bluuebunny/crossref_metadata_2025 huggingface dataset:
PDF of distance function for level‐set flamelet library modelling
Authors: Nilsson P. , Bai X. S.
Published: February 2003

The difference between a presumed distribution of flamelet position and a numerically simulated distribution of distance function (a signed distance to flamelet) is investigated. It is shown that even if the distribution of flamelet position is symmetrical and close to Gaussian, the distribution of distance function away from the mean flame position is skewed towards the mean position and the mean of the distance function is also different from the distance to the mean position. The difference depends on the distance to the mean flame and the flame wrinkling amplitude. An extension method for the variance of the distance function and an upwind scheme for solving the re‐initialization equation are presented. A numerical simulation of a premixed turbulent flame is compared to experimental data. Copyright © 2003 John Wiley & Sons, Ltd.
A cost‐minimisation study of alternative discharge policies after hip fracture repair
Authors: Polder Johan J. , van Balen Romke , Steyerberg Ewout W. , Cools Herman J.M. , Habbema J. Dik F.
Published: February 2003

It is widely assumed that health care costs can be reduced considerably by providing care in appropriate health care institutions without unnecessary technological overhead. This assumption has been tested in a prospective study. Conventional discharge after hip fracture surgery was compared with an early discharge policy in which patients were discharged to a nursing home with specialised facilities for rehabilitation. We compared costs for both strategies from a societal perspective, using comprehensive and detailed data on type of residence and all kinds of medical consumption during a 4‐month follow‐up period.

As expected, early discharge reduced the hospital stay (with 13 days, p=0.001). More patients were discharged to a nursing home (76% versus 53%). Total medical costs during follow‐up were reduced from an average of €15 338 to €14 281, representing relatively small and not significant savings (p=0.3). There are two explanations for this unexpected result. First, costs incurred by hip fracture patients were relatively less while in hospital. Hence, nursing home costs almost equalled hospital costs per admission day. Second, compared with the conventionally discharged group early discharged patients were subjected to more medical procedures during the first post‐operative days. We conclude that: (1) early discharge shifted rather than reduced costs; (2) the details of costing have a major influence on the cost‐effectiveness of alternative discharge policies. Copyright © 2002 John Wiley & Sons, Ltd.
The determinants of health care expenditure: testing pooling restrictions in small samples
Authors: Herwartz Helmut , Theilen Bernd
Published: February 2003

Health care expenditure has increased substantially in all Western industrialized countries in the last decades. The necessity to contain the increase in health care expenditure has motivated the analysis of its determinants to explain differences across countries and health systems. However, recent studies have questioned the use of cross section data arguing that health systems are too different to allow for such comparisons. In this paper we investigate whether this criticism is really justified. We analyze the variations of health care expenditure in OECD countries relative to income, population aging and technological change. Our analysis is based on pooled cross section data and time series. Firstly, formulating error correction models for individual countries we demonstrate that in almost all cases the investigated variables are cointegrated. Secondly, we use a bootstrap framework for inference and examine whether the influence of explanatory variables is unique across countries. Applying recursive estimation procedures we find evidence for cross country homogeneity during the period 1961–1979. In the last two decades health care dynamics become more and more country specific thus indicating divergence of health systems and the growing importance of country‐specific effects in the explanation of differences in health care expenditure. Copyright © 2002 John Wiley & Sons, Ltd.
Medical student indebtedness and the propensity to enter academic medicine
Authors: Fox Marc
Published: February 2003

This paper considers the potential impact of medical school indebtedness and other variables on the propensity of US doctors to enter academic medicine. Probit models provide some evidence that indebtedness reduces the likelihood that physicians will choose academic medicine as their primary activity. Nevertheless, the magnitude of this effect is not large. As indebtedness may be endogenous, the probits are rerun using an instrumental variables approach. These estimates imply that over time indebtedness may have an important impact on the propensity of physicians to enter academic medicine. Copyright © 2002 John Wiley & Sons, Ltd.
Deadweight loss of bacterial resistance due to overtreatment
Authors: Elbasha Elamin H.
Published: February 2003

Widespread use of antibiotics is considered the major driving force behind the development of antibiotic resistance. The benefits of exceeding the welfare‐maximizing level of antibiotic use are below the costs of resistance created by this excess quantity of antibiotics used, thereby resulting in a welfare deadweight loss. This paper uses a simple economic model to examine the theoretical and empirical aspects of the welfare loss generated by resistance and analyzes its policy implications. The annual deadweight loss associated with outpatient prescriptions for amoxicillin in the United States is estimated at $225 million. Published in 2002 by John Wiley & Sons, Ltd.
How measures of perception from survey data lead to inconsistent regression results: evidence from adolescent and peer substance use
Authors: Norton Edward C. , Lindrooth Richard C. , Ennett Susan T.
Published: February 2003

In studies of peer group behavior, the direct measure of peer group behavior is often not available, and so is replaced by perceptions from survey respondents. This study shows that regression estimators are inconsistent when the correctly measured independent variable of group behavior is replaced with perceived measures from survey respondents. The inconsistency is due to three sources: projection of own behavior onto the group, rescaling the marginal effect of the group, and simple random measurement error. We discuss why each effect may cause inconsistency, derive formulas for the probability limit to quantify their effects, and illustrate with three examples of adolescent smoking and drinking. Copyright © 2002 John Wiley & Sons, Ltd.
Managed care and technical efficiency
Authors: Shelton Brown H.
Published: February 2003

By focusing exclusively on consumer benefit, previous studies of the effects of managed care have ignored important hospital efficiency gains. This study uses the HCUP sample of hospitals for 1992–1996 to estimate a stochastic frontier model of hospital technical efficiency. After controlling for hospital and market area variables, the study finds strong evidence that increased managed care insurance in a given market is associated with improved technical efficiency in the area's hospitals, especially in tertiary cases. Using Battese and Coelli's one‐stage method (1995), the coefficients estimates are more efficient than for two‐stage methods found in the literature. Copyright © 2002 John Wiley & Sons, Ltd.
Determining the optimal combinations of mutually exclusive interventions: a response to Hutubessy and colleagues
Authors: Coyle Douglas
Published: February 2003

Hutubessy and colleagues have suggested a technique for decision‐makers to employ in determining the optimal combination of interventions. This technique requires the adoption of Monte Carlo simulation analysis to identify the probability that a certain program will be included in an optimal mix given the uncertainty around the program's expected costs and benefits.

In this response, it will be demonstrated that this methodology can lead to potential inefficiencies arising through the dependence of such probabilities on decisions relating to other programs and the failure to consider the opportunity costs of obtaining increased health benefits. A simple alternative approach is suggested which avoids these problems. Copyright © 2002 John Wiley & Sons, Ltd.
Double discounting of QALYs
Authors: MacKeigan Linda D. , Gafni Amiram , O'Brien Bernie J.
Published: February 2003

Quality‐adjusted life‐years (QALYs) calculated from time tradeoff (TTO) based preferences have a time preference component. To impose a conventional discount rate on these implicitly discounted QALYs introduces some degree of double discounting. The purpose of this study was to determine the magnitude of the double discounting effect and the effectiveness of a suggested method for avoiding double discounting in a TTO‐based QALY model. Our analysis used holistic and composite preference scores obtained with the TTO technique in a prior study of four hypothetical treatment paths in type 2 diabetes. Discounted composite preference scores were significantly discrepant from holistic preference scores. Adjusting TTO‐based quality weights prior to external discounting reduced the discrepancy only slightly. Since time preference effects may vary with health state context, the double discounting effect needs further investigation. Copyright © 2002 John Wiley & Sons, Ltd.
A new paradigm for R&D in water resources engineering
Authors: Pandit Chetan
Published: February 2003

The technology in water resources engineering (WRE) seems to be stagnant. No new technology of any significance has emerged for quite some time now and there seems to be none in the pipeline. In the WRE sector, R&D does not generate the same level of excitement and challenges that it does in other sectors. Shortage of funds does not seem to be the reason for this disappointing performance of R&D. The main problems are:

WRE R&D has very little potential for patents, Intellectual Property Rights (IPR) and profit and therefore the private sector does not take any interest in R&D in WRE.

Most of the research pursued by the universities is too theoretical. There is very little applied research.

There is a marked lack of creativity and inspiring ideas for R&D. There are neither any “technology dreamers” nor any dreams.

Users are not being involved in the planning.

The time is running out for R&D managers in WRE. The vision plans of most governments incorporate a set of measurable performance targets to be achieved in a stipulated time frame. Many of the targets are less than 10 years away. Therefore, if R&D is to be of any assistance in achieving the targets set for 2010, then that R&D must start now, not next year. The present approach to R&D has not produced desired results and, therefore, it must be changed immediately.

The paper proposes a new approach to provide an impetus to R&D in the WRE sector. Copyright © 2003 John Wiley & Sons, Ltd.
Addressing the unanswered questions in global water policy: a methodology framework
Authors: de Fraiture Charlotte , Cai Ximing , Rosegrant Mark , Molden David , Amarasinghe Upali
Published: February 2003

Are the available water resources sufficient to produce food for the growing world population while at the same time meet increasing municipal, industrial and environmental requirements? Projections for the year 2025, presented by different research groups at the second World Water Forum in The Hague, show an increase in global agricultural water use ranging from 4 to 17%. Estimates for the growth of total withdrawals, including domestic and industrial sectors, vary from 22 to 32%. This range is the result of differences in model structure and assumptions. Although these analyses were instrumental in raising awareness concerning the extent of present and future water scarcity problems, they raise many questions, which remain largely unanswered. The questions relate to the impact of water‐ and food‐related policies on global and regional water scarcity, food production, environment and livelihoods through the year 2025. The International Food Policy Research Institute (IFPRI) and the International Water Management Institute (IWMI) embarked on a joint modeling exercise to address these questions. This paper lays out the issues and discusses the methodology. During the 18th ICID Congress in July 2002 at Montreal, preliminary results will be presented. Copyright © 2003 John Wiley & Sons, Ltd.
Human uterine vascular structures in normal and diseased states
Authors: Hickey Martha , Fraser Ian
Published: February 2003

Menstrual bleeding disorders are one of the most common problems presenting to the gynaecologist. There is increasing evidence that alterations in human uterine vascular structures are associated with spontaneous and sex steroid–induced changes in menstrual bleeding patterns. This article will discuss the normal anatomy and physiology of uterine vascular growth, breakdown, and repair and will indicate where altered anatomy and function may contribute to menstrual disorder. In particular, impact of low‐dose progestogens on the endometrial vasculature and endometrial vascular fragility will be discussed. Disturbances of myometrial vascular growth and remodeling, including fibroids, adenomyosis, implantation, and arterio‐venous malformations will also be addressed. Microsc. Res. Tech. 60:377–389, 2003. © 2003 Wiley‐Liss, Inc.
Granulated metrial gland cells in the murine uterus: Localization, kinetics, and the functional role in angiogenesis during pregnancy
Authors: Wang Chunlian , Tanaka Tetsuji , Nakamura Hiroaki , Umesaki Naohiko , Hirai Kouzo , Ishiko Osamu , Ogita Sachio , Kaneda Kenji
Published: February 2003

Granulated metrial gland (GMG) cells are a major immune cell population in the murine pregnant uterus, and contribute to the maintenance of pregnancy by functioning as uterus‐specific natural killer (NK) cells. In order to reveal their kinetics, activation, and functional roles in pregnancy, we conducted quantitative and immunohistochemical analyses in normal and immuno‐modulator‐treated mice. Under a light microscope, GMG cells were identified by red cytoplasmic granules in periodic‐acid‐Schiff (PAS)‐stained sections. They progressively increased in number and size with the peak at day 12–14 of pregnancy in the decidua and metrial gland. New vessel formation was most prominent around day 8, and the total vascular area reached the peak at day 13. GMG cells were often located near the blood vessels, and expressed vascular endothelial growth factor (VEGF), suggesting their possible inducing role in angiogenesis during the development of decidua/metrial gland. While blood vessels in the non‐pregnant uterus were negative for vascular cell adhesion molecule (VCAM)‐1, those in the pregnant one were positive. Treatment with neutralizing antibody against VCAM‐1, however, did not decrease the number of GMG cells. On the other hand, mitosis of GMG cells was frequently observed. These data suggest that the increment of GMG cells during pregnancy may largely result from local proliferation in the uterus rather than an increased influx of precursor cells. Although we attempted to induce in vivo activation of GMG cells by administration of interleukin‐12 (IL‐12) or alpha‐galactosylceramide, a potent activator for natural killer‐T (NK‐T) cells, the number of GMG cells did not appreciably increase. The present study has demonstrated that GMG cells locally proliferate in the pregnant uterus, not being related to VCAM‐1 expression by the uterine vasculature or systemic activation of NK cells and NK‐T cells, and seem to be involved in angiogenesis in the pregnant uterus through VEGF production. Microsc. Res. Tech. 60:420–429, 2003. © 2003 Wiley‐Liss, Inc.
Use of the confocal laser scanning microscope in studies on the developmental biology of marine crustaceans
Authors: Buttino Isabella , Ianora Adrianna , Carotenuto Ylenia , Zupo Valerio , Miralto Antonio
Published: February 2003

Confocal Laser Scanning Microscope techniques have been applied to study the developmental biology of marine copepods and decapod larvae. The lipophylic probes DiI and DiOC6 were used to study both the external and internal morphology of these crustaceans, whereas the same DiOC6 and the specific nuclear probe Hoechst 33342 were used to study embryonic development of copepods in vivo. To distinguish viable from non‐viable copepod embryos, the vital dye dichlorodihydrofluorescein diacetate (H2DCFDA) was used. Major advantages and difficulties in the use of these non‐invasive techniques in studies of the reproductive biology of marine crustaceans are discussed. Microsc. Res. Tech. 60:458–464, 2003. © 2003 Wiley‐Liss, Inc.
Establishment of a nude mouse model of hepatic metastasis for evaluation of targeted retroviral gene delivery
Authors: Stapfer Maria , Hu Jie , Wei Denise , Groshen Susan , Beart Robert W.
Published: January 2003

Background and Objectives

The goal of this study was to establish a reproducible nude mouse model of liver metastasis and investigate the potential of deploying targeted injectable retroviral vectors for metastatic gastrointestinal cancer.

Methods

Human cancer cells were injected into the portal vein via an indwelling catheter. The animals were sacrificed at specified time intervals, and the number of tumor nodules was counted in histologic sections of harvested livers. A group of animals received either an extracellular matrix‐targeted or a nontargeted retroviral vector bearing a β‐galactosidase gene by portal vein infusion.

Results

The number of tumor nodules increased progressively over time at ≤50 days post‐infusion (r = 0.81; P < 0.0001). Transduction of tumor nodules was observed in the animals that received a matrix‐targeted, but not a nontargeted, vector.

Conclusions

We have established a reproducible nude mouse model of liver metastasis, and demonstrated the feasibility of gene delivery to metastatic tumor nodules in vivo by portal vein infusions of a matrix‐targeted retroviral vector. J. Surg. Oncol. 2003;82:121–130. © 2003 Wiley‐Liss, Inc.
Heterotopic ossification in rectal cancer: Rare finding with a novel proposed mechanism
Authors: Kypson Alan P. , Morphew Emilie , Jones Relief , Gottfried Marcia R. , Seigler Hilliard F.
Published: January 2003

The rare finding of heterotopic ossification in a case of primary rectal adenocarcinoma is described along with a review of the literature. Immunohistochemistry for a bone morphogenic protein (BMP‐2) and fibroblast growth factor (FGF‐2), both of which induce and stimulate bone formation, was performed and revealed overexpression of BMP‐2 by the tumor cells, elucidating a possible mechanism which up to now had been based merely on speculation. J. Surg. Oncol. 2003;82:132–136. © 2003 Wiley‐Liss, Inc.
p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer
Authors: Dong Ming , Nio Yoshinori , Yamasawa Kunihiro , Toga Tomoko , Yue Lishuang , Harada Takayuki
Published: January 2003

Background and Objectives

Mutations in the p53 gene are found in more than 50% of human cancers and are observed in 60–80% of pancreatic cancers. The clinicopathologic implications of p53 abnormalities and their effects on the efficacy of the adjuvant chemotherapy for pancreatic cancer remain controversial.

Methods

We investigated the p53 status in core exon‐4 to −9 (codon 33–331) by direct DNA sequencing in a series of 72 pancreatic cancers and analyzed the effects of p53 abnormalities on the patients' survival and the efficacy of adjuvant chemotherapy.

Results

p53 mutations were found in 62.5% (45/72) of cases, including 38 point mutations and 7 frameshift mutations. The subtypes of p53 mutations included 68.9% (31/45) transitions and 15.6% (7/45) transversions. 39.5% (15/38) of point mutations were CGT (Arg) to CAT (His) mutation at codon‐273 of exon‐8. 34.2% (13/38) of point mutations were CGG (Arg) to TGG (Trp) mutation at codon‐248 of exon‐7. Of seven frameshift mutations, four were seen at exon‐4, two at exon‐5, and one at exon‐6. Of overall cases, p53 abnormalities were not associated with a poorly differentiated grade and an advanced stage. The relationship of adjuvant chemotherapy to survival is approaching statistical significance. Univariate analysis showed that in the p53 mutation group, the patients who received adjuvant chemotherapy had a better survival ratio than that of patients who did not do. Multivariate analysis indicated that in the group with p53 mutations, the significant factors for survival were adjuvant chemotherapy, histologic grade, and clinical stage. However, in the group with a wild‐type p53 gene, only histologic grade was a significant factor. In addition, 34.7% (25/72) of the cases harbor p53 polymorphism mutation only at codon‐72 of exon‐4, which did not show any significant effect on the pathology, prognosis, and efficacy of adjuvant chemotherapy of the pancreatic cancers.

Conclusions

A p53 abnormality was not an independent factor for evaluating the prognosis of patients with pancreatic cancer, but was a beneficial indicator for selecting a reasonable strategy of adjuvant chemotherapy against pancreatic cancer. J. Surg. Oncol. 2003;82:111–120. © 2003 Wiley‐Liss, Inc.
Association between extent of axillary lymph node dissection and patient, tumor, surgeon, and hospital factors in patients with early breast cancer
Authors: Petrik David W. , McCready David R. , Sawka Carol A. , Goel Vivek
Published: January 2003

Background and Objectives

Axillary lymph node dissection (ALND) in patients with breast cancer is crucial for accurate staging, provides excellent regional tumor control, and is included in the standard of care for the surgical treatment of breast cancer. However, the extent of ALND varies, and the extent of dissection and the number of lymph nodes that comprise an optimal axillary dissection are under debate. Despite conflicting evidence, several studies have shown that improved survival is correlated with more lymph nodes removed in both node‐negative and node‐positive patients. The purpose of this study is to determine which patient, tumor, surgeon, and hospital characteristics are associated with the number of nodes excised in early breast cancer patients.

Methods

A random sample of 938 women with node‐negative breast cancer was drawn from the Ontario Cancer Registry and the data supplemented with chart reviews. The extent of axillary dissection was studied by examining the number of nodes examined in relation to the patient, tumor, surgeon, and hospital factors.

Results

The mean number of lymph nodes excised was 9.8 (SD = 4.8; range, 1–31), and 49% of patients had ≥10 nodes excised. Lower patient age was associated with the excision of more lymph nodes (≥10 nodes: 63% of patients <40 years vs. 38% of patients ≥80 years). Surgeon academic affiliation and surgery in a teaching hospital were highly correlated with each other and were significantly associated with the excision of ≥10 nodes. The number of nodes excised was not associated with any tumor factors, nor with the breast operation performed. These results were confirmed with multivariable models.

Conclusions

Even though the number of lymph nodes found in the pathologic specimen can be influenced by factors other than surgical technique (e.g., number of nodes present, specimen handling, and pathologic examination), this study shows significant variation of this variable and an association with several patient and surgeon/hospital factors. This variation and the association with survival warrant further study and effort at greater consistency. J. Surg. Oncol. 2003;82:84–90. © 2003 Wiley‐Liss, Inc.
Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients
Authors: Motomura Kazuyoshi , Komoike Yoshifumi , Hasegawa Yoshihisa , Kasugai Tsutomu , Inaji Hideo , Noguchi Shinzaburo , Koyama Hiroki
Published: January 2003

Background and Objectives

The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients.

Methods

Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc‐99m tin colloid, with a larger particle size (0.4–5 μm), rather than sulfur colloid and colloidal albumin.

Results

The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False‐negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%).

Conclusions

A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc‐99m tin colloid with a large particle size than by subdermal injection. J. Surg. Oncol. 2003;82:91–97. © 2003 Wiley‐Liss, Inc.
Significance of reduction surgery in multidisciplinary treatment of advanced hepatocellular carcinoma with multiple intrahepatic lesions
Authors: Wakabayashi Hisao , Ushiyama Takafumi , Ishimura Ken , Izuishi Kunihiko , Karasawa Yukihiko , Masaki Tsutomu , Watanabe Seishiro , Kuriyama Shigeki , Maeta Hajime
Published: January 2003

Background and Objectives

By comparing the survival rates of patients treated with or without surgery, the significance of, and the indication for, reduction surgery in the multidisciplinary treatment of patients with HCC with multiple intrahepatic lesions were examined.

Methods

In patients with HCC with multiple intrahepatic lesions, cumulative survival rates were determined and compared for 28 patients (group S) who underwent reductive hepatic resection and 43 (group N) who were treated nonsurgically by transcatheter arterial infusion chemotherapy (TAI), transcatheter arterial chemoembolization (TACE), or percutaneous transhepatic ethanol injection therapy. In group S, 20 patients had adjuvant therapy, consisting of ethanol injection therapy or microwave coagulonecrotic therapy for the remaining satellite lesions during hepatectomy, and all patients in this group underwent TAI or TACE postoperatively. The influence of surgery on patient survival was examined by multiple regression analysis using the Cox's hazard model; then, for each prognostic factor, survival rates were obtained and compared between the groups.

Results

In group S, the 1‐, 3‐, and 5‐year cumulative survival rates were 58.2%, 27.1%, and 21.7%, whereas the corresponding values in group N were 34.3%, 4.7%, and 4.7%, the difference being statistically significant (P = 0.0239). In group S, the 1‐, 3‐, and 5‐year cumulative survival rates for patients without intraoperative adjuvant therapy were 25%, 0%, and 0%, whereas those for patients with intraoperative adjuvant therapy were 72.7%, 41.3%, and 33.0% (P = 0.001). Multiple regression analysis showed that hepatic resection, the Child‐Pugh score, and the size of the main tumor affected survival independently. Univariate analysis of differences in the cumulative survival rates between the groups as a function of prognostic factor showed that group S had statistically significant better survival rates than group N in those subgroups of patients who were <60 years old, with HBV infection, with a Child‐Pugh score of 5 or 6, with a main tumor of <5‐cm diameter, with <5 tumors, or without portal thrombi.

Conclusions

When combined with intraoperative adjuvant therapy for remaining satellite tumors, reduction surgery provided survival benefit for patients with HCC with multiple intrahepatic lesions in those groups of patients selected by criteria determined in this study. J. Surg. Oncol. 2003;82:98–103. © 2003 Wiley‐Liss, Inc.
Prognostic use of growth characteristics of early gastric cancer and expression patterns of apoptotic, cell proliferation, and cell adhesion proteins
Authors: Pan Wensheng , Ishii Hideaki , Ebihara Yoshiro , Gobe Glenda
Published: January 2003

Background and Objectives

Selection of suitable treatment for early gastric cancers, such as endoscopic mucosal resection or the major surgical option of resection of the cancer together with a radical lymph node dissection, may be assisted by comparing the growth characteristics of the cancer with selected molecular characteristics. The results could be used to predict those cases that have a higher risk of developing secondary metastases.

Methods

A total of 1,196 Japanese patients with early gastric cancers (648 mucosal cancers and 548 submucosal) were included in the selection of two groups: a metastatic group made up 57 cancers with lymph node metastasis (9 mucosal, 48 submucosal), and a nonmetastatic group of 61 cases (6 mucosal, 55 submucosal) without lymph node metastasis. Growth characteristics of the cancers (superficially spreading, penetrating or invasive, lymph node metastasis) were compared with immunohistochemical expression of single‐stranded DNA (ssDNA) protein (apoptosis indicator), bcl‐2 and p53 (apoptosis‐associated), Ki‐67 (cell proliferation), and E‐cadherin (cell adhesion) proteins.

Results

The lesions in the nonmetastatic group had higher levels of apoptosis and lower expression of bcl‐2 than in the metastatic group, indicating an inhibitory role for apoptosis in malignant progression. Apoptosis was also higher in the superficial compared with the invasive lesions of both groups. The lesions in the metastatic group had higher p53 expression than that of the nonmetastatic group, whereas apoptosis in the metastatic group was lower than in the nonmetastatic group. An unproved explanation for this finding may be that, although increased, p53 was mutated and ineffective in promoting apoptotic control of metastatic progression. E‐cadherin was decreased in the invasive lesions of both groups, indicating a greater ability of these cells to lose adhesion, to invade the submucosa, and to metastasize. Cell proliferation was highest in the superficial lesions of both metastatic and nonmetastatic groups.

Conclusions

Early gastric cancers with low levels of apoptosis, increased bcl‐2, and high levels of p53 expression are more likely to invade and metastasize. J. Surg. Oncol. 2003;82:104–110. © 2003 Wiley‐Liss, Inc.
Reduction in lateral thermal damage using heat‐conducting templates: A comparison of continuous wave and pulsed CO2 lasers
Authors: Spector Nicole , Spector Jared , Ellis Darrel L. , Reinisch Lou
Published: January 2003

Background and Objectives

The advantages of the continuous wave (c.w.) CO2 laser are offset by the delay in laser wound healing secondary to thermal damage. We have developed novel heat‐conducting templates to reduce laser thermal damage. Because shortened pulse durations also decrease thermal damage, we tested the effectiveness of heat‐conducting templates with a c.w. CO2 clinical laser and a short‐pulsed CO2 laser to determine the best method and mechanism to minimize thermal damage.

Study Design/Materials and Methods

Comparison of 0.2‐second shuttered c.w. and 5‐microsecond pulsed CO2 lasers were made by doing incisions on 150 tissue samples from reduction mammoplasties and abdominoplasties. Copper, aluminum, glass, and Plexiglass heat‐conducting templates were tested against no template (air) with both lasers. Histological samples were evaluated using computerized morphometrics analysis.

Results

Statistically significant reductions in lateral thermal damage were seen with the copper (50%) and aluminum (39%) templates used with the c.w. CO2 laser. Only the copper template (39%) significantly reduced thermal damage when used with the pulsed CO2 laser. Less thermal damage was seen using the pulsed CO2 laser compared to the c.w. CO2 laser with each template.

Conclusions

Heat‐conducting templates significantly reduced the amount of lateral thermal damage when used with the c.w. CO2 laser (copper and aluminum) and short‐pulsed CO2 laser (copper). The c.w. CO2 laser with the copper template compared favorably to the short‐pulsed CO2 laser without a template. Therefore, both heat conductive templates and short‐pulse structure provide successful methods for reducing lateral thermal damage, and a combination of the two appears to provide optimal results. Lasers Surg. Med. 32:94–100, 2003. Published 2003 Wiley‐Liss, Inc.
Role of skin cooling in improving patient tolerability of Q‐switched Alexandrite (QS Alex) laser in nevus of Ota treatment
Authors: Chan Henry H.L. , Lam Lai‐kun , Wong David S.Y. , Wei W.I.
Published: January 2003

Background

The development of a high‐energy laser device with very short pulse duration has revolutionized the treatment of nevus of Ota. Nevertheless, patients still suffer from complications that range from the pain and swelling that occur immediately after laser surgery to post‐operative pigmentary changes and scarring. However, the simultaneous use of skin surface cooling and laser surgery may limit the damage of non‐target tissue.

Objectives

To assess whether epidermal cooling reduces the pain and swelling that commonly occur after laser treatment for nevus of Ota.

Study Design/Patients and Methods

Thirty‐seven patients with nevus of Ota were recruited from a dermatology outpatient clinic. Before treatment, the research nurse used an ink pen to divide the lesions into two halves. Half of each lesion was treated with a Q‐switched Alex laser system that had a cool sapphire plate in contact as a mean of skin cooling. The other half was treated with the same laser, but with the cooling device switched off. Immediately after treatment, and again 1 week later, the patients answered a questionnaire, which assessed the symptoms that are associated with laser surgery. Dose assessment was performed in each half of the nevus to obtain the optimal fluence that could be used for the treatment of nevus of Ota before the entire half was treated.

Results

There was no difference in terms of the optimal fluence that was used, but in terms of immediate pain the patients associated the side that was treated with the cooling plate with a significantly lesser degree of pain than the non‐cooled side (P = 0.001). Eighty two percent of the patients preferred the cooled side to the non‐cooled side.

Conclusions

Pre‐ and post‐operative skin cooling is effective in improving the tolerability of nevus of Ota patients to Q‐switched laser treatment. However, the use of cooling during laser treatment of nevus of Ota did not allow the use of higher fluence. Lasers Surg. Med. 32:148–151, 2003. © 2003 Wiley‐Liss, Inc.
Novel model for evaluation of epidermal preservation and dermal collagen remodeling following photorejuvenation of human skin
Authors: Kao Bunsho , Kelly Kristen M. , Majaron Boris , Nelson J. Stuart
Published: January 2003

Background and Objectives

In order to optimize photorejuvenation of human skin, a method must be developed to reliably compare the potential for epidermal preservation and dermal fibroblast stimulation of different laser devices and irradiation parameters. We describe a novel human skin tissue culture model developed for this purpose.

Materials and Methods

An artificial skin model, consisting of human keratinocytes in the epidermis and human fibroblasts and rat‐tail collagen in the dermis, was cultured using the floating collagen gel (RAFT) method. Repetitive low‐fluence Er:YAG laser irradiation was applied to test the applicability of our RAFT model for characterization of epidermal preservation and dermal fibroblast stimulation post‐laser treatment.

Results

Histopathologic evaluation revealed a thin layer of epidermal keratinocyte preservation immediately after low fluence sub‐ablative Er:YAG laser irradiation. One‐week post‐laser irradiation, the average increase in number of dermal fibroblasts as compared to control was statistically significant (P < 0.01).

Conclusions

The RAFT model can be used to assess the potential for epidermal preservation and dermal fibroblast stimulation of different photorejuvenation devices and irradiation parameters and offers several advantages over traditional animal and human skin models. Lasers Surg. Med. 32:115–119, 2003. © 2003 Wiley‐Liss, Inc.
In vitro study examining the effect of sub‐lethal QS 755 nm lasers on the expression of p16INK4a on melanoma cell lines
Authors: Chan Henry H.L. , Xiang Leihong , Leung Joseph C.K. , Tsang Kenneth W.T. , Lai Kar‐neng
Published: January 2003

Background and Objectives

Q‐switched lasers had been used in the treatment of lentigo maligna but their role remains controversial. While previous studies have addressed the change in adhesion molecule expression after sub‐lethal laser damage, no study has addressed the impact of sub‐lethal laser damage at a molecular level. The p16 gene has been proposed as the candidate gene for melanoma. Our objective is to examine the effect of sub‐lethal laser damage on p16 expression in melanoma cell lines.

Study Design/Materials and Methods

Three human melanoma cell lines—HTB 66, Sk‐mel‐24 (HTB 71), and G361—were irradiated by a Q‐switched 755 nm Alexandrite laser at fluencies that ranged from 0.85 to 2.0 J/cm2. HTB 66 was the only cell line with significant expression of p16INK4a while the other two cells lines were p16INK4a negative and served as negative control. Protein and mRNA expression for p16 were assessed by flow cytometry and RT‐PCR, respectively.

Results

The level of p16INK4a protein in cell line HTB 66 increased significantly after laser irradiation as compared with non‐irradiated cells. The level of p16INK4a protein did not change in p16INK4a‐negative cell lines (Sk‐mel‐24 and G361). However, there was only a slight increase in the percentage of G0/G1 phase cells.

Conclusions

Sub‐lethal laser damage could increase DNA damage leading to an increase in p16 expression, and such effect would be particularly undesirable for patients with p16 mutation. Further studies are warranted to examine the role of sub‐lethal laser damage in inducing p16 mutation. Lasers Surg. Med. 32:88–93, 2003. © 2003 Wiley‐Liss, Inc.
Cooling efficiency of cryogen spray during laser therapy of skin
Authors: Svaasand L.O. , Randeberg L.L. , Aguilar G. , Majaron B. , Kimel S. , Lavernia E.J. , Nelson J.S.
Published: January 2003

Background and Objectives

Cryogen spray cooling (CSC) is used extensively for epidermal protection during laser‐induced photothermolysis of port wine stains and other vascular skin lesions. The efficacy of CSC depends critically on the heat transfer coefficient (H) at the skin surface for which, however, no reliable values exist. Reported values for H, based on tissue phantoms, vary from 1,600 to 60,000 W/m2 K.

Study Design/Materials and Methods

A simple experimental model was designed and constructed, consisting of a pure silver‐measuring disk (diameter 10 mm, thickness ∼1 mm), embedded in a thermal insulator. The disk was covered with a 10 μm thick stratum corneum layer, detached from in vivo human skin. The heat transfer coefficient of the stratum corneum/cryogen interface was measured during CSC with short spurts of atomized tetrafluoroethane.

Results

H was found to be dependent on the specific design of the cryogen valve and nozzle. With nozzles used in typical clinical settings, H was 11,500 W/m2 K, when averaged over a 100 ms spurt, and 8,000 W/m2 K when averaged over a 200 ms spurt.

Conclusions

The presented model enables accurate prediction of H and thus improve control over temperature depth profile and cooling efficiency during laser therapy. Thereby, it may contribute to improvement of therapeutic outcome. Lasers Surg. Med. 32:137–142, 2003. © 2003 Wiley‐Liss, Inc.
Update on non‐ablative light therapy for rejuvenation: A review
Authors: Sadick Neil S.
Published: January 2003

Background and Objectives

Non‐ablative technologies are playing an increasing role in the management of photoaging. Newer radiofrequency technologies have added to this therapeutic armamentarium. Shorter wavelength technologies are more effective in targeting pilosebaceous vascular and pigmentary alterations while longer wavelength technologies are most effective in wrinkle reduction mediated through dermal remodeling. An overiew of the various technologies available to the practicing laser surgeon are outlined in the present review. Lasers Surg. Med. 32:120–128, 2003. © 2003 Wiley‐Liss, Inc.
Electrosurgical resurfacing: A clinical, histologic, and electron microscopic evaluation
Authors: Sarradet M. Dale , Hussain Mussarrat , Goldberg David J.
Published: January 2003

Background

Radiofrequency resurfacing is a new technology for ablative facial resurfacing.

Objectives

To evaluate the efficacy of radiofrequency resurfacing in reduction of perioral and periorbital rhytides, and to assess it's effects on collagen remodeling by electron microscopic evaluation.

Results

Fourteen of the fifteen subjects (93%) were 100% re‐epithelialized by day 7. All 15 patients (100%) had resolution of post‐treatment erythema by 3 months. Clinical investigator assessment evaluation revealed mild to moderate improvement in 100% of patients. Histologic changes were consistent with new upper papillary dermal collagen formation. Post‐treatment ultrastuctural changes showed either new Type III or mature Type I collagen formation.

Conclusions

Radiofrequency resurfacing is an effective ablative resurfacing method for mild to moderate improvement of Fitzpatrick Type I–III rhytides. It is a low risk procedure with potentially shorter periods of post‐operative re‐epithelialization and erythema as compared to standard ablative laser procedures. Lasers Surg. Med. 32:111–114, 2003. © 2003 Wiley‐Liss, Inc.
Dynamic behavior of cryogen spray cooling: Effects of spurt duration and spray distance
Authors: Aguilar Guillermo , Wang Guo‐Xiang , Nelson J. Stuart
Published: January 2003

Background and Objectives

Cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatologic surgery. Since optimization of CSC permits the safe use of higher light doses, which improves therapeutic outcome in many patients with superficial skin lesions, studies have focused on understanding spray–surface interactions and cooling dynamics. The objective of this study is to measure accurately temperature variations at the sprayed surface and the effects of spurt duration (Δt) and nozzle‐to‐sprayed surface distance (L) on cooling dynamics during CSC.

Study Design/Materials and Methods

A fast‐response temperature measurement sensor is built using thin (20 μm) aluminum foil placed on top of a poly methyl‐methacrylate resin (Plexiglass®) with a 50 μm bead diameter thermocouple positioned in between. Liquid film residence time (tr) and minimum surface temperature (Tmin) are systematically measured as a function of Δt and L.

Results

Two distinct spray–surface interaction mechanisms are recognized. The transition between them occurs at a critical length Lc≈25–30 mm. Noticeable characteristics include: (1) for spurts at L < Lc, shorter tr, and lower Tmin are reached as compared to L > Lc, Tmin is dependent on Δt and L, while tr is a function of Δt only; (2) for spurts at L > Lc, Tmin still depends on L but not on Δt, while tr becomes a function of both Δt and L. Finally, for all Δt, tr reaches a maximum at L = 40 mm.

Conclusions

Based on our results, a good choice to achieve low Tmin and tr for the treatment of superficial skin lesions may be met by using Δt of ≈30–50 milliseconds and the shortest spray distance that is tolerable by the patient. Spurt durations (Δt) of more than 30–50 milliseconds at spray distances (L) greater than Lc lead to higher Tmin and longer tr. These parameters may be appropriate for laser therapy of deeper targets. Lasers Surg. Med. 32:152–159, 2003. © 2003 Wiley‐Liss, Inc.
Using a “non uniform pulse sequence” can improve selective coagulation with a Nd:YAG laser (1.06 μm) thanks to Met‐hemoglobin absorption: A clinical study on blue leg veins
Authors: Mordon Serge , Brisot Dominique , Fournier Nathalie
Published: January 2003

Background and Objectives

Evaluation of the efficacy, on 1–2 mm blue leg telangiectasia, of a 1,064 nm Nd:YAG laser emitting in a non uniform pulse sequence calculated to consider Met‐Hb formation during laser irradiation of a blood vessel.

Materials and Methods

A 1,064 nm Nd:YAG laser (Quantel Medical, Athos, France) was used in a non uniform pulse sequence mode, fluences: 300–360 J/cm2 spot: 2 mm, + 5°C contact cooling. The clinical evaluation was performed on 11 female patients, average age: 43 (25–57) years, phototype I–VI. All subjects were previously examined with Doppler ultrasound. A treatment site (6 × 4 cm) was selected on each patient. The topography of the vessels network was reported on a tracing plastic frame before each session and 6 weeks after the last one. These frames were digitized and the number of vessels was determined using the Digitized Tracing Frames Technique. Side effects were noted before and after every treatment, and 6 weeks after the last one. This study lasted for 10 months.

Results and Discussions

Patients tolerated the procedure without anesthesia. Moderate pain, transient erythema and edema, one hyperpigmentation and one matting were noted. There was no hypopigmentation. 55% (P < 0.002) vessels clearance after one session, 86% after two sessions (P < 0.001), and 98% (P < 0.001) after three sessions were obtained. On two patients, the treatment was completed after two sessions with a full clearance. Data reported in this study were obtained thanks to a computerized calculation of vessels clearance. They are similar or superior to those reported in the literature about 1,064 nm Nd:YAG lasers and leg telangiectasia.

Conclusions

Since, it was developed to consider the modification of blood absorption and the methemoglobin formation which leads to an increase of the 1.06 μm wavelength absorption, the non uniform pulse mode emphasizes the efficacy of this 1,064 nm Nd:YAG laser concerning the treatment of blue leg veins telangiectasia between 1 and 2 mm. This mode gives the possibility to deliver high energy while preserving the surrounding tissue and leads to a rapid vessel clearance with reduced pain and few side effects when compared to previously published clinical studies using a 1.06 μm laser. Lasers Surg. Med. 32:160–170, 2003. © 2003 Wiley‐Liss, Inc.
Topical rose Bengal: Pre‐clinical evaluation of pharmacokinetics and safety
Authors: Wachter Eric , Dees Craig , Harkins Jay , Scott Timothy , Petersen Mark , Rush Rusty E. , Cada Amy
Published: January 2003

Background and Objectives

Rose bengal (RB) is a potent photosensitizer that has largely been overlooked as a potential photodynamic therapy (PDT) agent. In this study, the feasibility of topical delivery of RB to the epidermis has been evaluated.

Study Design/Materials and Methods

Topical formulations of RB were assessed on murine and rabbit skin for pharmacokinetic properties, cutaneous toxicity, and photosensitization.

Results

Hydrophilic formulations (≤1% RB) exhibited rapid, selective, uniform delivery to the epidermis, with no significant acute cutaneous toxicity in normal skin. Illumination (532 nm) elicited no acute phototoxicity for light intensities ≤100 mW/cm2 at a light dose of 100 J/cm2; use of higher intensities resulted in superficial thermal damage. Repeat treatment of rabbit skin (weekly for four weeks) elicited minor phototoxicity only at the highest concentration (1% RB).

Conclusions

These results indicate that RB is safe for PDT treatment of skin disorders, exhibiting negligible effects in normal skin. Lasers Surg. Med. 32:101–110, 2003. © 2003 Wiley‐Liss, Inc.