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Biomedical subjects

J K Larsen

Publications and source records attributed to J K Larsen.

At least 127 records · Page 7Linked to original sources
PubMed1985

How community mental health centers deal with cutbacks and competition.

The results of a survey of 71 directors of community mental health centers in 15 states in 1982 and 1983 indicate that CMHCs made major changes in their services, staffing, sources of revenue, administration, and organization to cope with shrinking budgets, increased state regulation, impending prospective payment systems, and accelerating competition from private for-profit health care providers. Services offered by the CMHCs became less comprehensive and more oriented toward chronic and severely ill patients in 1982 and 1983, and entrepreneurial principles were employed to increase efficiency and attract new sources of revenue. These strategies have been successful, but the authors believe more long-range planning is necessary if CMHCs are to retain their distinctive place in the health care system.

Community Mental Health Centers↗
PubMed1985

Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment.

The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin. A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression of these antigens in vivo was found in 11 of 12 examined patients with primary bronchial carcinoma. A concomitant increase in serum beta 2m (median 90%, P less than 0.001) was found in all patients. In contrast the amount of cell-associated HLA-ABC and beta 2m remained unchanged (P greater than 0.1 and P greater than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched healthy individuals. Treatment with IFN-alpha caused a significant redistribution of mononuclear cells resulting in both absolute and relative lymphopenia. Pre-treatment lymphocyte counts were 1.09 X 10(9)/1 (range 0.49-1.73), post-treatment counts were 0.55 X 10(9)/1 (range 0.39-1.06).

Adult↗
PubMed1984

Early diagnosis of cutaneous T-cell lymphoma by DNA flow cytometry on skin biopsies.

Seven patients with mycosis fungoides early plaque stage with nondiagnostic histology had single-cell DNA content measured by flow cytometry for estimation of clonal ploidy. A total of 63 skin specimens were examined by histology and DNA measurements concurrently during the course of the disease. In addition, six patients had blood samples studied. All seven patients demonstrated aneuploid DNA histograms when the specimens were obtained from skin lesions. In 36 specimens the aneuploid peaks were hyperdiploid. By sequential studies one patient demonstrated two different aneuploid cell clones, one located in the hyperdiploid region and one located in the hypotetraploid region. All patients developed mycosis fungoides which were histologically confirmed, and the time from first aneuploid DNA histogram until diagnostic histology varied from 5 to 21 months (median, 12 months). In six of the patients a normal diploid DNA histogram was found of peripheral blood lymphocytes. The finding of aneuploidy in patients with early mycosis fungoides who still have a nondiagnostic histology emphasizes the value of flow cytometry as a complementary diagnostic aid which facilitates an early diagnosis.

Aged↗
PubMed1984

Policy shifts and organizational adaptation: a review of current developments.

Changes in the operations and structure of local mental health centers are occurring in response to policy and funding shifts at the state and federal levels. Clinical and administrative staffing changes reflect both cutbacks in funding for traditional outpatient and inpatient services, as well as increases in partial care, community, residential and case management services. Centers are diversifying their funding sources, especially through increased revenues from Medicare-Medicaid sources. Governing boards remain active in center policy making, with few changes in their composition. Current adaptation strategies focus mainly on enhancing efficiency, reviewing service costs, expanding services to more viable markets, and improving business practices. These actions and strategies are compared to findings from previous studies, and their implications are discussed.

Ambulatory Care↗
PubMed1984

Tumor-induced growth-inhibitory activity isolated from the Yoshida ascites fluid by extraction with methanol.

Growth-inhibitory activity was isolated from the Yoshida ascites fluid by sequential precipitation with polyethylene glycol, extraction with methanol, LH 20 Sephadex chromatography and preparative agarose gel electrophoresis. The cell non-specific activity was tumor-related as far as analogous fractions prepared from normal sera were inactive. Flow cytometric analysis indicates that the inhibition of cell growth was caused by blockage of the G1-S and possibly the G2-M phase transitions. The active component migrates electrophoretically associated to an unidentified alpha 1-antigen. In aqueous solution the molecular size of the inhibitor is ill defined, due to a tendency to autoaggregation and hydrophobic interaction with the chromatographic media. The molecular weight of the inhibitor as estimated by LH 20 Sephadex chromatography in methanol is approximately 350 daltons. This chromatographic fraction contains prostaglandin-E2 cross-reactive material in amounts suggesting the participation of a prostaglandin derivative in the observed growth-inhibitory activity.

Animals↗
PubMed1984

Effects of the antioestrogen tamoxifen on the cell cycle kinetics of the human breast cancer cell line, MCF-7.

The effect of 10(-6) M tamoxifen on MCF-7 cells adapted to growth in 0.5% foetal calf serum has been studied. The growth inhibitory effect of this tamoxifen concentration was abolished by simultaneous addition of 10(-8) M oestradiol, indicating that tamoxifen may exert its effect via binding to the oestrogen receptor. Flow cytometric cell cycle analysis of tamoxifen-treated cultures showed an increase in the proportion of cells in the G1 phase of the cell cycle. By exposing the cells to BUdR before flow cytometry the growth fraction was determined and found to be dramatically decreased in tamoxifen-treated cultures. Cells were not only arrested in the G1 phase but also in the G2 phase of the cell cycle. A few colonies of MCF-7 cells were resistant to 10 days treatment with 10(-6) M tamoxifen.

Breast Neoplasms↗
PubMed1984

Circadian-stage dependence of methotrexate in a keratinized epithelium. An in-vivo study using flow cytometry on the hamster cheek pouch epithelium.

The partially synchronized cell system of the hamster cheek pouch epithelium shows a characteristic diurnal rhythm of cell proliferation. Bolus injections of methotrexate (Mtx) in both lethal (10 g/m2) and non-lethal (2 g/m2) doses were found to inhibit cell-cycle progression primarily by impairing the G1/S transition. The results were obtained by flow cytometric DNA analysis. The inhibitory effect of Mtx manifested itself as a relative decrease of the S fraction (drug-effector phase), and was found to be dependent both on the dose and on the time of the day it was given. A bolus injection of Mtx was given either at 1200 hr (when a minimal number of cells are in S phase) or at 0200 hr (when a maximum number of cells are in S phase). The greatest cumulative decrease in S fraction was seen when the injection was given at 1200 hr. The time between injection and the effect (seen as a decrease in S fraction) was independent of the time of the Mtx injection, but seemed instead to be related to the natural diurnal period of increasing flux from G1 to S phase (at the onset of the dark period). The main effect (the relative decrease in S fraction) was repeated during the following 24-hr period, pointing to a protracted effect of Mtx on G1 cells. G1 cells affected by the initial high Mtx plasma concentration seem to be responsible for the reduced influx into S phase in both the first and second 24-hr period. In earlier toxicological studies, the survival rate of hamsters was dependent on the time of injection and was highest after injection at 1200 hr. Thus maximum cytokinetic effect on epithelial cells was found at the time of the day when there was a minimum lethal effect on the animal.

Animals↗
PubMed1984

Effect of methotrexate on cells in a keratinized epithelium with an active thymidine salvage pathway assessed by autoradiography.

In the partially synchronized cell system of the hamster cheek pouch epithelium, the inhibitory effect of a bolus injection of methotrexate (Mtx) (2 g/m2, injected at 1200 hr) was analysed by means of both autoradiography and flow cytometry (FCM) in a 21-hr experiment. For autoradiography [3H]TdR and [3H]UdR were used as tracers for salvage and de novo pathways of thymidylate (TMP) synthesis, respectively. For FCM no tracers were injected. The autoradiographic studies demonstrated an active TdR salvage pathway for DNA synthesis, not affected by the impaired de novo TMP synthesis. The blocked de novo TMP synthesis was partially released 7 hr after Mtx injection, but it had not totally recovered at the end of the experiment. The decrease in the fraction of S-phase cells detected about 10 hr after Mtx injection by autoradiographic labelling with [3H]TdR and by FCM was found to be caused by a decrease in the number of cells entering S phase. However, Mtx did not influence the salvage TMP synthesis rate of cells entering S phase.

Animals↗
PubMed1984

Moclobemide and clomipramine in the treatment of depression. A randomized clinical trial.

Moclobemide (Ro 11-1163), a benzamide derivative, is a MAO-inhibitor which selectively and reversibly inhibits monoamine oxidase type A. Thirty-eight patients with episodic, chronic and atypical depressive disorder (DSM-III) were equally randomized to 6 weeks' treatment with either three daily doses of 100 mg moclobemide or 50 mg clomipramine. Both treatment groups improved with time as assessed weekly by the Hamilton Depression Scale and the Clinician's Overall Assessment of Depression State, and there was no interaction between treatment and time. Anticholinergic complaints, tremor and dizziness occurred more frequently on clomipramine, and they were longer lasting and more severe. Because of its low toxicity, good tolerance, its selectivity and reversibility moclobemide may be a better alternative than the older monoamine oxidase inhibitors.

Adult↗
PubMed1984

Human T-cell leukemia virus in cutaneous T-cell lymphoma in Denmark. A possible association of HTLV and aneuploidy.

Cutaneous T-cell lymphomas (CTCL) are neoplasias of mature T-cells and comprise Sezary syndrome, mycosis fungoides and some cases of lymphomatoid papulosis. Clinically this group of disorders differ from the more aggressive neoplasias of mature T-cells known as adult T-cell leukemia/lymphoma and T-cell lymphosarcoma leukemia which are associated with human T-cell leukemia virus (HTLV). We have found that of 68 patients from Denmark with CTCL ten were positive for HTLV antibodies and that the neoplastic T-cells from skin specimens in seven of eight HTLV-antibody positive patients studied by DNA flow cytometry exhibit DNA aneuploidy. Either one or two hyperdiploid cell clones were present. Aneuploidy was found in two patients with histologically verified mycosis fungoides, in four patients with histological non-diagnostic mycosis fungoides, and in one patient with lymphomatoid papulosis. The present data indicate that further seroepidemiologic survey studies of cutaneous T-cell lymphomas should include the early histological non-diagnostic stages, especially when aneuploidy is present.

Adult↗
PubMed1983

DNA ploidy-characteristics of human malignant melanoma analysed by flow cytometry and compared with histology and clinical course.

Flow cytometric analysis of nuclear DNA content is valuable for indicating ploidy- and proliferation abnormalities in surgically removed human malignant melanomas. In 35 primary cutaneous melanomas, 20 metastases of melanoma in skin and lymph nodes, and 16 nevi the DNA distribution was analyzed by flow cytometry and compared with a variety of histological parameters and the subsequent clinical course. Heteroploid DNA distributions with increased polyploid or aneuploid fractions were found in 26 primary melanomas (74%), 14 metastases (70%), and 4 nevi (25%) indicating tumor clones with an abnormal nuclear DNA content. Three or more cell clones in a single biopsy was found in 10 primary melanomas, 2 metastases, and 1 nevus. The frequency of heteroploidy was significantly higher in primary and secondary melanomas than in nevi (p less than 0.001) and was correlated significantly with a high mitotic activity (p less than 0.002), marked nuclear pleomorphism (p less than 0.01), large nucleoli (p less than 0.01) and a thickness of the primary melanoma of more than 2.25 mm (p less than 0.02). Such histologic findings in malignant melanomas have been shown previously to be correlated with a bad prognosis. No significant correlation was found between heteroploidy and the histologic type of melanoma or the level of invasion. A 2-year clinical follow-up showed that more patients died from melanoma if the DNA distribution in the primary or secondary melanoma was heteroploid (6/26; 23% and 8/13; 62% respectively) than if it was diploid (0/9; 0% and 2/5; 40% respectively). However, the differences were not statistically significant. It is concluded that heteroploidy 1) is not an absolute criterion of malignancy, 2) is significantly correlated with histologic features indicating marked cellular anaplasia, and 3) is apparently correlated with a bad prognosis.

Adolescent↗
PubMed1983

Dexamethasone suppression test and TRH test in endogenous depression.

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.

Adolescent↗