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Biomedical subjects

C J Fowler

Publications and source records attributed to C J Fowler.

At least 145 records · Page 8Linked to original sources
PubMed1994

Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases.

Multiple system atrophy is a disorder characterized by progressive neuronal atrophy at certain sites of the central nervous system, several of which are important in the control of urogenital function. The neuro-urological features of 62 patients with this condition are described. All patients had abnormal urethral or anal sphincter electromyography when individual motor unit analysis was performed, a finding diagnostic of the condition in the appropriate clinical setting. Impotence occurred in 96% of the men and was the first symptom alone in 37%. Urinary symptoms resulted from a combination of detrusor hyperreflexia and urethral sphincter weakness followed by failure of detrusor contraction. In men these symptoms simulated those of outflow obstruction so that 43% underwent prostatic or bladder neck surgery before the correct diagnosis was made. Stress incontinence occurred in 57% of the women and of these half had undergone surgery. The results of surgery in both sexes were poor. Treatment with intermittent catheterization, anticholinergic medication and desmopressin spray markedly improved continence in 82%. The importance of recognizing this disorder and introducing effective, nonoperative treatments is stressed.

Adult↗
PubMed1994

Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition.

Forty-eight men with multiple sclerosis and erectile dysfunction were evaluated. Emphasis was placed on the neurological features and the relationship between impotence and the bladder dysfunction in multiple sclerosis. Erectile failure was invariably associated with pyramidal signs in the lower limbs and with urinary symptoms. All of the men with impotence and marked pyramidal dysfunction in their legs were found by cystometric studies to have bladder hyperreflexia. The severity of the urinary symptoms was related to the degree of pyramidal impairment in the lower limbs. The posterior tibial and the pudendal cortical evoked potentials were abnormal in most of the men with multiple sclerosis and erectile failure. However, recording the pudendal cortical responses in patients with multiple sclerosis and impotence provided no more information than the tibial cortical evoked potentials. The neurological examination findings together with the results of the neurophysiological and cystometric tests suggest that erectile dysfunction in multiple sclerosis is due to spinal lesions situated proximal to the sacral cord. The feasability of papaverine intracorporeal injection therapy for men with multiple sclerosis and impotence was assessed. Papaverine intracorporeal injections produced satisfactory erections in the majority of the impotent men. Erectile failure in patients with multiple sclerosis was successfully managed for up to 2 years, by intracorporeal self-injection therapy.

Adult↗
PubMed1994

Intravesical capsaicin for treatment of detrusor hyperreflexia.

An intravesical instillation of 100 ml 1 or 2 mmol/l capsaicin has been used to treat detrusor hyperreflexia giving rise to intractable urinary incontinence in 12 patients with spinal cord disease and two other patients with detrusor overactivity of non-spinal origin. Nine patients, all of whom had spinal cord disease, showed some improvement in bladder function. The benefit was only shortlived and partial in four, but the remaining five achieved complete continence while performing intermittent self catheterisation. Urodynamic studies in these nine patients showed an increase in mean (SD) bladder capacity from 106 (57) to 302 (212) ml and a fall in the maximum detrusor pressure from 54 (20) to 36 (10) cm of water. There were no short term ill effects from the instillation and the improvement in bladder function lasted for between three weeks to six months, when in some patients it was repeated. The improvement in bladder behaviour shown in this study can be interpreted as showing that capsaicin sensitive afferents play an important part in the pathogenesis of detrusor hyperreflexia in spinal humans. Intravesical capsaicin seems a promising means of treating intractable detrusor hyperreflexia and studies with this substance may shed new light on other disorders of detrusor activity that cause incontinence.

Administration, Intravesical↗
PubMed1994

Cutaneous nerve fibre depletion in vibration white finger.

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the 'white attacks'. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Disrupted beta 1-adrenoceptor-G protein coupling in the temporal cortex of patients with Alzheimer's disease.

The efficacy of beta 1-adrenoceptor-G protein coupling was studied in postmortem temporal cortex synaptic membranes from a series of control and Alzheimer's disease subjects. For the control cases, the non-hydrolysable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) gave a significant reduction in the affinity of the agonist isoprenaline to displace binding of the radiolabelled antagonist (+/)-4-(3-t-butylamino-2-hydroxypropoxy)[5,7-3H]benzimidazol-2-one ([3H]CGP-12177). This effect was attributed to the conversion of high agonist-affinity sites to a lower-affinity state and was not found for the Alzheimer's disease cases. These data indicate that a disruption of beta 1-adrenoceptor-G protein coupling occurs in the temporal cortex of Alzheimer's disease patients.

Aged↗
PubMed1993

Inhibition of inositol 1,4,5-trisphosphate 5-phosphatase by micromolar concentrations of disulfiram and its analogues.

Following a preincubation period of 10 min, disulfiram and its analogues FLA 46, FLA 63, FLA 99, EWP 815 and EWP 840 inhibited the breakdown of 10 microM [3H]Ins(1,4,5)P3 by Ins(1,4,5)P3 5-phosphatase from GH3 cells, with IC50 values (in microM), for soluble/particulate enzymes respectively, of: disulfiram, 24/24; FLA 46, 23/30; FLA 63, 24/6; FLA 99, 50/48; EWP 815, 8/6; EWP 840, 11/8. The inhibition produced by FLA 99 was time-dependent in nature, although inhibition was found in the absence of a preincubation period. EWP 815 and EWP 840 were more potent inhibitors of Ins(1,4)P2 phosphatase than of Ins(1,4,5)P3 5-phosphatase. Thyrotropin-releasing hormone (TRH; 3/100 microM)-stimulated inositol phospholipid breakdown in prelabelled GH3 cells was inhibited by disulfiram (IC50 values 63/52 microM respectively), FLA 46 (89/110 microM), EWP 815 (83/71 microM) and EWP 840 (220/200 microM), without affecting basal breakdown rates. FLA 99 did not inhibit either basal or TRH-stimulated activity at any of the concentrations tested (30, 100 and 300 microM). [3H]Ins(1,4,5)P3 binding to its cerebellar receptor was not inhibited by any of the compounds over a concentration range of 3-300 microM, although an increased level of binding was seen at high concentrations. FLA 99 and EWP 840 increased the basal intracellular Ca2+ concentration in GH3 cells, but with no corresponding effect on the Ca2+ response to TRH stimulation. These compounds did not increase the cellular permeability to Trypan Blue, but did affect cell proliferation. It is concluded that disulfiram and related compounds produce dramatic effects on Ins(1,4,5)P3 metabolism in GH3 cells.

Animals↗
PubMed1993

Chronic fatigue: electromyographic and neuropathological evaluation.

Single fibre electromyography of extensor digitorum communis muscle (EDC) was performed on 35 patients with chronic fatigue, the majority of whom also had creatine kinase estimation and biopsy of EDC. The subjects were categorised as having an acute-onset post-viral fatigue syndrome, a non-specific chronic fatigue or possible muscle disease in view of pronounced myalgia. Of 11 subjects who had myalgia as a significant symptom, abnormalities in fibre density were found in 6, and 5 of these had some non-specific abnormalities on muscle biopsy, with creatine kinase levels being normal in all cases. Fibre density estimation may be a useful way of identifying a subgroup of chronic fatigue sufferers with a possible primary muscle disorder.

Adolescent↗
PubMed1993

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

AIDS-Related Complex↗
PubMed1993

Local anaesthetics do not affect protein kinase C function in intact neuroblastoma cells.

The effects of local anaesthetics on protein kinase C function in vitro were examined in two model systems: differentiation in mouse Neuro-2a neuroblastoma cells and muscarine M1-receptor mediated phosphoinositide breakdown in human SK-N-MC neuroblastoma cells. Staurosporin, a protein kinase C inhibitor, induced marked neuritogenesis in Neuro-2a cells after incubation for 5 h, whereas no effect could be seen after exposure to the local anaesthetics ropivacaine, lidocaine or bupivacaine. In the other model, protein kinase C-mediated regulation of phospholipase C was demonstrated for SK-N-MC cells. Phorbol 12-myristate 13-acetate, a protein kinase C activator, produced a dose-dependent decrease in both basal and carbachol-stimulated phosphoinositide breakdown. Staurosporin blocked this phorbol ester-induced subsensitivity completely, while ropivacaine, lidocaine or bupivacaine did not, suggesting that no functional protein kinase C antagonism is mediated by local anaesthetics. The present study suggests that unlike the reported inhibiting effects of local anaesthetics on purified protein kinase C isoforms, no such modulation is found in intact neuroblastoma cells.

Alkaloids↗
PubMed1993

Bowel dysfunction in young women with urinary retention.

Urinary retention in young women is rare, but a syndrome has recently been described in which urinary retention is associated with abnormal periurethral electromyography. The incidence of bowel dysfunction in these women was investigated, in an attempt to determine whether this might be a more widespread disorder. Of 12 patients with this urological abnormality, eight were constipated. No consistent anorectal abnormality was identified on anorectal physiological testing. The electromyographic abnormality was not seen in the external anal sphincter. One patient had an abnormality of the internal anal sphincter smooth muscle, while another had a generalised disorder of the gastrointestinal tract and urinary bladder resembling a visceral myopathy. Bowel symptoms are common in this group of women with urinary retention, but abnormalities of bowel function are not specific. A common mechanism for bladder and bowel symptoms remains a possibility.

Adolescent↗
PubMed1993

Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis.

One hundred and seventy patients with multiple sclerosis and bladder dysfunction were evaluated. Emphasis was placed on the relationship between their neurological features and urinary symptoms. The severity of the urinary symptoms was related to the degree of pyramidal impairment in the lower limbs so that both problems are thought to reflect the extent of spinal involvement. No other neurological features correlated with bladder dysfunction. Detrusor hyperreflexia was the commonest finding on cystometry and no patient had areflexia. More than half of the patients had a significantly raised post-micturition residual volume but symptoms were largely unreliable in predicting poor bladder emptying. In this series only two patients had evidence of upper tract disease: both men with severe, longstanding neurological disease who had indwelling catheters. Detrusor hyperreflexia can be anticipated in patients with MS who have irritative urinary symptoms and pyramidal signs in their lower limbs. After measurement of the residual volume appropriate treatment can be instituted.

Adult↗
PubMed1992

Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease.

The coupling of inhibitory guanine nucleotide binding (Gi) proteins to the adenylyl cyclase signal transduction complex was compared in 4 brain regions from a series of Alzheimer's disease and matched control subjects by measuring the inhibition of membrane enzyme activities in response to guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) and aluminium fluoride (AlF4-). Basal adenylyl cyclase activities were significantly lower in preparations of angular gyrus and frontal and temporal cortices, but not cerebellum, from the Alzheimer's disease cases compared to controls. Gpp[NH]p and AlF4- gave significant inhibitions of adenylyl cyclase activity in all brain regions. The magnitude of these inhibitions, when corrected for altered basal activities, were similar for the Alzheimer's disease and control cases. These results indicate that there is no impairment of Gi-protein mediated inhibition of adenylyl cyclase activity in Alzheimer's disease brain.

Adenylyl Cyclases↗
PubMed1992

Penetrating eye injuries related to assault. The National Eye Trauma System Registry.

From 1985 to 1991, 648 cases of assault-related penetrating ocular injury were reported to the National Eye Trauma System Registry. We examined the circumstances surrounding and initial clinical findings related to this case series of injuries. Eighty-three percent of the patients were male. The median age was 28 years; 77% were younger than age 40 years, and 17% were younger than age 20 years. The ocular injury was part of multiple trauma in 34% of cases. There was evidence of alcohol and illicit drug use by at least 48% and 6% of the injured persons, respectively. Seventeen percent of the injuries involved powder or nonpowder firearms. Fists, glass fragments, metal rods or pipes, knives, and scissors were among the other objects causing injury. Posterior segment trauma, which occurred in 70% of cases, included vitreous hemorrhage (40% of cases), retinal detachment (11%), presence of intraocular foreign bodies (6%), and optic nerve damage (4%). The initial visual acuity after injury was hand motion or worse in 74% of the cases. Strategies to prevent such injuries focus on the origins of violence in general and are more difficult to devise than strategies to prevent eye injuries in other settings. Public health efforts to reduce the use of alcohol, drugs, and firearms may reduce the incidence of these injuries.

Adolescent↗