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Biomedical subjects

S Lindström

Publications and source records attributed to S Lindström.

At least 19 recordsLinked to original sources

The C fibre reflex of the cat urinary bladder.

1. Reflexes evoked in bladder parasympathetic neurones by electrical stimulation of bladder C afferent fibres were studied in cats anaesthetized with alpha-chloralose. The responses were compared with the ordinary micturition reflex evoked by low-threshold Adelta afferents from bladder mechanoreceptors and mediated by a spino-ponto-spinal reflex pathway. 2. The bladder was catheterized for fluid instillations and pressure recordings. Efferent reflex discharges were recorded from the cut central end of a small distal bladder branch of the pelvic nerve. The remaining bladder pelvic nerve branches were stimulated electrically close to the bladder. 3. Stimulation at C afferent intensity evoked a late reflex discharge in bladder pelvic efferents in all animals. The response was centrally mediated, had a latency of 150-250 ms, and was much weaker after stimulation on the contralateral nerve. 4. The bladder C fibre reflex differed in several functional aspects from the ordinary Adelta micturition reflex. It could be evoked at a low rate of stimulation, with an empty bladder and no background activity from bladder mechanoreceptors. In this situation, the normal Adelta micturition reflex is not elicited. The C fibre reflex also survived an acute spinalization at a low thoracic level. 5. The C fibre reflex was strongly inhibited by dorsal clitoris or dorsal penis nerve stimulation, an effect that was maintained after spinalization. It was facilitated by bladder or urethra exposure to cold and menthol, stimuli that activate specific cold-sensitive receptors associated with unmyelinated C afferents. 6. It is concluded that the central pathway of the C fibre reflex is spinal and partly separate from that of the ordinary micturition reflex. These observations are in keeping with the clinical finding that a bladder cooling reflex can be elicited in patients with disturbed descending control of the bladder.

Animals

Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention.

Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

Animals

Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat.

OBJECTIVE: To investigate whether anogenital afferent stimulation induces a prolonged increase in the micturition threshold volume of anaesthetized rats. MATERIALS AND METHODS: Thirteen female rats, anaesthetized by alpha-chloralose and paralysed by pancuronium bromide were used for the experiments. The micturition threshold volume was determined by repeated cystometry. In two experiments, afferent activity was recorded from the exposed pudendal nerve; vaginal and anal afferents were stimulated electrically by ring electrodes. In one experiment, the dorsal clitoris nerves were exposed bilaterally and mounted for electrical stimulation. The afferents were stimulated continuously for 5 min at 10 Hz, using unipolar cathodic pulses of 0.5 ms duration with an amplitude of 10 mA (or 0.8 mA for the dorsal clitoral nerves). RESULTS: Anogenital stimulation for 5 min induced a significant and prolonged increase in the micturition threshold volume (from a median value of 0.35 mL before to 0.45 mL after stimulation; P < 0.01). The increase in threshold volume was maintained for about 40 min after the end of stimulation. There was no obvious difference in effect between the stimulation sites nor with direct dorsal clitoral nerve stimulation. Neither the micturition threshold pressure nor the maximal contraction pressure were altered by stimulation. No tonic afferent after-discharge could be detected in the pudendal nerve recordings. CONCLUSIONS: Artificial electrical stimulation of anogenital afferents induced a prolonged increase in the micturition threshold volume of anaesthetized rats. The change presumably involved the modulation of the synaptic transmission in the central micturition reflex pathway. It is proposed that the observed change represents the first step in the curative 're-education' process induced in patients with urge incontinence by electrical stimulation of anovaginal afferents.

Anal Canal

Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat.

PURPOSE: Intravesical electrical stimulation (IVES) has been used clinically to treat patients with voiding disorders. The aim of the present experimental study was to obtain objective evidence of a modulation of the micturition reflex by intravesical electrical stimulation (IVES). MATERIALS AND METHODS: Forty-one female rats, anesthetized by alpha-chloralose were used for the experiments. Intravesical electrical stimulation was given by a catheter electrode in the bladder (5 minutes of continuous stimulation at 20 Hz, 7 to 11 mA). The effect was evaluated by the change in cystometric micturition threshold volume. RESULTS: The threshold volume of the micturition reflex decreased significantly to 82% of controls after IVES (p<0.001; n=31). The effect was reversible and lasted for about 1 hour. The decrease was prevented by a transient blockade of the bladder nerves during IVES. CONCLUSIONS: Intravesical electrical stimulation induced a prolonged modulation of the micturition reflex in anesthetized rats. The effect was due to activation of bladder mechanoreceptor afferents and remained long after the period of stimulation. It is proposed that the modulation was due to a prolonged enhancement of excitatory synaptic transmission in the central micturition reflex pathway. Such a modulation may underlie the curative effect of IVES in certain voiding disorders.

Animals

Toward a new classification of overactive bladders.

Based on a large retrospective series, this study compares the International Continence Society's (ICS) classification of overactive bladders and a functional subtyping of our own, founded on clinical and urodynamic parameters. Functionally identical symptoms and urodynamic patterns were found within the Detrusor Hyperreflexia as well as the Unstable Detrusor categories. There are strong arguments for a revision of the current ICS classification system.

Adult

Diuresis and voiding pattern in healthy schoolchildren.

OBJECTIVE: To analyse how differences in diuresis affect the normal pattern of micturition of healthy children. SUBJECTS AND METHODS: Two hundred and six healthy continent schoolchildren, aged 7-15 years, completed a frequency/volume chart for 24 h by recording the time and volume of each micturition. Several diuresis variables were calculated from these charts and compared with sex, age, oral fluid intake, functional bladder capacity, voiding intervals and volumes. RESULTS: The weight-corrected mean diuresis per 24 h varied 10-fold between individuals, independently of recorded fluid intake. In the majority, the diuresis decreased during the night, but the opposite diurnal pattern occurred in 12% of the children. The individual night-time diuresis was positively correlated with functional bladder capacity and the daytime diuresis was positively correlated with voiding frequency. CONCLUSIONS: The weight-corrected diuresis varies many-fold among healthy continent children. A substantial proportion has a reversed diurnal pattern with a larger diuresis during the night. The individual bladder size is adapted to accommodate their typical nightly urine production.

Adolescent

Acute effects of 17 beta-estradiol on brain excitability studied in vitro and in vivo.

The acute effects of 17 beta-estradiol on brain excitability were studied in vitro and in vivo utilizing rat hippocampal slices and a cat cerveau isolé preparation. The hippocampal slices were perfused with 17 beta-estradiol (10(-7)-10(-10) M) for 30 min. No effects were observed on synaptic activation and inhibition and on the response to iontophoretically applied GABA in intact and ovariectomized female rats (n = 43). In males (n = 32), however, a small (12%) but significant increase in population spike amplitude was observed after 30 min exposure to 10(-9) M 17 beta-estradiol. Higher and lower concentrations were ineffective. In vivo, no acute effects of 17 beta-estradiol on focal epileptic seizure thresholds, evoked potentials, or augmenting response were observed in the visual cortex of non-estrous female cats (n = 11; median dose 1 micrograms/kg, range 0.5 microgram/kg-10 mg/kg).

Animals

Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.

Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.

Adolescent

Positive bladder cooling test in neurologically normal young children.

The bladder cooling test, which consists of rapid infusion of 0 to 8C saline into the bladder with simultaneous pressure measurement, was performed in 50 neurologically intact infants and children 6 months to 13 years old. The patients were referred for urodynamic investigation because of various disorders of the lower urinary tract. A positive bladder cooling test was defined as a sustained reflex detrusor contraction of about the same magnitude as the micturition contraction. The test was positive during the first 4 years of life but typically negative in children older than 5 years. These findings indicate that a positive bladder cooling test is an infant reflex response that, with the maturation of the central nervous system, becomes suppressed by descending signals from higher centers.

Adolescent

Pressure, volume and infusion speed criteria for the ice-water test.

OBJECTIVE: To define pressure, volume and infusion speed criteria for the ice-water test (IWT). PATIENTS AND METHODS: In this prospective clinical study, cystometry and IWTs were performed in 115 patients. RESULTS: The critical response for a positive IWT was found to be a peak detrusor pressure above 30 cm H2O, with or without fluid leakage. Neither the infusion speed nor the infused volume was critical for the outcome of the test provided that the bladder wall was sufficiently cooled. CONCLUSION: The IWT is a rapid, simple and robust test, whose results are easy to interpret. The test increases the precision of urodynamic diagnosis, especially in patients with an overactive detrusor dysfunction, at a small cost.

Administration, Intravesical

The effect of progesterone and its metabolite 5 alpha-pregnan-3 alpha-ol-20-one on focal epileptic seizures in the cat's visual cortex in vivo.

The acute effects of progesterone and its brain metabolite 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) on focal epileptic seizures in the cat's visual cortex was studied in vivo using an unanesthetized cervaux-isolé preparation. This model made it possible to study in parallel the effect of the drugs on ictal activity and synaptic transmission. A dose-dependent increase in seizure threshold was observed after i.v. injections of both 3 alpha-OH-DHP and progesterone, 3 alpha-OH-DHP being about 20 times as potent as the latter. I.v. injections of 3 alpha-OH-DHP 1.0 mg/kg increased the median seizure threshold to 265% of baseline. While 3 alpha-OH-DHP exerted an immediate effect on seizure thresholds, the maximal effect of progesterone was delayed about 20 min. Concerning the mechanisms underlying the antiepileptic effect, three changes occurred within the effective dose range: (1) a small, but significant reduction in the presynaptic nerve volleys, (2) a reduction in the postsynaptic excitatory field potentials in the dorsal lateral geniculate nucleus and cortex, and (3) an enhanced postsynaptic inhibition. Taken together, these observations point to both pre- and postsynaptic effects, supporting the hypothesis of a barbiturate-like mechanism of action of progesterone and its brain metabolites.

Animals

Subtypes of overactive bladder in old age.

The prevalence of urinary incontinence increases dramatically with age and is mainly related to urge incontinence and bladder overactivity. It is a reasonable hypothesis that bladder overactivity primarily results from a disturbed central neuronal control of the lower urinary tract. Different sites and extents of neurogenic lesions or dysfunctions should result in different functional and urodynamic characteristics. We have recently identified three distinct urodynamic subtypes of bladder overactivity, and we report a retrospective study of the distribution of these subtypes in elderly patients. Eight hundred and fourteen patients aged 65 years or older with symptoms of urgency and/or urge incontinence underwent cystometry and the ice-water test. Two hundred and sixty-seven of them (33%) presented an overactive bladder. The prevalence of overactive bladder was constant up to the age of 65. A marked increase above this age was almost entirely ascribed to an increase of the so-called uninhibited overactive bladder subtype. This dysfunction occurred in 70% of the older patients. Patients with this condition have a coordinated reflex micturition at normal bladder volumes, but an abnormal perception of bladder fullness and lack of voluntary inhibitory control. This constellation of symptoms and signs indicates a suprapontine dysfunction.

Aged

The bladder cooling reflex in man--characteristics and sensitivity to temperature.

The ice-water test is a simple supplementary urodynamic test that increases the precision of the diagnosis of overactive bladder subtypes. A similar bladder cooling reflex has recently been characterised in the cat and was found to originate from specific cold receptors in the bladder wall. In the present study, the threshold temperature of the human bladder cooling reflex was determined in patients with positive ice-water tests. Estimated threshold values were somewhat lower than those of the cat but still well above the temperatures required for cold stimulation of nociceptors. As in the cat, the strength of the cooling reflex varied inversely with the bladder temperature. These findings indicate that the human bladder cooling reflex is in principle organised in the same way as that of laboratory animals. The human bladder thus seems to be endowed with cold receptors with excitatory reflex connections to the detrusor.

Adult

The ice-water test--a simple and valuable supplement to routine cystometry.

The results of cystometrograms and ice-water tests (IWTs) were retrospectively evaluated in 557 patients with overactive bladders, lower motor neuron lesions or pure stress incontinence. The IWT was considered positive when, following ice-water instillation, the fluid was expelled from the bladder within 1 min. The test was considered false negative when no fluid escaped despite a sustained detrusor contraction of the same magnitude as the micturition contraction. Ninety-seven percent of patients with complete and 91% of those with incomplete upper motor neuron lesions had a positive or a false negative IWT. About 75% of the patients with multiple sclerosis, Parkinson's disease or previous cerebrovascular accident had a positive IWT. All patients with lower motor neuron lesions or pure stress incontinence had a negative IWT. There was a significant correlation between a positive IWT and an abnormal sensation of bladder filling and inability to inhibit micturition voluntarily, as well as between a negative IWT and the occurrence of phasic detrusor contractions during cystometry. The study shows that the IWT is a sensitive test for differentiating upper from lower motor neuron lesions. It is also a useful parameter for functional subdivision of overactive bladders. In patients with voiding dysfunction in the absence of lower urinary tract inflammation, a positive test is an indicator of a silent or overt neurological disorder.

Adolescent