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Biomedical subjects

P J Stanley

Publications and source records attributed to P J Stanley.

At least 19 recordsLinked to original sources

KCC3 and KCC4 expression in rat adult forebrain.

Potassium chloride ion cotransporters (KCCs) are part of a family of transporters classically described as being involved in cell volume regulation. Recently, KCC2 has been shown to have a role in the development of the inhibitory actions of amine transmitters, whereas KCC3 also plays a fundamental role in the development and function of the central and peripheral nervous system. We have re-assessed the expression of each of the known KCCs in the rat forebrain using RT-PCR and in situ hybridisation histochemistry. As well as confirming the widespread expression of KCC1 and KCC2 throughout the brain, we now show a more restricted expression of KCC3a in the hippocampus, choroid plexus and piriform cortex, as well as KCC4 in the choroid plexus and the suprachiasmatic nucleus of the hypothalamus. The expression of KCC4 in the latter and KCC2 in the lateral hypothalamic and ventromedial hypothalamic nuclei suggests that these cotransporters may have selective roles in neuroendocrine or homeostatic functions. Finally, we demonstrate the existence of a truncated splice variation of KCC3a in the rat that appears to be expressed exclusively in neurons (as is KCC2), whereas the native form of KCC3a and KCC4 appears to be expressed in glial cells.

Animals↗

Neuromedin U neurones in the rat nucleus of the tractus solitarius are catecholaminergic and respond to peripheral cholecystokinin.

Centrally administered neuromedin U (NMU) has profound effects on food intake and energy expenditure. In the rat, central expression of NMU mRNA is confined to the brainstem and the hypothalamus/pituitary, while mRNA for the receptor NMU2R is expressed in the hypothalamus and hippocampus, as well as in the lining of the ventricular system, but not in the brainstem. We demonstrate that a subpopulation of catecholaminergic neurones in the brainstem nucleus of the tractus solitarius contain NMU and are activated by the gut-derived peptide, cholecystokinin. This is consistent with NMU neurones having an anorectic action, probably via their interaction with other neurones in the paraventricular hypothalamus.

Animals↗

Unusual cryptosporidium species recovered from human faeces: first description of Cryptosporidium felis and Cryptosporidium 'dog type' from patients in England.

DNA was extracted from faecal samples collected from 1680 patients in which Cryptosporidium oocysts were recognised by light microscopy. DNA from faeces from five of these patients failed to amplify by PCR three gene fragments--the Cryptosporidium oocyst wall protein (COWP) gene, the thrombospondin-related adhesive protein of Cryptosporidium-1 (TRAP-C1) gene and the thrombospondin-related adhesive protein of Cryptosporidium-2 (TRAP-C2) gene--with primers designed from C. parvum sequences. However, DNA from these five patients did amplify cryptosporidial 18S rDNA gene fragments and a heat-shock protein (HSP70) gene fragment was also amplified from four of them. The purpose of this study was to characterise further the Cryptosporidium associated with infection in these patients. DNA sequence analysis of 18S rDNA genes showed that four of these patients were infected by C. felis, and the remaining one by an as yet un-named Cryptosporidium species designated the 'dog type' (C. dt). Infection by C. felis was further confirmed in all four patients by DNA sequence analysis of the HSP70 gene. Oocysts present in all five samples reacted strongly with two anti-cryptosporidial oocyst monoclonal antibodies, except for the C. dt, which was tested with only one of the antibodies. Two of the patients infected by C. felis had underlying illness; one 8-year-old male had an undefined severe inherited underlying condition, and the second patient, a 32-year-old male, was HIV positive. Two of the remaining three patients (two females aged 1 and 2 years, respectively) were apparently immunocompetent (one infected with C. felis and one with the C. dt). No information was obtained for the fifth patient. The patient infected by C. dt had a recent history of travel to Africa. This is the first report of infection with these two Cryptosporidium species in immunocompetent patients, and in any patient in the UK.

Adult↗

A case of Japanese encephalitis.

We report a case of Japanese encephalitis that occurred in a woman who had spent only a few days in an area where she could have been exposed to the virus. The risks and protective efficacy of vaccination against Japanese encephalitis virus for travellers who visit endemic areas for only a short period are discussed.

Acyclovir↗

Actinomycetes in pyogenic liver abscess.

Three patients with pyogenic liver abscesses had actinomycetes cultured from aspirated pus, although it is unusual for hepatic actinomycosis to present in this way. The spectrum of bacteria found in liver abscesses appears to be changing, with the increased isolation of anaerobes partly due to improved techniques. It is important to recognise the presence of actinomycetes so that appropriate chemotherapy can be given.

Actinomyces↗

Open study of ciprofloxacin in enteric fever.

Thirty adult patients with typhoid or paratyphoid fever were treated with ciprofloxacin. All patients were cured with eradication of the causative organism. No major adverse reactions were seen. Ciprofloxacin is an effective agent for the treatment of enteric fever.

Administration, Oral↗

New vaccines.

New technology is allowing the development of more effective and safer vaccines to replace old vaccines and provide protection against a wider range of diseases. The worldwide priority, however, must be to increase the uptake of existing vaccines to reduce childhood mortality and morbidity.

Humans↗

Amoebic liver abscess in a bisexual man.

A bisexual man who had not travelled outside the U.K. had an amoebic liver abscess. Although it is reported that Entamoeba histolytica is usually of a non-pathogenic type in homosexual men in the U.K., it is important to diagnose invasive amoebiasis in this high-risk group so that appropriate treatment can be given.

Adult↗

The effect of vidian neurectomy on nasal mucociliary clearance.

The physiological factors controlling mucociliary transport are largely unknown. Nasal mucociliary clearance was measured using the saccharin test in seven patients who had previously undergone vidian neurectomy for vasomotor rhinitis. Persistent denervation was suggested by impaired tear secretion. The control group consisted of thirty-four patients with vasomotor rhinitis who had not had surgery. There was no significant difference in clearance times between the two groups, suggesting that mucociliary transport is well preserved in the absence of neural control.

Adult↗

Effect of cigarette smoking on nasal mucociliary clearance and ciliary beat frequency.

Despite the in vitro ciliotoxicity of tobacco smoke and the abnormal mucociliary clearance found in smoking related chronic bronchitis, studies of mucociliary clearance in healthy smokers have produced variable results. The nasal mucociliary clearance of saccharin and the in vitro nasal ciliary beat frequency were studied in healthy smokers and non-smokers. One of 29 smokers had a nasal mucociliary clearance time of over 60 minutes; in the remaining 28 the mean (SD) clearance time was 20.8 (9.3) minutes, which was significantly longer (p less than 0.001) than the mean time of 11.1 (3.8) minutes in 27 lifelong non-smokers. There was no significant difference between the mean nasal ciliary beat frequency of 10 smokers and 10 non-smokers. There were no significant differences in mean ciliary beat frequency or mean nasal mucociliary clearance time after 10 healthy non-smoking volunteers had smoked two cigarettes each, exhaling the smoke through their nostrils. Unless there is a prompt reversal of any ciliotoxic effect of tobacco smoke when cilia are removed for in vitro examination, the defective clearance seen in chronic cigarette smokers seems unlikely to be due to slowed ciliary beat frequency. It may be due to reduction in number of cilia or to change in the viscoelastic properties of mucus. The failure to detect any acute effect of tobacco smoke is in keeping with this hypothesis.

Adult↗

Abnormal nasal mucociliary clearance in patients with rhinitis and its relationship to concomitant chest disease.

Nasal mucociliary clearance was measured using a saccharin technique in 172 patients with perennial rhinitis (76 also had asthma) and in 121 patients with chronic infected rhinosinusitis (40 had asthma, 35 had bronchiectasis). All patient groups had significantly longer mean nasal mucociliary clearance times than that of a group of healthy subjects. Grossly prolonged clearance (greater than 60 minutes) occurred in significantly more patients with the clinical syndrome of chronic infected rhinosinusitis and bronchiectasis than in the syndromes of chronic infected rhinosinusitis with or without asthma, and perennial rhinitis with or without asthma. The abnormal clearance was shown not to be due to an intrinsic ciliary defect by in vitro examination of nasal cilia but probably to be due to a combination of mucus and ciliary factors in vivo.

Adolescent↗

Thoracic lymphadenopathy in Asians resident in the United Kingdom: role of mediastinoscopy in initial diagnosis.

Although the incidence of superficial glandular tuberculosis is high in Asian immigrants, a clinical diagnosis without biopsy has previously been shown to be inaccurate in 22% of cases. The role of diagnostic mediastinoscopy and biopsy in thoracic lymphadenopathy was therefore evaluated in 41 consecutive Asian patients. Tuberculosis was diagnosed by histological examination or culture (or both) of gland biopsy material in 24 (59%). A further 12 patients, however, also received antituberculous chemotherapy, with a response in 10 cases. If these are included, 34 (83%) were finally considered to have tuberculosis. The symptoms and ages of the patients with tuberculosis were similar to those typically seen in caucasians with sarcoidosis. Six had tuberculous bilateral hilar lymphadenopathy. In only four cases (10%) was a positive diagnosis other than tuberculosis established; in two (lymphoma and thymoma) mediastinoscopy confirmed preoperative suspicions, and saved only two more (with sarcoidosis and vascular anomaly) from unnecessary antituberculous treatment. Complications included severe haemorrhage (1) and chronic tuberculous sinus in the endoscopy tract (2). Mediastinoscopy is unlikely to change management in most patients, produces an appreciable amount of morbidity, and should be reserved for cases in which there is additional clinical doubt. Any future decline in the prevalence of tuberculosis in Asians may, however, require its further evaluation.

Adolescent↗

Effect of betamethasone and betamethasone with neomycin nasal drops on human nasal mucociliary clearance and ciliary beat frequency.

The effects of two topical nasal preparations on human nasal ciliary beat frequency in vitro and on nasal mucociliary clearance in vivo were investigated. Betamethasone and betamethasone with neomycin drops were found to be ciliotoxic when ciliated epithelium was exposed to them in vitro, mainly owing to the effects of the preservatives benzalkonium chloride and thiomersal. The nasal mucociliary clearance and in vitro ciliary beat frequency of nasal ciliated epithelium taken from healthy subjects were not adversely affected after topical application; neither did treatment with betamethasone, with or without neomycin, for four weeks affect these indices in two groups of patients with rhinitis. Thus, despite a ciliotoxic effect when ciliated epithelium is exposed to these preparations in vitro, they do not affect nasal clearance or ciliary beat frequency (as measured in vitro) adversely when administered topically to the nose.

Administration, Intranasal↗

The concentrations of IgA and free secretory piece in the nasal secretions of patients with recurrent respiratory infections.

The concentrations of total IgA, 11S IgA, total and free secretory piece (SP) were measured in the nasal secretions of 39 patients with recurrent upper and lower respiratory tract infections during an infection free period. In all of eight patients who had selective serum IgA deficiency (less than 0.05 g/l) IgA was also undetectable in their nasal secretions and the mean concentration of free SP was significantly raised. However, the mean concentrations of 11S IgA, SP and free SP in nasal secretions of patients with normal or low (greater than 0.05 g/l but below the normal range) serum IgA were not significantly different from those of 10 healthy normal subjects. In patients with detectable nasal secretory IgA, 11S IgA concentrations correlated significantly (r = 0.57; P less than 0.001) with concentrations of free SP. One patient with normal serum IgA was found to have a large excess of free SP and therefore may have had a relative defect in local IgA production.

Chronic Disease↗