Time-response relationships for the accumulation of Cu, Ni and Zn by seven-spotted ladybirds (Coccinella septempunctata L.) under conditions of single and combined metal exposure.

Accumulation, and therefore toxicity, of trace metals in invertebrates may be affected by potential interactive effects that can occur amongst different metallic elements. However, there is little data on the nature and effects of such interactions in terrestrial systems. This work reports the interactions among Cu, Ni and Zn during accumulation by the beetle Coccinella septempunctata. Test animals were treated with 500mgkg(-1) of each metal singularly and in combination for 15d. The effects of treatment with a single metal had no effect on the baseline concentrations of the other two. Time-response relationships for Cu and Ni after treatment with one metal were curvilinear, demonstrating that the metals were initially accumulated, but after ∼8d regulatory mechanisms became effective. This resulted in decreasing concentrations in test animals despite continued treatment. In contrast, the time-response relationship for Zn was linear. Treatment with metals in combination markedly altered the time-response relationships with all three metals showing a linear trend and the slope of the Zn relationship increasing significantly. After 15d of exposure this had the effect of increasing the metal concentration in animals exposed in combination compared to those exposed singularly by 144% to 38.3mgkg(-1) for Cu, 141% to 27.5mgkg(-1) for Ni and 55% to 311mgkg(-1) for Zn. For all metals, differences amongst treatments were significant, indicating that inter-element interactions can enhance the concentration of trace metals in C. septempunctata.

Daily versus weekly azithromycin in cystic fibrosis patients.

Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly. A double-blind, randomised study was carried out in 208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia. Equivalence was demonstrated between the two groups (daily versus weekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of +/-10%. In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.

A semantically enabled formalism for the knowledge management of Parkinson's disease.

Bio-ontology is a formal representation of biological concepts that is used in the interchange of communication between computers and humans alike. They can then be used in the formulation and retrieval of knowledge. In developing a knowledge-based system for Parkinson's Disease, a procedure of knowledge map was used to capture and harness the intellectual resources of an organization, and new paradigms for knowledge mapping were also formulated. Knowledge bases for symptoms and drugs, physiotherapy, speech and language therapy, and dieting that affect patient care were developed. Finally, the knowledge bases were merged to form a single central repository of knowledge base.

A combined medical and surgical approach to hydatid disease: 12 years' experience at the Hospital for Tropical Diseases, London.

BACKGROUND: There is no consensus as to the most appropriate treatment for the varied and often complicated presentations of hydatid disease in Britain. We looked at our own results over a 12-year period to see if a consistent and logical plan had emerged. PATIENTS AND METHODS: 70 patients presenting between 1986 and 1998 were analysed retrospectively, with regard to their presentation, diagnosis, treatment and outcome, with particular reference to the use of chemotherapy, and to the difficulties of post-treatment assessment by serology and imaging. RESULTS: 37 patients had been treated previously. 35 had hepatic cysts and 26 multiple cysts. 4 patients were treated by surgery alone, 44 by chemotherapy and surgery, and 14 by chemotherapy alone. The combined use of albendazole and praziquantel pre-operatively reduced significantly the number of cysts that contained viable protoscolices: 1/25 versus 5/8 that received albendazole alone (P = 0.00013). During the 12-year period, it became our policy to aim for 3 months drug treatment (albendazole throughout with praziquantel for 2 weeks), re-assess and proceed either to surgery or to continue with chemotherapy. CONCLUSIONS: It is possible to construct an algorithm for the management of patients with hydatid disease by chemotherapy and surgery, but the assessment of results by indirect techniques remains difficult.

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Generation of human cytolytic T lymphocyte lines directed against prostate-specific antigen (PSA) employing a PSA oligoepitope peptide.

Prostate-specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity. T cell lines from different HLA-A2 and HLA-A3 donors were established by in vitro stimulation with PSA-OP; the CTL lines lysed PSA-OP as well as PSA-1- or PSA-3-pulsed C1R-A2 cells, and PSA-OP and PSA-9-pulsed C1R-A3 cells, respectively. The CTL lines derived from the PSA-OP peptide also lysed PSA-positive prostate cancer cells. PSA-OP-derived T cell lines also lysed recombinant vaccinia-PSA-infected targets but not targets infected with wild-type vaccinia. PSA-OP did not bind HLA-A2 and HLA-A3 molecules. The decrease in cytotoxicity in the presence of protease inhibitors suggests that the PSA-OP is cleaved into shorter peptides, which in turn can interact with HLA-class I molecules and, as a consequence, induce CTL-mediated lysis. We have also demonstrated that it is possible to induce CTL responses in HLA-A2.1/Kb transgenic mice by immunization with PSA-OP with adjuvant. These studies thus provide evidence that oligopeptides such as PSA-OP may be useful candidates for peptide-based cancer vaccines.

One-to-one midwifery care at the Wessex Maternity Centre.

Independent midwifery practice can offer women greater choice, flexibility and more personalised care than may be available in NHS maternity units. The Wessex Maternity Centre offers continuity of care through paired caseloading by midwives. If women need to go into hospital, there is an arrangement whereby their midwife goes with them and continues to provide care in hospital. 50% of clients at the Centre are primiparae. The Centre's midwives have their own clinical protocols based on up-to-date research and practice.

Staging of symptomatic primary breast cancer with MR imaging.

OBJECTIVE: This study was designed to investigate the accuracy of contrast-enhanced MR imaging in the locoregional staging of symptomatic primary breast cancer and to determine the impact of contrast-enhanced MR imaging in planning surgical management. MATERIALS AND METHODS: Ninety patients with primary breast cancer (including two bilateral cancers) diagnosed and treated on the basis of conventional triple assessment (clinical, cytologic, and mammographic examination) underwent MR imaging at 1.0 T using a three-dimensional fast low-angle shot T1-weighted pulse sequence before and after contrast enhancement. A short inversion time inversion recovery sequence was also obtained to evaluate the axilla of each patient. After resection, tumors were histopathologically mapped in detail and correlated with the extent of contrast enhancement on MR imaging. RESULTS: On the basis of triple assessment, 53 cancers were treated by wide local excision, of which 17 (32%) had positive margins at excision. Residual disease at reexcision was detected in eight of these 17 patients, a finding that correlated accurately with the extent of contrast enhancement on MR imaging. MR imaging was more accurate than mammography in determining invasive tumor size (r2 = .93 versus r2 = .59), in depicting multifocality and extensive intraductal component (sensitivity, 81% versus 62%), and in assessing nipple-retroareolar complex. MR imaging-histopathologic correlation was possible in 75 axillae. Sensitivity and specificity for axillary node metastases were 90% and 82%, respectively. CONCLUSION: MR imaging of the breast has value in the preoperative locoregional staging of symptomatic primary breast cancer and is useful in planning a single definitive surgical resection in patients with breast cancer.

Comparison of magnetic resonance imaging and conventional triple assessment in locally recurrent breast cancer.

BACKGROUND: Magnetic resonance imaging (MRI) was compared with triple assessment (clinical examination, cytology and mammography) in the differentiation of post-treatment changes from local recurrence of breast carcinoma. METHODS: Thirty patients treated previously by breast conservation surgery and radiotherapy with clinical suspicion of local recurrence were evaluated prospectively by triple assessment and MRI. Breast MRI was performed on a 1-tesla scanner using a T1-weighted three-dimensional fast low angle shot pulse sequence before and after contrast enhancement. RESULTS: Local recurrence was confirmed histologically in 14 patients. Of these, mammography identified seven (sensitivity 50 per cent), cytology 11 (sensitivity 79 per cent) and breast MRI 13 (sensitivity 93 per cent). Compared with histological measurement, breast MRI allowed an accurate estimation of the extent of local recurrence (r2 = 0.98). Morphologically abnormal areas without contrast enhancement correlated with postradiation changes. False-positive contrast enhancement was seen in two patients (specificity 88 per cent) in whom histology confirmed inflammatory changes only. CONCLUSION: Breast MRI is useful in the evaluation of patients with a high clinical suspicion of local recurrence within the irradiated conserved breast.

Brain of the conscious dog is sensitive to physiological changes in circulating insulin.

The aim of this study was to determine whether a selective, physiologically relevant increase in blood-borne insulin perfusing the brain has an impact on the counterregulatory response to hypoglycemia. Experiments were carried out on 12 conscious 18-h-fasted dogs. Insulin was infused (1 mU x kg(-1) x min(-1)) in separate, randomized studies into a peripheral vein (n = 6) or both carotid and vertebral arteries (n = 6). This resulted in equivalent systemic insulinemia (38 +/- 2 vs. 35 +/- 5 microU/ml) but differing head insulin levels (38 +/- 2 microU/ml during peripheral infusion and an estimated 90 microU/ml during head insulin infusion). Glucose was infused during peripheral insulin infusion to equate the level of hypoglycemia (58 +/- 2 mg/dl) to that obtained during head insulin infusion (57 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and hypoglycemia, incremental area under the curve responses for epinephrine, glucagon and cortisol were increased during head insulin infusion (P < 0.05). Net hepatic glucose output, gluconeogenesis, and lipolysis were increased 50-100% (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog 1) physiologically relevant increases of blood-borne insulin to the head can amplify neuroendocrine and metabolic counterregulatory responses and 2) glucagon secretion can be regulated, in part, by neural efferent activity.

In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen.

BACKGROUND: Protein antigens are presented to cytotoxic T lymphocytes as small peptides (approximately 9-10 amino acids long) bound to class I molecules of the major histocompatibility complex. The identification of tumor-associated antigens and specific peptide epitopes (i.e., antigenic determinants) may be useful in the development of anticancer vaccines. The generation of a cytotoxic T-cell response to one peptide epitope (amino acids 146-154) of human prostate-specific antigen (PSA) has been reported. PURPOSE: Our aim was to identify novel PSA peptides capable of eliciting specific cytotoxic T-cell responses. METHODS: Candidate peptides were identified on the basis of the following criteria: 1) they contained consensus amino acid motifs for binding to HLA-A2, which is the most common type of class I molecule; 2) they lacked strong homology with PSA-related kallikrein proteins; and 3) they were capable of stabilizing HLA-A2 class I molecules on the surface of human T2 (transport deletion mutant) cells, which are defective in antigen presentation. T-cell lines capable of killing (i.e., lysing) T2 target cells that had been pulsed with specific PSA peptides were generated from three different males (two disease-free individuals and one patient with prostate cancer) by incubating peripheral blood mononuclear cells with the peptides and interleukin 2. Specific cell lysis was monitored by the release of radioactivity from target cells that had been labeled with [111In]oxyquinoline. RESULTS: Two novel PSA peptides capable of eliciting cytotoxic T-cell responses were identified; these peptides were designated PSA-1 (amino acids 41-150) and PSA-3 (amino acids 154-163). Four different cytotoxic T-cell lines were generated in response to these peptides-three against PSA-3 and one against PSA-1. Specific lysis of peptide-pulsed T2 cells by the T-cell lines was blocked by the addition of a monoclonal antibody directed against class I molecules. The T-cell lines were also capable of lysing PSA-positive, HLA-A2-positive LNCaP cells (human prostate carcinoma cells). The specificity of LNCaP cell lysis was shown by the following: 1) the inability of added human K562 (chronic myelogenous leukemia) cells to inhibit it, 2) the ability of added anti-HLA-A2 antibodies to block it, and 3) the inability of the T-cell lines to induce substantial lysis of PSA-negative, HLA-A2-positive human cancer cells. IMPLICATIONS: Our studies form a rational basis for the use of PSA peptides or recombinant vectors encoding PSA in the development of anticancer vaccine immunotherapy protocols for patients with prostate cancer.

Vaginal birth after lower segment caesarean section.

One delivery in eight in the UK is by caesarean section. Women who have had a previous caesarean section may approach a midwife in subsequent pregnancies because they want more control over their labour. Vaginal birth after caesarean section (VBAC) is a safe option for women with a lower segment scar. Factors associated with a favourable outcome include spontaneous labour and freedom of movement during labour. Factors hindering successful outcome include reduced mobility, use of oxytocin, and time limits set on progress of labour.

Interstitial laser hyperthermia: a new approach for treating liver metastases.

The palliative management of hepatic metastases remains unsatisfactory. There is a need for a simple non invasive technique which can stop or retard the rate of tumour growth. In principle, Interstitial Laser hyperthermia may fulfil such a role. In experimental studies, this technique produced precise in situ necrosis within solid organs which healed safely. In a pilot feasibility study, we treated ten patients with a total of 18 hepatic metastases on 31 occasions using a percutaneous approach to achieve an overall objective response rate of 44%. The treatment proved simple to perform, was well tolerated and produced radiological evidence of necrosis in small metastases (diameter less than or equal to 3 cm). However, further research is required before the technique can be regarded as established. Its future role in most cases will be to control the growth of discrete hepatic metastases unsuitable for resection. In instances where the extent of necrosis can be matched accurately to tumour volume, the potential for cure exists.

Ultrasound features of low power interstitial laser hyperthermia.

Low power interstitial laser hyperthermia (ILH) is a reliable means of producing in situ thermal necrosis. Ultrasonic studies have been carried out of the changes that occur in canine liver during ILH performed at laparotomy. With a single fibre delivering Nd-YAG laser at 1-1.5 W for 670 s an hyperechoic region developed at the fibre tip measuring 5-6 mm in diameter; around this developed an area of hypoechoic change (up to 500s) giving a total area of changed echogenicity of 14-16 mm. With a multiple fibre system using 4 laser fibres simultaneously the sonographic changes were a summation of the changes seen with a single fibre, the hypoechoic areas overlapping. With this four fibre system the creation of large (3.5 x 2.8 cm) areas of thermal necrosis was possible. There was good correlation between the sonographic and pathological measurements of the region of thermal change. The sonographic studies showed the extension and overlap of regions of thermal necrosis and allowed visualization and accurate measurement of the area undergoing change. The same combined technique has been successfully applied in a small number of clinical cases and may be of use in the treatment of tumours in solid organs.

Multiple-fibre low-power interstitial laser hyperthermia: studies in the normal liver.

Multiple four-fibre low-power interstitial laser hyperthermia was performed in the canine liver to establish the parameters with which large areas of thermal necrosis could be made. Using 1.5 W for 670 s (4020 J in total) and a fibre spacing of 1.5 cm, lesions with dimensions of 3.6 x 3.1 x 2.8 cm were achieved in 75 per cent of those attempted. There was no mortality and a low morbidity rate. These lesions could be visualized in both their development and resolution using ultrasonography. Healing occurred by 1 year. Temperatures in the centre of the heated region were 60 degrees C, which is more than enough to cause thermal cell death. There was good correlation between the temperatures recorded, the sonographic changes seen, and the pathological evidence of necrosis. Multiple-fibre low-power interstitial laser hyperthermia performed with ultrasonic guidance may be of use in the treatment of liver tumours.

Interstitial laser hyperthermia: a new approach to local destruction of tumours.

The use of local hyperthermia to treat cancer of the internal organs has been limited by the difficulty of controlling delivery of heat and limiting the effects to the tumour, but this can be overcome by using laser light transmitted through thin flexible fibres. Laser energy was delivered to tumours through fibres inserted percutaneously through needles directly into the centre of the tumour area. Ultrasound scanning was used to locate the tumour, position the fibres correctly within the tumour, and monitor the development of thermal necrosis in real time during laser exposure and through the subsequent period of healing. Five patients were treated (one with a tumour of the breast, one with a subcutaneous secondary tumour, one with a recurrent pancreatic tumour, and two with secondary tumours in the liver). Tumour necrosis was found on ultrasonography or computed tomography in all, and there were no immediate or delayed complications. In one patient the size of the isolated secondary tumour in the liver had not increased over 10 months, and he subsequently showed no other evidence of residual cancer. To develop this technique careful studies are essential to ensure that in every case the extent of thermal necrosis produced by absorption of the laser light can be matched to the full extent of the tumour being treated and that there is always sufficient adjacent normal tissue to ensure safe healing. These preliminary results suggest that this simple technique can be applied safely and effectively to common tumours in humans; more extensive trials in a range of cancers of solid organs are warranted.