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Biomedical subjects

W Graf

Publications and source records attributed to W Graf.

At least 55 records · Page 3Linked to original sources
PubMed1997

Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.

BACKGROUND: The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients. PATIENTS AND METHODS: Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03). CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Adenocarcinoma↗
PubMed1997

Randomized trial of a biofragmentable bowel anastomosis ring in high-risk colonic resection.

BACKGROUND: Biofragmentable anastomosis ring (BAR) has been proven to be a safe anastomotic device in elective surgery. The use of this anastomotic ring in high-risk patients has not been established. METHODS: During a 5-year period (1990-1995), 100 high-risk patients undergoing colonic resection and suitable for a primary anastomosis were allocated randomly to a standard suture technique or to anastomosis performed with a BAR. High risk was defined as large bowel obstruction, complicated diverticular disease, Crohn's disease, local cancer recurrence, previously irradiated colon, and trauma to the colon or rectum. The patients were equally distributed to the two groups regarding sex, age, emergency surgery and concomitant diseases. RESULTS: In three patients allotted to the BAR group, the device could not be used. There were three (6 per cent) postoperative deaths in each group; none was related to anastomotic problems. Three anastomotic dehiscences were diagnosed, two (4 per cent) in the BAR group and one (2 per cent) in the suture group. Postoperative complications and postoperative recovery were similar. CONCLUSION: This study shows that the BAR anastomosis probably is as safe as the standard band-sewn anastomosis in high-risk colorectal surgery. As the cost of a BAR anastomosis is substantially higher than that for a hand-sewn anastomosis, the latter technique is still the preferred method in the authors' unit.

Adult↗
PubMed1997

Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish.

Electrophysiological, ultrastructural, and immunohistochemical techniques were utilized to describe the excitatory and inhibitory vestibular innervation of extraocular motor nuclei in the goldfish. In antidromically activated oculomotor motoneurons, electrical stimulation of the intact contralateral vestibular nerve produced short-latency, variable amplitude electrotonic excitatory postsynaptic potentials (EPSPs) at 0.5-0.7 ms followed by chemical EPSPs at 1.0-1.3 ms. Stimulation of the ipsilateral vestibular nerve produced small amplitude membrane hyperpolarizations at a latency of 1.3-1.7 ms in which equilibrium potentials were slightly more negative than resting potentials. The inhibitory postsynaptic potentials (IPSPs) reversed with large amplitudes after the injection of chloride ions suggesting a proximal soma-dendritic location of terminals exhibiting high efficacy inhibitory synaptic conductances. In antidromically identified abducens motoneurons and putative internuclear neurons, electrical stimulation of the contralateral vestibular nerve produced large-amplitude, short-latency electrotonic EPSPs at 0.5 ms followed by chemical depolarizations at 1.2-1.3 ms. Stimulation of the ipsilateral vestibular nerve evoked IPSPs at 1.4 ms that were reversed after injection of current and/or chloride ions. gamma-Aminobutyric acid (GABA) antibodies labeled inhibitory neurons in vestibular subdivisions with axons projecting into the ipsilateral medial longitudinal fasciculus (MLF). Putative GABAergic terminals surrounded oculomotor, but not abducens, motoneurons retrogradely labeled with horseradish peroxidase. Hence the spatial distribution of GABAergic neurons and terminals appears highly similar in the vestibuloocular system of goldfish and mammals. Electron microscopy of motoneurons in the oculomotor and abducens nucleus showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles establishing chemical, presumed excitatory, synaptic contacts with asymmetric pre- and/or postsynaptic membrane specializations. The majority of contacts with spheroidal vesicles displayed gap junctions in which the chemical and electrotonic synapses were either en face to dissimilar or adjacent to one another on the same soma/dendritic profiles. Another separate set of axosomatic synaptic endings, presumed to be inhibitory, contained pleiomorphic synaptic vesicles with symmetric pre- and/or postsynaptic membrane specializations that never included gap junctions. Excitatory and inhibitory synaptic contacts appeared equal in number but were more sparsely distributed along the soma-dendritic profiles of oculomotor as compared with abducens motoneurons. Collectively these data provide evidence for both disynaptic vestibular inhibition and excitation in all subdivisions of the extraocular motor nuclei suggesting the basic vestibulooculomotor blueprint to be conserved among vertebrates. We propose that unique vestibular neurons, transmitters, pathways, and synaptic arborizations are homologous structural traits that have been essentially preserved throughout vertebrate phylogeny by a shared developmental plan.

Abducens Nerve↗
PubMed1997

Sacculocollic reflex arcs in cats.

Neuronal connections and pathways underlying sacculocollic reflexes were studied by intracellular recordings from neck extensor and flexor motoneurons in decerebrate cat. Bipolar electrodes were placed within the left saccular nerve, whereas other branches of the vestibular nerve were removed in the inner ear. To prevent spread of stimulus current to other branches of the vestibular nerve, the saccular nerve and the electrodes were covered with warm semisolid paraffin-Vaseline mixture. Saccular nerve stimulation evoked disynaptic (1.8-3.0 ms) excitatory postsynaptic potentials (EPSPs) in ipsilateral neck extensor motoneurons and di- or trisynaptic (1.8-4.0 ms) EPSPs in contralateral neck extensor motoneurons, and di- and trisynaptic (1.7-3.6 ms) inhibitory postsynaptic potentials (IPSPs) in ipsilateral neck flexor motoneurons and trisynaptic (2.7-4.0 ms) IPSPs in contralateral neck flexor motoneurons. Ipsilateral inputs were about twice as strong as contralateral ones to both extensor and flexor motoneurons. To determine the pathways mediating this connectivity, the lateral part of the spinal cord containing the ipsilateral lateral vestibulospinal tract (i-LVST) or the central part of the spinal cord containing the medial vestibulospinal tracts (MVSTs) and possibly reticulospinal fibers (RSTs) were transected at the caudal end of the C1 segment. Subsequent renewed intracellular recordings following sacculus nerve stimulation indicated that the pathway from the saccular nerve to the ipsilateral neck extensor motoneurons projects though the i-LVST, whereas the pathways to the contralateral neck extensors and to the bilateral neck flexor motoneurons descend in the MVSTs/RSTs. Our data show that sacculo-neck reflex connections display a qualitatively bilaterally symmetrical innervation pattern with excitatory connections to both neck extensor motoneuron pools, and inhibitory connections to both neck flexor motoneuron pools. This bilateral organization contrasts with the unilateral innervation scheme of the utriculus system. These results suggest a different symmetry plane along which sacculus postural reflexes are organized, thus supplementing the reference planes of the utriculus system and allowing the gravistatic system to represent all three translational spatial degrees of freedom. We furthermore suggest that the sacculocollic reflex plays an important role in maintaining the relative position of the head and the body against the vertical linear acceleration of gravity.

Afferent Pathways↗
PubMed1996

Prognosis after surgery in patients with incurable rectal cancer: a population-based study.

In a defined population between 1973 and 1992 151 patients with irresectable metastatic or local rectal cancer were identified. Eighty-one patients underwent resection of the primary tumour (group 1) whereas the primary tumour was left in situ in 70 patients (group 2). During the same time period, 444 patients underwent curative resection. The median survival was 7.5 months in group 1, and 3.5 and 1.9 months for surgically and non-surgically treated patients respectively in group 2. A colostomy for intestinal obstruction became necessary in 12 per cent of the patients with a retained primary tumour. Bilateral hepatic involvement, abnormal liver function test results, peritoneal growth or abdominal lymph node metastases correlated with a short survival (P < 0.01). These results support a selective approach to patients with incurable rectal cancer.

Abdominal Neoplasms↗
PubMed1996

Factors influencing recurrence in Crohn's disease. An analysis of a consecutive series of 353 patients treated with primary surgery.

PURPOSE: This study was undertaken to investigate the factors that influenced the risk of symptomatic recurrence in patients with Crohn's disease who were treated with primary resective surgery. METHODS: Data regarding age, gender, time from diagnosis to surgery, medication, preoperative infectious complications, laboratory values, emergency/elective surgery, location and extent of disease, and resection margins were analyzed in relation to recurrence in 353 patients who were undergoing a "curative" resection in 1969 to 1986. RESULTS: Univariate analyses showed a higher risk of recurrence in women with ileal and ileocolonic disease than in men (P < 0.05), in patients with ileocolonic disease compared with those with isolated ileal disease (P < 0.05), and in ileal disease patients with an increased disease extent (P < 0.05). In a multivariate analysis performed on patients with ileal disease, increased disease extent, limited resection on the colonic side, and referral from other hospitals were three independent variables that indicated an increased risk of recurrence (P < 0.05). Length of disease-free resection margins did not influence the risk of recurrence either in univariate or in multivariate analysis (P > 0.05). CONCLUSIONS: Disease extent has prognostic value regarding the risk of symptomatic recurrence in Crohn's disease, whereas the length of resection margins does not influence the risk of relapse. These results favor a conservative approach, particularly in patients with extensive disease.

Adult↗
PubMed1996

A pilot study of factors influencing bowel function after colorectal anastomosis.

PURPOSE: This study was undertaken to assess subjective bowel function after anterior resection and to search for clinical characteristics that might affect the functional results. METHODS: A total of 70 patients answered a questionnaire concerning bowel function a median of 65 months after anterior resection, and 40 patients responded to the same questionnaire a median of 60 months after colonic resection. RESULTS: Median frequency of bowel movement per 24 hours was two (range, 0.2-9) after rectal resection and one (range, 0.4-6) after colonic resection (P < 0.001). Incontinence for loose stools (P < 0.01), need to wear a pad (P < 0.05), and need to return to the toilet after defecation (P < 0.05) was more common in the rectal resection group. In the latter group, advanced age, use of descending or transverse colon for anastomosis, and large amount of intraoperative bleeding was associated with fecal incontinence (P < 0.05). Preoperative radiotherapy was correlated with a high bowel frequency (P = 0.003). CONCLUSIONS: These data indicate that alterations of subjective bowel function frequently observed after colorectal anastomosis may be affected by both surgical technique and adjuvant radiotherapy.

Adult↗
PubMed1996

Does surgical repair of a rectocele improve rectal emptying?

PURPOSE: This study was undertaken to assess results of surgical repair of rectocele and to identify possible determinants of outcome from patient's history and preoperative defecography. Another aim was to evaluate how surgery affects rectal evacuation. METHOD: Thirty-four women with constipation and rectal emptying difficulties underwent surgery with a transanal technique. A preoperative defecography was performed in each patient. They were followed up after a median of 10 (range, 2-60) months with a questionnaire (n = 34) and a defecography (n = 31). Computer-based image analysis of defecographies was used to evaluate rectal evacuation. RESULTS: In 27 patients (79 percent), the result of surgery was good with subjectively improved emptying. The need for vaginal or perineal digitation preoperatively was related to a good result (P < 0.05), whereas a previous hysterectomy (P < 0.01) and a large rectal area on defecography (P < 0.01) related to a poor result. Preoperative use of enemas, motor stimulants, or several types of laxatives also related to a poor outcome (P < 0.05). Surgical treatment resulted in reduction of the rectocele (P < 0.001), an elevated position of the anorectal junction (P < 0.05), and improved rectal evacuation on defecographies (P < 0.001). CONCLUSIONS: Surgical repair reduces the size of the rectocele and improves rectal emptying. These changes are accompanied by a symptomatic improvement in the majority of patients. Preoperative patient data and defecography may help in selecting patients for surgery.

Adult↗
PubMed1996

Long-term results of anterior levatorplasty for fecal incontinence. A retrospective study.

PURPOSE: To review the long-term results of anterior levatorplasty for fecal incontinence. METHODS: Fifty-four women with obstetric trauma and 31 with idiopathic incontinence responded to a questionnaire 1.5 to 18.5 (median, 8.5) years after anterior levatorplasty. Results were classified as excellent, good, fair, or poor. RESULTS: An excellent or good result was reported in 40 of 54 (74 percent) patients with an obstetric injury and in 14 of 31 (45 percent) patients in the idiopathic group (P < 0.01). The presence of a cloaca (P < 0.05) and a young age (P < 0.05) were associated with a favorable outcome in the obstetric and idiopathic group, respectively. Length of follow-up and preoperative severity of incontinence were not significantly related to outcome. CONCLUSIONS: This study suggests that every second patient undergoing anterior levatorplasty for fecal incontinence has a successful result that is sustained in the long term. Obstetric trauma, presence of a cloaca, and young age are associated with a successful outcome.

Adult↗
PubMed1996

Evaluation of a questionnaire in the assessment of patients with faecal incontinence and constipation.

BACKGROUND: A self-reported questionnaire may be a useful instrument in assessing patients with faecal incontinence and constipation. METHODS: Reliability, discrimination, validity, and sensitivity were evaluated in 16 control subjects 36 patients with faecal incontinence, and in 38 with constipation. The reliability was measured by a test-retest procedure (kappa (kappa) statistics or Spearman rank test), and validity by comparing the questionnaire and a diary. Discrimination was assessed by comparing the patient groups with the controls, and sensitivity by comparing selected answers before and after treatment. RESULTS: Overall reliability (faecal incontinence group, mean kappa = 0.57; constipation group, mean kappa = 0.60; controls, mean kappa = 0.95) and validity were judged acceptable. In the incontinence group occurrence of faecal incontinence per se was reproducible (kappa = 0.66), as was the need to wear a pad (kappa = 0.85). Stool frequency, percentage toilet time spent straining and digitation was reproducible in patients with constipation (kappa = 0.80, r = 0.56; p < 0.001, kappa = 0.83 respectively). Several items distinguished both patient groups from healthy controls (p < 0.05 to p < 0.001). Sensitivity to surgical treatment was seen in several items in both patient groups. CONCLUSIONS: The questionnaire appears to be a valid measure of symptoms in faecal incontinence and constipation with sufficient discriminatory capacity.

Case-Control Studies↗
PubMed1996

Monitoring palliative chemotherapy in advanced gastrointestinal cancer using serial tissue polypeptide specific antigen (TPS) measurements.

Tissue polypeptide antigen specific (TPS) was analysed in serum taken prior to chemotherapy in 90 patients with advanced gastrointestinal cancer and prior to every treatment course in 68 of these patients in order to explore whether serial tumour marker measurements can be of importance in monitoring patients treated with palliative chemotherapy. Elevated TPS levels were seen in 83/90 (92%) patients (48/52 colorectal, 9/9 pancreatic, 9/11 biliary, 17/18 gastric). Baseline TPS level correlated with performance status, tumour response and survival. Based upon the change in TPS levels after the first two courses in relation to baseline, a decrease by >50% had a high sensitivity for a favourable treatment outcome (partial remission and prolonged stationary disease (90%) or a subjective response (100%)), whereas the specificity was lower (72% and 73% respectively). A similar result was seen when the TPS levels were analysed at the time of the response evaluation after 2 months (sensitivity 91 and 95%, specificity 74 and 75% for an objective or subjective response respectively). In 7 out of 15 patients with an initially favourable outcome, an increase in TPS levels of >50% at two occasions was seen 8-20 weeks prior to clinical disease progression. In advanced gastrointestinal cancer serial TPS measurements can with high accuracy early identify patients who will not benefit from the treatment. On the other hand, a response must be confirmed using other methods in the presence of a decrease, since this was also seen in non-responding patients.

Adult↗
PubMed1996

Different intravenous administration techniques for 5-fluorouracil. Pharmacokinetics and pharmacodynamic effects.

The pharmacokinetics after 20 min intravenous infusion or a 2 min bolus (push) injection of 5-fluorouracil (500 mg/m2) were studied in 14 colorectal cancer patients. Treatment effects and toxicity related to the administration technique of 5-fluorouracil were retrospectively analysed in 198 colorectal cancer patients. The AUC after bolus injection was 6158 +/- 874 micromol/l*min compared to 3355 +/- 428 micromol/l*min after short-time infusion of 5-fluorouracil (p < 0.01). The mean peak-level after bolus injection was 341 +/- 34 microM versus 161 +/- 17 microM after a short-time infusion (p < 0.01). Patients receiving bolus injections had significantly better treatment result (32% partial remission) than patients receiving infusion (10% partial remissions, p < 0.001). Toxic side-effects were more frequently encountered after bolus injection but subjective improvement was also more frequently experienced by these patients. Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique.

Aged↗
PubMed1996

Functional results after abdominal suture rectopexy for rectal prolapse or intussusception.

OBJECTIVE: To assess the functional outcome after suture rectopexy in patients with rectal prolapse or intussusception. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 33 patients with rectal prolapse and 19 patients with intussusception treated by abdominal suture rectopexy 1969-1992. MAIN OUTCOME MEASURES: Bowel function evaluated by a questionnaire a median of 97 months after operation. RESULTS: 10/33 patients (30%) reported less constipation after rectopexy in the prolapse group compared with 3/19 (16%) in the intussusception group (p = 0.33). Rectal emptying improved in 14/33 (42%) and 1/19 (5%), respectively (p = 0.005), and incontinence in 12/33 (36%) and 3/19 (16%), respectively (p = 0.20). Seventeen patients (52%) with prolapse and 3 (16%) with intussusception described the result of operation as excellent or good (p = 0.02). CONCLUSION: There is a reasonable chance of improved rectal emptying and continence in patients undergoing suture rectopexy for rectal prolapse, whereas bowel symptoms commonly worsen postoperatively in patients treated for intussusception.

Adult↗
PubMed1995

Selective sensitivity of solid tumors to suramin in primary cultures of tumor cells from patients.

The antineoplastic activity of suramin is currently the subject of clinical trials. We therefore used the semi-automated fluorometric microculture cytotoxicity assay (FMCA) to evaluate the cytotoxicity of suramin in vitro in primary cultures of cells from patients with hematological or solid tumors. The activity patterns of some standard cytotoxic agents were included for comparison. A total of 159 samples were tested using continuous drug exposure. Suramin showed relatively high activity against solid tumors, with colorectal, adrenal and kidney carcinomas being the most sensitive, whereas hematological malignancies were more resistant. Suramin and standard drugs showed very low cross-resistance. The results indicate that suramin is differentially active against some solid tumors with comparatively little activity against hematological tumors. The study provides an experimental motive for evaluation of suramin therapy in patients with solid tumors and exploration of less toxic suramin analogues.

Antineoplastic Agents↗
PubMed1995

Free radicals, anticonvulsants, and the neuronal ceroid-lipofuscinoses.

The relationship between free radicals and scavenger enzymes, and the disorders called the neuronal ceroid-lipofuscinoses, has long been an argumentative one. Recent evidence would seem to support the fact that such a relationship might exist but that it is indirect. The relationship does not seem due to an inborn error of free radical scavenger enzyme metabolism. Anticonvulsants play a role, as they influence free radical generating systems. At this juncture, no one has studied the relationship of anticonvulsant therapy, neuronal ceroid-lipofuscinosis, and the free radical-scavenging enzyme system, and their interplay. We have studied a large number of patients with epilepsy who are on either monotherapeutic or polytherapeutic regimens of most of the common anticonvulsants. We have found excessive free radical production in many of these patients, ranging from minor effects in the simpler anticonvulsants when used monotherapeutically, to more complex changes in polytherapeutic combinations. Likewise, we have found subtle and inconsistent findings in the free radical-scavenging enzyme system in a variety of examples of neuronal ceroid-lipofuscinosis. When refractory seizure disorders stimulate the vigorous use of polytherapy with a variety of free radical-facilitating anticonvulsants, free radical production becomes deleterious. Likewise, in certain types of neuronal ceroid-lipofuscinosis, polypharmacy with anticonvulsants, by enhancing the production of free radicals or suppressing scavenging enzymes, tends to be deleterious and induces a worsening in the disease process.

Adolescent↗