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Biomedical subjects

G Lipkin

Publications and source records attributed to G Lipkin.

At least 19 recordsLinked to original sources
PubMed2004

Improving prescribing using a rule based prescribing system.

OBJECTIVE: To test the hypothesis that the prescribing behaviour of doctors would improve after having experience with a computerised rule based prescribing system. DESIGN: A prospective observational study of changes in prescribing habits resulting from the use of a computerised prescribing system in (1) a cohort of experienced users compared with a new cohort, and (2) a single cohort at the beginning and after 3 weeks of computer aided prescribing. SETTING: 64 bed renal unit in a teaching hospital. INTERVENTION: Routine use of a computerised prescribing system by doctors and nurses on a renal unit from 1 July to 31 August 2001. MAIN OUTCOME MEASURES: Number of warning messages generated by the system; proportion of warning messages overridden; comparison between doctors of different grades; comparison by doctors' familiarity with the system. RESULTS: A total of 51,612 records relating to 5995 prescriptions made by 103 users, of whom 42 were doctors, were analysed. The prescriptions generated 15,853 messages, of which 6592 were warning messages indicating prescribing errors or problems. Doctors new to the system generated fewer warning messages after using the system for 3 weeks (0.81 warning messages per prescription v 0.42 after 3 weeks, p = 0.03). Doctors with more experience of the system were less likely to generate a warning message (Spearman's rho = -0.90, p = 0.04) but were more likely to disregard one (Spearman's rho = -1, p<0.01). Senior doctors were more likely than junior doctors to ignore a warning message. CONCLUSIONS: Doctors are influenced by the experience of using a computerised prescribing system. When judged by the number of warning messages generated per prescription, their prescribing improves with time and number of prescriptions written. Consultants and registrars are more likely to use their clinical judgement to override warning messages regarding prescribed drugs.

Contraindications↗
PubMed2002

Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.

The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.

Disease-Free Survival↗
PubMed1989

Castleman's tumor and erosive lichen planus: coincidence or association?Report of a case.

The rare association of severe erosive lichen planus and Castleman's tumor is presented. Castleman's tumor, or giant lymph node hyperplasia, is a benign neoplasm resembling thymic tumors and is associated with several immunologic abnormalities. Lichen planus also is associated with immunologic defects. One hypothesis linking these two diseases is that lymphocytes may become sensitized to tumor antigens on the Castleman's tumor and attack cross-reacting structures in the skin and other stratified squamous mucosae to produce the clinical picture of lichen planus.

Adult↗
PubMed1987

Contact-inhibitory factor induces alterations in the distribution and content of specific cytoskeletal elements in an established line of rat hepatic tumor cells.

Established 72/22 rat hepatic epithelial tumor cells, which possess intracellular aggregates of intermediate-sized filaments resembling Mallory-body-like inclusions, were used to assess changes in tumor cell growth and morphology associated with exposure to contact-inhibitory factor (CIF). CIF reduced 72/22 proliferative rate, increased mean population doubling time by 42%, lowered culture saturation densities to 34-50% of control values and inhibited formation of dense foci. These proliferative changes were due to an apparent prolongation of the G1 phase of the cell cycle during the period of CIF exposure. CIF concomitantly induced a marked increase (by 70%) in cell spreading and loss of both the usual tight (epithelioid) cell juxtaposition and typical ordered colony structure characteristic of untreated populations. However, CIF exposure failed to achieve complete cytoarchitectural "normalization" in 72/22 cells (i.e., dispersal of the Mallory-body-like aggregate of intermediate filaments and restoration of a more typical hepatocytic phenotype). Most obvious was a reduction in the integrity of the peripheral band of microfilaments (a structure involved in the maintenance of epithelial cell shape) and a decrease in the content of desmoplakin (a protein component of desmosomal plaques). Changes in these major structural elements appear to be critical events in development of the pleomorphic phenotype and reduced substratum adhesiveness observed during treatment. CIF-related fragmentation of peripheral band structures was not reflected in changes in either the total cellular or cytoskeletal-associated actin contents. The morphologic changes observed under conditions of CIF exposure closely paralleled induced decreases in the cellular content of the actin-associated membrane skeleton protein p35. These data collectively suggest that CIF may act to alter the composition of the cortical skeleton in cultured liver tumor cells.

Animals↗
PubMed1986

Susceptibility to NK cell lysis is abolished in tumor cells by a factor which restores their contact inhibited growth.

It is well recognized that physical contact between natural killer (NK) cells and tumor targets is necessary for cell lysis. Therefore, any modulation of the tumor cell surface that alters intercellular contact could affect NK cell cytotoxicity. To examine this hypothesis, a contact inhibitory factor (CIF), which had been shown to restore contact inhibition of growth to several malignant cell lines was tested for its ability to render such cells immune to recognition by NK cells. When three NK-sensitive melanoma and two NK-sensitive colon carcinoma targets were cultured with CIF, they did not only change morphologically, but also showed a 70% to 95% reduction in their sensitivity to lysis by NK cells. In addition, K562 cells, which grow in suspension and do not permit a morphologic evaluation of the CIF effect, also became resistant to lysis by NK cells after culture with CIF. CIF did not reduce the viability nor the cytotoxicity of NK cells. CIF did not contain interferon nor did the CIF-treated targets induce the production of interferon during the cytotoxicity assay. It is concluded that restoration of contact inhibition of growth and resistance to NK cell lysis are cell surface phenomena that may run in parallel.

Cell Line↗
PubMed1986

Contact inhibitory factor also restores anchorage and serum dependence to hamster melanoma cells.

Conditioned medium (CM) from confluent cultures of the contact-inhibited hamster melanocytic cell line, FF, contains a biologic activity, contact inhibitory factor (CIF), which reversibly restores density-dependent growth to melanoma cells. When a hydrophobic affinity-concentrated extract of CIF-containing CM was incorporated in agarose at a concentration of 1000 micrograms protein/ml, it restored anchorage-dependent growth to RPMI 1846 hamster melanoma cells. Colony-forming efficiency in CIF-treated wells decreased to 5% from levels of 51.5% in controls prepared with regular growth medium. In addition, CIF-containing CM restored serum-dependent growth to RPMI 1846 cells, markedly restricting proliferation in 1% calf serum-containing medium. Control cultures containing 1% calf serum and either complete growth medium or CM from the non-contact-inhibited hamster melanoma line itself, supported proliferation of RPMI 1846 cells to levels 3.9 X and 3.7 X that of CIF-treated cultures, respectively. CIF is the first factor derived from contact-inhibited mammalian cell cultures that has been shown to restore density-, anchorage-, and serum-dependent growth to malignant melanoma cells.

Animals↗
PubMed1986

Liposome-entrapped contact inhibitory factor: transfer of capacity for density-dependent growth to melanoma cells.

Contact inhibitory factor (CIF) is a growth inhibitor obtained from conditioned culture medium of a contact-inhibited line of hamster melanocytic cells, which reversibly restores density-, anchorage-, and serum-dependent growth to melanoma cells. The usefulness of liposomes as carriers for CIF was investigated in vitro. The stability of liposomes prepared both with and without CIF was demonstrated by measuring the rate of efflux of a K2CrO4 marker. Anionic multilamellar lipid vesicles (7 phosphatidylcholine:2 dicetyl phosphate:1 cholesterol) prepared with CIF-containing material and separated from unentrapped CIF by gel filtration on Sepharose 2B, showed retarded leakage of a K2CrO4 marker (half-efflux at 77 h) when compared with identical liposomes lacking CIF (half-efflux at 40 h). When added to subconfluent cultures of hamster melanoma cells, liposome-entrapped CIF restored contact-inhibited growth. Compared with aqueous solutions of CIF, liposome-CIF effects were characterized by longer latency and more sustained duration. The ability of CIF-bearing liposomes to effectively restore density-dependent growth in vitro should facilitate in vivo studies of the effects of this potent growth inhibitor on melanoma and other neoplasms.

Animals↗
PubMed1985

Vitiligo-related pigment cell differentiation antigens are expressed on malignant melanoma cells following phenotypic reversion induced by contact inhibitory factor.

Most vitiligo sera contain antibodies to surface antigens on pigmented human melanocytes but not to human or mouse amelanotic melanoma cells. A density-dependent line of hamster amelanotic melanocytic cells (FF) produces a diffusible factor (CIF) which restores contact inhibition of growth as well as several other normal phenotypic characteristics to hamster, murine, and human melanoma cells. The ability of CIF to induce the expression of a phenotypic characteristic of pigmented human melanocytic cells, i.e., the vitiligo-related surface antigens, on hamster and mouse amelanotic melanoma cells was investigated. Vitiligo and normal sera were reacted with CIF-treated and untreated hamster and mouse amelanotic melanoma cells for both indirect-immunofluorescence assays and ELISA. Immunofluorescence testing showed that about 80% of hamster and mouse melanoma cells had pigment-cell antigens (in the absence of pigmentation) in a granular surface pattern after, but not prior to, CIF-induced morphologic reversion and confluent growth. Less than 5% of the control hamster and mouse melanoma cells expressed such antigens at confluence. These results were confirmed by ELISA. Metabolic-labeling studies with 35S-methionine showed that the vitiligo antigens were synthesized by the CIF-treated melanoma cells. The slowing of melanoma cell proliferation in isoleucine-deficient medium failed to elicit the expression of vitiligo antigens. Since antigen appearance following phenotypic reversion occurred without pigment induction, it is concluded that vitiligo-related surface antigens and pigmentation are distinct aspects of a differentiated function which may be non-coordinately expressed. The expression of pigment-cell differentiation antigens on amelanotic melanoma cells is an additional feature of the pleiotypic trans-species response to CIF.

Animals↗
PubMed1984

Alpha 1-antitrypsin deficiency genes: contributory defect in a subset of psoriatics?

Since proteolytic processes are prominent in psoriasis, sera of forty-five psoriatics were examined for alpha 1-antitrypsin (alpha 1-AT) phenotype and eighteen sera, for alpha 1-AT content and function. Five sera (11.1%) had heterozygous phenotypes (2 MZ and 3 MS), a prevalence of Z and S variants similar to that reported in nonpsoriatic populations. Two of three variants examined for content and function exhibited marked reductions. Since MZ heterozygotes are almost always, and MS phenotypes sometimes, associated with decreased serum alpha 1-AT levels, and since Z and MZ phenotypes are associated with increased hepatic fibrosis or cirrhosis, these variants may be relevant to problems of spontaneous fibrosis or methotrexate-induced hepatotoxicity in psoriasis. alpha 1-AT deficiency may also contribute to guttate flares with infection and to increased O-2 . production by psoriatic sera-stimulated polymorphonuclear leukocytes (PMNs). Although no evidence exists that psoriasis is more prevalent among persons with hypomorphic alpha 1-AT phenotypes, such defects may contribute to severity of inflammation and hyperplasia.

Adolescent↗
PubMed1984

Expression of vitiligo antigen on a revertant line of hamster melanoma cells.

Our laboratory has recently reported that over 80% of patients with common vitiligo have circulating antibodies to cell-surface antigens on normal human melanocytes. The slow growth rate of these cells limits the assays that can be performed for antibody detection. We now have found that the antigens defined by vitiligo sera on melanocytes are also expressed on FF cells, a revertant line of hamster melanoma cells. These antigens can be detected both by indirect immunofluorescence and specific immunoprecipitation assays. The presence of "vitiligo" antigens on hamster FF cells will aid further study of the abnormal immune response in vitiligo.

Animals↗