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We present a calibration approach for the Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) based on the reflectance properties of the instrument's onboard diffuser. This technique uses SeaWiFS as a reflectometer, measuring the reflected solar irradiance from the Earth and from the onboard diffuser. Because the Sun is the common source of light for both measurements, the ratio of the SeaWiFS-measured radiances from the Earth and the diffuser provide the ratio for the reflectances of the two samples. The reflectance characterization of the onboard diffuser is the calibration reference for this approach. Knowledge of the value of the solar irradiance is not required for these measurements because it falls out of the ratio. Knowledge of the absolute calibration coefficient for the SeaWiFS measurements of each of the two samples is not required either. Instead, the result of the ratioing technique is based on the linearity of the instrument's response to the intensity of the input light. The calibration requires knowledge, however, of the reflectance of the onboard diffuser at the start of the SeaWiFS mission and the response of the instrument bands, in digital numbers, for measurements of the diffuser at that time.

For instruments that carry onboard solar diffusers to orbit, such as the Sea-Viewing Wide Field-of-View Sensor (SeaWiFS), it is possible to convert the instrument's reflectance measurements to radiance measurements by knowledge of the solar irradiance. This process, which generally requires the application of a solar irradiance model, is described. The application of the irradiance model is separate from the measurements by the instrument and from the instrument's reflectance calibration. In addition, SeaWiFS was calibrated twice before launch for radiance response by use of radiance sources with calibrations traceable to the National Institute of Standards and Technology. With the inclusion of the at-launch diffuser-based radiance calibration, SeaWiFS has three possible radiance calibrations forthe start of on-orbit operations. The combination of these three into a single calibration requires changes of 4% or less for the current at-launch radiance calibration of the instrument. Finally, this process requires changes of 4% or less for the reflectance calibration coefficients to provide consistency among the radiance calibration, the reflectance calibration, and the solar irradiance.

Due to the limitations of classical methods for the detection of systemic fungal infections and the high mortality rates associated with these infections, it has become essential to develop a quick, sensitive and specific detection assay. By using the Idaho Technologies Light-Cycler system, a qualitative real-time PCR system has been developed for the detection of the leading causes of systemic infection within the genus Candida. The sensitivity of the assay was comparable to previously described PCR methods (1-5 c.f.u. ml(-1)) and, by the use of a single Candida probe, it was able to detect, but not differentiate between, seven species of Candida (Candida albicans, Candida dubliniensis, Candida glabrata, Candida kefyr, Candida krusei, Candida parapsilosis and Candida tropicalis). Single-round amplification on the Light-Cycler allowed rapid turn-around of clinical samples (within one working day) and it was shown to be more sensitive than classical procedures, exposing 39 possible systemic infections that were not detected by blood culture.

High-temperature high resolution gas chromatography (HT-HRGC) and HT-HRGC coupled to mass spectrometry (HT-HRGC-MS) are powerful but relatively unexplored tools for the analysis of crude extracts and fractions of natural products. To illustrate the scope of the technique the direct characterization of several compounds, present in crude extracts of leaves and stems of Croton hemiargyreus Muell. Arg. var. hemiargyreus was undertaken, without derivatization or clean-up procedures. Both practical aspects and limitations of HT-HRGC and HT-HRGC-MS were evaluated resulting in a simple, straightforward and extremely powerful technique for the analysis of complex mixtures.

We present an overview of the calibration of the Sea-viewing Wide Field-of View Sensor (SeaWiFS) from its performance verification at the manufacturer's facility to the completion of its third year of on-orbit measurements. These calibration procedures have three principal parts: a prelaunch radiometric calibration that is traceable to the National Institute of Standards and Technology; the Transfer-to-Orbit Experiment, a set of measurements that determine changes in the instrument's calibration from its manufacture to the start of on-orbit operations; and measurements of the sun and the moon to determine radiometric changes on orbit. To our knowledge, SeaWiFS is the only instrument that uses routine lunar measurements to determine changes in its radiometric sensitivity. On the basis of these methods, the overall uncertainty in the SeaWiFS top-of-the-atmosphere radiances is estimated to be 4-5%. We also show the results of comparison campaigns with aircraft- and ground-based measurements, plus the results of an experiment, called the Southern Ocean Band 8 Gain Study. These results are used to check the calibration of the SeaWiFS bands. To date, they have not been used to change the instrument's prelaunch calibration coefficients. In addition to these procedures, SeaWiFS is a vicariously calibrated instrument for ocean-color measurements. In the vicarious calibration of the SeaWiFS visible bands, the calibration coefficients are modified to force agreement with surface truth measurements from the Marine Optical Buoy, which is moored off the Hawaiian Island of Lanai. This vicarious calibration is described in a companion paper.

We present an overview of the vicarious calibration of the Sea-Viewing Wide Field-of-view Sensor (SeaWiFS). This program has three components: the calibration of the near-infrared bands so that the atmospheric correction algorithm retrieves the optical properties of maritime aerosols in the open ocean; the calibration of the visible bands against in-water measurements from the Marine Optical Buoy (MOBY); and a calibration-verification program that uses comparisons between SeaWiFS retrievals and globally distributed in situ measurements of water-leaving radiances. This paper describes the procedures as implemented for the third reprocessing of the SeaWiFS global mission data set. The uncertainty in the near-infrared vicarious gain is 0.9%. The uncertainties in the visible-band vicarious gains are 0.3%, corresponding to uncertainties in the water-leaving radiances of approximately 3%. The means of the SeaWiFS/in situ matchup ratios for water-leaving radiances are typically within 5% of unity in Case 1 waters, while chlorophyll a ratios are within 1% of unity. SeaWiFS is the first ocean-color mission to use an extensive and ongoing prelaunch and postlaunch calibration program, and the matchup results demonstrate the benefits of a comprehensive approach.

A simple correction method to remove the spectral bandpass effects of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) on the derived normalized water-leaving radiances and ocean-near-surface chlorophyll concentration is developed and implemented in the SeaWiFS data-processing system. SeaWiFS has not only in-band response structures but also significant sensor out-of-band contributions. The effects of the SeaWiFS out-of-band contribution at the green bands is particularly significant for the derived normalized water-leaving radiances and therefore for the retrieved ocean-near-surface chlorophyll concentration. With the sensor spectral bandpass corrections, the low chlorophyll concentration is even lower in the clear ocean regions, whereas there are almost no changes for the oceans with a chlorophyll concentration of >0.2 mg/m(3).

Meningococcal meningitis and septicemia are serious infections with significant morbidity and mortality. A sensitive affordable test is required to provide evidence of meningococcal disease at the earliest opportunity to improve local management and give early warning of potential outbreaks of disease. Culture of organisms is considered the gold standard for diagnosis but is slow (24 h or more) and increasingly influenced by prior antibiotic treatment. Recently, the development of polymerase chain reaction (PCR) has improved diagnosis but this sensitive assay is costly, is not available at most primary care institutions and is not feasible for developing countries. Conventional latex agglutination (LA) enables rapid detection of bacterial antigen in cerebrospinal fluid (CSF) (1,2) and can also be used to test specimens of blood (3,4) or urine (5) and for serogroup determinations on primary cultures (6,7). We discuss here test-card agglutination and also describe a new technique based upon LA in an ultrasonic standing wave that retains the speed of direct antigen testing while significantly increasing sensitivity.

The risk of fungal infection is increasing in intensive care unit patients and the spectrum of pathogens is changing. A number of new antifungal agents are becoming available, but their use in critically ill patients has not been assessed in randomized controlled trials. Furthermore, distinguishing colonization from infection is problematic in intensive care unit patients. Clinicians who are involved in the management of intensive care unit patients must remain vigilant and devise a risk-based antifungal strategy that is based on local experience and susceptibility patterns.

We present the results of an experiment designed to measure the changes in the radiometric calibration of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) from the time of its manufacture to the time of the start of on-orbit operations. The experiment uses measurements of the Sun at the manufacturer's facility to predict the instrument outputs during solar measurements immediately after launch. Because an onboard diffuser plate is required for these measurements, the experiment measures changes in the instrument-diffuser system. There is no mechanism in this experiment to separate changes in the diffuser from changes in the instrument. For the eight SeaWiFS bands, the initial instrument outputs on orbit averaged 0.8% higher than predicted with a standard deviation of 0.9%. The greatest difference was 2.1% (actual output higher than predicted) for band 3. The estimated uncertainty for the experiment is 3%. Thus the transfer-to-orbit experiment shows no changes in the radiometric sensitivities of the SeaWiFS bands--at the 3% level--from the completion of the instrument's manufacture to its insertion into orbit.

The crude ethanol extracts from the leaves of three Croton hemiargyrus hemiargyreus plants are fractionated by thin-layer chromatography, yielding five fractions. The fractions and the crude extract are analyzed by high-temperature high-resolution gas chromatography coupled with mass spectrometry (HT-HRGC-MS). Several natural products, including thermolabile components, can be characterized directly in the samples, such as alkaloids, terpenes, flavonoids, acids, alcohols, etc. The cold on-column technique proves to be appropriate for the injection of these thermolabile compounds. HT-HRGC-MS is shown to be a valuable tool and an alternative technique to classical phytochemical procedures for the simple and fast routine analysis of natural products in crude extracts.

Background: Body temperature often is ignored during regional anesthesia, despite evidence that hypothermia occurs commonly. Because hypothermia is associated with adverse clinical outcomes, it is important to recognize predictors of hypothermia and to monitor and control body temperature in patients at risk. The current study was designed to determine the predictors of core hypothermia in patients receiving spinal anesthesia for radical retropubic prostatectomy., Methods: Forty-four patients undergoing radical retropubic prostatectomy were studied. A lumbar intrathecal injection of 18-22 mg bupivacaine, 0.75%, with 20 microg fentanyl was given. No active warming measures were used other than intravenous fluid warming. The following clinical variables were assessed as potential predictors of core (tympanic) temperature at admission to the postanesthesia care unit: duration of surgery, average ambient operating room temperature, body habitus, age, and spinal blockade level., Results: The mean core temperature at admission to the postanesthesia care unit was 35.1 +/- 0.6 degrees C (range, 33.6-36.3 degrees C). Duration of surgery, ambient operating room temperature, and body habitus were not predictors of hypothermia. A high level of spinal blockade and increasing age were predictors of hypothermia. For each incremental increase in block level, core temperature decreased by 0.15 degrees C, and for each increase in age, core temperature decreased by 0.3 degrees C., Conclusions: Although high-level spinal blockade has been associated with decreased thermoregulatory thresholds, no previous study has shown that a higher level of blockade is associated with a greater magnitude of core hypothermia in the clinical setting. As with general anesthesia, advanced age is associated with hypothermia during spinal anesthesia.

The distribution of Neisseria meningitidis serogroup B and C polysaccharide antigen in blood and the prognostic significance of antigen concentration was examined by ultrasound-enhanced immunoagglutination of coated microparticles. Specimens (169 sera/plasma from 145 patients with confirmed meningococcal disease) were tested retrospectively. The ultrasonic immunoassay detected serum antigen in 136 samples from 112 patients. Titration of antigen-positive specimens allowed estimation of blood antigen concentration. The modal blood antigen titre was 1/16, corresponding to an estimated polysaccharide concentration of 0.85 microg/ml. The lowest mean blood antigen concentration found ultrasonically was 0.05 microg/ml; compared to the 1.98 microg/ml found by conventional latex agglutination, this represents an approximately 30-fold improvement in sensitivity. Three grades of outcome were correlated with the presenting antigen titre in 83 patients: (i) <2 weeks hospitalisation, (ii) > or =2 weeks hospitalisation and (iii) mortality. High polysaccharide concentrations correlated with mortality. Nine of 15 patients with a serum antigen titre of 1/64 or greater (> or =3.4 microg/ml polysaccharide) died, whereas no patient with titres equal to or less than 1/4 (< or = 0.21 microg/ml) died, including those patients in whom antigen was undetectable by ultrasonic immunoassay. Increasing antigen concentration significantly correlated with severity of outcome (P<0.001). Ultrasound-enhanced agglutination provides a rapid prognostic indicator by sensitive measurement of serum antigen level.

Objectives: (1)To assess the diagnostic utility of quantitative cultures of non-bronchoscopic lung lavage (NBL) in ventilator-associated pneumonia and evaluate the role of the Bacterial Index; (2) To assess the predictive value of NBL surveillance quantitative cultures in ventilated patients; (3) To evaluate the Clinical Pulmonary Infection Score (CPIS) system in ventilated patients., Design: A prospective comparison of NBL with bronchoscopic bronchoalveolar lavage and protected specimen brush., Setting: Three intensive care units in academic tertiary care centres., Patients: 145 adults ventilated for 72 h, with and without clinical signs of pneumonia., Interventions: Sampling of lower airway secretions by NBL, bronchoalveolar lavage and protected specimen brush., Main Outcome Measures: Diagnostic reliability of quantitative cultures, Bacterial Index and CPIS., Results: 34 episodes of clinical ventilator-associated pneumonia were documented in 32 patients. 9 episodes were confirmed by concordant blood/pleural culture or post-mortem lung examination. Qualitative concordance of the predominant pathogen between sequential NBL: bronchoalveolar lavage and protected specimen brush was 83 %. Sensitivity and specificity of non-directed bronchial lavage at a threshold of 10(4) CFU/ml were 68 % and 70 % respectively (p = 0. 003) and were comparable with the bronchoscopic methods. However, the low positive predictive value of NBL indicates that quantitation in the absence of clinical signs is unlikely to be useful. Bacterial Index did not improve discriminatory power of quantitation compared with bacterial load of predominant organism. Mean CPIS for confirmed pneumonia cases was 8.4 +/- 1.01, significantly higher than for non-pneumonia observations (p = < 0.0001)., Conclusion: NBL is a simple, safe, cheap, readily-available method of diagnosing ventilator-associated pneumonia with comparable diagnostic accuracy to bronchoscopic techniques. Quantitation of respiratory tract cultures can exclude pneumonia in patients with equivocal clinical signs. The diagnostic threshold should vary depending on the length of ventilation, likelihood of pneumonia and antibiotic administration. The Bacterial Index is a flawed mathematical device that has no contributory role in pneumonia diagnosis. The CPIS has some diagnostic role in selected cohorts of ventilated patients.

We report on the lunar and solar measurements used to determine the changes in the radiometric sensitivity of the Sea-viewing Wide Field-of-view Sensor (SeaWiFS). Radiometric sensitivity is defined as the output from the instrument (or from one of the instrument bands) per unit spectral radiance at the instrument's input aperture. Knowledge of the long-term repeatability of the SeaWiFS measurements is crucial to maintaining the quality of the ocean scenes derived from measurements by the instrument. For SeaWiFS bands 1-6 (412-670 nm), the change in radiometric sensitivity is less than 0.2% for the period from November 1997 through November 1998. For band 7 (765 nm), the change is approximately 1.5% and for band 8 (865 nm) approximately 5%. The rates of change of bands 7 and 8, which were linear with time for the first eight months of lunar measurements, are now slowing. The scatter in the data points about the trend lines in this analysis is less than 0.3% for all eight SeaWiFS bands. These results are based on monthly measurements of the moon. Daily solar measurements using an onboard diffuser show that the radiometric sensitivities of the SeaWiFS bands have changed smoothly during the time intervals between lunar measurements. Because SeaWiFS measurements have continued past November 1998, the results presented here are considered as a snapshot of the instrument performance as of that date.

Preadmission administration of antibiotics to patients with suspected meningococcal infection has decreased the likelihood of obtaining an isolate and has stimulated development of rapid and reliable non-culture-based diagnostic methods. The sensitivity of the conventional test card latex agglutination test (TCLAT) for detection of capsular polysaccharide has been reported to be suboptimal. In the United Kingdom meningococcal DNA detection by PCR has become readily available and is now used as a first-line investigation. Recently, the performance of latex antigen detection has been markedly improved by ultrasound enhancement. Three tests for laboratory confirmation of meningococcal infection, (i) PCR assays, (ii) TCLAT, and (iii) ultrasound-enhanced latex agglutination test (USELAT), were compared in a retrospective study of 125 specimens (serum, plasma, and cerebrospinal fluid specimens) from 90 patients in whom meningococcal disease was suspected on clinical grounds. Samples were from patients with (i) culture-confirmed meningococcal disease, (ii) culture-negative but PCR-confirmed meningococcal disease, and (iii) clinically suspected but non-laboratory-confirmed meningococcal disease. USELAT was found to be nearly five times more sensitive than TCLAT. Serogroup characterization was obtained by both PCR and USELAT for 44 samples; all results were concordant and agreed with the serogroups determined for the isolates when the serogroups were available. For 12 samples negative by USELAT, the serogroup was determined by PCR; however, for 12 other specimens for which PCR had failed to indicate the serogroup, USELAT gave a result. USELAT is a rapid, low-cost method which can confirm a diagnosis, identify serogroups, and guide appropriate management of meningococcal disease contacts. A complementary non-culture-based confirmation strategy of USELAT for local use supported by a centralized PCR assay service for detection of meningococci would give the benefits of timely information and improved epidemiological data.

Objectives: The objective was to determine the current epidemiology of infective endocarditis., Patients and Methods: All microbiologically positive episodes of infective endocarditis treated at The University Hospital of Wales over a 9-year period from March 1987 to March 1996 was reviewed. Patients originated from the catchment area of The University Hospital of Wales or were referred from other hospitals in Wales. Data extraction was from records held in the Microbiology Department and, whenever possible, from patients' casenotes. The epidemiological parameters were: (1) age and sex of patients; (2) distribution of affected sites; (3) frequency of predisposing risk factors (cardiac and extracardiac); (4) incidence of early prosthetic valve endocarditis; and (5) mortality rates., Results: There were 128 microbiologically positive episodes of endocarditis in 125 patients. The mean age of the population was 53.1 years and the aortic valve was the most frequently involved site of infection (51.6%). A presumed source of infection was identified in 20% if episodes. The commonest predisposing cardiac risk factor in native valve episodes was bicuspid aortic valve (16.7%) but there was no identifiable cardiac risk factor in a much larger proportion (37.7%) of native valve episodes. There was a low incidence (0.6%) of culture positive early prosthetic valve episodes and low mortality rates for both native and prosthetic valve endocarditis (12.3% and 24.5%) in this study. Viridans streptococci were the predominant organisms. In prosthetic valve episodes with onset after the 60th postoperative day but within one postoperative year the identity of the isolate suggested, in most cases, perioperative valve contamination., Conclusions: The epidemiology of infective endocarditis has undergone significant change. Inability to detect clinically common predisposing lesions, and the frequent absence of any identifiable predisposing cardiac risk factor mean that initial diagnosis is often difficult and demands a high index of suspicion. There was a low incidence of culture positive early prosthetic valve episodes and there were low mortality rates for both native and prosthetic valve endocarditis; these figures suggest improvements in cardiac care. The microbiological evidence indicates that the duration of the postoperative time period used for classifying prosthetic valve endocarditis into 'early' and 'late' episodes should be extended from 60 days to 1 year.

Unlabelled: Monitoring and maintaining body temperature during the perioperative period has a significant impact on the risk of myocardial ischemia, cardiac morbidity, wound infection, surgical bleeding, and patient discomfort. To test the hypothesis that body temperature is inadequately monitored during regional anesthesia (RA), we randomly surveyed 60 practicing anesthesiologists to determine practice patterns for temperature monitoring. Only 33% of the clinicians surveyed routinely monitor body temperature during RA. Although skin temperature monitoring has limitations, it was the most commonly used method among the survey respondents. When temperature is monitored during RA, most clinicians use either liquid crystal skin-surface monitoring or axillary temperature probes. Of those surveyed, < 15% use acceptable core temperature monitoring techniques (urinary bladder or tympanic membrane). In conclusion, it seems that body temperature is often not monitored in patients receiving RA., Implications: The results of this survey of practicing anesthesiologists indicate that body temperature is often not monitored in patients receiving regional anesthesia. It is therefore likely that significant hypothermia goes undetected and untreated in these patients.

Detailed instructions for performance and interpretation of ultrasound-enhanced latex agglutination tests for the rapid identification of bacteria causing meningitis are described. This recently developed technique, which enhances the sensitivity of most latex immunoagglutination assays, has been studied mainly in the context of detection of antigens of meningitis-causing bacteria. The test concentrates on the Wellcogen bacterial antigen kit (Murex Diagnostics Ltd) that contains five latex suspensions specific for Haemophilus influenzae type b, Neisseria meningitidis ACYW135, N. meningitidis B/Escherichia coli K1, Streptococcus group B and Streptococcus pneumoniae. Light photomicrographs of positive agglutination are shown. Particular attention is paid to the appearance of the latex in negative control samples following exposure to ultrasound. Guidance is given on interpretation and assessment in clinical samples.

Fungal infection in critically ill patients is an increasingly prevalent problem. Candida spp. cause the majority of these infections in ICU. They occur most commonly in patients with severe underlying illness, multiple courses of antibiotics and intravascular catheters. Clinical diagnosis is difficult due to nonspecific signs and the frequent occurrence of widespread superficial colonization with Candida spp. in ventilated patients. Most patients are diagnosed using inferential evidence of infection, such as persistent pyrexia despite antibiotics, raised serum C-reactive protein and the presence of individual risk factors. Amphotericin B and fluconazole are the most commonly used anti-fungals dependent on the identity of the fungus. Most of these infections are endogenous; however, a proportion may be caused via the hands of healthcare staff or contaminated medical equipment.

Antigen detection in the urine and serum may be useful in the diagnosis of suspected meningococcal disease, especially after previous antibiotic treatment. Current test card procedures using commercial agglutination kits are often too insensitive to contribute to diagnosis. Diagnosis of meningococcal disease rose from 37% with the test card procedure to 74% following ultrasonic enhancement.

We report three cases of deep-seated and systemic Candida albicans infection in which inadequate dosages of fluconazole were used, leading to breakthrough fungaemia, candidal osteomyelitis and endocarditis. The need to modify fluconazole dosage in patients receiving continuous venovenous haemofiltration is discussed.

The standard test card agglutination of antibody-coated latex by Neisseria meningitidis. Streptococcus group B, Haemophilus influenzae type b and Streptococcus pneumoniae antigens has been compared with a technique involving local concentration of the coated latex in an ultrasonic standing wave. The detection of positive control antigen was enhanced, compared with the test-card procedure, over a 16 to 64 fold range on exposure to ultrasound. Sample filtration eliminated non-specific agglutination on ultrasonic exposure of latex in control serum, urine or concentrated urine. Tests of meningitis patient body fluids showed increased detection of antigen with ultrasound for CSF (11/14 > 7/14) serum (8/13 > 3/13) and concentrated urine (8/17 > 2/17) compared to test card assays. The ultrasound detection of antigen in serum or concentrated urine was comparable to that achieved with CSF on test cards. Serum dilution experiments showed that ultrasound could detect antigen in serum over a 1000 fold concentration range.

A convenient dipstrip method (Bacteruritest; Mast Diagnostics) for bacterial quantification was evaluated with 42 endotracheal aspirates. For 31 specimens, the dipstrip method yielded counts within a 10-fold range of surface plate counts. Two specimens yielded counts by the dipstrip within a 100-fold range of plate counts. Six specimens yielded confluent growth at the greatest dilution tested by the dipstrip method, and counts > 10(10) cfu/ml in the surface plate method. Three specimens yielded no detectable growth by the dipstrip and surface plate counts < 10(2) cfu/ml. Dipstrips provide a cheap, convenient method for the routine quantification of the bacterial load in endotracheal aspirates.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.

This article describes the current situation with regard to intrinsic and acquired resistance to antifungal compounds and progress with the development of standardized methods of susceptibility testing for amphotericin B, flucytosine, and the azoles. Recommendations for testing of isolates from patients destined to receive antifungal drug treatment, or in whom therapeutic failure or relapse is suspected, are presented.

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment with ultrasound has been employed to greatly enhance the sensitivity of commercially available latex agglutination tests for fungal antigens. This 5 min procedure detects 40 pg ml-1 of Candida albicans mannan and 70 pg ml-1 of Aspergillus fumigatus galactomannan, a 250 and 500-fold improvement respectively over conventional agglutination test sensitivities. The ultrasound-enhanced test offers the possibility of improved diagnosis and management of patients with systemical candidosis or invasive aspergillosis.

The shoe can be thought of as a powerful tool for controlling human movement. A well-designed shoe can assist in reducing the number of lower limb injuries arising from sport and training activities. The purpose of this paper is to present a summary of the main thrusts of research in this field by means of a digest of current thinking and practice. The paper initially presents a survey of work in the biomechanical field with particular reference to the design of footwear. A review of the types of injury acquired by sportsmen in both training and playing is then followed by a discussion of aspects of footwear design and their role in both contributing to and preventing lower limb injury. Finally, the paper considers support and shock absorption techniques in the context of footwear design. It is concluded that research has been wide-ranging and thorough. However, the complexity of the biomechanical system being studied has prevented definitive recommendations for the prevention of injury being made in every case. Nonetheless, it is clear that a number of guiding principles have been established which should be the basis for future developments in footwear design to minimize the chance of lower limb injury.

Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM-enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotoxaemia was significantly reduced (P = 0.02) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P = 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core-glycolipid was significantly raised (P < 0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the anti-endotoxin antibody activity of the IVIG. These results suggest a role for IgM-enriched IVIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients.

In a study of 63 allogeneic and autologous bone marrow transplants, patients were randomized to receive the IgM and IgA enriched intravenous immunoglobulin (IVIG) preparation (Pentaglobin). Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection. The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction. Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant, although it was not actually possible to document bacterial infections as the cause of death in the control patients. Peak endotoxin levels were significantly reduced (p = 0.02) in those patients receiving Pentaglobin. Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70% of pyrexial episodes were associated with endotoxaemia. Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia.

Two ELISAs were used to detect serum and urinary aspergillus antigen in 121 patients who were profoundly neutropenic after leukaemia therapy or bone marrow transplantation. The presence of antigen correctly predicted development of invasive pulmonary aspergillosis (IPA) in 16 patients. In 2 other cases antigen appeared after the clinical diagnosis had been made, while in only 1 case was antigen not detected. In 11 of 13 episodes of clinically suspected fungal infection antigen was detected before clinical diagnosis was made. By contrast, antigen was detected in only 1 of 90 patients who had no evidence of IPA. Both ELISAs gave positive and negative predictive values for IPA of greater than 95%, demonstrating the value of antigen detection in early diagnosis of aspergillus infection and the assay's ability to predict subsequent development of IPA. We conclude that neutropenic patients should be screened for aspergillus antigen, and propose that initial detection of fungal antigen justifies commencement of empirical antifungal therapy. Such an approach should improve the survival of patients who are at risk of developing this usually fatal infection.

A semistructured interview was used to collect information on a consecutive series of 163 self-harm patients (suicide attempters); 65.8% of the patients had a history of previous self-harm (repeaters). Male repeaters were more likely than men with no self-harm history (first cases) to have left school before ninth grade, to have alcohol abuse problems, and to have family stress. Female repeaters were younger than first cases and reported more difficulties with sexual adjustment and loneliness. Repeaters were more likely to have contacted distress centers and to have had previous mental health contact, including psychiatric hospitalization. A 6-month follow-up indicated four suicides in the repeaters' group and none in the first cases' group. Repeaters appear to be much more dependent than first cases on professional care and to present a high short-term risk for suicide.

The authors assessed the prevalence and demography of depressive symptoms, their association with specific chronic diseases, and their influence on health service use in a large sample of elderly men seen in a primary care setting. Twenty-four percent of respondents reported clinically significant depressive symptoms; the prevalence of major depressive disorders was estimated at 10%, but only 1% reported receiving mental health treatment by a specialist. Self-reported marital separation or divorce and physical disability affecting employment were strongly associated with high depression scores, whereas the normative stresses of aging (widowhood, retirement, social isolation) were not. Only chronic lung disease was differentially associated with high depression scores, and this effect was weak. The authors discuss the implications of these findings for the design of comprehensive health services for the elderly with chronic disease.

A prospective study was undertaken to determine the effectiveness of an empirical antibiotic therapy regimen in 34 neutropenic patients undergoing bone marrow transplantation or remission-induction chemotherapy for leukaemia. Throughout the study period a total of 90 pyrexial episodes were monitored in which organisms designated to be pathogens were isolated from blood cultures on 38 occasions. The response rate to the combination of a ureidopenicillin with gentamicin fell sharply from 50% during patients' first pyrexial episodes to zero during the third and subsequent episodes. The preponderance of Gram-positive bacteria and the high overall resistance of bacterial isolates to these antibiotics have led us to reconsider our approach to empirical therapy and to include antibiotics with greater activity against Staphylococcus epidermidis. The emergence of fungi as a major cause of morbidity in patients with prolonged neutropenia underlines the necessity to introduce early empirical antifungal therapy in this group of patients.

The dexamethasone suppression test (DST) was used in an in-patient crisis unit to determine whether the test could identify suicidal patients who might benefit from tricyclic antidepressants. DST results, DSM-III diagnoses, and measures of symptom levels were obtained for 72 patients admitted for a 3-5 day period; 31 were non-suppressors. Abnormal DST results were not related to DSM-III diagnosis or to scores on measures of depression and symptom levels. Only three patients met DSM-III criteria for major depression with melancholia; 26 patients had a diagnosis of alcohol or substance abuse. The poor specificity of the DST in this patient population suggests that its routine use in such patients could be highly misleading.

In the course of construction of a new bone marrow transplantation (BMT) unit, six of nineteen children undergoing BMT in the adjacent ward area died of invasive pulmonary aspergillosis (IPA). Ward air samples confirmed that heavy fungal spore contamination had occurred. The introduction of laminar air flow (LAF) isolation terminated the outbreak and no subsequent cases of IPA have been documented in patients nursed entirely in LAF. LAF has not reduced the rates of other complications associated with BMT.