Early onset neonatal sepsis: diagnostic dilemmas and practical management.

Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms.

Engaging children and parents in service design and delivery.

The involvement of all user groups, including children, young people (CYP) and their parents, encourages people to take responsibility for healthier lifestyle behaviours, improves treatment compliance and leads to more appropriate use of healthcare resources. Initiatives to engage CYP in the UK are gathering momentum, but significant improvements are still needed. There is a national drive from the department of health (DH) and NHS England, strategic clinical networks, operational delivery networks (including newborn networks), charities, parent groups and a number of other bodies to embed CYP involvement in service design and delivery. User engagement and patient choice, is underpinned by the NHS outcomes framework, and a myriad of other DH and NHS England policies and practice frameworks. It is now everybody's business.

Could peripartum antibiotics have delayed health consequences for the infant?

Antibiotics are increasingly prescribed in the peripartum period, for both maternal and fetal indications. Their effective use undoubtedly reduces the incidence of specific invasive infections in the newborn, such as group B streptococcal septicaemia. However, the total burden of infectious neonatal disease may not be reduced, particularly if broad-spectrum agents are used, as the pattern of infections has been shown to alter to allow dominance of previously uncommon organisms. This area has been relatively understudied, and there are almost no studies of long-term outcome. Recent findings suggest that such long-term data should be sought. First, there is evidence that organisms initially colonising the gut at birth may establish chronic persistence in many children, in contrast to prompt clearance if first encountered in later infancy, childhood or adulthood. Second, there is a rapidly advancing basic scientific data showing that individual members of the gut flora specifically induce gene activation within the host, modulating mucosal and systemic immune function and having an additional impact on metabolic programming. We thus review the published data on the impact of perinatal antibiotic regimens upon composition of the flora and later health outcomes in young children and summarise the recent scientific findings on the potential importance of gut flora composition on immune tolerance and metabolism.

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.

OBJECTIVES: The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy. DESIGN: Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups. RESULTS: Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001). CONCLUSIONS: In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.

Trends in motor vehicle deaths in Wisconsin, 1986-1996: a decade of progress?

Motor vehicle-related injuries are a major cause of death and economic burden in Wisconsin. We examined motor vehicle-related mortality trends in Wisconsin from 1986 to 1996. During this time, overall mortality decreased by 12% and Wisconsin has met its year 2000 goal. However, mortality rates did not improve for women and non-whites. In addition, mortality rates increased in persons over 75 years. There are several explanations that may account for the overall mortality rate decline, but the reasons for the differences between age, racial, and gender groups are unclear.

New modalities for treating neonatal infection.

While the overall incidence of infection has remained constant at approximately 7/1000 livebirths, the last decade has witnessed a reduction in early onset infections and a relative increase in nosocomial sepsis, chiefly with coagulase-negative staphylococci. Immaturity of host defence mechanisms contributes to an increasing susceptibility to infection with decreasing gestational age and birth weight. In the past, efforts to enhance host defence have included the use of granulocyte infusions, fresh frozen plasma, exchange blood transfusions and immunoglobulin therapy. Current trials are investigating the use of agents which enhance endogenous defence mechanisms, such as, recombinant human granulocyte colony-stimulating factant and recombinant human granulocyte-macrophage colony-stimulating factor and of pentoxifylline. In the meantime strict attention to handwashing and aseptic technique remain the best methods of preventing nosocomial sepsis.

The in vitro effects of granulocyte and granulocyte-macrophage colony-stimulating factor on interleukin-3-dependent proliferation of human neonatal circulating progenitor cells.

Recombinant human granulocyte (rhG) colony-stimulating factor (CSF) and recombinant human granulocyte-macrophage (rhGM) CSF have been used to enhance neonatal neutrophil host defense. We aimed to determine the comparative efficacy of rhG-CSF and rhGM-CSF in increasing numbers of granulocyte colony-forming unit (CFU-G) and granulocyte-macrophage colony-forming unit (CFU-GM) in recombinant human (rh) IL-3-dependent cultures of human neonatal circulating hematopoietic progenitor cells, including cells from infants born to hypertensive mothers. We also investigated the relationship between fractional increase in CFU-G and endogenous plasma concentration of G-CSF. Circulating mononuclear cells were harvested from 25 neonates, and standard short-term assays in semisolid agar were established in the presence of rhIL-3 alone, rhIL-3 with rhG-CSF and rhGM-CSF, and both rhG-CSF and rhGM-CSF. CFU-G and CFU-GM were counted on d 14. Total colony number and CFU-G were significantly greater in cultures supplemented with rhG-CSF, with or without rhGM-CSF (p < 0.001 and p < 0.0005 for total colony number and CFU-G, respectively), when compared with cultures with rhIL-3 alone. Progenitor cells from three infants born to hypertensive mothers responded similarly. Total colony numbers and CFU-G were not increased by rhGM-CSF alone or by addition of rhGM-CSF to rhG-CSF; however, the proportions of CFU-GM were (p < 0.05 and p < 0.001, respectively, compared with rhIL-3 alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte colony stimulating factor treatment for neonatal neutropenia.

In a pilot study recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered to 12 neutropenic preterm infants to determine if neonatal neutropenia is secondary to decreased endogenous G-CSF production. Respiratory variables were monitored because of the possible link between inflammatory cells and hyaline membrane disease. All infants showed increased neutrophil counts. The only possible side effect observed was an exacerbation of thrombocytopenia.

Production of tissue factor by monocyte progenitor cells.

Tissue factor (TF) is known to be produced by monocytes from human peripheral blood. However the production of this factor by haematopoietic progenitor cells is not yet known. We thus studied human monocyte progenitor cells isolated from bone marrow of normal and diseased individuals. These cells were non-adherent, monocytic and able to phagocytose particles ranging from 0.3-1 microns. Unactivated partial thromboplastin time clotting assay demonstrated procoagulant activity consistent with TF function, which was blocked by a neutralizing anti-TF monoclonal antibody, G12. The production of TF messenger RNA was demonstrated on dot blot and northern blot analysis utilizing an oligonucleotide probe.

Plasma granulocyte-colony stimulating factor concentrations ([G-CSF]) in the early neonatal period.

We studied G-CSF concentrations ([G-CSF]) at birth and their relationship with neutrophil count, incidence of infection, gestational age, labour, and the presence of maternal pregnancy-induced hypertension. Plasma [G-CSF] were significantly elevated in babies with suspected infection and in those of hypertensive mothers, compared to healthy babies delivered by elective caesarian section (median [range] = 3101 [75- > 5000] pg/ml and 153 [45-857] pg/ml versus 32 [11-266] pg/ml; P < 0.0001); and were unrelated to neutrophil count and gestational age. Initial high concentrations (> 100 pg/ml) declined by 7 d (P < 0.0001).

The development of anti-HLA antibodies in multiply transfused preterm infants.

The development of antihuman leucocyte antigen antibodies (aHLAA) in response to multiple transfusions in preterm infants was studied prospectively. Fifty seven infants requiring a minimum of two blood transfusions were recruited after obtaining informed written parental consent. They were randomised to receive either whole blood or blood that had been passed through a leucocyte filter. Anti-HLAA were sought in maternal and cord blood so as to ensure that any aHLAA detected after transfusion had not been passively transferred antenatally, and in 1 ml samples drawn monthly from the baby, at least 10 days from a previous transfusion, until discharge from hospital. Anti-HLAA were detected by microlymphocytotoxicity assay. Results were obtained in 42 babies, 19 in the filter and 23 in the no filter group. Fifteen babies had to be excluded because of protocol violation or because they died. None of the babies receiving filtered blood developed aHLAA, but seven babies in the no filter group developed aHLAA. In conclusion, multiply transfused preterm infants have the ability to elaborate antibodies to HLA and leucocyte filters may prevent this.

Accidental ingestion of 'Ecstasy' (3,4-methylenedioxymethylamphetamine).

There is no report of the effects of 'Ecstasy' (3,4-methylenedioxymethylamphetamine) poisoning in childhood. The case of a 13 month old boy who ingested one capsule of Ecstasy is reported. Neurological and cardiovascular side effects predominated, which responded well to treatment with a chlormethiazole infusion.

Adjuvant radiotherapy and chemotherapy in breast cancer.

Three hundred and twenty-two women with involvement of axillary lymph nodes following surgery for operable breast cancer were randomized to receive either postoperative radiotherapy, chemotherapy (CMF) or radiotherapy followed by chemotherapy. There was an increase in disease free interval in pre- and postmenopausal patients receiving radiotherapy and chemotherapy regardless of the number of nodes involved. However, there was a trend towards an improvement in disease related survival only in those patients with more than three nodes involved.

The social, emotional and financial implications of adjuvant chemotherapy in breast cancer.

The incidence and severity of toxicity, the extent of emotional disturbance and cost of adjuvant chemotherapy were assessed in patients with early breast cancer randomized to receive either radiotherapy, chemotherapy (CMF) or radiotherapy followed by chemotherapy. Nausea and vomiting occurred in 85 per cent of patients receiving chemotherapy and contributed significantly to distress. Over one-third of patients required a wig or developed mucosal ulceration. Nevertheless, most patients were able to return to work during treatment. Leucopoenia was more commonly encountered in those patients who received radiotherapy prior to chemotherapy. Twelve months after mastectomy, psychiatric morbidity was present in 13 of 34 patients receiving chemotherapy with or without radiotherapy, compared with only 1 of 18 receiving radiotherapy alone. Anxiety was common in both groups. This trend was still present 6 months after the completion of chemotherapy. The cost of chemotherapy is discussed.