The UK defence anaesthesia experience with the Zambia Anaesthesia Development Programme.

For 18 months UK military anaesthetic trainees have been travelling to Zambia for a 3-month fellowship under the auspices of the Zambia Anaesthesia Development Programme. In this article we will discuss the history, current state and future intent of the fellowship in order to better inform the anaesthetic cadre and wider UK Defence Medical Services.

Contingency: the likely spectrum of injuries based upon a review of three recent undeveloped theatres of operations--CORPORATE, TELIC 1 and HERRICK 4.

Contingency operations are by their nature unpredictable and high-risk, with undeveloped logistical support, and medical provision is no exception. Can the contingency experiences of the last three decades help to predict the type of casualties that may be seen in future contingency operations? By reviewing published casualty statistics available from Operations CORPORATE, TELIC 1 and HERRICK 4 it can be demonstrated, unsurprisingly, that gunshot wounds and blast injuries dominate battle injuries, but that disease non-battle injuries also constitute a significant draw on medical provision, particularly gastrointestinal illness in hot environments. Planning for medical support for future contingency operations should anticipate this. Disease non-battle injuries have the potential to render a large proportion of a force combat-ineffective, requiring preventative measures to avoid overwhelming the available medical facilities. When operations occur in populated areas civilian casualties are likely to pose difficulties to medical support, due to issues with onward evacuation and a wider case mix, such as paediatrics.

Levels of substance P and IgE decapeptide in nasal polyp fluid and matching sera: a preliminary study.

Sixteen unselected patients with nasal polyps had the levels of substance P and IgE decapeptide measured by ELISA in the oedema fluids and their matched sera. All 16 samples had low levels of substance P in their sera and had high level of substance P in eight samples of nasal polyp oedema. There was a considerable variation in the values of IgE decapeptide found in the sera but 14 polyp oedema fluids had high levels of IgE decapeptide. This study supports the idea that there is a linkage between the cellular and neurovascular responses. High levels of IgE decapeptide suggest that mast cell reactions occur in the majority of cases and that IgE may be implicated in the process of mast cell degranulation.

The impact of missile warfare on self-reported sleep quality. Part 1.

During the 1991 Gulf War, we investigated the effect of missile attacks through two telephone surveys of a large sample of an urban population that evaluated self-reported sleep quality, stress, fear, depressed mood, fatigue and power of concentration. We surveyed 1,045 people during the Gulf War itself, and we interviewed them again (excluding the chronic insomniacs) 30 days after the war. During the war, 51% of the subjects claimed to be suffering from disturbed sleep. Whereas 13% of the survey population had been chronic insomniacs before the war, 38% developed insomnia during the war. The war provoked reported stress (67.5% of subjects), depressed mood (50.9%), difficulties in concentration (39.7%) and increased fatigue (25%). Four weeks after it ended, 19% of the previously normal subjects were still suffering from insomnia; 5% of the cases of insomnia were developed postbellum. Stress, depressed mood and impaired concentration were found to correlate significantly with subjectively evaluated insomnia. We concluded that modern missile warfare may induce long-lasting insomnia in one-third of the population under threat. A small percentage may develop insomnia postbellum. The risk of developing long-lasting insomnia is higher in those who reported experiencing prolonged stress and depressed moods.

Aggregation of the Fc epsilon RI in mast cells induces the synthesis of Fos-interacting protein and increases its DNA binding-activity: the dependence on protein kinase C-beta.

The ability of c-Fos to dimerize with various proteins creates transcription complexes which can exert their regulatory function on a variety of genes. One of the transcription factors that binds to c-Fos is the newly discovered Fos-interacting protein (FIP). In this report we present evidence for the regulation of the synthesis of FIP by a physiological stimulus. We found that the aggregation of the mast cell high affinity receptor for IgE (Fc epsilon RI) induced the synthesis of FIP and increased its DNA binding activity. Moreover, down-regulation of the isoenzyme protein kinase C-beta (PKC-beta) by a specific antisense phosphorothioate oligonucleotide resulted in profound inhibition of FIP-Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells elicits a PKC-beta dependent signaling pathway which regulates FIP-Fos DNA binding activity.

Molecules, management and medical outcomes: an international review.

The first major joint conference between the Royal College of Physicians of London and the American College of Physicians was held at the Royal College of Physicians on 7-8 June 1993. The large enthusiastic audience from the UK and the USA demonstrated the cordiality which exists between the two colleges. The objective of the conference was to further an exchange of ideas about the influence of science and technology upon current and future medical practice. Four major areas were chosen for review: diabetes, viral hepatitis, cerebrovascular disease and asthma. Presentations within each area were devoted first to scientific principles, secondly to aspects of clinical management, and finally to issues of clinical outcome.

Regulation of AP-1 expression and activity in antigen-stimulated mast cells: the role played by protein kinase C and the possible involvement of Fos interacting protein.

We have recently observed that protein kinase C (PKC) was involved in the regulation of the accumulation of mRNAs of the AP-1 components in cultured Abelson-transformed murine fetal-liver-derived mast cells stimulated by exocytotic stimuli. Here we analyzed the probable regulatory effect of PKC on the synthesis and DNA-binding activity of AP-1 complexes in immunologic stimulated mast cells. In this study we used the interleukin-3--dependent murine fetal-liver--derived mast cells that were not transformed by the Abelson oncogene. Study of PKC-depleted cells showed PKC dependency of c-fos mRNA accumulation and protein expression in IgE-Ag stimulated cells. In contrast, the c-jun mRNA accumulation was unaffected by PKC depletion, whereas its protein expression was dependent on this enzymatic activity. This suggests the involvement of PKC in the regulation of translation of c-Jun, a level of c-Jun regulation that was not previously described. The amount of AP-1 DNA-bound complex was also lowered in PKC-depleted cells. Therefore, PKC plays an important regulatory role in different stages of the signal transduction pathway because of IgE-Ag stimulation. Surprisingly, we have observed that although the amount of total synthesized c-Fos began to increase 15 minutes after immunologic stimulation, the amount of c-Fos associated with Juns did not increase, even after 45 minutes. This association was not affected by PKC. Using a Fos-interacting protein (FIP)-cDNA probe, an expression of 2.9 kb mRNA was detected in these cells. Furthermore, immunologic stimulation caused an increase in the amount of a Fos-containing protein complex that bound to an FIP-binding DNA oligonucleotide. Therefore, we propose that this protein complex that contains most of the immunologically induced c-Fos has an important role in IgE-Ag-stimulated signal transduction.

Emotional experiences during the three trimesters of pregnancy.

This study examined the emotional changes that occur during the trimesters of pregnancy. Two hundred eighty-two women were asked, one day after giving birth, to indicate at what frequency they had experienced various symptoms during each trimester of pregnancy and to fill out the Repression-Sensitization scale (Byrne, Barry, & Nelson, 1963). Results showed that while women's feelings during the first trimester are characterized by symptoms related to physiological changes (e.g., nausea, vomiting, dizziness), during the last trimester anxiety and emotional distress become the most significant symptoms. The level at which these symptoms were experienced was affected by the subject's socioeconomic level, number of previous births (primaparae or multiparae), and her personality type (repressor or sensitizer).

Serum modulates mast cell responses to IgE antigen stimulation.

Serum induces the expression of the fos and jun gene families, which encode the transcription factor AP-1. Since we previously found that activation of mast cells by IgE-antigen (Ag) induces the mRNA accumulation of c-fos, c-jun, junB and junD proto-oncogenes, we were prompted to investigate whether serum could affect such accumulation in these cells. In addition, we investigated whether serum could modulate inhibition of DNA synthesis in immunologically stimulated mast cells. Mast cells, which were cultured in the presence of fetal calf serum (FCS), were characterized by a high proliferation rate and high accumulation of the mRNA of c-fos, junB and junD proto-oncogenes. After sustained FCS deprivation both DNA synthesis and the level of c-fos mRNA were significantly decreased, as expected, whereas the level of c-jun, junB and junD mRNA were not affected. As opposed to mast cells which were cultured in the presence of FCS, immunological stimulation of FCS-deprived cells resulted in DNA synthesis inhibition and an increase in c-fos expression. The results also show that the level of c-fos mRNA was increased by either IgE-Ag or FCS up to a similar level, while these two triggers could not act synergistically to enhance this expression further. Thus, changes in DNA synthesis, induced by FCS, block the ability of the immunological challenge to inhibit mast cell growth and to enhance c-fos mRNA accumulation.

Anti-IgG autoantibodies in HIV-infected hemophilia patients.

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')2 gamma, IgM-anti-F(ab')2 gamma, and IgG-anti-Fc gamma serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fc gamma was not. IgG-anti-F(ab')2 gamma activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (less than 50,000/microliters platelet counts) had significantly higher IgM-anti-IgG activity than patients with greater than 50,000/microliters platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV-infected patients.

The association and predictive value of the complex immunoglobulin A-alpha 1-antitrypsin in the development of erosions in early rheumatoid arthritis.

Immunoglobulin A-alpha 1 antitrypsin complex (IgA-AT), its constituent components and nine other clinical or laboratory variables were measured in thirty-three patients with early, non-erosive rheumatoid arthritis (RA) in order to assess their value in predicting the subsequent development of erosions. After 12 months, eighteen patients had developed erosions. Comparison of variables measured at outset between the group of patients subsequently developing erosions and those not, showed only the complex IgA-AT level to be significantly different, the mean being higher in the erosive group. In the subgroup of patients with high IgA-AT levels (greater than 3.0 arbitary units) all developed erosions. The possible therapeutic implications of these findings are discussed.

Allergy treatment with a peptide vaccine.

An antiserum, obtained by immunising rabbits with a human peptide-protein conjugate, was shown to inhibit histamine release from rat mast cells both in vitro and in vivo. Immunisation of sensitised rats with the same peptide reduced IgE antibody formation and serum histamine concentration, and abolished systemic anaphylactic reactions in response to allergen challenge. This peptide may form the basis of a vaccine in a new approach to the immunotherapy of atopic disease.

Development and evaluation of a rapid, semi-automatic micro-method for CH50 estimation using a computer program.

Established methods for the estimation of serum complement are often unsatisfactory. Problems include complex mathematical and/or technical manipulations, lack of objectivity, and poor sensitivity. Here we present an assay that is rapid, sensitive, quantitative, simple and semi-automatic by using an 'ELISA' reader to estimate released haemoglobin. It compares very favourable with a more manual, old established method. We have used this new method to establish a normal range, investigate serum storage conditions, and demonstrate that the sensitised sheep red blood cells are suitable targets after overnight storage at 4 degrees C. Furthermore we confirm that serum from patients with systemic lupus erythematosus or Sjögren's syndrome frequently has reduced levels of CH50. Patients with rheumatoid arthritis, scleroderma, Bechet's disease or arteritis have a mean CH50 within the normal range.

Anti-viral antibodies in HIV (HTLV-III) infection possess auto-antibody activity against a CH1 domain determinant in human IgG: possible immunological consequences.

Two regions of the envelope glycoprotein gp120 of the human immunodeficiency virus were shown to have a significant degree of homology to human immunoglobulin-gamma heavy-chain constant domains. We have now synthesized three short linear peptides, the first representing a sequence within the CH1 domain, the second an analogue of it, and the third representative of a region within the viral gp120. Polyclonal antibodies against these peptides were raised in rabbits and used to demonstrate that they all reacted well with human native IgG. Vice-versa, we observed the reaction of these antisera to the virus in an ELISA system. The proportion of sera reacting with the human gamma-chain peptide was significantly higher in HIV-positive individuals than in HIV-negative individuals, suggesting production of anti-viral antibodies in AIDS patients with auto-antibody activity against a CH1 domain determinant in human IgG.

Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin.

Serum levels of immunoglobulin A (IgA) and the complex immunoglobulin A-alpha 1 antitrypsin (IgA-alpha 1AT) were measured at the commencement and after 3 months of a double-blind, placebo-controlled trial of sulphasalazine (SAS) in patients with active ankylosing spondylitis (AS). Twenty-eight patients were evaluated, 15 on sulphasalazine, 13 on placebo. Significant falls were seen in both IgA (p less than 0.01) and IgA-alpha 1AT (p less than 0.001) in the actively treated patients. In addition, significant improvement in clinical and laboratory measures of disease were observed. It is concluded that SAS is effective in AS and modulates the immune response.

IgA-alpha 1 antitrypsin complexes in ankylosing spondylitis.

A study of 95 serum samples from 61 patients with ankylosing spondylitis (AS) showed that 21 patients (34%) had raised levels of IgA-alpha 1 antitrypsin complexes. These were associated with active disease as measured by a clinical index and also with erythrocyte sedimentation rate, C reactive protein, and serum IgA. In particular, an association was noted between 'extraspinal' manifestations of AS such as synovitis, uveitis, and active inflammatory properties of these complexes. It is suggested that these complexes may have a role in the pathogenesis of such clinical manifestations.

The relationship between the complex of immunoglobulin A and alpha-1-antitrypsin, its constituent components and the acute-phase response as measured by C-reactive protein in rheumatoid arthritis treated with gold or D-penicillamine.

Serum levels of immunoglobulin A (IgA), alpha 1-antitrypsin (AT), their complex (IgA-alpha 1AT) and C-reactive protein (CRP) were measured prior to treatment and at 6 months, in 45 rheumatoid arthritis (RA) patients. Twenty-five patients were treated with D-penicillamine (DPA) and 20 patients with gold (sodium aurothiomalate). The level of circulating complex was reduced by both treatments (p less than 0.001). There was a significant correlation between the circulating levels of IgA-alpha 1AT complex and serum IgA (p less than 0.05). No relationship was observed between the level of circulating complex and CRP. These findings suggest that formation of IgA-alpha 1AT complex in RA is dependent on the level of IgA. The complex is reduced by gold and DPA but it does not reflect an acute phase response as measured by CRP.