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Biomedical subjects

P Frost

Publications and source records attributed to P Frost.

At least 145 records · Page 8Linked to original sources

Immunology of metastasis. Can the immune response cope with disseminated tumor?

The application of immunologic methods to the treatment of neoplasia has been a goal of research in tumor immunology. Unfortunately, no clearly defined success for such therapy has been achieved. However, the most recent advances in tumor biology have provided for a more valid conceptual framework upon which to plan further research in this area. The more general awareness of tumor progression and heterogeneity, particularly in the context of tumor metastasis, while imposing a sense of gloom regarding all therapeutic modalities, shifted immunologic thinking toward the development of nonspecific modalities. We herein propose that this 'shift' may be premature and that immunotherapy using cytolygic T cells could still be feasible. Our views are based on newer approaches for selecting immunogenic variants of malignant tumors and a better understanding of the relationship of the immune response to metastases.

Animals↗

The roles of lactose and Clostridium difficile in the pathogenesis of enteral feeding associated diarrhoea.

This study investigated the influence of the disaccharide lactose on the incidence of clinically significant enteral feeding associated diarrhoea. In this double blind study both groups each of 25 patients were randomised to receive either a lactose containing diet Clinifeed 400 in 25 patients or a lactose free diet Ensure in 25 patients. Diarrhoea occurred with equal frequency in both treatment groups, even in those patients with symptomatic and biochemical evidence of impaired lactose handling. Although the onset of diarrhoea was significantly associated with antibiotic administration (p<0.01), Cl. difficile was not isolated from the stools of any patient with diarrhoea.

Journal Article↗

A controlled trial of aseptic enteral diet preparation--significant effects on bacterial contamination and nitrogen balance.

This study was performed to evaluate the clinical effectiveness of the 'standard' and aseptic enteral diet preparation techniques and to investigate the relationship between bacterial contamination of diets and symptoms during enteral nutrition. In this controlled study patients were prescribed isonitrogenous polymeric diets prepared using either 'standard' or aseptic techniques, administered by 24 nasogastric infusion. 'Standard' diet preparation resulted in significant bacterial contamination (p<0.01), but this did not increase incidence of diet related symptoms. Use of sterile techniques permitted safe use of large volumes (1.5-2 litre) containers, and this resulted in significantly better nitrogen intake (p<0.05) and balance (p<0.05).

Journal Article↗

Comparison of an elemental and polymeric enteral diet in patients with normal gastrointestinal function.

In a prospective controlled clinical trial, 70 patients with normal gastrointestinal function were randomised to receive either an elemental diet based on Vivonex HN or an isonitrogenous isocalorie polymeric diet based on Clinifeed 400, administered by continuous 24 hour nasogastric infusion. The two groups of patients were well matched for age, sex, diagnosis, prior starvation, duration of feeding, initial nutritional status, and metabolic status. Nitrogen losses were significantly less on the polymeric feed, despite similar intakes. Serum transferrin rose significantly (1.85 +/- 0.2 to 2.30 +/- 0.2 g/l, p less than 0.05) only in the Clinifeed group, but nutritional parameters were otherwise maintained in both groups. The incidence of diarrhoea (Vivonex, 23.5%; Clinifeed, 30.6%) was not significantly different and was attributable to antibiotics in most cases. Hypokalaemia, which occurred in nearly half the patients, was equally distributed in the two groups, but hypophosphataemia occurred more often in the Vivonex group (p less than 0.05). Liver enzyme disturbances were similar in both groups. The present findings, therefore, provide no evidence that chemically defined 'elemental' diets containing free amino acids as their nitrogen source are in any way superior to polymeric diets containing whole protein and fat when administered to patients with normal gastrointestinal function.

Clinical Trials as Topic↗

Transfer of topically applied tetracycline in various vehicles.

Fifty hospitalized dermatology patients participated in a study to evaluate the transfer of topically applied tetracycline hydrochloride-containing fluorescent ointments, creams, lotions, and tinctures from various sites of application. Patients were examined with a Wood's lamp 24 hours after application to determine the sites and areas of transfer. The topically applied medications did not remain confined to sites of initial application. The anatomic sites of initial application determined the pattern of transfer. Certain patterns of transfer were characteristic among groups of patients and for specific patients. The vehicle of the topical preparation greatly influenced the extent and sites of transfer.

Administration, Topical↗

Abrogation of the in vitro generation of the cytotoxic T-cell response to a murine tumor: the role of suppressor cells.

A reproducible in vitro assay for the effect of suppressor T cells on the generation of an in vitro cytotoxic response to a metastatic murine tumor is described. Suppression in this system is maximal. The model uses splenic T cells from DBA/2 mice bearing the MDAY-D2 metastatic tumor as suppressors of the in vitro generation of a cell mediated cytotoxic response by syngeneic tumor-bearer (i.e., primed) peripheral lymph node cells stimulated with mitomycin C-treated MDAY-D2 tumor cells. The effect of the cell mediated cytotoxic response is profound, specific and mediated by splenic T cells. The suppressor T cells appear to impair precursor rather than mature cytotoxic cells. A highly immunogenic variant of MDAY-D2, namely MDWI, does not generate a suppressor response. Suppressor T cells from an MDAY-D2 tumor-bearer cannot suppress the in vitro response to MDWI. This model of potent suppressor T-cell action is highly reproducible and offers an opportunity for the analysis of why some tumors generate an effective cell mediated cytotoxic response which others stimulate dramatic suppressor T-cell response.

Animals↗

Tumor progression in metastasis: an experimental approach using lectin resistant tumor variants.

A novel model of tumor progression in metastatic cancer is described which grew out of attempts to derive stable non-metastatic variants from a highly metastatic mouse tumor called MDAY-D2. The variants were obtained by selection of so-called lectin-resistant (LecR) membrane mutants using toxic concentrations of wheat germ agglutinin (WGA) as the selective agent, after mutagenesis. Cloned WGAR variants almost all appeared to be highly tumorigenic and metastatic, but displayed altered growth properties which were highly suggestive of major cellular phenotypic alterations occurring prior to metastasis. This were confirmed with the discovery that spontaneous visceral metastases always consisted of WGA-sensitive (WGAS) 'revertant' tumor cells. Such revertants also arose at the site of the subcutaneous inoculation and, with time, comprised an increasing proportion of the tumor cells at that location. The WGAS/high metastatic phenotype was stable in vitro or in vivo, implying the WGAR leads to WGAS shift had an underlying genetic basis. Thus, it appeared that the WGAR tumor cells could not metastasize, because of either an intrinsic cellular defect or a host imposed barrier, but that this block could be circumvented through a genetic change in the WGAR tumor cells which was accompanied by reversion of the WGAR phenotype. Non-tumorigenic (tum-) WGAR variants were also obtained, but in these cases the mutagenesis treatment itself appeared responsible for development of the tum- phenotype. The reduced tumorigenicity had an underlying immunological basis, a finding which could be exploited to immunotherapeutically treat established visceral metastases of poorly immunogenic tumors. Throughout these studies, emphasis was placed on the considerable potential of using tumor cell populations having various stable drug-resistant genetic markers to monitor aspects of tumorigenesis, tumor progression, and metastasis.

Animals↗

Reduction of the erythema response to ultraviolet light by nonsteroidal antiinflammatory agents.

The effect of three nonsteroidal antiinflammatory agents (NSAIA) on ultraviolet B (UV-B)-induced erythema was studied in normal human volunteers. Aspirin, indomethacin, and ibuprofen were administered orally 2 h before exposure to UV-B from fluorescent sunlamps and at 4-h intervals for a total of four doses. The minimal dose of light to produce erythema (MED) was determined for each subject with and without drugs. There was a 240% increase in the mean MED when the NSAIA were given. NSAIA, given orally, can increase the threshold for UV-B-induced erythema when administered near the time of irradiation.

Anti-Inflammatory Agents↗

Clinical comparison of alclometasone dipropionate and desonide ointments (0.05%) in the management of psoriasis.

This was a double-blind, randomized, parallel-groups comparison of alclometasone dipropionate and desonide ointments (0.05%) applied twice daily without occlusion for 3 weeks by patients with moderate to severe psoriasis. Data from thirty-three patients in each group showed that both treatments produced rapid amelioration of erythema, induration, and, especially, scaling; substantial improvement was evident after 1 week and continued thereafter. Differences between the groups were not statistically significant, but trends consistently favoured alclometasone. No adverse drug reaction occurred.

Administration, Topical↗

Immunoselection in vitro of a non-metastatic variant from a highly metastatic tumor.

Immunoselection of a non-metastatic variant of the highly metastatic MDAY-D2 tumor of DBA/2 mice was achieved by means of an antiserum directed to the LY6.2 surface marker of MDAY-D2. While the new tumor (MDAY-D2.L61) expresses no detectable LY6.2, other measurable surface markers including H2d, FcR and TAA remain unchanged. The phenotypic behavior of MDAY-D2.L61 is that of a non-metastatic tumor and has remained stable after 1 year of maintenance in vivo and in vitro. Immunoselection can now be used to derive variants with stable phenotypic behavior from heterogeneous parent tumor cell populations.

Animals↗

Generation of highly metastatic tumors in DBA/2 mice. Oncogenicity of a strain tumor cells.

The sequential intraperitoneal injection of five different A strain tumors into DBA/2 mice resulted in the de novo generation of new DBA/2 tumors. These new tumors share many identical characteristics including the expression of surface H2d, FcR, LY6.2 and tumor antigens. All have the same karyotype which differs in number and in the presence of two metacentric chromosomes from the original A strain tumors. Phenotypically, all are vigorously metastatic after intraperitoneal, subcutaneous, intradermal or intravenous injection. None of the original A strain tumors are metastatic in the A strain host. These tumors have thus provided us with a good model for the study of metastasis while raising questions regarding the oncogenicity of tumors.

Animals↗

A phototherapy cabinet for ultraviolet radiation therapy.

A newly designed cabinet can be used for the treatment of psoriasis with fluorescent ultraviolet (UV) lamps. the new design provides more uniform distribution of UV radiation in both the horizontal and vertical axes, and several safety features have been added. The distribution and uniformity of UV output in this and in a previously described cabinet are compared. The UV output at the vertical center of the older UV light cabinet was six times greater than that at either the top or bottom, while the design of the present cabinet provides uniform UV radiation except for a slight increase at head height and at the level of the lower legs compared with the middle third of the cabinet. The variation in output of the older cabinet may, in part, explain the commonly encountered difficulty in the phototherapy of psoriasis of the scalp and lower extremities.

Phototherapy↗