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The article looks at Charles Darwin's views on forms of life and its Greek connection. According to Darwin, it is nature, rather than history that produces new forms. The Greek echo in his view of forms whether species of varieties, show in his understanding of the whole and its parts. The article states that Darwin regards forms as inherently variable and he does not even understand the principle of their change, that is the origin of species. The article also presents comments regarding the conflict between the Darwinian and Aristotelian teachings when it comes to forms of life.

The article offers information about the evidences that prove Cytochromes c′ are biological models for the S = 3⁄2,5⁄2 spin-state admixture. The study aims to ascertain the presence of a quantum mechanical spin-admixture ground state in the Cytochromes c′ and to clarify the significance and possible involvement of Arg/Lys-ImH interactions in its physico-chemical characteristics as well as its other properties.

The chloroiron(III) complexes of the partially peripherally crowded 2,3-diethyl-2,3,12,13-tetraethyl-, 2,3,7,8-tetraethyl-, and 2,3,7,8,12,13-hexaethyl-5,10,15,20-tetraphenylporphyrins have been synthesised and their X-ray structures have been determined. The porphyrins present in these molecules are non-planar and assume asymmetric predominately saddle shapes. They are also slightly ruffled and domed according to an analysis of the out-of-plane distortions performed by using normal-coordinate structural decomposition (NSD). The saddle deformations, dominant in these chloroiron(III) complexes, are larger than those observed in all the cytochromes c’, whose structures were analysed by this method. Despite the large saddle-shaped distortions of the porphyrins present in these species, the quantum mechanical S = 3/2 spin admixtures into the S = 5/2 high-spin state (QMS state) observed are small. The EPR spectra of these Cβ-ethyl-substituted tetraphenylporphyrin complexes indicate S = 3/2 admixtures of 0% in Fe(detpp)Cl (1), 0.75% in Fe(trans-tetpp)Cl (2), 1.20% in Fe(cis-tetpp)Cl (3) and 2.75% in Fe(hetpp)Cl (4). The large saddle distortions of the porphyrins present in these compounds and the small S = 5/2,3/2 spin admixtures found indicate that the saddle distortions alone are probably not sufficient to cause the QMS states observed in several ferricytochromes c’ isolated from photosynthetic bacteria and in plant peroxidases. [Copyright &y& Elsevier]

SummaryBackground: The efficacy of high-dose chemotherapy with progenitor-cell rescue for women with breast cancer is a controversial issue. Although historically controlled trials have suggested a survival advantage for high-dose chemotherapy, several randomised studies have yet to confirm this advantage. Two studies, however, by Bezwoda, of patients with high-risk and metastatic disease, seemed to show a significant survival advantage for high-dose compared with conventional-dose chemotherapy for metastatic and high-risk primary breast cancer.Methods: To corroborate the study results before starting a large international confirmatory study, a US team did an on-site review of records for patients in the high-risk study. Limited numbers of records were made available for review, all of which were for patients who received the high-dose-chemotherapy regimen.Findings: There was much disparity between the reviewed records and the data presented at two international meetings. In addition, the reviewers saw no signed informed consent, and the institutional review committee had no record of approval for the investigational therapy. After the site visit, Bezwoda admitted scientific misconduct by using a different control chemotherapy regimen from that described in presented data.Interpretation: The Bezwoda study should not be used as the basis for further trials to test the efficacy of the cyclophosphamide, mitoxantrone, etoposide regimen for high-dose chemotherapy in women with high-risk primary breast cancer. This review validates the essential nature of on-site audits, especially in single-institution studies. [ABSTRACT FROM AUTHOR]

Presents information on a study looking at the synthesis and spectroscopic characterization of a series of porphyris with ether-linked straps. Methods and materials employed in the study; Results of experiments; Conclusion of the study.

Reports on data collected during on-site audits of source documents in the Cancer and Leukemia Group B (CALGB). Audit reports in four audit cycles; Results of institutional audits conducting clinical trials in cancer treatment; Scientific improprieties in CALGB clinical trials; Protocol compliance in assessing patient eligibility; Administrative compliance to consent forms; Review board approval.

Background Endoscopic posterior nasal nerve (PNN) resection has been described as an efficacious surgical treatment of allergic and nonallergic rhinitis, but the requirement for surgery under general anesthesia has limited its acceptance. We report the first series of patients treated for chronic rhinitis using a novel device designed for office-based cryosurgical ablation of the PNN. Methods Twenty-seven patients with chronic rhinorrhea and/or nasal congestion for >3 months were recruited (allergic or nonallergic rhinitis), with minimum rhinorrhea and/or congestion subscores of 2 as part of the Total Nasal Symptom Score [TNSS]). Under local anesthesia, the cryotherapy device was applied endoscopically to the posterior middle meatus and was used to freeze the PNN region bilaterally. Patients were followed up after 7, 30, 90, 180, and 365 days to assess TNSS. Results The procedure was successfully completed in 100% of patients, with no complications; 74% reported no or mild discomfort by the first postprocedure day. TNSS was reduced significantly at 30 days (mean ± standard deviation: 6.2 ± 0.5 at baseline, 2.6 ± 0.3 at 30 days, n = 27, p < 0.001), with continued reduction at 90 (2.7 ± 0.4, n = 24, p < 0.001), 180 (2.3 ± 0.5, n = 21, p < 0.001), and 365 days (1.9 ± 0.3, n = 15, p < 0.001). Both rhinorrhea and congestion subscores decreased significantly at 30, 90, 180, and 365 days compared to baseline ( p < 0.001). Allergic and nonallergic subcohorts both appeared to benefit from treatment. Conclusion Office-based cryotherapy of the PNN region is safe and well tolerated. Symptom scores were significantly decreased by 7 days postprocedure and remained lower at 30, 90, 180, and 365 days. [ABSTRACT FROM AUTHOR]

Objectives: This study assesses the safety and effectiveness of balloon catheters used as instruments in sinus surgery in a "real-world" multicenter registry of 1,036 patients across 27 US otolaryngology practices. Methods: Data were collected by standardized chart review with centralized database administration for all consecutive functional endoscopic sinus surgeries that included the use of balloon catheters across the 18-month time period from December 2005 to May 2007. Results: Balloon catheters were used in 3,276 peripheral (maxillary, frontal, and sphenoid) sinuses, for an average of 3.2 sinuses per patient. There were no major adverse events related to the use of balloon catheter instruments. The revision rate was 1.3% of sinuses treated with a balloon catheter after an average follow-up of 40.2 weeks. Sinus symptoms were improved in 95.2%, unchanged in 3.8%, and worse in 1.0% of patients. Postoperative sinus infections were significantly less frequent and less severe compared to infections before surgery. The results were consistent across all patient categories, including balloon-only patients and revision patients. Conclusions: Use of balloon catheters as instruments in sinus surgery appears to be relatively safe and effective and to improve the patient's quality of life. The results are consistent and generalizable across a wide range of sinusitis patients and physician practices. The complication rates, revision rates, and patient symptom improvement rates all compare favorably with previously reported results of functional endoscopic sinus surgery. [ABSTRACT FROM AUTHOR]

Abstract: The catalytic cycle intermediates of heme peroxidases, known as compounds I and II, have been of long standing interest as models for intermediates of heme proteins, such as the terminal oxidases and cytochrome P450 enzymes, and for non-heme iron enzymes as well. Reports of resonance Raman signals for compound I intermediates of the oxo-iron(IV) porphyrin π-cation radical type have been sometimes contradictory due to complications arising from photolability, causing compound I signals to appear similar to those of compound II or other forms. However, studies of synthetic systems indicated that protein based compound I intermediates of the oxoiron(IV) porphyrin π-cation radical type should exhibit vibrational signatures that are different from the non-radical forms. The compound I intermediates of horseradish peroxidase (HRP), and chloroperoxidase (CPO) from Caldariomyces fumago do in fact exhibit unique and characteristic vibrational spectra. The nature of the putative oxoiron(IV) bond in peroxidase intermediates has been under discussion in the recent literature, with suggestions that the FeIV ght be better described as FeIV–OH. The generally low FeIV ing frequencies observed for proteins have been difficult to mimic in synthetic ferryl porphyrins via electron donation from trans axial ligands alone. Resonance Raman studies of iron–oxygen vibrations within protein species that are sensitive to pH, deuteration, and solvent oxygen exchange, indicate that hydrogen bonding to the oxoiron(IV) group within the protein environment contributes to substantial lowering of FeIV cies relative to those of synthetic model compounds. [Copyright &y& Elsevier]

Context: Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain.Objective: To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older.Design and Setting: Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic.Patients: A total of 6487 women with lymph node-positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70 years or older.Main Outcome Measure: Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups.Results: Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy.Conclusion: Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health. [ABSTRACT FROM AUTHOR]

Context Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain. Objective To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older. Design and Setting Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic. Patients A total of 6487 women with lymph node--positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70 years or older. Main Outcome Measure Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups. Results Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy. Conclusion Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health. [ABSTRACT FROM AUTHOR]

Part II. Examines the synthesis, electrochemistry and spectroscopic properties of (BCA)Co[sub 2] and (BCB)Co[sub 2] biscorroles. Ligand binding properties of the compounds; Modification of the Co corroles by anthracenyl or biphenylenyl bridge; X-ray crystal structure.

Part I. Examines the synthesis, electrochemistry and spectroscopic properties of alkyl- and aryl-substituted Co(III) corroles. X-ray structure of the corroles; Reversible oxidation of the Co compounds in CH[sub 2]Cl[sub 2]; Analysis of ligand binding constants.

Presents a study on how synthesis of new symmetrick cylindrical macrotricyclic ligands, where two cyclam subunits are linked through nitrogen atoms by two aromatic chains of various lengths where achieved. Preparation of the compounds; Determination of the crystal structure of the [Ni](CIO4)4.2Ch3-CN complex; Findings of the study.

Oxoferrylporphyrin cation radical complexes were generated by m-chloroperoxybenzoic acid oxidation of the chloro and trifluoromethanesulfonato complexes of tetramesitylporphyrinatoiron(III) [(TMP)Fe] and the trifluoromethanesulfonato complex of tetra(2,6-dichlorophenyl)porphyrinatoiron(III) [TPP(2,6-Cl)Fe]. Coupling between ferryl iron (S = 1) and porphyrin radical (S' = 1/2) spin systems was investigated by Mössbauer and EPR spectroscopy. The oxoferrylporphyrin cation radical systems generated from the TMP complexes show strong ferromagnetic coupling. Analysis of the magnetic Mössbauer spectra, using a spin Hamiltonian explicitly including a coupling tensor J, suggests an exchange-coupling constant J > 80 cm-1. The EPR spectra show non-zero rhombicity, the origin of which is discussed in terms of contributions from the usual zero-field effects of iron and from iron-radical spin-dipolar interaction. A consistent estimate of zero-field splitting parameter D ≈ + 6 cm-1 was obtained by EPR and Mössbauer measurements. EPR and Mössbauer parameters are shown to be slightly dependent on solvent, but not on the axial ligand in the starting (TMP)Fe complex. In contrast to the TMP complex, the oxoferrylporphyrin cation radical system generated from [TPP(2,6-CI)FeOSO2CF3] exhibits Mössbauer and EPR spectra consistent with weak iron-porphyrin radical coupling of J ≈ 1 cm-1. [ABSTRACT FROM AUTHOR]

Two dioxygen adducts of thiolato‐iron(II) porphyrins, [K(⊂ 222)][Fe(TPpivP)(SC6HF4)(O2)] 1a and [Na(⊂ 18c.6)][Fe(TPpivP)(SC6HF4)(O2)] 2 were synthesized by reaction of O2 with five‐coordinate, high‐spin, cryptated alkali metal thiolato‐iron(II) ‘picket fence’ porphyrinate. They were characterized by visible and infrared spectroscopy: λmax (log ɛ) = 360 nm (4), 427 nm (4.69), 560 nm (3.69), 610 nm (3.40) for both compounds; v(16O‐16O) = 1139 cm−1 in chlorobenzene and fluorobenzene for 1a and 2. Single crystals of composition [K(⊂ 222)][Fe(TPpivP)(SC6HF4)(O2)] · [K(⊂ 222)](SC6HF4)(C6H5Cl)(H2O) 1b were obtained by diffusion of pentane/xylene mixtures into chlorobenzene solutions of 1a at – 5°C. Single crystals of composition [Na(⊂ 18c.6)][Fe(TPpivP)(SC6HF4)(O2)] were obtained by slow diffusion of pentane into benzene solutions of 2. Structures of 1b and 2 were studied at 20°C (1b) and – 100°C (1b and 2). 1b: space group P21/c (monoclinic), a= 16.806(5) Å (1.6806 nm), b= 14.331(4) Å (1.4331 nm), c= 52.000(15) Å (5.2000 nm), β= 92.95(2)°, V= 12507 Å3 (12.507 nm3), Z= 4, Dcal= 1.28 g · cm−3 (t= 20°C). The final R1 factor was 0.085 for 5238 reflections having I > 3 σ(I). 2: space group P21/c (monoclinic), a= 13.107(3) Å (1.3107 nm), b= 27.055(4) Å (2.7055 nm), c= 25.029(4) Å (2.5029 nm), β= 96.84(2)°, V= 8812 Å3 (8.812 nm3), Z= 4, Dcal= 1.18 g · cm−3 (t=−100°C). The final R1 factor was 0.088 for 6587 reflections having I > 3 σ(I). The iron atom is, in both compounds, bonded to the four porphyrinato nitrogens (Np), the sulfur atom of the axial thiolate and one oxygen atom of the axially end‐on bonded dioxygen molecule. The average Fe‐Np distance found in 1b [1.994(4) Å, 0.1994 nm] is not significantly different from that found in 2 [1.993(3) Å, 0.1993 nm]. The Fe‐S bond length is 2.367(3) Å (0.2367 nm) in 1b and 2.365(2) Å (0.2365 nm) in 2. The Fe‐O1 distances with the oxygen atom of O2 bonded to iron are respectively 1.837(9) Å (0.1837 nm) and 1.850(4) Å (0.1850 nm). The end‐on bonded O2 molecule is disordered in both complexes 1b and 2. This disorder is, however, slightly different from one structure to the other. Whereas the terminal oxygen atom of O2 occupies two positions in 1b [τ(O2A) = 78%, τ(O2B) = 22% at 20°C], it occupies three sites in 2 [τ(O2A) = 51%, τ(O2B) =τ(O2C) = 24.5% at – 100°C] (τ= occupancy). The estimate of the magnitude of the non‐bonded interactions between O2 and its environment located in a sphere of 7‐Å (0.7‐nm) radius in 1b and 2 is consistent with a static disorder of O2 in 1b and a dynamic distribution in 2. Mössbauer measurements were performed with polycrystals of 1b and 2 in the temperature ranges 5 – 197 K and 4.2 – 295 K, respectively, and under externally applied magnetic field (6.76 T) at 4.2 K (1b and 2) and at 173 K (2). The temperature variation of the Lamb‐Mössbauer factor indicates that the iron atom in these oxycytochrome P450 models is not very firmly bonded, more like that in pentacoordinated than in other hexacoordinated hemes. From the specific temperature behavior of quadrupole splitting, asymmetry parameter and line width obtained for 2, the structural disorder of the terminal oxygen atom of O2 is identified as dynamic distribution over three different sites. Corresponding values obtained for 1b are consistent with a static disorder of O2. Magnetic spectra reveal that the oxycytochrome P450 models are purely diamagnetic. [ABSTRACT FROM AUTHOR]