PubMed Health⌕ Search

Biomedical subjects

A Sell

Publications and source records attributed to A Sell.

At least 19 recordsLinked to original sources
PubMed2006

Isobaric bupivacaine via spinal catheter for hip replacement surgery: ED50 and ED95 dose determination.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of the local anaesthetic and, consequently, less haemodynamic change. However, little is known about the required doses. Therefore, we designed a study to assess the local anaesthetic doses of isobaric bupivacaine which were effective in 50% (ED50) and 95% (ED95) of patients undergoing hip replacement surgery. METHODS: Forty-eight patients undergoing hip replacement surgery were randomly allocated to one of six possible groups of eight patients to receive 6, 7, 8, 9, 10 or 12 mg of isobaric bupivacaine in a double-blind manner. The ED50 and ED95 values were calculated by a logistic regression model. The position of the spinal catheter tip was confirmed by X-rays. RESULTS: The ED50 and ED95 values were 7.1 mg (95% confidence interval, 6.0-8.4) and 12.3 mg (95% confidence interval, 8.9-15.7), respectively. The location of the tip of the intrathecal catheter had no effect on local anaesthetic requirements. Eight patients required ephedrine after anaesthesia induction and a further 11 patients required ephedrine for correction of hypotension during surgery. CONCLUSION: The observed ED50 and ED95 values may guide us to use small doses of isobaric bupivacaine for hip replacement surgery. Hypotension is still possible even if low doses of isobaric bupivacaine are used.

Adult↗
PubMed2004

Minimum effective local anaesthetic dose of isobaric levobupivacaine and ropivacaine administered via a spinal catheter for hip replacement surgery.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of local anaesthetic and, consequently, less haemodynamic changes. However, little is known about the required doses. Therefore, we designed a study to assess the minimum effective local anaesthetic dose (MLAD) of levobupivacaine and ropivacaine in this context. METHODS: Forty-one patients undergoing hip replacement surgery were randomly allocated to one of the two local anaesthetic groups in a double-blind manner. The initial dose of local anaesthetic was determined by the response of the previous patient: the effective dose resulted in a 1 mg decrease in the dose of levobupivacaine or ropivacaine, and an ineffective dose resulted in a 1 mg increase. The MLAD was calculated by the Dixon up-and-down method. RESULTS: The MLAD of levobupivacaine was 11.7 mg (95% CI, 11.1-12.4) and that of ropivacaine 12.8 mg (95% CI, 12.2-13.4). CONCLUSIONS: These doses are significantly smaller than doses reported before for single-shot spinal anaesthesia. Continuous spinal anaesthesia allows the use of relatively small doses of local anaesthetic.

Adult↗
PubMed1999

Hypoxic upregulation of tyrosine hydroxylase gene expression is paralleled, but not induced, by increased generation of reactive oxygen species in PC12 cells.

Oxygen sensing was investigated in rat pheochromocytoma PC12 cells. They respond to hypoxia with an increased intracellular generation of reactive oxygen species (ROS), measured by oxidation of dihydrorhodamine 123. This increase is abolished by intracellular superoxide scavenging by Mn(III)-tetrakis(1-methyl-4-pyridyl)-porphyrin, and reduced or absent in the presence of the flavoprotein/complex I inhibitors, diphenyl-eneiodonium and rotenone. The same inhibitors, but neither intra- nor extracellular (superoxide dismutase) superoxide scavenging, abolish the hypoxia-induced increase in tyrosine hydroxylase (TH) gene expression. Thus, ROS production increases in PC12 cells during hypoxia, but this is not the cause of hypoxic TH mRNA upregulation that involves a flavoprotein.

Animals↗
PubMed1996

Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated.

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.

Base Sequence↗
PubMed1996

[The development of radiotherapy in Denmark through 100 years. From radiology to oncology].

A short review is given of the development of radiotherapy from its early beginning in 1896 to the establishment of the first three radium centres in 1913/14 which caused strong protest from the surgeons. The Radium Foundation was established on private initiative and was, via money collections, able to finance purchase of radium and in the 1930s erection of new buildings for the three centres. Radiotherapy became a basic specialty from 1950. In the beginning of the 1960s megavoltage therapy was introduced and at the same time chemotherapy was becoming interesting for therapy of solid tumours. This caused a centralisation of the patients to the centres for non-surgical therapy resulting in need for building of two centres (Aalborg and Herlev), and a gradual closing down of the decentral treatment with low voltage equipment in the counties. After 1970 the counties became responsible for the health care including running of the hospitals. This caused a return of some of the patients to decentral treatment facilities, usually the biggest hospital in the county and predominantly for adjuvant or palliative chemotherapy. The speciality has changed name to oncology in 1987.

Cancer Care Facilities↗
PubMed1995

The development of radiotherapy in Denmark during 100 years. From radiology to oncology.

The evolution of radiotherapy in Denmark is traced from its early inception in 1896 to the first three radium centres in 1913-1914, the establishment of which caused a roar of protests among the surgeons of that time. Private initiative pioneered the Radium Foundation which raised money for radium and financed erection of new buildings for the three centres in the 1930's. Radiotherapy became a separate speciality in 1950. The early 1960s saw the introduction of megavoltage therapy and the first promising results from chemotherapeutic management of solid tumors. The consequent referral of patients to centres for non-surgical therapy created a need for two new centres (Aalborg and Herlev) and called for a gradual closing down of decentralized low-voltage treatment at county level. However, the decentralization of health care in 1970 partly reversed this trend and some patients were therefore referred for decentralized treatment at major county hospitals. Such treatment mainly consisted of adjuvant or palliative chemotherapy, though in a few countries palliative therapy was supported by low-voltage therapy. In 1987 the medical speciality of radiotherapy was officially renamed oncology.

Denmark↗
PubMed1994

Deletion analysis of the m4 muscarinic acetylcholine receptor. Molecular determinants for activation of but not coupling to the Gi guanine-nucleotide-binding regulatory protein regulate receptor internalization.

In order to investigate whether coupling to and/or activation of guanine-nucleotide-binding proteins (G proteins) is involved in agonist-induced internalization of m4 muscarinic acetylcholine receptors (mAChRs), a deletion mutant [des-(264-394)mAChR] was constructed that lacks a substantial portion of the putative third intracellular loop. The wild-type receptor and des-(264-394)mAChR stably expressed in Chinese hamster ovary cells in essentially comparable amounts, exhibited identical antagonist-binding affinities. Consistent with the reported importance of the third cytoplasmic loop for Gi protein activation, the des-(264-394)mAChR showed a drastically reduced potential to mediate agonist-induced inhibition of adenylyl cyclase. In contrast, the ability of the mutant receptor to couple to Gi proteins was not impaired, as demonstrated by a similar guanine-nucleotide-sensitive and pertussis-toxin-sensitive high-affinity agonist-receptor binding for both mAChRs. In contrast, des-(264-394)mAChR was hardly able to stimulate the GTPase activity of G proteins, suggesting impaired activation of Gi proteins rather than ineffective coupling to Gi proteins. Internalization of wild-type receptor and des-(264-394)mAChR was observed with similar agonist concentrations and showed similar maximal values. However, des-(264-394)mAChR displayed a significantly reduced rate of receptor internalization. A similar attenuation of wild-type mAChR internalization was obtained upon pertussis toxin treatment. In conclusion, our data provide evidence that the molecular determinants of the m4 mAChR involved in Gi-protein coupling and activation are not identical and that activation of, but not coupling to, Gi proteins regulates m4 mAChR internalization.

Adenylyl Cyclases↗
PubMed1993

A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma.

The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30 patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months. The 3-year actuarial survival rate was 9% (median 12 months). Only patients who achieved CR became long-time survivors (63% 3-year actuarial survival). Similarly, performance status had a strong association with survival. Multivariate analysis showed complete response and high performance status to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33% vs. 13% after irradiation alone).

Adult↗
PubMed1992

Time to loco-regional recurrence after resection of Dukes' B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis.

Factors influencing time to loco-regional recurrence were identified in a multivariate regression analysis of data from a series of 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. A number of clinical and pathological characteristics were prospectively collected and recorded. In addition, carcinoembryonic antigen (CEA) was measured within 1 week before surgery. The endpoint used was recurrence below the level of the umbilicus. All patients were followed for at least 5 years or until time of death. The two Dukes' stages B and C were analysed in two separate analyses using the Cox proportional hazards model. In patients with Dukes' B tumours, an increased risk of loco-regional recurrence was associated with perineural invasion, tumour located less than 10 cm from the anal verge, patient aged above 70 years, and small tumour size. In patients with Dukes' C tumours, the necessity to resect neighbour organs, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and large tumour size were all associated with a poor loco-regional outcome. Postoperative radiotherapy was not a significant prognosticator for loco-regional control. An update of the 5-year results of the randomised study of post-operative radiotherapy (50 Gy with 2 Gy per fraction in an overall treatment time of 7 weeks) showed no survival benefit from adjuvant radiotherapy in either Dukes' category and no statistically significant improvement in the 5-year loco-regional control rate. However, when the comparison was restricted to a group of high-risk patients there was a statistically significant benefit from radiotherapy with respect to loco-regional control (P = 0.03) but not with respect to survival (P = 0.23). The potential advantage, in terms of the required number of patients, of restricting clinical trials of intensified loco-regional therapies to the high-risk patients, is illustrated.

Adult↗
PubMed1991

Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.

From 1983 to 1986 183 patients with transitiocellular carcinoma of the urinary bladder, category T2-T4a, entered a randomized study. The patients were allocated to receive either preoperative irradiation (40 Gy) followed by cystectomy or radical irradiation (60 Gy) followed by salvage cystectomy in cases of residual tumor. The two randomization groups were comparable in regard to sex, age, T-categories, tumor size, histological grade and concomitant dysplasia. The two randomization groups included 88 and 95 patients respectively. The treatment plan was followed by 66 patients (75%) in the planned cystectomy group and by 88 (92%) in the radical radiotherapy group of which 27 (28%) were treated with salvage cystectomy. The results showed a trend to a higher survival rate following the combined treatment with preoperative irradiation and cystectomy compared to radical irradiation followed by salvage cystectomy in case of residual tumor, but a statistical significant difference could not be demonstrated. The lack of difference also applied according to the actually given treatment. There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients. The type of late complications was different in the two treatment groups, but there were no major differences in the number of complications except for the fact that all male patients experienced erective impotence after cystectomy. The T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗
PubMed1990

Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer.

From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.

Abdomen↗
PubMed1990

Blood transfusion and prognosis in Dukes' B and C colorectal cancer.

To evaluate the prognostic influence of blood transfusion in cancer patients, transfusion data were reviewed on 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. Data on whole blood and packed red blood cell transfusions were recorded together with a number of clinical, pathological and histochemical characteristics. The endpoint used was death with cancer. All patients were followed for 2-7 years or until time of death. Univariate statistical methods revealed a highly significant trend towards worsened prognosis with increasing volume of transfusion blood. However, this effect was insignificant when multivariate statistical methods were employed: patients receiving whole blood or packed red blood cell transfusions did no worse than expected from their clinico-pathological characteristics. It is concluded that in this series the observed association between transfusion status and prognosis is adequately explained by a multivariate prognostic model including well-established prognostic factors.

Aged↗
PubMed1989

[Prognosis in synchronous liver metastasis from colorectal cancer. A multicenter study of patients with cancer of the rectum and cancer of the rectosigmoid colon].

A prospective investigation of 188 patients with cancer of the rectum and rectosigmoid colon with synchronous liver metastases is described. The mean survival time for 183 patients who did not receive any treatment for the liver metastases was six months and only one survived for longer than 37 months. After extirpation of the primary tumour, the most significant prognostic factors were etrahepatic metastases, enlarged liver on account of metastases and more than three liver metastases. Serum basic phosphatases had the greatest significance among a series of laboratory tests. In the sub-groups with the best possible prognoses, the mean survival time was 12 months. 25% five-year survival has been described in the literature following resection of the liver in patients with a maximum of three metastases, no other metastases and age under 70 years. Provided this holds true, liver surgery will be a therapeutic possibility in at least 100 patients per annum in Denmark with synchronous liver metastases and 25 of these will be cured. This figure requires an improved programme for the diagnosis of synchronous liver metastases than at present and the same high frequency of extirpation of the primary colorectal cancer on a national basis which was achieved in the present material.

Aged↗
PubMed1989

Preoperative measurement of cancer antigen 125 (CA 125) in the differential diagnosis of ovarian tumors.

The purpose of the present study was to evaluate the information preoperative measurements of cancer antigen 125 (CA 125) may give concerning the nature of an ovarian tumor. Serum samples from 61 patients were analyzed and the results compared with regard to malignancy, FIGO-stage, and histologic type of the tumor. All patients were deemed to have a malignant tumor by clinical examination. Elevated serum levels (greater than 35 U/ml) were found in 44 patients and of these patients 38 had carcinomas, 5 had borderline tumors, and one had a benign tumor (false positive). Normal serum levels (less than or equal to 35 U/ml) were registered in 17 patients. Fourteen of these had benign tumors and 3 had malignant (false negative). The false positive sample and the 3 false negative samples observed in the present study result in a positive and negative predictive value of the CA 125 analysis of 98% (43/44) and 82% (14/17) respectively. The positive predictive value of the clinical examination was 75% (46/61). It is concluded that measurement of CA 125 is a valuable adjunct to the preoperative examination of patients with ovarian tumors.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1989

Diagnostic value of lymphography in cervical cancer stage Ib.

The value of lymphography in the diagnosis of lymph node metastases was investigated in 89 patients with stage Ib cervical carcinoma. All patients underwent radical hysterectomy. The lymphography (radiological diagnosis) was compared with the histopathological examination of the corresponding lymph nodes. The positive predictive value of the lymphography was 13% and that of the negative predictive value 98%. It is concluded that lymphography is not reliable for the diagnosis of lymph node metastases in cervical cancer stage Ib.

Female↗
PubMed1989

Bladder tumour treatment in the aarhus region. 25 years of experience.

We report on the clinical studies of bladder tumours carried out at the centre for oncology in the Aarhus area and describe the experience and results of the past three decades. The 1960's saw the replacement of intracavitary techniques with external megavoltage irradiation. In the 1970's a large-scale regional trial was conducted assessing irradiation, which was now the dominant treatment principle, at all stages of the disease. In the 1980's a country-wide randomized trial was designed to compare the effect of cystectomy and definitive irradiation and to address the quality of life question. The report also mentions several associated projects on epidemiology, diagnostics (urinary cytology, DNA distribution) and factors pertinent to treatment (radioprotective agents, CT-based dose planning). Finally, we describe a country-wide randomized trial on the use of adjuvant chemotherapy scheduled for the 1990's.

DNA, Neoplasm↗
PubMed1989

Quality of life in patients with advanced bladder cancer. A randomized study comparing cystectomy and irradiation--the Danish Bladder Cancer Study Group (DAVECA protocol 8201).

The "quality of life" after treatment for advanced bladder cancer was investigated. The study was part of a randomized trial comparing the effect of preoperative irradiation (40 Gy) and cystectomy with radical radiation therapy (60 Gy) and salvage cystectomy. Patients answered a mailed questionnaire on psycho-social aspects. The first was filled in 6 months after treatment and was answered by 107 patients. The second was sent out 12-18 months later and was answered by 68 patients. From a general point of view, there were no consistent differences between the two treatment groups. In the first questionnaire, patients treated with radical irradiation and salvage cystectomy expressed a slightly more pessimistic outlook than patients treated with pre-operative irradiation and cystectomy. There was not such difference in the second questionnaire, but the latter group reported the largest reduction of social (sports, hobbies, etc.) and sexual activities. In conclusion, pre-operative information about treatment and post-operative life is an important but often neglected issue.

Combined Modality Therapy↗