is on a continuum and that prevention of recurrences may require early intervention and restricted use of antidepressants.     

European guideline for the management of pelvic inflammatory disease

Pelvic inflammatory disease (PID) remains one of the most important consequences of sexually transmitted infections (STIs) resulting in severe morbidity and acting as the economic justification for STI screening programmes. Early and appropriate therapy has the potential to significantly reduce the long-term complications of PID, and these evidence-based guidelines provide advice on the management of pelvic infection including the use of appropriate antimicrobial regimens.     

Galanin plays a role in the conditioning lesion effect in sensory neurons

Sensory neurons show enhanced neurite outgrowth in vivo and in vitro following a conditioning lesion. Previous studies have shown that these effects are dependent on two members of the gp130 family of cytokines, leukemia inhibitory factor and interleukin-6. Here, we asked whether galanin, a neuropeptide induced by these cytokines, plays a role in the conditioning lesion response. Following a conditioning lesion, neurite outgrowth in culture was reduced in sensory neurons from galanin -/- mice compared with those from wild type controls. In neurons from wild type mice, the length of the longest neurite was increased 2.4-fold after a conditioning lesion, compared with 1.8-fold in neurons from knockout animals. The results indicate that the induction of galanin plays an important role in triggering the conditioning lesion response.     

Body iron and individual iron prophylaxis in pregnancy—should the iron dose be adjusted according to serum ferritin?

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 μg/l in pregnancy and <15 μg/l postpartum; IDA as serum ferritin <12 μg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin ≤30 μg/l, 37.7% ferritin 30–70 μg/l and 11.6% ferritin >70 μg/l. At 32 weeks, women with ferritin ≤30 μg/l had an ID frequency of: 20-mg group 54.1%, 40 mg 29.7%, 60 mg 24.4%, 80 mg 20.6% (p<0.001); women with ferritin >30 μg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 μg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin ≤30 μg/l had an IDA frequency of: 20-mg group 2.7%, 40 mg 2.7%, 60 and 80 mg 0%; none of the women with ferritin >30 μg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80–100 mg ferrous iron/day to women having ferritin ≤30 μg/l and 40 mg ferrous iron/day to women having ferritin 31–70 μg/l. In the prevention of IDA, we suggest 40 mg ferrous iron/day to women having ferritin ≤70 μg/l. Women with ferritin >70 μg/l have no need for iron supplement.     

Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model

Transfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.