bluuebunny/crossref_metadata_2025 huggingface dataset:
An extremely low frequency magnetic field attenuates insulin secretion from the insulinoma cell line, RIN‐m
Authors: Sakurai Tomonori , Satake Akira , Sumi Shoichiro , Inoue Kazutomo , Miyakoshi Junji
Published: March 2004

In this study, we investigated the effects of exposure to an extremely low frequency magnetic field (ELFMF) on hormone secretion from an islet derived insulinoma cell line, RIN‐m. We stimulated RIN‐m cells to secrete insulin under exposure to an ELFMF, using our established system for the exposure of cultured cells to an ELFMF at 5 mT and 60 Hz, or under sham exposure conditions for 1 h and observed the effects. In the presence of a depolarizing concentration of potassium (45 mM KCl), exposure to ELFMF significantly attenuated insulin release from RIN‐m cells, compared to sham exposed cells. Treatment with nifedipine reduced the difference in insulin secretion between cells exposed to an ELFMF and sham exposed cells. The expression of mRNA encoding synaptosomal associated protein of 25 kDa (SNAP‐25) and synaptotagmin 1, which play a role in exocytosis in hormone secretion and influx of calcium ions, decreased with exposure to an ELFMF in the presence of 45 mM KCl. These results suggest that exposure to ELFMF attenuates insulin secretion from RIN‐m cells by affecting calcium influx through calcium channels. Bioelectromagnetics 25:160–166, 2004. © 2004 Wiley‐Liss, Inc.
Response of cyclic AMP by DMSO differentiated HL‐60 cells exposed to electric interferential current after prestimulation
Authors: Sontag W.
Published: March 2004

The action of interferential current (IFC) upon intracellular content of cyclic adenosine monophosphate (cAMP) after prestimulation with the chemotactic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) has been investigated. Human promyelocytes (HL‐60) differentiated to granulocytes by dimethylsulphoxide (DMSO) have been treated with different concentrations of fMLP. This enhances their cAMP content. The half maximal effective concentration (EC50) was about 4 nM. Exposure to IFC with modulation frequencies of 35 and 125 Hz (5 min, 250 µA/cm2) after prestimulation with various concentrations of fMLP had no enhancing effect at low or high concentrations of fMLP. In contrast, at medium concentrations in the range of about 100 pM fMLP, a significant enhancement of cAMP could be observed. This synergistic effect of fMLP and IFC has been examined in detail by varying the modulation frequency, current density, and exposure time. Enhancement of cAMP content could be observed at certain modulation frequencies and exposure times suggesting a window effect, whereas for the current density in the range measured (8.5 µA/cm2–2.5 mA/cm2) a constant enhancement could be observed. The synergistic effect of fMLP and IFC could only be observed in the treatment sequence of fMLP followed by IFC; an inverse sequence had no effect on the cAMP content. Bioelectromagnetics 25:176–184, 2004. © 2004 Wiley‐Liss, Inc.
Static magnetic field influence on rat brain function detected by heart rate monitoring
Authors: Veliks Viktors , Ceihnere Edīte , Svikis Igors , Aivars Juris
Published: March 2004

The aim of the present study was to identify the effects of a static magnetic field (SMF) on rat brain structures that control autonomic functions, specifically heart rate and heart rhythmicity. The experiments were carried out on 44 male Wistar rats under ketamine–xylazine anesthesia. SMF was induced using samarium‐cobalt fused magnets (20 × 20 × 10 mm in size) placed bitemporally. Magnetic induction intensity was 100 mT on the surface of the head. Duration of magnetic field application was 15 min. An electrocardiogram was recorded from limb lead II, and both heart rate (average duration of cardiac cycles) and heart rhythmicity were analyzed before and after SMF application. SMF evoked changes in both heart rate and rhythm in 80% of the animals; the predominant effects were bradycardia and disappearance of respiratory sinus arrhythmia. However, the effectiveness of SMF in large measure depends on both functional peculiarities and functional activities of brain autonomic centers. Bioelectromagnetics 25:211–215, 2004. © 2004 Wiley‐Liss, Inc.
60 Hz electric field upregulates cytosolic Ca2+ level in mouse splenocytes stimulated by lectin
Authors: Harakawa Shinji , Inoue Noboru , Saito Atsushi , Doge Fuyuki , Nagasawa Hideyuki , Suzuki Naoyoshi , Martin David E.
Published: March 2004

The effect of a 60 Hz electric field (EF) on alteration of cytosolic free Ca2+ level ([Ca2+]c) was examined in mouse splenocytes stimulated by lectins, namely concanavalin A (ConA) or phytohemagglutinin. In order to understand the role of EF on alterations in [Ca2+]c and to determine whether EF exposure increased cell mortality the splenocytes were cultured under the 60 Hz EFs producing current densities of 6 or 60 μA/cm2 for 30 min or 24 h. Cell mortality was less than 2% in experimental all conditions. [Ca2+]c in the splenocyte was not changed by the 6 μA/cm2 exposure alone, while a lectin‐induced [Ca2+]c elevation in the EF exposed cells was significantly higher than that of the sham exposed cells (P < .05: ANOVA, P < .05: paired t‐test). Moreover, the enhanced increase of [Ca2+]c in the EF exposed, lectin stimulated cells was only observed in the presence of extracellular Ca2+. The EF dependent upregulation of [Ca2+]c persisted after EF exposure (P < .05: paired t‐test). The results clearly indicate that Ca2+ influx across the plasma membrane is responsible for the enhanced increase of [Ca2+]c in the EF exposed, lectin stimulated cells and that EF has persistent effect on the cells. Although the precise mechanisms of the EF dependent upregulation of [Ca2+]c is not fully elucidated, the present results demonstrate that the 60 Hz EF (6 μA/cm2) affects [Ca2+]c during cell activation via a Ca2+ influx pathway induced by lectin stimulation. Bioelectromagnetics 25:204–210, 2004. © 2004 Wiley‐Liss, Inc.
Resting EEG is affected by exposure to a pulsed ELF magnetic field
Authors: Cook Charles M. , Thomas Alex W. , Prato Frank S.
Published: March 2004

An increasing number of reports have demonstrated a significant effect of extremely low frequency magnetic fields (ELF MFs) on aspects of animal and human behavior. Recent studies suggest that exposure to ELF MFs affects human brain electrical activity as measured by electroencephalography (EEG), specifically within the alpha frequency (8–13 Hz). Here we report that exposure to a pulsed ELF MF with most power at frequencies between 0 and 500 Hz, known to affect aspects of analgesia and standing balance, also affects the human EEG. Twenty subjects (10 males; 10 females) received both a magnetic field (MF) and a sham session in a counterbalanced design for 15 min. Analysis of variance (ANOVA) revealed that alpha activity was significantly higher over the occipital electrodes (O1, Oz, O2) [F1,16 = 6.858; P = .019, eta2 = 0.30] and marginally higher over the parietal electrodes (P3, Pz, P4) [F1,16 = 4.251; P = .056, eta2 = 0.21] post MF exposure. This enhancement of alpha activity was transient, as it marginally decreased over occipital [F1,16 = 4.417; P = .052; eta2 = 0.216] and parietal electrodes [F1,16 = 4.244; P = .056; eta2 = 0.21] approximately 7 min after MF exposure compared to the sham exposure. Significantly higher occipital alpha activity is consistent with other experiments examining EEG responses to ELF MFs and ELF modulated radiofrequency fields associated with mobile phones. Hence, we suggest that this result may be a nonspecific physiological response to the pulsed MFs. Bioelectromagnetics 25:196–203, 2004. © 2004 Wiley‐Liss, Inc.
Prooxidant and antioxidant action of 4‐(4‐phenoxybenzoyl)benzoic acid derivatives
Authors: Aboul‐Enein Hassan Y. , Kladna Alexandra , Kruk Irena , Lichszteld Krzysztof , Marchlewicz Mariola , Michalska Teresa , Salem Ola I. A. , Hartmann Rolf W.
Published: March 2004

4‐(4‐Phenoxybenzoyl)benzoic acid derivatives (PBADs) were found to inhibit rat and human α‐reductase isozymes 1 and 2 in vitro. Chemiluminescence (CL), electron spin resonance, spin trapping techniques, and spectrophotometry were used to examine the effect of PBADs on reactive oxygen species (superoxide radical, ; hydroxyl radical, HO•; singlet oxygen, 1O2) generating systems. All test compounds at a concentration of 0.5 mM enhanced the CL from up to fivefold, which was recorded as the light sums during 1 min. At 0.38 mM PBAD enhanced production of HO• from H2O2 in the presence of Co(II) up to 90%, as measured by a deoxyribose assay. Using the spin trap agent 5,5‐dimethyl‐1‐pyrroline‐N‐oxide, it was found that the amplitude of the signal arising from the Fenton‐like reaction [Co(II)/H2O2] was significantly diminished by the test compounds. The compounds also inhibited the 1O2 dependent 2,2,6,6‐tetramethylpiperidine‐N‐oxide radical, which is generated in the acetonitrile/H2O2 system. The measured rate constants of 1O2‐dimol quenching by PBAD were in the range of (0.8–2.6) × 108 M−1 s−1. The interaction between PBAD and 1O2 was also checked using a spectrophotometry method based on bleaching of p‐nitrosodimethylaniline. These results indicate that PBAD may directly scavenge HO• and 1O2, but not . However, the compounds that wer examined had prooxidant ability under some reaction conditions. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Theoretical aspects of genomic variation screening using DNA microarrays
Authors: Vainrub Arnold , Pettitt B. Montgomery
Published: March 2004

We present a theoretical model for typical microarray‐based single nucleotide polymorphism (SNP) assay of small genomic DNA amount. We derived the adsorption isotherm expressing the on‐array hybridization efficiency in terms of genomic target sequence and concentration, oligonucleotide probe sequence and surface density, hybridization buffer, and temperature. This isotherm correctly describes the surface probe density effects, the sensitivity peak, and the melting temperature depression, and is in accord with published experiments. We discuss optimization of parallel SNP genotyping. Our estimates show that SNP detection at a single temperature in aqueous hybridization buffer is restricted by DNA regions that differ by less than 20% in GC content. We predict that the variety of genotyped SNPs could be substantially extended using an assay design with high probe density and a large fraction of probes hybridized. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Synthesis of sequential polydepsipeptides utilizing a new approach for the synthesis of depsipeptides
Authors: Katakai Ryoichi , Kobayashi Kyoko , Yamada Keiichi , Oku Hiroyuki , Emori Nobu
Published: March 2004

Sequential polydepsipeptides were synthesized by the depsipeptide active ester method using a new approach for the direct synthesis of N‐protected depsipeptide free acids from hydroxy acids. The method uses synthesis of Boc‐didepsipeptides by reaction of free hydroxy acids with Boc‐amino acid N‐hydroxysuccinimide esters catalyzed by 4‐dimethylaminopyridine and chain elongation of the free depsipeptides by the reaction with Boc‐amino acid N‐hydroxysuccinimide esters in an organic solvent system of acetonitrile‐tetrahydrofuran. The Boc‐depsipeptide free acids were activated as their N‐hydroxysuccinimide esters, which were polymerized after removal of the Boc‐protecting group. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine‐ and lysine‐rich peptide: Study at molecular and cellular levels
Authors: Boukhalfa‐Heniche Fatima‐Zohra , Hernández Belén , Gaillard Stéphane , Coïc Yves‐Marie , Huynh‐Dinh Tam , Lecouvey Marc , Seksek Olivier , Ghomi Mahmoud
Published: March 2004

Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single‐stranded 20‐mer phosphorothioate oligodeoxynucleotide with a 15‐mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/− charge ratio. At the molecular level, CD and Raman spectra were consistent with a α‐helix conformation of the peptide in water or in a methanol–water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its α‐helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5′‐terminus with the peptide into human glioma cells after 1 h of incubation at 37° C. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Patients' recall of clinical information following laparoscopy for acute abdominal pain
Authors: Murphy S M , Donnelly M , Fitzgerald T , Tanner W A , Keane F B V , Tierney S
Published: March 2004

Background

Failures in doctor–patient communication and patients' understanding continue to confound improvements in the delivery of quality healthcare. In the context of acute abdominal pain managed by means of laparoscopy, it was hypothesized that patients are either not adequately informed, or do not reliably retain simple relevant information transmitted at the time of the procedure. This study was designed to evaluate the reliability of information transfer between doctor and patient in this setting, including the diagnosis and whether or not the appendix was removed.

Methods

A retrospective study of 350 consecutive patients who had undergone laparoscopy for acute abdominal pain over 3·5 years was designed. Each patient completed a telephone questionnaire that was used to evaluate the accuracy of patients' information.

Results

In total, 26·9 per cent of patients did not know or were incorrect regarding the surgical procedure performed. Similarly, 20·0 per cent of all patients did not know or were incorrect regarding the status of their appendix after surgery and 30·0 per cent of patients were incorrect regarding the diagnosis. Despite all of these statistics, 91·4 per cent of patients were happy with the information they had received regarding the procedure.

Conclusion

Some 26·9 per cent of patients who underwent laparoscopy for acute abdominal pain were incorrect or did not know about the procedure that had been performed. This could lead to a further unnecessary operation should they re-present with similar symptoms.
Diagnostic laparoscopy and diverting sigmoid loop colostomy in the management of civilian extraperitoneal rectal gunshot injuries
Authors: Navsaria P H , Shaw J M , Zellweger R , Nicol A J , Kahn D
Published: March 2004

Background

This prospective study reviews the management of isolated civilian extraperitoneal rectal gunshot injuries using a protocol of diagnostic laparoscopy and abdominal wall trephine diverting loop colostomy, without laparotomy, distal rectal washout and presacral drainage.

Methods

Patients admitted to the trauma unit at Groote Schuur Hospital between January 2000 and December 2002 with a rectal injury were evaluated. A rectal injury was confirmed by digital rectal examination and proctosigmoidoscopy. Missile peritoneal violation was excluded by diagnostic laparoscopy. Normal laparoscopy was followed by creation of a diverting sigmoid loop colostomy through an abdominal wall trephine, without a laparotomy. No distal rectal washout or presacral drainage was performed.

Results

Of the 104 patients admitted with 106 rectal injuries, 20 (19·2 per cent) qualified for inclusion in the study. All had sustained low-velocity gunshot injuries of which 18 exhibited a transpelvic trajectory. Diagnostic laparoscopy was normal and a trephine diverting loop sigmoid colostomy was performed in all 20 patients. No pelvic sepsis occurred. Two patients developed rectocutaneous fistulas, both of which resolved without surgical treatment. Nineteen stomas have since been closed.

Conclusion

Low-velocity gunshot injuries isolated to the extraperitoneal rectum can be managed safely by laparoscopic exclusion of intraperitoneal missile penetration and diverting sigmoid loop colostomy, without laparotomy, distal rectal washout or presacral drainage
Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic
Authors: Phillips S M , Banerjea A , Feakins R , Li S R , Bustin S A , Dorudi S
Published: March 2004

Background

Patients with colorectal cancer that display high-level microsatellite instability (MSI-H) appear to have a better prognosis. This may be explained by the pronounced T cell infiltrate seen in MSI-H tumours that is related to a specific antigen-driven immune response. The nature of tumour-infiltrating lymphocytes in colorectal cancers was investigated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry.

Methods

Quantitative fluorescent hydrolysis probe-based reverse transcriptase–PCR assays were used to detect levels of mRNA specifying T cell markers in fresh frozen colorectal tissue from MSI-H tumours and those with little or no microsatellite instability (microsatellite stable (MSS) tumours). In addition, immunohistochemistry was performed on paraffin-embedded sections to compare expression of the same T cell markers and the activation markers granzyme B and interleukin 2 receptor α-subunit (IL-2Rα) in MSI-H and MSS tumours.

Results

MSI-H tumours contained higher ratios of CD8/CD3 mRNA copy numbers than MSS tumours (P = 0·016), confirming the cytotoxic nature of lymphocyte infiltrates in this subset of colorectal cancers. Furthermore, immunohistochemistry confirmed that MSI-H tumours contained more infiltrating lymphocytes than MSS tumours, as shown by increased expression of CD3 (P = 0·003) and CD8 (P = 0·008). Consistent with other studies, the lymphocytes in MSI-H tumours were activated as indicated by significantly higher granzyme B counts (P = 0·020) and a significantly higher level of expression of IL-2Rα (P = 0·017).

Conclusion

The results support the hypothesis that MSI-H colorectal cancers may be more immunogenic than MSS tumours.
Tumour morphology as a predictor of outcome after local excision of rectal cancer
Authors: Chambers W M , Khan U , Gagliano A , Smith R D , Sheffield J , Nicholls R J
Published: March 2004

Background

The aim of this study was to determine whether the morphology of rectal cancer predicts outcome following treatment by local excision, and whether morphology should therefore be added to the criteria presently used for case selection.

Methods

The hospital notes and histological findings of 91 patients who had undergone a local surgical procedure for rectal cancer were reviewed retrospectively. Eight patient and tumour characteristics including morphology were analysed with respect to 5-year survival, local recurrence and cancer-specific death within 5 years. Morphology was divided into four types: polypoid, sessile, ulcerated and flat raised.

Results

Survival and local recurrence were significantly better for patients with exophytic (polypoid and sessile) carcinomas than for those with non-exophytic (ulcerated and flat raised) lesions. Multivariate logistic regression analysis showed that age, depth of invasion, lymphatic invasion and venous invasion were significant predictors of outcome. The exophytic group included significantly more stage T1 and fewer T2 and T3 cancers, and a significantly smaller proportion of tumours that showed venous and lymphatic invasion than the non-exophytic group.

Conclusion

Morphology is a clinical guide to prognosis after local excision. Non-exophytic cancers are associated with high-risk histopathological features that render tumours of this type unsuitable for local excision.
Randomized clinical trial of hand-assisted laparoscopic versus open Roux-en-Y gastric bypass for the treatment of morbid obesity
Authors: Sundbom M , Gustavsson S
Published: March 2004

Background

Roux-en-Y gastric bypass (RYGBP) has increased in popularity since the introduction of the laparoscopic procedure, but this approach requires extensive surgical skill and the learning curve is steep. The present study examined the suitability of hand-assisted laparoscopy for RYGBP.

Methods

In a prospective trial, 50 patients (median age 38 years, body mass index 45 kg/m2) were randomized to either hand-assisted (n = 25) or open (n = 25) RYGBP. The hand-assisted device was introduced through a right subcostal incision. Laparoscopic staplers were also used in the open group, allowing a short upper midline incision. The gastrojejunostomy was made by means of a circular stapler and the Roux limb placed behind the colon and excluded stomach.

Results

The postoperative outcome, with respect to morphine consumption, complications, hospital stay (6 days) and weight loss, was similar in the two groups. The operating time was significantly longer in the hand-assisted group (150 versus 85 min; P < 0·001) but there was no conversion to open operation. One patient in the hand-assisted group was reoperated owing to leakage and one patient developed an incisional hernia after open RYGBP.

Conclusion

The hand-assisted technique was feasible and allowed good working conditions in all patients. However, the postoperative outcome was excellent in both groups and there was no advantage to the hand-assisted technique.
Critical evaluation of the different staging systems for hepatocellular carcinoma
Authors: Wildi S , Pestalozzi B C , McCormack L , Clavien P-A
Published: March 2004

Background

Diagnostic and therapeutic options for hepatocellular carcinoma (HCC) have improved substantially in recent years. A number of new palliative and potentially curative treatment strategies are now available. However, evaluation of the therapeutic modalities and assessment of the prognosis of HCC remain difficult owing to the lack of consensus on a single staging system and the availability of a number of new staging systems, each claiming to be the most appropriate.

Methods

The most frequently used staging systems for HCC are presented here. Their ability to stratify patients into different treatment groups and to define prognosis are discussed. In addition, the advantages and disadvantages of each system are analysed.

Results and conclusion

None of the currently used staging systems fulfils all the requirements for stratification of patients with HCC into groups of different prognosis and therapeutic recommendations. An international agreement on a single staging system is urgently needed in order to permit comparable randomized clinical trials. Only in this way will the outcome for those with HCC be improved.
Surgical site infection after groin hernia repair (Br J Surg 2004; 91: 105–111)
Authors: Gaunt A , McKain E S , Feroz A , Stephenson B M
Published: March 2004

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses can be sent electronically via the BJS website (www.bjs.co.uk) or by post. All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Letters submitted by post should be typed on A4-sized paper in double spacing and should be accompanied by a disk.
Multiple arterial variations in the upper limb of a South Indian female cadaver
Authors: Kumar M.R.
Published: March 2004

In a routine dissection of a female cadaver, a variation in the course of the radial artery in the cubital fossa and a communication between the brachial artery and radial artery were observed. A rare origin and course of the median artery was also found. These anomalies are discussed in detail and their clinical relevance is highlighted. Clin. Anat. 17:233–235, 2004. © 2004 Wiley‐Liss, Inc.
Vascular pedicles of infrahyoid muscles: An anatomical study
Authors: Görmüs Gökhan , Bayramoğlu Alp , Aldur M. Mustafa , Çelik H. Hamdi , Maral Tugrul , Sargon Mustafa F. , Demiryürek Deniz , Aksit M. Dogan
Published: March 2004

This study was designed to determine the entering sites of vascular pedicles of the infrahyoid muscles. The neck regions of 12 cadavers were investigated bilaterally. The vascular pedicles of the infrahyoid muscles (except the thyrohyoid and inferior belly of the omohyoid muscle) were dissected and measurements taken with a caliper in reference to the attachments of the muscles. For the sternothyroid muscle, two vascular pedicles were found bilaterally in all cadavers. Two vascular pedicles were found bilaterally for the sternohyoid muscle in 11 cadavers; in one cadaver the inferior vascular pedicle was absent bilaterally. One vascular pedicle was found bilaterally for the superior belly of the omohyoid muscle in all cadavers. These data regarding the vascular pedicles of the infrahyoid muscles might be useful for preserving the vascular supply of the infrahyoid muscles during flap preparation. Clin. Anat. 17:214–217, 2004. © 2004 Wiley‐Liss, Inc.
Unilateral occurrence of a chondroepitrochlearis muscle
Authors: Sarikcioglu Levent , Yildirim Fatos Belgin , Chiba Shoji
Published: March 2004

An abnormal muscle slip was encountered during routine dissection studies of a male cadaver. According to its origin, attachment and innervation, the abnormal slip was identified a chondroepitrochlearis muscle. Arterial and nervous supply were from the lateral thoracic artery and the medial pectoral nerve, respectively. Furthermore, no axillary arch muscle was observed. In addition, an abnormality in the attachment of the pectoralis major muscle was observed. Clin. Anat. 17:272–275, 2004. © 2004 Wiley‐Liss, Inc.
Histological changes in radial forearm skin flaps in the oral cavity
Authors: Sinclair A. , Johnston E. , Badran D.H. , Neilson M. , Soutar D.S. , Robertson A.G. , McDonald S.W.
Published: March 2004

We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The “changed” flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy. Clin. Anat. 17:227–232, 2004. © 2004 Wiley‐Liss, Inc.
Biochemotherapy in patients with metastatic anorectal mucosal melanoma
Authors: Kim Kevin B. , Sanguino Angela M. , Hodges Cynthia , Papadopoulos Nicholas E. , Eton Omar , Camacho Luis H. , Broemeling Lyle D. , Johnson Marcella M. , Ballo Matthew T. , Ross Merrick I. , Gershenwald Jeffrey E. , Lee Jeffrey E. , Mansfield Paul F. , Prieto Victor G. , Bedikian Agop Y.
Published: March 2004

BACKGROUND

Patients with metastatic anorectal melanoma generally have an unfavorable prognosis, but no effective systemic therapy has been reported.

METHODS

The authors retrospectively evaluated the medical records of all patients with metastatic anorectal melanoma treated with biochemotherapy between January 1991 and December 2001 at the University of Texas M. D. Anderson Cancer Center (Houston, TX).

RESULTS

The search yielded 18 patients. Of these patients, 14 had undergone treatment with cisplatin (CDDP), vinblastine (VB), dacarbazine (DTIC), interferon alpha‐2b (IFN), and interleukin 2 (IL‐2); 2 had undergone treatment with CDDP, VB, DTIC, and IFN; 1 had undergone treatment with CDDP, IFN, and IL‐2; and 1 had undergone treatment with CDDP, VB, temozolomide, IFN, and IL‐2. All IL‐2 treatments were administered intravenously. The median follow‐up time was 12.2 months (range, 3.5–43.7 months). Eight patients (44%) had major responses, including two (11%) complete responses (CRs). Three patients were lost to follow‐up evaluation after the completion of treatment. The median time to progression among the 15 remaining patients was 6.2 months. Four patients, including 1 with a CR, were alive at their last documented follow‐up visits (survival: 14.0, 20.7, 31.3, and 43.7 months, respectively). The median overall survival was 12.2 months. Among 13 patients who received biochemotherapy as first‐line systemic therapy, 6 patients (46%) had major responses, including two (15%) CRs. The median time to progression for this group was 6.2 months, and the median overall survival was 12.9 months.

CONCLUSIONS

Biochemotherapy had substantial activity against metastatic anorectal melanoma and should be considered for use in the treatment of metastatic disease from primary anorectal melanoma. Cancer 2004;100:1478–83. © 2004 American Cancer Society.
5‐fluorouracil‐induced oligodendrocyte death and inhibitory effect of cycloheximide, trolox, and Z‐VAD‐FMK in murine cortical culture
Authors: Cho Ki‐Hyun , Choi Sung‐Min , Kim Byeong‐Chae , Lee Seung‐Han , Park Man‐Seok , Kim Myeong‐Kyu , Kim Jong‐Keun
Published: March 2004

BACKGROUND

5‐fluorouracil (5‐FU) is a widely used anticancer drug. One of the adverse effects of this drug is selective cerebral white matter injury, but to the authors' knowledge its mechanism has not been well documented. The current study was performed to investigate the mechanism of cerebral white matter injury caused by 5‐FU and to develop the intervention to attenuate its injury in vitro.

METHODS

Mixed oligodendrocyte/astrocyte cells were dissociated from specimens taken from approximately 2‐day‐old postnatal mouse cortex and cultured for 3–4 weeks. The culture cells were exposed to 5‐FU, cycloheximide, emetine, Z‐VAD‐fmk, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(F)‐quinoxaline (NBQX), Trolox, and epigallocatechin gallate. Oligodendrocyte cell death was assessed by counting the number of viable galactocerebroside‐positive cells per × 100 field.

RESULTS

Mixed oligodendrocyte/astrocyte culture cells that were exposed to 5‐FU (at doses of 10 μM, 30 μM, and 100 μM) for 24 hours ensued concentration‐dependent oligodendrocyte death. The majority of oligodendrocytes, but few astrocytes, were injured by 100 μM 5‐FU. Trolox, a vitamin E analog antioxidant, as well as cycloheximide (a protein synthesis inhibitor) and Z‐VAD‐fmk (a caspase inhibitor), significantly attenuated the 5‐FU–induced oligodendrocyte death. However, NBQX, an alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, did not appear to effect the 5‐FU–induced oligodentrocyte death.

CONCLUSIONS

The findings of the current study suggested that 5‐FU led to oligodendrocyte death rather than astrocyte death by way of the apoptotic process, whereas antioxidants may prevent the 5‐FU–induced oligodendrocyte cell death in vitro. Cancer 2004;100:1484–90. © 2004 American Cancer Society.
Sequential dose‐dense doxorubicin and ifosfamide for advanced soft tissue sarcomas
Authors: Maurel Joan , Fra Joaquín , López‐Pousa Antonio , García del Muro Xavier , Balañá Carmen , Casado Antonio , Martín Javier , Martínez‐Trufero Javier , de las Peñas Ramón , Buesa José M.
Published: March 2004

BACKGROUND

Combinations of high‐dose ifosfamide (IF; 10–12 g/m2) plus doxorubicin (DX; 50–90 mg/m2) have been administered to patients with advanced soft tissue sarcoma (ASTS) in an attempt to improve therapeutic efficacy. Although these combination regimens appear to yield higher response rates than do standard‐dose regimens, they also are associated with significant hematologic toxicity, despite the administration of hematopoietic growth factor support. As a potentially less toxic alternative, the authors designed a sequential, dose‐dense schedule of DX and IF and explored its feasibility and toxicity, as well as patient compliance with the schedule, in a Phase II trial.

METHODS

Chemotherapy‐naive patients with unresectable locally advanced or metastatic ASTS were to receive DX at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by IF at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles. Granulocyte–colony‐stimulating factor was administered subcutaneously for 7 days beginning 24 hours after the completion of each DX or IF cycle. Additional IF cycles were allowed if an objective response was achieved.

RESULTS

Sixty patients were enrolled in the trial. Three were ineligible, 9 had locally advanced disease, and 48 had metastatic disease. At the completion of therapy, the mean dose intensities for DX and IF were 40 mg/m2 per week and 3.87 g/m2 per week, respectively. Sixty‐six percent of patients completed the regimen projected by the protocol. Grade 3 or 4 granulocytopenia, febrile neutropenia, and stomatitis occurred in 46%, 24%, and 27% of patients, respectively. Twenty of 53 assessable patients (38%; 95% confidence interval [CI], 25–51%) achieved objective responses, with a median time to progression of 24 weeks (95% CI, 18–30 weeks).

CONCLUSIONS

Sequential administration of dose‐dense DX and high‐dose IF is feasible and exhibits an acceptable hematologic toxicity profile and a level of activity that is within the range described for schedules that combine high‐dose IF with an anthracycline. Cancer 2004;100:1498–506. © 2004 American Cancer Society.
Results of a randomized, population‐based study of biennial screening using serum prostate‐specific antigen measurement to detect prostate carcinoma
Authors: Hugosson Jonas , Aus Gunnar , Lilja Hans , Lodding Pär , Pihl Carl‐Gustav
Published: March 2004

BACKGROUND

The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate‐specific antigen (PSA) levels were measured.

METHODS

From a group of 20,000 men born between January 1, 1930, and December 31, 1944, 10,000 men were randomized into a screening group and 10,000 were randomized into a control group. Patients in the screening group were invited to undergo initial PSA testing between 1995 and 1996 and then were invited to receive testing every second year thereafter for 8 years (for a total of 4 PSA tests). Men with PSA levels ≥ 3 ng/mL (or ≥ 2.54 ng/mL, in the third and fourth screening rounds) were invited to undergo clinical investigation, which included sextant biopsy of the prostate. By linking to the regional cancer registry, the authors were able to obtain the true and expected incidence rates for the screening and control groups.

RESULTS

The screening participation rate was high (73%). A total of 884 malignancies have been detected to date, with 640 having been detected in the screening group. There was an early and marked shift toward more favorable disease stage and grade for malignancies detected on repeat screening. In the fourth screening round, only 2 of 82 detected malignancies were classified as advanced disease. Of the 227 screen‐detected tumors on which surgery was performed, only 20 (8.8%) had small volume (< 0.2 cm3). Forty‐three interval malignancies were detected, but only five were accompanied by symptoms. At 8 years, the cumulative disease incidence rate among screening participants was 7.3%, compared with 2.4% in the control arm. The incidence rate observed in the screening population corresponds to the cumulative incidence rate observed in the Swedish male population at age 72 years.

CONCLUSIONS

Biennial PSA screening was very successful in diagnosing prostate carcinoma at an early stage, when curative treatment typically is effective. In addition, the results regarding interval malignancies were favorable. Thus, decreased mortality should be observed on long‐term follow‐up. The lead time associated with screening appears to fall within the range described in earlier studies involving frozen sera (i.e., 5–9 years). Cancer 2004;100:1397–405. © 2004 American Cancer Society.
Neoadjuvant therapy changes the lymphocyte composition of tumor‐draining lymph nodes in cervical carcinoma
Authors: Fattorossi Andrea , Battaglia Alessandra , Ferrandina Gabriella , Coronetta Ferdinando , Legge Francesco , Salutari Vanda , Scambia Giovanni
Published: March 2004

BACKGROUND

The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma.

METHODS

Uninvolved tumor‐draining lymph nodes (TDLN) (n = 158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)‐treated patients, and 19 chemoradiation (CR)‐treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon‐γ (IFN‐γ) production. Lymphocyte subsets in peripheral blood also were assessed.

RESULTS

TDLNs from CR‐treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT‐treated patients (P values ranged from < 0.05 to < 0.01). TDLNs from CR‐treated patients were enriched in activated‐type CD4+ cells (HLA‐DR+, CD134+, CD62L−, and CD25+ at an intermediate expression level; P values ranged from < 0.05 to < 0.01) and activated‐type CD8+ cells (CD62L−, P <0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of naïve‐type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P< 0.01 and < 0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN‐γ. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy‐induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood.

CONCLUSIONS

To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma. Cancer 2004;100:1418–28. © 2004 American Cancer Society.
DNA repair and breast carcinoma susceptibility in women
Authors: Ramos Juan M. , Ruiz Abigail , Colen Rivka , Lopez Ivette D. , Grossman Lawrence , Matta Jaime L.
Published: March 2004

BACKGROUND

Breast carcinoma is the most common cancer and the second leading cause of cancer‐related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma.

METHODS

A retrospective case–control clinical study was performed to compare age‐matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer‐free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors.

RESULTS

Women with breast carcinoma had a mean DRC of 5.6% ± 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P < 0.001) in DRC when compared with the control group (DRC = 8.7% ± 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age‐matched controls. Family (odds ratio [OR] = 4.1), maternal lineage (OR = 5.5), and maternal (OR = 12.4) history of breast carcinoma were found to be the only statistically significant (P < 0.05) risk factors associated with the disease.

CONCLUSIONS

The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility. Cancer 2004;100:1352–7. © 2004 American Cancer Society.
A prospective study of concurrent cyclophosphamide/methotrexate/5‐fluorouracil and reduced‐dose radiotherapy in patients with early‐stage breast carcinoma
Authors: Bellon Jennifer R. , Shulman Lawrence N. , Come Steven E. , Li Xiaochun , Gelman Rebecca S. , Silver Barbara J. , Harris Jay R. , Recht Abram
Published: March 2004

BACKGROUND

Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early‐stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5‐fluorouracil (CMF) and reduced‐dose radiotherapy, focusing on tumor control and patient tolerance.

METHODS

One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0–3 positive axillary lymph nodes were enrolled in a prospective single‐arm study of concurrent CMF and reduced‐dose radiotherapy (39.6 gray [Gy] to the whole breast, 16‐Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age < 40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow‐up period was 94 months.

RESULTS

The 5‐year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (< 1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed.

CONCLUSIONS

Concurrent CMF and reduced‐dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted. Cancer 2004;100:1358–64. © 2004 American Cancer Society.
Familial association of specific histologic types of ovarian malignancy with other malignancies
Authors: Bermejo Justo Lorenzo , Rawal Rajesh , Hemminki Kari
Published: March 2004

BACKGROUND

Population‐based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy.

METHODS

The nationwide Swedish Family‐Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age‐ and histology‐specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites.

RESULTS

Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40–45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma.

CONCLUSIONS

Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Cancer 2004;100:1507–14. © 2004 American Cancer Society.
Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening
Authors: Ernst Miranda F. , Voogd Adri C. , Coebergh Jan Willem W. , Roukema Jan A.
Published: March 2004

BACKGROUND

The introduction of breast carcinoma screening leads to early detection and is believed to reduce mortality and increase the proportion of patients for whom breast‐conserving surgery is possible.

METHODS

In 1992, a population‐based mammographic screening program was introduced in the Dutch city of Tilburg and its surroundings; the program achieved total coverage in 1996. The authors examined the effects of this screening program by investigating disease stage, treatment, and survival among women diagnosed with breast carcinoma at a teaching hospital in Tilburg during the periods 1985–1991 and 1992–1999.

RESULTS

Between January 1, 1985, and December 31, 1999, 1400 patients were diagnosed with breast carcinoma. Among patients ages 50–69 years, the proportion of TNM Stage I breast carcinoma increased from 24% in 1985–1991 to 45% in 1992–1999 (P < 0.001). The proportion of patients age < 50 years with invasive breast carcinoma who underwent breast‐conserving surgery decreased from 45% to 33% (P = 0.011). Among patients ages 50–69 years, the overall survival rate during the period from 1992 to 1999 was significantly greater than the corresponding rate during the period from 1985 to 1991 (P = 0.0009). Even after adjustments were made for tumor stage and patient age, a slight reduction in mortality risk was observed in this age group. No difference in stage distribution or prognosis was found among patients age < 50 years or among patients age ≥ 70 years. Of the 168 invasive malignancies found in patients ages 50–69 years between 1997 and 1999, 68 (40%) were detected by the screening program, 47 (28%) were interval malignancies, and 53 (32%) were detected in nonparticipants or in women who did not participate in 1 or more screening rounds. Patients with screen‐detected tumors had a much more favorable prognosis than did patients with interval malignancies (P = 0.0018) or patients with clinically detected breast carcinoma (P < 0.0001).

CONCLUSIONS

Between 1992 and 1999, after the introduction of breast carcinoma screening, improved prognosis and more favorable tumor stage were observed among patients ages 50–69 years. Even after the screening program was fully implemented in 1996, the majority of invasive malignancies still were detected between screening rounds or in patients who did not participate in the program. Cancer 2004;100:1337–44. © 2004 American Cancer Society.