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W Graf

Publications and source records attributed to W Graf.

At least 91 records · Page 5Linked to original sources
PubMed1994

The effect of 5-fluorouracil on wound healing and collagen synthesis in left colon anastomoses. An experimental study in the rat.

In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5-FU) treatment of colorectal carcinoma 86 male Wistar rats were operated with a standardized left colon resection and anastomosis with interrupted sutures. Treatment was given as daily intraperitoneal (i.p.) injections. The animals were randomized to one of two groups: (A) 5-FU (20 mg/kg) i.p., and (B) NaCl i.p. from the day of operation to sacrifice. Anastomotic complications were registered. In experiment 1 animals were randomized within treatment groups to be tested for anastomotic breaking strength with or without sutures in place when sacrificed 7 days postoperatively. In experiment 2 collagen synthesis was studied by an in vivo incorporation and hydroxylation of 3H-proline in the anastomotic segment during 24 h prior to sacrifice. The animals were sacrificed in groups on the third or seventh postoperative day. A higher number of anastomotic complications was registered when 5-FU was given. The anastomotic breaking strength was only 40% of controls both when tested with and without sutures. A reduced radioactivity of 3H-hydroxyproline in the anastomotic segment after 7 days of 5-FU treatment was found implying a reduction in collagen synthesis. In our model colonic healing was impaired after i.p. 5-FU treatment and this could be attributed to a reduced collagen synthesis in the wound gap as well as in the adjacent tissue responsible for the suture-holding capacity.

Anastomosis, Surgical↗
PubMed1993

Vestibular control of skeletal geometry in the guinea pig: a problem of good trim?

Motor control of different segments of the body with multiple degrees of freedom appears to be coordinated by utilizing preferred axes of motor activity. This hypothesis may also be applied to vestibular control of posture. To explore this question we studied the anatomical relationship between the head and the cervical vertebral column by taking radiographs of the head-neck region in unrestrained alert guinea pigs. We determined that biomechanical constraints contribute to the stereotypical skeletal geometry observed in the resting animal and to a functional segmentation of the head-neck movement apparatus. Subsequent lesion studies of vestibular end organs with quantification of the resulting postural syndromes suggest that the functional segmentation of the cervical vertebral column corresponds to a functional partitioning of vestibular afferents. Our findings also indicate that the sensorimotor transformation mechanisms necessary to convert a given head velocity signal into the appropriate neck motor frame are already embedded in the networks provided by second-order vestibular neurons. Good trim of postural control will be the end result of an appropriate internal representation of the objective vertical.

Afferent Pathways↗
PubMed1993

Sensorimotor transformation in the cat's vestibuloocular reflex system. I. Neuronal signals coding spatial coordination of compensatory eye movements.

1. Coordinate transformation between vestibular and oculomotor reference frames is required to produce compensatory, vestibuloocular reflex (VOR) eye movements in view of the differing, although similar, peripheral three-dimensional geometry of the semicircular canals and the extraocular muscles. This transformation requires convergence of canal-specific signals at some level in the VOR arc. 2. To investigate the networks that underlie the transformation between oculomotor and vestibular reference frames for spatial coordination of compensatory eye movements, we recorded intracellularly in decerebrate cats from 93 identified second-order vestibulooculomotor and abducens internuclear neurons in the medial longitudinal fasciculus (MLF) between abducens and trochlear nuclei and characterized their spatial response properties. Neurons were classified according to whether they were activated from the labyrinth ipsi- or contralateral to the recording site and according to the canal from which they received their strongest input. Our data revealed neurons that carried single- and multiple-canal signals. 3. Twenty-two neurons received their primary input from the ipsi- or contralateral anterior canal (AC). Ten nonconvergent AC neurons responded maximally to rotation in a plane within 10 degrees of the AC plane, whereas 6 AC neurons received sufficient convergent input from the orthogonal vertical canals to shift their plane of maximum response > 10 degrees from the AC plane. Of 29 ipsi- and contralateral posterior canal (PC) neurons, 9 were non-convergent, whereas 13 received sufficient convergent input from the orthogonal vertical canals to shift their response plane > 10 degrees from the PC plane. The rotational responses of 6 AC and 12 PC neurons indicated that they received convergent input from the horizontal canals. However, when these responses were averaged, the horizontal responses tended to cancel, leaving little net population response to horizontal rotation. We also encountered 19 ascending axons of second-order neurons activated primarily from the horizontal canals. Nine of these received significant input from the vertical canals, but the mean population response was within 4 degrees of the horizontal canal plane. 4. Our results demonstrate single canal responses and specific canal-canal convergence within the population of vertical vestibulooculomotor neurons. This convergence is thought to participate in the coordinate transformation within the specific geometry of the VOR system. The data indicate response shifts of a population of AC neurons toward the plane of the inferior oblique muscle, and of a population of PC neurons toward the plane of the superior oblique muscle. Conspicuously absent are neurons that fall into the plane of either the superior rectus or the inferior rectus muscles. (ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗
PubMed1993

Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat. Aspects of tumour implantation site and mode of antibody administration.

Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.

Animals↗
PubMed1992

[Monotherapy with the ACE-inhibitor ramipril or the calcium antagonist nitrendipine in essential hypertension].

Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have, by reason of their potentially favourable pharmacological profile, become increasingly established in the treatment of hypertension in recent years. In a double-blind randomized study with an initial placebo phase, carried out by practising physicians and thus aimed at the "usual" practice patients with essential hypertension, we assessed (1) the antihypertensive effect and tolerability of an ACE inhibitor (ramipril, 5 mg/d) or a calcium antagonist (nitrendipine, 20 mg/d) given in a single daily dose, and (2) a possible age-dependent blood pressure (BP) effect of these therapies. In the 4 weeks' placebo phase, the two treatment groups were comparable as regards average age (49.6 and 49.4 years), age-range (27-67 and 25-64 years) and BP. Fifty-two patients completed the following 6 weeks' phase with active drug therapy. On ramipril (n = 26), the BP measured 24-25 hours after the last drug administration was reduced in the supine position from an average of 155/102 to 142/91 mmHg (mean reduction -10.1%) and in the upright position from 156/106 to 141/96 mmHg (-9.3%). Nitrendipine (n = 26) reduced the average BP from 155/102 to 147/94 mmHg (-6.8%) and from 155/106 to 146/99 mmHg (-6.6%) respectively. BP-lowering effects of both treatments were largely independent of age. Including the patients who discontinued the study prematurely because of side effects (1 on ramipril, 4 on nitrendipine), the "intention to treat analysis" shows BP normalization rates (diastolic < or = 90 mm Hg) of 55% (ramipril) and 30% (nitrendipine) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Influence of 5-fluorouracil and folinic acid on colonic healing: an experimental study in the rat.

Male Wistar rats were subjected to colonic resection and randomized to one of four groups: control group (intraperitoneal NaCl, intravenous NaCl); 5-fluorouracil (5-FU) group (intraperitoneal 5-FU, intravenous NaCl); folinic acid group (intraperitoneal NaCl, intravenous folinic acid); and 5-FU-folinic acid group (intraperitoneal 5-FU, intravenous folinic acid). Treatment was started immediately after surgery and continued until the animals were killed at 3 or 7 days. Anastomotic complications (abscesses or dehiscence) occurred in four of 33 animals in the control group, 12 of 36 in the 5-FU group, one of 32 in the folinic acid group and nine of 36 in the 5-FU-folinic acid group. Anastomotic and skin breaking strength did not differ between groups on day 3 but by day 7 were significantly reduced in the 5-FU group. In rats given 5-FU-folinic acid, breaking strength was also reduced, but less so than in the 5-FU group. Breaking strength in animals receiving folinic acid was similar to that in the control group. In this model colonic healing was impaired after intraperitoneal 5-FU administration, but when folinic acid was added no further deterioration occurred.

Anastomosis, Surgical↗
PubMed1992

Differences in optokinetic and vestibular ocular reflex performance in teleosts and their relationship to different life styles.

Horizontal eye movements in response to vestibular and optokinetic stimulation were investigated in 20 species of marine and fresh water teleosts. Most species performed spontaneous saccadic eye movements in light and in darkness. Successive saccades occurred either at irregular intervals and in different directions (few species), or in bursts of smaller saccades in one direction followed by saccades in the opposite direction (majority of species). Thus, in the latter group the lines of sight shifted cyclically from one side to the other about every 10-15 s. Eye movement responses in goldfish and toadfish were prototypical for two major functional groups. Optokinetic and vestibular nystagmus in the goldfish were much more regular and attained significantly higher gains than in the oyster toadfish. Optokinetic afternystagmus (OKAN) and per-/postrotatory nystagmus lasted about 10-12 s in the goldfish, but only 2-3 s in the oyster toadfish. Bilateral labyrinthectomy in goldfish resulted in optokinetic gains and OKAN durations that were very close to those of intact toadfish. These results indicate the presence (in goldfish) and the absence (in toadfish) of a functioning velocity storage network, respectively. Other non-ostariophysan teleosts failed to show a 'goldfish-like' response pattern as well. Ostariophysan species differed in their reflex performance as well. A 'goldfish-like' response pattern was observed in five of the seven cypriniform species and in two of the four characiform species but not in the four siluriform species. Positively correlated, combined response properties suggest that some species are better equipped for gaze stabilization at higher velocities than other species. These behavioral differences may parallel different specializations in locomotor pattern and mode of life. Absence of a functioning velocity storage network in bottom-dwelling teleosts (as in Amphibia) may be related to the sporadic, slow locomotion of these species and the resulting small requirements for continuous gaze stabilization during self-motion at higher velocities.

Animals↗
PubMed1992

General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study.

A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period.

Adult↗
PubMed1992

Delorme's operation for rectal prolapse in elderly or unfit patients.

OBJECTIVE: To evaluate the results after Delorme's operation for rectal prolapse in elderly and unfit patients. DESIGN: Retrospective analysis and telephone interview. SETTING: Akademiska sjukhuset, Uppsala, Sweden. SUBJECTS: A consecutive series of 14 women (median age 82, range 32-92) operated on for rectal prolapse 1987-1992 and followed up after a median of 18 months. RESULTS: There were no serious postoperative complications. Continence was improved in 6/11 incontinent patients. The recurrence rate was 3/14 (21%). CONCLUSION: Delorme's operation is an attractive alternative in elderly or unfit patients, but is not recommended for younger and low risk patients because of the recurrence rate.

Adult↗
PubMed1992

Induction and quantification of hepatic metastases from a human colonic cancer in the nude rat.

Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.

Animals↗
PubMed1992

Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat.

Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.

Animals↗
PubMed1991

Determinants of prognosis in advanced colorectal cancer.

The relations between patient characteristics and prognosis were examined in 340 patients with advanced colorectal cancer treated with chemotherapy. Variables were tested for relation to survival and responses in univariate and multivariate analyses. Performance status (P less than 0.001), number of symptoms (P less than 0.001) and haemoglobin level (P less than 0.001) were the most important variables for survival in univariate analyses. In the multivariate analyses of survival, haemoglobin level (P less than 0.001) and disease-free interval (P less than 0.01) were the most influential variables. In addition, number of symptoms (P less than 0.01), performance status (P less than 0.05) and treatment of the primary tumour (P less than 0.05) were independently related to survival. The main independent determinant of response was haemoglobin level (P less than 0.01). Besides these pretreatment characteristics, type of chemotherapy regimen influenced both response rate and survival in multivariate analyses (P less than 0.001). We conclude that haemoglobin level, disease-free interval, symptoms and performance status are important prognostic factors in advanced colorectal cancer. The distribution of these variables may influence the results of clinical trials.

Adult↗
PubMed1991

Complications after double and single stapling in rectal surgery.

Stapled anterior resections were carried out in 131 patients between October 1980 and July 1990. Double stapling was used in 87 cases and single stapling in 44. Clinical leaks occurred in 20 patients (15%) and subclinical leaks in 10 (8%) giving a total leak rate of 30/131 (23%). This proportion was similar after double (19/87, 22%) and single (11/44, 25%) stapling. Three fistulas to adjacent organs developed (two after double and one after single stapling). Stenoses occurred in 27 patients (21%), 15/87 (17%) after double, and 12/44 (27%) after single stapling. A permanent stoma was the outcome of an anastomotic complication in 9/87 (10%) patients after double and in 4/44 (9%) after single stapling. The main risk factors were: the number of blood transfusions was related to the risk of dehiscence (p = 0.01), a small cartridge size increased the risk of stenosis (p = 0.002) and previous radiotherapy increased the probability of a permanent stoma (p = 0.0005).

Adult↗
PubMed1990

Neuronal adaptation accompanying metamorphosis in the flatfish.

Flatfish provide a natural paradigm to investigate adaptive changes in the central nervous system of vertebrates. During their metamorphosis, the animals undergo a 90 degrees tilt to one side or the other to become the bottom-adapted adult flatfish. The eye on the down side is pushed over to the up side. Thus, vestibular and oculomotor coordinate systems rotate 90 degrees relative to each other. As a result, during swimming movements different types of compensatory eye movements are produced before and after metamorphosis by the same vestibular stimulation. Intracellular staining of central neurons with horseradish peroxidase revealed that in postmetamorphic flatfish second-order horizontal canal neurons contact vertical eye muscle motoneuron pools on both sides of the brain via pathways that are absent in all other vertebrates studied. These unique connections provide the necessary and sufficient connectivity to adapt the flatfish's eye movement system to the animals' postmetamorphic existence. Although the adult fish has a bilaterally asymmetric appearance, the central nervous connectivity reestablishes symmetry in the vestibulo-oculomotor system.

Adaptation, Physiological↗
PubMed1990

Sequential 5-fluorouracil and leucovorin in patients with advanced symptomatic gastrointestinal cancer.

50 patients with advanced symptomatic gastrointestinal cancer were treated with sequential 5-fluorouracil (5-FU)/leucovorin. Patients received an intravenous bolus injection of 5-FU (500 or 600 mg/m2) and leucovorin 30-40 min later, either 50 mg (41 patients) or 200 mg (9 patients). Treatment was given in repeated courses either once weekly or on 2 consecutive days every other week until progression. Toxicity was mild with the lower leucovorin dose, although grade 2 toxicity, particularly diarrhoea, occurred in 27 (66%) patients. All patients receiving the higher leucovorin dose had grade 2-4 toxicity. Toxicity was less with the lower 5-FU dose. Out of 40 patients with colorectal cancer, 34 received leucovorin 50 mg and 6 received 200 mg. Partial response occurred in 10 (29%) and 1 of these patients, respectively. This sequential 5-FU and intermediate-dose leucovorin regimen has acceptable toxicity and a definite anti-tumour activity.

Adult↗
PubMed1990

Potential value of immunoperoxidase technique in assessment of genital herpes.

Cervicovaginal smears from 86 patients with suspicious genital herpes were screened by routine Papanicolaou stain. The slides were then destained and restained by a commercial immunoperoxidase kit for the detection of herpes simplex virus. Results were compared with standard viral cultures performed on the same lesions. A statistically significant difference (P less than 0.05) was observed between the results of Papanicolaou-stained cytology and the immunoperoxidase technique. This study suggests that the immunoperoxidase technique is a rapid and reliable method of confirming a suspected diagnosis of herpetic infection. It is particularly useful in those patients without prenatal care who present in early labor when a rapid diagnostic test is required.

Cost-Benefit Analysis↗
PubMed1990

Anterior versus abdominoperineal resections in the management of mid-rectal tumours.

In order to assess if results after anterior resections (AR) compared with abdominoperineal resections (APR) for mid rectal tumours have changed since the circular stapler was introduced into clinical practice, two consecutive series of patients were reviewed. The first series comprises 81 patients treated between 1974-79. Sixteen were treated with AR and 65 with APR. Except for the later part of 1979, the stapling instrument was not available during this period. The second series comprises 156 patients (51 AR and 105 APR) operated on during the period 1980-85, when the circular stapler was in extensive use. All patients had curative operations for tumours 6-11 cm from the anal verge. In the first series the local recurrence rate was 5/13 (39%) after an AR and 25/61 (41%) after an APR, and in the second series 8/50 (16%) and 17/100 (17%) after AR and APR, respectively. Cancer specific survival did not differ between operations in any of the series. Thus no deterioration in results could be detected since the stapling technique became part of surgical routine.

Abdomen↗