Subdermal Injection Research Articles

The unilocular fat-cell graft

Autologous fat grafting has become a common procedure for augmenting soft tissue. However, there are still some problems with resorption and cyst formation after injection, which mainly arise from insufficient nourishment of the transplanted fat tissues. In this study, using a mouse model, we enzymatically digested fat tissues into unilocular fat cells, and then transplanted the unilocular fat cells by sub-dermal injection to allow the transplanted cells to easily spread within the injected area. Fat tissue was harvested from a green fluorescent protein transgenic mouse (C57BL/6), and the optimal digestion time was determined to be 30 min. The fat cells were then injected into the sub-dermal layer of the head skin of a C57BL/6 mouse. As a control, minced fat without digestion was also injected. The animals were sacrificed immediately after injection and on days 1, 2 and 3, as well as at weeks 1, 2 and 4 after injection, and the recipient skins were collected for microscopic observation. The unilocular fat cells were observed to spread in a solitary manner among the recipient tissues, and no necrotic areas or cysts were observed. The minced-fat-graft control showed central necrosis in the transplanted region. In addition, the minced fat tissue needed to be injected with an 18-gauge syringe, but the unilocular fat cells could be injected with a 26-gauge syringe. Thus, the unilocular fat-cell graft was determined to be a superior alternative to conventional fat grafts.

Sentinel lymph node biopsy in the pediatric population

Background Sentinel lymph node biopsy (SLNB) has only been recently used for childhood neoplasms. Methods We reviewed all patients younger than 19 years who underwent SLNB for 5 years. Results Twenty patients were identified (11 male, 9 female). Sentinel lymph node biopsy was performed for 10 sarcomas (5 synovial, 3 rhabdomyosarcoma, 1 epitheliod, 1 other); 9 skin neoplasms (4 melanomas, 3 Spitz nevi, 2 melanocytomas); and 1 acinic cell carcinoma. All patients underwent Technetium 99m sulfur microcolloid injection and 4-quadrant subdermal injection with Lymphazurin 1% (Autosuture, Norwalk, Conn). Six patients required either sedation for lymphoscintigraphy. Intraoperative gamma probe was used. Primary lesions were found in lower extremity (n = 8), upper extremity (n = 6), trunk (n = 3), and head and neck (n = 3). The lymphatic basins were inguinal (n = 8), axilla (n = 8), neck (n = 3), and both inguinal and axilla (n = 1). At least one lymph node was identified in each procedure. Of 20 patients, 5 (25%) had metastatic disease (4 skin neoplasms and 1 sarcoma). There were no complications in our series, and all patients are alive with no recurrence at an average follow-up of 2.2 years. Conclusions Sentinel lymph node biopsy allows for an accurate biopsy in children. However, some younger patients may require sedation, and it may be more challenging to isolate the sentinel node.

Radioguided occult lesion localization (ROLL) for treatment and diagnosis of malignant and premalignant breast lesions combined with sentinel node biopsy: A prospective clinical trial with 100 patients

Advanced breast cancer screening techniques and their availability increased the number of non-palpable breast lesions requiring surgery. Consequently reliable and efficient therapeutic management permitting accurate localization and removal of these occult lesions is essential. Aims In our study we evaluated radioguided occult lesion localization (ROLL) for effectiveness of localization, oncological safety and feasibility of concomitant sentinel node biopsy. Methods Hundred patients (120 lesions) underwent ROLL and tumour excision with or without sentinel node biopsy after confirmed histopathological findings via intra-tumoral injection of Tc99m-labelled macro-aggregate albumin for ROLL and Tc99m-labelled nanocolloids with periareolar–subdermal injection for simultaneous sentinel node biopsy. Results Our detection rate for ROLL was 98.3%, respectively, 98.6% for sentinel nodes in cases of concomitant sentinel node biopsy. We had a radical excision rate of 55 out of 69 cases of invasive ductal cancer and 17 out of 26 cases of DCIS to achieve 1 mm, respectively, 10 mm tumour-free margins. Conclusions Intra-tumoral tracer injection of for ROLL and periareolar–subdermal tracer injection for simultaneous sentinel node biopsy seem to be a sensitive technique. According to our results ROLL is a safe, precise and simple technique permitting definitive therapeutic removal of malignant or premalignant breast lesions. The high detection rate of the sentinel node in cases with concomitant sentinel node biopsy shows that the combination of both procedures is possible and safe. In our opinion ROLL is an excellent therapeutic option after histological confirmation of malignancy or premalignant disease.

022 Extracorporal Shock Wave is More Effective than Gene Therapy with TGF-Beta to Reduce Ischemic Necrosis in a Rat Epigastric Skin Flap Model

In this study, we evaluated and compared the effectivity of two modalities, gene therapy with adenovirus-mediated transforming growth factor-β and extracorporal shock waves (ESW) therapy, to treat ischemically challenged epigastric skin flaps in a rat model. Thirty male Sprague-Dawley rats were divided into three groups of ten rats each. An epigastric skin flap model, based solely on the right inferior epigastric vessels, was used as the model in this study. Rats received either subdermal injections of adenovirus encoding TGF-β(Ad-TGF-β) or ESW treatment with 750 impulses at 0.15 mJ/mm2. The third group received no treatment and served as a control group. A flap measuring 8 × 8 cm was outlined on the abdominal skin. The TGF-β injections were given subdermally in the left upper corner of the flap just prior to flap elevation, whereas the ESW treatment was immediately after the flap was sutured back to its bed. Flap viability was evaluated seven days after the initial operation. Digital images of the epigastric flaps were taken and areas of necrotic zones relative to total flap surface area were measured and expressed as percentages by using a software program. Overall, there was a significant increase in mean percent surviving area in the Ad-TGF-β group and the ESW-group compared to the control group (ESW-group: 97.7 ± 1.8% vs. Ad-TGF-β: 90.3 ± 4.0% and control group: 82.6 ± 4.3%; p < 0.05). Furthermore, in the ESW group mean percent surviving areas were significantly larger than in the Ad-TGF-β group (ESW-group: 97.7 ± 1.8% vs. Ad-TGF-β: 90.3 ± 4.0%; p < 0.05). We conclude that treatment with ESW enhances epigastric skin flap survival significantly more than Ad-TGF-β treatment and, thus, represents a modality that is more feasible, cost effective and less invasive compared to gene therapy with growth factors to improve blood supply to ischemic tissue.

Comparison of Different Injection Sites of Radionuclide for Sentinel Lymph Node Detection in Breast Cancer

There are still ongoing controversies about several aspects of lymphatic mapping and sentinel lymph node biopsy for breast cancer, including injection site of radioisotope and blue dye. This study aims to evaluate the success rate of different radiocolloid injection techniques in the detection of sentinel lymph nodes (SLN) in early breast cancer. One hundred ninety-two women with early breast cancer were included. For SLN mapping with lymphoscintigraphy (LSG), 5 different injections were used. Group A (36 patients) had 4 peritumoral (PT), group B (n = 36) had 1 subdermal (SD) injection of Tc-99m rhenium sulfide colloid over the tumor quadrant. Group C (59 patients) had 1 PT and 1 SD combined injections. In group D (56 patients), lymphatic mapping was performed with 2 intradermal periareolar (ID-PA) injections. In group E (n = 41), 2 ID-PA and 1 PT combined injections were performed. Early dynamic and delayed images were obtained. A surgical gamma probe was used to explore the SLNs. Surgical specimens were evaluated histopathologically. The SLN identification rate, false negative rate, and comparison of groups were evaluated by statistical methods. The SLN identification rate by LSG in groups A, B, C, D, and E were 72%; 92%, 93.2%, 98%, and 95%, respectively. The highest detection rates for the axilla (98%) and mammary internal (MI) drainage (22%) were obtained with ID-PA injections and a peritumoral injection, respectively. Seventy of 192 patients (36.4%) had positive axillary lymph nodes. The only statistically significant difference was between the PT and SD injection groups in axillary SLN identification rate by LSG (P = 0.016). The success rate was superior with intradermal periareolar injection compared with PT and SD injection to visualize the axillary SLN. However, PT deep injection combined with ID-PA injections may be more favorable to demonstrate the primary internal mammary (IM) lymphatic drainage.

Evaluation of Breast Lymphatic Pathways with Indocyanine Green Fluorescence Imaging in Patients with Breast Cancer

In patients with early breast cancer, sentinel lymph node biopsy (SLNB) has been emerging as a new standard of care. The use of SLNB with a blue dye is convenient and safe, but it requires a high level of technical skill. Recently, an instrument that can provide fluorescence imaging of lymphatic flow has been introduced. In the present study, we analyzed breast lymphatic pathways and discussed its potential as a modality to complement the use of SLNB with a blue dye. Thirty-seven consecutive patients with breast cancer were examined. To obtain fluorescence imaging, an invisible near-infrared fluorescence imaging system was used. After indocyanine green was subdermally injected in the subareolar site and at two sites around the tumor, the subcutaneous lymphatic drainage pathway (LDP) was observed. In 27 (72.9%) of the patients, the number of LDP from the periareolar area was one or two. In 21(63.6%) of 33 patients with subdermal injection around the tumor, no LDP was observed from the peritumoral area. Lymphatic connection between the peritumoral area and the periareolar area was observed very frequently (91.7%). In 26 (70.3%) of the patients, multiple routes joined together and only one route was ultimately directed to the axilla. Significant correlation was seen between body mass index (BMI) and the transit time to the axilla after injection (p = 0.0038). Additionally, a significant correlation was seen between the number of LPD from the periareolar area and the distance between detected SLNs and the fluorescence line-disappearing point (p = 0.034). This instrument can provide some important information, and can be an available and reliable navigator for SLNB with a blue dye.

Effect of local, long-term delivery of platelet-derived growth factor (PDGF) on injected fat graft survival in severe combined immunodeficient (SCID) mice

Autogenous fat injection is widely used for the correction of acquired and congenital soft tissue defects. However, the high absorption rate results in the need for over-correction of the defect and repeat procedures. We hypothesised that platelet-derived growth factor (PDGF), a potent mitogen and known stimulant for murine preadipocytes, would improve fat graft survival when concentrations were sustained with a gelatine microsphere delivery system. Abdominal fat was harvested from an otherwise healthy 43-year-old woman during a breast reconstruction. Prior to subdermal injection into severe combined immunodeficient (SCID) mice, the fat grafts were divided into 1-ml aliquots, mixed with microspheres bound to PDGF, free PDGF, or nothing depending on its experimental group, and weighed. The following experimental groups were thus created (minimum n=8 per group): (1) fat graft control, (2) fat graft with free PDGF, (3) fat graft with blank microspheres, and (4) fat graft with microspheres bound to PDGF. After 12 weeks, the fat xenografts were harvested for analysis of weight maintenance and histological and morphometric evaluation. The addition of PDGF bound to gelatine microspheres was effective in improving xenograft weight maintenance (P=0.018) and preservation of adipose tissue architecture (P<0.0005) compared to controls at 3 months. The microspheres were completely absorbed at 12 weeks. Sustained, local delivery of PDGF via a gelatine microsphere delivery system resulted in improved weight maintenance of the xenografts with greater preservation of adipose tissue architecture at 3 months compared to controls.

Methylene Blue Dye-A Safe and Effective Alternative for Sentinel Lymph Node Localization

Sentinel lymph node (SLN) biopsy has emerged as an effective diagnostic tool in axillary staging in breast cancer. The commonly used technique employs isosulfan blue/patent blue V combined with radioactive colloid tracer. Methylene blue (MB) is a less expensive and readily available alternative dye. The study evaluated the safety and efficacy of MB in SLN localization. A retrospective study of 329 patients with early breast cancer who had SLN localization as part of an ethically approved prospective evaluation study of SLN localization technique was carried out. Lymph node positive, tumors >2 cm on clinical and radiological evaluation, those with previous breast and axillary surgery, neo-adjuvant chemotherapy were excluded from the study. One hundred seventy three patients underwent SLN localization using 1 mL of 1% MB, and a combined MB-radio colloid tracer technique was used in the other 156 patients. Allocation to the groups was by simple randomization. Injection of the dye and radioisotope was into the subdermal plane in the sub-areolar region. Patients underwent breast conservation surgery or mastectomy with SLN directed four node axillary sampling +/- axillary clearance. The lymph node was examined by standard microscopy. There were no reported complications with the use of MB aside from temporary tattooing. The technique failed in eight patients giving an identification rate of 97.6%. Ten of the 258 (3.9%) patients had false-negative SLN, with negative predictive value of 96.1%, sensitivity of predicting further axillary disease of 73%, specificity of 87.3%, and overall accuracy of 85.7%. Reported adverse reaction to isosulfan blue/patent blue V varied from minor to severe anaphylactic reactions (1-3%) requiring vigorous resuscitation. Subdermal sub-areolar injection of MB is safe and effective readily available dye for SLN localization in axillary staging of breast cancer with no major adverse reaction.

Effects of lidocaine and epinephrine on cutaneous blood flow

Local anaesthetic agents in combination with epinephrine are frequently used in local reconstructive procedures such as skin tumour excision and local flap closure. The purpose of this study was to measure the effect of subdermal injection of lidocaine combined with epinephrine on cutaneous blood flow in the forearm and in the face. Thirty injections were performed on the forearm and 40 injections were performed on the face in five healthy volunteers. In both anatomical regions, 0.9% phosphate buffered saline (PBS) was used as a control, and experimental injections included 1% lidocaine either alone or in combination with 1:100,000 epinephrine, and an additional combination of 1% lidocaine with 1:200,000 epinephrine used in the facial experiments. Cutaneous blood flow was measured indirectly using laser Doppler imaging (moorLDI-Mark 2). A statistically significant increase in blood flow was achieved with injection of lidocaine in the forearm compared to saline, whereas a non-statistically significant increase was achieved with saline injection compared to lidocaine in the face. This occurred in the first 5 min in the forearm and 2 min in the face. The addition of 1:100,000 epinephrine to lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 10 min in the forearm and 8 min in the face. This was statistically significant compared to all other injections except for the combination of 1:200,000 epinephrine with lidocaine, injected in the face. The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine. Incisions should be delayed for 10 min in the forearm and 8 min in the face following lidocaine+epinephrine injection to allow maximal benefit to take effect. There were no significant differences between 1:100,000 and 1:200,000 epinephrine combined with lidocaine in facial injections his study.

Sentinel lymph node biopsy in multiple breast cancer using subareolar injection of the tracer

We performed subdermal injection of (99m)Tc-labelled albumin combined with subareolar (SA) injection of blue dye to axillary lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with multifocal and multicentric breast cancer to evaluate the feasibility and accuracy of this technique. A retrospective analysis of our experience on 235 SLNB showed that 30(12.7%) had multiple cancer (MC) on final pathologic examination and was considered in relation to the aim of the study. Mean age was 57.19 years (range 24-90). Mean number of SLNs identified was 1.93 (range 1-5). Mean number of axillary LNs examined was 18.10 (range 12-27). Overall successful identification was 100% with a false negative (FN) rate of 6.25%. Overall accuracy of lymphatic mapping and sensitivity was 96.6% and 93.7%, respectively. SLNB using the SA injection technique may be an alternative to complete axillary dissection in patients with multiple breast cancers and a clinically negative axilla.

Sentinel lymph node biopsy is feasible even after total mastectomy

Previous mastectomy is unanimously considered to represent an absolute technical contraindication to sentinel lymph node biopsy (SLNB). Four patients who underwent total mastectomy and plastic reconstruction with prosthesis, developed, during the follow up, a unique invasive limited local subdermic recurrence amenable to surgical excision, with clinically negative axillary nodes. In all patients preoperative lymphoscintigraphy with subdermal injection of (99m)Tc-labeled colloidal particles correctly showed an axillary sentinel lymph node (SLN). Metastases in SLN were detected in two patients, and a complete axillary dissection followed. The remaining two patients had a negative SLN and no axillary clearance was performed. In selected cases, the subdermal injection of radioisotope permits the identification of an axillary SLN, even in mastectomized patients. Despite SLNB in mastectomized patients being technically feasible, only a larger population and longer patient follow up could confirm its true predictive value. However, there are no anatomical or physiological reasons to exclude "a priori" this diagnostic opportunity.

A comparison of conventional capture versus PIT reader techniques for estimating survival and capture probabilities of big brown bats (Eptesicus fuscus)

We compared conventional capture (primarily mist nets and harp traps) and passive integrated transponder (PIT) tagging techniques for estimating capture and survival probabilities of big brown bats (Eptesicus fuscus) roosting in buildings in Fort Collins, Colorado. A total of 987 female adult and juvenile bats were captured and marked by subdermal injection of PIT tags during the summers of 2001–2005 at five maternity colonies in buildings. Openings to roosts were equipped with PIT hoop-style readers, and exit and entry of bats were passively monitored on a daily basis throughout the summers of 2002–2005. PIT readers ‘recaptured’ adult and juvenile females more often than conventional capture events at each roost. Estimates of annual capture probabilities for all five colonies were on average twice as high when estimated from PIT reader data ( = 0.93–1.00) than when derived from conventional techniques ( = 0.26–0.66), and as a consequence annual survival estimates were more precisely estimated when using PIT reader encounters. Short-term, daily capture estimates were also higher using PIT readers than conventional captures. We discuss the advantages and limitations of using PIT tags and passive encounters with hoop readers vs. conventional capture techniques for estimating these vital parameters in big brown bats.

Komplikationen nach Faltenunterspritzung und ihre Behandlung

All dermal fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of these risks and be prepared to accept them. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., the implantation of a long-lasting filler substance was too superficial). Such adverse events can be treated with intradermal 5-fluorouracil and steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunological phenomena such as late-onset allergy and non-allergic foreign body granulomas. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions should remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granulomas in the subcutaneous fat.

Lichen Sclerosus: Subdermal Steroid Injection Therapy. A Large, Long-Term Follow-Up Study

Objective: Lichen sclerosus (LS) is a chronic progressive skin disease of inflammatory etiology, which often occurs in the female external genital area and presents therapeutic dilemmas. This condition can affect women from adolescence to senescence. Intense and recalcitrant pruritus is a symptomatic hallmark of LS. The aim of our long-term study was to quantify the termination of pruritus, reduction of active disease progression, and cessation of scarring in response to a program of subdermal steroid injection regimen for LS. Study Design: The primary outcome of our study was to quantify the number and intervals of steroid injections required to obtain the cessation of active disease progression and symptoms of itching and pain. The study was a clinical chart review of 88 patients who were referred to a specialized vulvovaginal clinic at a large private hospital. Referrals came from general obstetricians and gynecologists, family physicians, and dermatologists. Results: Sixty-two (62) patients (72.9%) cl...

An evaluation of Fluorescent elastomer for marking killifish, &lt;i&gt;Epiplatys bifasciatus&lt;/i&gt; and &lt;i&gt;Epiplatys spilargyreius&lt;/i&gt; in abundance and growth studies

We evaluated the subdermal injection of fluorescent elastomer for tagging two sympatric aplocheilids, Epiplatys bifasciatus and E. spilargyreius, in pond and stream conditions. The smallest size that could be injected without mortality was 28 mm TL. The Visible Implant Elastomer (VIE) tag did not affect the growth or survival of adults of these fishes. Marks were retained throughout the 70 days of the pond experiment. The best position for injection of VIE in these fishes is the belly. VIE is most appropriate for mark-recapture population size estimation and movement studies. The tag could not be used for growth studies of these species because they become juveniles at about 21 mm TL, two weeks after hatching, and become sexually mature at about 26 mm TL, while the smallest tangible specimen was 28 mm TL. Keywords: tagging, visible implant elastomer, mark-recapture, aplocheilids, killifish Journal of Aquatic Sciences Vol. 21(1) 2006: 29-31

The Value of Combined Peritumoral and Subdermal Injection Techniques for Lymphoscintigraphy in Detection of Sentinel Lymph Node in Breast Cancer

The aim of this study was to evaluate the success rate of combined peritumoral and subdermal injection techniques based on our previous experience on different injection techniques for lymphoscintigraphy. Fifty-nine women with early breast cancer (mean tumor size, 20.5 mm) were prospectively studied. On the morning of the operation, each patient had 2 injections, one peritumoral (PT) medial to the lesion and one subdermal (SD) into the skin over the tumor quadrant. Each injection consisted of 20 MBq (540 mCi) Tc-99m rhenium sulfide colloid. Early dynamic and delayed static images were obtained up to 4 hours after injections. An intraoperative gamma probe was used to explore the axillary sentinel lymph nodes (SLN). All surgical specimens were evaluated histopathologically. Forty patients had breast-preserving surgery and 19 had modified radical mastectomy. Thirty-eight patients had axillary dissection. All but 4 patients showed axillary lymphatic drainage. Twelve of 59 patients (20%) showed extraaxillary drainage with lymphoscintigraphy. Combined injection technique yielded a 93.2% success rate in detecting axillary SLN. In 2 of 4 patients with no drainage on lymphoscintigraphy, intraoperative gamma probe revealed SLN during the surgery. Twenty patients (33%) had positive axillary lymph nodes. In 14 of them, the SLN was the only positive node. A false-negative rate was found 1.6% (one of 59 patients). This results suggest that a combination of both PT and SD techniques increases the success rate of visualization SLN and enhances the visualization of extraaxillary nodes for further treatment planning.

Avoiding and Treating Dermal Filler Complications

All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat.

O.390 Efficacy of lymphoscintigraphic sentinel node detection for cervical staging of patient with squamous cell carcinoma

Sentinel lymph node (SLN) biopsy is an alternative to axillary node dissection for staging breast cancer treatment. In this article, we investigated nodal drainage patterns and tumor location using lymphoscintigraphy to predict the axillary sentinel lymph node status. We enrolled 88 patients with clinically suspicious or biopsy-proven breast cancer from March 2001 to October 2002. The average age of subjects was 48 ± 4 years and the clinical stage was T1-2N0Mx. Tc-99m sulfur colloid was used in a hybrid combination of subdermal and perilesional injections around the selected corners of the tumor or biopsy site. Sentinel lymphoscintigraphy was performed 16-20 hours before surgery. Sentinel nodes were marked on the skin. An intraoperative gamma probe was used to confirm the sentinel lymph node location before biopsy. Most primary tumors were in the outer upper quadrant (52.3%), followed by the inner upper quadrant (17.0%), outer inferior quadrant (12.5%), central areolar area (11.4%), and inner inferior quadrant (6.8%). The nodal drainage patterns on 2-hour lymphoscintigraphy were as follows: axillary alone (76.1%), internal mammary nodes alone (1.1%), both axillary and internal mammary nodes (11.4%), and no drainage (11.4%). Internal mammary lymphatic drainage is related to tumor location in the inner quadrants of the breast. About 11.4% of all patients had poorly identified SLNs on lymphoscintigraphy within a 2-hour period, but there was improvement in the overall detection rate up to 95% by intraoperative gamma probe the next day. Preoperative lymphoscintigraphic mapping has value in providing individual lymphatic drainage patterns and tumor location that are important in the interpretation of the results of SLN biopsy during surgery.

Risk of Brain Tumors Associated with Exposure to Exogenous Female Sex Hormones

The etiology of brain tumors is largely unknown. Prior observations have implicated gender-specific hormones in the pathogenesis of these tumors. In a population-based case-control study, the authors identified all women aged 20-69 years who had been diagnosed with meningioma or glioma during 2000-2002 in four regions of Sweden. Controls were randomly selected from the study base. Detailed information on hormone usage, including use of hormonal contraceptives, hormonal treatment for gynecologic problems, and hormone replacement therapy, was collected from 178 meningioma cases, 115 glioma cases, and 323 controls. Data were analyzed using unconditional logistic regression, adjusting for age, residential area, education, and parity. An increased relative risk of meningioma was found among postmenopausal women for ever use of hormone replacement therapy, with an odds ratio of 1.7 (95% confidence interval: 1.0, 2.8). Women who had used long-acting hormonal contraceptives (subdermal implants, injections, or hormonal intrauterine devices) had an increased risk of meningioma; the odds ratio for at least 10 years of use was 2.7 (95% confidence interval: 0.9, 7.5). Hormone usage was not associated with glioma risk in this study. The findings suggest that the use of female sex steroids may increase the risk of meningioma.

The tetrapeptide acetyl‐serine‐aspartyl‐lysine‐proline improves skin flap survival and accelerates wound healing

The tetrapeptide acetyl-serine-aspartyl-lysine-proline (AcSDKP) has recently been recognized as a potent angiogenic factor. Given the importance of vascular blood supply in the process of tissue repair we have investigated the ability of AcSDKP to contribute to the repair of cutaneous injuries by using dorsal and abdominal skin flap models. Postoperative subdermal AcSDKP injections (5 microg/kg/injection twice a day for 3 days following flap elevation) prevented marginally perfused areas from undergoing necrosis. Mean skin survival area of abdominal and dorsal flaps ranged, respectively, from 50.9+/-19.3 and 53.4+/-4.2% in the control groups to 66.4+/-7.5 and 74.7+/-6.6% in AcSDKP-treated groups. Furthermore, in an ex vivo assay, AcSDKP applied locally to skin explants at doses from 10(-8) to 10(-5) M improved survival of the explanted skin exposed to UVB irradiation at 10 J/cm2. Increased reepithelialization, as well as higher levels of expression of basal keratin 14 and increased expression of fibronectin was observed after topical application of AcSDKP. These data provide experimental evidence that AcSDKP can improve the viability of ischemic skin flaps in the rat by promoting angiogenesis. Moreover, it enhances wound healing of injured avascular skin explants. Thus, these findings identify AcSDKP as a new tissue-repair agent and suggest its potential clinical use for the management of skin wounds.