A symposium on Sigmund Freud and art at the David and Alfred Smart Museum of Art.
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Biomedical subjects
Publications and source records attributed to S Taylor.
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Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting.
The effects of endotoxin on mouse liver phospholipid fatty acid composition have been investigated. Administration of endotoxin from Salmonella abortus equi led to a decrease in the polyunsaturated fatty acid content of livers from mice sensitized with Bacille Calmette Guérin (BCG). The content of arachidonic acid fell significantly in both the phosphatidylcholine and phosphatidylinositol fractions whereas in the phosphatidylethanolamine fraction the linoleic acid content was significantly reduced. The polyunsaturated fatty acids were replaced by increased amounts of oleic acid and palmitic acid, leading to a reduction in the polyunsaturated to saturated fatty acid ratio.
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Because coronary atherosclerosis after heart transplantation has been a limiting problem in long-term survival of adults, we reviewed the coronary angiograms, and autopsy data when available, from 21 of 30 children who underwent orthotopic heart transplantation and survived the perioperative period. Six patients had coronary atherosclerosis, and five of these patients died 6 months to 3 years after heart transplantation. The late deaths were sudden and unexpected. Coronary angiography demonstrated several types of lesions, including concentric narrowing, tubular segmental lesions, and abrupt obliteration of major coronary vessels. Risk factors assessed included hypertension, hyperlipidemia, cytomegalovirus infection, type of immunosuppressive regimen, number of rejection episodes, and major histocompatibility antigen mismatches. Only the frequency and duration of rejection episodes seemed to be more prevalent in the patients in whom coronary atherosclerosis developed. Despite the benefits of heart transplantation in treating children with end-stage heart disease, coronary atherosclerosis may limit long-term survival. We suggest that these children should undergo serial coronary angiography to identify those at risk for subsequent events related to coronary artery disease.
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The origin and cell lineage of stromal cells in the bone marrow is uncertain. Whether a common stem cell exists for both haemopoietic and stromal cells or whether these cell lines arise from distinct stem cells is unknown. Using in situ hybridisation for detection of the Y chromosome, we have examined histological sections of bone marrow from seven patients who received marrow transplants from HLA-matched donors of the opposite sex. Stromal cells (adipocytes, fibroblasts, endothelial cells, osteoblasts and osteocytes) were identified in these recipients as being of host origin. This result is consistent with the concept of a distinct origin and separate cell lineage for cells of the haemopoietic and stromal systems. It also shows that engraftment of marrow stromal cell precursors does not occur and that host stromal cells survive conditioning regimens for marrow transplantation. With the exception of one case, with a markedly hypocellular marrow, mixed chimaerism was seen in haemopoietic cells, indicating that this is not a rare event after marrow transplantation.
Immunoglobulins were synthesized and secreted by human B cells cultured with T cells with receptors for FcM (TM) helper cells, monocytes, null cells and PWM for 7 days. Immunoglobulin synthesis did not take place if the null cells were omitted from the cultures irrespective of the duration of the culture period. Null cells incorporated into the cultures at only 25% of their optimal concentration did not affect immunoglobulin synthesis markedly by the cultured B cells. However, the number of B cells in the culture could not be diluted without an accompanying marked reduction in immunoglobulin synthesis. The B cells synthesized and secreted significant quantities of immunoglobulin even when the null cells were added as late as day 6 of the 7-day culture whereas no or very little immunoglobulin was synthesized if the B cells were not present from the beginning of the 7-day culture. It was demonstrated that cultured null cells do not transform into B cells and do not attain their immunoglobulin-synthesizing function. Furthermore, cultured B cells do not transform into null cells and do not attain their helper function. The null cells can also be distinguished from the B cells on the basis of cell-surface markers, receptors, and blastogenic responsiveness to phytomitogens. It is concluded that (i) the human circulating B cells require the null cells, in addition to the TM cells, monocytes and PWM, in culture in order to synthesize and secrete immunoglobulin; (ii) the null cell signal that stimulates immunoglobulin synthesis and secretion by the B cells is probably the last signal following the TM helper cell, monocyte and PWM signals received by the B cells; and (iii) the null cells and the B cells constitute distinct lineages of cells.
In the accompanying communication, it was demonstrated that the null cells, the TM cells, monocytes and PWM are all obligatory participants in the synthesis and secretion of immunoglobulins by human B cells in culture. Here we demonstrate that the null cells secrete a factor, referred to as human immunoglobulin synthesis/secretion-facilitating factor (HISFF) that can replace the null cells in the cultures. HISFF is distinct from the known T cell-derived interleukins. HISFF functions in an HLA-unrestricted fashion since it can facilitate the synthesis and secretion of immunoglobulins by allogeneic B cells. The null cells cultured with TM helper cells and PWM required monocytes in the culture in order to secrete HISFF. Furthermore, B cells cultured with TM cells in medium containing HISFF, monocyte-derived factors and PWM nevertheless required monocytes in order to respond to the HISFF signal. Thus, the monocyte plays a pivotal role in the secretion of and response to HISFF. Normal levels of immunoglobulin were synthesized even when HISFF was added to the cultures of B cells, TM cells and monocytes, in the presence of PWM, as late as day 6 of the 7 day culture. We conclude that the null cells participate in immunoglobulin synthesis by the B cells by secreting a soluble mediator, HISFF, capable of replacing the null cells in the culture; and that the HISFF signal is the last signal received by the B cell before it begins to synthesize and secrete immunoglobulins.
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We have investigated thyroid structure and function in mice homozygous for the chromosome 15 mutation, congenital goitre (cog). Abnormal thyroidal hypertrophy and reduced iodine uptake in cog/cog mice were observed as early as day 18 of gestation, corresponding to the onset of thyroid function. Growth continued unabated in mutants throughout the 10-month period of observation. By 2 months of age, thyroid cell hypertrophy obliterated nearly all follicular lumina in cog/cog glands and by 10 months mean mutant thyroid mass exceeded that of age-matched littermates. Twenty-fold serum concentrations of thyrotrophin were significantly increased at all ages examined. While wild type (+/+) and heterozygote (+/cog) mice are indistinguishable from each other, thyroids of homozygote mutants (cog/cog) and the +/cog type are easily discernible from thyroids of the +/+ type by microscopic and thyroglobulin (Tg) analyses. Thyrofollicular cells of both cog/cog and +/cog genotypes contain large vesicles of accumulated, nonglycosylated proteinaceous material not observed in cells from +/+ mice. Autoradiography showed 125I was incorporated only into Tg within recognizable follicular lumina of thyroids from +/cog mice. Serum concentrations of tri-iodothyronine are depressed during development in cog/cog mice. Serum concentrations of thyroxine are depressed during postnatal development but increase progressively to normal concentrations by 10 months of age. Our analyses indicate that full size Tg is produced in thyroid cells from cog/cog mice, though in a greatly reduced quantity, and that Tgs which are several sizes smaller than normal are also produced in both homozygote and heterozygote thyroids.(ABSTRACT TRUNCATED AT 250 WORDS)
In studying patients with mild hypertension, we used a double-blind, randomly allocated crossover, 2 x 2 factorial design to obtain more precise estimates of the effectiveness of individual hypertensive drugs and of the interactions when used in combination. In the present study, we reanalysed data from our own previously completed crossover factorial studies in order to determine the optimal length of phases and to try to exploit patient heterogeneity by comparing blood pressure responses within each patient to the two different drugs in each study. An analysis of the 'weeks within phases' variation (analysis of variance) applied to all phases, to the placebo phases alone and to the active treatment phases alone, of the individual factorial studies and of pooled data from studies of similar design, only revealed differences in the first week of our 4-week phases. Accordingly, we suggest that 4 weeks is an optimal phase length, since only the values from the third and fourth weeks showed the full expression of a drug's antihypertensive effect, avoiding the problem of a carryover effect and the need for a more complex intervening washout placebo phase. Comparing the blood pressure reductions shown by individual patients in response to different antihypertensive drugs using arbitrary criteria of greater than or equal to 5, 10 and 15 mmHg for diastolic and greater than or equal to 5, 10 and 20 mmHg for systolic pressure, we were unable to distinguish between the two separate drugs in each factorial study, due to the magnitude of the background variation which had a coefficient of variation of 5-7%.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical impression suggests that many cases of detrusor instability are psychosomatic. We evaluated 63 women with urinary incontinence and 27 continent controls using the Minnesota Multiphasic Personality Inventory, Uplift and Hassle Scales, and a structured questionnaire screening sexual dysfunction. All incontinent women underwent diagnostic urodynamic studies including uroflowmetry, subtracted water cystometry with provocation, and urethral closure pressure profilometry. Thirty-five women had genuine stress incontinence and 28 had detrusor instability, including nine with mixed incontinence. No differences in psychological test results were noted between the detrusor-instability and genuine-stress-incontinence groups. On the Minnesota Multiphasic Personality Inventory, subjects with detrusor instability scored significantly higher than controls on the hypochondriasis (P = .006), depression (P = .01), and hysteria (P = .0009) scales. Compared with continent controls, the detrusor-instability group reported a lower frequency of uplifts (P less than .05) and a greater intensity of hassles (P less than .05). Both incontinent groups reported more sexual dysfunction than did controls. We conclude that many women with urinary incontinence have abnormal psychological and sexual test results reflecting moodiness, feelings of helplessness and sadness, pessimism, general hypochondriasis/somatization, and sexual dysfunction. These abnormalities appear to be associated with urinary incontinence in general rather than with specific diseases of the urinary tract.
Family Medicine Programme vocational trainees are requested to assess by means of a detailed questionnaire the teaching they have received in their general practice training attachments. This paper describes the methods and presents the results of a survey of South Australian and Northern Territory trainees over a three year period. The results show that a survey by questionnaires is an effective method of measuring perceived standards of teaching in training practices.
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