Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.

Reactive oxygen species trigger cellular responses by activation of stress-responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal of MAPK activation requires the transcriptional induction of specialized cysteine-based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative stresses generally inactivate cysteine-based phosphatases by thiol modification and thus could lead to sustained or uncontrolled MAPK activation. Here we describe how the stress-inducible MAPK phosphatase, Sdp1, presents an unusual solution to this apparent paradox by acquiring enhanced catalytic activity under oxidative conditions. Structural and biochemical evidence reveals that Sdp1 employs an intramolecular disulphide bridge and an invariant histidine side chain to selectively recognize a tyrosine-phosphorylated MAPK substrate. Optimal activity critically requires the disulphide bridge, and thus, to the best of our knowledge, Sdp1 is the first example of a cysteine-dependent phosphatase that couples oxidative stress with substrate recognition. We show that Sdp1, and its paralogue Msg5, have similar properties and belong to a new group of phosphatases unique to yeast and fungal taxa.

Comparison of 40 mg famotidine nightly and 150 mg ranitidine b.d.: ulcer healing and symptom relief in benign gastric ulcer.

Two hundred and eight patients with benign gastric ulcers seen on endoscopy were recruited by 13 hospitals in the United Kingdom and Ireland into this double-blind study. Patients were assigned by pre-randomized schedule to 8 weeks of treatment with either 40 mg famotidine at night or 150 mg ranitidine b.d. Repeat endoscopy confirmed complete ulcer healing in 62 of 77 evaluable patients in the famotidine group (81%) and 58 of 71 in the ranitidine group (82%). The treatments were equally effective in promptly relieving day and night pain. Adverse events were uncommon; dizziness and headaches were the most frequently reported in both groups. In conclusion, night-time famotidine is as effective as twice daily ranitidine in healing benign gastric ulcers and provides similarly rapid symptomatic relief.

Single night-time doses of 40 mg famotidine or 800 mg cimetidine in the treatment of duodenal ulcer.

Famotidine (40 mg) and 800 mg cimetidine as single night-time doses were compared in a randomized, double-blind, multicentre study of acute treatment for duodenal ulceration. Fifteen centres recruited 304 patients into the study. Of these, 274 were included for analysis, with 136 receiving famotidine and 138 receiving cimetidine. After 4 weeks, 75% of the patients who received famotidine and 77% of the patients who received cimetidine were healed. At 6 weeks the cumulative healing rates were 91% with famotidine and 87% with cimetidine. Differences between the groups were not significant at 4 or 6 weeks. No significant difference in healing rates between smokers and non-smokers was found. Day and night pain resolved rapidly in both groups. Both treatments were well-tolerated; adverse events were reported in 17 patients on famotidine and 18 on cimetidine, with headache the most frequent event in both groups. Famotidine is effective and well-tolerated in the short-term treatment of duodenal ulcer.

Rectal organ culture as a model for the investigation of bacterial adhesion and invasion.

A system was developed for the in vitro culture of human rectal mucosa. Its viability was proved by histological appearances and by metabolic studies. Biopsy samples were cultured in the presence of appropriate bacteria isolated from the faeces of patients with ulcerative colitis or with dysenteric illnesses. Attempts to show adhesion of bacteria to the mucosa or invasion of the cultured tissue failed. Problems with the use of this model are discussed.

Post-ERCP pancreatitis and hyperamylasaemia: the role of operative and patient factors.

BACKGROUND AND AIM: Pancreatitis and hyperamylasaemia are common complications of ERCP and this study was designed to explain which operative and patient factors predispose to them. PATIENTS AND METHODS: A 1 year prospective study of consecutive patients in a single operator centre with detailed attention to technical factors and the findings. RESULTS: Four hundred and thirty ERCPs were performed. Pancreatitis occurred in 12 cases (2.8%). Amylase results were available in 407 cases; 17 were excluded because of pre-operative hyperamylasaemia (n = 5) and because of pancreatitis (n = 12). Of the remaining 390, 30 (7.7%) had hyperamylasaemia. Pancreatitis and hyperamylasaemia usually occurred after difficult procedures in which pancreatography was achieved. Smaller common bile-ducts, pre-cut papillotomy and some preoperative indications also significantly increased the risk of pancreatitis, while prior papillotomy was protective. Pancreatitis occurred in patients with a younger median age (52.5 vs 68.0; P < 0.05) and was more common in women (F:M = 11:1 vs 241:177; P < 0.05). CONCLUSION: Operative factors are, in part, responsible for the development of pancreatitis and hyperamylasaemia but the age and sex of the patient also appear to be important.

Miniature ultrasonic probe construction for minimal access surgery.

The increasing use of minimal access techniques for surgery has produced a need for imaging technologies that can be used during such interventions. Ultrasound imaging has the advantage that the probe itself can be interventional. Interventional ultrasound probes must be sufficiently small to gain access to the surgical site, and any rigid portion must be limited in length to permit adequate flexibility. In practice this means the ultrasound probes have to operate at high frequencies, and a set of design curves have been produced which relate the number of elements and the ultrasound frequency to the probe dimensions for both linear and cylindrical array configurations. Constructing high-frequency sub-miniature probes presents a number of technical challenges, in particular relating to interconnects and packaging. Solutions to these challenges are discussed using the fabrication of a 1 mm diameter intravascular probe as an example.

Ultrasonic B-scanning: a computer simulation.

A method has been developed which can predict the appearance and properties of B-scan images. The theoretical basis for the tissue models used, and the assumptions made in the simulation concerning the nature of pulse-echo imaging, are discussed. A key feature of the simulation is the Fourier domain synthesis of the tissue model, which permits convenient specification of some statistical properties of a randomly inhomogeneous scattering medium. Other characteristics that may be specified include the ultrasonic pulse and beam shapes, and subsequent signal processing. Both the initial tissue model and the simulated B-scan image are displayed as grey-scale pictures, allowing visual comparison in the same way that clinical B-scans are currently observed. Preliminary results of applying the simulation are shown to have a number of features in common with clinical images and with scans of a test object. A better understanding of the nature of pulse-echo images is gained and conclusions drawn regarding the range of system and tissue parameters over which these images convey information about the tissue structure. The method may also be of use to determine optimum design of equipment for imaging and tissue characterisation, and to investigate the extent to which the acoustic structure of tissues can be described in terms of simple mathematical models.

Spontaneous pseudomembranous colitis not associated with Clostridium difficile.

This paper describes two patients who developed macroscopically and microscopically typical pseudomembranous colitis without prior exposure to antimicrobial agents and without detectable Clostridium difficile or its toxin in the faeces.

Measurement of soft tissue motion using correlation between A-scans.

The advent of real-time B-scanning has led to interest in the diagnostic value of the dynamic properties of soft tissue. Present ultrasonic techniques for investigating motion cannot measure the motion of homogeneous tissues. A technique has been developed which uses the correlation coefficient between A-scans to measure the amplitude and frequency of their motion, both in water tank experiments and in vivo. The success of the technique, which is digitally implemented, supports the validity of stochastic models for the acoustic structure of soft tissues. The motion pattern observed in vivo can be correlated with the arterial pressure pulse.

Abdominal scintigraphy with 99Tcm-labelled red cells in the detection of rebleeding from peptic ulcers.

The technique of 99Tcm-labelled red cell scintigraphy as a means of detecting rebleeding was investigated in 33 patients with bleeding peptic ulcers. Scintigrams were performed twice during the 24 h period succeeding diagnostic endoscopy. There was scintigraphic evidence of rebleeding in 23 patients but this was clinically manifest in 14 patients only. Thirteen of the 14 patients with clinical rebleeding had positive scintigrams while only in one patient with clinical rebleeding was the scintigram negative (P less than 0.05). These results show that rebleeding is common and often clinically inapparent during the first 24 h following gastroscopy but that in the absence of scintigraphic rebleeding serious clinical rebleeding is unlikely to occur.

Massive gastrointestinal bleeding in Crohn's disease.

Massive gastrointestinal bleeding is rare in Crohn's disease. Three young adult patients are reported in whom the diagnosis of Crohn's disease was made following investigation for life-threatening gastrointestinal bleeding.

Morbidity and mortality in salmonella food poisoning. A review of 47 in-patient cases.

Forty-seven new patients with salmonella food poisoning were admitted to the Infectious Diseases Unit at the City Hospital, Edinburgh, during 1975. Although all the patients had diarrhoea at some stage of their illness, the wide variety of presenting symptoms caused some diagnostic difficulties prior to the isolation of the organism. A probable predisposing factor to serious disease was recognised in 15 patients. Twenty patients (42.5%) were seriously ill and 4 patients (8.5%) died. This series stresses the potential severity of this common disease.

Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.

BACKGROUND: Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols. OBJECTIVES: Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued. METHODS: Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker. RESULTS: NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count. CONCLUSIONS: NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.