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Notes: Abstract:  The decision to recommend bilateral prophylactic mastectomy (PBM), one treatment modality used to reduce the development of breast carcinoma, may be influenced by physician bias. This investigation tested the hypothesis that there are physician-in-training biases in recommendations of PBM. All second-year medical students, general surgical residents, and internal medicine residents at our institution participated in a survey in which they were asked at what percent risk of developing breast carcinoma the physicians-in-training would recommend PBM for 1) their patients, 2) themselves, and 3) their significant others, as applicable. A total of 198 physicians-in-training responded. Univariate analysis demonstrated an association between both the type of physician-in-training (p 〈 0.03) and gender (p 〈 0.004) with the percent risk for which respondents would recommend PBM. However, with multivariate analysis, only gender was associated with percent risk (p 〈 0.05). Physicians-in-training also chose PBM at a lower risk for their significant others than for themselves (67.5% versus 57.2%; p 〈 0.02). Respondents also chose PBM at a similar risk for themselves or significant others as for their patients (r = 0.83, r = 0.98; p 〈 0.001). This investigation suggests that males (compared to females) are more likely to recommend PBM for the prevention of breast cancer. 

Notes: Abstract: Advances in stereotactic breast biopsies have introduced a variety of devices that yield different sizes of tissue samples. The choice of biopsy device should be based on which technique is most likely to yield a definitive diagnosis at the time of the initial biopsy. This is a prospective study of 104 patients who underwent a total of 125 stereotactic breast biopsies using the SiteSelect large-core biopsy device. From May 1999 to June 2001, 104 patients underwent 125 stereotactic breast biopsies with the SiteSelect large-core biopsy device. One hundred four 15 mm SiteSelect biopsies, eighteen 10 mm SiteSelect biopsies, and three 22 mm SiteSelect biopsies were performed. Atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were found in 15% of the biopsies and infiltrating cancer was found in another 15% of the biopsies. Seventy-eight percent of the ADH and 90% of the DCIS lesions were associated with indeterminate calcifications noted on mammogram. Two of the 22 mm SiteSelect excisions yielded a specimen that contained the entire cancer with clear surgical margins. All of the patients with DCIS or invasive carcinoma underwent definitive surgical and adjuvant therapy. The sensitivity and specificity of SiteSelect in this series of patients was 100%. The SiteSelect biopsy procedure is safe, well tolerated by patients, and can be performed under local anesthesia. SiteSelect is comparable to an open excisional biopsy in its ability to obtain adequate tissue for accurate diagnosis, but excises significantly less normal surrounding breast tissue. Based on the data, indications for primary use of SiteSelect are indeterminate calcifications on mammogram, rebiopsy of a vacuum-assisted biopsy site that yielded atypia on pathologic examination, and complete excision of a lesion suspicious for invasive carcinoma in order to assess actual size and margin status.

Notes: Abstract:  This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second-line therapy in postmenopausal women with hormone-responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first-line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease.

Notes: Abstract: The purpose of the study was to demonstrate the feasibility of a hybrid functional/anatomic breast imaging platform with biopsy capability for facilitating lesion detection and diagnosis. This platform consists of an investigative dedicated positron emission mammography (PEM) device mounted on a stereotactic X-ray mammography system, permitting sequential acquisition of mammographic and emission images during a single breast compression. There is automatic coregistration of images from both modalities, and these results can be successfully correlated with histopathologic findings. The potential utility of functional images correlated to anatomic images would include noninvasively detecting clinically and radiographically occult cancers, assessing response to therapy, discriminating between benign and malignant breast masses, and ultimately reducing the number of invasive and costly surgical interventions. A spot-digital mammogram and subsequent PEM image, collected over a 4-minute period, were obtained in a single patient with the breast in compression after intravenous injection of (F-18)-2-deoxy-2-fluoro-D-glucose (FDG) at the time of stereotactic biopsy. The authors conclude that FDG-based lesion localization information may be combined with the lesion X-ray attenuation characteristics using this common imaging platform.

Notes: Abstract: Axillary nodal status is the most significant prognosticator for predicting survival and guiding adjuvant therapy in breast cancer patients. Sentinel lymph node biopsy (SLNB) represents a minimally invasive procedure with low morbidity for staging axillary nodal status. In this article we review and report our experiences in patients with early breast cancer who underwent SLNB at the Revlon/UCLA Breast Center. Between September 1998 and May 2000, a total 83 SLNBs were performed in 81 patients with proven breast cancer and negative axillary examination who elected to have SLNB as the first step of nodal staging. Two patients had bilateral breast cancer. SLNB was localized by using both 99Tc sulfur colloid (83 cases) and isosulfan blue dye (75 cases). Data of these patients were prospectively collected and analyzed. The clinical and pathologic characteristics of women with positive and negative sentinel lymph nodes (SLNs) were compared to identify features predictive of SLN metastasis. Of the 83 cases, the SLN was successfully localized in 82 (98.8%). Sixty-three percent of patients had SLNs found in level I only, 18.3% in both level I and II, and 4.9% in level II alone. The vast majority (84.3%) of these cases had T1 breast cancer with an average size of 1.55 cm for the entire series. Twenty-three patients (28%) had positive SLNs, with an average of 1.5 positive SLNs per patient. Fifteen had metastases detected by hematoxylin and eosin staining and 8 had micrometastases detected by immunohistochemistry (IHC) using anticytokeratin antibodies. Ten of the former group agreed to and 2 of the latter group opted for full axillary lymph node dissection (ALND). An average of 17.5 lymph nodes were removed from each ALND procedure. Additional metastases or micrometastases were found in seven patients (in a total of 28 lymph nodes). Three patients with completely negative SLNs experienced additional axillary lymph node removal due to their election of free flap reconstruction. None had metastases detected in these lymph nodes. The absence of estrogen and progesterone receptors (ER/PR) by IHC (p = 0.036) and the presence of lymphatic/vascular invasion (LVI) (p = 0.002) predicted positive SLNs in patients with early breast cancer in a univariate analysis; in a multivariate analysis only LVI was predictive (p = 0.0125). Histologic type, nuclear grade, tumor differentiation, HER-2/neu and p53 status, S-phase fraction, and DNA ploidy did not predict SLN status. Immediate postoperative complications were uncommon and delayed complications completely absent. Because of the high detection rate, accurate staging, and minimal morbidity, SLNB should be offered as a choice to women with small breast cancers and clinically negative nodes. Because positive LVI and negative ER/PR status are highly predictive of pathologically positive SLNs in small breast cancers, women whose cancers meet these criteria should be advised preoperatively about their risk of having a positive SLN and may benefit from intraoperative assessment (frozen section and/or touch preparation) of their SLNs.

Notes: Abstract: Conservatively treated premenopausal breast cancer has a higher rate of local relapse as well as an increased genetic predisposition to cancer. The current study's purpose was to evaluate the interactions between BRCA-1/2 status and molecular biologic markers in a cohort of conservatively managed breast cancer patients. Seventy-six premenopausal women treated with breast-conserving surgery and radiation therapy were this study's focus. All patients were treated with wide local excision with or without axillary dissection, followed by radiation to the intact breast. Systemic therapy was administered as clinically indicated. All patients in this study had an available paraffin block from the primary tumor and agreed to undergo complete sequencing of the BRCA-1 and BRCA-2 genes. The primary breast tumor tissue from each patient was immunohistochemically stained for estrogen receptor (ER), progesterone receptor (PR), p53, HER-2/neu, and Proliferating Cell Nuclear Antigen (PCNA). Of the 76 patients tested for BRCA, 50 patients had wild-type BRCA-1 and BRCA-2, 15 had variants of unclear significance, 6 had deleterious mutations in BRCA-1, and 5 had deleterious mutations in BRCA-2. p53 positivity correlated with deleterious mutations in BRCA-1 (p = 0.023), but not in BRCA-2. Though not significant, there was a trend for ER and PR negativity to correlate with BRCA-1 mutation (p = 0.087 and 0.054, respectively); there were no correlations between ER, PR, and BRCA-2. Though not significant, all 11 tumors with BRCA mutations were HER-2/neu negative. Patients with BRCA mutations have a unique molecular profile. These data can be helpful in understanding differences in the biologic behavior of patients with familial breast cancers.

Notes: Abstract:  This study reviewed mammographic screening related to breast carcinoma diagnosis and treatment between 1987 and 1997 at Brooke Army Medical Center, San Antonio, TX. Epidemiologic data from the Department of Defense Automated Central Tumor Registry were merged with data from patients’ medical records and responses of the patients or their families to a mailed survey. The cases of 907 women grouped by race—white, African American, and Hispanic—were analyzed. Breast carcinoma diagnosed by mammographic screening showed a reversed ratio of early to late stage of cancer occurring for all three groups. That ratio was 1.45 for African Americans, 2.67 for Hispanics, and 3.08 for whites. For those women diagnosed with screening mammography, no statistically significant difference in 5-year survival was found between the races: 86% for whites, 83% for Hispanics, and 80% for African Americans. Mammographic screening as a diagnostic tool appears to equalize survival among whites, Hispanics, and African Americans, in spite of differences in age, stage of diagnosis, and military rank used as a proxy for socioeconomic status. When not controlling for mammographic diagnosis, Kaplan–Meier analysis revealed significant differences in survival patterns between whites, Hispanics, and African Americans. Five-year survival rates were 71% for whites, 74% for Hispanics, and 53% for African Americans. Screening mammography reduced 5-year mortality by almost 59% in African Americans, 52% in whites, and 36% in Hispanics. Whites were diagnosed with breast carcinoma, on average, at 57 years of age—11 years later than African Americans (average age 46 years) and 7 years later than Hispanic women (average age 50 years). As a diagnostic tool, screening mammography was used to discover breast cancer in 36% of white women, 33% of Hispanics, and 22% of African Americans. Further research is recommended to examine the use of mammography among various racial/ethnic groups.

Notes: Abstract: Estrogens and growth factors stimulate the proliferation of human breast cancer cells by primary binding and activation of specific receptors that regulate downstream signaling events. Receptors for estrogen are phosphoproteins, and the biologic function of these proteins can be modulated by changes in their phosphorylation state. Signal transduction by growth factor receptors, including HER-2/neu and epidermal growth factor (EGF) receptors, can alter the phosphorylation of estrogen receptor (ER) and the biologic activity of ER-dependent signaling networks both in the presence and in the absence of estrogenic ligands. In addition, both estrogen and growth factor signaling pathways regulate the secretion of vascular endothelial growth factors that stimulate tumor-associated angiogenesis. These molecular interactions significantly impact breast cancer cell growth and survival, and integration of selected signal transduction inhibitors with antiestrogen therapies show promise as a new antitumor treatment strategy that will soon be evaluated in the clinic. Sensitive and reliable assays of estrogen, HER-2/neu, and EGF receptors and tumor-associated angiogenesis will be important biologic factors to consider in the choice of optimal antitumor therapies for patients with breast cancer. 

Notes: Abstract:  We report a case of occult breast cancer presenting as paraneoplastic sensory and motor neuropathy. The paraneoplastic antibody panel was negative and no other unknown identifiable antibody could be detected in the serum. Systemic treatment with four cycles of Adriamycin and cyclophosphamide was given with no significant improvement in the neurologic condition. We reviewed the literature of the last 10 years and identified 31 reported cases of paraneoplastic neurologic syndrome due to breast cancer. Paraneoplastic antibodies could be found in only 36% of patients, no identifiable antibodies in 32% of patients, and unknown antibodies in 16% of patients. The status of the paraneoplastic antibodies was not reported in 16% of patients. Only 29% of patients responded to chemotherapy with improvement in neurologic deficits. The role of systemic treatment in the progression of neurologic impairment is unclear.

Notes: Abstract:  The advent of sentinel lymph node (SLN) biopsy for breast cancer has had a considerable impact on clinical oncology. The SLN procedure has been widely adopted, but major clinical issues remain unresolved pending the outcome of randomized trials. Pathologic handling of SLNs is less controversial; however, significant pitfalls in their handling have been reported. Herein we report two additional uncommon situations that demonstrate the need for the utmost vigilance in both the macroscopic examination (i.e., trimming of “positive” nodal tissue) and microscopic examination (i.e., presence of nevus cell aggregates mimicking metastatic carcinoma) of SLN specimens.

Notes: Abstract:   Inflammatory pseudotumor (IP) is a benign lesion that can affect any tissue in the body and which may be confused clinically and in imaging for malignancy. Despite the widespread performance of breast biopsy, the finding of inflammatory pseudotumor of the breast is exceedingly rare. Excision of the tumor is the treatment of choice, but there is a relatively high rate of recurrence. The aim of this report is to describe the clinical, imaging, and pathologic features in a case of breast IP, the first reported case in a postpartum woman still nursing her infant.

Notes: Abstract: Three significant advances are responsible for the recent evolution in breast reconstruction. The first of these is the introduction of the transverse rectus abdominis musculocutaneous (TRAM) flap, which made reliable autologous breast reconstruction a reality. The subsequent application of microsurgical principles to this procedure brought further refinements in terms of improved blood supply and lessened donor site morbidity. Finally, the wide acceptance of the skin-sparing mastectomy by oncologic surgeons has allowed further progress in the aesthetic possibilities that can be realized by the plastic surgeon. The authors discuss each of these factors and provide an overview of the current state of the art of autologous free tissue breast reconstruction.

Notes: Abstract: Interest in intraoperative radiation therapy (IORT) for breast cancer is increasing as the possible benefits of this technique for the patient become apparent. The rationale for the use of this segmental radiation therapy in place of whole-breast irradiation is based on the finding that approximately 85% of breast relapses are confined to the same quadrant of the breast as the primary tumor. Phase I and II trials have demonstrated no increase in postsurgical complication rates following the use of single-dose IORT in localized breast cancers. Longer follow-up is needed to assess the cosmetic outcome. Clinical trials to evaluate the effectiveness of IORT in the treatment of breast cancer are currently under way at the European Institute of Oncology (EIO) at the University of Milan, Italy, and at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York. Here we report the two different techniques in use in these trials. 

Notes: Abstract: The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30–13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p 〈 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were ≤2 cm in size (RR = 13.68, 95% CI 1.06–175.76), whereas no such association was observed among patients with HER-2-positive tumors larger than 2 cm. Eligible patients without available tumor tissue tended to have smaller tumors compared to study participants. Our results might partly explain the variation in evidence across HER-2 prognostic studies using fixed tissue and might apply to other putative markers of prognosis in breast cancer. 

Notes: Abstract: We present the first case of primary vulvar mucinous adenocarcinoma of ectopic breast origin. The patient is an 84-year-old woman with a mass on the left side of her vulva. A left partial vulvectomy with bilateral inguinal lymph node dissections revealed a mucinous adenocarcinoma that involved the dermis and subcutaneous tissue. The tumor cells were positive for estrogen receptors (ERs), progesterone receptors (PRs), and BRST-1 markers. The clinical and pathologic features, differential diagnosis, and treatment are discussed. 

Notes: Abstract: Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant. 

Notes: Abstract: Treatment of selected patients with anti-HER-2/neu antibodies alone (1) or in combination with chemotherapy (2) may be of benefit to patients with refractory breast cancer. Approximately 30% of breast cancers overexpress HER-2/neu, a member of the epidermal growth factor receptor family. These patients may have a poorer overall prognosis (3) due to relative resistance to both hormonal therapy and chemotherapy (4–6).We recently observed a patient with refractory breast cancer who responded to rhuMAB HER-2 (trastuzumab) plus paclitaxel after progressing on paclitaxel alone. While on combination treatment she developed cerebellar metastases. Follow-up computed tomography (CT) scan revealed that her disease continued to respond in the liver, lungs, and bone. This case suggests that failure of trastuzumab to cross the blood–brain barrier may compromise its overall effectiveness and raises the possibility that the central nervous system (CNS), or other sanctuary sites, may become clinically more significant in patients with breast cancer in the era of antibody-based therapies. 

Notes: Abstract: Increasing numbers of women of all ages are electing to have reduction mammaplasty for very large breasts. Breast cancer can be an incidental finding in reduction mammaplasty specimens. We report here the discovery of breast cancer in specimens from four patients who underwent elective breast reduction, three of whom had not had recent mammograms. All four patients underwent modified radical mastectomy. The role of mammography, surgical options, specimen evaluation, and practical guidelines are discussed. 

Notes: Abstract: Atypical lobular hyperplasia (ALH) is occasionally found in specimens obtained by percutaneous stereotactic vacuum-assisted breast biopsy for microcalcifications. Since malignancy is often found at surgical excision when atypical ductal hyperplasia is found at percutaneous biopsy, we reviewed our pathologic findings from surgery for ALH at percutaneous biopsy. This was a retrospective review of all percutaneous breast biopsy specimens for mammographic microcalcifications obtained from a single institution over a 30-month period. The pathologic findings from percutaneous biopsy were correlated with the radiologic appearance and the pathology from surgical excision. ALH was found in 13 of 766 (1.7%) stereotactic vacuum-assisted core needle biopsies performed for mammographic microcalcifications. Subsequent surgery in six patients revealed ductal carcinoma in situ (DCIS) in two patients and one case of invasive ductal carcinoma. Surgical excision is indicated for areas with ALH discovered by percutaneous biopsy for mammographic microcalcifications. 

Notes: Abstract: We describe a 45-year-old woman who presented with a spontaneous unilateral nipple discharge. With a negative breast examination and screening tests (mammography and ultrasonography) she underwent mammary ductography, which revealed a small 3–4 mm intraluminal filling defect. A core biopsy showed high-grade ductal carcinoma in situ (DCIS). An attempted wide local excision was unsuccessful, and the patient underwent a mastectomy. Pathologic assessment revealed high-grade DCIS and multiple foci of invasive mucinous ductal adenocarcinoma. Rare tumor cells were identified in the subcapsular sinuses in both sentinel lymph nodes. We report this case to point out the importance of the diagnostic examination for patients with a pathologic nipple discharge and review current and possible future diagnostic management. 

Notes: Temporally controlled expression of genes in transgenic mice has advanced our understanding of many physiological processes. One of the more common modes of acutely altering gene levels involves the doxycycline-regulated “tet-on/tet-off” systems. There has been concern that the administration of doxycycline in itself might compromise many aspects of wound repair. Here we report that oral ad libitum administration of doxycycline (2 mg/ml in drinking water) to mice does not alter dermal or epidermal wound healing. The healing of both full- and partial-thickness skin wounds proceeded similarly regardless of doxycycline administration; in fact, collagen organization and tensile strength development appeared to accelerate in the presence of doxycycline. These data suggest that wound healing studies incorporating transgene expression can utilize tet-on/tet-off regulation of gene expression without interference from doxycycline. (WOUND REP REG 2003;11:373–379)

Notes: Hypertrophic scars result from excessive collagen deposition at sights of healing dermal wounds and can be functionally and cosmetically problematic. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. We tested the ability of the phenanthrolinone derivative FG-1648 (in 0.5% Carbopol 971 PNF gel, pH 6.5), a prolyl 4-hydroxylase inhibitor, to reduce hypertrophic scar formation in a rabbit ear hypertrophic scar model. New Zealand White rabbits were divided into two treatment groups (n = 12 wounds per group with an equal number of controls): low-dose group: 0.5% FG-1648; high-dose group: 1% FG-1648. Left ears were used for treatment and right ear for control. Four 7-mm dermal ulcer wounds were made on each ear. The inhibitor was topically applied to the wound at the time of wounding and once daily up to postoperative day 7. Wounds were harvested at postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. All wounds showed complete healing. Treatment of wounds with 1% prolyl 4-hydroxylase inhibitor decreased the scar elevation index by 26% compared to control wounds (p 〈 0.01). Wounds treated with 0.5% FG-1648 inhibitor showed no difference in scar elevation compared to control wounds. These results suggest that inhibition of prolyl 4-hydroxylase may be a suitable agent for topical treatment for the prevention of hypertrophic scar tissue. (WOUND REP REG 2003;11:368–372)

Notes: The role of the plasminogen activator/plasmin system in fibrinolysis has been well established. Indeed, clinicians worldwide have successfully utilized recombinant tissue-type plasminogen activator as first-line treatment of acute myocardial infarction for almost 2 decades. Outside the field of cardiology, there has been increasing excitement regarding the possible contribution of this system in many other important biological processes, including cell adhesion, cell migration, cell–cell signaling, tumor invasion and metastasis, ovulation, and wound healing. In this review, we present evidence in the current literature that the plasminogen activator/plasmin system does have a role in wound healing, looking at both normal and abnormal healing. Furthermore, the invaluable insights provided by numerous transgenic animal experiments are summarized. (WOUND REP REG 2003;11:239–247)

Notes: Inflammatory cells are generally assumed to be the primary source of most growth factors/cytokines that participate in wound healing. Correspondingly, most attempts to enhance wound healing have been directed at the wound itself. However, certain key factors such as insulin-like growth factor-I (IGF-I) and related proteins are present in blood in sufficient quantities to suggest significant contributions from outside the wound. Because little is known of the dynamics of IGF family members in wounds, particularly in human wounds, we serially measured the mRNAs and proteins of the IGF family in fluid and tissues taken from acute as well as chronically inflamed human wounds and compared them to their corresponding concentrations in blood. We also measured transforming growth factor-β1 and -β3, vascular endothelial growth factor, interleukin-1β, matrix metalloproteinases and selected isomers/receptors, all of which are associated with inflammation. All IGF proteins reached their highest concentrations immediately after injury. No difference between IGF-I mRNA expression between acute and inflamed wounds was found. As a group, IGF-related proteins, in contrast to transforming growth factor-β, vascular endothelial growth factor, and interleukin-1β, are highly correlated to and are generally below their concentrations in blood and are not elevated by inflammation. The IGF family therefore appears to enter wounds, even inflamed wounds, mainly from blood. If blood IGF-I is low, wound levels are lower. This data suggests that healing impairment due to IGF-I deficiency can be readily detected and is, at least in part, easily and safely correctable. (WOUND REP REG 2003;11:253–260)

Notes: We have previously shown that reconstructed human skin engineered from autologous keratinocytes, fibroblasts, and sterilized donor allodermis stimulates angiogenesis within 5–7 days when placed on well-vascularized wound beds in nude mice. When this reconstructed skin was used clinically in more demanding wound beds, some grafts were lost, possibly due to delayed vascularization. As this reconstructed skin lacks any endothelial cells, our aim in this study was to develop an angiogenic reconstructed skin model in which to explore strategies to improve angiogenesis both in vitro and in vivo. We report that culture of small-vessel human dermal microvascular endothelial cells (HuDMECs) was achieved using magnetic beads coated with an antibody to platelet cell adhesion molecule as a means of purifying the culture. Keratinocytes, fibroblasts, and HuDMECs could be cultured from the same skin biopsy. Initial studies culturing HuDMECs and other sources of endothelial cells with the tissue-engineered skin showed that these cells were capable of slowly entering the dermis under standard culture conditions in vitro. In conclusion, this provides us with a model in which to explore strategies for improving angiogenesis in vitro and also establishes the culture methodologies for the production of reconstructed skin containing autologous keratinocytes, fibroblasts, and endothelial cells. (WOUND REP REG 2003;11:275–284)

Notes: Novel approaches to healing of chronic wounds, such as venous leg ulcers, include the use of tissue-engineered skin substitutes, e.g., human fibroblast-derived dermis. The exact mechanisms of action of these products and their effects on wound healing at a cellular level are yet to be fully defined. The aim of our study was to evaluate the potential effects of human fibroblast-derived dermis on the healing of chronic wounds using an experimental model. We used a tissue expansion model to examine the effect of human fibroblast-derived dermis on the growth of human tissue biopsied from venous leg ulcers. Further characterization of the cytokine profile produced by human fibroblast-derived dermis in culture was performed using enzyme-linked immunosorbent assay techniques. Addition of medium conditioned with human fibroblast-derived dermis significantly increased the outgrowth of cells from venous leg ulcer biopsies (p = 0.001). We detected bioactive levels of hepatocyte growth factor/scatter factor and interleukin-8 in media conditioned with human fibroblast-derived dermis. Therefore, conditioned media from human fibroblast-derived dermis enhances ex vivo expansion of tissue taken from chronic venous leg ulcers, and contains potent angiogenic factors. These experimental findings may explain the enhanced healing seen with clinical applications of human fibroblast-derived dermis on chronic wounds. (WOUND REP REG 2003;11:292–296)

Notes: The aim of the current study was to evaluate the influence of platelet-derived growth factor (PDGF) on skin microcirculation during normal and impaired wound healing. Secondary healing wounds were created on the ears of hairless mice and treated once with 3 µg of PDGF-BB immediately after wound creation. Intravital fluorescence microscopy was used to quantify reepithelialization, revascularization, vessel diameters, vascular permeability, and leukocyte–endothelium interactions up to 24 days after wound creation. Microvascular perfusion was assessed by laser Doppler flowmetry. Wound healing was studied in normal (n = 15) and ischemic skin tissue (n = 15) as well as in mice (n = 17) rendered hyperglycemic by an intravenous injection of streptozotocin 7 days prior to wound creation. Treatment with PDGF accelerated reepithelialization and reduced the time for complete wound closure in ischemic skin from 14.9 ± 2.5 (control) to 12.3 ± 1.8 days (p 〈 0.03), and in hyperglycemic animals from 15.0 ± 2.4 (control) to 12.0 ± 3.0 days (p 〈 0.04). Revascularization of these wounds was also significantly enhanced after PDFG application. No other parameters were influenced by the treatment. Normal wound healing was not affected. This study confirms the positive influence of PDGF on wound healing under pathophysiological conditions. The effects in this model seem to be primarily due to the mitogenic potency of PDGF on keratinocytes and endothelial cells. A significant effect on leukocyte activation during the inflammatory process was not observed. (WOUND REP REG 2003;11:361–367)

Notes: There are many useful technologies to describe patterns of gene expression that occur during tissue repair and regeneration. Results from different methods used in one experimental setting are not often compared. In this case study of chondrogenesis, we compare two methods to identify differentially expressed genes, representational difference analysis and targeted macroarray analysis, as a model for investigating genes that may be relevant to tissue repair. We sought to identify genes whose expression was altered when human dermal fibroblasts were cultured in a three-dimensional, porous collagen sponge with the chondroinductive agent, demineralized bone. Both representational difference analysis and macroarray experiments revealed several functional families of genes as up-regulated or down-regulated in chondroinduced fibroblasts. An advantage of representational difference analysis is that altered expression of specific mRNA transcripts can be revealed. In this example, representational difference analysis uncovered the up-regulation of a specific transcript of Wnt5a in fibroblasts cultured with demineralized bone. Representational difference analysis is limited, however, as there can be false negatives for genes not readily amplified by polymerase chain reaction. We conclude that small arrays containing functional classes of genes can be used to ask specific, hypothesis-driven questions at minimal cost. It may be prudent, however, to use more than one method to survey differences in gene expression in order to validate and expand findings. (WOUND REP REG 2003;11:386–392)

Notes: Matrix degradation and remodeling occurs during wound healing, thereby aiding tissue repair, angiogenesis, and cell migration. It is dependent on the balance between proteinases and their inhibitors, namely the matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Acute wound fluid samples (n = 58 patients) were collected daily from the intraperitoneal drain placed after colorectal surgery from the first postoperative day until drain removal. Three laboratory techniques were performed: enzyme linked immunosorbent assays (MMP-1, MMP-3, TIMP-1, TIMP-2), gelatinase activity assays (MMP-2, MMP-9), and quenched fluorescent substrate hydrolysis (total MMP activity). Levels were correlated with each postoperative day, wound healing, and surgical outcome (p 〈 0.05, Spearman's correlation). Significant negative (MMP-9, MMP-3, MMP-8, TIMP-2, total MMP activity) and positive (MMP-2, TIMP-1) correlations were observed with the postoperative day, e.g., total MMP-9: day 1, median, 121 (range, 12–189) ng/ml; day 3, 46 (8–179); day 5, 31 (0–155), day 7, 20 (6–58). Differences were also observed with the type of operation, estimated blood loss, and length of operation and with postoperative complications. MMPs and TIMPs are involved in wound healing after elective colorectal cancer surgery and their levels in drain fluid may act as markers of wound healing and surgical outcome. (WOUND REP REG 2003;11:268–274)

Notes: The retinal pigment epithelium (RPE) plays a major role in the development of the anomalous retinal scarring response termed proliferative vitreoretinopathy. The present study was undertaken to investigate whether agaricus bisporus lectin inhibited human RPE proliferation in vitro. Fluorescein isothiocyanate-labeled agaricus bisporus lectin was used to study binding of lectin to cultured human RPE. The effect of a 24-hour exposure of agaricus bisporus lectin on RPE proliferation was measured using (methyl-3H)-thymidine incorporation into DNA. Toxicity studies were assessed using morphologic evaluation, trypan blue exclusion, and a cell viability assay. Agaricus bisporus lectin bound to RPE cells and was inhibited by preincubation of lectin with asialomucin. Agaricus bisporus lectin caused a dose-dependent inhibition of RPE proliferation (one-way ANOVA, F = 94.470, p 〈 0.001) that was partially reversible on removal of the lectin. Compared with controls, cells remained viable and no morphological changes or trypan blue staining was noted in RPE exposed to agaricus bisporus lectin. Human RPE binds agaricus bisporus lectin and inhibits proliferation without apparent cytotoxicity. It therefore merits consideration as a potential antiproliferative agent in the prevention and treatment of proliferative vitreoretinopathy and other nonocular anomalous wound healing processes. (WOUND REP REG 2003;11:285–291)

Notes: Full-thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four-millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was evaluated microscopically 4–5 times per week for 2 weeks. A semiquantitative wound scoring system to evaluate the neovasculature at the wound periphery was investigated. A vascular score was calculated for each wound at each observation. Two independent observers analyzed the microscopic wound images using the scoring system. At the end of the 14-day period, repeat biopsies were performed on some of the volunteers, and the granulation tissue was stained with anti-CD31. The Kaplan-Meier method was used to estimate the distribution of the time to reach predetermined target average vascular scores. A mixed-effects regression model indicated that time, age, and observer were predictors for the average vascular score outcome. The pattern and time course for wound neovascularization was highly reproducible in this group of healthy volunteers, and the assay was feasible and well tolerated. This wound angiogenesis model may be useful for monitoring the effects of antiangiogenic agents on normal wound neovascularization. (WOUND REP REG 2003;11:306–313)

Notes: Reactive oxygen species have been implicated in the impaired healing of chronic leg ulcers but little direct evidence is available. We have observed a significant (p 〈 0.01) elevation of the allantoin : uric acid percentage ratio, a marker of oxidative stress, in wound fluid from chronic leg ulcers (median 17, range 8–860) compared to both paired plasma (median 2, range 1–8) and acute surgical wound fluid (median 4, range 3–7). However, the allantoin : uric acid percentage ratio did not differ significantly between chronic wounds that healed and those that failed to heal. Neutrophil elastase was elevated 30- to 1300-fold in chronic wound fluid compared to plasma and there was a correlation (r 2 = 0.742) between wound fluid elastase and the allantoin : uric acid percentage ratio. Total antioxidant capacity of wound fluid, as measured with a chemiluminescence assay, did not show a correlation (r 2 = 0.03) with the observed oxidative stress. These observations suggest that conditions of localized oxidative stress, possibly related to neutrophil-associated production of reactive oxygen species, are present in chronic leg ulcers. It is possible that future therapeutic strategies aimed at reducing oxidative stress, in addition to good standard care, could improve healing rates of chronic wounds. (WOUND REP REG 2003;11:172–176)

Notes: To compare a four-layer bandage system with a two-layer system in the management of chronic venous leg ulceration, a prospective randomized open parallel groups trial was undertaken. In total, 112 patients newly presenting to leg ulcer services with chronic leg ulceration, screened to exclude the presence of arterial disease (ankle brachial pressure index 〈0.8) and causes of ulceration other than venous disease, were entered into the trial. Patients were randomized to receive either four-layer (Profore™) or two-layer (Surepress™) high-compression elastic bandage systems. In all, 109 out of 112 patients had at least one follow-up. After 24 weeks, 50 out of 57 (88%) patients randomized to the four-layer bandage system with follow-up had ulcer closure (full epithelialization) compared with 40 out of 52 (77%) on the two-layer bandage, hazard ratio = 1.18 (95% confidence interval 0.69–2.02), p = 0.55. After 12 weeks, 40 out of 57 (70%) patients randomized to the four-layer bandage system with follow-up had ulcer closure compared with 30 out of 52 (58%) on the two-layer bandage, odds ratio = 4.23 (95% confidence interval 1.29–13.86), p = 0.02. Withdrawal rates were significantly greater on the two-layer bandage (30 out of 54; 56%) compared with the four-layer bandage system (8 out of 58; 14%), p 〈 0.001, and the number of patients with at least one device-related adverse incident was significantly greater on the two-layer bandaging system (15 out of 54; 28%) compared with four-layer bandaging (5 out of 54; 9%), p = 0.01. The higher mean cost of treatment in the two-layer bandaging system arm over 24 weeks ($1374 [£916] vs. $1314 [£876]) was explained by the increased mean number of bandage changes (1.5 vs. 1.1 per week) with the two-layer system. In conclusion, the four-layer bandage offers advantages over the two-layer bandage in terms of reduced withdrawal from treatment, fewer adverse incidents, and lower treatment cost. (WOUND REP REG 2003;11:166–171)

Notes: Epiregulin is a broad specificity epidermal growth factor family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. Our objective was to determine whether topical epiregulin enhanced repair of murine excisional wounds. Wounds were treated on days 0–4 with either topical epiregulin (1 µg/ml), epidermal growth factor (10 µg/ml), or vehicle. At day 5 postinjury, wounds receiving epiregulin were significantly smaller than those treated with epidermal growth factor or vehicle. Treatment with epiregulin promoted greater epidermal proliferation and thickening than epidermal growth factor or vehicle due to an expansion of the proliferative compartment of keratinocytes. Dermal thickness was also increased in epiregulin-treated wounds as compared to those treated with epidermal growth factor or vehicle. In day 5 wounds, matrix metalloproteinase-3 (stromelysin-1) mRNA levels were significantly lower in epiregulin- or epidermal growth factor-treated wounds than in vehicle-treated controls, suggesting that growth factor-treated wounds were more mature and required less ongoing proteolytic activity than their same-day vehicle-treated counterparts. This is the first report that topical epiregulin accelerates repair of full-thickness murine excisional wounds as compared to vehicle or epidermal growth factor. Furthermore, epiregulin is more potent and more effective than epidermal growth factor in promoting proliferation and maturation of the epidermis as well as enhancement of the neodermis. (WOUND REP REG 2003;11:188–197)

Notes: To examine the significance of chemokine activation of CXCR2 in wound healing after chemical burn, cutaneous injury was created by topical application of nitrogen mustard on CXCR2 wild type (+/+), heterozygous (+/–), and knockout (–/–) mice. Wounds were analyzed histologically for neutrophil and monocyte infiltration and for reepithelialization at postwound days 4, 7, and 10. Neutrophil recruitment to the wound site was reduced through postwound day 7 in CXCR2 –/– mice as indicated by myeloperoxidase assay and by visual quantitation. Because there is always concern that mice with targeted deletion of a specific receptor may undergo developmental adaptations to offset the loss of the receptor, we also accessed chemical wound repair in the presence of a small molecule antagonist of CXCR2. Dietary supplementation with a CXCR2 antagonist (SB-265610) during the wound repair process also markedly delayed healing parameters in CXCR2 +/+ mice, even greater than treatment with glucocorticoids. These parallel studies further establish that mice deficient in CXCR2 function exhibit delayed cutaneous wound healing that may be primarily linked to impaired neutrophil recruitment after chemical burn with nitrogen mustard. Thus, there may be a potential therapeutic benefit of treating nitrogen mustard-induced skin lesions with agonists of CXCR2 to facilitate the wound repair process. (WOUND REP REG 2003;11:213–219)

Notes: Overexpression of matrix metalloproteinases (MMPs) has been observed in chronic, compared to acute, wounds and altered levels might impair healing. During treatment of wounds, examination gloves are routinely used, and the wound environment thus gets exposed to gloves. The aim of this study was to characterize secretion of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in cultured fibroblasts with or without exposure to gloves. Cultures were exposed to glove washings from powdered or powder-free latex examination gloves and compared to untreated controls. MMP-1, -2, -3, -9 and their inhibitors TIMP-1 and -2 were assayed in conditioned media. Cells exposed to gloves reduced their release of MMP-1, -2, and -3 with no differences between the manufacturers of the gloves. The inhibitor TIMP-1 was reduced to 10–15% of untreated control values (p 〈 0.001), being less affected by the powder-free than by the powdered glove (p 〈 0.05). MMP-9 and TIMP-2 were not significantly altered. We therefore conclude that secretion of MMPs and TIMPs from cultured fibroblasts were affected by glove washings. Powdered and powder-free gloves had similar effects, except for a less pronounced reduction of TIMP-1 production by the powder-free glove. Examination gloves might therefore affect wound healing, with the least pronounced effect observed using the powder-free glove. (WOUND REP REG 2003;11:230–234)

Notes: Seattle, Washington, USA May 4–7, 2003 The following compilation of abstracts represents a list of all submissions accepted for presentation at this meeting. Abstracts are numbered and categorized according to the meeting schedule. Abstract # Session Names 1–12 Young Investigator Presentations 13–17 Oxygen 18–22 Scar 24–29 Stem Cells/Morphogens 30–34 Growth Factors I 35–39 Infection 40–45 Matrix Biology 46–51 Biomaterials 53–58 Epithelialization 59–64 Growth Factors II 65–70 Inflammation 71–76 Chronic Wounds 77–84 Dermal Responses 85–91 Wound Repair Models 92–133 Posters Due to author requests and withdrawals, abstracts do not appear in sequential order.

Notes: Deep groin infections after prosthetic vascular surgical procedures represent a serious complication of surgical practice. Septicemia and/or erosive hemorrhage can both be consequences. In this situation, removal of the graft appears to be the only option. However, if the infection is detected early (type Szilagyi III), local treatment to eradicate the infection could serve as an alternative. Twenty-four patients with confirmed infection of the soft tissue adjacent to the prosthetic material in the groin were treated locally by implantation of a vacuum sponge system. Duration of this treatment was 2 weeks. All patients showed excellent tissue granulation of the wound area and the microbial stains were negative at the end of therapy. In 21 patients the wound could be primarily closed after explantation of the sponge. Three patients underwent open treatment because of a skin defect. After 12 months, the wounds had healed well in all patients. Histologic evaluation revealed a physiological healing process. Deep soft tissue infections of the groin adjacent to prosthetic vascular material (type Szilagyi III) can be treated effectively and safely with the vacuum sponge system. The treatment is inexpensive, easy to perform, and the initial vascular reconstruction can be preserved. (WOUND REP REG 2003;11:104–109)

Notes: The combination of cultured autologous keratinocytes with the dermal regeneration template Integra™ could offer increased possibilities for reconstructive surgery and wound healing. A single-step application of cells, centrifuged deep into an Integra™-like matrix at the silicone–matrix junction, has been described but might prove technically complex for clinical use. We have investigated the possibility of simplifying this procedure by applying cultured cells directly to the underside of the Integra™ or directly to the wound bed immediately prior to grafting. The objective was to see whether cells would migrate through the matrix in an upward direction. We tested the principle of this concept using a pig wound healing model. Integra™ was seeded directly with cultured cells and grafted onto fresh full-thickness wounds, or unseeded Integra™ was applied to freshly excised wound beds that had just been seeded with the same number of cells. Biopsies were taken at 3, 7, 11, and 14 days. Histological sections showed that the cells moved through the Integra™ to give a confluent surface epithelium. Direct seeding onto the Integra™ was the most efficient method. Transduction of cultured autologous keratinocytes in vitro with a MFGlacZnls retrovirus confirmed that the epidermis was derived from the cultured autologous keratinocytes. (WOUND REP REG 2003;11:132–138)

Notes: We hypothesized that hyperbaric oxygen treatment (HBO) would reduce neovascularization following partial-thickness skin grafting in the Yucatan pig. Results show that capillary density 4 days postgraft is increased twofold in grafts not treated with HBO, compared to normal, ungrafted skin or skin grafts from pigs treated with HBO, p 〈 0.05. Similarly, the expression of vascular endothelial growth factor, a growth factor associated with neovascularization, was also reduced by HBO. Cell density in the graft boundary increased gradually after grafting, reaching a maximum 2.7-fold increase, relative to normal skin, at day 4, p 〈 0.05. Cell nuclei positive for proliferating cell nuclear antigen, a marker of proliferation, increased threefold by day 2, p 〈 0.05, and then declined to normal levels by day 7. HBO had no effect on cell density or proliferation in the boundary region or on shear strength of the graft. In the epidermis, proliferation declined 80% 2 days after grafting and then returned to levels observed in normal skin by day 4, p 〈 0.05; however, in pigs treated with HBO, we observed no decline in proliferation. These findings confirm the hypothesis that HBO reduces neovascularization in the partial-thickness skin graft while preserving regenerative capacity in the graft boundary and normal proliferative capacity of the epidermis. (WOUND REP REG 2003;11:139–144)

Notes: Interferon-inducible protein 10 (IP-10) is a key regulator of neutrophils, monocytes, and lymphocytes, cells infiltration whose secretory products play a key role in peritoneal wound healing. The objective of the present study was to determine whether IP-10 is expressed by parietal peritoneum and whether its temporal and spatial expression is altered following surgically induced peritoneal injury during healing. Peritoneal sidewall injuries were induced in mice (N = 60), and the severity of adhesions were graded at 12 hours and 1, 2, 4, and 7 days postsurgery. After collection of peritoneal washes, the injured peritoneum with associated adhesion and intact parietal peritoneum were collected to determine IP-10 mRNA and protein expression using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Peritoneal injury resulted in adhesion formation with increased severity by day 7 postsurgery. The intact parietal peritoneum expressed IP-10 mRNA, whose level of expression significantly increased following peritoneal injury and reached a maximum at day 4 (p = 0.001), declining to the uninjured control levels by day 7 post-injury. The level of IP-10 in peritoneal washes also increased as a result of peritoneal injury. Immunohistochemically, IP-10 was localized to various inflammatory and immune cells, adhesion fibroblasts, and mesothelial cells, and its intensity increased during the course of wound healing. In conclusion, we showed that parietal peritoneum expresses IP-10 and peritoneal tissue injury results in an elevated level of its expression throughout the early phase of wound healing. The results suggest that IP-10 and its elevated expression may play a role in peritoneal cellular activities that influence the early phases of tissue repair and, possibly, the development of peritoneal adhesions. (WOUND REP REG 2003;11:120–126)

Notes: Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. Thymosin β4 has previously been found to promote dermal and corneal repair in normal rats. Here we report that thymosin β4 was also active in accelerating wound repair in full-thickness dermal wounds in both db/db diabetic and aged mice. We found that thymosin β4 in either phosphate-buffered saline or a hydrogel formulation is active in promoting dermal wound repair in normal rats. In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin β4 in either phosphate buffered saline solution or a hydrogel formulation. No difference was observed in keratinocyte migration, with all of the diabetic animals showing almost complete coverage of the wound at 8 days. Wound healing in 26-month-old (aged) animals was significantly delayed. Thymosin β4 accelerated wound healing in these aged mice, with increases in keratinocyte migration, wound contracture, and collagen deposition. The hydrogel formulation generally showed similar wound healing activity with thymosin β4 in PBS. The actin-binding domain of thymosin β4 duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in the aged animals comparable to that observed with the parent molecule. These studies show that thymosin β4 is active for wound repair in models of impaired healing and may have efficacy in chronic wounds in humans. (WOUND REP REG 2003;11:19–24)

Notes: During the past 5 years, progress in the treatment of pressure ulcers appears to have reached a plateau. Several factors in the design of recent clinical studies may have contributed to this situation. These factors include the criteria chosen for patient selection, small sample size, and lack of a concisely defined final clinical outcome. Hunt noted that wound stratification according to a patient's physiological characteristics may be a key to quantifying differences among clinical treatments.1To address this issue, we examined the expression of cyclin D/cdk4 in pressure ulcer fibroblasts taken from tissues during a recent clinical trial. The treatment groups included patients treated with the following regimens: placebo, granulocyte macrophage-colony stimulating factor alone, basic fibroblast growth factor alone, or granulocyte macrophage-colony stimulating factor and basic fibroblast growth factor given in sequence.2 Immunocytochemical colocalization of cyclin D and cdk4 showed that, before the initial treatment began, patients were distributed disproportionately among treatment subgroups in regards to the initial expression of these markers. For example, we found that compared with other subgroups, ulcer fibroblasts in the basic fibroblast growth factor treatment group showed a much lower expression of cyclin D/cdk4 at day 0. However, this group exhibited higher levels of expression of this complex after 35 days of treatment. This study shows that measurement of cyclin D/cdk4 expression permits more accurate stratification of patients within treatment subgroups, measurement of a cell's ability to detect the presence of functional cytokines, identification of area(s) of failure within the G1 of the cell cycle, and a basis for critical evaluation of various treatments. (WOUND REP REG 2003;11:11–18)

Notes: Zircon from a lower crustal metapelitic granulite (Val Malenco, N-Italy) display inherited cores, and three metamorphic overgrowths with ages of 281 ± 2, 269 ± 3 and 258 ± 4 Ma. Using mineral inclusions in zircon and garnet and their rare earth element characteristics it is possible to relate the ages to distinct stages of granulite facies metamorphism. The first zircon overgrowth formed during prograde fluid-absent partial melting of muscovite and biotite apparently caused by the intrusion of a Permian gabbro complex. The second metamorphic zircon grew after formation of peak garnet, during cooling from 850 °C to c. 700 °C. It crystallized from partial melts that were depleted in heavy rare earth elements because of previous, extensive garnet crystallization. A second stage of partial melting is documented in new growth of garnet and produced the third metamorphic zircon. The ages obtained indicate that the granulite facies metamorphism lasted for about 20 Myr and was related to two phases of partial melting producing strongly restitic metapelites.Monazite records three metamorphic stages at 279 ± 5, 270 ± 5 and 257 ± 4 Ma, indicating that formation ages can be obtained in monazite that underwent even granulite facies conditions. However, monazite displays less clear relationships between growth zones and mineral inclusions than zircon, hampering the correlation of age to metamorphism. To overcome this problem garnet–monazite trace element partitioning was determined for the first time, which can be used in future studies to relate monazite formation to garnet growth.

Notes: A suite of spinel–cordierite granulites from Viziangram, Eastern Ghats Belt, India preserve mineral assemblages and reaction textures indicative of peak metamorphic conditions of 〉1000 °C, 〉8〈10 kbar, followed successively by near isobaric cooling (down to 750–800 °C), near isothermal decompression (to 4–5 kbar), and late hydration. P–T conditions of each stage are evaluated through a combination of petrogenetic grid approach and thermobarometry. Sapphirine is developed in sillimanite-bearing acid pegmatite veins that intruded the spinel–cordierite granulite close to peak metamorphic conditions, and also in the host rock in immediate contact with the pegmatite. Both sillimanite and sapphirine in the pegmatite are considered to be magmatic phases. Field observations and textural characteristics suggest that Al-metasomatism of the spinel–cordierite granulite due to the intrusion of pegmatite was responsible for sapphirine formation in the spinel granulite.

Notes: Whereas geologists have known for three-quarters of a century that there was significant crustal thickening in the central East Greenland Caledonides, the crucial role of extensional faulting during Caledonian orogenesis has only been recognized during the past decade. In this paper, new petrographic and thermobarometric observations are presented from migmatitic metasedimentary gneisses of the Forsblad Fjord region (c. 72.5°N). Samples of the Krummedal Sequence, collected from the footwall of the upper of two significant splays of the main extensional fault system in the region—the Fjord Region Detachment (FRD)—enable us to establish a relative sequence of metamorphism. Our pressure (P)–temperature (T) results imply a clockwise loop in P–T space. As recorded by mineral assemblages in the Krummedal gneisses, prograde metamorphism involved a net increase of c. 4 kbar and 250 °C, with peak conditions of c. 10.5 kbar at 785 °C. Early burial and heating was followed by near-isothermal decompression of 4.5 kbar, a process which is attributed to roughly 18 km of tectonostratigraphic throw on the upper splay of the FRD. Combining data reported here with the published data, it is estimated that the approximate tectonostratigraphic throw along the lower splay of the FRD was c. 16 km. In situ U–Th–Pb-monazite electron microprobe dating suggests that the earliest phase of metamorphism recorded in the Krummedal Sequence gneisses of Forsblad Fjord occurred during the Caledonian orogeny. Furthermore, the combination of our new data with existing conventional TIMS U-Pb and 40Ar/39Ar data imply that: (1) movement along the uppermost splay of the FRD (c. 425–423 Ma) occurred at maximum time-averaged slip-rates equivalent to c. 9 mm of vertical displacement per year; and (2) that the final stages of metamorphism occurred prior to c. 411 Ma, although part of this denudation was likely accommodated on overlying extensional structures that may have been active more recently. There is close agreement between our data and results from the Krummedal Sequence north of the field area (72.5°−74°N), and rocks of the Smallefjord Sequence (75°−76°N) that are suggested to correlate with the Krummedal Sequence. This leads us to infer that the events recorded in the Forsblad Fjord region are of orogen-scale significance.

Notes: New data on the metamorphic petrology and zircon geochronology of high-grade rocks in the central Mozambique Belt (MB) of Tanzania show that this part of the orogen consists of Archean and Palaeoproterozoic material that was structurally reworked during the Pan-African event. The metamorphic rocks are characterized by a clockwise P–T path, followed by strong decompression, and the time of peak granulite facies metamorphism is similar to other granulite terranes in Tanzania. The predominant rock types are mafic to intermediate granulites, migmatites, granitoid orthogneisses and kyanite/sillimanite-bearing metapelites. The meta-granitoid rocks are of calc-alkaline composition, range in age from late Archean to Neoproterozoic, and their protoliths were probably derived from magmatic arcs during collisional processes. Mafic to intermediate granulites consist of the mineral assemblage garnet–clinopyroxene–plagioclase–quartz–biotite–amphibole ± K-feldspar ± orthopyroxene ± oxides. Metapelites are composed of garnet-biotite-plagioclase ± K-feldspar ± kyanite/sillimanite ± oxides. Estimated values for peak granulite facies metamorphism are 12–13 kbar and 750–800 °C. Pressures of 5–8 kbar and temperatures of 550–700 °C characterize subsequent retrogression to amphibolite facies conditions. Evidence for a clockwise P–T path is provided by late growth of sillimanite after kyanite in metapelites. Zircon ages indicate that most of the central part of the MB in Tanzania consists of reworked ancient crust as shown by Archean (c. 2970–2500 Ma) and Palaeoproterozoic (c. 2124–1837 Ma) protolith ages. Metamorphic zircon from metapelites and granitoid orthogneisses yielded ages of c. 640 Ma which are considered to date peak regional granulite facies metamorphism during the Pan-African orogenic event. However, the available zircon ages for the entire MB in East Africa and Madagascar also document that peak metamorphic conditions were reached at different times in different places. Large parts of the MB in central Tanzania consist of Archean and Palaeoproterozoic material that was reworked during the Pan-African event and that may have been part of the Tanzania Craton and Usagaran domain farther to the west.

Notes: Abstract An analytical electron microscope study of almandine garnet from a metamorphosed Al–Fe-rich rock revealed detailed composition profiles and defect microstructures of resorption zoning along fluid-infiltrated veins and even into the garnet/ilmenite (inclusion) interface. This indicates a limited volume diffusion for the cations in substitution (mainly Ca and Fe) and an interface-controlled partition for the extension of a composition-invariant margin. A corrugated interface between the Ca-rich margin/zone and the almandine garnet core is characterized by dislocation arrays and recovery texture further suggesting a resorption process facilitated by diffusion-induced recrystallization, diffusion-induced dislocation migration and diffusion–induced grain boundary migration. Integrated microstructural and chemical studies are essential for understanding the underlying mechanisms of processes such as garnet zoning and its modification. Without this understanding, it will not be possible to reliably use garnet compositions for thermobarometry and other applications that rely on garnet chemical information.

Notes: Abstract Granulite facies metapelites of the Mather and Filla Paragneisses within the Rauer Group, east Antarctica, possess markedly different compositions. The metamorphic evolution of the two metapelite types has been interpreted as temporally distinct, with the Rauer Group preserving at least two distinct granulite facies tectonothermal episodes. Calculated P–T pseudosections and orthopyroxene Al content indicate the revised maximum-preserved P–T conditions within the Mather Paragneiss to lie in the vicinity of 950–975 °C and 10–10.6 kbar, less extreme than previous estimates. The range of possible P–T paths for the Mather Paragneiss consistent with mineral textural relationships and pseudosections contoured for mineral proportion are significantly shallower (dP/dT) than previous estimates. A near-isothermal decompression P–T path, and extreme peak metamorphic conditions, are not necessary to explain the development of preserved mineral reaction textures. The Filla Paragneiss contains pelitic assemblages less amenable to rigorous quantitative analysis. Nevertheless, possibilities for the shared or otherwise metamorphic evolution of the Mather and Filla Paragneisses may be postulated on the basis of calculated pseudosections in the context of existing geochronology for the Rauer Group and preserved microstructures. A shared evolution, most likely during Pan-African granulite facies metamorphism, is plausible and consistent with mineral assemblage development, geochronology and microstructures. A revised interpretation of the Rauer Group's preserved metamorphic evolution may warrant the revision of existing tectonic models, applicable also to the remainder of Prydz Bay. More generally, the employed approach may incite a revision of peak P–T and P–T paths in other granulite facies terranes.

Notes: The solid-state reaction magnesite (MgCO3) + calcite (aragonite) (CaCO3) = dolomite (CaMg(CO3)2) has been identified in metapelites from western Tianshan, China. Petrological studies show that two metamorphic stages are recorded in the metapelites: (1) the peak mineral assemblage of magnesite and calcite pseudomorphs after aragonite which is only preserved as inclusions within dolomite; and (2) the retrograde glaucophane-chloritoid facies mineral assemblage of glaucophane, chloritoid, dolomite, garnet, paragonite, chlorite and quartz. The peak metamorphic temperatures and pressures are calculated to be 560–600 °C, 4.95–5.07 GPa based on the calcite–dolomite geothermometer and the equilibrium calculation of the reaction dolomite = magnesite + aragonite, respectively. These give direct evidence in UHP metamorphic rocks from Tianshan, China, that carbonate sediments were subducted to greater than 150 km depth. This UHP metamorphism represents a geotherm lower than any previously estimated for subduction metamorphism (〈 3.7 °C km−1) and is within what was previously considered a ‘forbidden’ condition within Earth. In terms of the carbon cycle, this demonstrates that carbonate sediments can be subducted to at least 150 km depth without releasing significant CO2 to the overlying mantle wedge.

Notes: Field data define two lithologically distinct basement-cover sequences within the ultrahigh-pressure metamorphic (UHPM) unit of the Dabie Shan, eastern China. One of the cover units, the Changpu unit, comprises calc-arenitic metasediments in stratigraphic contact with a basement consisting of gneisses of the Yangtze craton. The second cover unit, the Ganghe unit, consists of felsic-intermediate metavolcanics and clastic metasediments. Basement exposure of the Ganghe unit is not known. Fold axes in the Ganghe unit are oblique to those of the Changpu unit, which are parallel to those of the Yangtze gneisses. Preservation of primary textures in some volcanic rocks, and tectonic separation from the Yangtze gneisses by a greenschist facies mylonite, support an interpretation of the Ganghe unit as a low-strain domain. Protolith associations in the Ganghe and Changpu units are compatible with deposition in a rift setting and along a passive continental margin, respectively. A U–Pb single zircon age of 761 ± 33 Ma for volcanoclastic rocks of the Ganghe unit demonstrates a Neoproterozoic deposition age, concordant with inferred rifting at that time. Eclogite facies parageneses in the gneisses and both cover units, along with P–T data demonstrate regional UHPM in the Dabie Shan.

Notes: The Xugou garnet peridotite body of the southern Sulu ultrahigh-pressure (UHP) terrane is enclosed in felsic gneiss, bounded by faults, and consists of harzburgite and lenses of garnet clinopyroxenite and eclogite. The peridotite is composed of variable amounts of olivine (Fo91), enstatite (En92−93), garnet (Alm20−23Prp53−58Knr6−9Grs12−18), diopside and rare chromite. The ultramafic protolith has a depleted residual mantle composition, indicated by a high-Mg number, very low CaO, Al2O3 and total REE contents compared to primary mantle and other Sulu peridotites. Most garnet (Prp44−58) clinopyroxenites are foliated. Except for rare kyanite-bearing eclogitic bands, most eclogites contain a simple assemblage of garnet (Alm29−34Prp32−50Grs15−39) + omphacite (Jd24−36) + minor rutile. Clinopyroxenite and eclogite exhibit LREE-depleted and LREE-enriched patterns, respectively, but both have flat HREE patterns. Normalized La, Sm and Yb contents indicate that both eclogite and garnet clinopyroxenite formed by high-pressure crystal accumulation (+ variable trapped melt) from melts resulting from two-stage partial melting of a mantle source.Recrystallized textures and P–T estimates of 780–870 °C, 5–7 GPa and a metamorphic age of 231 ± 11 Ma indicate that both mafic and ultramafic protoliths experienced Triassic UHP metamorphism in the P–T forbidden zone with an extremely low thermal gradient (〈 5 °C km−1), and multistage retrograde recrystallization during exhumation. Develop of prehnite veins in clinopyroxenite, eclogite, felsic blocks and country rock gneiss, and replacements of eclogitic minerals by prehnite, albite, white mica, and K-feldspar indicate low-temperature metasomatism.

Notes: This paper provides further evidence for the ongoing discussion as to whether the Dabie UHPM belt formed in Triassic or Palaeozoic time, and whether the Sulu UHPM belt formed in Triassic or Neoproterozoic time. Combined use of laser Raman spectrometer (LR), cathodoluminescence imaging (CL), and ion probe U–Pb in-situ dating (SHRIMP) provided accurate ages of UHPM from rocks collected from Weihai, NE Sulu UHPM belt. LR was used to identify coesite and other UHP minerals as inclusions in zircon separates from an amphibolized peridotite and an eclogite. CL was used to examine the zoning structure of these zircon, and SHRIMP dating was performed on specific spots on zircon to obtain ages of different geological events. An age of 221 ± 12 Ma was obtained for coesite-bearing zircon from the amphibolized peridotite; an age of 228 ± 29 Ma for eclogite was obtained from the lower intercept of a concordia plot. These ages are interpreted as the time of UHPM in the Weihai region. Ultramafic rocks to the east of Weihai yield a magmatic age at 581 ± 44 Ma. The zircon in the ultramafic rocks possibly also records a thermal event at c. 400 Ma, but no independent geological evidence for this event has been found. The eclogite protolith formed in the Middle Proterozoic (1821 ± 19 Ma), which is similar to the age of country rock gneisses of 1847–1744 Ma. The new geochronological data confirm that UHPM occurred in the Triassic in the Sulu area when subduction took the ultramafic body and the eclogite protolith, together with the adjacent supracrustal rocks, to mantle depths.

Notes: Oxygen isotopic compositions of silicates in eclogites and whiteschists from the Kokchetav massif were analyzed by whole-grain CO2-laser fluorination methods. Systematic analyses yield extremely low δ18O for eclogites, as low as −3.9‰ for garnet; these values are comparable with those reported for the Dabie-Sulu UHP eclogites. Oxygen isotopic compositions are heterogeneous in samples of eclogite, even on an outcrop scale. Schists have rather uniform oxygen isotope values compared to eclogites, and low δ18O is not observed. Isotope thermometry indicates that both eclogites and schists achieved high-temperature isotopic equilibration at 500–800 °C. This implies that retrograde metamorphic recrystallization barely modified the peak-metamorphic oxygen isotopic signatures. A possible geological environment to account for the low-δ18O basaltic protolith is a continental rift, most likely subjected to the conditions of a cold climate. After the basalt interacted with low δ18O meteoric water, it was tectonically inserted into the surrounding sedimentary units prior to, or during subduction and UHP metamorphism.

Notes: A combined oxygen-isotope and fluid-inclusion study has been carried out on high- and ultrahigh-pressure metamorphic (HP/UHPM) eclogites and garnet clinopyroxenite from the Dabie-Sulu terranes in eastern China. Coesite-bearing eclogites/garnet clinopyroxenite and quartz eclogites have a wide range in whole-rock δ18OVSMOW, from 0 to 11‰. The high-T oxygen-isotope fractionations preserved between quartz and garnet preclude significant retrograde isotope exchange during exhumation, and the wide range in whole-rock oxygen-isotope composition is thought to be a presubduction signature of the precursors. Aqueous fluids with variable salinities and gas species (N2-, CO2-, or CH4-rich), are trapped as primary inclusions in garnet, omphacite and epidote, and in quartz blebs enclosed within eclogitic minerals. In high-δ18O HP/UHPM rocks from Hujialin and Shima, high-salinity brine and/or N2 inclusions occur in garnet porphyroblasts, which also contain inclusions of coesite, Cl-rich blue amphibole and dolomite. In contrast, in low-δ18O eclogites from Qinglongshan and Huangzhen, the Cl concentrations in amphibole are very low, 〈 0.2 wt.%, and low-salinity aqueous inclusions occur in quartz inclusions in epidote porphyroblasts and in epidote cores. These low-salinity fluid inclusions are believed to be remnants of meteoric water, although the fluid composition was modified during pre- and syn-peak HP/UHPM. Eclogites at Houshuichegou and Hetang contain CH4-rich fluid inclusions, coexisting with high-salinity brine inclusions. Methane was probably formed under the influence of CO2-rich aqueous fluids during serpentinisation of mantle-derived peridotites prior to or during plate subduction. Remnants of premetamorphic low- to high-salinity aqueous fluid with minor N2 and/or other gas species preserved in the Dabie-Sulu HP/UHPM eclogites and garnet clinopyroxenite indicate a great diversity of initial fluid composition in the precursors, implying very limited fluid–rock interaction during syn- and post-peak HP/UHPM.

Notes: Coesite relics were discovered as inclusions in clinopyroxene in eclogite and as inclusions in zircon in felsic and pelitic gneisses from Higher Himalayan Crystalline rocks in the upper Kaghan Valley, north-west Himalaya. The metamorphic peak conditions of the coesite-bearing eclogites are estimated to be 27–32 kbar and 700–770 °C, using garnet–pyroxene–phengite geobarometry and garnet–pyroxene geothermometry, respectively. Cathodoluminescence (CL) and backscattered electron (BSE) imaging distinguished three different domains in zircon: inner detrital core, widely spaced euhedral oscillatory zones, and thin, broadly zoned outermost rims. Each zircon domain contains a characteristic suite of micrometre-sized mineral inclusions which were identified by in situ laser Raman microspectroscopy. Core and mantle domains contain quartz, apatite, plagioclase, muscovite and rutile. In contrast, the rim domains contain coesite and minor muscovite. Quartz inclusions were identified in all coesite-bearing zircon grains, but not coexisting with coesite in the same growth domain (rim domain). 206Pb/238U zircon ages reveal that the quartz-bearing mantle domains and the coesite-bearing rim were formed at c. 50 Ma and 46.2 ± 0.7 Ma, respectively. These facts demonstrate that the continental materials were buried to 100 km within 7–9 Myr after initiation of the India–Asia collision (palaeomagnetic data from the Indian oceanic floor supports an initial India-Asia contact at 55–53 Ma). Combination of the sinking rate of 1.1–1.4 cm year−1 with Indian plate velocity of 4.5 cm year−1 suggests that the Indian continent subducted to about 100 km depth at an average subduction angle of 14–19°.

Notes: The Solund–Hyllestad–Lavik area affords an excellent opportunity to understand the ultrahigh-pressure Scandian orogeny because it contains a near-complete record of ophiolite emplacement, high-pressure metamorphism and large-scale extension. In this area, the Upper Allochthon was intruded by thec. 434 Ma Sogneskollen granodiorite and thrust eastward over the Middle/Lower Allochthon, probably in the Wenlockian. The Middle/Lower Allochthon was subducted to c. 50 km depth and the structurally lower Western Gneiss Complex was subducted to eclogite facies conditions at c. 80 km depth by c. 410–400 Ma. Within 〈 5–10 Myr, all these units were exhumed by the Nordfjord–Sogn detachment zone, producing shear strains 〉 100. Exhumation to upper crustal levels was complete by c. 403 Ma. The Solund fault produced the last few km of tectonic exhumation, bringing the near-ultrahigh-pressure rocks to within c. 3 km vertical distance from the low-grade Solund Conglomerate.

Notes: New petrographic evidence and a review of the latest radiometric age data are taken to indicate that formation of the ultra-high pressure (UHP) eclogites within the Western Gneiss Region of Norway probably occurred within the 400–410 Ma time frame. Thus, this event took place significantly later than the previous, widely accepted age of c. 425 Ma for the timing of the high pressure metamorphism in this part of the Scandinavian Caledonides. Garnet growth under UHP (coesite-stable) conditions is recognised as a discrete, younger event following on from earlier garnet formed under firstly amphibolite facies then quartz-stable, eclogite facies conditions. Currently, the best constrained and most precise age, specifically for UHP mineral growth, is the 402 ± 2 Ma U–Pb age for metamorphic zircon (some of which retain coesite inclusions) from the Hareidland eclogite. Exhumation must have followed shortly thereafter and, based on synoptic pressure–temperature and depth–time curves, must have been very fast. Our data and those of others indicate an initial fast exhumation to about 35 km depth by about 395 Ma at a mean rate of about 10 mm a−1. This rapid exhumation rate may have been driven by the appreciable residual buoyancy of the deeply subducted continental crustal slab due to incomplete eclogitization of the dominant Proterozoic orthogneisses during the short-lived UHP event. Subsequent exhumation to 8–10 km depth by about 375 Ma occurred at a much slower mean rate of about 1.3 mm a−1 with the late-stage extensional collapse of the Caledonian orogen playing an increasingly important role, especially in the final unroofing of the Western Gneiss Region with some remarkably preserved UHP rocks.

Notes: Widespread evidence for ultrahigh-pressure (UHP) metamorphism is reported in the Dulan eclogite-bearing terrane, the North Qaidam–Altun HP–UHP belt, northern Tibet. This includes: (1) coesite and associated UHP mineral inclusions in zircon separates from paragneiss and eclogite (identified by laser Raman spectroscopy); (2) inclusions of quartz pseudomorphs after coesite and polycrystalline K-feldspar + quartz in eclogitic garnet and omphacite; and (3) densely oriented SiO2 lamellae in omphacitic clinopyroxene. These lines of evidence demonstrate that the Dulan region is a UHP metamorphic terrane. In the North Dulan Belt (NDB), eclogites are characterized by the peak assemblage Grt + Omp + Rt + Phn + Coe (pseudomorph) and retrograde symplectites of Cpx + Ab and Hbl + Pl. The peak conditions of the NDB eclogites are P = 2.9–3.2 GPa, and T = 631–687 °C; the eclogite shows a near-isothermal decompression P–T path suggesting a fast exhumation. In the South Dulan Belt (SDB), three metamorphic stages are recognized in eclogites: (1) a peak eclogite facies stage with the assemblage Grt + Omp + Ky + Rt + Phn at P = 2.9–3.3 GPa and T = 729–746 °C; (2) a high-pressure granulite facies stage with Grt + Cpx (Jd 〈 30) + Pl (An24–29) + Scp at P = 1.9–2.0 GPa, T = 873–948 °C; and (3) an amphibolite facies stage with the assemblage Hbl + Pl + Ep/Czo at P = 0.7–0.9 GPa and T = 660–695 °C. The clockwise P–T path of the SDB eclogites is different from the near-isothermal decompression P–T path from the NDB eclogites, which suggests that the SDB was exhumed to a stable crustal depth at a slower rate. In essence these two sub-belts formed in different tectonic settings; they both subducted to mantle depths of around 100 km, but were exhumed to the Earth's surface separately along different paths. This UHP terrane plays an important role in understanding continental collision in north-western China.

Notes: Mineral assemblages in Al2O3-rich, SiO2- and K2O-poor metapelitic rocks from the western Odenwald Crystalline Complex (Variscan Mid-German Crystalline Rise, southern Germany) include corundum, spinel, cordierite, sillimanite, garnet and staurolite. Quartz is absent from almost all samples. Therefore, the applicability of conventional geothermobarometry is very limited or even impossible. Detailed petrographic investigation on selected samples permits inference of the sequence of appearance and disappearance of several mineral assemblages. The recognition of such partial re-equilibration stages and their associated mineral assemblages, together with mineral stabilities predicted from KFMASH pseudosections, enables the determination of the pressure-temperature (P–T) trajectories experienced by these rocks during the Variscan metamorphism. The rocks were metamorphosed under low-P/high-T conditions and underwent an anti-clockwise P–T evolution. A pressure increase from about 2 kbar to 4 ± 0.5 kbar was accompanied by heating. Peak metamorphic conditions were reached at pressures of 4 ± 0.5 kbar and temperatures of at least 640 °C, probably even higher. The retrograde evolution is characterised by near-isobaric cooling from ≥ 640 °C to approximately 550 °C. The rocks underwent the anti-clockwise evolution in a subduction-related magmatic arc setting. The close spatial association of the low-P/high-T rocks with recently discovered metabasic eclogites in the eastern part of the Odenwald Crystalline Complex may indicate a fossil paired metamorphic belt in the Central European Variscides.

Notes: The influx of a H2O–CO2-dominated fluid into actinolite-bearing metabasic rocks during greenschist facies metamorphism in the Kalgoorlie area of Western Australia resulted in a zoned alteration halo around inferred fluid conduits that contain gold mineralisation. The alteration halo is divided into two outer zones, the chlorite zone and the carbonate zone, and an inner pyrite zone adjacent to the inferred fluid conduits. Reaction between the fluid and the protolith resulted in the breakdown of actinolite and the development of chlorite, dolomite, calcite and siderite. In addition, rocks in the pyrite zone developed muscovite-bearing assemblages as a consequence of the introduction of potassium by the fluid. Mineral equilibria calculations undertaken using the computer software thermocalc in the model system Na2O–CaO–K2O–FeO–MgO–Al2O3–SiO2–H2O–CO2 show that mineral assemblages in the outer zones of the alteration halo are consistent with equilibrium of the protoliths with a fluid of composition XCO2 = CO2/(CO2 + H2O) = 0.1–0.25 for temperatures of 315–320 °C. The inner zone of the alteration halo reflect equilibrium with a fluid of composition XCO2≈ 0.25. Fluid-rock buffering calculations show that the alteration halo is consistent with interaction with a single fluid composition and that the zoned structure of the halo reflects the volume of this fluid with which the rocks reacted. This fluid is likely to have also been the one responsible for the gold mineralisation at Kalgoorlie.

Notes: Nanometric solid inclusions in diamond incorporated in garnet and zircon from felsic gneiss of the Kokchetav massif, Kazakhstan, have been examined utilizing electron microscopy and focused ion beam techniques. Host garnet and zircon contain numerous pockets of multiple inclusions, which consist of 1–3 diamond crystals intergrown with quartz, phengite, phlogopite, albite, K-feldspar, rutile, apatite, titanite, biotite, chlorite and graphite in various combinations. Recalculation of the average chemical composition of the entrapped fluid represented by multiple inclusion pockets indicates that such fluid contained a low wt% of SiO2, suggesting a relatively low-temperature fluid rather than a melt. Transmission electron microscopy revealed that the diamond contains abundant nanocrystalline inclusions of oxides, rare carbonates and silicates. Within the 15 diamond crystals studied, abundant inclusions were found of SiO2, TiO2, FexOy, Cr2O3, ZrSiO4, and single grains of ThxOy, BaSO4, MgCO3, FeCr2O4 and a stoichiometric Fe-rich pyroxene. The diversity of trace elements within inclusions of essentially the same stoichiometry suggests that the Kokchetav diamond crystallized from a fluid containing variable amounts of Si, Fe, Ti, Cr, Zr, Ba, Mg and Th and other minor components such as K, Na, P, S, Pb, Zn, Nb, Al, Ca, Cl. Most of the components in crystals included in diamond appear to have their origin in the subducted metasediments, but some of them probably originate from the mantle. It is concluded that Kokchetav diamond most likely crystallized from a COH-rich multicomponent supercritical fluid at a relatively low temperature (hence the apparently low content of rock-forming elements), and that the diversity of major and minor components suggests interactions between subducted metasediments and mantle components.

Notes: A high-P granulite facies gneiss complex occurs in north-west Payer Land (74°28′−74°47′N) in the central part of the East Greenland Caledonian (Ordovician–Devonian) orogen. High-P metamorphism of the Payer Land gneiss complex resulted in formation of the assemblages Grt + Cpx + Amp + Qtz + Ru ± Pl in mafic rocks, and Grt + Ol + Cpx + Opx + Spl in rare ultramafic pods. Associated metapelites experienced anatexis in the kyanite stability field. Peak metamorphic assemblages formed around 800–850 °C at pressures of c. 1.4–1.7 GPa, corresponding to crustal depths of c. 50 km. Mafic granulites contain abundant reaction textures, including the replacement of garnet by symplectites of Opx + Spl + Pl, indicating that the high-P event was followed by decompression while the granulites remained at elevated temperatures. Charnockitic gneisses from Payer Land show evidence of late Archean (c. 2.8–2.4 Ga) crustal growth and subsequent Palaeoproterozoic (c. 1.85 Ga) metamorphism. The gneiss complex experienced intense reworking during the Caledonian continental collision. On the basis of Caledonian monazite ages recorded from the high-P anatectic metapelites, the clockwise P–T evolution and formation of the high-P granulite facies assemblages is related to Caledonian crustal thickening, which resulted in formation of eclogites approximately 300 km north of Payer Land. The Payer Land granulites comprise a metamorphic core complex, which is separated from the overlying low-grade supracrustal rocks (the Neoproterozoic Eleonore Bay Supergroup) by a late Caledonian extensional fault zone, the Payer Land Detachment. The steep, nearly isothermal, unloading P–T path recorded by the granulites can be explained by erosional and tectonic unroofing along the Payer Land Detachment.

Notes: High-pressure granulites are characterised by the key associations garnet-clinopyroxene-plagioclase-quartz (in basic rocks) and kyanite-K-feldspar (metapelites and felsic rocks) and are typically orthopyroxene-free in both basic and felsic bulk compositions. In regional metamorphic areas, two essential varieties exist: a high- to ultrahigh-temperature group and a group representing overprinted eclogites. The high- to ultrahigh-temperature type formerly contained high-temperature ternary feldspar (now mesoperthite) coexisting with kyanite, is associated with garnet peridotites, and formed at conditions above 900 °C and 1.5 GPa. Clinopyroxene in subordinate basic rocks is Al-rich and textural evidence points to a high-pressure–high-temperature melting history. The second variety contains symplectite-like or poikilitic clinopyroxene-plagioclase intergrowths indicating former plagioclase-free, i.e. eclogite facies assemblages. This type of rock formed at conditions straddling the high-pressure amphibolite/high-pressure granulite field at around 700–850 °C, 1.0–1.4 GPa. Importantly, in the majority of high-pressure granulites, orthopyroxene is secondary and is a product of reactions at pressures lower than the peak recorded pressure. In contrast to low- and medium-pressure granulites, which form at conditions attainable in the mid to lower levels of normal continental crust, high-pressure granulites (of nonxenolith origin) mostly represent rocks formed as a result of short-lived tectonic events that led to crustal thickening or subduction of the crust into the mantle. Short times at high-temperature conditions are reflected in the preservation of prograde zoning in garnet and pyroxene. High-pressure granulites of both regional types, although rare, are known from both old and young metamorphic terranes (e.g. c. 45 Ma, Namche Barwa, E Himalaya; 400–340 Ma, European Variscides; 1.8 Ga Hengshan, China; 1.9 Ga, Snowbird, Saskatchewan and 2.5 Ga Jianping, China). This spread of ages supports proposals suggesting that thermal and tectonic processes in the lithosphere have not changed significantly since at least the end of the Archean.

Notes: The Mollendo–Camana Block (MCB) is a 50 × 150 km Precambrian inlier of the Andean belt that outcrops along the Pacific coast of southern Peru. It consists of stromatic migmatites of Paleoproterozoic heritage intensely metamorphosed during the Grenville event (c. 1 Ga; U-Pb and U-Th-Pb ages on zircon and monazite). In the migmatites, aluminous mesosomes (FMAS) and quartzofeldspathic leucosomes (KFMASH), contain various amounts of K-feldspar (Kfs), orthopyroxene (XMg Opx = 0.86), plagioclase (Pl), sillimanite (Sil; exceptionally kyanite, Ky) ilmenite (Ilm), magnetite (Mag), quartz (Qtz), and minor amounts of garnet (XMg Grt = 0.60), sapphirine (XMg Spr = 0.87), cordierite (XMg Crd = 0.92) and biotite (XMg Bt = 0.83). The ubiquitous peak mineral assemblage is Opx-Sil-Kfs-Qtz-(± Grt) in most of the MCB, which, together with the high Al content of orthopyroxene (10% Al2O3) and the local coexistence of sapphirine-quartz, attest to regional UHT metamorphism (〉 900 °C) at pressures in excess of 1.0 GPa. Fluid-absent melting of biotite is responsible for the massive production of orthopyroxene that proceeded until exhaustion of biotite (and most of the garnet) in the southern part of the MCB (Mollendo-Cocachacra areas). In this area, a first stage of decompression from 1.1–1.2 to 0.8–0.9 GPa at temperatures in excess of 950 °C, is marked by the breakdown of Sil-Opx to Spr-Opx-Crd assemblages according to several bivariant FMAS reactions. High-T decompression is also shown by Mg-rich garnet being replaced by Crd-Spr- and Crd-Opx-bearing symplectites, and reacting with quartz to produce low-Al-Opx-Sil symplectites in quartz-rich migmatites. Neither osumilite nor spinel-quartz assemblages being formed, isobaric cooling at about 0.9 GPa probably followed the initial decompression and proceeded with massive precipitation of melts towards the (Os) invariant point, as demonstrated by Bt-Qtz-(± pl) symplectites in quartz-rich migmatites (melt + Opx + Sil = Bt + Grt + Kfs + Qtz). Finally, Opx rims around secondary biotite attest to late fluid-absent melting, compatible with a second stage of decompression below 900 °C. The two stages of decompression are interpreted as due to rapid tectonic denudation whereas the regional extent of UHT metamorphism in the area, probably results from large-scale penetration of hot asthenospheric mantle at the base of an over-thickened crust.

Notes: The Arthur River Complex is a suite of gabbroic to dioritic orthogneisses in northern Fiordland, New Zealand. The Arthur River Complex separates rocks of the Median Tectonic Zone, a Mesozoic island arc complex, from Palaeozoic rocks of the palaeo-Pacific Gondwana margin, and is itself intruded by the Western Fiordland Orthogneiss. New SHRIMP U/Pb single zircon data are presented for magmatic, metamorphic and deformation events in the Arthur River Complex and adjacent rocks from northern Fiordland. The Arthur River Complex orthogneisses and dykes are dominated by magmatic zircon dated at 136–129 Ma. A dioritic orthogneiss that occurs along the eastern margin of the Complex is dated at 154.4 ± 3.6 Ma and predates adjacent plutons of the Median Tectonic Zone. Rims on zircon cores from this sample record a thermal event at c. 120 Ma, attributed to the emplacement of the Western Fiordland Orthogneiss. Migmatitic Palaeozoic orthogneiss from the Arthur River Complex (346 ± 6 Ma) is interpreted as deformed wall rock. Very fine rims (5–20 µm) also indicate a metamorphic age of c. 120–110 Ma. A post-tectonic pegmatite (81.8 ± 1.8 Ma) may be related to phases of crustal extension associated with the opening of the Tasman Sea. The Arthur River Complex is interpreted as a batholith, emplaced at mid-crustal levels and then buried to deep crustal levels due to convergence of the Median Tectonic Zone arc and the continental margin.

Notes: Petrological data provide a good record of the thermal structure of deeply eroded orogens, and, in principle, might be used to relate the metamorphic structure of an orogen to its deformational history. In this paper, we present two-dimensional thermal modelling of various subduction models taking into account varying wedge geometry as well as variation of density and topography with metamorphic reactions.The models clearly show that rock type accreted in the wedge has important effects on the thermal regime of orogenic wedges. The thermal regime is dominated by radiogenic heat production. Material having high radioactive heat production, like the granodioritic upper crust, produces high temperature metamorphism (amphibolitic conditions). Material with low radioactive heat production results in low temperature metamorphism of greenschist or blueschist types depending on the thickness of the wedge.Application of this model to seemingly unrelated areas of the Central Alps (Lepontine Dome, Grisons) and Eastern Alps (Tauern Window) explains the coexistence and succession of distinct Barrovian and blueschist facies metamorphic conditions as the result of a single, continuous tectonic process in which the main difference is the composition of the incoming material in the orogenic wedge. Accretion of the European upper continental crust in the Lepontine and Tauern Domes produces Barrovian type metamorphism while accretion of oceanic sediments results in blueschist facies metamorphism in the Valaisan domain.

Notes: Abstract  The purpose of this study was to describe public health nurses' views of the everyday problems of families and their needs for special support. Seventy-four nurses filled in a tripartite questionnaire. The needs varied by region and were seen in 4% to 23% of all families expecting a baby or with a child younger than 3 age in the nurses' clientele. Approximately one-third of the families were considered to have a pressing need for support. More than half of families (54%) had difficulties coping with parenthood and family structure, almost one-third (30%) with raising their children and with childcare, and nearly one-third (27%) with their social network. In 20% of the families, the parents experienced problems relating to their relationship as a couple; 20% of the families had problems connected to the children's development, growth, and health; and in 19% of the families, the parents had health problems. Special needs were also caused by the parents' use of alcohol (15%) and by disputes over the children's custody and visiting rights (7%). The information provided by the study can be used in developing clinical services and the family work supporting them.