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The current surgical workload assessments in KwaZulu-Natal (KZN) are inadequate to inform strategies to improve surgical services. Breast diseases have a well-defined spectrum and surgical treatment options, analysis of which could guide health policy in the field. This project aimed to quantify and analyse the operative workload for breast pathology in KZN.A retrospective review of breast-related operations conducted at public sector hospitals in KwaZulu-Natal province between 1 July and 31 December 2015 was undertaken. Data was collected from theatre operative registers and manually categorised as follows: sepsis, benign pathology, malignant pathology, and by hospital, according to geographic location, and complexity of care to determine factors to improve the service for breast care in the province.In the 6-month study period, 13 282 general surgical procedures were performed of which 776 (5.8%) were breast-related operations. There were 372 (47.9%) operations for breast sepsis, 140 (18%) for benign breast lesions, 17 (2.2%) for cosmetic indications and 27 (3.5%) for diagnostic procedures. There were 223 (28.7%) procedures for nonbenign disease: 21 (2.6%) wide local excisions (WLE), 203 (26.2%) mastectomies of which 161 (72.2%) mastectomies had an axillary lymph node dissection and 26 (11.7%) were performed as onco-plastic procedures. Hospitals in the Durban and Pietermaritzburg metropolitan areas performed 75% of the breast-related procedures. The majority (69.6%) of sepsis-related procedures were performed at secondary/regional facilities, while 58.3% of non-benign breast surgeries were performed at tertiary and quaternary centres.Breast sepsis accounts for almost 50% of the surgery and is mainly dealt with at hospitals above district level. One-third of breast surgery in KZN province is for non-benign disease. There is a paucity of breast-conserving surgery. Elucidation of these observations can guide improvement in the provincial breast care service.

The thermoresponsive behavior of two molecular brushes having poly(propylene oxide)–poly(ethylene oxide) copolymer side chains is investigated in aqueous solution, where the side chains have longer contour lengths than the backbone. The brushes differ in the side-chain architecture; they are either a diblock (PbE) or a random copolymer (PrE). For both types of brushes, an overall rodlike shape at room temperature is revealed by cryo-electron microscopy. A polymer-rich central part and a water-rich outer part are identified by small-angle neutron scattering (SANS). Upon heating up to the cloud point, the shell of PbE weakly dehydrates, while the one of PrE severely dehydrates along with a cylinder-to-disk transformation. Moreover, the aggregates formed above the cloud points feature significantly different inner structures: PbE aggregates are composed of strongly interpenetrating brushes, while PrE aggregates consist of loosely packed brushes. These differences indicate the important role of the side-chain architecture in the thermal dehydration behavior and the associated structural changes.

Necrotizing fasciitis and toxic shock syndrome are life-threatening conditions that can be seen after any surgical procedure. With only 4 previous published case reports in the obstetrics and gynecology literature of these two conditions occurring secondary toClostridium septicum, we describe a case of necrotizing fasciitis and toxic shock syndrome occurring after a term cesarean delivery caused by this microorganism, requiring aggressive medical and surgical intervention.

Purpose: To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local con trol (LC), disease-free survival (DFS) and/or overall survival (OS). Material and methods: Aretrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpo stat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. Results: The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a me dian survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with sta tistically significantly inferior LC ( p= 0.035) and inferior DFS ( p= 0.011) for patients with mean Point A dose of > 80 Gy . Insufficient evidence existed to conclude an association with OS. Conclusions: LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC. J Contemp Brachyther 2012; 4, 1: 3-7 DOI: 10.5114/jcb.2012.27945

BACKGROUND: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. METHODS: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER

The variety of microstructures that form at low solidification speed in peritectic alloys, bands, and islands, or even coupled (or cooperative) growth of the primary α and peritectic β phases, have been previously explained by nucleation-growth mechanisms. In a recent investigation on Cu-Sn, a new growth mechanism was conjectured on the basis of two-dimensional (2-D) optical microscopy and electron backscattered diffraction (EBSD) observations made in longitudinal sections. In the present contribution, synchrotron-based tomographic microscopy has been used to confirm this mechanism: α and β phases totally interconnected in three dimensions and bands (or islands) can result from an overlay mechanism, rather than from a nucleation events sequence. When the lateral growth of a new layer is too fast, an instability can lead to the formation of a lamellar structure as for eutectic alloys.

Single pan thermal analyses (SPTA) have been performed on Cu-14.5 wt.% Sn, Cu-21.3 wt.% Sri and Cu-26.8 wt.% Sit peritectic alloys. For this purpose, a SPTA assembly has been built and calibrated. As the latent heat is a function of temperature and composition during solidification of alloys, a new heat flow model coupled to a Cu-Sn thermodynamic database has been defined for the calculation of the corresponding evolutions of the solid mass fraction, f(s)(T). To verify the accuracy of this model, a close comparison with a micro-segregation model that includes back-diffusion in the primary alpha-solid phase has also been conducted successfully. The thermal analyses have finally shown that the Cu-Sn phase diagram recently assessed in the review of Liu et al. is the most reliable. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

International loans, especially those made to foreign sovereign lenders, differ in a number of ways from most loans made by domestic banks to residents of their own country. They are usually larger than most domestic loans, the lender has more difficulty in obtaining reliable data on the borrower, and, most importantly, lender and borrower are under different jurisdictions. This last factor makes enforcing a loan contract considerably more difficult, and provides incentives for the borrower to avoid prompt repayment, even if such repayment is feasible. Guttentag and Herring equate the presence of such incentives loosely with moral hazard. Eaton and Gersovitz develop a formal model of lending (with a single borrower and multiple lenders acting in unison) that explicitly takes debt repudiation into account. In their model, borrowers are inherently dishonest, i.e., they will default on their loans if their expected utility maximization so dictates. We prefer to characterize such behavior by the somewhat more neutral term rational. This paper simultaneously expands and simplifies the Eaton-Gersovitz model and places it in a game theoretic context borrowed from Dixit. We consider only two time periods, the present and the future, and take lending decisions that were made in the past as given. Additional keywords include: One-period and multiple period mathematical models.

This paper presents a hygrometer setup for measuring the concentration of water vapor in air by means of infrared absorption spectroscopy. Recently developed vertical-cavity surface-emitting lasers (VCSELs) emitting near 1.84 /spl mu/m are used as source of the infrared light. The laser hygrometer is able to calculate the density of water molecules from the measurement of one single light-current characteristic, without any additional reference measurement. The absolute and relative humidity are calculated from the water molecule density and the temperature of the ambient air.

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Objective: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). Methods: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non-consanguineous relatives. Results: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. Conclusion: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts.

Objectives Tandem placement as part of low-dose-rate (LDR) brachytherapy boost for cervical cancer may be complicated by uterine perforation. The objective of this study was to describe a 10-year experience of using intraoperative ultrasound guidance in an attempt to minimize the risk of uterine perforation. Methods Operative and inpatient records were reviewed to identify cases in which intraoperative ultrasound guidance was employed in order to assist tandem placement, and to determine whether clinical or radiographic findings subsequently suggested uterine perforation. Demographic factors were collected in order to determine the baseline risk of perforation within this population. Results Between 1998 and 2008, 71 patients underwent 110 ultrasound-guided placements of tandem applicators. The median age was 48 (range, 26–88) years, and 20% were older than 60 years. Disease stage was FIGO IB1 (n = 10), IB2 (n = 13), IIA (n = 4), IIB (n = 19), IIIA (n = 2), IIIB (n = 16), IVA (n = 5) and IVB (n = 2). The median gravidity was 3 (range 1–10) and median parity was 3 (range 0–10). Seven patients had a preimplant history of pelvic infection, four had a history of intrauterine contraceptive device use, and 10 had a prior history of Cesarean section delivery. Only one patient experienced infection that may have been attributable to tandem placement-associated uterine perforation. At median survivor follow-up of 34 months, 19 patients had died. The estimated 3-year disease-free and overall survival rates for the entire population were 60% and 66%, respectively. Conclusions Within the present population, intraoperative ultrasound guidance of tandem placement was associated with no confirmed cases of uterine perforation. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously.

A recently developed model for 1-alkanol+alkane mixtures is extended to methanol mixtures and to the non-polar mixing partners tetrachloromethane and benzene. The model contains chemical and physical terms, which are combined in a thermodynamically consistent way. For our calculations on methanol mixtures, we have measured g E of methanol+ hexane via static vapor pressure measurements. In order to check the model predictions for systems with higher alkanols and alkanes, we have also determined g E of 1-octanol+tetradecane by measuring the melting curve. The reproduction of the excess properties of methanol+hexane, the agreement between predicted and measured values of g E for 1-octanol+ tetradecane, and the capability to deal also with other non-polar mixing partners demonstrate the power and reliability of the model.

Summary Pemphigus foliaceus (PF) is an autoimmune bullous epidermal disease, characterized by autoantibodies specific to the desmosomal protein desmoglein 1 (dsg1) and by acantholysis, the rupture of the cellular junctions among keratinocytes. Known also as fogo selvagem (wild fire) in Brazil, the disease has distinct epidemiological characteristics, being endemic in certain regions of South America. It is a multifactorial (complex) disease, with oligo- or polygenic disease susceptibility. In view of the previously reported evidences of a role for apoptosis dysregulation in pemphigus pathogenesis, we hypothesized that genetic variants of molecules participating in apoptosis may contribute to interindividual variation of susceptibility to PF. The TP53 12139(G,C) and the BAX−248(G,A) single nucleotide polymorphisms (SNP) were analysed in a genetic association study. The allelic, genotypic and allele carrier frequencies for these SNPs did not differ statistically between the patient and the control groups, for both the Euro- and the Afro-Brazilian population strata. The results of this study lead us to conclude that, although the TP53 and BAX alleles analysed differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere with the development of the disease.

23 pages, 8 figures, 6 tables, 20 references., In this work we tested the influence of different solutions of a hydrophobic polymer named Guilspare1, applied to the soil surface to reduce soil evaporation, on the soil water status, soil temperature, crop performance and weed emergence. Two tests were carried out on a farm of the Guadalquivir river valley, southwest Spain, one with a maize crop and the other with bare soil. In the test with maize, we evaluated the effect of applying a solution of 2% v/v of Guilspare1 in water, at the rate of 3 l m 2, on the crop performance and weed emergence. On both the treated and the untreated control plots, three rates of irrigation were applied, namely 100, 75 and 50% of the locally determined optimal irrigation depth to cover the crop needs for an optimum development and yield. For the case of 50% of the irrigation dose, the performance of the crop treated with the polymer (T50) was much better than that of the untreated control plot (C50). The crop height and green leaf area index for T50 were nearly as good as for the C100 control plants receiving 100% of the irrigation dose. The T50 crop was 73% of the yield of the treated and fully irrigated T100 crop, while the C50 yield was only 38% of the C100 yield. The treated crop reached the different phenological stages quicker than the untreated crop. The polymer was effective in reducing weed emergence. In the test with bare soil, 0.8% v/v of Guilspare1 in water, at the rate of 1 l m 2, kept levels of water content in the soil as high as other solutions with greater amounts both of polymer and water. The average soil water content during the irrigation period in this lower treatment was 34 and 53% higher at depths of 0.15 and 0.25 m, respectively, than in the untreated plots. No influence of the polymer on soil temperature was observed. Results from additional measurements on weed emergence and hydraulic conductivity of the soil surface showed that the polymer was still effective 7 months after application. In fact, the hydraulic conductivity in the range near saturation was 44% greater in the treated plots than in the untreated ones, and the number of weeds was 27% lower.

Objective. The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. Methods. Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. Results. The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I ( n = 18), Stage II ( n = 7), and Stage III ( n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3–119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina ( n = 5) or at distant sites ( n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis ( n = 2), fistula ( n = 2), and radiation stricture ( n = 1). Conclusion. Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.

In this article, SPTA curves were analyzed with the help of the Brody–Flemings [1] microsegregation model. However, this model does not conserve solute in the solid phase and is limited to small Fourier numbers (Lever rule is recovered for Fos = 0.5 instead of Fos = 1). In our article, the calculated value of Fos was 1.411 and this value was unfortunately used in the coupling with thermophysical data. While the heat flow model presented is still valid, a corrected analysis is presented here using Ohnaka’s model [2]. By enforcing a solute balance over the solid and liquid phases and assuming a parabolic distribution of concentration in the solid phase, Ohnaka [2] showed that the composition of the liquid phase, Cl, is given for a linearized phase diagram by

OBJECTIVE: Computerized tools may be useful in speeding up and facilitating the laborious task of coding patient information. This paper describes a method of objectively evaluating their efficiency. DESIGN: 38 study subjects were randomly assigned to a manual coding group or an automated coding group, with stratification according to two variables (used to coding yes/no, physician yes/no). Subjects then coded the same standardized set of diagnoses in a limited time. The numbers of exact codes retrieved were compared using a global analysis of variance model. RESULTS: The two groups were not significantly different with regard to the number of physicians (p = 0.74) and the number of usual coders (p = 0.52) they included. Significantly more exact codes were achieved in the group using automated coding than among the manual group (p = 0.04). Physicians were significantly more efficient at coding than non-physicians (p = 0.02). CONCLUSION: This study describes an objective means of evaluating the performance of an automated coding tool. It shows that better results were achieved with the computerised compared to the manual method, even when the superior abilities of physicians were taken into account.

Four cases of relapse of acute lymphoblastic leukemia (ALL) in pregnancy have been reported previously. During the past 2 decades, ALL has become curable in a majority of children, many of whom have entered their reproductive years. Thus, additional occurrences of relapsing ALL during pregnancy can be anticipated. We present the fifth case in the English- language medical literature of recurrent ALL in pregnancy. A 20-year-old woman with ALL experienced a relapse during the third trimester of her first pregnancy. Reinduction therapy was started with vincristine and prednisone and the baby was delivered 3 weeks later. Umbilical cord blood was collected and stored. The patient then received intensive chemotherapy with whole body radiotherapy and autologous peripheral blood stem cell rescue. The ALL has been in second remission for 22 months. Our patient is the only current survivor of a relapse of ALL during pregnancy. In addition, the collection of umbilical cord blood from a pregnant woman with leukemia has not been reported previously.

BACKGROUND Women diagnosed with invasive cervical carcinoma during pregnancy are faced with difficult decisions regarding therapy and the fate of their unborn child. A modest treatment delay for International Federation of Gynecology and Obstetrics Stage I cervical lesions is considered acceptable in patients who wish to continue their pregnancy. METHODS Two patients with locally advanced cervical carcinoma diagnosed early in the second trimester strongly desired continuation of their pregnancies. They were treated with neoadjuvant chemotherapy until the third trimester, and then underwent delivery and definitive surgical treatment. The patients were evaluated during pregnancy for evidence of a clinical response to chemotherapy. Intraoperative findings and pathologic analysis of the surgical material provided further objective data regarding disease status. RESULTS Both patients experienced a dramatic reduction in tumor volume, rendering radical hysterectomy feasible at the time of cesarean section. In addition, both patients tolerated chemotherapy well and there were no adverse fetal effects. Favorable neonatal outcomes were achieved. One patient experienced recurrence within 5 months of surgery, whereas the other patient remained without evidence of disease for 2 years. CONCLUSIONS To the authors' knowledge, these reports constitute the first description of the use of neoadjuvant chemotherapy for invasive squamous cell carcinoma of the cervix in pregnancy (MEDLINE 1966-1997). This therapeutic option should be considered in selected women with locally advanced cervical carcinoma who do not want termination of their pregnancy. Cancer 1998;82:1529-34. © 1998 American Cancer Society.

An allelotype analysis of endometrial carcinoma was undertaken to identify chromosomal loci that are relevant to this tumor type. A total of 70 highly polymorphic microsatellite markers, distributed among all nonacrocentric chromosome arms, were examined for evidence of loss of heterozygosity or allelic imbalance in DNA samples from matched normal and tumor tissues. An average of 21 informative tumor cases were obtained for each marker. Allelic deletions or imbalance were observed on 31 of 41 chromosome arms with no marker showing an allelic loss ratio of greater than 33%. Those chromosome arms most frequently involved were 3p, 8p, 9p, 14q, 16q and 18q. There was a strong correlation between loss of heterozygosity on chromosome 14q and death from disease. These data indicate that the molecular genetic character of endometrial carcinoma is complex and that a relatively large number of different chromosomal loci are likely to play a role in the etiology and progression of this tumor type.

The UMLS is a complex collection of interconnected biomedical concepts derived from standard nomenclatures. Designing a specific subset of the UMLS knowledge base relevant to a medical domain is a prerequisite for the development of specialized applications based on UMLS. We have developed a method based on the selection of the appropriate terms in original nomenclatures and the capture of a set of UMLS terms that are linked to them in the network to a certain degree. We have experimented it as the foundation for a concept base applied to urology. Results depend on the exhaustiveness of the relationships between the Metal concepts. A preliminary analysis of the sub-base reveals that some adaptations of vocabulary and ontology are required for clinical applications.

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by a familial predisposition to colorectal carcinoma and extracolonic cancers of the gastrointestinal, urological, and female reproductive tracts, notably the endometrium. A genetic locus for HPNCC was recently determined by linkage analysis to exist on chromosome 2p; both sporadic and HNPCC-associated colorectal carcinomas exhibit a "replication error" phenotype, characterized by instability of dinucleotide repeat sequences throughout the genome. Here, we address the hypothesis that the replication error phenotype would be evident in some fraction of sporadic endometrial carcinomas or in those associated with HNPCC. Microsatellite instability was observed in 17% of sporadic endometrial carcinomas and in 75% of those tumors associated with HNPCC. These data indicate that the HNPCC gene is also involved in heritable and somatic forms of endometrial carcinoma.

Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.

Mutation and overexpression of the p53 gene have been noted in a wide range of human cancers and are thought to play a role in malignant transformation. Previously, immunohistochemical detection of p53 has been possible only in fresh-frozen tissues. We examined p53 expression in paraffin-embedded tissues from 50 epithelial ovarian cancers and 25 primary breast cancers with a modified immunohistochemical (IHC) technique developed in this laboratory, using monoclonal antibody (MAb) PAb1801. The 75 cases were selected from a group of patients in whom the expression levels had already been assessed in a fresh-tissue IHC assay. An identical staining reactivity was observed in both formalin-fixed, paraffin-embedded tissue and fresh-frozen tissue in 48 of 50 (96%) epithelial ovarian cancers and in 23 of 25 (92%) primary breast cancers. Immunodetection of p53 in paraffin-embedded tissue blocks will be a useful alternative to the standard fresh-tissue assay and can accurately reflect the level of p53 expression in human tumors.

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.

Continuous-wave operation of an electrically pumped vertical-cavity surface-emitting laser (VCSEL) with an emission wavelength of 2.01 µm employing a heavily strained active region is reported.

High-performance lnGaAlAs/InP vertical-cavity surface-emitting lasers (VCSELs) at 1.55 /spl mu/m, are demonstrated with superior output characteristics and modulation bandwidths up to 10 Gbit/s.

Improved 1.55 µm InGaAlAs/InP vertical-cavity surface-emitting lasers were fabricated in the buried tunnel junction technology yielding sub-mA threshold currents, 0.9 V threshold voltage, 10–40 Ω series resistance, output power up to 7 mW (20°C, CW) and CW operation up to > 110°C.