Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action.

Human endometrial tissue and primary stromal cell culture contain immunoreactive epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-AB as well as EGF and PDGF-beta receptors. The immunostaining for EGF, EGF receptor, and PDGF beta-receptor were associated with endometrial luminal and glandular epithelial and stromal cells, whereas only the stromal cells contain immunoreactive PDGF-AB. The immunostaining intensity of EGF, EGF receptor, and PDGF-AB was similar in both phases of the menstrual cycle, whereas, PDGF-beta receptor immunostaining was highest in proliferative phase and considerably reduced, particularly in luminal and glandular epithelial cells in the secretory phase. In addition primary stromal cell cultures express EGF, PDGF-AB, and contain EGF and PDGF-beta receptors, and very low levels of PDGF-alpha receptor. 3H-Thymidine incorporation indicate that after 48 h of incubation in serum-free medium approximately 75-80% of stromal cells are quiescent. Incubation of quiescent stromal cells with 10% fetal bovine serum stimulate 3H-thymidine incorporation in a time-dependent manner reaching maximal after 30-48 h, with a doubling time of 38.2 h. EGF (1.5-15 ng/ml) stimulates 3H-thymidine incorporation by quiescent stromal cells (P less than 0.001). This effect was significantly reduced at concentrations above 15 ng/ml (P less than 0.005). PDGF-AB (3-10 ng/ml) and PDGF-BB (0.5-10 ng/ml) also stimulate 3H-thymidine incorporation in quiescent stromal cells compared to controls (P less than 0.005). The action of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) was time dependent, reaching maximal after 36 and 48 h of incubation (P less than 0.002). Addition of PDGF-AB (10 ng/ml) to EGF (15 ng/ml) significantly enhanced the action of EGF or PDGF-AB used individually (P less than 0.001). 17 beta-estradiol or progesterone at 1 microM did not stimulate 3H-thymidine incorporation, although they were stimulatory in combination (P less than 0.001), they did not alter the action of EGF or PDGF when added in combination. These observations provide further evidence that human endometrial tissue contains specific immunoreactive EGF receptors. It also demonstrates the presence of immunoreactive EGF, PDGF-AB, and PDGF-beta receptors in endometrial tissue as well as stromal cells in primary culture. Both EGF and PDGF are mitogenic for endometrial stromal cells, suggesting an autocrine/paracrine role in modulation of endometrial cell growth and differentiation.

Presence of epidermal growth factor, platelet-derived growth factor, and their receptors in human myometrial tissue and smooth muscle cells: their action in smooth muscle cells in vitro.

Immunohistochemical observations indicate that human myometrial smooth muscle cells express epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-AB and contain EGF and PDGF-beta receptors with no variation in intensity with phases of the menstrual cycle. Furthermore, immunofluorescent microscopic studies revealed that primary myometrial smooth muscle cell cultures also express EGF, PDGF-AB, and contain EGF and PDGF-beta, but not alpha-receptor. Incubation of subconfluent smooth muscle cells in serum-free medium leads to quiescence within 48 h as demonstrated by 3H-thymidine incorporation and labeling index. Exposure of quiescent cells to 10% fetal bovine serum stimulates resumption of DNA synthesis and proliferation in a time-dependent manner with a doubling time of 41.6 h. EGF (1.5-50 ng/ml) and PDGF-AB (1-10 ng/ml) in a dose- and time-dependent manner significantly stimulated 3H-thymidine incorporation by quiescent myometrial smooth muscle cells (P less than 0.05). Combinations of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) significantly increased 3H-thymidine incorporation induced by either growth factor alone (P less than 0.05). PDGF-BB at 10 ng/ml also stimulated 3H-thymidine incorporation and its effect was similar to that induced by PDGF-AB at the same concentration. 17 beta-Estradiol (E2) at 1 microM inhibited 3H-thymidine incorporation by the smooth muscle cells (P less than 0.05). E2 also reduced the stimulatory effect of EGF (15 ng/ml) and PDGF (3 ng/ml). Progesterone at 1 microM either alone or in combination with E2 did not have any effect on 3H-thymidine incorporation or alter the mitogenic action of EGF and PDGF. The effect of EGF and PDGF on cell growth and 3H-thymidine incorporation by myometrial smooth muscle cells was independent of phases of the menstrual cycle. In summary, the results of present studies indicate that human myometrial tissue and myometrial smooth muscle cells in primary culture locally produce EGF and PDGF-AB and contain EGF and PDGF-beta, but not alpha-receptors. Moreover, the myometrial smooth muscle cells in culture respond to the mitogenic action of EGF and PDGF.

In vivo and in vitro degradation of monofilament absorbable sutures, PDS and Maxon.

Two new absorbable monofilament suture materials polydioxanone and Maxon are being employed increasingly in abdominal surgery because of increased strength retention and decreased tissue reactivity compared with previously available materials. As part of our investigation of the behaviour of suture materials, 3-0 sutures of polydioxanone and Maxon were enclosed in nylon pouches, a technique developed for in vivo experiments to prevent cellular interaction with implanted devices. The pouched sutures were gas sterilized, then implanted in either the extrafascial space or peritoneal cavity for periods of 1-5 wk. Sterilized sutures were also incubated in Ringer's lactate at 37 degrees C. Tensile strength of the exposed sutures was measured. For a given suture material and duration of incubation, there was no significant difference in tensile strength degradation among the three test environments. Although the strength of unexposed Maxon is greater than that of polydioxanone, the residual strength of Maxon decreases more rapidly in use, so that, after 2 wk, the strength of polydioxanone is greater. Scanning electron microscope examination of the suture surfaces reveals that polydioxanone develops surface crazing with time, whereas the surface morphology of Maxon remains relatively unaltered.

Stress relaxation of organic suture materials.

Sutures fabricated from synthetic polymeric materials exhibit the phenomenon of stress relaxation, that is, when held under tension at a fixed elongation, there is a gradual realignment of the microstructure to accommodate the developed tensile stress. This property has been characterized for three modern suture materials, polypropylene, polydioxanone and poly(glycolic acid). All three materials exhibited stress relaxation but to different degrees, with polypropylene exhibiting the greatest stress relaxation (to approximately 40% of the initial load). The initial rate of stress relaxation increased with the rate of loading but the residual stress level was found to be independent of elongation rate except at extremely low rates of loading.

Characterization of surgical needles.

The acuity (sharpness) of surgical needle points was assessed by measuring the force required for repeat needle penetrations through a medium-gauge latex sheet glued to a perforated Plexiglas frame. The data on the variation in the applied force with repeat penetrations showed that needles obeyed the general relation: P = A + B.n; where P is the applied penetration force in grams, n is the number of penetrations and A and B are constants. Constant A characterized the needle-point acuity and B the maintenance of acuity. This relationship indicated both needle acuity and acuity maintenance with repeated passes through a reproducible target material. Determining the microhardness of needles provided data on their strength which helped to account for differences in the acuity of apparently similar needles. The tensile strength of the union between suture and needle was determined to evaluate the security of suture attachment.

Tensile properties of suture materials.

The tensile properties of three new sutures, two non-absorbable and one absorbable material, have been evaluated and compared with those of polypropylene and nylon sutures. It was found that the five materials differed significantly in their tensile strengths and elastic/plastic deformation characteristics but displayed comparable elongations at failure. All sutures showed a decrease in failure load and elongation at failure when knotted. Most materials showed an increased tensile strength and decreased elongation at failure for smaller suture gauges, and this behaviour is thought to be related to their internal molecular organization.

Tensile characteristics of PTFE sutures.

The tensile strength load to failure and knotting characteristics of the six gauges of a new PTFE suture have been studied. In its unstressed state, the suture comprises 50% by volume of air but this diminishes upon stretching so that its diameter appears to be very large and the tensile strength low. The low surface-surface friction necessitates fairly complex knotting regimens (3 = 1 = 3 = 2 or 3 = 1 = 3 = 3) to ensure stable knot configurations, i.e. failure of the loop before knot failure. However, the relatively simple 2 = 1 = 1 = 1 configuration was found to have an adequate tensile strength.

The use of nylon pouches to prevent cellular attachment to implanted materials.

A nylon pouch system has been developed to permit the in vivo exposure of implantable materials to tissue fluids without complications arising from cellular attachment or from the bacterial attack. SEM observations have indicated that the pouches were effective in reducing the ingress of bacteria as well as reducing, and in some cases eliminating, cell infiltration through their mesh structure. Over a 7 d implantation period, the exterior surfaces of the nylon pouches were heavily infested with microorganisms but there was minimal growth of bacteria within the pouches. Non-infected pouches that were implanted for up to 25 wk showed heavy deposits of cellular matter on the external surfaces of the pouches and minimal deposits within the pouches.

Giant uterine tumors: case report and review of the literature.

This is a case report of the management and surgical removal of a 65-lb uterine leiomyoma. This is the 56th reported case of a giant uterine tumor (25 lb or over) and the eighth such case reported in the last 35 years. The literature concerning these large tumors is reviewed, and a discussion of some of the important aspects of surgical management is presented.

Localization of transforming growth factor beta isoforms TGF-beta 1, TGF-beta 2, and TGF-beta 3 in surgically induced pelvic adhesions in the rat.

OBJECTIVE: To investigate the presence and cellular distribution of transforming growth factor (TGF)-beta s in surgically induced pelvic fibrous adhesions in rat uterine horns subjected to burn, crush, and debridement injury. METHODS: Thirty injured and 20 uninjured rats were treated postoperatively with intraperitoneal administration of either 2 micrograms/mL of recombinant human TGF-beta, 10 micrograms/mL TGF-beta neutralizing antibody, or phosphate-buffered saline + 500 micrograms rat serum albumin for 5 consecutive days. The intact (uninjured) and fibrous tissues were analyzed immunohistochemically for the presence of TGF-beta s using polyclonal antibodies to TGF-beta s 1-3. RESULTS: The intact peritoneum immunostained with a lower intensity than fibrous adhesive tissues for TGF-beta 1, TGF-beta 2, and TGF-beta 3. The immunoreactive TGF-beta s were present in fibroblasts, inflammatory cells infiltrated into the fibrous adhesion, and endothelial and smooth-muscle cells of the arterioles. In the uterine tissue at the site of injury, the following immunostained for TGF-beta s: uterine serosal tissue, myometrial smooth-muscle cells, endometrial luminal and glandular epithelial cells, and inflammatory cells. However, endometrial stromal cells did not immunostain for TGF-beta s. There were no substantial differences in immunostaining intensities of fibrous adhesive tissues in the TGF-beta group, neutralizing TGF-beta antibody group, and the controls. CONCLUSION: The data suggest that TGF-beta s may play a role in the formation and maintenance of fibrous adhesions following intraperitoneal injury.

Mechanical properties of coated absorbable multifilament suture materials.

The mechanical properties of coated polyglactin 910 (Vicryl) and coated plyglycolic acid (Dexon) were defined. Scanning electron microscopy of 0 gauges of both materials showed some differences. Coated polyglycolic acid had minimal surface aberrations. Unknotted tensile strength measurements of gauges 1, 0, 00, and 000 demonstrated no statistically significant difference between the two materials. Both materials reached knot security at the 2=1=1=1 configuration. The in vivo tensile strength measurement of 0 gauges showed polyglactin 910 to be significantly stronger at 21 days. Histologic evaluation revealed no statistically significant difference between the materials.

Management of condylomata acuminata with the carbon dioxide laser.

Ninety-four patients with condylomata acuminata of the lower genital tract and perianal region were treated with the carbon dioxide laser. Most were managed in the outpatient clinic, but 1 to 4 treatments were required depending upon extent of involvement. Of 90 patients, 75 (83.3%) were free of lesions on all follow-up examinations after initial treatment. Of 15 patients with recurrent lesions, 13 underwent a second laser treatment; 7 of these 13 have been subsequently free of condylomata. The overall success rate was 91%. The carbon dioxide laser provides an appealing method of management of condylomata acuminata because of its precision, rapid healing without scarring, and safety when used during pregnancy.

Comparison of clinical and surgical-staging in patients with endometrial carcinoma.

The preoperative clinical and radiologic findings and staging were compared with the operative and pathological findings and surgical staging in 62 consecutive patients with endometrial carcinoma. Overall, the tumor grade was changed in 33.8% of the patients, and the histologic type of tumor was changed in 27.4% of the patients. The preoperative clinical staging was changed in 51% of the patients after surgery. The change for the stage was as follows: stage I, 30.4%; stage II, 62.5%, stage III, 60%; and stage IV, 0%. The endocervical curettage was found to have a 50% false-positive rate and a 13% false-negative rate.

Effects of thermal knives on wound healing.

Tissue response to injury caused by the electrosurgical scalpel, the hemostatic Shaw scalpel, the CO2 laser, and a standard steel scalpel have been compared. Subcutaneous incisions in pigs were evaluated histologically at 1, 4, 7, 14, and 22 days postincision. The least damage was produced by the standard steel scalpel at all time periods. Epithelial migration started on day 1 for the standard steel scalpel, on day 4 for the Shaw scalpel, and only on day 7 for the electrosurgical scalpel and laser knives. Lateral thermal necrotic zones were found for all three thermal knives. Tensile testing showed no significant differences in the early postincision tissue strength. By day 14 wounds made with the standard steel scalpel were stronger than those made with the Shaw and electrosurgical scalpel. These findings indicate that thermal injury delays the wound healing process.

Extraspinal ependymomas. Report of three cases.

Spinal ependymomas may rarely arise from heterotopic ependymal cell clusters and thus occur in an extraspinal location. Presentation of three cases and a review of the literature reveal that these tumors have characteristic radiographic and clinical features. They occur mainly in patients in the third decade of life, and present either in the soft tissue posterior to the sacrum or in the pelvis. In the case of posterior tumors, the patient exhibits a mass which is usually mistaken for a pilonidal cyst. Patients whose tumor is pelvic in location present with sphincter disturbances or dysfunction of the sacral nerve roots. Conventional and computerized tomographic studies will reveal erosion of the sacrum. Myelography will demonstrate an extradural mass indenting the thecal sac from below. The protein in the cerebrospinal fluid will be normal. A combined posterior and anterior approach with the goal of complete tumor removal is the procedure of choice. If this is not feasible, then radiation therapy should be employed. Because of the increased incidence of systemic metastases, the average postoperative survival is approximately 10 years.

Oral contraceptive agents: current status.

Oral contraceptives are the most widely prescribed and ingested drug in human history. The difficulty in establishing their clear-cut side effects is compounded by the rarity of these side effects and their occurrence with multiple other factors and cofactors that may be etiologically more important. For the prudent surgeon, suffice it to say that should operation require bedrest postoperatively, oral contraceptives should be stopped at least 2 weeks preoperatively and barrier methods begun. Barrier methods should also be used when drugs that interfere with oral contraceptives are prescribed. Oral contraceptives and anticoagulants should not be given together because of the chemical changes in the blood caused by the steroid content of the contraceptive. As surgeons, we must remember the contraindications noted herein and become familiar with the current literature as new developments unfold in the dynamic field of conception control.

Selection of incisions for gynecologic procedures.

Progress is being made in the employment of abdominal incisions. The use of mass closure has greatly decreased the incidence of disruption. The avoidance of subcutaneous sutures has likewise decreased the rate of wound infections, and modern aggressive management has lessened the time that patients must contend with incisional abscesses when they do occur. There will always be considerable discussion and debate on the choice of an abdominal incision. However, the primary consideration remains always to choose and construct a surgical incision large enough to operate through comfortably and effectively.

Descriptive and predictive validity of a high-risk alcoholism relapse model.

A major problem with alcoholism treatment is the high rate of early recidivism to drinking and re-admission for alcoholism treatment. The objective of this study was to retest a model or predict early (within 6 months) re-admission to alcoholism treatment using a second independent sample. Additionally, we compared a high-risk alcoholism relapse (HAR) model (defined by chronicity of heavy drinking, daily alcohol consumption and previous treatment history) with three previously defined alcoholism typologies for descriptive and predictive validity. Male alcoholics (N = 299) admitted for treatment at a Veterans Affairs inpatient treatment program were interviewed and then followed for 6 months after discharge. The HAR model identified 107 (35.8%) alcoholics at high-risk for relapse prior to discharge. Of the HAR group 61% were re-admitted within 6 months compared to 28% of the low-risk alcoholism relapse (LAR) group (OR = 4.0, 95% CI = 2.4-6.8). The HAR group was older with a lower socioeconomic status, fewer legal problems, more physical and mental health problems and decreased evidence of social support. The HAR model was more successful than were the typologies for predicting early relapse. The HAR model demonstrates descriptive and predictive validity and compares favorably to existing typology models.

Cyclophosphamide and cisplatinum combination chemotherapy for the treatment of epithelial ovarian carcinoma.

A review of 18 patients with Stage III epithelial ovarian carcinoma treated by surgery and followed by cyclophosphamide and cisplatinum combination chemotherapy is presented. At the end of 12 months from the initiation of chemotherapy, 88.9% of the patients were alive and 77.8% remained free of tumor progression. At the end of 2 years 77.8% of the patients were alive and 44.4% of the patients were free of tumor progression. The combination of cyclophosphamide and cisplatinum has low toxicity, a simple pattern of administration, and has provided satisfactory results.

Squamous cell carcinoma of the vulva and Fanconi anemia.

Malignant neoplasia frequently occurs with Fanconi anemia. Generally this represents hematologic disease; however, solid tumors may also appear. The woman described here developed squamous cell carcinoma of the vulva at age 28, and is the third such case in a patient with Fanconi anemia that has been reported. It is a diagnosis to be considered for the young patient with this type of carcinoma. Increased chromosomal breakage in this syndrome may be important in the pathogenesis of these neoplastic changes.