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J Sanderson

Publications and source records attributed to J Sanderson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Calcium ionophore induced proteolysis and cataract: inhibition by cell permeable calpain antagonists.

Two dipeptide aldehyde cell permeable calpain inhibitors, cBz-Val-Phe and calpeptin, have been assessed for their ability to prevent cytoskeletal proteolysis and loss of transparency in whole rat lenses. Calcium overload, induced by ionomycin in artificial aqueous humor with 1mM calcium, resulted in lens opacification and degradation of cytoskeletal proteins including spectrin, filensin, and vimentin. No such changes resulted from incubation in ionomycin in the absence of calcium. In calcium overload lenses both inhibitors gave some protection against cytoskeletal protein degradation and loss of transparency. These experiments indicate that calpain has a role in cortical opacification in high calcium lenses and that cell penetrating calpain inhibitors do indeed enter lens cells and reduce both proteolysis and opacification.

Animals↗
PubMed1996

Omeprazole and visual disorders: seeing alternatives.

In the WHO data base, visual disorders reported spontaneously with omeprazole, ranitidine and cimetidine, are very rare in the context of the widespread use of these drugs. There is a maximum reporting rate of severe visual impairment possibly ascribed to i.v. omeprazole of 0.94 reports per million treatment days in one year and in one country, Germany. This gives the worst quantitative case scenario for omeprazole by a single route of administration, to be compared with the worldwide reporting rate of all severe visual disorders by all routes of administration--0.008 reports per million treatment days. Moreover, the reported visual abnormalities have a varied pathophysiological aetiology and their number increased in Germany after the first signal was raised in that country. Thus, apart from a direct causal relationship, solicited reporting artifact is one alternate plausible explanation for the apparent excess of cases of visual disturbance to omeprazole compared with cimetidine and ranitidine. That reporting rates of clinical events on newly marketed drugs are generally higher than with older drugs is a second factor for higher reporting rates with omeprazole. Vasculitis has been suggested as an aetiological factor, but the even lower reporting rate of this reaction makes this an unlikely hypothesis without any other supporting evidence. The authors are unaware of any drug that has caused a vasculities solely affecting the eye. Information on the prevalence of relevant visual disorders in the community would have been of considerable help in interpreting this signal, and a case control study of visual events in relationship to severe illness would be of public health interest, since no data seems to exist concerning this.

Journal Article↗
PubMed1996

Somatostatin reduces gastric mucosal blood flow in patients with portal hypertensive gastropathy: a randomized, double-blind crossover study.

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO2) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO2 were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (-27.0,-12.6%); P = 0.0008] after a 250-microg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [-10.2% (-23.4, 0.4%)] and in the corpus [-5.8% (-16.6, 5.6%)] compared to placebo (P = 0.02 and 0.04, respectively). Intravenous bolus injection of 250 microg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.

Aged↗
PubMed1996

IS900 PCR to detect Mycobacterium paratuberculosis in retail supplies of whole pasteurized cows' milk in England and Wales.

IS900 PCR for Mycobacterium paratuberculosis was applied to cream, whey, and pellet fractions of centrifuged whole cows' milk. The test and simultaneous control reactions gave correct results for spiked milk and for native milk samples obtained directly from M. paratuberculosis-free, subclinically infected, and clinically infected cows. The test was then applied to units of whole pasteurized cows' milk widely obtained from retail outlets throughout central and southern England from September 1991 to March 1993. With peak periods in January to March and in September to November, when up to 25% of units were affected, an overall 22 of 312 samples (7%) tested positive for M. paratuberculosis. In 18 of the 22 positive samples (81%), the PCR signal segregated to the cream or pellet fractions or both, consistent with the presence of intact mycobacteria. Nine of 18 PCR-positive milk samples (50%) and 6 of 36 PCR-negative milk samples (16%) yielded long-term liquid cultures which tested positive for M. paratuberculosis after 13 to 40 months of incubation, despite overgrowth by other organisms. Taken together with data on the prevalence of M. paratuberculosis infection in herds in the United Kingdom, the known secretion of M. paratuberculosis in milk from subclinically infected animals, and the inability of laboratory conditions simulating pasteurization to ensure the killing of all these slowly growing or unculturable organisms, there is a high risk, particularly at peak times, that residual M. paratuberculosis will be present in retail pasteurized cows' milk in England.

Animals↗
PubMed1995

Calcium localization and ultrastructure of clear and pCMPS-treated rat lenses.

PURPOSE: The sulfhydryl complexing agent p-chloromercuri-phenylsulfonate (pCMPS) has been shown to increase lens membrane permeability, Na+ and Ca2+ content, and light scatter in the rat lens in vitro. This study aimed to investigate the ultrastructural changes accompanying the increase in light scatter. In addition, high-resolution histochemistry was used to study the cellular distribution of Ca2+ in normal and cataractous lenses. METHODS: Rat lenses were incubated for 4 hours in normal (1 mM) and high (5 mM) Ca2+ containing media supplemented with 40 microM pCMPS. Control lenses were incubated in 1 mM Ca2+ containing medium. They were prepared for scanning and transmission electron microscopy and for Ca2+ localization using the oxalate-pyroantimonate procedure. RESULTS: Control lenses incubated for 4 hours had normal morphology and showed no evidence of light scatter. Calcium distribution as observed with the oxalate-pyroantimonate precipitation method was low in superficial fibers, high in the membranes of intermediate fibers, and declined again toward the nucleus. In the deeper cortex, there also were small vacuoles of calcium accumulation. pCMPS treatment (in 1 and 5 mM Ca2+) induced a significant influx of calcium into the lens cytoplasm. Calcium-containing extracellular vacuoles also were seen in the intermediate cortex in both cases. The presence of these vacuoles appeared to correlate with the major areas of light scatter in the lens. In 5 mM Ca2+, intracellular vacuoles were observed throughout the superficial cortex. CONCLUSIONS: Most of the calcium observed by oxalate-pyroantimonate in the normal lens is located at the membrane, and the staining appears strongest in the intermediate cortex. In pCMPS treatment, large extracellular vacuoles are present in this intermediate zone and appear to be the major source of light scatter. This zone may be the initiation site of many different types of cataract, including some described in human lenses.

4-Chloromercuribenzenesulfonate↗
PubMed1994

Calmodulin antagonists induce changes in lens permeability and transparency.

Calmodulin has been shown to perform several important functions in the lens including regulation of the plasma membrane Ca(2+)-ATPase. This study investigated the effects of a variety of different CaM antagonists on rat lens membrane potential, membrane resistance, intracellular Na+ and Ca2+ content and transparency, in order to examine the role of CaM in control of lens membrane permeability. W7, calmidazolium and trifluoperazine caused biphasic changes in lens membrane electrical characteristics. Phase 1 consisted of a depolarization of the membrane potential and an increase in resistance, indicating that K+ channels were being blocked. This was confirmed by application of the K+ channel antagonist, quinine, which inhibited Phase 1 changes. Phase 2 was a further depolarization coupled with a decrease in resistance, indicating the activation of a cation conductance. Application of W7 in low Na+ medium slowed the Phase 2 depolarization and decrease in resistance indicating that Na+ is the main charge carrier through the activated conductance. The CaM inhibitors also led to a large increase in the Na+ and Ca2+ contents of the lens. W5, a less potent analogue of W7, caused a depolarization and increase in membrane resistance, but no Phase 2 changes were observed. Na+ and Ca2+ contents were similar to control lenses after 4 hours incubation in 200 microM W5. In addition, exposure to W7, TFP and calmidazolium resulted in a loss of transparency, while W5 treated lenses remained clear. It appears, therefore, that CaM is involved in control of lens membrane permeability. Loss of control of these channels leads to catastrophic changes in the intracellular ionic environment and hence opacification of the lens.

Animals↗
PubMed1993

Use of thrombolysis for acute myocardial infarction by general practitioners.

The early administration of thrombolytic agents significantly reduces mortality following a myocardial infarct and ideally they could be given by general practitioners when the patient is first seen. However, the diagnosis of myocardial infarction in the early stages can be very difficult especially if an electrocardiogram is not available. This may limit the use of thrombolytic drugs by general practitioners. We assessed the accuracy of diagnosis in general practice by asking general practitioners referring patients with chest pain, the likelihood that the event was due to a myocardial infarction and if they would use thrombolysis if it were available. Diagnostic accuracy and appropriate use of thrombolysis was analysed retrospectively, comparing the general practitioner with the admitting hospital doctor. One hundred consecutive patients were studied. The general practitioners accurately diagnosed myocardial infarctions in approximately 45% of cases and would have given thrombolysis inappropriately on 67% of occasions mainly because the final diagnosis in most of these patients was unstable angina rather than infarction. The hospital doctors administered streptokinase inappropriately to 33% of the patients and four had complications during treatment. Of those patients receiving thrombolysis, the average time delay from the general practitioner referring the patient to hospital to the patient being treated was 107 minutes. This study confirms that the diagnosis of myocardial infarction in the early stages is difficult and that thrombolytic therapy may be given inappropriately (mainly to patients with unstable angina). We conclude that until the accuracy of diagnosis of myocardial infarction can be improved in general practice it would seem inappropriate for thrombolysis to be given in the community at the moment.

Adult↗
PubMed1993

pCMPS-induced changes in lens membrane permeability and transparency.

PURPOSE: To investigate the role of externally facing membrane protein sulfhydryl groups in controlling lens permeability and transparency using the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). METHODS: Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitored by measuring 22Na+ and 45Ca2+ fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quantified by photographing and analyzing back-scattered light. RESULTS: pCMPS, at concentrations above 1 microM, produced a depolarization of membrane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in 22Na+ and 45Ca2+ influxes into the lens. There was a concomitant loss of lens transparency, mainly in the bow region. The pCMPS-induced electrical changes could be prevented by substituting N-methyl-D-glucamine for Na+ in the external medium. Na(+)-free solution alone increased 45Ca2+ influx, and the addition of pCMPS further stimulated the influx. Quinine (300 microM) was found to reduce the pCMPS-induced stimulation of 22Na+ and 45Ca2+ influxes and also to reduce opacification. CONCLUSIONS: pCMPS at low concentrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quinine can ameliorate pCMPS-induced changes in ion movements and opacification suggests a novel approach for membrane-based anticataract strategies.

4-Chloromercuribenzenesulfonate↗
PubMed1990

Molecular biology of Crohn's disease mycobacteria.

A Glasgow surgeon, T.K. Dalziel, published a detailed description of chronic enteritis in humans in 1913. He proposed that the disease was caused by the same organisms as those responsible for chronic enteritis, Johne's disease, in animals described a few years earlier (1895). Dalziel's dilemma was that he could see acid-fast bacilli in the diseased animal tissues but not in the diseased human tissues. Little real progress in the medical understanding of the causes of chronic enteritis in humans occurred over the next half a century or more. From 1978, a decade of research in many laboratories using improved methods for the culture of environmental mycobacteria showed that these could be grown in bacillary form from about one in five cases of Crohn's disease, from the same proportion of cases of ulcerative colitis, and from about one in ten control tissues. Spheroplasts were grown from two in five cases of Crohn's disease, one in five cases of ulcerative colitis, and rarely from control tissues. The nature of these agents was often uncertain. We describe work which began in 1985 and led rapidly to the identification of IS900, a DNA repetitive element in an uncharacterized Crohn's disease mycobacterial isolate. With other isolates, these were then shown by DNA fingerprinting to be indistinguishable from Mycobacterium paratuberculosis, Johne's bacillus. Similar techniques also demonstrated the wood-pigeon strain of M. avium in some Crohn's disease cultures. This bacillus can also cause chronic enteritis in calves. IS900 is the first of a family of unusual DNA insertion sequences which extend widely throughout environmental mycobacteria. Use of assays based on PCR amplification of highly specific DNA sequences from these insertional elements, and recombinant and synthetic peptides from their predicted proteins, will revolutionize the detection and characterization of these agents. These methods, applied to animal, human and environmental samples, will indicate new ways for the prevention and treatment of chronic enteritis, as well as other disorders associated with infections by environmental mycobacteria.

Actinomycetales↗
PubMed1989

Hypophosphataemic rickets and melorheostosis.

Hypophosphataemic rickets/osteomalacia has been described in association with fibrous dysplasia and neurofibromatosis. This is the first reported case of melorheostosis associated with hypophosphataemic rickets. The literature is reviewed regarding the known association with the other bone dysplasias.

Child↗
PubMed1988

Recent clinical experience with the vena cava filter.

In the past at our institution, insertion of the vena cava filter was recommended almost exclusively for recurrent pulmonary emboli in anticoagulated patients or in those with emboli and contraindications to anticoagulation. More recently, prophylaxis has become a frequent indication for patients with extensive deep vein thrombosis and contraindications to anticoagulation. Herein, we review a recent series of caval filter insertions to determine if increased utilization of this technique is justified in terms of morbidity and effectiveness. Twenty-one filters were inserted in 20 patients during a 1-year period. The operative mortality rate was 0 and satisfactory filter placement was achieved in 90 percent of patients. There were no documented instances of recurrent emboli or vena cava thrombosis. These data suggest that use of the filter is justified as prophylaxis for patients at high risk for an initial pulmonary embolus in a clinical setting where heparin therapy is not appropriate.

Adult↗
PubMed1987

Previous ear, nose and throat surgery in children presenting with allergic perennial rhinitis.

Children with allergic perennial rhinitis had a four-fold greater likelihood of having had an ear, nose and throat (ENT) operation than children with orthopaedic problems. Whilst the patients who had ENT operations had significantly lower serum IgA and IgE levels than the non-operated patients, there was no difference in clinical features of atopy or allergy skin-test responses between the two groups of rhinitic patients. Forty per cent of the perennial rhinitics had an improvement in symptoms following ENT operations, whereas 90% improved on medical therapy. Thus, patients with perennial rhinitis should have allergy investigations and the benefit of medical treatment prior to consideration for surgery.

Adenoidectomy↗
PubMed1982

Occupational mercury exposure and its consequences for behaviour.

Mercury is a known neurotoxin. Evidence from animal studies show behavioural impairment which can be long-lasting, after low-level exposure to mercury. Human research, however, has not been conclusive. Chronic, high-level mercury exposure such as occurred in Japan, and the Middle East, Causes long-lasting and profound neurological damage. However the effects of low-level exposure, such as occurs in occupational exposure, are far from clear. This study used a comprehensive test battery based on an information processing framework to compare a group of twelve chronically mercury-exposed workers with a matched control group. The mercury-exposed group showed poorer psychomotor co-ordination and premature fatigue, although simple motor responses were not affected. General arousal levels also remained unaffected but mercury-exposed workers were superior in sustaining attention. In spite of this, the mercury-exposed group showed clear deficits in short-term memory.

Attention↗
PubMed1981

Gonadotrophin levels in women with Cushing's syndrome before and after treatment.

Basal serum concentrations of LH and FSH and their response to LHRH were studied in twelve pre- and ten post-menopausal women with Cushing's syndrome before and after treatment. Subnormal basal concentrations of LH were found in twelve out of twenty-two, and of FSH in ten of the twenty untreated patients. There was a correlation between the urinary free cortisol (UFC) and basal LH values, r = -0.59 (P less than 0.05), and UFC and basal FSH values, r = -0.76 (P less than 0.02) in the premenopausal women. All seven patients with a UFC value greater than 1080 nmol/24 h (normal range less than 270) had both a subnormal basal gonadotrophin level and a subnormal response of at least one gonadotrophin to the releasing hormone. In those patients in whom successful remission was obtained and who did not require replacement therapy, subnormal basal gonadotrophins were usually restored towards or into the normal range. It is concluded that while gonadotrophin levels may be normal in women with Cushing's syndrome, they are subnormal in those with the highest cortisol values. This may be due to a direct suppressive effect of cortisol on the release of stored pituitary hormone, and/or on LHRH release from the hypothalamus.

Adult↗
PubMed1981

Modified development to improve the performance of AR10 stripping emulsions for use with the more energetic isotopes.

Gold latensification of the image to increase the efficiency of the more energetic isotopes, such as 14 carbon, has been used before for liquid emulsions, with mild developers, but never successfully with AR10 stripping emulsion. This paper describes the performance of different developers and assesses their ability to suppress background fog on Kodak AR10 emulsion. A 14 carbon source was used and the effect of gold latensification was examined. Kodak D19, an efficient Metol/hydroquinone developer, could be usefully modified by altering the sodium carbonate and sulphite contents (D19 A/S). This developer discriminated well against the background with AR10 emulsion, producing a far better signal:background ratio than Kodak D19. A pretreatment in aurous thiocyanate for 4 min before development in D19 A/S for 4 min at 291 K increased the signal:background ratio by 200% compared with ordinary development in Kodak D19. When gold latensification was used with D19 developer, the signal was increased, but not more than with D19 A/S, and the gain was offset by the intense background that resulted.

Autoradiography↗