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Biomedical subjects

J L Semple

Publications and source records attributed to J L Semple.

At least 19 recordsLinked to original sources

Clinical determinants of patient satisfaction with breast reconstruction.

The main objective of this study was to examine the relationship between specific treatment variables and patient satisfaction with breast reconstruction. A questionnaire was developed that included questions on population demographics and satisfaction with the reconstruction. Of 206 women who completed the questionnaire, 23 (11.2 percent) responded that they were not satisfied, whereas 183 (88.8 percent) indicated that they were satisfied overall. A detailed retrospective chart review permitted a comparison of the treatment received by these two groups. Variables analyzed included patient age, time since surgery, reason for surgery, method and timing of reconstruction, additional surgical procedures received (mound revisions and nipple-areola complex reconstruction), and postoperative complications. Data analysis showed that the treatment received by the two groups was similar in many respects. There was no statistical association between the method or timing of reconstruction and a patient's satisfaction with the results. Furthermore, there was no difference in the number of mound revisions or nipple reconstructions performed on satisfied versus dissatisfied patients. However, the latter group experienced a substantially higher incidence of postsurgical complications (27 percent versus 61 percent, p = 0.0015). Patients were also asked to provide a written response explaining their feelings on breast reconstruction. Satisfied patients described benefits from reconstruction such as improved appearance or feelings of normalcy and wholeness. Conversely, unsatisfied patients were displeased because of poor cosmetic results, complications with the reconstructed breast, or abdominal problems. Although overall satisfaction with breast reconstruction is undoubtedly determined by multiple and complex clinical, emotional, and psychological factors, this study suggests that postoperative complications are a particularly important indicator of dissatisfaction with reconstruction.

Female↗

A guide to establishing the risk for breast cancer in the plastic surgery patient.

Plastic surgeons with a practice that includes breast augmentation, breast reduction, and breast reconstruction should have a working knowledge of both genetic and environmental breast cancer risk factors and of risk stratification of these patients. Specific tests to determine genetic susceptibility to certain cancers have become increasingly prevalent during recent years. Such testing is carried out by multidisciplinary teams, which may include plastic surgeons. Patients with a very strong family history of positive genetic testing for BRCA1 or BRCA2 may be offered prophylactic mastectomies. The authors present an overview of risk factors so that surgeons can stratify women appropriately with respect to their breast cancer risk. In addition to a brief literature review, the authors present 2 patients who represent the type of personal and family history of breast and/or ovarian cancer, and environmental risk factors that one would typically encounter in a plastic surgery patient population.

Breast Neoplasms↗

Pharmacological characterization of vasomotor activity of human musculocutaneous perforator artery and vein.

Vasospasm is one of the main causes of skin ischemic necrosis in cutaneous and musculocutaneous flap surgery, but the pathogenic mechanism is unclear. We planned to test the hypothesis derived from clinical impression that veins are more susceptible to vasospasm than arteries in flap surgery and, once established, that venous vasospasm is difficult to resolve and more detrimental than arterial vasospasm. To this end, we investigated the differences in sensitivity to vasoconstrictors and vasodilators between the human musculocutaneous perforator (MCP) artery and vein by measuring the isometric tension of arterial and venous rings suspended in organ chambers. Vascular contraction was expressed as a percentage of the tension induced by 50 mM KCl. Relaxation was expressed as a percentage of contraction induced by a submaximal concentration (3 x 10(-9) M) of endothelin-1 (ET-1). We observed that the vasoconstrictor potency of norepinephrine was significantly higher in the MCP vein than in the MCP artery. The vasoconstrictor potency of ET-1 and the thromboxane A(2) mimetic U-46619 were similar in the MCP vein and artery, but the maximal contraction induced by ET-1 and U-46619 was significantly higher in the MCP vein than in the MCP artery. On the other hand, the MCP vein was less sensitive than the MCP artery to the relaxation effect of nitroglycerin, nifedipine, and lidocaine. These differences between the human MCP artery and vein in response to vasoactive agents lend support to the clinical impression in flap surgery that veins appear to be more susceptible to vasospasm than arteries and venous vasospasm seems to be more difficult to resolve than arterial vasospasm in cutaneous and musculocutaneous flap surgery.

Arteries↗

Beta-defensin expression in human mammary gland epithelia.

Milk of mammalian species contains a wide spectrum of anti-infectious factors, some of which are heat stable. Focusing on recently discovered heat-stable antibacterial peptides called defensins, which are expressed in epithelial tissues such as airway, skin, and kidney, we hypothesized that mammary gland epithelia produce and secrete defensins onto the epithelial surface and into milk. Using a reverse-transcription PCR assay, we identified the human beta-defensin-1 (hBD-1) gene transcript in a human mammary gland epithelial cell line, MCF-12A, and in mammary glandular tissue of nine nonlactating women. Epithelial cells harvested from milk of lactating women also expressed hBD-1 mRNA. Presence of hBD-1 peptide in mammary epithelia was confirmed by immunostaining with an hBD-1 antibody. In contrast, expression of human beta-defensin-2 was not apparent both at mRNA and protein levels. Our findings suggest a biologic role of hBD-1 in the human mammary gland.

Amino Acid Sequence↗

Breast milk contamination and silicone implants: preliminary results using silicon as a proxy measurement for silicone.

In response to concerns about contamination of human breast milk from silicone gel-filled breast implants, and because silicon levels are assumed to be a proxy measurement for silicone, we compared silicon levels in milk from lactating women with and without implants. Two other sources of infant nutrition, cow's milk and infant formulas, were also analyzed for silicon. The survey took place at the Breast-feeding Clinic at Women's College Hospital in Toronto. A convenience sample of lactating women, 15 with bilateral silicone gel-filled implants and 34 with no implants, was selected. Women with foam-covered or saline implants or with medically related silicone exposures were ineligible. Collection of samples was scrupulously controlled to avoid contamination. Samples were prepared in a class 100 "ultraclean" laboratory and analyzed using graphite furnace atomic absorption spectrophotometry. Silicon levels were analyzed in breast milk, whole blood, cow's milk, and 26 brands of infant formulas. Comparing implanted women to controls, mean silicon levels were not significantly different in breast milk (55.45 +/- 35 and 51.05 +/- 31 ng/ml, respectively) or in blood (79.29 +/- 87 and 103.76 +/- 112 ng/ml, respectively). Mean silicon level measured in store-bought cow's milk was 708.94 ng/ml, and that for 26 brands of commercially available infant formula was 4402.5 ng/ml (ng/ml = parts per billion). We concluded that lactating women with silicone implants are similar to control women with respect to levels of silicon in their breast milk and blood. Silicon levels are 10 times higher in cow's milk and even higher in infant formulas.

Adult↗

Light and electron microscopic evaluation of the pectoralis major muscle following tissue expansion for breast reconstruction.

The placement of tissue expanders under the pectoralis major muscle has become a common procedure in breast reconstruction after mastectomy. Little information is available regarding the changes caused by tissue expansion on human skeletal muscle. In this study, we report the light and electron microscopic changes observed in 20 expanded pectoralis major muscles from 12 patients undergoing two-stage breast reconstruction procedures. Standard 400-cc round Radovan tissue expanders were placed, eight bilaterally and four unilaterally. Three biopsies were taken from each muscle at different locations during both the first stage (pre-expansion) and 23 weeks later at the second stage (postexpansion). The operative procedures and expansion protocol were the same in all reconstructions. No postoperative radiation therapy was added. The histologic changes were reported in a blind fashion by one pathologist. Light microscopy did not show significant pathologic changes. All but one of the pre-expansion specimens examined by electron microscope were reported as normal, whereas all of the postexpansion biopsies were grossly altered. Focal muscle fiber degeneration with glycogen deposits and mild interstitial fibrosis was noted. In addition, some fibers showed disorganization of the myofilaments in the sarcomeres. The above ultrastructural changes are significant morphologic alterations, which may be the result of muscle hypoxia. Whether these changes indicate permanent or transient transformation is yet unclear. Patient follow-up did not reveal any functional muscular deficit. We conclude that there is definite evidence to suggest significant muscular structural damage after routine subpectoral expansion for breast reconstruction.

Adult↗

The surgical and oncologic significance of the axillary arch during axillary lymphadenectomy.

An uncommon and often-overlooked anatomic variation of the latissimus dorsi muscle is the axillary arch. It is formed by an anomalous slip of the muscle that arises from the body of the latissimus dorsi but then inserts along with the pectoralis major muscle anterior to the axillary vein and neurovascular bundle. If an axillary arch is encountered during axillary lymphadenectomy, the lymph nodes posterior and lateral to the arch should be excised. Experience with a number of cases is used to consider local therapeutic and staging factors.

Aged↗

A 40-100 MHz B-scan ultrasound backscatter microscope for skin imaging.

There is a growing interest in high resolution, subsurface imaging of cutaneous tissues using higher frequency ultrasound, and several commercial systems have been developed recently which operate at 20 MHz. Some of the possible applications of higher frequency skin imaging include tumour staging, boundary definition, and studies of the response of tumours to therapy, investigations of inflammatory skin conditions such as psoriasis and eczema, and basic studies of skin aging, sun damage and the effects of irritants. Investigation of these areas is quite new, and the role of ultrasound skin imaging is continuing to evolve. Lateral resolution in the 20 MHz imaging systems ranges from 200 to 300 microns, which limits imaging applications to cutaneous structures which are relatively large in size. In this paper, a real-time ultrasound backscatter microscope (UBM) for skin imaging is described which operates in the 40-100 MHz range, providing axial resolution between 17 and 30 microns and lateral resolution between 33 and 94 microns. This improvement in resolution over current skin ultrasound systems should prove useful in determining the margins of small skin lesions, and in obtaining more precise, in vivo skin thickness measurements to characterize nonmalignant skin disease. Example images of normal skin, seborrhoeic keratosis and malignant melanoma illustrate the imaging potential of this system.

Analog-Digital Conversion↗

Does high-frequency (40-60 MHz) ultrasound imaging play a role in the clinical management of cutaneous melanoma?

The assessment of cutaneous melanoma in the clinical setting is often difficult, and important features such as depth and width remain unknown until the pathology report is received. Access to prognostic features such as vertical height before excisional biopsy would offer a basis for guidance in defining surgical margins and early planning of treatment options. Recently developed high-frequency ultrasound imaging in the 40-to 60-MHz range is a noninvasive method that provides in vivo information about cutaneous lesions. Imaging at these frequencies provides high-resolution data within the range of the epidermis and dermis (3-4 mm in depth). Ten cutaneous melanomas and seven pigmented lesions were assessed in this fashion. Vertical height was documented and compared to histopathological findings. High-frequency ultrasound imaging determination of vertical height correlated well with the standard measurement of Breslow's thickness on histological sections only in midrange (1.0-3.0 mm) lesions. Inflammatory cells at the base of three melanomas provoked an overestimation of the depth measurement with ultrasonography. Thick keratin layers such as those found on the feet acted as a virtual block to the high-frequency scanner. The application of this new advance in noninvasive imaging technology to the clinical assessment of cutaneous melanoma provides interesting in vivo data but in its present state does not replace the need for the biopsy of pigmented lesions and histopathological diagnosis.

Humans↗

Repeated exposure to silicone gel can induce delayed hypersensitivity.

The possible immunologic reactivity of silicone gel remains speculative and controversial. In this laboratory, a quantitative lymphocyte localization assay has been developed and well studied using pure lymphocytes collected by the technique of lymph vessel cannulation in sheep. The kinetics of antigen-specific immune responses (e.g., tuberculin reaction) in this model are well described and accepted. Using the known parameters regarding the response to purified protein derivative and the classic adjuvant Freund's Complete Adjuvant, this study was designed to identify the possible antigen-specific immunologic response, in the form of delayed-type hypersensitivity, after repeated exposure to silicone gel. Pure lymphocytes were collected by cannulating the efferent vessel of a subcutaneous lymph node in four groups of primed sheep which, 30 days previously, had received intradermal injections of 0.9% saline (negative controls; n = 6), Freund's Complete Adjuvant only (positive controls; n = 6), silicone gel (n = 7), or Freund's Complete Adjuvant homogenized with silicone gel (n = 7) in an attempt to induce sensitization. Multiple (1040) intradermal skin tests were performed using silicone gel, purified protein derivative, and 0.9% saline. After the skin lesions had developed for 48 hours, 5 x 10(8) lymphocytes were labeled in vitro with indium-111, returned intravenously, and allowed to circulate for 3 hours. Sheep were euthanized, the skin lesions were removed, and the radioactivity was counted in a gamma spectrometer. The radioactivity in each skin lesion is considered a measure of lymphocyte accumulation. The occurrence of augmented accumulation after reexposure to an antigen is a hallmark of delayed-type hypersensitivity. The purified protein derivative and saline lesions functioned as positive and negative controls, with counts per minute (cpm +/- standard error) of 2404 +/- 478 (Freund's Complete Adjuvant group) and 149 +/- 21 (saline group), respectively. Significantly greater (p = 0.0021) radioactivity was found in the silicone gel sites (310 +/- 35) in the silicone gel-primed group and the Freund's Complete Adjuvant plus silicone gel group (453 +/- 44; p = 0.0004) than in normal skin in each group. These data suggest that it may be possible to induce an antigen-specific lymphocyte-mediated response to silicone gel.

Animals↗

Variables affecting symmetry of the nipple-areola complex.

Currently, little is known about which variables are most critical to the subjective appearance of symmetry of the nipple-areola complex. Clinical photographs were transferred onto a compact disc and then imported into a computer photoshop program. Alterations to the nipple-areola complex were then performed, creating 1 symmetrical image and 19 asymmetrical images. The asymmetries were produced by altering position, diameter, or pigmentation. The images were converted to 35-mm slides and shown to four separate panels of three members each. A "symmetry score" was given for each slide. Results showed that any deviation from symmetrical was reliably detectable by the observers. Changes in areola diameter were detected most easily, and the specific direction of positional change was not found to be a significant factor. Differences were seen between individual panel assessments. This study has shown an application for CD-ROM technology in analyzing well-identified variables and has helped in delineating which factors are most critical to the subjective impression of symmetry of the nipple-areola complex.

CD-ROM↗

Retrograde microvascular augmentation (turbocharging) of a single-pedicle TRAM flap through a deep inferior epigastric arterial and venous loop.

Modern trends in breast reconstruction with the TRAM flap have promoted adequate blood supply to the flap while minimizing the donor-site defect in the anterior abdominal wall. Preservation of the rectus abdominis muscle (both unipedicled and bipedicled), supercharging, delayed, and free-flap techniques all have promoted these principles. A new technique is presented utilizing the single pedicle with a transmidline retrograde microvascular loop anastomosis of the deep inferior epigastric artery and vein. The turbocharging allows increased blood flow to the remote areas of the flap as well as augmented venous outflow. In addition, the abdominal-wall donor site is similar to that of a single pedicle. This technique is ideal for reconstruction where the entire flap is required, a lower abdominal scar is present, or the recipient vessels for the free flap are absent or damaged.

Abdominal Muscles↗

Benomyl-induced craniocerebral anomalies in fetuses of adequately nourished and protein-deprived rats.

Benomyl, a benzimidazole fungicide, produced craniocerebral and systemic malformations in fetal rats when administered by gavage in doses of 31.2, 62.5, and 125 mg/kg of maternal body weight on days 7-21 of gestation. Malformations increased in incidence and severity with increasing benomyl dosage and nearly doubled when coupled with a protein-deficient diet. Protein deficiency alone produced only decreased fetal weight. High benomyl doses produced higher percentages of fetal resorptions and late fetal deaths, and these percentages also increased with protein deficiency. A benomyl dose of 62.5 mg/kg in protein-deficiency dams, the optimal combination for a high incidence of anomalies and low fetal wastage, produced hydrocephalus in 69.4% of fetuses, meningocele in 8.2%, encephalocele in 14.3%, exencephaly in 44.9%, anencephaly in 14.3%, corpus callosum agenesis in 26.5%, periventricular necrosis in 26.5%, and periventricular cellular "overgrowth" in 55.1%. The most common combination of anomalies was hydrocephalus, exencephaly, and periventricular "overgrowth." Common systemic malformations included cleft palate, micromelia, hydroureter, and misshapen tails. No fetus was entirely normal at the highest benomyl dose. Benomyl has been shown by others to bind tubulin and inhibit the formation of microtubules that are important in neurulation, mitosis, and cell migration during early brain development. Thus, it is suggested that benomyl, coupled with a protein-deficient diet, offers a teratogenic model with a spectrum of abnormalities similar to hypervitaminosis A but with a higher yield of specific craniocerebral anomalies.

Animals↗

Effects on the fetus of maternal nitrofen exposure in the protein-deprived rat.

The separate and combined effects of protein deprivation and nitrofen exposure were studied in the pregnant rat. Animals were fed diets containing 24, 8, 6 or 4% casein throughout gestation. Within each diet group, subgroups were gavage-fed with 12.5 (lower dose) and 25 (higher dose) mg nitrofen/kg body weight or with oil carrier only on days 7-21 of gestation. Dams were weighed and food intake was measured daily. On day 21 of gestation, cesarean-derived pups were examined for congenital anomalies and dissected for determination of organ weights. Skeletons were alizarin-stained and examined for skeletal anomalies and developmental stage. No effects on the skeleton or gross congenital anomalies were seen. Fetal size and weights of liver, kidney, intestine, heart, lung and brain were reduced with decreasing casein content of the diet and as a result of the higher dose of nitrofen. An effect of interaction between diet and nitrofen exposure was shown in the kidney, intestine and lung weights. Specific toxicity affecting organ size was shown to occur in the intestine and lung. An interaction between diet and nitrofen specifically affected kidney and intestine. Brain size tended to be preserved, a possible protective mechanism negated by nitrofen exposure. The data suggest also that kidney, intestine and lung are particularly affected. Effects, however, occur primarily in young of severely malnourished dams receiving a relatively high dose of nitrofen.

Abnormalities, Drug-Induced↗

Effects on the fetus of maternal benomyl exposure in the protein-deprived rat.

The separate and combined effects of protein deprivation and benomyl [(methyl 1-butylcarbomoyl)-2-benzimidazole carbamate] exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups were gavaged at 31.2 mg/kg body weight with benomyl or corn-oil carrier only on d 7-16 or 7-21 of gestation. No effects on the skeleton were seen. Benomyl exposure in the last 2 wk in dams fed the 24% casein diet resulted in a high incidence of fetal brain anomalies. This effect did not occur in those with benomyl exposure during the period of organogenesis only and was reduced in groups fed the protein-deficient diet. Exposure to benomyl in the last 2 wk in the protein-deprived rat resulted in a decrease in the weight of the fetal heart in excess of that attributable to diet alone. Lungs were a smaller portion of body weight in fetuses of benomyl-treated dams in both diet groups. The teratogenic effect on the brain in animals exposed to benomyl in wk 2 and 3 of gestation suggests that screening for teratogenic effects during organogenesis only may be insufficient.

Administration, Oral↗