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Biomedical subjects

W Graf

Publications and source records attributed to W Graf.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sacculo-ocular reflex connectivity in cats.

The otolith system contributes to the vestibulo-ocular reflexes (VOR) when the head moves linearly in the horizontal plane or tilts relative to gravity. The saccules are thought to detect predominantly accelerations along the gravity vector. Otolith-induced vertical eye movements following vertical linear accelerations are attributed to the saccules. However, information on the neural circuits of the sacculo-ocular system is limited, and the effects of saccular inputs on extraocular motoneurons remain unclear. In the present study, synaptic responses to saccular-nerve stimulation were recorded intracellularly from identified motoneurons of all twelve extraocular muscles. Experiments were successfully performed in eleven cats. Individual motoneurons of the twelve extraocular muscles--the bilateral superior recti (SR), inferior recti (IR), superior obliques (SO), inferior obliques (IO), lateral recti (LR), and medial recti (MR) were identified antidromically following bipolar stimulation of their respective nerves. The saccular nerve was selectively stimulated by a pair of tungsten electrodes after removing the utricular nerve and the ampullary nerves of the semicircular canals. Stimulus intensities were determined from the stimulus-response curves of vestibular N1 field potentials in order to avoid current spread. Intracellular recordings were performed from 129 extraocular motoneurons. The majority of the neurons showed no response to saccular-nerve stimulation. In 17 (30%) of 56 extraocular motoneurons related to vertical eye movements (bilateral SR and IR), depolarizing and/or hyperpolarizing postsynaptic potentials (PSPs) were observed in response to saccular-nerve stimulation. The latencies of PSPs ranged from 2.3 to 8.9 ms, indicating that the extraocular motoneurons received neither monosynaptic nor disynaptic inputs from saccular afferents. The majority of the latencies of the depolarization, including depolarization-hyperpolarization, were in the range of 2.3-3.3 ms. Latencies of hyperpolarizations were typically longer than those of depolarizations. Only one contralateral SO motoneuron of 43 recorded oblique extraocular motoneurons (bilateral SO and IO) showed a depolarization-hyperpolarization in response to saccular-nerve stimulation at a latency of 2.5 ms. None of 30 recorded horizontal extraocular motoneurons (bilateral LR and MR) responded to stimulation of the saccular nerve. The neural linkage in the sacculo-ocular system is relatively weak in comparison to the utriculo-ocular and sacculo-collic systems, suggesting that the role of the sacculo-ocular system in stabilizing eye position may be reduced when compared with utriculo-ocular and semi-circular canal-ocular reflexes.

Animals↗
PubMed2000

Differential activity of topotecan, irinotecan and SN-38 in fresh human tumour cells but not in cell lines.

The topoisomerase I inhibitors topotecan irinotecan (CPT-11) and its metabolite SN-38 were studied in a panel of cell lines and in primary tumour cells from patients, using a non-clonogenic cytotoxicity assay. All three substances showed similar activity patterns in the panel of cell lines established to classify the drugs mechanistically. In the patient tumour cells the drugs had different effects. In haematological and ovarian cancer samples, SN-38 was much more potent than topotecan, followed by irinotecan, while in colorectal cancer samples only irinotecan showed substantial activity. This in vitro activity pattern seems to agree with clinical experiences to date. The inactivity of SN-38 in colorectal cancer suggests irinotecan may also have some other role in addition to being a prodrug to SN-38. This study raises questions as to the role and relevance of early preclinical model systems in anticancer drug development, and suggests that important information can be obtained from studies using primary cultures of human tumour cells.

Antineoplastic Agents↗
PubMed2000

Factors influencing the functional outcome of restorative proctocolectomy in ulcerative colitis.

BACKGROUND: Restorative proctocolectomy is considered to be the procedure of choice in the operative treatment of ulcerative colitis. The aim of this study was to evaluate the functional outcome following operation and to identify possible predictive factors. METHODS: Some 168 patients (median age 32 years, 102 men) with ulcerative colitis underwent restorative proctocolectomy. The functional outcome was evaluated by a symptom index created from a questionnaire at a median of 29 (13-123) months of follow-up. The records of these patients were reviewed, and preoperative, peroperative and postoperative variables were registered and related to outcome. RESULTS: The response rate to the questionnaire was 155 (92 per cent) of 168. The symptom index was related to patients' overall assessment of outcome. In spite of a perceived good result many patients experienced a number of symptoms. Age over 50 years (P < 0.01), presence of extraintestinal manifestations (P < 0.05) and late complications, such as anastomotic stricture (P < 0.05), pouchitis (P < 0.01) and anal pain (P < 0.05), were related to a less favourable outcome. CONCLUSION: While preoperative data may help in selecting patients suitable for restorative proctocolectomy, prevention of late complications seems most important in improving the functional outcome.

Adolescent↗
PubMed2000

Results of surgical treatment for faecal incontinence.

BACKGROUND: This prospective study was designed to evaluate the results of anterior levatorplasty and sphincteroplasty for faecal incontinence with respect to symptomatic and physiological outcome. METHODS: Thirty-one patients with idiopathic (neurogenic) faecal incontinence underwent anterior levatorplasty and 20 patients with traumatic anal sphincter injury underwent anal sphincteroplasty. The outcome of repair was evaluated at 3 and 12 months using a validated questionnaire and anorectal manometry/manovolumetry. RESULTS: Eighteen of 31 patients in the levatorplasty group reported continence to solid and liquid stools 1 year after operation compared with two patients before surgery (P < 0.01). The corresponding figures in the sphincteroplasty group were ten and two of 20 respectively (P < 0.05). The incontinence score was improved in both groups after 1 year, from a median score of 14 to 3 in the levatorplasty group (P < 0.001) and from 8.5 to 3.5 in the sphincteroplasty group (P < 0.01). Improvements in the degree of social and physical handicap were also observed in both groups. No changes were seen in anal canal pressures or rectal sensation in either group. CONCLUSION: Despite different aetiologies and surgical approaches, anterior levatorplasty and sphincteroplasty yielded similarly successful results in patients with faecal incontinence. Although a marked symptomatic improvement was seen in both groups, no associated physiological alterations could be detected. The reason for the improvement is thus unclear, but it may result from a stenosing effect in the anal canal.

Adult↗
PubMed1999

Eye position encoding in the macaque ventral intraparietal area (VIP).

Many neurons in area VIP encode the location of visual stimuli in a non-retinocentric frame of reference. In this context the question needed to be addressed whether the underlying coordinate transformation of the incoming visual signals could be generated within area VIP or whether this information would have to arrive from other areas. We tested 74 neurons in area VIP of two awake monkeys for an influence of eye position while animals performed a fixation task. More than half of the neurons (40/74) revealed an eye position effect. At the population level, however, this effect was balanced out. We suggest that local connections within area VIP could be used to generate an encoding of visual information in a non-retinocentric frame of reference.

Animals↗
PubMed1999

Is electrostimulation of the pelvic floor an effective treatment for neurogenic faecal incontinence?

BACKGROUND: This study was designed to evaluate the results of electrostimulation of the pelvic floor for faecal incontinence. METHODS: Twenty-four patients with neurogenic (n = 20) or idiopathic (n = 4) incontinence were treated on 12 occasions. Twenty were women, and the mean age was 63 years (range, 26-85 years). The result was evaluated at 3 and 12 months with a validated questionnaire and anorectal manometry. RESULTS: Eleven patients (46%) reported improvement after 3 months, and the Miller's incontinence score was reduced (P < 0.01). Resting pressures, rectal compliance, and the length of the high-pressure zone were unchanged, but squeeze pressures tended to decrease. A lower threshold was seen for the rectoanal inhibitory reflex (RAIR) (P < 0.01), and the saline infusion test tended to show improved retention (P = 0.07). Nine of 13 patients followed up for 1 year claimed improvement. The most pronounced subjective improvement was seen in patients with moderate incontinence. CONCLUSIONS: Electrostimulation was successful in a substantial proportion of the patients. The threshold for RAIR was lowered, and the saline infusion test tended to improve, but variables reflecting sphincter competence did not improve. Moderate incontinence was prognostically favourable, and electrostimulation might therefore be an alternative to surgery in this group.

Anal Canal↗
PubMed1999

The longitudinal high-pressure zone profile in patients with fecal incontinence.

OBJECTIVE: The aim of this study was to evaluate differences in the longitudinal high-pressure zone (HPZ) profile between incontinent patients and healthy controls. METHODS: One hundred and fifty-six patients with fecal incontinence (mean age 63 yr; 139 women, 17 men) and 25 healthy controls (mean age 54 yr; 20 women, five men) underwent anorectal manometry with a perfused catheter using a station pull-through technique. RESULTS: Maximum resting pressure (MRP) and maximum squeeze pressure (MSP) were lower in patients (p < 0.001) and the HPZ was shorter in patients (p < 0.05). The ratio MRP/sum of resting pressures within HPZ did not differ between the groups. The severity of incontinence measured as an incontinence score was correlated to MSP (p < 0.05) and sum of squeeze pressure within HPZ (p < 0.05), but not to any other variable. The relative pressure amount during rest in the distal half of HPZ was higher in controls (63% vs 56%, p < 0.05), but this was not seen during squeeze. CONCLUSIONS: These results suggest that the main difference between incontinent patients and healthy controls is a greater magnitude of the pressure profile in the latter group. Furthermore, the relative pressure accumulation during rest tended to be more distally located within the HPZ.

Adult↗
PubMed1999

Defecographic study of rectal evacuation in constipated patients and control subjects.

PURPOSE: To validate a computer-based area calculation method of quantification of rectal evacuation by using defecography videotapes and to use that method to compare evacuation in constipated patients with that in control subjects. MATERIALS AND METHODS: For validation of the method, simultaneous defecography and weight measurements were compared in 36 patients with constipation or incontinence. Evacuation was calculated as the rate of change of the contrast medium-covered rectal area (percentage per second) or of the evacuated amount of contrast medium (percentage per second [relative] and grams per second [absolute]). After method validation, from a series of 215 consecutive constipated patients, individuals with an isolated radiologic diagnosis of intussusception greater than 0.6 cm (n = 27), rectocele greater than 2 cm (n = 19), enterocele (n = 12), or paradoxic puborectal muscle contraction (n = 12) were selected. Rectal evacuation in these groups was compared with that in 30 control subjects. RESULTS: Rectal evacuation rates measured at defecography correlated well with weighed amounts of evacuated contrast medium during the initial and total evacuation periods in 21 patients without contrast medium leak (r = 0.92, P < .001). Constipation overall, a rectocele greater than 2 cm, or paradoxic puborectal muscle contraction were associated with impaired evacuation (P < .001). CONCLUSION: Area calculations of rectal evacuation reflect rectal emptying. A rectocele greater than 2 cm or a paradoxic puborectal muscle contraction may be associated with obstructed defecation.

Adult↗
PubMed1998

Morphology of single afferents of the saccular macula in cats.

The morphology of single saccular afferents was studied by the intracellular horseradish peroxidase (HRP) method. Four neurons were sufficiently stained to allow reconstruction of their axonal arborizations. The main axon of these neurons bifurcated into an ascending and a descending branch at the level of the lateral nucleus. The ascending branches of two axons gave off collaterals with boutons in the caudal part of the superior nucleus, while the other two ascending branches lacked such terminations. By contrast, characteristics of the descending axonal arborization patterns of all the four neurons were substantially the same. The descending branches coursed caudally through the lateral part of the descending nucleus, and gave off up to 14 collaterals with boutons that extended throughout this nucleus. These collaterals also reached the ventral part of the lateral nucleus, the lateral border of the medial nucleus, and group f. A few axon collaterals ramified even outside the border of the vestibular nuclei into the spinal trigeminal nucleus and the reticular formation surrounding it. Axon collaterals from the stem axon also terminated in the interstitial nucleus of the vestibular nerve. There was a noticeable absence of any projection to the y group.

Action Potentials↗
PubMed1998

Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study.

PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose (5 x 5 Gy) radiotherapy reduces local failure rates and improves overall survival. This will have an impact on the primary treatment of rectal cancer. This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection. METHODS: A questionnaire was answered by 92 percent (203/220) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years. Thirty-two patients were excluded, mainly because of postoperative stomas and dementia, which left 171 for analysis. RESULTS: Median bowel frequency per week was 20 in the irradiated group (n = 84) and 10 in the surgery-alone group (n = 87; P < 0.001). Incontinence for loose stools (P < 0.001), urgency (P < 0.001), and emptying difficulties (P < 0.05) were all more common after irradiation. Sensory functions such as "discrimination between gas and stool" and "ability to safely release flatus" did not, however, differ between groups. Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction, compared with 10 percent of the surgery-alone group (P < 0.01). CONCLUSIONS: The study indicates that high-dose radiotherapy influences long-term bowel function, thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques.

Adult↗
PubMed1998

Paradoxical puborectalis contraction is associated with impaired rectal evacuation.

The role of paradoxical puborectalis contraction in the aetiology of constipation and how to best diagnose this condition is controversial. The aims of this study were to investigate whether absolute or relative paradoxical electrical activity during electromyography (EMG) are related to rectal emptying and to compare EMG, defecography and digital examination in the diagnosis of paradoxical puborectalis contraction. Included in the study were 171 consecutive patients with idiopathic constipation; 136 of these cases were also classified as paradoxical or unclear or not paradoxical at digital examination. Absolute amplitudes and a strain/squeeze index were used to grade the EMG activity in the puborectalis and external sphincter muscle. Rectal evacuation was analysed by defecography with image analysis of rectal area. The results showed that 142 patients had paradoxical EMG activity during straining. There was a correlation between rectal evacuation and amplitudes (r = -0.20 to -0.03, P < 0.01) and between evacuation and index (r = -0.34 to -0.39, P < 0.0001). Forty-two patients with an index of > 50 had impaired rectal evacuation compared with those with an index < or = 50 (P < 0.0001). Thirty-three of 34 cases (n = 136) with an index of > 50 also were paradoxical at defecography whereas 19 were diagnosed digitally. In conclusion, paradoxical puborectalis contraction is associated with impaired rectal evacuation. The activity seems to be best reflected by a strain/squeeze index. The best correlation in diagnostic methods was between EMG and defecography.

Adult↗
PubMed1998

Bolus injection (2-4 min) versus short-term (10-20 min) infusion of 5-fluorouracil in patients with advanced colorectal cancer: a prospective randomised trial. Nordic Gastrointestinal Tumour Adjuvant Therapy Group.

The use of bolus 5-fluorouracil (5-FU) as a short-term infusion over 10-30 min is increasing at the cost of a push injection, mainly due to practical advantages. Since even a short prolongation of the administration time results in lower 5-FU peak and area under the curve (AUC) levels, there might be a risk of decreased efficacy. The aim of this study was to compare a rapid intravenous (i.v.) 5-FU injection and a short-term 5-FU infusion with respect to objective responses and toxicity in patients with advanced colorectal cancer. 203 patients with measurable advanced colorectal cancer were randomised to bolus 5-FU either as an injection for 2-4 min or as a short-term infusion lasting 10-20 min. In both groups, the 5-FU dose was 500 mg/m2 and leucovorin 60 mg/m2 was given 40 min after the start of 5-FU. Treatment was given on two successive days every other week until progression. Objective tumour regression was seen in 27/100 (27%) in the injection group and in 13/103 (13%) in the infusion group (P = 0.02). Severe toxicity was rare and did not differ significantly between the groups. Progression-free survival tended to be longer in the injection group (P = 0.07), but overall survival did not differ between the groups. Bolus 5-FU should be administered as a rapid i.v. injection rather than as a short-term infusion, since the former rate of administration results in a higher response rate without being significantly more toxic.

Adult↗
PubMed1998

Uptake of hyaluronan in hepatic metastases after blocking of liver endothelial cell receptors.

To follow the biodistribution of exogenous hyaluronan in tumor-bearing animals, a total of seventeen inbred rats with hepatic metastases from a colonic adenocarcinoma received 125I-labelled hyaluronan by intravenous injections. Group I received only labeled hyaluronan (25 microg), whereas group II received 2.5 mg chondroitin sulphate prior to labeled hyaluronan, to block receptor uptake in normal liver endothelial cells. Animals in group III received intravenous, as well as intraperitoneal chondroitin sulphate (2.5 mg), to see if a better and prolonged blocking could be achieved. Radioactivity was visualized by whole body autoradiography, using phosphorimaging and the average radioactivity determined as phosphoimaging density units of the total area of hepatic metastases, normal liver, and skeletal muscle by computer-based image analysis. At 5 h, tumors in groups II and III showed higher uptake (4.8+/-1.8, P = .01 and 3.6+/-1.1, P = .01, respectively), in comparison to group I (1.8+/-0.6), and the mean normal liver/tumor concentration ratio was reduced from 21.4+/-10.1 in group I to 5.7+/-2.7 in group II and 3.5+/-1.1 in group III (P = .008 and P = .01, respectively). Our study shows that hyaluronan targets liver metastases of a colon adenocarcinoma. Furthermore, chondroitin sulphate pretreatment increases tumor uptake, while uptake at normal receptor sites is significantly reduced. The results also suggest that after blocking of normal hyaluronan/chondroitin sulphate receptors in healthy tissue, hyaluronan may be used to deliver drugs to specific hyaluronan receptor-positive sites of pathology.

Adenocarcinoma↗
PubMed1997

Spatial invariance of visual receptive fields in parietal cortex neurons.

Spatial information is conveyed to the primary visual cortex in retinal coordinates. Movement trajectory programming, however, requires a transformation from this sensory frame of reference into a frame appropriate for the selected part of the body, such as the eye, head or arms. To achieve this transformation, visual information must be combined with information from other sources: for instance, the location of an object of interest can be defined with respect to the observer's head if the position of the eyes in the orbit is known and is added to the object's retinal coordinates. Here we show that in a subdivision of the monkey parietal lobe, the ventral intraparietal area (VIP), the activity of visual neurons is modulated by eye-position signals, as in many other areas of the cortical visual system. We find that individual receptive fields of a population of VIP neurons are organized along a continuum, from eye to head coordinates. In the latter case, neurons encode the azimuth and/or elevation of a visual stimulus, independently of the direction in which the eyes are looking, thus representing spatial locations explicitly in at least a head-centred frame of reference.

Animals↗
PubMed1997

Results of biofeedback in constipated patients: a prospective study.

PURPOSE: The aims of this study were to assess the results of biofeedback treatment in constipated patients and to identify variables that might be used to predict the outcome. METHOD: Twenty-eight patients (5 men; median age, 46 (range, 22-72) years) with any degree of paradoxical activation measured with thin hook needle electromyography in the external sphincter or puborectalis muscle were included. The symptom duration varied between 1 and 30 (median, 9) years. The patients had eight outpatient training sessions with electromyography-based audiovisual feedback. All patients were followed up prospectively with a validated bowel function questionnaire from which a symptom index was created. RESULTS: At three months, nine patients had no improvement and underwent other treatments. The remaining 19 patients were followed up for a median of 14 (range, 12-34) months. Twelve patients (43 percent) stated they had improved rectal emptying. A good result was associated with increased stool frequency (P < 0.05), improved symptom index (P < 0.01), and reduction of laxative use (P < 0.05). A long symptom duration, a high pretreatment symptom index, and laxative use were related to a poor result (P < 0.01-0.05). The improved group had less perineal descent (P < 0.05), and a prominent puborectalis impression on defecography tended to be more common (P = 0.06). CONCLUSION: With the use of wide inclusion criteria, biofeedback was successful in 43 percent of patients, with a treatment effect lasting at least one year. The results suggest that biofeedback should be used as the initial treatment of constipated patients with a paradoxical puborectalis contraction.

Adult↗
PubMed1997

Short-term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients.

BACKGROUND AND PURPOSE: This study was undertaken to investigate down-staging effects after short-term, high-fractionated preoperative radiotherapy. MATERIAL AND METHODS: The relationships between preoperative radiotherapy 25-25.5 Gy given over 5-7 days and clinical variables (sex, age, tumour level, metastatic disease, and tumour size) and the risk of lymph node metastases were examined in 1316 patients with rectal adenocarcinoma by uni-, and multivariate analyses. RESULTS: Irradiated specimens contained smaller tumours (P < 0.00001) and nodal metastases were less common (P < 0.001). In a logistic regression model, tumour size in cm was positively related to the risk for nodal spread (odds ratio, OR = 1.14, 95% confidence limits, CL, of OR 1.08-1.22). In the same model, radiotherapy decreased the risk for nodal involvement (OR 0.73, 95% CL 0.58-0.92. This risk was particularly reduced when the time interval between start of radiotherapy and surgery equalled 10 days or more. CONCLUSIONS: These results demonstrate a down-staging effect by a short course of preoperative radiotherapy which should be considered in the interpretation of radiotherapy trials and in the recruitment of patients for further postoperative adjuvant treatment.

Adenocarcinoma↗