Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents.

Microbubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>1012vs. >1010 NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were suficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.

Colonic malignancy arising in colitis - a single unit experience.

OBJECTIVES: Colorectal malignancy complicating inflammatory bowel disease constitutes 1% of all colorectal malignancies. Although its overall numbers are low it represents the greatest cause of colitis related mortality in these patients. This paper describes the management of 24 patients presenting to a single unit over a period of 10 years. METHODS: The names of patients were collected prospectively when they presented with malignancy. Clinical details were collected by retrospective review of charts. RESULTS: In all, 24 patients with 27 malignancies were identified. The median age of presentation with malignancy was 56 years. Most patients were treated with proctocolectomy. Other patients were treated with segmental colectomy. In these patients the surgical procedure was dictated by the stage of the cancer, the age and comorbid state of the patient and the severity of ongoing colitis. CONCLUSIONS: Malignancy arising in colitis will constitute only a small part of a colorectal practice. The optimum method for detecting early, and potentially curable, disease has not been defined. Surgery should be tailored to the individual needs of the patient.

No unique role for nausea attributed to eating a food in the recalled acquisition of sensory aversion for that food.

Currently in the U.K., as in the U.S.A. 20 years ago, when students were asked to name a food that they did not like, more dislike for the food was attributed to nausea or vomiting after eating than to other gastrointestinal symptoms or to illness in other parts of the body. However, when members of the public first identified adverse symptoms and then attributed them to foods, and dislike for the food was first enquired about on a later occasion, there was no evidence for a unique role for a causal association with nausea in the human acquisition of food aversions. Furthermore, fear of the symptom was more prevalent than acquired sensory aversion when there was more precise recall of memories of the food being followed by nausea or vomiting and greater likelihood of there having been causal contingency rather than mere coincidence. Therefore, the more frequent invocation of nausea than of some other symptoms as the cause of a sensory aversion to a food may result from personal theory of the body, rather than from a veridically recalled occasion when nausea was contingent on eating the food---an event that must occur for aversion to arise from associative conditioning.

Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis.

BACKGROUND: Tumour necrosis factor (TNF) alpha has been implicated in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the contribution of TNF to the pathogenesis of hapten-induced colitis. METHODS: Colitis was induced in Wistar rats using intracolonic instillation of the hapten trinitrobenzenesulphonic acid (TNBS) in ethanol. Animals were treated with monoclonal anti-TNF antibody (cTN3), an idiotype control antibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was assessed quantitatively. RESULTS: The use of either TNF inhibitor attenuated the acute-phase response in the early stages of colitis. Median (interquartile range (i.q.r.)) alpha 2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) micromol/ml) or pentoxifylline (567 (253-1454) micromol/ml) compared with levels in untreated colitic animals (1552 (1406-1998) micromol/ml) (P < 0.001 and P = 0.006, respectively). In established colitis, administration of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weight): colitic animals -2.3 (- 5.5 to 9.2) per cent versus cTN3-treated rats 15 (7.5-16.7) per cent; P < 0.05. CONCLUSION: The systemic response to TNBS-induced colitis appears to be at least partially dependent on TNF. This study did not provide evidence to support a role for TNF in the pathogenesis of colonic inflammation in this model. Presented in part to the 86th meeting of the Surgical Research Society in Nottingham, UK, 9-11 July 1997, and published in abstract form as Br J Surg 1997; 84: 1613

Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis.

BACKGROUND: Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflammatory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIALS AND METHODS: Colitis was induced in Wistar rats. Selective (AMG) and non-selective (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide synthase were given in the drinking water. Colonic citrulline and arginine concentrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system. RESULTS: Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the agents reduced the severity of colonic inflammation. CONCLUSIONS: Oral administration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colitis.

Immunohistochemical changes in the anterior olfactory nucleus of the developing rat.

The anterior olfactory nucleus (AON) is located caudal to the olfactory bulb in the olfactory peduncle. Although this important structure is involved in the bilateral coordination of olfactory information, relatively little is known about its development, structure, or function. The present report details results from an immunohistochemical examination of specific neuronal (microtubule-associated protein-2: MAP2, calbindin D28-k, neuropeptide-Y: NPY) and glial (astrocytes: glial fibrillary-associated protein, or GFAP, oligodendrocytes; RIP) populations in postnatal Days 10, 20, and 30 rats. MAP2-immunoreactivity (-ir), was present throughout the AON, although most dense in the outer plexiform layer. Increases in labeling occurred from Day 10 to Day 30, reflecting the maturation of dendritic processes. Both temporal and regional differences in expression were found with the two neuronal markers. For example, although substantial numbers of calbindin-ir cells were observed as early as Day 10, relatively few cells exhibited NPY-ir. An apparent decline in the number of stained figures was observed from Days 20-30 with both markers. Most cells exhibiting calbindin- or NPY-ir were found in the inner half of the cellular zone of the AON. GFAP-ir was localized mainly to the subependymal zone and the lateral olfactory tract (LOT) at Day 10, with successive increases in staining in the cellular and plexiform layers at Days 20 and 30. Oligodendrocyte-ir was restricted to the anterior commissure and the LOT at Day 10, with dramatic increases in labeling of the cellular and plexiform layers observed by Days 20 and 30. These results represent some of the first analyses of the maturation of specific cellular phenotypes within this large neural region.

Tumour necrosis factor and inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine produced largely by macrophages and T lymphocytes. It has been implicated in the pathogenesis of numerous immunoinflammatory processes. Recently, a number of studies have indicated that anti-TNF antibodies may be of value in the treatment of inflammatory bowel disease. METHODS: The literature is reviewed regarding the role of TNF in the pathogenesis of inflammatory bowel disease and the results of administering TNF inhibitors. RESULTS AND CONCLUSIONS: TNF may have a role in the pathogenesis of inflammatory bowel disease. The effects of TNF inhibitors are complex and incompletely understood. Anti-TNF antibody strategies may have a role in the treatment of acute exacerbations of the disease but are unlikely to be appropriate therapies for long-term management.

Apoptosis in the rostral migratory stream of the developing rat.

The rostral migratory stream consists of a large number of cells migrating from the lateral ventricles to the rostral telencephalon, primarily the olfactory bulb. The pathway continually provides neuro- and glioblasts throughout life. The present paper indicates that a considerable number of cells undergo apoptotic cell death en route, even in young (day 3) rats when presumably many vacant sites are still available in the developing brain.

The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.

Increased lipid peroxidation and reduced antioxidant status may contribute to the development of complications in diabetes. The aim of this study was to assess the effects of dietary treatment of noninsulin-dependent diabetes on these parameters. Twenty patients with newly diagnosed noninsulin-dependent diabetes were recruited along with 20 age, sex, and smoking-status-matched control subjects. Dietary intake was assessed by food frequency questionnaire and 24-h dietary recall and blood collected for biochemical analyses before and 2 months after dietary treatment was initiated. Carbohydrate, fat, and protein intake fell in patients following dietary advice. Among micronutrients, intakes of vitamins C, E, and A, carotene, selenium, copper, zinc, and iron were similar in patients and controls. Vitamin C intake in patients rose following dietary advice (44.6 +/- 11.7 vs. 49.5 +/- 5.5 mg/d, p < .05), while there was no change in intake of other micronutrients. Fasting plasma glucose in diabetic subjects fell from 13.6 +/- 1.1 mmol/l at recruitment to 9.7 +/- 1.1 mmol/l after diet (p < .01), and this was accompanied by a fall in hemoglobin Alc from 7.44 +/- 0.67% to 5.91 +/- 0.57% (p < .01). Serum malondialdehyde was higher in patients than controls at T0 (2.39 +/- 0.55 mumol/l vs. 1.48 +/- 0.33; p < .01), and fell following diet to 1.42 mumol/l (p < 0.01). Ascorbate was lower in patients than controls (1.27 +/- 2.9 mumol/k vs. 41.4 +/- 9.3; p < .01) at baseline and rose after diet to 27.8 +/- 6.4 (p < .01). beta-Carotene also rose after diet in patients (0.13 +/- 0.04 mumol/l vs. 0.17 +/- 0.04; p < 0.05), as did lipid corrected alpha-tocopherol (4.39 +/- 1.09 mumol/mmol cholesterol vs. 5.16 +/- 1.18; p < .05). Reduced lipid peroxidation and improved antioxidant status may be one mechanism by which dietary treatment contributes to the prevention of diabetic complications.

Deaths from injury and poisoning of children in Liverpool: a ten-year survey 1978-1987.

Deaths of children in Liverpool under 16 years of age from injury and poisoning were examined for the period 1978-1987: 174 deaths occurred during the 10-year period. The commonest causes of death were road traffic accidents: 103 cases (60%). Of these 87 were of pedestrians struck by vehicles. Many of these children were very young and were unsupervised, or poorly supervised by other children. Drivers of vehicles were largely responsible for the accidents in 20 cases. The ability of children to cope in various traffic situations is discussed and responsibilities of parents and drivers are considered in relation to matters of accident prevention.

Unplanned re-attendance in the accident and emergency department.

The notes of patients who re-attended the Accident and Emergency Department with a problem for which they had already been seen and treated were reviewed over a five-week period. Such patients comprised 2.5% of total attendances. The commonest reason for re-attendance was persistent pain following an injury and of such patients, about a half required a significant change in management. It was estimated that two-thirds of re-attendances were unavoidable. Twenty patients were admitted following re-attendance, and of these, two had serious medical conditions which were missed on initial presentation. The role of senior Accident and Emergency doctors is discussed in the light of these findings.

The use of chromic catgut in the primary closure of scalp wounds in children.

A prospective clinical trial examining the benefits of using an absorbable suture for the closure of scalp wounds, is described. One hundred wounds were included, of which 50 were closed with chromic catgut, and 50 were closed with silk. On examination 5 days later, there were no complications in either group. The advantages of using an absorbable suture material in children's scalp wounds are discussed.

Transient hyperphosphatasaemia of infancy following rotavirus infection.

A child with transient hyperphosphatasaemia of infancy is reported. The syndrome followed rotavirus infection. Reports of transient hyperphosphatasaemia of infancy are reviewed.