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Biomedical subjects

K Anders

Publications and source records attributed to K Anders.

At least 19 recordsLinked to original sources

Evaluating ambulatory urodynamics: a prospective study in asymptomatic women.

OBJECTIVE: To identify abnormal detrusor contractions in asymptomatic women undergoing ambulatory urodynamics, to standardise the investigation technique for women with urinary symptoms for clinical practice. DESIGN: Prospective observational study. SETTING: Two tertiary referral urogynaecology units: one in London, UK and one in Varese, Italy. METHODS: Women without urinary symptoms were recruited into the study. Ambulatory urodynamics was performed according to the King's College Hospital protocol. All the traces were analysed in four different ways: 1. without the second bladder transducer measurements displayed on the screen and without the diary; 2. as in 1. but with the diary; 3. with the second bladder sensor displayed on the screen but without the diary; 4. as in 3. but with the diary. The diary was always interpreted at the end of the test with the woman present. For each method we reported the total number of detrusor contractions and whether the woman would have been diagnosed as having abnormal detrusor contraction. Cochran's Q test was used for statistical analysis. RESULTS: Twenty-six women (mean age 31.7 years) were recruited. Ambulatory urodynamic testing lasted an average of 3.57 hour. The diagnosis of abnormal detrusor contraction varied by 65.4% depending on the method of analysis used. The diary and the women's symptoms during the test were the most discriminating factors. A significant difference between the diagnoses was obtained when comparing the four different ways of analysis. According to our protocol only three women (11.5%) had abnormal detrusor contractions. CONCLUSIONS: Using our protocol almost 90% of asymptomatic women have a stable bladder on ambulatory urodynamics. This is similar to the results of labouratory urodynamic testing of asymptomatic women but is in contrast to previous reports of ambulatory urodynamics of asymptomatic women. The technique used during ambulatory urodynamics determines the tests ability to detect detrusor instability with an accurate symptom diary being the most important.

Adult↗

Accelerated radiotherapy with concomitant ACNU/Ara-C for the treatment of malignant glioma.

PURPOSE: To evaluate activity and toxicity of simultaneous ACNU and Ara-C with concurrent accelerated hyperfractionated radiotherapy in the treatment of high-grade glioma. PATIENTS AND METHODS: Thirty patients aged 23-71 years (median 47.5), 16 patients with glioblastoma multiforme (GBM) and 14 patients with grade-III glioma, received 93 courses of ACNU/Ara-C (median 4 courses) at following dose levels (ACNU/Ara-C in mg/m2/day): 70/90 (11 courses), 75/100 (36 courses) and 90/120 (46 courses). ACNU was administered IV on day 1 of each cycle, Ara-C as a 2 h-intravenous infusion on days 1-3. Patients received concomitant radiation therapy with 2 daily fractions of 1.75 Gy up to 57 Gy (median). RESULTS: Median survival of all patients was 13 months, 11 months for GBM and > 28 months for grade-III glioma; 31% (9 patients) survived longer than 24 months. The percentage of grade IV hematological toxicity was dose-dependent: 33% at the 70/90 dose level, 40% at 75/100 and 58% at 90/120. Six patients required platelet transfusion, 1 patient red blood cells; no febrile neutropenia occurred. Among 18 patients evaluable for response, 3 (17%) showed PR, 8 (44%) NC and 7 (39%) PD at completion of chemoradiation. No acute or late neurological toxicity occurred in this study. Younger age (p = 0.0001) and grade-III histology (p = 0.0009) were important prognostic factors for prolonged survival. CONCLUSION: This chemoradiation regimen is active in malignant gliomas and can be safely recommended at a dose level using 70 mg/m2 ACNU together with 90 mg/m2 Ara-C.

Adult↗

Coping strategies for women with urinary incontinence.

Incontinence is a common and complex condition affecting women of all ages, social and cultural backgrounds. 'Coping strategies' play an important role for managing incontinence and include changes in lifestyle, protection, aids, and catheters, whether they are indwelling or intermittent. By the time women seek medical advice for urinary incontinence they have usually tried various tactics to either limit the leakage or protect themselves from it. The most common tactics to limit leakage include fluid restriction, regular toileting, exercises and weight reduction. With medical advice, women can change concomitant medication that may be exacerbating the problem. Aids for mobilization can also have a dramatic effect on the ability to cope with urinary problems. Pads used for protection are often unsuitable and some even wear 'home-made' pads in the form of rolled up tissue, commonly to save money. Many different types of pads are available although women are often ignorant as to what is best for them. Catheters should only be used for intractable incontinence and following appropriate investigation. When possible intermittent catheterization should be considered. It is essential that all women are assessed and investigated before any form of containment becomes long-term management.

Adaptation, Psychological↗

Lower urinary tract symptoms and their impact on women with anorexia nervosa.

Anorexia nervosa is a condition which is associated with extremely low body weight and endocrine problems including persistent anovulation and a hypo-oestrogenic state. As the lower urinary tract is oestrogen sensitive, it is possible that women suffering from anorexia nervosa may experience similar distressing urinary problems. Of 29 anorexic women assessed, the majority had significant irritative urinary symptoms of which frequency, urgency and nocturia were the most common. These symptoms also had an unfavorable impact on their quality of life.

Adolescent↗

Bladder retraining.

Bladder retraining is a behavioural therapy which offers many women with continence problems a return to normal or near normal voiding patterns. However, full commitment is required from patients and nurses for it to be successful.

Behavior Therapy↗

Videocystourethrography with a ring pessary in situ. A clinically useful preoperative investigation for continent women with urogenital prolapse?

The aim of the study was to evaluate the use of a vaginal pessary in the detection of genuine stress incontinence (GSI) in women with urogenital prolapse undergoing urodynamic investigation. Continent women with urogenital prolapse, with or without associated urinary symptoms, were studied. All underwent videocystourethrography using a standardized protocol. None had evidence of incontinence on provocative testing in the upright position. A well-fitting vaginal ring pessary was inserted to reduce the prolapse and mimic a vaginal repair. The provocative tests were then repeated while the bladder was screened. Seventy women with a mean age 59.0 years (range 34-83) were recruited over a 21-month period: 15 women complained of prolapse alone and 55 had concurrent urinary symptoms; 19 women (27%) developed GSI only following the insertion of a vaginal pessary. The women who became incontinent were significantly older (mean age 63.9 years) than those who remained continent (mean age 56.8 years) (P < 0.020). The use of a vaginal pessary increases the detection rate of GSI in continent women with urogenital prolapse undergoing videocystourethrography. These findings are important because women with prolapse and coexisting incontinence should be offered a continence procedure rather than a simple vaginal repair.

Female↗

Reducing artefacts in ambulatory urodynamics.

OBJECTIVE: To compare the diagnoses derived from a retrospective analysis of 50 ambulatory urodynamic recordings, unaware of the final diagnosis, and to evaluate the importance of the symptom diary and the presence of two transducers in the bladder rather than one. PATIENTS AND METHODS: Fifty women underwent ambulatory urodynamics (duration 4 h) after video cysto-urethrography. A single solid-state microtip pressure catheter was inserted with both transducers inside the bladder, and another was inserted in the rectum. The women were asked to complete a symptom diary and the results were analysed with the active participation of the patient. Detrusor 'instability' was diagnosed on ambulatory urodynamics if there was a simultaneous increase in detrusor pressure and in the 'urethral' line in the presence of symptoms (urgency or leakage). All 50 recordings were analysed retrospectively in four combinations, i.e. with and without the additional 'urethral' line displayed on the screen and with and without the diary information. The total number of detrusor contractions was then calculated for each reading and 'abnormal detrusor activity' diagnosed when a contraction occurred with or without symptoms as recorded in the diary. The final diagnosis for each reading was then compared with that made at the time of the test with the patient present. RESULTS: Using the information from the diary reduced the number of pressure rises classified as 'abnormal detrusor activity' by 58%; using a second bladder pressure transducer further reduced the number of pressure rises classified as 'abnormal' by 19%. Overall, using both techniques together reduced the number of spurious pressure rises misclassified as 'abnormal detrusor activity' by 64%. CONCLUSIONS: Both the symptom diary and the placement of two transducers in the bladder can decrease, by almost two-thirds, the diagnosis of pathological detrusor activity on ambulatory urodynamics.

Ambulatory Care↗

Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.

We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures synchronized by three independent methods: alpha factor arrest, elutriation, and arrest of a cdc15 temperature-sensitive mutant. Using periodicity and correlation algorithms, we identified 800 genes that meet an objective minimum criterion for cell cycle regulation. In separate experiments, designed to examine the effects of inducing either the G1 cyclin Cln3p or the B-type cyclin Clb2p, we found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins. Furthermore, we analyzed our set of cell cycle-regulated genes for known and new promoter elements and show that several known elements (or variations thereof) contain information predictive of cell cycle regulation. A full description and complete data sets are available at http://cellcycle-www.stanford.edu

Base Sequence↗

GAX collagen in the treatment of urinary incontinence in elderly women: a two year follow up.

OBJECTIVE: To determine the efficacy of GAX collagen in the treatment of elderly women with genuine stress incontinence. DESIGN: A single centre prospective study. SETTING: A London teaching hospital. PARTICIPANTS: Thirty-four women older than 60 years of age with genuine stress incontinence diagnosed on videocystourethrography. INTERVENTIONS: Up to three paraurethral injections of GAX collagen. MAIN OUTCOME MEASURES: Subjective and pad test assessments performed pre-operatively, after one month, one year and two years after the first injection of collagen. Videocystourethrography and urethral pressure profilometry were carried out pre-operatively, after three months and one year. RESULTS: There was a reduction in urinary leakage as measured on pad testing. After two years 77% of the surviving 26 women were symptomatically cured. Objectively after two years 48% of the women were cured and 9% were improved over their initial pre-treatment level of incontinence. The cure rate was the same whether or not the women had undergone previous vaginal surgery. The maximum urethral closure pressure was not increased with treatment indicating that collagen injections do not act by producing obstruction, but this should be interpreted with caution due to the small sample size. CONCLUSION: GAX collagen is an effective method of treating urinary incontinence in the elderly and especially women who have undergone previous continence procedures. The technique is easy to perform and particularly suitable in those who are frail, but if failure occurs after two years consideration needs to be given to its cost effectiveness.

Aged↗

Synapses between slowly adapting lung stretch receptor afferents and inspiratory beta-neurons in the nucleus of the solitary tract of cats: a light and electron microscopic analysis.

Previous neuroanatomic and physiologic studies indicated that afferent fibres from slowly adapting pulmonary stretch receptors (SAR) project to the nuclei of the solitary tract and terminate on inspiratory beta-neurons. In the present study we combined electrophysiologic and morphologic approaches to verify the presumed monosynaptic connections between SARs and beta-neurons. Single identified beta-neurons and single identified SAR afferent fibres were labelled intrasomally and intraaxonally, respectively, with horseradish peroxidase (HRP) in the same anesthetized cats. Under the light microscope, we analyzed the morphology of beta-neurons and their dendritic fields and of the terminal projection pattern of fibres from SARs and identified potential synaptic connections between boutons of SAR afferent fibres and the soma and dendrites of beta-neurons. The identified tissue was then processed further for electron microscopic analysis. On average, beta-neurons had 6 primary dendrites that bifurcated 3-8 times. The dendritic trees extended 1.5 mm both rostrocaudally in the ventrolateral nucleus of the solitary tract and medially into the intermediate subnucleus. Axons of beta-neurons curved toward the midline and no collateral branches were evident over its stained length (2.5-3.4 mm). Axodendritic synaptic contacts between SAR fibres and beta-neurons were identified electron microscopically in four of six tissue samples chosen by light microscopy. In addition, we located 2 axodendritic and 2 axosomatic synaptic contacts that were not observed under light microscopic screening. The boutons of SAR fibres contained clear, round vesicles and formed asymmetrical synapses with beta-neurons. Multiple synaptic connections were found between collaterals of a single SAR and single beta-neurons, indicating a dense terminal projection of single SAR afferent fibres onto beta-neurons. These morphologic data prove monosynaptic connections between electrophysiologically identified SAR afferent fibres and beta-neurons.

Animals↗

Synaptic interaction between medullary respiratory neurones during apneusis induced by NMDA-receptor blockade in cat.

1. Termination of inspiration is an essential component of respiratory rhythm generation and its perturbation can result in apneusis, i.e. significant prolongation of mechanisms, we studied the postsynaptic events in respiratory neurones during apneustic respiratory periods, and compared them to normal respiratory cycles. 2. Experiments were performed in pentobarbitone-anaesthetized, paralysed, thoracotomized cats ventilated with a constant volume or a cycle-triggered constant pressure pump. Apneusis, separated by normal cycles, was induced as follows: the animal was ventilated by a cycle-triggered pump that normally inflated the lungs during the inspiratory burst of phrenic nerve discharge. The NMDA-receptor blocker MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-iminemaleate] (0.3-0.7 mg/kg) was administered intravenously, and, for designated breaths, inflation of the lungs was withheld during neural inspiration. 3. Membrane potential trajectories of forty-one late expiratory (E-2) and eight postinspiratory (PI) neurones of the caudal ventral respiratory group were analysed before and/or after MK-801 administration, during normal and apneustic periods. 4. Before MK-801 administration, withholding lung inflation caused modest (10-20%) lengthening of the inspiratory period; after MK-801 administration, withholding inflation caused apneusis. Provided that the lungs were inflated during the inspiratory phase, the temporal pattern of phrenic nerve, recurrent laryngeal nerve and membrane potential trajectories of E-2 and PI neurones were not significantly altered by MK-801. Apneusis following NMDA-receptor blockade produced consistent changes in the synaptic activation patterns of E-2 neurones. In particular, the slow late inspiratory-related depolarization pattern of E-2 neurones was consistently retarded during apneustic inspiratory phases when compared to normal inspiratory phases. This was due to continuation of Cl(-)-mediated synaptic inhibition of E-2 neurones. Superior laryngeal nerve stimulation stopped apneusis and sustained membrane hyperpolarization of E-2 neurones similar to lung inflation. 5. During the plateau phase of apneusis, correlated 10-20 Hz oscillations could be observed in the integrated phrenic and recurrent laryngeal nerve activities as well as in the membrane potential of E-2 neurones. 6. We conclude that: (i) the prolonged inhibition of E-2 neurones during apneusis is indicative of the process responsible for the prolongation of the inspiratory phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A network model of respiratory rhythmogenesis.

A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm.

Animals↗

The medullary respiratory network in the rat.

1. In urethane or Nembutal anaesthetized and artificially ventilated Wistar rats, respiratory neurones of the ventrolateral medulla oblongata were analysed in extracellular (n = 74) and intracellular (n = 43) recordings. 2. Some respiratory neurones were identified as bulbospinal by their antidromic response to spinal cord stimulation at the C4 level. The neurones examined were not antidromically excited by vagal nerve stimulation. 3. Based on their discharge pattern in relation to efferent phrenic and vagal nerve activity, six types of respiratory neurones were classified: early-inspiratory, throughout-inspiratory, late-inspiratory, post-inspiratory, expiratory, and phase-spanning expiratory-inspiratory neurones. 4. Analysis of postsynaptic activities and IPSP reversal following chloride injection revealed post-inspiratory and expiratory inhibition in inspiratory neurones a pronounced early-inspiratory and a relatively weak expiratory inhibition in post-inspiratory neurones, and an early-inspiratory and post-inspiratory inhibition in expiratory neurones. 5. In phase-spanning expiratory-inspiratory neurones the post-inspiratory inhibition was strong and effectively blocked action potential discharge. Expiratory-inspiratory neurones were quite similar to the group of inspiratory neurones, but seemed to receive tonic excitatory inputs not shunted by weak expiratory inhibition. This pre-inspiratory discharge was readily blocked by weak negative DC injection. 6. Under conditions of experimental hypoxia, or long lasting lung inflation and non-inflation, post-inspiratory neurones displayed a second burst of discharge at the end of the expiratory phase in addition to their longer lasting post-inspiratory discharge. 7. We conclude that in the rat the central respiratory rhythm is organized in three (inspiratory, post-inspiratory, expiratory) phases, and that synaptic interaction within the medullary respiratory network of the rat occurs similarly to that described for the cat.

Action Potentials↗

Inhibition of caudal medullary expiratory neurones by retrofacial inspiratory neurones in the cat.

1. Comparisons between the spike discharge of inspiratory neurons within the retrofacial area (RFN), and the membrane potential of expiratory neurones within the caudal medulla were made in pentobarbitone-anaesthetized, vagotomized, artificially ventilated cats. Spike-triggered averaging (STA) of synaptic potentials, triggered by the discharge of inspiratory RFN neurones, was utilized to test for synaptic connectivity. 2. Eighty-nine neurons with respiratory-phased discharge patterns were recorded in the vicinity of the RFN. Fifty-four neurones discharged at or slightly before the onset of the inspiratory burst activity of the phrenic nerve and continued firing throughout inspiration. Two continued to fire during post-inspiration. Forty-five of fifty-four inspiratory RFN neurones exhibited incrementing discharge patterns, six discharged with a plateau pattern, while only three neurones had a decrementing discharge pattern. 3. The membrane potential trajectories of caudal expiratory neurones revealed a typical wave of early inspiratory hyperpolarization. Occasionally, a second wave of hyperpolarization occurred during late inspiration, in conjunction with increased phrenic nerve activity. 4. Spike-triggered averaging revealed averaged inhibitory postsynaptic potentials (IPSPs), indicative of inhibitory synaptic connections, between eight and sixty-three pairs of RFN inspiratory and caudal expiratory neurones. 5. Inhibitory postsynaptic potentials detected by STA exhibited a relatively long latency and a slow time course. The IPSPs began, on average, 3.8 ms after an RFN action potential. The rise times, half-widths and durations of IPSPs were longer than expected for a monosynaptic somal input from myelinated axons of inspiratory RFN neurones. It is suggested that an inhibitory relay neurone in the immediate vicinity of the expiratory neurones is activated by a collateral of the RFN inspiratory neurone. 6. Retrofacial inspiratory neurones were antidromically activated only when high-intensity electrical stimulation was applied in the vicinity of caudal expiratory neurones. 7. The averaged IPSPs were preceded by diphasic and triphasic 'spike potentials'. The averaged spike potentials were highly entrained to the action potentials of RFN inspiratory neurones which triggered IPSPs. The spike potentials may be terminal potentials recorded from axons of RFN inspiratory neurones. 8. Evidence for convergence of synaptic inputs was obtained from STA tests in a caudal expiratory neurone receiving IPSPs from four RFN neurones. 9. The functional significance of this observation is discussed. We conclude that RFN inspiratory neurones exert a moderate inhibitory influence and act conjointly with other types of medullary inspiratory neurones.

Animals↗