Biomedical subjects
M S Granick
Publications and source records attributed to M S Granick.
Elective plastic surgery in a Jehovah's Witness: a case series and review of the literature.
"Bloodless" plastic surgery in the Jehovah's Witness patient is an area that has received little attention in the surgical literature. Given the unique and firmly held beliefs of this group of patients, caring for them can be particularly challenging for the plastic surgeon. The authors report a case of bilateral breast reconstruction with saline-filled implants complicated by a postoperative hematoma and one involving a staged approach to massive breast reduction, both in Jehovah's Witness patients. A third patient involving a staged panniculectomy for a complicated wound infection is also described. The historical background, philosophical views, ethical issues, legal aspects, surgical outcomes, and management techniques relevant to caring for this unique patient population are also reviewed in detail.
Thrombospondin 1 and its specific cysteine-serine-valine-threonine-cysteine-clycine receptor in fetal wounds.
Thrombospondin 1 (TSP-1), an adhesive glycoprotein, plays an important role in platelet adhesion, inflammation, cell-cell interaction, and angiogenesis. TSP-1 is expressed by endothelial cells, fibroblasts, and macrophages. The unique cysteine-serinevaline-threonine-cysteine-glycine (CSVTCG) binding domain of TSP-1 also plays an important role in cell binding and modulation of cellular processes. The purpose of this study was to evaluate histologically and quantitatively TSP-1 and its CSVTCG receptor in fetal skin wounds over time. Pregnant ewes underwent laparotomy and hysterotomy. At 65 days gestation (term, 145 days), incisional and excisional wounds were created on the fetal back in a similar position on each animal. The uterus and laparotomy were closed. The wounds were harvested on days 1, 3, 7, 21, and 28. Expression of TSP-1 and its CSVTCG receptor was evaluated immunohistochemically and quantitated by computer image analysis in units of absorbance. Immunoglobulin G (negative) controls were performed and subtracted from the TSP-1 sample to eliminate background absorbance readings. Serum (negative) control was used for the CSVTCG receptor. Platelet concentrates were used as the positive control: TSP-1, 63.43; CSVTCG, 58.72. Results are expressed as absorbance+/-SEM. Results of TSP-1 are as follows: day 1, 33.02+/-0.26; day 3, 22.21+/-0.14; day 7, 20.56+/-1.07; day 21, 7.76+/-0.40; and day 28, 5.99+/-0.03. TSP-1 displays an early peak during fetal skin repair, followed by a steep decrease over the viewed time period. Results of CSVTCG receptor are as follows: day 1, 26.19+/-2.43; day 3, 30.20+/-0.64; day 7, 24.56+/-0.80; day 21, 24.70+/-0.40; and day 28, 21.65+/-1.39. Thus, CSVTCG receptor displays a slowed decrease in expression over time during fetal repair. No significant differences were noted between incisional and excisional samples. Temporal and histological differences exist in the localization and expression of TSP-1 and its CSVTCG receptor during fetal wound repair. TSP-1 is upregulated in tissues early. This corresponds with the known role of TSP-1 in cell-cell interaction, including potentiation of growth factor activity. TSP-1 also modulates matrix, allowing scar-free provisional matrix in the earlier stages of repair deposited by platelets. The potentiation of cell-associated protease activity by TSP-1 can support tissue and matrix turnover. This activity of TSP-1 may contribute to the formation of a scarless wound. TSP-1 destabilizes extracellular matrix contacts, and facilitates mitosis and migration. The action of TSP-1 as an adhesive protein allows numerous different cells to adhere to the extracellular membrane. CSVTCG receptor expression decreases during fetal repair as the cells migrate to the epithelial surface, suggesting a significant role of the CSVTCG receptor in keratinocytic maturation, differentiation, and epithelization.
A new educational role for plastic surgery in the fourth year of medical school.
At most medical schools, students are offered limited or sporadic experiences in plastic surgery. This is unfortunate because all physicians need to possess the knowledge and skills to evaluate skin lesions and participate in wound management. Also, students who are considering a career in plastic surgery do not have adequate information to make informed decisions. With the restructuring of plastic surgery training programs, career decisions of individuals interested in plastic surgery are being made earlier than ever before in the education continuum, and the aforementioned problem assumes greater magnitude both for the students and the faculty. At MCP-Hahnemann School of Medicine, basic plastic surgery experiences have been integrated into the third-year surgery clerkship as a requirement for all students, and a Plastic Surgery Pathway has been designed in conjunction with the school's pathway system for fourth-year students. The Pathway provides a framework for the student to select a combination of rotations that will best provide an appropriate broad-based education in preparation for training in plastic surgery, and it provides extensive guidance by faculty members in the discipline to assist with career decisions, rotation selection, and preparations for the residency application process. Students in the Plastic Surgery Pathway are required to take rotations in medicine, neurology, and plastic surgery. The remaining rotations are selected from a list of options based on the student's individual learning needs, interests, and career aspirations. Early experience with the Plastic Surgery Pathway has shown that it has been well received by students and faculty, has assisted students with their career decisions, and has led to an increased student awareness of the importance and relevance of the specialty.
Microvascular tissue transfer in a pregnant patient.
Pregnancy is a relative contraindication for elective surgery. The primary concerns are for the safety of the fetus and the mother. However, there are particular problems involving microvascular surgery due to the pregnancy-associated hypercoagulable state. The authors were presented with a 35-year woman, 20 weeks pregnant, with a degloved foot and ankle associated with an open distal tibia/fibula fracture (Gustilo IIIB). Salvage of her leg required a microvascular tissue transfer. Accordingly, a combined latissimus dorsi-serratus anterior free flap was performed with a saphenous vein graft to the popliteal vessels. The patient was hypercoagulable and there were extensive platelet clots. Her consumption of heparin was enormous. Postoperatively, she was treated with intravenous dextran for 5 days and for 17 days with intravenous heparin. After discharge, she was placed on subcutaneous heparin until she delivered a healthy baby. The flap survived and her leg was salvaged. The hypercoagulable state of pregnancy, as well as thromboprophylaxis, are discussed.
Soft-tissue complications of intra-arterial chemotherapy for extremity sarcomas.
High-grade sarcomas have a high rate of local recurrence as well as distant metastases. This has led to the development of intra-arterial chemotherapy (IAC) as part of a multimodal approach to control local disease and/or reduce the extent of surgical resection. Intra-arterial catheters are positioned by an interventional radiologist into the feeding vessels of the tumor. Adriamycin and 5-fluorodeoxyuridine are infused intra-arterially. Cisplatinum, with or without granulocyte colony stimulating factor, is given systemically. Patients usually experience acute self-limited soft-tissue inflammation in the treated area. In our experience of 118 patients, 3 patients experienced soft-tissue necrosis that required excision and reconstruction. The first was treated for synovial sarcoma of a metatarsal. After IAC with Adriamycin, she sloughed the skin, subcutaneous tissue, and some of the posterior compartment musculature of her calf. This tissue was debrided. A gastrocnemius flap and skin graft were used for coverage. She is free of disease and ambulatory. The second patient was treated with IAC Adriamycin for a radial head chondrosarcoma. She developed soft-tissue slough, which became infected with Pseudomonas. She required extensive debridement of the skin, subcutaneous tissue, and muscle, and was subsequently reconstructed with a latissimus flap and a split-thickness skin graft (STSG). She later developed a local recurrence requiring amputation. The latissimus was elevated and used to cover the distal stump. She also is free of disease. The third patient was treated with IAC Adriamycin for Ewing's sarcoma of the right femur. This was complicated by fat necrosis and persistent pain. Subsequent radiotherapy only worsened her symptoms. She underwent wide excision and muscle flap/STSG repair, which relieved her pain. She is currently ambulatory and free of disease. In conclusion, as the use of IAC continues, its complications may become more common. Our experience with this previously unknown entity is illustrated and therapeutic options are discussed.
Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer.
Growth factors play a crucial role in the regulation of cellular proliferation and matrix degradation in wound healing and cancer. We have shown that thrombospondin 1 (TSP-1) and its cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG)-specific receptor play a key role in cell invasion and matrix degradation in different carcinomas. The present study was done to determine whether TSP-1 and its receptor show a similar pattern of expression in wound healing and cancer. Expression and localization of TSP-1 and its receptor were determined in fetal wounds, adult burn wounds, and different human malignancies by immunohistochemical staining and computerized image analysis. In healing wounds, TSP-1 was expressed in the stroma early in the process, followed by a steep decline. The TSP-1 receptor localized to neovessels and highly proliferating cells (i.e., fibroblasts, basal cells), its levels remaining relatively constant. Cancer cells and tumor-associated microvessels expressed the TSP-1 receptor, whereas TSP-1 localized predominantly to the tumor-associated stroma. These data suggest a critical role for TSP-1 and its CSVTCG-specific receptor in wound healing and cancer.
Bipedicle muscle flaps in sternal wound repair.
Infection following median sternotomy is a devastating and potentially life-threatening complication. The use of muscle flaps has become widely accepted as a mainstay in the treatment of these problems. We have previously described our successful use of a bipedicle muscle flap for reconstruction of sternal defects in 16 patients. In this paper, we describe follow-up in those patients as well as an evaluation of this procedure in an additional 26 patients. All records of those patients who had sternal reconstruction using the bipedicle pectoralis major-rectus abdominis flap were reviewed. Factors analyzed included the type of cardiac surgery, associated conditions, complications of surgery, and outcome. There were 42 patients in this group from 1989 to 1996. There were a variety of cardiac procedures represented. Associated conditions included diabetes, chronic hypertension, prolonged postcardiotomy hypotension, prior radiation therapy, pulmonary failure, and steroid use. There were no deaths in this series. There was one flap failure, one persistent infection, one pneumothorax, and one hernia in this series. Three patients developed hematomas after surgery. The most common complication was a skin slough, which occurred in nine patients. This technique provides a large flap that can fill the entire mediastinum. The dissection is rapid, and the complication rate compares favorably to that of other methods.
Outcome assessment of an in-hospital cross-functional wound care team.
A multidisciplinary wound care team was developed at the Medical College of Pennsylvania Hospital in 1993 to standardize wound management, appropriately allocate resources, prevent the occurrence of hospital-acquired decubitus ulcers, and effectively manage existing pressure ulcers. This report presents 4 years of prevalence survey data (n = 690 patients over 4 years), which affords an outcome analysis regarding the efficacy of the multidisciplinary wound care team. A significant reduction in the number of patients with pressure ulcers, hospital acquired pressure ulcers, and patients with hospital acquired ulcers occurred. There was, also, a significant improvement in skin integrity documentation, and in the implementation of nutritional assessments. These findings suggest that the multidisciplinary wound care team has been an effective means of gaining some control of decubitus ulcers, which are associated with increased patient morbidity and have an adverse economic impact on hospitals.
Localization of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue.
Thrombospondin-1 (TSP-1) is a matrix protein implicated in mechanisms of wound healing. TSP-1 contains the sequence cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) that has been shown to function primarily as a cell adhesion domain. Our laboratory has isolated a novel receptor specific for the CSVTCG adhesive domain of TSP-1. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate TSP-1 and its CSVTCG receptor in surgically created colon anastomotic wounds. Histopathologic and quantitative examination demonstrated increased expression of TSP-1 and its CSVTCG receptor in areas of wound healing. These findings suggest a role for TSP-1 and its CSVTCG receptor in wound healing. The control of expression and activity of these molecules may eventually be the basis for the development of wound healing agents that could significantly reduce the morbidity from surgical intervention.
Localized cutaneous Nocardia brasiliensis mimicking foreign body granuloma.
Nocardia brasiliensis is recognized in the United States as an infectious agent of the skin that may present as an abscess, ulcer, or granuloma with or without "sporotrichoid" spread, and rarely causes systemic disease. Treatment with trimethoprim/sulfamethoxazole is usually curative. We present a patient with multiple erythematous, painful, draining nodules that developed thirty-six months after trauma and subsequent contamination with soil in Bermuda. A foreign body granuloma was suspected clinically, and excision was performed followed by recurrence of the lesions. Histologic examination and culture were consistent with nocardiosis. Differential diagnosis of foreign body granulomas also should include infection with N. brasiliensis even after a long incubation period. Culture and drug susceptibility testing of affected tissue should be performed for diagnosis and management.
A multidisciplinary approach to wound care in the hospitalized patient.
Wound care services at a tertiary level teaching hospital were reorganized to improve patient care and control costs. A multidisciplinary wound care team was implemented to develop an aggressive, proactive approach to prevent and minimize pressure ulceration. Outcome data demonstrate the efficacy of the wound care team.
Alma Dea Morani, MD: a pioneer in plastic surgery.
Alma Dea Morani was the first female member of the American Society of Plastic and Reconstructive Surgeons. She is now retired from active practice and living in Philadelphia, but her life continues to reflect her role as a plastic surgeon. She was drawn to medicine by the Women's Medical College of Pennsylvania (now part of Allegheny University), graduating in 1931. Her love of art, which she learned from her sculptor/father, Salvatore Morani, drew her to plastic surgery. Her difficulty obtaining training in the specialty would have caused others to abandon the goal, but she pursued it with great vigor. Her career path as a plastic surgeon was diverse and challenging. She returned to the Women's Medical College to start her practice, treating the broad spectrum of problems that we all see, and rose to the rank of clinical professor of surgery. In that capacity she was a role model for a whole generation of women who, in turn, acted as mentors for many others to pursue careers in plastic surgery. Dr Morani never shied from politics, playing an international role in women's issues in health care and medical education. Throughout all of this she maintained her interest in art not only as a collector, but as an artist, creating her own works until just a few years ago. Dr Morani was the driving force behind the creation of the Morani Gallery of Art at the Medical College of Pennsylvania. This facility is the only ongoing art gallery and collection at any medical school in the United States. As a tribute to her, the chair of surgery at Allegheny University is endowed in her name. She continues to serve as an inspiration to all of us-from medical students to practicing physicians of all types-not only with her ideas, but with the realization that through active participation with the world of art we become stronger, more humane physicians. Alma Dea Morani has inspired a generation of women to pursue careers in plastic surgery. At 89 years of age she continues to serve as an inspiration to young physicians, especially women, who wish to combine the skills of a plastic surgeon with an appreciation of the role of art in the maturation of the individual.
Histopathology and clinical assessment correlate with the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) receptor of thrombospondin-1 in breast tumors.
Thrombospondin-1 (TSP-1) is a matrix protein implicated in mechanisms of tumor metastasis. TSP-1 has a characteristic Cysteine-Serine-Valine-Threonine-Cysteine-Glycine (CSVTCG) sequence that functions as a tumor cell adhesion domain. Our laboratory has isolated a novel CSVTCG specific tumor cell receptor. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate the CSVTCG receptor of TSP-1 in a wide spectrum of human archival breast tumors. Histopathologic and quantitative examination was correlated with clinical findings two years post operation. Increasing amounts of CSVTCG receptor correlated positively with worsening histopathologic and clinical findings. These findings suggest a role for the TSP-1 CSVTCG receptor in breast tumor progression. This receptor may have utility for the diagnosis, staging, and treatment of this common and deadly disease.
Squamous cell and adnexal carcinomas of the skin.
The diagnosis and treatment of adnexal cancers continues to pose a challenge to a wide range of clinicians. The diseases are a diverse lot, owing to the wide range of skin structures and large surface area. Early recognition and treatment are key to improved outcomes. Education of the patients as to their role in their care, especially early detection, is also of crucial importance. Further study may yield information to improve diagnosis and treatment.
Mycobacterium fortuitum infection of the sternum. Review of the literature and case illustration.
Sternal wound infection with atypical mycobacteria following open heart surgery is a rare occurrence. Previous reports have described infection by Mycobacterium fortuitum, an acid-fast bacillus and member of a larger family of rapidly growing mycobacteria. The source and mode of transmission have not been identified. Surgical debridement and the combination of aminoglycosides and quinolones have been shown to be effective methods of treatment. More recently, clarithromycin has been shown to be the drug of choice against rapidly growing mycobacteria. We describe a 49-year-old woman who underwent infundibular stenosis repair and in whom M fortuitum sternal osteomyelitis developed. Total sternectomy, muscle flap reconstruction, and antibiotic treatment successfully eradicated the infection.
Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer.
TSP-1 is a matrix-bound adhesive glycoprotein, which plays a role in tumor cell proliferation and tumor angiogenesis. The purpose of this study was to investigate the effect of TSP-1 on breast tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. Four breast cell lines were studied in serum-free media: the malignant MDA-MB-231, SKBR-3, and MCF-7 cell lines, and the benign MCF-10A cell line. Invasion was measured as the summation of the number of cells in five representative high power fields (400x) traversing the collagen barrier after a 3-hr incubation period. The effect of an anti-TSP-1 antibody (100 microgram/ml) was also evaluated in the malignant cell lines. Statistical analysis was performed by ANOVA and Student's unpaired t test. TSP-1 promoted a dose-dependent increase in invasion as compared to buffer controls in all three malignant cell lines. TSP-1 (100 nM) promoted a greater than five-fold increase over controls in tumor cell invasion for MDA-MB-231, SKBR-3, and MCF-7 cell lines (P < 0.005). TSP-1 had no effect on the invasiveness of the benign cell type MCF-10A. Anti-TSP-1 antibody inhibited TSP-1 promoted invasion in the MDA-MB-231, SKBR-3, and MCF-7 cell lines by 45, 48, and 39%, respectively (P = 0.003, 0.044, 0.047). TSP-1 promotes tumor cell invasion of collagen by breast cancer cells. Therapy designed to inhibit TSP-1 may prevent invasion and metastasis in breast cancer.
Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor.
BACKGROUND: Thrombospondin-1 (TSP-1) is a matrix-bound adhesive glycoprotein. Breast carcinoma cells exhibit increased expression of a novel TSP-1 receptor. We evaluated the role of this receptor in breast cancer adhesion and progression. METHODS: Adhesion assays were performed to evaluate MDA-MB-231 breast cancer cell adhesion to TSP-1 in vitro in the presence of either nonimmune immunoglobulin G(IgG) or anti-TSP-1 receptor IgG. Receptor-mediated tumor cell progression was evaluated in athymic nude mice. Mice were inoculated with MDA-MB-231 breast cancer cells and randomized to treatment with intraperitoneal injections of saline solution, nonspecific IgG antibody, or an anti-TSP-1 receptor antibody every other day for 20 days. Mice were killed at 21 days. The peritoneal cavity was examined grossly for primary tumor implantation. The liver and lungs were examined histologically for micrometastases. RESULTS: MDA-MB-231 breast cancer cells adhered to TSP-1 in vitro. This adhesion was inhibited to 10% of control by anti-TSP-1 receptor antibody (p < 0.005). Anti-TSP-1 receptor antibody inhibited in vivo breast cancer progression. Mice treated with control IgG antibody or saline solution alone exhibited extensive intraperitoneal seeding. Only one mouse treated with the anti-TSP-1 receptor antibody exhibited any intraperitoneal tumor seeding (p < 0.01). CONCLUSIONS: These data suggest that TSP-1 and its receptor play an important role in breast cancer progression.