bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiroptical properties of binuclear rhodium complexes of lanostane alcohols
Authors: Frelek Jadwiga , Jagodziński Jacek , Meyer‐Figge Heike , Sheldrick William S. , Wieteska Edyta , Szczepek Wojciech J.
Published: August 2002

The circular dichroism (CD) of the in situ‐formed Rh2(OCOCF3)4 complexes of sterically hindered, secondary lanostane alcohols was investigated. The main object of the present studies are derivatives of 3β‐, 7α‐, 7β‐, and 11β‐hydroxylanostanes with or without an additional functional group, e.g., double bond, oxo‐, hydroxy‐, or acetoxy groups. Up to five Cotton effects (CEs) can be found in the CD spectra of Rh‐complexes of these alcohols in the spectral range between 650–300 nm. Correlation of the CEs signs with the absolute stereochemistry at the carbon atom bearing the hydroxy group was investigated. The Rh‐complex with the 3β‐acetoxylanostan‐11β‐ol ligand was isolated in the crystalline form. Its polymeric structure, determined by the X‐ray method, shows the di‐Rh‐units linked by the axially ligating oxygen atoms of the hydroxy and acetoxy groups. In the latter case, the coordination takes place through the carbonyl oxygen. Chirality 13:313–321, 2001. © 2001 Wiley‐Liss, Inc.
Chirality recognition in solvent‐free solid‐state crystallization: Chiral adduct formation by bis‐β‐naphthol derivatives and benzoquinone crystals
Authors: Kuroda Reiko , Imai Yoshitane , Sato Tomohiro
Published: August 2002

New adduct crystals were obtained by simply mixing/grinding component crystals of bis‐β‐naphthol (BN) derivatives with benzoquinone (BQ) under solvent‐free conditions. Chiral recognition was found to operate during this process and either a racemic or a chiral crystal of a BN derivative produced an adduct crystal with BQ by solid‐state crystallization. The chirality preference changed subtly according to the molecular structure of the BN derivative. Even in circumstances in which no adduct was formed, addition of a third component, such as crystals of naphthalene, to the grinding mixture yielded an adduct crystal. Remarkably, these adduct crystals were found to decompose spontaneously with time and revert to the starting crystal of the BN derivative by losing BQ molecules from the crystal lattice. Local melting of crystals by the grinding pressure was found unlikely to be the mechanism of adduct formation. Overall, these results demonstrate that molecules in the solid state could change their relative location and hydrogen bonding partners, thereby exerting chiral discrimination. Chirality 13:588–594, 2001. © 2001 Wiley‐Liss, Inc.
Micropatterning tractional forces in living cells
Authors: Wang Ning , Ostuni Emanuele , Whitesides George M. , Ingber Donald E.
Published: August 2002

Here we describe a method for quantifying traction in cells that are physically constrained within micron‐sized adhesive islands of defined shape and size on the surface of flexible polyacrylamide gels that contain fluorescent microbeads (0.2‐μm diameter). Smooth muscle cells were plated onto square (50 × 50 μm) or circular (25‐ or 50‐μm diameter) adhesive islands that were created on the surface of the gels by applying a collagen coating through microengineered holes in an elastomeric membrane that was later removed. Adherent cells spread to take on the size and shape of the islands and cell tractions were quantitated by mapping displacement fields of the fluorescent microbeads within the gel. Cells on round islands did not exhibit any preferential direction of force application, but they exerted their strongest traction at sites where they formed protrusions. When cells were confined to squares, traction was highest in the corners both in the absence and presence of the contractile agonist, histamine, and cell protrusions were also observed in these regions. Quantitation of the mean traction exerted by cells cultured on the different islands revealed that cell tension increased as cell spreading was promoted. These results provide a mechanical basis for past studies that demonstrated a similar correlation between spreading and growth within various anchorage‐dependent cells. This new approach for analyzing the spatial distribution of mechanical forces beneath individual cells that are experimentally constrained to defined sizes and shapes may provide additional insight into the biophysical basis of cell regulation. Cell Motil. Cytoskeleton 52:97–106, 2002. © 2002 Wiley‐Liss, Inc.
Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis
Authors: Rossi Carlo R. , Foletto Mirto , Mocellin Simone , Pilati Pierluigi , De Simone Michele , Deraco Marcello , Cavaliere Francesco , Palatini Pietro , Guasti Fabiola , Scalerta Romano , Lise Mario
Published: August 2002

BACKGROUND

Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and cisplatin in patients with peritoneal carcinomatosis or sarcomatosis.

PATIENTS AND METHODS

Thirty‐one patients with peritoneal carcinomatosis or sarcomatosis (PCS) were enrolled for the study. After completion of CS, HIIC was administered with drug doses that were increased for each consecutive cohort following a three‐patient cohort scheme. Thereafter, the accrual was stopped when Grade 4 locoregional or systemic toxicity was observed. The maximum tolerated dose (MTD) was considered the dose in the previous triplet. Drug pharmacokinetics and procedure costs also were analyzed.

RESULTS

After CS, residual tumors were not present or measured less than or equal to 3 mm (in dimension) in all cases. Maximum tolerated dose was 15.25 and 43.00 mg L−1 for doxorubicin and cisplatin, respectively. The perfusate/plasma area under the curve ratios were favorable for both drugs, at 162 ± 113 and 20.6 ± 6.0, respectively, for doxorubicin and cisplatin. Doxorubicin levels in the peritoneum were higher than in tumor or normal tissue samples. There were no postoperative deaths. Surgery‐related complications were observed in 25% of cases. Findings at cost analysis showed that the length of stay in the operation room and intensive care unit were the major cost drivers.

CONCLUSIONS

Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging, a Phase II study is now advisable to verify the activity of this promising treatment. Cancer 2002;94:492–9. © 2002 American Cancer Society.
Selective upregulation of vascular endothelial growth factor receptors neuropilin‐1 and ‐2 in human neuroblastoma
Authors: Fakhari Mitra , Pullirsch Dieter , Abraham Dietmar , Paya Kurosh , Hofbauer Reinhold , Holzfeind Paul , Hofmann Michael , Aharinejad Seyedhossein
Published: August 2002

BACKGROUND

Recent studies show that vascular endothelial growth factor (VEGF) and its receptors Flt‐1 and KDR, and a series of other angiogenic molecules, are upregulated in advanced but not low stage human neuroblastoma. Neuropilin‐1 and 2 (NRP) are novel specific receptors of VEGF165, whose role is unknown in human neuroblastoma.

METHODS

Tissue biopsies of 37 children with Stage I‐IV neuroblastoma were obtained, as well as biopsies of 7 normal adrenals as controls. The mRNA expression of VEGF165 and its receptors Flt‐1, KDR, NRP1, and NRP2 was evaluated by real‐time reverse transcripton polymerase chain reaction. NRP protein expression was detected by immunocytochemistry and Western blotting.

RESULTS

VEGF165 mRNA was upregulated in Stage III and IV and Flt‐1 and KDR gene expression was increased in Stage III, while NRP1 and 2 mRNA and protein levels were higher in Stages I‐IV vs. controls (P < 0.05). NRP was expressed in vascular endothelial but not tumor cells.

CONCLUSIONS

These results show for the first time that human neuroblastoma expresses NRP, and that NRP co‐regulates VEGF angiogenic effect in human neuroblastoma. NRP might be a sensitive angiogenic measure of VEGF systems in neuroblastoma, particularly in its early stages. Cancer 2002;94:258–63. © 2002 American Cancer Society.
Prostate specific antigen complexed to α‐1‐antichymotrypsin in patients with intermediate prostate specific antigen levels
Authors: Saika Takashi , Tsushima Tomoyasu , Nasu Yasutomo , Kusaka Nobuyuki , Miyaji Yoshiyuki , Takamoto Hitoshi , Takeda Katsuji , Uno Satoru , Kumon Hiromi ,   for the Okayama Urological Cancer Collaborating Group
Published: August 2002

BACKGROUND

The authors attempted to evaluate prospectively the usefulness of serum prostate specific antigen (PSA) complexed to α‐1‐antichymotrypsin (PSA‐ACT) in the early detection of prostate carcinoma and its ability to discriminate between prostate carcinoma and benign prostatic hyperplasia (BPH), especially among patients with intermediate PSA levels.

METHODS

Between December 1999 and August 2000, systematic sextant biopsies were performed on 281 prospective patients with prostate carcinoma who had serum PSA levels between 4.1 ng/mL and 20.0 ng/mL. The serum samples were assayed by using kits that were designed specifically for measuring serum PSA, PSA‐ACT, and free PSA levels. The clinical values of PSA, PSA‐ACT, the free PSA to total PSA ratio (F/T ratio), the free PSA to PSA‐ACT ratio, PSA density (PSAD), and PSA‐ACT density (ACTD) were compared by using receiver operating characteristic (ROC) curve analysis.

RESULTS

Biopsy yielded no evidence of malignancy in 198 patients, and prostate carcinoma was confirmed in 83 patients. ROC analysis demonstrated that the area under the curve (AUC) for PSA‐ACT was greater than that for total PSA and was equivalent to that for the F/T ratio in both groups of patients (PSA ranges of 4.1–20.0 ng/mL and 4.1–10.0 ng/mL, respectively). The AUC for the ACTD was greater than the AUC for the PSAD and had the highest value of all parameters.

CONCLUSIONS

The measurement of PSA‐ACT represents an alternative to the use of total and free PSA. The ACTD value is the most useful for discriminating between BPH and prostate carcinoma. Cancer 2002;94:1685–91. © 2002 American Cancer Society.

DOI 10.1002/cncr.10377
Downregulation of Hus1 by antisense oligonucleotides enhances the sensitivity of human lung carcinoma cells to cisplatin
Authors: Kinzel Bernd , Hall Jonathan , Natt Francois , Weiler Jan , Cohen Dalia
Published: August 2002

BACKGROUND

In Schizosaccharomyces pombe, Hus1 is a component of the radiation sensitive (Rad) machinery that has been identified as playing a role in DNA repair and cell cycle G2/M checkpoint control pathways. Hus1 has been shown to exist in a discrete complex with at least two Rad family members, Rad1 and Rad9. Furthermore, Hus1 is essential for checkpoint activation, since Hus1 mutants fail to arrest the cell cycle in response to DNA damage or unreplicated DNA. To establish the role and relevance of human Hus1 in cell cycle regulation, the authors applied antisense technology to selectively downregulate the expression of Hus1 mRNA.

METHODS

Transfection of 2′‐O‐methoxyethyl‐modified Hus1 antisense oligoribonucleotides into human H1299 nonsmall lung carcinoma cells was performed using Lipofectin as the carrier. The authors prepared RNA from transfected cells, and levels of Hus1 expression were analyzed by real time polymerase chain reaction. The growth and viability of cells treated with Hus1 antisense oligonucleotides in the presence or absence of cisplatin were analyzed and compared to controls.

RESULTS

Transfection of selected Hus1 antisense oligonucleotides into p53 deficient H1299 cells resulted in significant downregulation of Hus1 mRNA, up to 80%; RNA analyses reveal a maximal Hus1 antisense activity at a concentration of 200 nM with an IC50 determined to be 90 nM. The design and transfection of oligonucleotides containing three mismatches to their corresponding antisense counterparts had no or only minor effects on Hus1 mRNA levels, showing the specificity of Hus1 mRNA downregulation. The cisplatin IC50 in untransfected H1299 cells was found to be 20 μM and could be reduced significantly to only 7 μM after transfection of a Hus1 antisense oligonucleotide.

CONCLUSIONS

Experiments addressing the proliferation and viability of transfected H1299 cells suggest that downregulation of Hus1 by specific antisense oligonucleotides sensitizes human cells to treatment with the DNA damaging agent cisplatin. Cancer 2002;94:1808–14. © 2002 American Cancer Society.

DOI 10.1002/cncr.10383
A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma
Authors: Chan Annie O. , Yuen Man‐Fung , Hui Chee‐Kin , Tso Wai‐Kuen , Lai Ching‐Lung
Published: August 2002

BACKGROUND

Hepatocellular carcinoma (HCC) is a common cause of cancer death throughout the world. The majority of patients are not suitable for curative resection either because of the advanced stage of the disease at the time of presentation or because of underlying cirrhosis. Transcatheter intraarterial lipiodol chemoembolization (TACE) has been reported to be one of the most effective palliative measures for HCC. However, its severe side effects continue to make its use controversial.

METHODS

In the current study, the authors prospectively evaluated 197 sessions of TACE performed in 59 patients with HCC.

RESULTS

Acute hepatic decompensation occurred in 20% of the 197 sessions with 3% of cases being irreversible. Significant elevation of bilirubin was associated with the dosage of cisplatin used (P = 0.0001), basal bilirubin level (P = 0.0001), basal prothrombin time (P =0.004), basal aspartate aminotransferase (AST) level (P = 0.013), and stage of cirrhosis (P < 0.0001). Patients with irreversible hepatic decompensation were more likely to have higher pre‐TACE bilirubin levels (P = 0.009), more prolonged prothrombin time (P = 0.015), received a higher dose of cisplatin (P = 0.033), and more advanced cirrhosis (P < 0.0001). The majority of the other side effects were self‐limiting with the exception of one patient who died of liver and splenic abscesses. Approximately 36% of the patients achieved a tumor response, 39% achieved stable disease, and 29% developed progressive disease.

CONCLUSIONS

The results of the current study identified factors that appeared to predispose patients to irreversible hepatic decompensation after TACE. Despite the high percentage of patients who developed hepatic decompensation after TACE, irreversible damage occurred in only a minority. Cancer 2002;94:1747–52. © 2002 American Cancer Society.

DOI 10.1002/cncr.10407
Incidence of the superficial fascia and its relevance in skin‐sparing mastectomy
Authors: Beer Gertrude M. , Varga Zsuzsanna , Budi Srecko , Seifert Burkhardt , Meyer Viktor E.
Published: August 2002

BACKGROUND

With the move away from classical radical mastectomy to ever more skin‐sparing procedures, there has been an ongoing discussion about how much skin and subcutaneous tissue should be resected to perform an adequate mastectomy while leaving viable skin flaps. One of the common recommendations is to dissect just superficial to the superficial layer (SL) of the superficial fascia of the breast. This, in turn, has revived the old, unsolved controversy about the existence or absence of the SL, a fascia that reportedly encloses the mammary gland ventrally. In skin‐sparing mastectomies (SSM), which combine tumor resection with immediate breast reconstruction, the ideal would be to create skin flaps that are thin enough to remove all breast tissue but at the same time are thick enough to preserve flap circulation. The feasibility of meeting these two goals simultaneously and the possible role and relevance of the SL as a guide to dissection in SSM was examined in this study.

METHODS

Sixty‐two breast resection specimens from 31 women who underwent breast reduction were examined histologically to determine whether the SL was present, whether breast tissue could be detected within or beyond this SL, the measured distance between the caudal border of the dermis and the SL or the breast tissue, and whether the thickness of the subcutaneous fat layer was correlated with the patients' physical data, such as body weight or body mass index (BMI).

RESULTS

The SL was absent in 44% of resection specimens. When the SL was present, 42% of specimens contained several islands of breast tissue within the SL. No breast tissue was found beyond the SL. The minimal distance between the SL and the dermis varied from 0.2 mm to 4.0 mm; the minimal distance between the breast tissue and the dermis was 0.4 mm. In 50% of specimens, the minimal distance between the dermis and the SL or breast tissue was < 1.1 mm. A distance of ≥ 5 mm was encountered in only 17% of specimens, and a distance of ≥ 10 mm was encountered in only 5% of specimens. No significant correlation between the right and left breast was found with any of the parameters examined. A weak negative correlation was seen between the BMI and the mean thickness of the subcutaneous fat (P = 0.049; correlation coefficient [r] = −0.39; Spearman rank correlation).

CONCLUSIONS

Histologic evaluation revealed that the SL is not present in all breasts and, thus, cannot serve as a reliable plane of dissection. Furthermore, if the SL is present microscopically, then it often is too thin and delicate to be detectable macroscopically. Finally, even if the SL is present and visible macroscopically, the distance to the overlying skin is so small in the majority of patients that a dissection superficial to the SL would not leave viable skin flaps in skin‐sparing mastectomies. Cancer 2002;94:1619–25. © 2002 American Cancer Society.

DOI 10.1002/cncr.10429
Adenoid cystic carcinoma of the breast
Authors: Arpino Grazia , Clark Gary M. , Mohsin Syed , Bardou Valerie J. , Elledge Richard M.
Published: August 2002

BACKGROUND

The objective of this study was to comprehensively characterize the clinical and biologic features of adenoid cystic carcinoma (ACC) and to assess the implications for management in a large cohort of patients.

METHODS

From a database of 50,000 patients, 28 were identified with ACC for which clinical follow‐up and biologic information was available. The biologic features examined included estrogen receptor and progesterone receptor status, DNA ploidy, and S‐phase fraction. Median follow‐up was 83 months with a range of 29 to 144 months. Overall survival and disease free survival curves were drawn using Kaplan and Meier estimates and were compared by the log‐rank test.

RESULTS

All but one patient were postmenopausal with a median age at diagnosis of 66 years (range, 40–96 years). One patient had macroscopic metastatic disease at diagnosis. Median tumor size was 1.9 cm (range, 0.5–7.0 cm). Axillary lymph node dissection was performed in 23 patients. Only 1 patient (4%) had histologic positive lymph nodes (2 of 10), and no recurrence was detected for this patient. Forty‐six percent were ER positive (median, 16 fmol/mg protein; range, 5–1017 fmol/mg), and 35% were PgR positive (median, 61 fmol/mg protein; range, 6–854 fmol/mg). S‐phase fraction and DNA ploidy were assessable in 24 cases. Ninety percent of tumors had low S‐phase (median, 3.3%; range, 0.1–34.2%), and 92% were diploid. Simple or modified radical mastectomy was performed in 22 patients, and 6 patients were treated by lumpectomy. Five of these six patients also received radiation therapy after lumpectomy. Despite the different surgical approaches, there were no local recurrences. The 5‐year disease free survival rate was 100%, and the 5‐year overall survival rate was 85% (95% confidence interval, 71.7–98.6%).

CONCLUSIONS

Adenoid cystic carcinomas of the breast have very favorable biologic characteristics and, consistent with this, an excellent prognosis. Good local control can be achieved by lumpectomy with radiation or by simple mastectomy. Axillary lymph node dissection is not helpful in clinical management. Cancer 2002;94:2119–27. © 2002 American Cancer Society.

DOI 10.1002/cncr.10455
Low natural killer activity and central nervous system disease as a high‐risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis
Authors: Imashuku Shinsaku , Hyakuna Nobuyuki , Funabiki Tetsunori , Ikuta Koichiro , Sako Masahiro , Iwai Asayuki , Fukushima Takashi , Kataoka Satoshi , Yabe Miharu , Muramatsu Kazuhiro , Kohdera Urara , Nakadate Hisaya , Kitazawa Katsuhiko , Toyoda Yasunori , Ishii Eiichi
Published: August 2002

BACKGROUND

Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL.

METHODS

The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2).

RESULTS

In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5–9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT.

CONCLUSIONS

Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure. Cancer 2002;94:3023–31. © 2002 American Cancer Society.

DOI 10.1002/cncr.10515
Patient and provider characteristics that affect the use of axillary dissection in older women with Stage I–II breast carcinoma
Authors: Edge Stephen B. , Gold Karen , Berg Christine D. , Meropol Neal J. , Tsangaris Theodore N. , Gray Luther , Petersen Bert M. , Hwang Yi‐ting , Mandelblatt Jeanne S. ,   Outcomes and Preferences for Treatment in Older Women Nationwide Study Research Team
Published: August 2002

BACKGROUND

Axillary dissection for the evaluation and treatment of patients with breast carcinoma often is not performed in older women. The objective of this study was to examine patient, clinical, and surgeon characteristics associated with the use of axillary dissection after breast‐conserving surgery (BCS).

METHODS

A cohort of 464 women age ≥ 67 years who were newly diagnosed with Stage I–II breast carcinoma and who underwent BCS were surveyed along with their 158 surgeons, and their medical records were reviewed. Patient, tumor, and provider characteristics were examined for association with the omission of axillary dissection.

RESULTS

The majority of women (63.4%) underwent axillary lymph node dissection after BCS. Increasing age was associated strongly with decreasing odds of undergoing axillary lymph node dissection, even after considering patient health and preferences, clinical factors, and provider factors (odds ratio [OR], 0.11; 95% confidence interval [95%CI], 0.05–0.27). Independent of age and other factors, women in the lowest quartile of physical functioning were 37% less likely to undergo axillary lymph node dissection compared with women in the highest quartile (OR, 0.63; 95%CI, 0.62–0.64). Patients who were cared for by surgeons with subspecialty training in oncology were 60% less likely to undergo axillary lymph node dissection compared with patients who were cared for by other surgeons, even after considering other factors (OR, 0.41; 95%CI, 0.25–0.68).

CONCLUSIONS

The results of this study demonstrated a correlation between lower use of axillary dissection and advancing age, lower functional status, and greater surgeon training. These findings suggest that simple, age‐based considerations are important but are not the sole determinants of variations in treatment. Cancer 2002;94:2534–41. © 2002 American Cancer Society.

DOI 10.1002/cncr.10540
Predictors for pneumonitis during locoregional radiotherapy in high‐risk patients with breast carcinoma treated with high‐dose chemotherapy and stem‐cell rescue
Authors: Lind Pehr A. , Marks Lawrence B. , Jamieson Timothy A. , Carter Dennis L. , Vredenburgh James J. , Folz Rodney J. , Prosnitz Leonard R.
Published: August 2002

BACKGROUND

To study the predictive value of serial pulmonary function testing (PFT) for toxicity in patients who have received high‐dose chemotherapy (HDCT) and stem‐cell rescue for breast carcinoma. These patients are at risk of developing therapy‐related pneumonitis (TRP) during or after radiotherapy (RT).

METHODS

Sixty‐eight patients who received induction chemotherapy (CT) and consolidation HDCT (cyclophosphamide, cisplatin, carmustine) underwent serial PFTs before induction CT, after HDCT, and before locoregional RT. The rate of TRP, i.e., pulmonary complications of Grade 2 or higher (World Health Organization classification), was studied during and 2 months after RT. We analyzed the time‐course of changes in the diffusing capacity of carbon monoxide (DLCO) and forced expiratory volume at one second (FEV1) and studied the differences between patients who developed TRP and those who did not.

RESULTS

The incidence of TRP was 46%. There were marked reductions in DLCO and FEV1 at the time of RT compared with baseline (Wilcoxon signed rank test: P < 0.001). However, pre‐RT PFT values did not predict subsequent development of TRP. Instead, the ratio of pre‐RT DLCO to the minimum post‐ HDCT DLCO, i.e., trend of improvement, predicted the development of TRP in patients (logistic regression analysis: P = 0.048). At a cutoff level of 1, the positive and negative predictive values for this ratio were 61% and 87%, respectively. There was an association between this ratio and a longer interval between HDCT and RT (Spearman rank correlation: P = 0.002).

CONCLUSIONS

The results suggest that the directional trend of DLCO after HDCT, i.e., no recovery from nadir values, is a predictor for TRP. TRP patients have a shorter median interval between HDCT and RT than asymptomatic patients. To minimize the occurrence of TRP, one should consider either delaying RT beyond 2 months following carmustine‐based HDCT to allow the PFTs to partly recover, or confirm apositive directional trend for improvement of DLCO at the start of RT compared to the post‐HDCT nadir value. Cancer 2002;94:2821–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10573
Evaluating a risk‐based model for mammographic screening of women in their forties
Authors: McPherson Carol P. , Nissen Mary J.
Published: August 2002

BACKGROUND

A risk‐based model was developed for recommendations for mammography screening of women in their 40s. We determined retrospectively the proportion of women already diagnosed in their 40s with breast cancer (BC) who would have been recommended for mammography screening by this model.

METHODS

Information was obtained from 404 women who were diagnosed with BC in their 40s from 1990 to 1998 at a large midwestern hospital. Data on BC detection method, mammography history, and BC risk factors existing before diagnosis were obtained from 353 of these women by mailed questionnaires. Data for an additional 51 women who had died were obtained by chart review. Two algorithms, the Exact Age Procedure (EAP) and the Grouped Age Procedure (GAP), were used to calculate the proportion of women who would have been recommended for mammography screening based on age, race, and BC risk factors.

RESULTS

Of women diagnosed with BC in their 40s, 74.5% would have been recommended for screening by the EAP and 70.5% by the GAP. The model would have recommended screening for approximately one half of the women who had no conventional risk factors (54% by EAP, 48% by GAP).

CONCLUSION

Although use of the risk‐based model could result in more recommendations for screening than individual recommendations based on patient‐physician discussions about the woman's risk factors, one in four women diagnosed with breast cancer in their 40s would not have been recommended for mammography screening. Cancer 2002; 94:2830–5. © 2002 American Cancer Society.

DOI 10.1002/cncr.10579
Phase I trial of subcutaneous recombinant human interleukin‐2 in patients with metastatic melanoma
Authors: Eton Omar , Rosenblum Michael G. , Legha Sewa S. , Zhang Wehei , Jo East Mary , Bedikian Agop , Papadopoulos Nicholas , Buzaid Antonio , Benjamin Robert S.
Published: August 2002

BACKGROUND

Interleukin‐2 (IL‐2) has activity in metastatic melanoma when given in high doses by the intravenous (IV) route, but its side effects and effectiveness when given in intermediate to high doses by the subcutaneous (SC) route have not been studied adequately. This study sought to determine the maximum tolerated dose (MTD) of IL‐2 administered once daily by the SC route.

METHODS

Outpatients with progressive metastatic melanoma after chemotherapy were enrolled in a Phase I trial of IL‐2 administered SC daily for 5 days per week for 4 consecutive weeks, repeated at 6‐week intervals. Patients were instructed to drink at least 2 L of fluid daily. IL‐2 pharmacokinetic studies were performed at the two highest dose levels. Toxicity was recorded weekly using the National Cancer Institute Common Toxicity Criteria. Response was assessed at 6‐week intervals.

RESULTS

Three patients, 6 patients, 6 patients, and 4 patients received a median of 2 courses of SC IL‐2 at dose levels of 6 MIU/m2, 9 MIU/m2, 12 MIU/m2, and 15 MIU/m2, respectively. Failure to maintain adequate fluid intake was responsible for 2 episodes of syncope at the 9 MIU/m2 dose level and for 2 incidents of reversible prerenal azotemia at the 15 MIU/m2 dose level. IL‐2 treatment was resumed in these patients without incident. At the 15 MIU/m2 dose level, 2 patients had severe headaches, depression, and visual hallucinations requiring discontinuation of treatment. Cough and fluid retention at the end of the third and fourth weeks at the 15 MIU/m2 dose level approximated the symptoms reported by inpatients treated by continuous IV infusion at 9 MIU/m2 on the same schedule. There was a partial response and a complete response in subcutaneous disease at the 12 MIU/m2 and 15 MIU/m2 dose levels, respectively, each lasting < 2 months. Plasma IL‐2 levels after SC injection of 1000–5000 pg/mL reached maximum by 3 hours and were detectable for up to 48 hours after administration. The half‐lives for SC IL‐2 absorbance and clearance were 1.6 hours and 5.2 hours, respectively, and the calculated area under the curve was 30,584 pg/mL × hour.

CONCLUSIONS

SC IL‐2 was well tolerated and had high sustained bioavailability at the higher doses studied. The MTD for a daily SC regimen was 12 MIU/m2 and is recommended for future studies. Cancer 2002;95:127–34. © 2002 American Cancer Society.

DOI 10.1002/cncr.10631
Patterns of Care Study quantitative evaluation of the quality of radiotherapy in Japan
Authors: Tanisada Kazuaki , Teshima Teruki , Ohno Yuko , Inoue Toshihiko , Abe Mitsuyuki , Ikeda Hiroshi , Owen Jean B. , Hanks Gerald E. , Masuda Kouji , Honke Yoshifumi ,   the Japanese Patterns of Care Study 1992–1994 Working Group
Published: August 2002

BACKGROUND

Quality assurance (QA) of clinical practice is important for any medical specialty. Programs based on the Patterns of Care Study (PCS) have been developed to compare the quality of radiotherapeutic care at individual institutions, with the national average representing the process and outcome of radiotherapy. The feasibility of these programs was analyzed.

METHODS

Calculation programs for the national average and standard score were developed to evaluate quantitatively the process and outcome of radiotherapy at individual institutions as well as at the national level. The programs were used to evaluate the quality of radiotherapy for 561 esophageal carcinoma patients surveyed in the Japanese PCS.

RESULTS

As a representative example of QA measurement, the national average for the 5‐year survival rate for these patients in the nonsurgery group was 5%. The regional averages for those in academic and nonacademic institutions were 9% and 1%, respectively (P = 0.0142), showing a significant difference between these two institutional strata. The standard score compared with the national average for institution No.105, for example, was 16.3 (P < 0.0001), with the positive value indicating that the outcome at this institution was significantly higher than the national average. The corresponding figure compared with the regional average was −0.3 (P = 0.7391), with the negative value indicating the outcome is not superior to the regional average of academic institutions.

CONCLUSIONS

These programs make it possible to compare quantitatively the quality of radiation therapy at individual institutions with the national and regional averages. They should also be useful for nationwide QA projects in radiation oncology as well as in other medical specialities. Cancer 2002;95:164–71. © 2002 American Cancer Society.

DOI 10.1002/cncr.10633
Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion
Authors: Mercadante Sebastiano , Villari Patrizia , Ferrera Patrizia , Casuccio Alessandra , Fulfaro Fabio
Published: August 2002

BACKGROUND

Cancer pain emergencies presenting with severe excruciating pain require a rapid application of powerful analgesic strategies. The aim of the current study was to evaluate a method of rapid titration with intravenous morphine to achieve relief of cancer pain of severe intensity.

METHODS

Forty‐nine consecutive patients admitted to a Pain Relief and Palliative Care Unit for severe and prolonged pain were enrolled in the study. Pain was evaluated on a numeric scale of 0–10 (0 indicated no pain and 10 indicated excruciating pain). After the initial assessment (T0), an intravenous line was inserted and boluses of morphine (2 mg every 2 minutes) were given until the initial signs of significant analgesia were detected or severe adverse effects occurred (T1). A continuous reassessment was warranted and the effective total dose administrated intravenously was assumed to last approximately 4 hours and was calculated for 24 hours. The dose immediately was converted to oral morphine (a 1:3 ratio for low doses and a 1:2 ratio for high doses).

RESULTS

Data from 45 patients was analyzed. A significant decrease in pain intensity was achieved in a mean of 9.7 minutes (95% confidence interval [95% CI], 7.4–12.1 minutes), using a mean dose of intravenous morphine of 8.5 mg (95% CI, 6.5–10.5 mg). The doses administered rapidly were converted to oral morphine and pain control was mantained until the patient's discharge, which occurred in a mean of 4.6 days (95% CI, 4.1–5.2 days). The incidence of adverse effects was minimal.

CONCLUSIONS

The results of the current study demonstrate that cancer pain emergencies can be treated rapidly in the majority of cancer patients with an acceptable level of adverse effects. Intravenous administration of morphine requires initial close supervision and continuity of medical and nursing care. Cancer 2002;95:203–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10636
Dichotomy in phasic‐tonic neuromuscular structure of crayfish inhibitory axons
Authors: Kirk Mark D. , Meyer Jason S. , Miller Mark W. , Govind C.K.
Published: August 2002

Crustacean muscles are unique in their innervation by both excitatory and inhibitory neurons; therefore, they exhibit polyneuronal and multiterminal innervation. Because excitatory motoneurons are broadly divided into phasic and tonic types, we hypothesized that inhibitory neurons would follow a similar dichotomy. The abdominal extensor muscles in crayfish are separated into parallel deep and superficial bundles; the former has fast muscle fibers innervated by phasic excitatory motoneurons, and the latter has slow fibers supplied by tonic excitatory motoneurons. Each muscle also is innervated by a single, separate inhibitory neuron that uses γ‐aminobutyric acid (GABA) as the inhibitory neurotransmitter. The pattern of axonal branching by the separate inhibitory axons in phasic and tonic abdominal extensor muscles was visualized with confocal microscopy in preparations labeled for GABA‐like immunoreactivity. Initial observations indicated that the phasic muscle was covered by extensive GABAergic, filiform axon terminals, whereas innervation of the tonic muscle was comprised of more localized and varicose terminals. With quantitative analyses, we found that the phasic axon has a more highly branched nature than the tonic in first‐ and second‐order branches. The phasic axon branches also were significantly longer than the tonic branches in the second‐ and third‐order branches. Synaptic varicosities in the phasic branches were smaller and less frequent than those in the tonic branches. The fine structure of the inhibitory nerve terminals near synaptic contacts examined with thin‐serial‐section electron microscopy revealed distinct differences between the phasic system and the tonic system. The phasic terminals were smaller in cross‐sectional area than the tonic terminals, and they had smaller synapses and fewer mitochondria. The presynaptic active zone dense bodies were similar in length and number between phasic and tonic synapses. However, their number per synaptic area was two‐fold higher in phasic synapses compared with tonic synapses because of the smaller size of the phasic synapses. Thus, within the same neuromuscular system, inhibitory synaptic terminals revealed unique phasic and tonic identities similar to those observed for the excitatory axons. J. Comp. Neurol. 435:283–290, 2001. © 2001 Wiley‐Liss, Inc.
Differential distribution of the glutamate transporters GLT‐1 and GLAST in tanycytes of the third ventricle
Authors: Berger Urs V. , Hediger Matthias A.
Published: August 2002

The ventral one‐third of the ventricular lining in the hypothalamus is formed by specialized ependymal cells called the tanycytes. These cells may serve a neuroendocrine transport function because of their structural specializations, which include apical microvili on the ventricular surface and long basal processes that terminate on blood vessels or on the glia limitans. Here, we describe the expression of mRNA and protein for the glutamate transporters GLT‐1 and GLAST in unique tanycyte populations of the third ventricle in rat brain. Using nonisotopic in situ hybridization, we demonstrate GLAST mRNA labeling in tanycytes of the ventral floor and lateral walls in the tuberal and mammillary recess portions of the third ventricle. This GLAST mRNA labeling had a higher intensity than the labeling intensity observed in regular ependymal cells throughout the ventricular system. Furthermore, we have identified strong GLT‐1 mRNA labeling in a population of tanycytes situated in the dorsolateral walls of caudal tuberal and mammillary recess portions. Immunocytochemical staining indicates that both GLT‐1 and GLAST protein are expressed in the tanycyte populations as well. These data corroborate previous findings that third ventricle tanycytes are functionally heterogeneous. Furthermore, the GLT‐1‐expressing tanycytes represent a population of tanycytes that, to date, has not been recognized as functionally distinct. The strong GLAST expression by the ventral tanycytes in the hypophysiotropic area suggests a role of tanycyte‐mediated glutamate transport in neuroendocrine activity. The functional role of GLT‐1 in dorsal wall tanycytes remains to be explored. J. Comp. Neurol. 433:101–114, 2001. © 2001 Wiley‐Liss, Inc.
Demonstration of a rhodopsin‐retinochrome system in the stalk eye of a marine gastropod, onchidium, by immunohistochemistry
Authors: Katagiri Nobuko , Terakita Akihisa , Shichida Yoshinori , Katagiri Yasuo
Published: August 2002

The stalk eye of Onchidium sp. (Gastropoda, Mollusca) is the principal photoreceptor in a multiple photoreceptive system that consists of the stalk and dorsal eyes, dermal photoreceptor cells, and photosensitive neurons. To examine the localization of photopigments, the stalk eyes were immunostained with specific antibodies to rhodopsin, retinochrome, and retinal‐binding protein (RALBP), which had been generated against squid retinal proteins. The retina of the stalk eye was divided into villous, pigmented, somatic, and neural layers. It was comprised mainly of two types of visual and pigmented supportive cells. The type 1 visual (VC1) cell was characterized by well‐developed microvilli on its apical protrusion and photic vesicles in the cytoplasm. The photic vesicles were specifically blackened by prolonged osmification. The type 2 visual (VC2) cell had less numerous, shorter microvilli on its concave apical surface and lacked photic vesicles. The anti‐squid rhodopsin antiserum was localized specifically to the villous layer that corresponded to the VC1 microvilli. With the anti‐retinochrome peptide antibody, the somatic layer showed specific but patchy, positive staining that corresponded to the cytoplasm of the VC1 cells. Because the photic vesicles are known to contain retinochrome, these results indicate that this retinochrome is localized in the VC1 cytoplasm. Anti‐RALBP antibody stained the supranuclear cytoplasm to the distal cytoplasm of VC1 cells. This is the first demonstration of the localization of RALBP in the Gastropoda Onchidium stalk eye. In squid retina that were immunostained as positive controls, the anti‐rhodopsin antibody stained rhabdomeric microvilli, the anti‐retinochrome antibody stained the inner segment and the basal region of the outer segment, and the anti‐RALBP antibody stained the outer and inner segments, respectively. These results suggest that the rhodopsin‐retinochrome system that has been established in cephalopod eyes is present in the Onchidium stalk eye. J. Comp. Neurol. 433:380–389, 2001. © 2001 Wiley‐Liss, Inc.
Neuromodulator content of hamster intergeniculate leaflet neurons and their projection to the suprachiasmatic nucleus or visual midbrain
Authors: Morin Lawrence P. , Blanchard Jane H.
Published: August 2002

The intergeniculate leaflet (IGL) of the lateral geniculate complex has widespread, bilateral, and reciprocal connections with nuclei in the subcortical visual shell. Its function is poorly understood with respect to its role in visual processing. The most well‐known IGL projection, and the only one with a clear function, is the geniculohypothalamic tract (GHT) that terminates in the suprachiasmatic nucleus (SCN), site of the primary circadian clock. The hamster GHT is derived, in part, from IGL neurons containing neuropeptide Y and enkephalin. IGL neurons containing these peptides also project to the pretectal region. The present studies used a combination of immunohistochemical, lesion, and retrograde tracing techniques to study neuron types in the IGL and their projections to hamster SCN and pretectum. Two additional neuromodulators, γ‐aminobutyric acid (GABA) and neurotensin, are shown to be present in IGL neurons. The GABA‐ and neurotensin‐immunoreactive neurons project to the SCN with terminal field patterns very similar to those for neuropeptide Y and enkephalin. IGL neurons of all four types also send projections to the pretectum, but rarely do individual cells project to both the SCN and the pretectum. Nearly all neurotensin is colocalized with neuropeptide Y in IGL neurons, although about half of the neuropeptide Y cells do not contain neurotensin. Otherwise, the extent to which the four neuromodulators are colocalized varies from 6% to 54%. Nearly every SCN neuron appears to contain GABA. In the IGL, the majority of cells studied are not identifiable by GABA immunoreactivity. Putative functions of the various neuromodulator projections from the IGL to pretectum or SCN are discussed. J. Comp. Neurol. 437:79–90, 2001. © 2001 Wiley‐Liss, Inc.
Immunohistochemical localization of atrial natriuretic factor and autoradiographic distribution of atrial natriuretic factor‐binding sites in the brain of the cave salamander Hydromantes genei (Amphibia, Plethodontidae)
Authors: Mathieu Maura , Trabucchi Michele , Vallarino Mauro , Pedrazzi Andrea , Serra Giuliana , Spiga Saturnino , Vaudry Hubert
Published: August 2002

The distribution of atrial natriuretic factor (ANF)‐like immunoreactivity in the central nervous system of the cave salamander Hydromantes genei (Amphibia, Plethodontidae) was investigated by using antisera raised against rat and human ANF(1–28). Concurrently, the location of ANF‐binding sites was determined by autoradiography, using radioiodinated human ANF(1–28) as a tracer. In several regions of the brain, including the olfactory bulb, the preoptic area, the ventral thalamus, the tectum of the mesencephalon, and the choroid plexuses inside the ventricles, a good correlation was observed between the distribution of ANF‐immunoreactive elements and the location of ANF‐binding sites. Mismatching was found in the habenular nucleus, the commissura habenularis, the fasciculum retroflexus, and the interpeduncular nucleus, which contained high levels of binding sites but were devoid of ANF‐immunoreactive structures. In contrast, a few other regions, such as the pineal gland and the subcommissural organ, showed a high concentration of ANF‐like immunoreactivity but did not contain ANF‐binding sites. This study provides the first localization of ANF‐like immunoreactivity and ANF‐binding sites in the brain of an urodele amphibian. The results show that the ANF peptidergic system in the cave salamander has an organization more simple than the organizations described for the brain of frog or other vertebrates. This feature is probably related to the expression of highly pedomorphic characters in plethodontids. The anatomical distribution of ANF‐immunoreactive elements and ANF‐binding sites suggests that ANF‐related peptides may act as hypophysiotropic hormones as well as neurotransmitters and/or neuromodulators in the salamander brain. J. Comp. Neurol. 437:240–258, 2001. © 2001 Wiley‐Liss, Inc.