Note: A miniature oscillating microbalance for sampling ice and volcanic ash from a small airborne platform.

A lightweight and low power oscillating microbalance for in situ sampling of atmospheric ice and volcanic ash is described for airborne platforms. Using a freely exposed collecting wire fixed at only one end to a piezo transducer, the instrument collects airborne materials. Accumulated mass is determined from the change in natural frequency of the wire. The piezo transducer is used in a dual mode to both drive and detect the oscillation. Three independent frequency measurement techniques are implemented with an on-board microcontroller: a frequency sweep, a Fourier spectral method, and a phase-locked loop. These showed agreement to ±0.3 Hz for a 0.5 mm diameter collecting wire of 120 mm long, flown to 19 km altitude on a weather balloon. The instrument is well suited to disposable use with meteorological radiosondes, to provide high resolution vertical profiles of mass concentration.

In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes.

Interleukin-13 (IL-13) sequentially binds to IL-13Ralpha1 and IL-4Ralpha forming a high affinity signalling complex. This receptor complex is expressed on multiple cell types in the airway and signals through signal transducer and activator of transcription factor-6 (STAT-6) to stimulate the production of chemokines, cytokines and mucus. Antibodies have been generated, using the UCB Selected Lymphocyte Antibody Method (UCB SLAM), that block either binding of murine IL-13 (mIL-13) to mIL-13Ralpha1 and mIL-13Ralpha2, or block recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. Monoclonal antibody (mAb) A was shown to bind to mIL-13 with high affinity (K(D) 11 pM) and prevent binding of mIL-13 to mIL-13Ralpha1. MAb B, that also bound mIL-13 with high affinity (K(D) 8 pM), was shown to prevent recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. In vitro, mAbs A and B similarly neutralised mIL-13-stimulated STAT-6 activation and TF-1 cell proliferation. In vivo, mAbs A and B demonstrated equipotent, dose-dependent inhibition of eotaxin generation in mice stimulated by intraperitoneal administration of recombinant mIL-13. In an allergic lung inflammation model in mice, mAbs A and B equipotently inhibited muc5ac mucin mRNA upregulation in lung tissue measured two days after intranasal allergen challenge. These data support the design of therapeutics for the treatment of allergic airway disease that inhibits assembly of the high affinity IL-13 receptor signalling complex, by blocking the binding of IL-13 to IL-13Ralpha1 and IL-13Ralpha2, or the subsequent recruitment of IL-4Ralpha.

Epidemiology of diabetic retinopathy and macular oedema: a systematic review.

AIMS: To systematically review the literature on the prevalence and incidence of diabetic retinopathy (DR) and macular oedema (MO). METHODS: A search of the bibliographic databases (Medline, Embase, CINAHL) was conducted up to October 2001. Selected relevant studies were scrutinized and included in the review. RESULTS: A total of 359 studies were included. The studies were reported in nearly 100 different journals and in over 50 countries. The majority of the studies were US-based, with large studies such as the Wisconsin Epidemiologic Study of Diabetic Retinopathy dominating the literature. The studies were quite dated and highly heterogeneous in nature in terms of patient selection with variable inclusion criteria (age range, gender, diabetes duration and type, ethnicity, comorbidity, and DR status, assessment, and classification). CONCLUSIONS: There are inconsistencies between epidemiological studies, and differences in study methods may contribute to conflicting reports of prevalence and incidence of DR and MO in diabetic populations. As new therapies for DR and its associated complications emerge, the need to capture and monitor new epidemiological data becomes increasingly important to be able to assess the impact and effectiveness of these therapies. Robust, longitudinal capture of patient data is, therefore, essential to evaluate the impact of current practice on the epidemiology of diabetic eye complications.

Descriptive epidemiology of adult critical care transfers from the emergency department.

AIMS: To describe the nature, frequency, and characteristics of adult critical care transfers originating from the emergency department (ED). METHODS: A one year prospective regional descriptive study using multiple data sources of all critically ill adults transferred from an ED or a minor injuries unit (MIU) within the former Yorkshire Regional Health Authority Area or into a regional critical care facility if originating from an ED or MIU elsewhere. RESULTS: 29 EDs transferred 349 adults into the regional critical care facilities. The median number of transfers per department within the region was 18 (range 1 to 42). Seventeen were transferred from outside the region. A total of 263 (75%) patients were transferred for specialist care and 76 (22%) for non-clinical reasons. Altogether 294 (84%) were admitted to intensive care or a high dependency unit at the receiving hospital. The in-hospital documented mortality rate was 26%. A total of 170 patients (49%) had traumatic pathology of which 101 were principally transferred for management of a head injury. Median time in the ED was 3 hours 5 minutes (range 11 minutes to 17 hours 47 minutes). In 146 (42%) patients the decision to transfer was primarily made by the emergency medicine clinician. A total of 251 (72%) patients were intubated. The documented critical incident rate was 15%. CONCLUSION: Trauma is the most common reason for transfer of the critically ill adult from the ED. A significant number of patients are transferred, however, with medical and surgical conditions and for non-clinical reasons. There continues to be problems with the quality of care that these patients receive. Emergency medicine clinicians must be actively involved in the development of regional critical care systems as a significant proportion of all critically ill adults transferred originate from the ED.

Variation in clinical decision making is a partial explanation for geographical variation in lower extremity amputation rates.

BACKGROUND: Rates of lower extremity amputation vary significantly both between and within countries. The variation does not appear to support differences in need as an explanation. This study set out to see if variations in clinical decision making might contribute to the explanation. METHODS: Based on an extensive audit database of lower extremity amputations and revascularization operations, a decision model was produced. Drawing on items in this model allowed the selection of six clinical cases that differed in their probability of having amputation as the outcome. Two cases had 80 per cent or more, two cases had 45--55 per cent and two cases had 20 per cent or less probability of amputation. Each of ten consultant vascular surgeons looked at these cases without knowledge of their probability of outcome and decided on amputation or revascularization. RESULTS: Overall the chance-adjusted level of agreement (kappa coefficient) between the decisions made by ten surgeons on the six clinical cases and the actual outcome was 0.46, indicating a moderate level of agreement. The kappa coefficient for individual surgeons showed complete agreement (kappa = 1) for four, substantial agreement (kappa = 0.66) for four, fair agreement (kappa = 0.32) for one and no agreement other than at a chance level (kappa = 0) for one surgeon. CONCLUSION: Variations in the clinical decisions made by vascular surgeons given the same patient are likely to explain at least a part of the observed geographical variation in rates of lower extremity amputation. Consensus guidelines may enable more consistent decision making for this problem.

Aldose reductase inhibitors for the prevention and treatment of diabetic peripheral neuropathy.

OBJECTIVES: To assess the efficacy of aldose reductase inhibitors in the prevention, reversal or delay in the progression of diabetic peripheral neuropathy. SEARCH STRATEGY: The Cochrane Diabetes Group's database was searched and the citation lists of identified trials and previous reviews checked. Investigators identified as active in the field were approached for overlooked studies. SELECTION CRITERIA: Randomised controlled trials of aldose reductase inhibitors versus placebo, no treatment or other treatment in diabetic patients with or without clinical neuropathy. DATA COLLECTION AND ANALYSIS: Nerve conduction velocity was the only end point measured in all trials. Treatment effect was evaluated in terms of nerve conduction velocity mean difference in median and peroneal motor and median and sural sensory nerves. MAIN RESULTS: 19 trials, testing 4 different aldose reductase inhibitors for between 4 to 208 weeks duration (median 24 weeks), met the inclusion criteria for the meta-analysis. A small but statistically significant reduction in decline of median and peroneal motor nerve conduction velocities was present in the treated group when compared to the control group (weighted mean 0.66 m/s 95% CI 0.18-1.14 m/s and 0.53 m/s 95% CI 0.02-1.04m/s respectively). No clear benefit of aldose reductase inhibitor treatment was observed in either of the sensory nerves. REVIEWER'S CONCLUSIONS: Although aldose reductase inhibitor treatment has been demonstrated to diminsh the reduction in motor nerve conduction velocity, the clinical relevance of such a change in this outcome measure is uncertain. There was no effect in terms of this outcome measure in the smaller sensory fibres, degeneration of which is primarily responsible for the most common neuropathic syndrome associated with diabetes, that of severe pain and loss of sensation in the extremity leading in some cases to ulceration and eventual amputation.

Management of major trauma: changes required for improvement.

AIMS: To describe the views of key healthcare professionals on the changes they considered to be important in the reduction of major trauma mortality between 1988 and 1995 in Leeds. METHODS: Qualitative unstructured interviews with a purposive sample of 10 healthcare professionals deemed to be key personnel by an experienced consultant who had provided acute trauma care throughout the relevant period. Each interview was tape recorded and transcribed; each transcript was analysed for important themes by two independent researchers who then discussed their results to resolve any differences in interpretation. RESULTS: Three categories of change became evident: "policy", "infrastructure", and "philosophy of care". Each of these categories seemed to be equally important. Policy changes identified as important were the Royal College of Surgeons of England's report into trauma care (1988), the setting of standards for paramedic training, and the national audit of major trauma outcomes. Important infrastructure changes identified were training in advanced trauma life support, decreased ambulance response times, reorganisation towards "consultant led" hospital services, and an emphasis on quality monitoring. Changes in philosophy of care were increases in levels of teamwork, commitment, communication, and confidence. Together these facilitated an overall restructuring and refocusing of care. CONCLUSIONS: No individual change is seen as dominant for improved care, but rather a strategic mixture of facilitating national and regional policy guidance, organisational restructuring, and congruent professional attitudes were integral components leading to the observed changes. Improving outcomes in other areas is likely to involve an integrated series of changes which must be managed as a total system.

WITHDRAWN: Aldose reductase inhibitors for the prevention and treatment of diabetic peripheral neuropathy.

BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes mellitus. OBJECTIVES: To assess the efficacy of aldose reductase inhibitors in the prevention, reversal or delay in the progression of diabetic peripheral neuropathy. SEARCH STRATEGY: The Cochrane Diabetes Group's database was searched and the citation lists of identified trials and previous reviews checked. Investigators identified as active in the field were approached for overlooked studies. SELECTION CRITERIA: Randomised controlled trials of aldose reductase inhibitors versus placebo, no treatment or other treatment in diabetic patients with or without clinical neuropathy. DATA COLLECTION AND ANALYSIS: Nerve conduction velocity was the only end point measured in all trials. Treatment effect was evaluated in terms of nerve conduction velocity mean difference in median and peroneal motor and median and sural sensory nerves. MAIN RESULTS: 19 trials, testing 4 different aldose reductase inhibitors for between 4 to 208 weeks duration (median 24 weeks), met the inclusion criteria for the meta-analysis. A small but statistically significant reduction in decline of median and peroneal motor nerve conduction velocities was present in the treated group when compared to the control group (weighted mean 0.66 m/s 95% CI 0.18-1.14 m/s and 0.53 m/s 95% CI 0.02-1.04m/s respectively). No clear benefit of aldose reductase inhibitor treatment was observed in either of the sensory nerves. AUTHORS' CONCLUSIONS: Although aldose reductase inhibitor treatment has been demonstrated to diminish the reduction in motor nerve conduction velocity, the clinical relevance of such a change in this outcome measure is uncertain. There was no effect in terms of this outcome measure in the smaller sensory fibres, degeneration of which is primarily responsible for the most common neuropathic syndrome associated with diabetes, that of severe pain and loss of sensation in the extremity leading in some cases to ulceration and eventual amputation.

Improvements in trauma survival in Leeds.

One hundred and eighty-six cases of major trauma (Injury Severity Score > 15) admitted to the two Leeds hospitals in 1988/89 were compared with 198 cases admitted in 1992/93 to ascertain if a system of trauma care which had evolved in the hospitals during this time had affected outcome of these patients. Injury severity score, age, and sex distribution were similar for the two groups. There were significantly fewer deaths in 1992/93, particularly in those patients with a score less than 41. It would appear that the emphasis, since 1988, on timely and definitive management of patients with major trauma has led to improved survival of the seriously injured in Leeds.

Enzyme transfer from pancreas to plasma during acute pancreatitis. The contribution of ascitic fluid and lymphatic drainage of the pancreas.

Acute pancreatitis was induced in anaesthetised dogs in order to investigate the relative contribution of peritoneal ascitic fluid and thoracic duct lymph as routes of transfer of pancreatic enzymes from the inflamed gland to the blood. In eight animals the exudate from the gland was collected in a plastic bag and continuously drained away, and in a further eight it was allowed to accumulate within the peritoneal cavity. The thoracic duct was cannulated and in four of the animals of each group the lymph which drained was discarded; in the other four it was returned via a venous cannula. The initial rise of plasma amylase and lipase was probably because of the direct transfer of enzyme into veins draining the pancreas or peri-pancreatic tissues. Thereafter transfer of enzyme via the thoracic duct significantly influenced plasma concentrations of amylase and lipase. The majority of enzyme released from the gland accumulated within the peritoneal ascitic fluid, but this intraperitoneal accumulation did not appear to have a significant influence upon lymph or plasma concentrations of amylase or lipase.