PubMed Health⌕ Search

Biomedical subjects

J Ramsay

Publications and source records attributed to J Ramsay.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immunohistochemical and hysteroscopic assessment of postmenopausal women with uterine bleeding whilst taking Tibolone.

The gonadomimetic steroid Tibolone, is currently widely used for the treatment of menopausal symptoms. Up to 20% of women have been reported to have episodes of bleeding whilst on therapy. We investigated 37 cases who experienced bleeding episodes whilst on Tibolone and compared these to six cases who experienced no bleeding whilst on therapy and who underwent similar investigations in the course of a clinical study. All women underwent a diagnostic hysteroscopy and an endometrial biopsy, under a local anaesthetic. The endometrium was assessed by histology and with immunohistochemical markers for cellular proliferation (Ki67, PCNA), Heat Shock Protein 27 (HSP27) and bcl-2. There were 17 women with intracavitary lesions on hysteroscopy (including one in the control group), 10 with polyps, five with fibroids, two with congenital uterine anomalies. Histological diagnosis was not obtained in 16 cases. The high incidence of uterine polyps in the group who bled on Tibolone suggests an etiologic relation. The staining pattern with HSP27 demonstrated an oestrogenic effect. There were no differences in the bcl-2 immunoreactivity between those who bled and those who did not bleed on treatment which suggests absence of a link. Similarly, there were no differences in the expression of the proliferation markers. We conclude that episodes of bleeding in patients receiving Tibolone for hormone replacement therapy, whilst warranting investigation, should not cause undue concern.

Adult↗
PubMed1996

The National Mental Health strategy.

The National Mental Health Strategy aims to assist people with a mental illness to have access to improved services and support, with community based services as the option of first choice. The Commonwealth, State and Territory governments are working together with consumers, professionals and other key parties so that mental health services are 'mainstreamed' within the general health system. This will also ensure that permanent improvements are made in the way Australia responds to the needs of people with mental disorders. Access to an integrated network of different services, including those outside the health system, is an essential component of the strategy. Ensuring that residents of rural and remote areas have adequate access to mental health services is a priority of the Strategy.

Australia↗
PubMed1995

Normal tissue radiosensitivity in breast cancer patients.

PURPOSE: To investigate whether in vitro radiosensitivity of lymphocytes derived from a blood sample will predict late effects from radiotherapy in breast cancer patients. METHODS AND MATERIALS: Blood samples were collected from consenting patients who had received radiotherapy for breast cancer. Lymphocytes were extracted and transformed by the Epstein-Barr virus. The resulting lymphoblastoid cell lines (LCLs) were assessed for in vitro radiosensitivity using a tetrazolium-based colorimetric assay (MTT). Survival curves were generated using doses of 0.5 to 2 Gy. For each analysis an LCL derived from an individual with the radiosensitive condition ataxia-telangiectasia (AT) was run as control. Some patients also consented to give skin biopsies from which fibroblast cultures were derived. Clonogenic assays were performed to generate survival curves using doses in the range of 0.5 to 4 Gy. Comparison was made with the data obtained from LCLs. Late effects of radiotherapy were assessed using the Radiation Therapy Oncology Group (RTOG) scoring scheme and compared with the in vitro radiosensitivity data. RESULTS: LCLs from 56 breast cancer patients were assessed for in vitro radiosensitivity. Surviving fraction to 2 Gy (SF2) generated from survival curves ranged from 0.04-0.35 with coefficient of variation for the whole group of 41%. None of the LCLs equalled the sensitivity of the AT line, but 16% showed equal or greater sensitivity to a line derived from an AT heterozygote. Comparison of LCL and fibroblast radiosensitivity showed reasonable correlation for 12 paired samples (r = 0.64). The majority of patients showed no or minimal effects after radiotherapy (Grade 0, 1 effects) but seven developed a Grade 2 reaction and four a Grade 3 or 4 reaction. Patients with a Grade 2-4 reaction were found to be more sensitive in vitro than those with a Grade 0-1 reaction (p < 0.02). CONCLUSIONS: The use of the MTT assay to assess LCL radiosensitivity has demonstrated considerable heterogeneity amongst the breast cancer population. The presence of a proportion of patients showing in vitro sensitivity but normal clinical response to radiotherapy would limit the usefulness of the assay for predictive purposes.

Breast Neoplasms↗
PubMed1995

The curative treatment by radiotherapy alone of stage I non-small cell carcinoma of the lung.

This review was initiated to assess the outcome of treatment with radical radiotherapy with curative intent for patients diagnosed as having stage I non-small cell lung cancer. The study involved a retrospective review of 347 patients with T1 and T2N0M0 tumors treated at the Queensland Radium Institute during the period 1985 to 1992. The main reasons for not proceeding to surgery included poor performance status, old age, or refusal to submit to surgery. The median age for the group was 70 years, with the range being 34 to 90 years. Patients in this group were all treated by a standard technique involving external-beam radiotherapy to 50 Gy, minimum tumor dose, in 20 fractions over 4 weeks. The overall survival rate was 27% at 5 years with a median survival of 27.9 months. The 5-year recurrence-free survival was 23% with the median being 19.5 months. There was a strong correlation of survival to tumor size with 5-year survival rates being 32% and 21% for T1 and T2 tumors, respectively. Multivariate analysis found only T stage to be associated with overall survival (p < 0.01). In addition, the analysis showed that age younger than 70 years was a prognostic factor that approached statistical significance at the p < 0.05 level of significance. We conclude from this large series of patients with stage I non-small cell lung cancer that radical radiotherapy with curative intent may be a viable alternative to surgery in those patients who either refuse surgery or are judged to be unfit for operation.

Adult↗
PubMed1994

Identification of a potentially radiosensitive subgroup among patients with breast cancer.

BACKGROUND: The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility. PURPOSE: Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity. METHODS: Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of gamma radiation, and the percentages of cells in G1 and G2 phases were determined at 18 and 24 hours after irradiation by fluorescence-activated cell sorter analysis. Postirradiation delay in G2 phase was determined by calculating the percentage of cells in G2 and by using the ratio G2/G1. RESULTS: When we determined the percentage of cells in G2 phase at 18 hours after irradiation in 108 lymphoblastoid cells from breast cancer patients, we observed an increase of between 3% and 38% in the number of cells in G2 phase in comparison with cells that were not irradiated. Comparison with previous G2-phase arrest data for ataxia-telangiectasia heterozygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category (P < .001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G2/G1 ratio showed that 18% of the breast cancer patients and 8% of the control subjects were in the high range. When G2 arrest was correlated with other prognostic factors, we found that case patients with a greater G2 block were more likely to have had a family history of breast cancer (P < .006) and more aggressive tumors when assessed by number of involved lymph nodes (P < .002) and tumor size (P < .05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G2 arrest. IMPLICATIONS: While the postirradiation increase in G2-phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities important to breast cancer.

Adult↗
PubMed1994

Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat.

From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme.

PURPOSE: Many radiobiologic mechanisms may contribute to the clinical radiation resistance of Glioblastoma Multiforme. One of them is considered to be an unusually low intrinsic radiation sensitivity. This is a collaborative study between three laboratories to evaluate the intrinsic radiation sensitivity of 85 cell lines derived from human malignant gliomas as the major cause of the poor clinical results of radiation treatment to these tumors. METHODS AND MATERIALS: Fifty-one cell lines were early passage. The distribution by histologic type was: 58 glioblastoma, 17 anaplastic astrocytoma, six oligodendroglioma and four astrocytoma grade 2. The intrinsic radiation sensitivity will be expressed by the surviving fraction at 2 Gy (SF2). The SF2 has been determined for single dose irradiation for cell lines on exponential phase, under aerobic conditions, growing on plastic. The patient age, Karnofski Status, histological grade, survival, dose of irradiation for 50 patients are investigated for correlation with SF2 of the corresponding newly established cell lines. RESULTS: The mean SF2 of the 85 cell lines was 0.46 (0.12-0.87). The mean SF2 by histologic type was 0.50, 0.34, 0.54 and 0.38 for glioblastoma, anaplastic astrocytoma, oligodendroglioma and astrocytoma grade 2 cell lines, respectively. No correlation was found between SF2 and the patient age or Karnofski status. The difference in SF2 between the 58 glioblastoma and 17 anaplastic astrocytoma cell lines was significant p = 0.002. The difference in actuarial survival between glioblastoma and anaplastic astrocytoma patients was borderline of significance (p = 0.08). The difference in SF2 of cell lines derived from these two groups of patients was of borderline significance (p = 0.08). The difference in radiation sensitivity for anaplastic astrocytoma and glioblastoma cell lines was clearly reflected in the difference in survival for the two groups of patients from where the cell lines were derived. However, no correlation was found between SF2 and survival within each grade. In a multivariate analysis the age, grade and Karnofski status were found to be significant prognostic values for survival with a p values of 0.032, 0.03 and 0.038, respectively, however, the ln SF2 was not significant (p = 0.40). The mean SF2 of the 6 oligodendroglioma cell lines (0.54) was comparable to that of glioblastoma multiforme (0.50). The high SF2 for oligodendroglioma does not accord with the much better clinical outcome of these tumors. CONCLUSIONS: These data on 85 malignant glioma cell lines show a very broad distribution of SF2 values for irradiation in vitro. SF2 reflected the difference in sensitivity between AA (Grade 3) and GBM (Grade 4). This may suggest that the parameter SF2 is useful to discriminate between the sensitivity of different grades or types of histology in vitro. However, SF2 was not a predictor of the clinical outcome on individual basis for malignant gliomas. The in vitro studies will need to be supplemented by physiologic characterization of the tumors in vivo. Such conclusions would limit the predictive value of current radiation sensitivity assays based on in vitro dose-survival measurement for at least high grade malignant gliomas.

Astrocytoma↗
PubMed1992

Radiosensitivity testing of human malignant gliomas.

Radiotherapy remains the main treatment modality for patients with malignant gliomas and is the only treatment which significantly prolongs survival. Clonogenic and tetrazolium based colorimetric assays (MTT) of early passage cultures have been performed following 2 Gy doses of x-rays in order to determine if in vitro radiosensitivity is a factor in response to treatment. Of 47 biopsies received, 39 were established in primary culture. A value of surviving fraction to 2 Gy (SF2) was obtained in 85% of growth assays and 64% of clonogenic assays. The mean SF2 value for the MTT was 0.56 which was significantly higher than the 0.42 obtained for the clonogenic assay. There was, however, reasonable qualitative agreement in assessing relative radiosensitivity/radioresistance (r = 0.7). Mean SF2 values for grade 3 tumors were 0.52 (MTT) and 0.35 (clonogenic) as against mean SF2 values of 0.63 (MTT) and 0.47 (clonogenic assay) for grade 4 tumors. In 24 patients with adequate follow-up, no direct correlation was found between SF2 and survival, although mean SF2 values for patients surviving greater than 18 months was significantly less (p = 0.01) than patients surviving less than 18 months as determined by the MTT assay.

Brain Neoplasms↗
PubMed1992

Holter monitor recording for the detection of myocardial ischemia: validation of a new recorder and chest lead positions.

OBJECTIVE: To validate the Reynolds Tracker II Holter system using newly described lead positions during both upright treadmill exercise and in the recumbent position following exercise. The specific lead positions HL1 and HL2 were chosen to detect anterior and postero-inferior myocardial ischemia, respectively, without interfering with the surgical field in the hypothetical situation of open-heart surgery. Similar lead positions have previously been used to monitor myocardial ischemia during induction of anesthesia, but have never been validated by comparison with 12-lead modified electrocardiogram (ECG) recording. METHODS: To validate the authors' 'chosen' Holter lead positions (HL1 and HL2), both at the fifth intercostal space just lateral to the midclavicular line and on the back, 1.5 cm to the left of the vertebral column, respectively) 49 candidates for routine treadmill exercise testing underwent a simultaneous Holter monitor recording using the described lead positions. DATA ANALYSIS: The Holter ECG recordings were separately analyzed by two physicians unaware of patients' identity. RESULTS: Using the modified 12-lead ECG as the 'gold standard', the sensitivity of Holter for detecting ischemia (defined as 0.1 mV or ST depression lasting at least 60 s) was 77 and 83%, and its specificity was 100 and 92%, respectively, for observers 1 and 2. Most episodes of myocardial ischemia were detected by the modified lead V5 for the 12-lead ECG and by HL1 for the Holter recording. Using the Holter Tracker II system and the chosen lead positions, it was possible to detect successfully most episodes of exercise-induced myocardial ischemia. CONCLUSION: Holter monitoring might be useful in detecting perioperative myocardial ischemia.

Coronary Disease↗
PubMed1990

Radiation response of xenografts of a human squamous cell carcinoma and a glioblastoma multiforme: a progress report.

Human cell lines derived from squamous cell carcinomas of the pharynx (FaDu and HSCC6) and glioblastoma multiforme (U87, A2, A7, MMC-1, MMC-2) have been studied in vitro as monolayers in exponential (all 7 cell lines) or plateau phase (FaDu and U87), and as 1 mm diameter spheroids in vitro (FaDu and U87) and as 6 mm diameter xenografts growing in the legs of athymic NCr(nu/nu) nude mice (FaDu, HSCC6, U87, A7 cells). For SF2s and D values, there was broad overlap of values between SCC and glioma cell lines. In contrast, the D0 values were higher for U87, A2, A7, and MCC-1 than the two SCC cell lines, while the extrapolation numbers were greater for the two SCC lines than any of the glial tumor lines (these differences were not regularly significant). Complete dose response assays for local control of FaDu, HSCC6, U87, and A7 xenografts have been performed under conditions of normal blood flow and clamp hypoxia for tumors growing in mice which had received 6 Gy WBI at 24 hr before transplantation. Under the latter circumstances, irradiations have been performed on FaDu and U87 as single doses or as 2, 4, or 8 equal doses; for the fractionated irradiation, treatments were given on a BID basis with 4 hr between the treatments on any 1 day. For irradiation of 1 mm diameter spheroids, radiation was administered as single doses under conditions of equilibration with AIR. The TCD50 for the FaDu was significantly higher and the dose response curve steeper for tumors growing in immune suppressed (6 Gy WBI 24 hr prior to transplantation) than in control nude mice. Tumors, exponential or plateau phase cells, and spheroids derived from U87 were significantly and substantially more resistant under all conditions and fractionation schedules than for FaDu. Thus, the in vitro results do not indicate a clearly greater resistance by the glioma cell lines, while the more limited TCD50 data (single dose and 8 fractions irradiation) show more resistance in vivo by the glial tumors. We noted that the TCD50 values for U87 and A7 glial tumors overlap those for spontaneous tumors of the C3H mouse but are higher than the human squamous cell carcinoma xenografts in the nude mice. Substantial additional data from xenografts are needed to determine if the higher TCD50 values for GBMs, especially for fractionated irradiation, is a regular finding and is of sufficient magnitude to be pursued by studies to explain the observed differences.

Animals↗
PubMed1989

Quantitative transplantation assays of the rat rhabdomyosarcoma BA1112 isografts into the WAG/Rij Y rat and xenotransplantation into the athymic NCr (nu/nu) nude mouse.

Quantitative tumor cell transplantation assays have been performed to compare the transplantability of rat rhabdomyosarcoma BA1112 into isologous WAG/Rij Y rats and athymic NCr(nu/nu) nude mice. The end-point was the TD50 or the number of viable tumor cells which would transplant the tumors into half of the recipients. At Yale, two sets of 2-fold dilutions were prepared, one was sent to the MGH by Air Express. That afternoon, concurrent assays were performed at Yale using the WAG/Rij Y rat and at MGH using the NCr(nu/nu) mouse. The TD50 values were the same for iso- and xenotransplantation. Furthermore, the TD50s in rats and mice were unaffected by standard immunization procedures prior to challenge of the TD50 assay. The BA1112 (10(7) trypan blue excluding cells) grew to 10-12 mm and then completely regressed if transplanted into NCr(nu/+) mice which had received 6 Gy whole body irradiation but did not grow in control NCr(nu/+) mice. The times for the BA1112 to grow to 10 mm were the same in normal or preimmunized WAG/Rij Y rats or NCr(nu/nu) mice and in 6 Gy WBI NCr(nu/nu) mice. All of the experimental data show that the xenogenic NCr(nu/nu) mice accept the BA1112 as readily as do the isologous WAG/Rij Y rats.

Animals↗