Search PubMedSearch

Biomedical subjects

J Kjaergaard

Publications and source records attributed to J Kjaergaard.

At least 19 recordsLinked to original sources

Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy.

The systemic transfer of ex vivo-activated tumor-sensitized T lymphocytes can mediate immunologically specific regression of established tumors. However, it has not been conclusively established whether the infiltration of systemically transferred T cells into metastases is required for their effector function. In this study, T cells from lymph nodes draining the murine fibrosarcoma MCA 205 cells were activated ex vivo with anti-CD3 monoclonal antibody and interleukin-2. During the final 24 h of culture, the T cells were treated with pertussis toxin (PTX) to inhibit signaling through G protein-coupled chemokine receptors required for diapedesis. Systemically transferred PTX-treated cells did not have any therapeutic efficacy against 3-day established pulmonary metastases. This lack of efficacy correlated with their failure to infiltrate the tumor parenchyma. However, PTX-treated cells responded to tumor antigen stimulation with IFN-gamma secretion in vitro. More importantly, PTX-treated effector T cells prevented tumor growth when they were admixed with tumor cells and inoculated s.c. These results demonstrate that systemically transferred tumor-reactive T lymphocytes need to infiltrate the tumor parenchyma through the endothelium to initiate tumor regression, but PTX-sensitive proteins are not required for either antigen recognition or effector functions.

Animals

Tumor infiltration by adoptively transferred T cells is independent of immunologic specificity but requires down-regulation of L-selectin expression.

Adoptive immunotherapy with anti-CD3/IL-2 activated tumor-draining lymph node (LN) T cells is capable of eradicating tumor established at various histological sites. Tumor-specific effector lymphocytes have recently been identified to be LN T cells with down-regulated L-selectin (L-selectin-). Using fluorochrome labeling, the present study determined the early trafficking pattern of systemically transferred cells. In mice with 10-day established pulmonary 3-methylcholanthrene (MCA) 205 metastases, accumulation of cells in tumors was evident as early as 2 h after i.v. cell transfer, and, by 24 h, >50-fold higher numbers of cells were seen in metastases than in normal tissues. Similarly, transferred cells selectively infiltrated s.c. tumors, albeit at a lower rate. Analysis of the transferred cells isolated from recipient mice revealed that tumor-infiltrating cells were mostly L-selectin- (>95%). By contrast, only 24% and 58% L-selectin- cells were found in the LN and spleen, respectively. The ability of L-selectin- cells to accumulate at tumor sites was confirmed by the transfer of purified cell populations. Despite this selective tumor infiltration, the trafficking pattern did not reflect antigenetic specificity, and tumor regression occurred only after the transfer of tumor-specific effector cells. These results, thus, suggest that there are two distinct mechanisms operative in successful adoptive immunotherapy. Early infiltration of tumors by transferred cells is dictated by the physiological properties of cells and is independent on their immunologic specificity. Tumor regression, however, requires immunologically specific interactions at the site of tumor.

Adoptive Transfer

[A single physician or a group of specialists in the surgical ward. I: Impact on quality of the care provided by specialists].

The impact on quality of ward care provided by surgeons within two continuity schedules was assessed by explicit and implicit audit. In one schedule one surgeon provided care and in another a staff of surgeons provided care. The study included 214 consecutive inpatients. The study demonstrated that quality of ward care was unaffected by continuity schedule. In the single surgeon continuity schedule, however, nearly twice as many discharge letters were posted within four days (p < 0.001). Likewise, twice as many contained information that the patients had been informed about the diagnosis (p < 0.05). In both continuity schedules about 20% of the patients received inadequate care. Analysis of this finding demonstrated that more patients had been subject to inadequate follow-up in the single surgeon continuity schedule, whereas more patients had been subject to inadequate postoperative observation in the staff continuity schedule. In both schedules an equal number of patients had been subject to incomplete diagnoses and inadequate medical care.

Continuity of Patient Care

[Fibromyalgia].

Explore the source record for details and available documents.

Fibromyalgia

Infiltration patterns of short- and long-term cultured A-NK and T-LAK cells following adoptive immunotherapy.

Direct contact between lymphokine-activated killer (LAK) cells and tumour cells is believed to be imperative for initiating tumour cell lysis in vitro as well as in vivo. In order to optimize adoptive immunotherapy (AIT) it is therefore desirable to identify the LAK cell subtype, which ensures maximal infiltration of tumours as well as a substantial cytotoxic reactivity. In this report we have compared short- and long-term cultured murine adherent natural killer (A-NK) cells and mitogen-stimulated, lymphokine-activated T-killer (T-LAK) cells with respect to their proliferative potential, cytotoxicity, requirement for interleukin-2 (IL-2) and ability to infiltrate B16 pulmonary metastases following adoptive transfer. We found that short-term (5 days) cultured A-NK and T-LAK cells both showed a substantial accumulation of tumour tissues. However, A-NK cells gradually lost this ability during in vitro culture whereas T-LAK cells cultured for as long as 20 days retained their ability to infiltrate metastases as efficiently as their short-term cultured counterparts. Moreover, the low requirement of IL-2 by T-LAK cells to achieve maximal infiltration of tumours sharply contrasted with the excessive doses necessary to ensure maximal infiltration by A-NK cells. In conclusion, these data demonstrate that short-term cultured LAK cells of both NK- and T-cell origin are able to infiltrate B16 pulmonary metastases effectively. Importantly, the T cells retain this ability for a considerably longer time and require much less IL-2 support than do A-NK cells, making T-LAK cells attractive for AIT.

Animals

[Malignant mesothelioma: incidence, survival and relative risks in selected municipalities 1943-1992].

The development in incidence rates and survival in Denmark, and the rate-ratio in selected municipalities that had industries utilizing asbestos was studied in 1865 cases of malignant mesothelioma identified in the Danish Cancer Registry 1943-1992. For men a steady increase in the incidence to 1.6 per 100,000 personyears in 1992 was found, while the rate for women decreased to 0.28 per 100,000 personyears. Age-specific incidence rates were highest for the older age-groups. An unexplained difference in the distribution of pleural and peritoneal cancers was seen between men and women. The average survival was 6.9 months for men and 7.8 for women and had not changed during the period of observation. The average rate-ratio for the selected municipalities was 1.97 (95% confidence intervals: 1.73-2.24) for men and 1.35 (1.08-1.69) for women. Improvements in working conditions in terms of minimizing asbestos exposure were introduced in 1980. Considering the latency period from exposure to diagnosis of 25-30 years, the impact of this measure on the rate of incidence cannot be expected before the year 2000.

Adult

[Junior physicians educate themselves. Educational value of trainees' work at a department of surgery].

UNLABELLED: In order to investigate the educational value of trainee surgeons' work, all work done by trainees at a Department of Surgery was recorded in a prospective and consecutive way for four weeks. It was recorded as fixed categories divided into intervals of 15 minutes. The work could be classified in three dimensions: Character, educational value and geography. The youngest trainees performed routine work without educational value. They had some practical jobs which could be done by other personnel. The work did not fulfil the educational claims for a trainee surgeon in phase I. The second group of trainees performed much routine work without educational value. They had no practical jobs that could have been performed by non-doctors. They had some work with educational value but not enough to fulfil the goals of a trainee surgeon in phase II. CONCLUSION: Doctors' clinical education could be improved by giving them work with educational value and supervision. Supervision should be performed by specialists who should also contribute to the routine work without educational value.

Denmark

[Colorectal cancer in Denmark 1943-1988].

Nation-wide incidence rates are presented of colorectal cancer in Denmark from 1943 to 1988. In Denmark notification of malignant and related diseases is mandatory. The percentage of histologically confirmed tumours is now 95. The annual incidence rate of colon cancer in Denmark has been increasing among men and women combined from 684 cases in 1943-1947 to 2020 cases in 1988. In the same period the incidence of rectal cancer has increased from 762 cases in 1943-1947 to 1108 cases in 1988. We analyzed the effects of age, calender time, and birth cohort with multiplicative Poisson models. We did not find consistent period effects in the models. We suggest an etiologic distinction between carcinoma of the rectum, the left colon and the right colon.

Colonic Neoplasms

[Knowledge about colorectal cancer among surgeons in training].

Ninety-five participants in five theoretical courses on colorectal cancers were prior to the course asked to attend a multiple choice examination about colorectal cancer. All participants were under education in general surgery. Their experience in years as doctors was registered as was the time each participant had used for preparation before this course. For thirty-six of the participants the course ended with an examination and the participants had knowledge of that before they attended the course. We found a statistically significant relation between the amount of time spent in preparation and the results obtained in the multiple choice examination. There was no relation between results obtained and experience as a doctor. Participants who knew that an examination was to be held used significantly longer time for preparation and obtained a significantly better results than participants who did not attend any examination at the end of the course. It is concluded that the reading of text books extends the knowledge on colorectal cancer and that doctors during education are more eager to prepare when they know that an examination is waiting.

Clinical Competence

Convalescence after inguinal herniorrhaphy.

BACKGROUND: The aim of this investigation was to evaluate factors influencing the length of convalescence after ambulant inguinal hernia repair. METHODS: One hundred and twenty-three patients were followed up to assess when they returned to work, considered that they had regained full working capacity, and resumed leisure time activities. The length of sick leave was recommended on the basis of the load of the occupation. RESULTS: Half of the patients had a longer sick leave than recommended by the surgeon. Active and heavy work showed an independent significant positive correlation to the length of sick leave. Median sick leave among these patients was 42 days, which was the time they considered that they had regained full working capacity and 1 week after they had resumed their leisure time activities. Median sick leave among patients with sedentary or moderately active work was 9 days before regaining full working capacity and 12 days before resuming leisure time activities. CONCLUSIONS: Other factors than load of work and surgeon's advice seem to play a role in the patient's decision about when to resume normal activities on the job.

Adult

[Hartmann's procedure in the treatment of acute obstructive left-sided colonic cancer].

This retrospective study included all patients over a five-year period who underwent the Hartmann's procedure because of a malignant left-sided large bowel obstruction. Twenty-nine patients were treated with this procedure. The cumulative operative mortality was 14%, and the five-year survival was 31%. Intestinal continuity was restored in seven patients (24%). There were no anastomotic leakages. The treatment resulted in a permanent colostomy in 62% of the patients. The Hartmann's procedure can be employed as a treatment of malignant left-sided large bowel obstruction, but will cause a high frequency of permanent colostomy.

Acute Disease

Colorectal cancer in Denmark 1943-1988.

Nation-wide incidence rates are presented of colorectal cancer in Denmark from 1943 to 1988. In Denmark notification of malignant and related diseases is mandatory. The percentage of histologically confirmed tumours is now 95. The annual incidence rate of colon cancer in Denmark has been increasing among men and women combined from 684 cases in 1943-47 to 2020 cases in 1988. In the same period the incidence of rectal cancer has been increasing from 762 cases in 1943-47 to 1108 cases in 1988. We analyzed the effects of age, calendar time, and birth cohort with multiplicative Poisson models. We did not find consistent period effects in the models. We suggest the trends in colorectal cancer incidence rates may be due to changes in environmental factors such as dietary habits and in physical activity. Furthermore, we suggest an etiologic distinction between carcinoma of the rectum, the left colon and the right colon.

Cohort Effect

[3-layer anastomoses after resection of colorectal cancer. A prospective study of 1015 anastomoses].

This study included patients who underwent elective curative resection of adenocarcinoma of the large bowel with primary suture of the anastomosis. The overall incidence of clinical anastomotic leakage was 5%. The incidence of anastomotic leakage was significantly higher in men than in women after low anterior resection. The three-layer anastomosis has no advantage in large bowel surgery when compared with data from other sutured anastomoses reported in the literature.

Adenocarcinoma