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Biomedical subjects

W H Goodson

Publications and source records attributed to W H Goodson.

At least 19 recordsLinked to original sources

Physician-patient sexual contact. Prevalence and problems.

To document the current prevalence of physician-patient sexual contact and to estimate its effect on involved patients, 10,000 family practitioners, internists, obstetrician-gynecologists, and surgeons were surveyed. Of the 1,891 respondents, 9% acknowledged sexual contact with 1 or more patients. Even in the unlikely case that none of the nonrespondents had sexual contact with patients, its prevalence among all 10,000 physicians surveyed would still be 2%. Of respondents, 23% had at least 1 patient who reported sexual contact with another physician; 63% thought this contact was "always harmful" to the patients. Almost all (94%) responding physicians opposed sexual contact with current patients; 37% also opposed sexual contact with former patients. More than half of respondents (56%) indicated that physician-patient sexual contact had never been addressed in their training; only 3% had participated in a continuing education course focusing on this issue. Clear and enforceable medical ethics codes concerning physician-patient sexual contact are needed, as well as preventive educational programs for medical schools and residency programs.

Ethics, Medical

Cigarette smoking decreases tissue oxygen.

Subcutaneous wound-tissue oxygen (PsqO2) tension in eight volunteers fell rapidly and significantly in response to smoking, and remained low for 30 to 50 minutes. Sham "smoking" had no effect. These data suggest that a typical "pack-per-day" smoker experiences tissue hypoxia during a significant portion of each day. The degree of hypoxia found in these subjects has been associated with poor wound healing in animal and human studies. The onset and duration of tissue hypoxia paralleled the well-established plasma pharmacokinetics of nicotine. This suggests that peripheral vasoconstriction, induced by the adrenergic effects of nicotine, may contribute to the observed decrease in PsqO2.

Connective Tissue

In vivo measurement of breast cancer growth rate.

S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion.

Breast Neoplasms

Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients.

Oxygen tension and collagen deposition were measured in standardized, subcutaneous wounds in 33 postoperative surgical patients. Pertinent clinical and wound parameters were analyzed by Pearson's correlation test and sequential linear regression analysis. Collagen deposition was directly and significantly proportional to wound oxygen tension and measures of perfusion. There were no significant correlations with hematocrit, estimated blood loss, length of operation, smoking, age, weight, sex, or urine output. This study in humans confirms animal experiments showing that collagen deposition and tensile strength in wounds are limited by perfusion and tissue oxygen tension. It appears unnecessary to maintain hemoglobin at normal levels to support repair, provided that peripheral perfusion can be maintained at a high level in compensation for anemia. These circumstances reflect the fact that although oxygen is essential to many aspects of healing, and must be delivered at adequate partial pressures, reparative tissue consumes relatively little of it.

Anemia

Proliferation of normal breast epithelial cells as shown by in vivo labeling with bromodeoxyuridine.

The proliferative activity of normal acinar and ductal breast epithelial cells was studied by in vivo labeling with 5-bromodeoxyuridine (BrdUrd) in 26 cases with concurrent breast carcinoma. The BrdUrd-labeled cells were recognized in histologic sections of paraffin-embedded tissue, using an anti-BrdUrd antibody and an immunoperoxidase reaction. The percentage of BrdUrd-labeled cells showed great variability for both acinar (0% to 2.66%; mean, 0.70%; standard deviation [SD], 0.80%) and ductal cells (0% to 1.99%; mean, 0.51%; SD, 0.57%). The fraction of proliferating epithelial cells declined with the age of the patients and was significantly higher in premenopausal women (1.16% +/- 0.85% for acinar and 0.94% +/- 0.60% for ductal cells) as compared with the postmenopausal women (0.27% +/- 0.46% for acinar and 0.17% +/- 0.22% for ductal cells), P less than 0.01 for acinar and P less than 0.001 for ductal cells, respectively. In some patients, great variability in distribution of proliferating acinar and ductal cells among different lobules and ducts was observed. No difference was found in the number of proliferating acinar and ductal cells situated near or far from their corresponding tumors. No correlation was seen between cell proliferation of normal acinar or ductal cells and cell proliferation of the respective tumors.

Adult

Lack of correlation of clinical breast examination with high-risk histopathology.

PURPOSE: Routine breast examination frequently finds differences in palpable density and palpable nodularity, but it is not known if these differences correlate with the presence of high-risk histopathology. PATIENTS AND METHODS: To test for a relationship between clinical breast examination and histopathology, we devised separate, 4-point scales of clinical density and nodularity and validated these scales by repeat examinations 4 or more months apart in 199 separate breasts (the scale was the same or within 1 point on repeat examination 87% of the time for density and 90% for nodularity). We then used these two clinical scales to compare density and nodularity to histopathology of breast tissue at the margins of segmental resections in 60 women undergoing breast-conserving treatment of primary breast cancer. In cases such as these, a large sample of "normal" tissue is intentionally removed when the wide excision is done to obtain negative margins. Histopathology at the margins was graded according to the consensus panel of the American College of Pathology; as might be expected in women with previous cancer, some higher-risk histopathology was found in 37% of cases. A relationship was sought using Spearman's rank correlation coefficient. RESULTS: Neither clinical breast density (rho = 0.16) nor clinical breast nodularity (rho = 0.01) related to the presence of high-risk histopathology in the underlying tissue. Interestingly, breast nodularity increased with age (rho = 0.28), and clinical density and nodularity were inversely related (rho = -0.28). CONCLUSION: We conclude that neither clinical breast density nor nodularity correlates with histopathology and that it is unlikely that a larger study would find a clinically useful correlation. Therefore, a clinical examination should not be used to decide that high-risk histopathology is likely to be present in an individual woman's breast.

Adult

Breast fluid cholesterol and cholesterol beta-epoxide concentrations in women with benign breast disease.

Because cholesterol 5,6-epoxides have been reported to be mutagenic, carcinogenic, and cytotoxic, we investigated the relationship of these substances in breast fluid to histopathologically defined breast disease. We measured cholesterol and its oxidation product, 5 beta,6 beta-epoxide, in breast fluids from 68 women with biopsied benign breast disease (BBD) and 135 women with no history of breast disease (controls). Each biopsy was classified according to the most severe epithelial change: (a) nonproliferative epithelia; (b) hyperplasia without atypia; or (c) hyperplasia with atypia. Similar to our previous findings in control women, breast fluid cholesterol and beta-epoxide concentrations in women with BBD were associated with factors of interest in relation to breast cancer: concentrations increased with age and were higher in white than nonwhite women and in women who were past or current smokers; concentrations were lower in women who had given birth or breastfed within 2 yr. Increased breast fluid cholesterol and beta-epoxide concentrations were significantly associated with proliferative BBD (hyperplasia with or without atypia) compared to controls. After adjustment for covariates, the odds ratio for proliferative BBD associated with detectable versus nondetectable beta-epoxide concentrations was 8.5 (95% confidence intervals, 1.1, 68.8). Our findings suggest that the histological progression from normal epithelium to hyperplasia without atypia to atypical hyperplasia is associated with progressively increasing concentrations of both cholesterol and cholesterol beta-epoxide.

Adult

Selective effects of tumor necrosis factor-alpha on wound healing in rats.

Many growth factors are believed to act simultaneously in wounds. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine released by activated macrophages. In various concentrations it has inflammatory, cytolytic, mitogenic, antitumor, and possibly angiogenic or antiangiogenic effects; therefore it is likely to affect wound healing. With stainless steel wire mesh wound cylinders implanted in rats, we tested topical TNF-alpha in wounds, alone and in combination with platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). The cylinders were injected daily for a total of 12 days, after which we measured the accumulation of protein, DNA, and hydroxyproline in each cylinder. TNF-alpha had little effect by itself; it inhibited the growth-promoting effects of TGF-beta, but it did not influence the effects of PDGF. These results agree with the in vitro studies showing synergism of TNF-alpha and PDGF and antagonism between TGF-beta and TNF-alpha. They also suggest that TGF-beta may have a negligible role in normal healing and emphasize that interaction of growth factors must be understood before appropriate clinical use can be planned.

Animals

Wound healing.

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Blood Volume

Oxygen tension measurements using an oxygen polarographic electrode sealed in an implantable silastic tonometer: a new technique.

Our new method is comparable to the standard, "open-end" tonometer system and incorporates all its abilities to monitor oxygen tension and perfusion. The new device has the advantage of being completely sealed, providing a true, continuous direct measurement over several days, with freedom of movement for the patient without operator attention and with improved stability of the electrode, which minimizes the drift artifacts previously encountered. These improvements will facilitate routine clinical monitoring of tissue oxygen tension.

Animals

The lumpy breast.

"Topics in Primary Care Medicine" presents articles on common diagnostic or therapeutic problems encountered in primary care practice. Physicians interested in contributing to the series are encouraged to contact the series' editors.

Breast Diseases

Assessment of perfusion in postoperative patients using tissue oxygen measurements.

Subcutaneous tissue oxygen tension was measured as an index of perfusion in 44 postoperative patients. Hypoperfusion was defined as suboptimal tissue oxygen tension unresponsive to increased inspired oxygen but becoming responsive after increased fluid infusion. Twelve of thirty patients who underwent major abdominal and flank operations were found to be suboptimally perfused by this definition despite adequate fluid maintenance according to standard clinical criteria including urine output. Apparently, a significant number of postoperative abdominal surgery patients are not optimally perfused, and this state is not recognized by the present clinical criteria. Tissue oximetry may be a useful objective method of assessing tissue perfusion.

Blood Gas Analysis

Three year follow-up of benign fine-needle aspiration biopsies of the breast.

Benign fine-needle aspiration, taken in context, is a reasonable alternative to open biopsy. We found a false-negative rate comparable to that for frozen section or routine histologic examination of benign surgical breast biopsies. Fine-needle aspiration must always be interpreted in context. It is never satisfactory to use this test to ignore or choose not to surgically biopsy a lump that is suspicious on clinical grounds or on the basis of other tests.

Adult

The influence of a brief preoperative illness on postoperative healing.

In a study of wound healing at high altitude, subcutaneously implanted PTFE tubes were used to stimulate and measure accumulation of wound hydroxyproline (an index of collagen) in 26 patients who had appendectomy and in 38 patients who had cholecystectomy. Patient age, length of surgery, and postoperative recovery seemed to predict better healing in patients who had appendectomy, but there was a difference in the preoperative illness of the two groups: acute cholecystitis was treated medically and cholecystectomy performed after resolution of the acute phase of illness, whereas patients who had appendectomy were taken to surgery as soon as a diagnosis was made. It was observed that patients who had appendectomy accumulated 20% less hydroxyproline than patients who had cholecystectomy (p less than 0.02), and that the depression of hydroxyproline accumulation was significantly related to length of preoperative illness (p = 0.008). This decrease in wound hydroxyproline accumulation is attributed to the acute preoperative illness. Conceptually, this is a unique situation since the brief illness did not produce lasting debility, and the source of illness, the inflamed appendix, was not present during healing. This indicates that even a brief preoperative illness has a more prolonged influence on postoperative healing than usually anticipated.

Adult

Cardiac cryolesions as an experimental model of myocardial wound healing.

The standard coronary ligation model for experimental myocardial infarction results in variable areas and patterns of necrosis; therefore, the healing of such infarctions is also variable. The authors developed an experimental myocardial injury model using simple cryoinjury, which allows standardization of the size, depth, and location of the wound. Thirty-eight left ventricular cryolesions were created in 19 dogs, which were then killed from 3 to 35 days after injury. A consistent decrease in the depth of scar (p less than 0.005) and accumulation of collagen (p less than 0.0001) over time characterized this healing myocardial wound. Histologic examination revealed that the cellular pattern of healing myocardial cryolesions is similar to that of a healing myocardial infarction but with less variability. The authors advocate the use of cardiac cryolesions as a model of experimental myocardial wound healing.

Animals

Application of expanded polytetrafluoroethylene (ePTFE) tubing to the study of human wound healing.

Wounds are a part of daily life. They range from minor nicks and cuts to the incisions of major surgery. In the sequence of evolution the process of healing arose long before modern science. The events which we are beginning to unravel have occurred routinely for a very long time despite our lack of understanding. We have learned how to nurture healing, but how to modify healing in a positive sense is only an approaching reality. Standardized tests of human healing are a necessary part of future research in wound healing. In the Wound Healing Laboratory we have used tubes of expanded polytetrafluoroethylene (ePTFE) as a tissue-sampling device in small, experimental, needle-stick wounds. Ingrowth into ePTFE is influenced by surface and structural characteristics. These are held constant, and "normal" values can be established and used as a base with which to study effects of various clinical states on healing in humans.

Biocompatible Materials