Biomedical subjects
L Humphrey
Publications and source records attributed to L Humphrey.
Immediate postoperative 5-FU does not decrease colonic anastomotic strength.
BACKGROUND AND OBJECTIVES: The use of continuous infusion 5-Fluorouracil (5-FU) immediately after surgery may improve the adjuvant treatment of resected colon cancer and is the subject of a national phase III trial (Intergroup no. 0136). The aim was to determine the effect of continuous infusion 5-FU on the bursting pressure of a colon anastomosis. METHODS: Twenty Lewis rats weighing approximately 300 g were subject to sigmoid colectomy and single-layer anastomosis. Ten rats received 5-FU continuously at 600 mg/m2 per day for 7 days; 10 rats served as controls. Ten days postoperatively, the rats were sacrificed and bursting pressure of the colon containing the anastomosis was determined. RESULTS: No anastomotic leaks or intra-abdominal abscesses were identified. Burst pressure of the colon in controls (124+/-13 mm Hg; mean+/-SEM) was not significantly different from those animals receiving 5-FU (115+/-9, P > 0.05). The control rats gained weight (13+/-7 g), which is significantly different from the rats receiving 5-FU (-19+/-13, P=0.04). CONCLUSIONS: Continuous infusion 5-FU postoperatively results in weight loss, but does not affect anastomotic bursting strength in rats. This evidence supports the safety of continuous infusion 5-FU postoperatively in humans.
Taphonomy and palaeoecology of Olduvai Bed-I (Pleistocence, Tanzania).
Detailed taxonomic and taphomonic studies of rodents and palaeoecological analysis have been undertaken to investigate faunal change in Olduvai Bed-I. The palaeoenvironments inferred from rodent faunas recorded in Olduvai Bed-I suggest a change between the middle (FLK + FLKNN) and the top of the series (FLKN). Changes have also been observed from taxonomic studies of large mammals and from palynological studies. These differences have been attributed in the past to climatic change, but taphonomic studies suggest a more complex scenario. The environment at Olduvai Bed-I is here interpreted through analysis of fossil faunas and fossilization processes. Identification of the causative agents that could have altered the faunal composition provides information on the environment and on the nature of the change observed between the middle and top of Bed-I. This information can then be used to test conflicting hypotheses about the origins and amount of faunal and pollen change. Results show evidence of predation in all units of Bed-I and can be attributed to different predators along the series. Different predator behaviours explain some of the variability observed by previous authors in the small mammal species composition between the middle and the top of Bed-I. After taking taphonomy into account, the remaining faunal differences point to environmental differences between middle and upper Bed-I and even greater within the upper Bed-I sequence. These differences go beyond the range that is present today in the tropical woodland-savanna biome. Our interpretation of the palaeoenvironments is that the middle Bed-I faunas indicate a very rich closed woodland environment, richer than any part of the present-day savanna biome in Africa, changing to less rich woodland in upper Bed-I with a trend towards more open and seasonal woodlands at the top of the series.
Moving & managing images.
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Release from quiescence stimulates the expression of integrin alpha 5 beta 1 which regulates DNA synthesis in human fibrosarcoma HT1080 cells.
We show that integrin alpha 5 subunit expression is stimulated when human fibrosarcoma HT1080 cells are released from quiescence. The alpha 5 subunit mRNA level in quiescent HT1080 cells was increased 24 hr after their release by 10% fetal bovine serum-containing medium reaching a maximum of 2.5 fold on day 2. Similar levels of induction of cell-surface alpha 5 subunit protein as well as beta 1 subunit protein were also observed. This resulted in a significant increase of cell attachment to fibronectin. The serum stimulation also increased alpha 5 subunit promoter activity by twofold which was protein synthesis independent. Subsequent deletion of alpha 5 subunit promoter DNA showed that the cis-element responsible for the activation is located between -92 bp and the transcription start site. The promoter activity was not induced until 12 hr after the release. Comparison of the effect of a serum-free medium and a 10% fetal bovine serum-supplemented medium revealed that both the DNA synthesis and alpha 5 subunit induction were independent of exogenous growth factors. The increased integrin alpha 5 beta 1 appears to function by reducing mitogenic activity since blockade of fibronectin binding to its receptor with a RGD peptide, a monoclonal anti-fibronectin antibody, or a monoclonal anti-alpha 5 subunit antibody during the release from quiescence significantly stimulated DNA synthesis. On the other hand, stable overexpression of the alpha 5 subunit resulted in decreased DNA synthesis.
Interval breast cancers are not biologically distinct--just more difficult to diagnose.
BACKGROUND: Breast cancer diagnosed within 1 year of a negative annual screening examination is called interval breast cancer (IBC) and is considered to be a more virulent subtype of disease. METHODS: We reviewed clinical data on 24 women who were diagnosed as having IBC while participating in the Breast Cancer Detection Demonstration Project at Ellis Fischel Cancer Hospital and the Women's Cancer Control Program screening project in Columbia, Missouri, between 1974 and 1992. We reinterpreted mammograms from the visit prior to the diagnosis of IBC for possible misdiagnosis, changes suggestive of malignancy, and Wolfe's patterns. Archival paraffin blocks from 19 patients were used to determine qualitative expression of tumor markers. RESULTS: Observed 5-, 8-, and 10-year survival rates were identical to published data for patients with non-IBC. Seventy-four percent of the mammograms evidenced dysplastic Wolfe's patterns (P2 and DY), and one patient was found retrospectively to have shown evidence of cancer which was missed. Compared to breast cancers in general, fewer IBC tumors expressed tumor markers associated with poor prognosis. CONCLUSIONS: Survival rates and tumor marker expressions in this retrospective cohort suggest that IBC tumors are not more biologically aggressive than noninterval tumors. They are more difficult to diagnose both by physical examination and mammography.
Repression of autocrine transforming growth factor beta 1 and beta 2 in quiescent CBS colon carcinoma cells leads to progression of tumorigenic properties.
Previous work has shown that repression of negative autocrine transforming growth factor (TGF) beta 1 did not alter the growth rate of a human colon carcinoma cell line, but the time required for the cells to enter exponential growth from lag phase was reduced (S. P. Wu, D. Theodorescu, R. Kerbel, J. K. V. Willson, K. M. Mulder, L. E. Humphrey, and M. G. Brattain, J. Cell Biol., 116: 187-196, 1992). These results have led to the hypothesis that the tumor suppressive activity of autocrine TGF-beta 1 was directed at quiescent nondividing cells rather than actively dividing cells. In order to test this hypothesis, a weakly tumorigenic, well-differentiated human colon carcinoma cell line designated CBS, which expressed autocrine TGF-beta 1 and -beta 2 activity in quiescent cells, but not in exponential growth phase cells, was identified. This cell line was stably transfected with a full-length TGF-beta 1 antisense complementary DNA. Constitutive expression of TGF-beta 1 antisense mRNA in CBS cells resulted in repression of autocrine TGF-beta 1 and -beta 2 protein activity in quiescent cells of approximately 10-fold. TGF-beta 2 repression could have been due to interaction with TGF-beta 1 antisense mRNA, since these two isoforms have a high degree of homology, or it could have been indirectly due to TGF-beta 1 repression, since this isoform has been shown to affect transcriptional and posttranscriptional control of TGF-beta 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Septal geometry in the unloaded living human heart.
Right ventricular loading leads to diastolic septal flattening in man without necessarily requiring right ventricular pressure to exceed left ventricular pressure. This observation suggested that the unstressed septal configuration is flat and that its normal concave shape is due to the left-to-right transseptal pressure gradient. To examine this hypothesis, we studied septal configuration by two-dimensional echocardiography in nine patients with normal global and regional left ventricular function during surgery for coronary artery disease. The transseptal pressure gradient was obtained from pulmonary capillary wedge pressure minus right atrial pressure. Measurements were obtained at control (open chest, intact pericardium [C]), with the pericardium open (OP), on cardiopulmonary bypass (CPB), and after cardiac arrest (CA). There were no changes in any measurements between C and OP or between CPB and CA. Left ventricular end-diastolic cavity area decreased from 16.5 +/- 2.1 cm2 at C to 11.1 +/- 4.5 cm2 after CPB, and further decreased to 8.9 +/- 3.5 cm2 after CA (p less than .001), yet the septum flattened, as shown by an increase in its radius of curvature from 1.7 +/- 0.5 cm during C to 2.5 +/- 0.7 cm after CPB, and to 2.9 +/- 1.0 cm after CA (p less than .001), or from 0.4 +/- 0.1 to 0.8 +/- 0.4 to 1.1 +/- 0.5 U (p less than .001) when normalized for cavity area. Diastolic transseptal pressure gradient was reduced from 4.1 +/- 2.3 mm Hg during C to 1.1 +/- 1.8 mm Hg after CPB, and to 0.5 +/- 1.4 mm Hg after CA (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Infection control ties boost MM efficiency.
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Developing a management style: no universal method.
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The splintering of health care. Part 1.
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MMs tackle resale issue: "gray" area of the law.
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Sizing up groups.
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Hands-on administrator has hands on MM department.
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Part II: The splintering of health care.
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Cole's precancerous hyperplasia of the breast.
Due to his recognition as the discoverer of the first test for visualization of the gallbladder, his profile research on dissemination of cancer and his stimulation and interest in stress and immunity, one of Warren Cole's most significant reports has not been accorded due recognition. In 1944, Cole presented data at the Southern Surgical Association Meeting which clearly identified the premalignant histologic change in the breast. In the published report, Cole and Rossiter [Ann Surg 119:573-590, 1944] presented a classification of benign breast histology: 1) adenofibrosis, 2) parenchymatous hyperplasia, 3) precancerous hyperplasia, and 4) cystic disease. Following the work of Warren in 1940 [Surg Gynecol Obstet 71:257-273], who stated that the chronic cystic mastitis had an incidence of breast cancer over 3 times the expected rate, this report of Cole and Rossiter focused on the worrisome lesion atypical epithelial hyperplasia. Since then, Haagensen ["Diseases of the Breast," Philadelphia: Saunders] has stressed that gross cystic disease is the lesion most associated with increased risk of cancer. In an attempt to resolve these seeming contraindications, we reviewed the charts of patients referred to a private breast clinic. With the advent of mammography, sonography, and thermography, the incidence and management of benign breast diseases has changed over the years. This study focuses on the current management of breast masses and reinforces the significance of Cole's classification.
Need for immunologic stimulators during immunosuppression produced by major cancer surgery.
Although surgery, radiology, and anticancer chemicals have been effective in the treatment of cancer, the immunologic phase of therapy deserves more effort and thought, because the possibilities are considerable. However, the immunologic phase is so complicated that, without the advances made during the past few years, little could be expected from immunology. The focus of this paper is on the immunosuppression produced by major cancer operations, at which time the patient needs immunologic help.
Role of tumor immunity in ovarian cancer.
Antigens associated with ovarian cancer tissue have been identified by the use of heteroantisera. It has also been reported that lymphocytes from patients with ovarian cancer responded to phytohemagglutinin (PHA) and keyhole-limpet hemocyanin (KLH) but had failed to respond to autologous tumor extracts. In our series, pretreatment sera from 37 patients with stage III and IV ovarian cancer failed to react with ovarian cancer antigen preparations. After therapy, serum from only three patients was reactive: all three patients were treated by chemoimmunotherapy. Preliminary data from this clinical trial for treating stage III and IV ovarian cancer with chemotherapy, immunotherapy, or combined chemoimmunotherapy show that survival of patients treated by chemotherapy or immunotherapy corresponded to that of nonresponders to L-PAM therapy as described in another study. Interestingly, combined chemoimmunotherapy produced a survival curve depicting significant improvement, similar to that for the responders to L-PAM therapy reported in that study.