Past progress in environmental nanoanalysis and a future trajectory for atomic mass-spectrometry methods.

The development of engineered nanotechnology has necessitated a commensurate maturation of nanoanalysis capabilities. Building off a legacy established by electron microscopy and light-scattering, environmental nanoanalysis has now benefited from ongoing advancements in instrumentation and data analysis, which enable a deeper understanding of nanomaterial properties, behavior, and impacts. Where once environmental nanoparticles and colloids were grouped into broad 'dissolved or particulate' classes that are dependent on a filter size cut-off, now size distributions of submicron particles can be separated and characterized providing a more comprehensive examination of the nanoscale. Inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS), directly coupled to field flow fractionation (FFF-ICP-QMS) or operated in single particle mode (spICP-MS) have spearheaded a revolution in nanoanalysis, enabling research into nanomaterial behavior in environmental and biological systems at expected release concentrations. However, the complexity of the nanoparticle population drives a need to characterize and quantify the multi-element composition of nanoparticles, which has begun to be realized through the application of time-of-flight MS (spICP-TOFMS). Despite its relative infancy, this technique has begun to make significant strides in more fully characterizing particulate systems and expanding our understanding of nanoparticle behavior. Though there is still more work to be done with regards to improving instrumentation and data processing, it is possible we are on the cusp of a new nanoanalysis revolution, capable of broadening our understanding of the size regime between dissolved and bulk particulate compartments of the environment.

Enhancement of second-order nonlinear-optical signals by optical stimulation.

Second-order nonlinear optical interactions such as sum- and difference-frequency generation are widely used for bioimaging and as selective probes of interfacial environments. However, inefficient nonlinear optical conversion often leads to poor signal-to-noise ratio and long signal acquisition times. Here, we demonstrate the dramatic enhancement of weak second-order nonlinear optical signals via stimulated sum- and difference-frequency generation. We present a conceptual framework to quantitatively describe the interaction and show that the process is highly sensitive to the relative optical phase of the stimulating field. To emphasize the utility of the technique, we demonstrate stimulated enhancement of second harmonic generation (SHG) from bovine collagen-I fibrils. Using a stimulating pulse fluence of only 3 nJ/cm2, we obtain an SHG enhancement >10(4) relative to the spontaneous signal. The stimulation enhancement is greatest in situations where spontaneous signals are the weakest--such as low laser power, small sample volume, and weak nonlinear susceptibility--emphasizing the potential for this technique to improve signal-to-noise ratios in biological imaging and interfacial spectroscopy.

Referral letters for 2-week wait suspected colorectal cancer do not allow a 'straight-to-test' pathway.

INTRODUCTION: Some clinicians have argued that 2-week wait suspected colorectal cancer patients can go 'straight-to-test' to facilitate time to diagnosis and treatment. The aim of this study was to evaluate whether the currently used referral letters are reliable enough to allow that pathway. PATIENTS AND METHODS: General practitioner (GP) letters referring patients under the Two Week-Wait Rule for suspected colorectal cancer were prospectively reviewed over a 6-month period. Three examining consultants were asked to outline the tests they would perform having only read the letter, and then again after a clinical consultation with the patient. The outcome of these tests was tracked. RESULTS: A total of 217 referral letters of patients referred under Two Week Wait Rule for suspected colorectal cancer were studied. Having just read the referral letter, the most frequently requested test was colonoscopy (148), then CT scan (48), barium enema (44), followed by gastroscopy (23) and flexible sigmoidoscopy in 15 patients (some patients would have had more than one test requested). After consultation with the patients, tests requested as guided by the GP letter were changed in 67 patients (31%), where 142 colonoscopies, 61 CT scans, 37 barium enemas, 23 flexible sigmoidoscopies and 19 gastroscopies were organised. The referral indication which had tests changed most often was definite palpable rectal mass (67%), while patients referred with definite palpable right-sided abdominal mass had their tests least often changed (9%). A total of 22 patients were found to have colorectal cancers (10%) and 30 patients were diagnosed with polyps (14%). Out of 142 colonoscopies performed, 19 (13%) showed some pathology beyond the sigmoid colon and of the 23 patients who had flexible sigmoidoscopy initially, only three went on to have colonoscopy subsequently. During the 6-month period of the study, only five breaches of the waiting time targets were recorded (1 to the 31-day target and 4 to the 62-day target). CONCLUSIONS: A significant number of patients would have had tests changed after a clinical consultation. However, only a small number required further investigations having had a consultation prior to their initial investigations. We conclude that 2-week wait suspected colorectal cancer patients should be seen in the clinic first and should not proceed 'straight-to-test'.

The association of gastric leptin with oesophageal inflammation and metaplasia.

BACKGROUND: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. AIMS: To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia. METHODS: From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. RESULTS: Of 269 individuals enrolled, 105 were Helicobacter pylori-negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123-333) pg/mg) compared with normal (126 (78-221) pg/mg) or inflamed (114 (76-195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus. CONCLUSIONS: Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression.

Model systems for flavoenzyme activity. Control of flavin recognition via specific electrostatic interactions.

[structure: see text] A model system has been used to study the interactions of dipole-containing aromatic systems with oxidized and reduced flavin. Ab initio computational and experimental studies show that dipole orientation within the host is a critical determinant for recognition and redox behavior of the flavin guest.

Serum phospholipase A2 activity in acute pancreatitis: an early guide to severity.

Daily measurements of serum phospholipase A2 activity were carried out on 73 consecutive patients admitted to hospital with acute pancreatitis. During the first 6 days there were significant differences in activity in those patients predicted as severe by multiple prognostic criteria when compared with those with mild disease. Follow-up studies at 6 weeks showed no difference between those graded as mild and those graded as severe at the time of attack. In the patients with elevated activity, nine had this at the time of admission and all were raised within 24 h. Elevated activity correlated well with the clinical outcome and showed good agreement with the multiple prognostic criteria in the prediction of severe disease. It is suggested that measurement of serum phospholipase A2 activity may provide a simple test for the early identification of most patients with severe acute pancreatitis.

Phospholipase A2 activity in taurocholate-induced acute pancreatitis in the rat model.

The activity of phospholipase A2 (PA2) was measured in the plasma of rats after the induction of acute pancreatitis. Buffered sodium taurocholate (3.75% w/v), injected into the pancreatico-biliary duct, was used to induce acute pancreatitis. Blood was taken at 1-h intervals for the measurement of phospholipase A2, glucose, lipase, and arterial gases. Plasma lipase was markedly elevated in the test groups, indicating acute pancreatitis, but no significant difference in PA2 activity was seen between the controls and the test group. However, in four animals the PA2 activity was elevated and in all cases this was accompanied by a low arterial pO2. This supports the theoretical role of PA2 in the pathogenesis of the respiratory complications observed in severe acute pancreatitis.

Gastric carcinoma and familial adenomatous polyposis (FAP).

We report two cases of FAP associated with gastric carcinoma. The literature on this subject, with special reference to 'fundic gland polyposis' is reviewed.

Abdominal wall and gastric infarction in acute pancreatitis.

We report a case of severe acute pancreatitis associated with both gastric and abdominal wall infarction. The early skin changes on the anterior abdominal wall could be confused with Grey-Turner's sign.

Effect of the pre-operative response to H2 receptor antagonists on the outcome of highly selective vagotomy for duodenal ulcer.

From 1979 to 1984, 141 consecutive patients (110 men, 31 women) underwent highly selective vagotomy (HSV) for duodenal ulcer (DU). All patients had received pre-operative treatment with full dose H2 receptor antagonists (H2RA). Indications for surgery were: persistent relapse on withdrawal of H2RA, 107 (75.9 per cent); no response to H2RA, 30 (21.3 per cent); intolerance of H2RA, 1 (0.7 per cent); acute DU bleed, 2 (1.4 per cent); duodenal stenosis, 1 (0.7 per cent). Follow-up with a median of 47 months (24-85 months) revealed six patients (4.4 per cent) with endoscopically proven recurrence, three of whom were on non-steroidal anti-inflammatory drugs (NSAIDs). Only one patient with recurrent DU was a non-responder to H2RA pre-operatively. Twenty-five patients remained symptomatic after HSV without ulcer recurrence, of which a highly significant proportion (41 per cent) were non-responders (P less than 0.001). The pre-operative response to H2RA does not indicate the likelihood of ulcer recurrence after HSV. However, non-responders are more likely to continue with dyspeptic symptoms despite the successful healing of their ulcers. The DU recurrence rate in patients taking long-term NSAIDs is disappointingly high (33 per cent), putting the use of HSV in these patients into question.

Antiprotease capacity in acute pancreatitis.

Serial measurements of circulating antiproteases were carried out on 42 consecutive patients admitted with acute pancreatitis. In the 7 days following admission the serum levels of alpha 1 antitrypsin (alpha 1 AT), alpha 1 antichymotrypsin (alpha 1 ACT) and the trypsin inhibitory capacity (TIC) increased by more than 300 per cent. The serum concentration of alpha 2 macroglobulin (alpha 2 M) alone showed a decline which was most profound in those patients with severe acute pancreatitis. Initial experience of fresh frozen plasma as a source of extrinsic antiproteases in severe acute pancreatitis is that it fails to prevent the decline in alpha 2 M or increase the already elevated TIC of the patients' serum.

Detection of gall stones after acute pancreatitis.

Four methods of gall stone diagnosis after an attack of acute pancreatitis are analysed. Of 128 consecutive patients with acute pancreatitis, 99 patients were discharged from hospital without a definite aetiology. These patients had biochemical tests performed on admission and ultrasonography and oral cholecystography performed six weeks later. The sensitivity for ultrasonography was 87% and the specificity was 93%; the respective figures for oral cholecystography were 83% and 90%. The predictive value of positive ultrasonography was 100% and of negative ultrasonography 75%; the respective values for oral cholecystography were 95% and 68%. A combination of ultrasonography and oral cholecystography failed to detect nine of 70 patients with gall stones (13%). Of 35 patients with normal ultrasonography and oral cholecystography, 33 patients had an endoscopic retrograde cholangiogram (ERCP) which showed gall stones in a further seven patients. All three methods failed to reveal gall stones in two patients, confirmed by laparotomy. The sensitivity of admission biochemical analysis was 73% and the specificity was 94%; the predictive value of a positive result was 97% and of a negative result was 57%. Biochemical analysis predicted gall stones in six of the seven patients shown by ERCP. Only 9% of patients were finally considered to be idiopathic. In conclusion ultrasonography is the investigation of choice and ERCP should be undertaken in all patients who have normal ultrasonography and/or oral cholecystography but have biochemical criteria indicative of gall stones.