Search PubMed⌕ Search

Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 109 records · Page 6Linked to original sources
PubMed1997

A phase 1 study to address the safety and efficacy of granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in active rheumatoid arthritis.

OBJECTIVE: To examine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) alone for the mobilization of peripheral blood progenitor cells in patients with resistant active rheumatoid arthritis (RA). METHODS: Five patients with resistant active RA were studied. A dose of 5 microg/kg of G-CSF (Filgrastim) was given subcutaneously each day for 5 days, and the number of stem cells mobilized into the peripheral blood was assessed by daily CD34 counts. RA disease activity was assessed by standard clinical methods. RESULTS: The absolute numbers of peripheral blood CD34+ cells peaked on day 4, with a mean value of 0.025 x 10(9)/liter (range 0.013-0.048 x 10(9)/liter). There was no significant change in disease activity during the study or in the month following therapy. CONCLUSION: Using G-CSF alone, CD34+ progenitor peripheral blood cells were mobilized in numbers suitable for leukopheresis. G-CSF therapy was well-tolerated in patients with active RA, and was not associated with a flare during treatment or in the month following treatment.

Adult↗
PubMed1997

Aspects of calcium transport by the ovine placenta: studies based on the interplacentomal region of the chorion.

An in vitro technique for the measurement of calcium uptake into the maternal-facing fetal chorionic membrane (apical trophoblast) was used to study the relationship between calcium uptake and stage of pregnancy in the sheep. The effects on calcium uptake of varying calcium concentration and temperature of the incubation medium, of adding calcium channel blockers or heavy metals (lanthanum and nickel) or calcium ionophore/agonist were also studied. The data indicate a saturable calcium uptake process, plateauing after 15 min incubation. This uptake remained constant throughout the last third of gestation until a significant fall in uptake was noted during the final week prior to parturition. This uptake was not due to extracellular cellular diffusion since there was no significant uptake of tritiated inulin over the same period in each case. Calcium uptake in this system was also shown to be a temperature dependent process which was abolished at temperatures of 0-4 degrees C. A decrease in calcium concentration to 0.12 mM in the incubation medium also caused a corresponding decrease in calcium uptake to 21 per cent of control (1.2 mM). The addition of the heavy metals lanthanum and nickel also significantly reduced calcium uptake as did the calcium channel blockers verapamil, metoprolol and diltiazem. The calcium channel ionophore A23187 increased calcium uptake into the material facing chorion. Although the interplacentomal chorion may not be representative of the whole of the placental unit, it clearly contains a specific calcium uptake process under local physiological control. The blocking of calcium uptake by the specific I-type calcium channel blocker verapamil may indicate the presence of I-type channels of unusually low sensitivity since the concentration needed to block them was much higher than would be required for excitable I-type channels in isolated cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Quantitative analysis throughout pregnancy of intraepithelial large granular and non-granular lymphocyte distributions in the synepitheliochorial placenta of the cow.

Intraepithelial lymphocytes are a constant feature of ruminant uterine epithelium. Light microscope quantitation on semithin sections of resin embedded perfused material from pregnant and non-pregnant cows shows that although the proportion of large granular lymphocytes to non-granular lymphocytes in interplacentomal areas increases during pregnancy, the total number of lymphocytes in these areas remains at a similar level. However all types of lymphocytes are eliminated from the caruncular uterine epithelium of the cow by 28 days of pregnancy at the initiation of placentomal development. Despite the subsequent enormous growth in area of this region during pregnancy, no lymphocytes are found in the bovine placentomal cellular uterine epithelium. This pattern is similar to that in the ewe and goat although in these species the placentomal uterine epithelium is modified to maternofetal hybrid syncytial plaques. However, in the deer, a similar cellular placentomal epithelium has numerous intraepithelial lymphocytes and large granular lymphocytes are closely associated with fetomaternal hybrid trinucleate cells formed by binucleate cell migration throughout pregnancy. Cow interplacentomal large granular lymphocytes and trinucleate cells show similar apposition but the formation and fate of cow placentomal trinucleate cells does not involve lymphocytes. Since the caruncular (placentomal) area is 10-20 times that of the intercaruncular this suggests a very different function for intraepithelial lymphocytes in the deer compared with the other ruminant species.

Animals↗
PubMed1997

Does waiting time affect the outcome of larynx cancer treated by radiotherapy?

AIM: To determine the impact of waiting for radiotherapy on local control in early larynx cancer treated by radiotherapy alone. METHODS: Records of patients with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres. Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2) time from presentation to radiation department to start of radiotherapy and (3) the minimum of (1) and (2). Time to relapse was the major end point. RESULTS: There were 581 patients with a median follow-up of 6.8 years. Stage distribution was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18. Median times from biopsy, presentation and minimum time to treatment were 24, 16 and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31 days. The median dose was 61 Gy in a median of 30 fractions over a median 46 days. Local recurrence occurred in 126 patients. The actuarial recurrence free rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant predictors of relapse were higher T stage, longer treatment duration and increasing field area. Waiting time was not significantly associated with local relapse. CONCLUSION: This study did not show longer waiting time to be a significant predictor of relapse in early larynx cancer. Other end-points which are relevant, such as quality of life, have not been examined. Longer treatment times were significantly associated with relapse.

Adult↗
PubMed1997

Deleterious effects of prostaglandin E2 in oesophageal carcinogenesis.

Oesophageal carcinoma is a devastating disease with a poor prognosis. This hypothesis shows how prostaglandin E2 exerts carcinogenic effects in the oesophagus. The contribution of prostaglandin E2 is related to other factors that predispose to oesophageal carcinoma. The implication of the hypothesis is that nonsteroidal anti-inflammatory drugs such as aspirin may be useful in the prevention of oesophageal carcinoma.

Animals↗
PubMed1997

The use of SCID mice for the growth of retinoblastoma cell lines and for the establishment of xenografts from primary tumours.

We investigated the possibility of growing primary retinoblastoma tumour tissue in SCID mice. In preliminary experiments with the WERI retinoblastoma cell line injected subcutaneously in SCID mice, tumours arose at only 25% of the inoculation sites. After mixing these cells with a reconstituted basement membrane extracellular matrix (Matrigel) prior to inoculation, tumours arose at 100% of inoculated sites. When primary retinoblastoma cells were injected subcutaneously into SCID mice in the presence of Matrigel, tumours arose in 5/8 cases. On average, the latency period was 4 months before the tumours were palpable. Histopathological examination of the tumours showed that they resembled surgically resected human retinoblastomas and one of the tumours formed pseudo-rosettes which is a characteristic of these tumours. Unfortunately, when these xenografted tumours were introduced into tissue culture, it was not possible to establish cell lines directly and the cultures were soon overgrown by mouse cells which could clearly be shown to be infiltrating the tumour. The ability to grow retinoblastoma cell lines and primary tissue subcutaneously in SCID mice offers a convenient model system to study the genetics of tumorigenesis in this tumour type and possibly an opportunity to study the role of chemotherapy in the treatment and progression of the disease.

Animals↗
PubMed1997

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy.

The increasing interest in 5-fluorouracil (5-FU) modulation and the development of new antifolates has focused attention in recent studies on the expression of the target enzyme thymidylate synthase (TS) as a determinant of drug sensitivity and resistance. Resistance to TS-directed drugs has been shown to occur in vitro and in vivo with increased expression of the enzyme (determined by enzymatic assays as well as protein and gene expression assays). Several studies have evaluated the role of TS as a prognostic indicator of clinical response to chemotherapy containing TS-directed drugs. We have used a polyclonal antibody to recombinant human TS to establish a silver-enhanced immunogold staining method to localize TS in human tumours. Human tumour cell lines with acquired resistance to TS inhibitors owing to increased levels of TS were used to confirm the specificity of immunostaining. Stained sections were evaluated by image analysis. Immunostaining in tumour sections was greatly reduced (>80%) by preabsorption of the antiserum with recombinant TS. The method was used to determine the extent of TS immunostaining in 134 primary human colorectal tumours. The results were then compared with the clinical outcome and response to chemotherapy for the treatment of subsequent metastatic disease. A wide range (approximately 100-fold) of TS immunostaining was observed in these primary tumour sections. Normal mucosal tissue levels were 5-10 times lower than those observed in the adjacent tumour tissue. The values for TS immunostaining did not correlate with clinical endpoints, such as time from diagnosis to relapse, response to chemotherapy for disseminated disease, nor with Dukes' staging. This lack of correlation may be because this group of patients was selected on the basis of their need for palliative chemotherapy and did not include patients who were cured of their disease. Also, primary tumour TS expression may not give a good indication of the TS expression in metastatic lesions. The prognostic significance of TS protein expression in primary and metastatic lesions requires further evaluation.

Aged↗
PubMed1997

Allogeneic peripheral blood stem cell transplantation for haematological malignancies--an analysis of kinetics of engraftment and GVHD risk.

We have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLA-matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl-prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+ cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14 (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg had significantly accelerated neutrophil and platelet engraftment and this number of CD34+ cells would appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out of 36 evaluable patients, there was no significant difference between the standard- and poor-risk groups in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further evidence supporting the potential of PBSC to replace bone marrow as the major source of haemopoietic cells for allogeneic transplantation.

Adolescent↗
PubMed1997

Management of seminoma of the testis: recommendations based on treatment results.

BACKGROUND: The results of management of seminoma of the testis at the Department of Radiation Oncology St Vincent's Hospital, Sydney were evaluated retrospectively to: (i) establish that outcomes were in keeping with published results from centres in Australia and overseas; (ii) assess the impact of chemotherapy on management; and (iii) to determine 'best practice' management protocols based on our results and a review of the relevant literature. METHODS: (i) Assessment of treatment results for stage I and II seminoma of the testis treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's Hospital between 1979 and 1993; (ii) literature review of published data from Australian and overseas centres on the management of seminoma of the testis, and in particular the use of surveillance or chemotherapy either alone, at time of relapse or combined with radiotherapy; and (iii) development of recommendations for use as management protocols in our department. RESULTS: Our data and a review of the literature suggest that post-orchidectomy radiotherapy with chemotherapy for relapse in stage I and IIA disease results in long-term cure rates approaching 100%. Treatment with chemotherapy either routinely or selectively or using a surveillance policy is unlikely to show any improvement in outcome and may be less cost-effective and/or produce increased morbidity and the risk of secondary leukaemia. For stage IIB disease (5-10 cm) the use of initial combination chemotherapy with or without subsequent radiotherapy did not appear to give better outcomes than initial radical radiotherapy alone, reserving chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease (> 10 cm), the use of initial chemotherapy plus consolidation radiotherapy appeared to be an appropriate treatment. CONCLUSIONS: Management protocols for seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation Oncology currently are (i) stage I, IIA and IIB (5-10 cm): post-orchidectomy radiotherapy alone with chemotherapy or further radiotherapy for relapse; and (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed by radiotherapy to sites of initial disease involvement.

Adolescent↗
PubMed1997

Aspirin for the second hundred years: new uses for an old drug.

The history of aspirin can be traced back to ancient Egypt where extract of willow bark was used to treat inflammation. The active component of the extract was identified as the glucoside of salicylic alcohol. The severe gastric side effects associated with the use of sodium salicylate prompted the synthesis of the o-acetyl-derivative as a possible pro-drug. In fact, acetylsalicylic acid was antiinflammatory, analgesic and antipyretic but also ulcerogenic to the stomach. Acetylsalicylic acid was synthesized one hundred years ago, and was mass-produced under the commercial name of 'Aspirin' (Dreser, 1899) by the German company Bayer for the treatment of fever and rheumatism.

Alzheimer Disease↗
PubMed1997

Cryptosporidium parvum infection of human intestinal epithelial cells induces the polarized secretion of C-X-C chemokines.

Cryptosporidium parvum infects intestinal epithelial cells and does not invade deeper layers of the intestinal mucosa. Nonetheless, an inflammatory cell infiltrate that consists of neutrophils and mononuclear cells is often present in the lamina propria, which underlies the epithelium. This study investigated the host epithelial cell response to C. parvum by assessing in vitro and in vivo the expression and production of proinflammatory cytokines by intestinal epithelial cells after infection. The human colon epithelial cell lines HCT-8 and Caco-2 and human intestinal xenografts in SCID mice were infected with C. parvum. The expression and secretion of the C-X-C chemokines interleukin-8 (IL-8) and GROalpha were determined by reverse transcription-PCR analysis and enzyme-linked immunosorbent assay. Our results demonstrate that upregulated expression and secretion of IL-8 and GROalpha after C. parvum infection of intestinal epithelial cells first occurred 16 to 24 h after infection and increased over the ensuing 1 to 2 days. The kinetics of C-X-C chemokine production by C. parvum-infected epithelial cells contrast markedly with the rapid but transient expression of C-X-C chemokines by epithelial cells infected with invasive enteric bacteria. C-X-C chemokine secretion in C. parvum-infected epithelial cells occurred predominantly from the basolateral surface in polarized monolayers of Caco-2 cells grown in Transwell cultures, whereas cell lysis occurred at the apical surface. The basolateral secretion of IL-8 and GROalpha from C. parvum-infected epithelial cells suggests that C-X-C chemokines produced by those cells contribute to the mucosal inflammatory cell infiltrate in the underlying intestinal mucosa.

Animals↗
PubMed1997

Serum IgD levels in children under investigation for and with defined immunodeficiency.

BACKGROUND: The function and regulation of circulating IgD are unclear. Serum IgD levels were increased in a wide range of immunological diseases but these associations did not give a clue to the regulation of serum IgD production. METHODS: Serum IgD levels in 131 children with various non-HIV-related immunodeficiency diseases were investigated to examine their relationship with immunoglobulin or antibody production and activation of the immune system. Data from a group of 109 nonimmunodeficient children were also available for comparison. RESULTS: There was a bimodal distribution of serum IgD levels. In 87 patients IgD levels fell below the limit of detection of 5 IU/ml, while the remainder showed an approximately normal distribution skewed to the right after log transformation. The proportion of children with undetectable IgD levels (< 5 IU/ml) was significantly increased in immunodeficient children (87/131 vs. 28/109, p < 0.001). No difference in the occurrence of immunoglobulin or antibody deficiencies was demonstrated in immunodeficient children with detectable and nondetectable IgD levels. There was a positive correlation of serum IgD with age, serum IgA and IgE, white blood count and CD4+CD25+ lymphocytes but not with other immunoglobulin isotypes or immune activation markers. CONCLUSION: Determination of serum IgD levels did not seem to be of particular clinical benefit in the investigation of HIV-negative immunodeficient children and serum IgD levels were not associated with the general picture of immune activation. Observed distribution patterns and associations may have implications for the regulation of serum IgD production.

Age Factors↗
PubMed1997

Changing trends in the incidence of non-Hodgkin's lymphoma in Europe. Biomed Study Group.

Non-Hodgkin's lymphoma (NHL) is not a uniform disease entity, and in order to investigate the reported changes in incidence we have set up a study in seven population-based cancer registries in Europe. The study is designed to look at changes in the incidence of total NHL and disease subgroups using standard definitions and methodology. The registries are based in Leeds, Dijon, Kuopio, Odense, Florence, Eindhoven, and Ragussa. The classification system we have used is based on the REAL classification and has utility for epidemiological studies. We have used it to convert data sets which have utilized both local cases and the ICD-O classification. In order to improve data reproducibility, CLL/LL, myeloma/MGUS, lymphoblastic disease, and Hodgkin's disease have been excluded because of the difficulty in defining incident cases accurately. The preliminary results of this study show that there is still an upward trend in incidence rate and that in Yorkshire this is 3% per annum in total NHL. The subgroups which are increasing are extranodal and nodal peripheral T-cell lymphoma. Similar increases in incidence have been reported for the other registries. We conclude that there is a continued upward trend in incidence of NHL, the causes of which are uncertain.

Europe↗