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Biomedical subjects

C J Fowler

Publications and source records attributed to C J Fowler.

At least 73 records · Page 4Linked to original sources
PubMed2000

The effect of intravesical capsaicin on the suburothelial innervation in patients with detrusor hyper-reflexia.

OBJECTIVE: To determine the effect of intravesical capsaicin on the suburothelial innervation in patients with detrusor hyper-reflexia, in whom a single dose of intravesical capsaicin (1-2 mmol/L) increases the bladder capacity for 3-6 months. PATIENTS AND METHODS: Thirteen patients with detrusor hyper-reflexia underwent cystometry and had flexible cystoscopic biopsies taken before and 6 weeks after receiving instillations of intravesical capsaicin (1 mmol/L). Similar biopsies were also obtained from a control group of 12 neurologically normal patients with microscopic haematuria and normal bladders. Frozen sections were stained using antibodies to S100 and PGP 9.5. Using computerized analysis, the mean nerve density scores were expressed as nerves/mm2 for S100-positive structures and 'red%' and 'red in frame' for PGP 9.5. RESULTS: The mean (SEM) functional bladder capacity increased from 193.2 (28.17) mL before to 396.3 (41.96) mL at 6 weeks after treatment with capsaicin, in nine of the 13 patients. The mean nerve density of S100-positive structures in the control group was 83 (3.18) nerves/mm2. In hyper-reflexic patients who responded to capsaicin by improved bladder capacity, the mean nerve density of S100-positive structures was reduced from 100 (12.2) before to 66 (9.4) nerves/mm2 6 weeks after treatment. In those who did not respond to capsaicin there was no significant difference in these scores. Similarly the 'red%' and 'red in frame' reduced from 3.41 (1.06) to 1.15 (0.32) and 824.7 (246.3) to 297.9 (83.5) units, respectively, before and 6 weeks after capsaicin treatment. The difference in those not responding was not significant. CONCLUSIONS: Intravesical capsaicin causes a reduction in suburothelial nerve densities in the bladder of patients with detrusor hyper-reflexia. This may explain its prolonged beneficial effect in these patients.

Administration, Intravesical↗
PubMed2000

Sacral neuromodulation for women with Fowler's syndrome.

Neuromodulation of the sacral nerves has been found to be an effective therapy for a variety of lower urinary tract dysfunctions. The reported success rate for the period of trial stimulation (peripheral nerve evaluation test) prior to permanent implantation of a sacral nerve stimulator is variable, but generally reported to be in the region of 30-50%. We present here the results of the peripheral nerve evaluation test in 38 patients with urinary retention. 34 of the 38 had been found to have an abnormality of their striated urethral sphincter on electromyography using a concentric needle electrode, i.e., they had the disorder which was described by Fowler and coworkers in 1988. The overall success rate in this group was 68%. We believe that our relatively high success rate is due to sacral neuromodulation working via a mechanism which involves the urethral sphincter, an abnormality which had been demonstrated in 89% of these patients. Twelve of the patients subsequently underwent permanent implantation of a sacral nerve stimulator, and all of them have experienced a return of voiding. However, in 2 patients, there is a persisting need for self-catheterization. There is, however, a high reoperation rate.

Adolescent↗
PubMed2000

Investigation into the rapid effects of 17 beta-estradiol and neuroactive steroids upon beta-amyloid(25-35)-induced activation of phosphoinositide-specific phospholipase C in human platelets.

In the present study, the rapid effects of five steroids (17 beta-estradiol, progesterone, allopregnanolone, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one) and the plant steroid trans-resveratrol upon the calcium response to beta-amyloid(25-35) peptide (A beta(25-35)) in human platelets was measured. A beta(25-35) produced a robust increase in intracellular calcium due to a direct activation of phosphoinositide-specific phospholipase C. None of the steroids significantly affected the response to A beta(25-35). In contrast, trans-resveratrol appeared to increase the response to A beta(25-35) at a concentration that decreased the response to thrombin, although the possibility that these changes are artifactual could not be ruled out. It is concluded that although steroids affect human platelet Ca2+ homeostasis, this is not a rapid event, unless very high concentrations are used.

Amyloid beta-Peptides↗
PubMed2000

Investigation into the effects of amyloid (1-42) beta-peptide upon basal and antigen-stimulated hexosaminidase and serotonin release from rat RBL-2H3 basophilic leukemia cells.

There is evidence that beta-amyloid (A beta) peptide infusion in vivo produces a degranulation of vascular mast cells. It would be useful to investigate the interaction between A beta and mast cells in a simple in vitro model system in order to determine the cellular mechanism by which exposure to A beta peptides results in mast cell degranulation. In the present study, the effect of A beta(1-42) upon the release of granular hexosaminidase and serotonin has been investigated using the cognate rat mast cell line, RBL-2H3. Sensitization of these cells for 1 h with anti-DNP IgE (monoclonal anti-dinitrophenyl) results in a large release of hexosaminidase and serotonin due to degranulation when the cells are exposed to DNP-HSA (albumin, human dinitrophenyl). Pretreatment overnight with A beta(1-42) (10 and 30 microM) did not affect either the basal or antigen-stimulated release of hexosaminidase or serotonin. A similar lack of effect of A beta(25-35) and the lipid peroxidation product HNE upon antigen-stimulated release of hexosaminidase or serotonin was also found. It is concluded that RBL-2H3 cells are not a useful model for mechanistic studies into the effects of beta-amyloid peptides upon vascular mast cells.

Amyloid beta-Peptides↗
PubMed2000

beta-Amyloid(25-35) inhibits the activity of inositol(1,4,5)-trisphosphate-5-phosphatase.

beta-amyloid (A beta) peptides are known to disrupt calcium homeostasis in cells. In the present study, the effects of A beta(25-35) upon the activity of soluble Ins(1,4,5)P3-5-phosphatase have been investigated. A beta(25-35) inhibited, and dithiothreitol (DTT) increased the activity of soluble rat cerebellar Ins(1,4,5)P3-5-phosphatase. The change in activity was not accompanied by an obvious change in the sensitivity of the Ins(1,4,5)P3-5-phosphatase to inhibition by glucose-6-phosphate or phytic acid. A beta(35-25) also inhibited soluble Ins(1,4,5)P3-5-phosphatase activity, but at a lower potency than A beta(25-35). It is concluded that A beta(25-35) affects the metabolism of Ins(1,4,5)P3 although the potency is not sufficiently high to contribute to any significant extent to the effects of this peptide upon calcium homeostasis.

Amyloid beta-Peptides↗
PubMed2000

Studies of the latency of pelvic floor contraction during peripheral nerve evaluation show that the muscle response is reflexly mediated.

PURPOSE: Whether neuromodulation using an implanted sacral nerve stimulator acts by its effects on pelvic afferent or efferent nerves remains to be determined. However, it has been observed that eliciting an "anal wink" is helpful in the optimal siting of the foraminal stimulating electrode. This observation has been interpreted as indicating that a direct effect on efferent pelvic innervation is an important functional component of the technique. We studied the latency of this motor response to determine whether it is consistent with neuromodulation working via a direct efferent mechanism. MATERIALS AND METHODS: We studied 9 women with urinary retention undergoing the first stage of a stimulator implant (peripheral nerve evaluation). Stimulation was applied to an electrode placed in the S3 foramen and the latency of the response of the striated anal sphincter, a contraction which gives rise to the "anal wink," was measured using a concentric needle electrode placed in the striated part of the anal sphincter. RESULTS: Mean latency of response was 98 milliseconds (range 52 to 140), which is approximately 10 times longer than would be expected from that resulting from direct motor nerve stimulation. CONCLUSIONS: Our results indicate that anal sphincter contraction observed during peripheral nerve evaluation is the result of an afferent mediated response.

Adult↗
PubMed1999

Evidence for cooperative binding of (-)Isoproterenol to rat brain beta1-adrenergic receptors.

In the present study, the effects of the thiol oxidising agent diamide upon the properties of rat brain beta1-adrenergic and human platelet serotonin2A receptor recognition sites have been investigated using [3H](-)CGP-12177 (in the presence of ICI-118551) and [3H]LSD as ligands. (-)Isoprenaline inhibited [3H](-)CGP-12177 binding with nH values of 0.87, 0.67, and 0.56 for added Mg2+ concentrations of 0, 2.5, and 25 mM, respectively. Pretreatment with diamide increased the nH to above unity for the inhibition of the binding by (-)isoprenaline, without a concomitant effect on the inhibition of the binding by (-)propranolol. In contrast, diamide reduced the affinity of human platelet serotonin2A-receptors for antagonists, but did not consistently induce nH values above unity for the inhibition of antagonist binding by serotonin. These results suggest that cooperative interactions reported for cardiac muscarinic receptors may also occur for beta1-adrenergic receptors in the rat brain.

Adrenergic beta-1 Receptor Agonists↗
PubMed1999

Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.

The endogenous cannabimimetic anandamide is hydrolyzed by a fatty acid amide hydrolase to yield arachidonic acid and ethanolamine. In the present study, the regional distribution of the activity and its sensitivity to inhibition by the enantiomers of ibuprofen, ketorolac, and flurbiprofen has been investigated. The rate of [3H]anandamide hydrolysis was found in both 7-week-old and 90-week-old rats to be in the order hippocampus > cerebral cortex > cerebellum > striatum approximately midbrain, with higher rates of hydrolysis for the 7-week-old rats than for the 90-week-old rats. In whole brain (minus cerebellum), the R(-)-enantiomer of ibuprofen was a mixed-type inhibitor of anandamide hydrolysis and was approximately 2-3 times more potent than the S(+)-enantiomer, IC50 values of 230 and 750 microM, respectively, being found. A similar pattern of inhibition of anandamide hydrolysis was seen when intact C6 rat glioma cells were used. Ketorolac inhibited rat brain anandamide hydrolysis, with IC50 values of 50, 440, and 80 microM being found for the R-, S-, and R,S-forms, respectively. The IC50 value for R-flurbiprofen (60 microM) was similar to the IC50 value for the S-enantiomer (50 microM). These data demonstrate that there is no dramatic enantiomeric selectivity of NSAID compounds as inhibitors of fatty acid amide hydrolase enzyme(s) responsible for the hydrolysis of anandamide. The enantiomers of flurbiprofen and R-ketorolac are the most potent NSAID inhibitors of fatty acid amide hydrolase yet reported.

Aging↗
PubMed1999

Consensus statement on the diagnosis of multiple system atrophy.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Autonomic Nervous System Diseases↗
PubMed1999

Voiding and MRI analysis of the brain.

Observations of surgery, angiography and postmortem studies have indicated that the frontal lobe is a higher center important in the control of micturition. CT and MRI have made it possible to extend these early observations, and we report here the results of imaging in patients with hemispheric and brain-stem strokes. In a series of stroke patients urinary dysfunction was found in 68% with frontal lesions 20% with parietal, 14% with temporal and none with occipital lobe lesions. With lesions in the frontal lobe, it appears that medial aspects are particularly important in the prefrontal lobe, cingulate gyrus, paracentral lobule and the orbital area in micturition control. Frontal lobe disease may cause disorders of storage as well as voiding, as shown by urodynamics: detrusor hyperreflexia, detrusor areflexia, uninhibited sphincter relaxation and unrelaxing sphincter on voiding were found. We have also had the opportunity to make observations about the role of the basal ganglia and pons in micturition control in humans.

Basal Ganglia↗
PubMed1999

Serotonin stimulation of calcium mobilisation in human platelets: choice of units of measurement, effects of age and tobacco use, and correlation with serotonin2A receptor density.

The calcium responses to serotonin and thrombin, as assessed using the fluorescent indicator Fura-2, have been investigated in platelets taken from 59 non-smokers and 17 smokers. The peak responses above baseline, calculated either as fluorescence ratios or calibrated calcium concentrations, were in the order of magnitude thrombin 520 mU/ml > thrombin 52 mU/ml >> serotonin 1 micromol/l approximately serotonin 100 micromol/l. Multiple regression analyses indicated that the responses to 1 micromol/l serotonin, but not the responses to thrombin, were significantly correlated with the serotonin2A receptor density measured using [3H]LSD as radioligand. No effects of age, gender, smoking habit or the time of year of sampling were seen on the calcium responses to serotonin and thrombin. It is concluded that cellular processes distal to the serotonin2A receptor recognition site may compensate to some extent for the large differences in recognition site expression, thus underlining the importance of providing a functional correlate in addition to [3H]LSD binding site densities when studying platelet serotonin2A receptors in neuropsychiatric disorders. The measurement of Ca2+ responses to serotonin provides a useful such functional correlate.

Adolescent↗
PubMed1999

Dopamine and glutamate neurotoxicity in cultured chick telencephali cells: effects of NMDA antagonists, antioxidants and MAO inhibitors.

In a recent study, it was found that the intrastriatal administration to rats of the organophosphorous compound soman and kainic acid produced a rapid release not only of glutamate but also of dopamine in this brain region. Dopamine is a potent source of free radicals and is known to produce cytotoxic effects, per se. This raises the possibility that the released glutamate and dopamine act synergistically to produce the neurotoxicity found after soman administration. In order to investigate the feasibility of this hypothesis in an in vitro system, the effects of dopamine and glutamate upon cell survival were investigated using chick neurons (7 DIV) in serum-free primary culture. The neurons were treated with dopamine and/or glutamate for up to 24 h and cell toxicity was then assessed either by determination of cell densities, by the release of cytoplasmic LDH or by the MTT cytotoxicity assay. L-Glutamate produced a concentration-dependent cytotoxicity that was seen as early as after 30 min of exposure, and was accompanied by an increased level of lipid peroxidation. The L-glutamate toxicity could to a large extent by prevented by NMDA receptor antagonists and to a lesser extent by catalase, superoxide dismutase or glutathione ethyl ester added 30 min before the glutamate. Dopamine was also cytotoxic, and the cytotoxicity was reduced by the combination of catalase and glutathione ethyl ester but not by the MAO inhibitors clorgyline or L-deprenyl, or by the selective dopamine uptake inhibitor GBR 12783. The cytotoxic effects of dopamine and L-glutamate were additive rather than synergistic, regardless of the incubation time used. It is concluded that chick neurons in serum-free culture are a useful in vitro model system for the study of cell toxicity produced by oxidative stress and by glutamate. The cytotoxic effects of dopamine in this model are not due to the monoamine oxidase-mediated production of hydrogen peroxide but appear at least in part to be related to oxidative stress.

Animals↗
PubMed1999

The effect of hydrogen peroxide upon beta-adrenoceptor density and function in C6 rat glioma cells.

Hydrogen peroxide has been suggested to play an important role in the pathogenesis of Alzheimer's disease. In the present study, the effects of hydrogen peroxide upon the functional integrity of beta-adrenoceptors have been investigated in C6 glioma cells. Treatment of cells for 24 h with hydrogen peroxide in serum-free medium produced a concentration-dependent cell toxicity, seen both using cell counting and LDH release into medium as end point. There were no large nor consistent changes in either the density of cell surface beta 1, or beta 2-adrenoceptors, measured using the hydrophilic ligand [3H](-)-CGP 12177, nor in either basal, forskolin and isoprenaline-stimulated cAMP responses, following hydrogen peroxide treatment. It is concluded that the decreased adenylyl cyclase activity and responsiveness to Gs stimulation found in post-mortem brain samples from Alzheimer's disease autopsy cases is unlikely to be mediated by hydrogen peroxide.

Adenylyl Cyclases↗
PubMed1999

Neurological disorders of micturition and their treatment.

An overview of the current concepts of the neurological control of the bladder is given, based on laboratory experiments and PET scanning studies in human subjects. This is followed by a description of the various causes of the neurogenic bladder, discussed in a hierarchical order starting with cortical lesions and descending through the basal ganglia and brainstem, spinal cord, conus and cauda equina to disorders of peripheral innervation. Then follows a description of the condition of isolated urinary retention in young women. The article concludes with a review of the methods available for treating neurogenic bladder disorders. These are largely medical but brief mention of appropriate surgical procedures is made.

Animals↗
PubMed1999

Further studies of the effects of diamide and hydrogen peroxide on calcium signaling in the human platelet.

Intracellular calcium levels were measured in Fura-2/AM loaded human platelets. Diamide (30 microM) reduced the Ca2+ response to serotonin (1 microM), but not to 4-bromo-A23187 (1 microM). The small reduction in the maximum fluorescence produced by diamide was not mirrored by a change in the sensitivity of Fura-2 pentapotassium salt to Ca2+. Changes in the spectral properties of Fura-2 thus cannot wholly explain the reduced serotonin response following diamide treatment. Hydrogen peroxide (500 microM) produced a steady increase in the observed fluorescence ratio that was partially inhibited by the phospholipase C inhibitor U-73122 (1.5 microM). In the absence of platelets, H2O2 reduced the Ca(2+)-sensitivity of Fura-2 pentapotassium salt, although it is not clear the extent to which this effect contributes to the reduction in the Ca2+ response to serotonin seen after H2O2. It is concluded that some caution may be warranted in the interpretation of the effects of H2O2 upon receptor-mediated Ca2+ signaling as measured using Fura-2.

Blood Platelets↗
PubMed1998

Consensus statement on the diagnosis of multiple system atrophy.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Autonomic Nervous System Diseases↗