Electric field effect in diluted magnetic insulator anatase Co: TiO2.

An external electric field induced reversible modulation of a room temperature magnetic moment and coercive field is achieved in an epitaxial and insulating thin film of dilutely cobalt-doped anatase TiO2. This first demonstration of an electric field effect in any oxide-based diluted ferromagnet is realized in a high quality epitaxial heterostructure of PbZr(0.2)Ti(0.8)O(3)/Co: TiO(2)/SrRuO(3) grown on (001) LaAlO3. The observed effect, which is about 15% in strength in a given heterostructure, can be modulated over several cycles. Possible mechanisms for electric field induced modulation of insulating ferromagnetism are discussed.

On the origin of high-temperature ferromagnetism in the low-temperature-processed Mn-Zn-O system.

The recent discovery of ferromagnetism above room temperature in low-temperature-processed MnO(2)-ZnO has generated significant interest. Using suitably designed bulk and thin-film studies, we demonstrate that the ferromagnetism in this system originates in a metastable phase rather than by carrier-induced interaction between separated Mn atoms in ZnO. The ferromagnetism persists up to approximately 980 K, and further heating transforms the metastable phase and kills the ferromagnetism. By studying the interface diffusion and reaction between thin-film bilayers of Mn and Zn oxides, we show that a uniform solution of Mn in ZnO does not form under low-temperature processing. Instead, a metastable ferromagnetic phase develops by Zn diffusion into the Mn oxide. Direct low-temperature film growth of Zn-incorporated Mn oxide by pulsed laser deposition shows ferromagnetism at low Zn concentration for an optimum oxygen growth pressure. Our results strongly suggest that the observed ferromagnetic phase is oxygen-vacancy-stabilized Mn(2-x)Zn(x)O(3-delta.).

Self-assembled single-crystal ferromagnetic iron nanowires formed by decomposition.

Arrays of perpendicular ferromagnetic nanowires have recently attracted considerable interest for their potential use in many areas of advanced nanotechnology. We report a simple approach to create self-assembled nanowires of alpha-Fe through the decomposition of a suitably chosen perovskite. We illustrate the principle behind this approach using the reaction 2La(0.5)Sr(0.5)FeO(3) --> LaSrFeO(4) + Fe + O(2) that occurs during the deposition of La(0.5)Sr(0.5)FeO(3) under reducing conditions. This leads to the spontaneous formation of an array of single-crystalline alpha-Fe nanowires embedded in LaSrFeO(4) matrix, which grow perpendicular to the substrate and span the entire film thickness. The diameter and spacing of the nanowires are controlled directly by deposition temperature. The nanowires show uniaxial anisotropy normal to the film plane and magnetization close to that of bulk alpha-Fe. The high magnetization and sizable coercivity of the nanowires make them desirable for high-density data storage and other magnetic-device applications.

Co-occurrence of superparamagnetism and anomalous hall effect in highly reduced cobalt-doped rutile TiO2-delta films.

We report a detailed magnetic and structural analysis of highly reduced Co doped rutile TiO(2-delta) films displaying an anomalous Hall effect (AHE). The temperature and field dependence of magnetization, and transmission electron microscopy, clearly establish the presence of nanosized superparamagnetic cobalt clusters of approximately 8-10 nm size in the films at the interface. The co-occurrence of superparamagnetism and AHE raises questions regarding the use of the AHE as a test of the intrinsic nature of ferromagnetism in diluted magnetic semiconductors.

Multiferroic BaTiO3-CoFe2O4 Nanostructures.

We report on the coupling between ferroelectric and magnetic order parameters in a nanostructured BaTiO3-CoFe2O4 ferroelectromagnet. This facilitates the interconversion of energies stored in electric and magnetic fields and plays an important role in many devices, including transducers, field sensors, etc. Such nanostructures were deposited on single-crystal SrTiO3 (001) substrates by pulsed laser deposition from a single Ba-Ti-Co-Fe-oxide target. The films are epitaxial in-plane as well as out-of-plane with self-assembled hexagonal arrays of CoFe2O4 nanopillars embedded in a BaTiO3 matrix. The CoFe2O4 nanopillars have uniform size and average spacing of 20 to 30 nanometers. Temperature-dependent magnetic measurements illustrate the coupling between the two order parameters, which is manifested as a change in magnetization at the ferroelectric Curie temperature. Thermodynamic analyses show that the magnetoelectric coupling in such a nanostructure can be understood on the basis of the strong elastic interactions between the two phases.

High temperature ferromagnetism with a giant magnetic moment in transparent co-doped SnO(2-delta).

The occurrence of room temperature ferromagnetism is demonstrated in pulsed laser deposited thin films of Sn(1-x)Co(x)O(2-delta) (x<0.3). Interestingly, films of Sn(0.95)Co(0.05)O(2-delta) grown on R-plane sapphire not only exhibit ferromagnetism with a Curie temperature close to 650 K, but also a giant magnetic moment of 7.5+/-0.5 micro(B)/Co, not yet reported in any diluted magnetic semiconductor system. The films are semiconducting and optically highly transparent.

Soft tissue sarcomas: ultrasonographic evaluation of local recurrences.

OBJECTIVE: The diagnosis of early local recurrence of soft tissue sarcomas, especially in those treated with surgery and radiotherapy, is a difficult clinical problem. Financial constraints led us to use ultrasonography instead of CT or MR imaging. The aim of this study was to evaluate the role of ultrasonography (US) in detecting local recurrence. METHODS AND RESULTS: Fifty patients with previous treatment for soft tissue sarcomas were evaluated prospectively for recurrence by US and histopathology. Seven of the 50 patients were clinically suspected to have recurrent tumour. Ultrasonography showed recurrence in 26, no recurrence in 18, benign disease in four and was indeterminate in two cases. Ultrasonography was instrumental in guiding fine needle aspiration biopsies of small local recurrences and indeterminate lesions in 17 patients. In the sonographically tumour positive patients, histopathology confirmed recurrence in 24; one case had benign disease and one patient refused surgery. Thirteen of the 18 sonographically tumour negative patients were operated upon; all were negative for tumour on histopathology. Both the indeterminate cases showed recurrence on histopathology. The benign cases were confirmed by histopathology correlation. Ultrasound guided fine needle aspiration cytology (FNAC) was positive in 14 out of 17 patients (88%). The sensitivity and specificity of US was 92.30% and 94.4% respectively. CONCLUSION: Our study concludes that US is an extremely useful and cost effective method in the detection of early local recurrences of soft tissue sarcomas and should therefore be used for initial routine follow-up and guided biopsies.

Natural killer cell function and genetic instability in unaffected individuals from breast cancer families.

Several recent reports highlight the importance of modifying factors in determining the risk for cancer of a person carrying a mutant allele of a tumour susceptibility gene. The study of two such risk modifying factors namely, natural killer (NK) cell function and constitutional cytogenetic anomalies in members of families with familial breast cancer is presented in this paper. We observed that, compared to healthy controls, a significant proportion of unaffected persons from breast cancer families not only display lower NK cell function or genetic instability alone, but also in conjunction. The significance of these observations is discussed. We propose that amongst the unaffected members, persons with lower NK cell function as well as constitutive cytogenetic anomalies may be at a higher risk for cancer. The need for a set of suitable biomarkers to identify individuals at high risk from familial breast cancer families has been recognized for many years. Constitutional cytogenetic anomalies, otherwise seen in breast tumours, have also been observed in lymphocyte cultures from unaffected persons from such families. Lowered NK cell function has previously been demonstrated in first degree relatives of cancer patients. Both these parameters have been implicated in determining the risk of developing malignancy. In the present study these aspects have been investigated simultaneously in order to assess their utility as potential biomarkers.

Studies on functional status of circulating lymphocytes in unaffected members from cancer families.

That the inheritance of mutations in tumor susceptibility genes alone cannot determine risk for developing cancer is now well accepted. Immune functions have long been recognized as one of the important risk modifying factors in this regard. In an attempt to develop a multiparametric approach to identify high risk individuals from cancer families, we have examined NK cell function in unaffected members from familial breast cancer families. We have also carried out a parallel study of T lymphocyte functions in these individuals. Our studies demonstrate a significantly lower NK cell activity in members from cancer families. T lymphocyte activity also showed a similar trend, with the unaffected members demonstrating a notably lowered T lymphocyte function. In addition the data from patients reveals differential sensitivity of NK and T lymphocyte function to the disease phenotype. Implications of these observations are discussed.

Reduced DNA repair capacity in breast cancer patients and unaffected individuals from breast cancer families.

It has been suggested that increased fragile site expression in lymphocyte cultures can be used as a marker for genetic predisposition to cancer. We wished to determine whether aphidicolin (APC), an inhibitor of the DNA repair enzyme DNA polymerase alpha, could be used as a reliable biomarker in identification of DNA repair capacity in unaffected individuals at high risk from breast cancer families. PHA-stimulated lymphocyte cultures, with and without APC, were set up in 65 individuals, of whom 14 were breast cancer patients, 26 were unaffected individuals from breast cancer families, and 25 were controls. A significant proportion of breast cancer patients and unaffected individuals from familial breast cancer (FBC) families exhibited premature separation of centromeres (PSC) and aneuploidy in the untreated cultures. In the APC treated cultures, almost all such individuals exhibited a marked depression of mitotic index and increased aneuploidy, as compared to controls. Our results indicate that these individuals have defective DNA repair capacity. Such individuals could thus have a much higher risk of cancer as compared to persons exhibiting PSC and aneuploidy or DNA repair defects alone. We propose that APC may be a valuable biomarker in identifying individuals with genetic predisposition to cancer from FBC families.

Transhiatal esophagectomy for squamous cell carcinoma of the esophagus.

Eighty patients underwent transhiatal esophagectomy for squamous cell carcinoma of the esophagus. Dysphagia for solids was the presenting symptom in 90% of the patients. The standard technique of transhiatal esophagectomy was used and cervical anastomosis were hand sewn. The average operative time and blood loss were 190 min and 350 cc respectively. The 30 day mortality rate was 7.5% (six patients). Major respiratory complications were observed in 15 (18.7%) patients. Anastomotic leak rate was 10% (eight patients). The incidence of recurrent laryngeal nerve injury was 6.2% (five patients). The average hospital stay was 14 days. Four patients had stage I, 30 had stage II and 46 had stage III disease. Forty-nine patients (60%) had lymph node involvement. The overall actual survival at 2 years was 55% and at 5 years was 37%. Of the operative survivors, 87% patients resumed normal swallowing and 10 patients (13.5%) required dilatation for anastomotic stricture. Transhiatal esophagectomy can be performed with low operative mortality, acceptable morbidity and offers good long-term functional results without compromising the survival of patients.

Preoperative diagnosis of carcinoma of the breast: Is a "cost-cutter" algorithm tenable?

BACKGROUND: Decision making in favor of conservative breast surgery is dependent upon the accuracy of preoperative evaluation of tumor stage, of which imaging modalities occupy a pivotal role. Systematic studies correlating the relative accuracy of various evaluating strategies are few, but remain vital means of making the optimal selection of diagnosis and subsequent treatment option. In this study, we evaluated the relative efficacy of: (1) palpation (P), (2) ultrasonography (US), and (3) bilateral mammography (MG) of the breast and axilla. METHODS: In a prospective study, 109 female patients undergoing a modified radical mastectomy were subjected to a preoperative diagnostic assessment protocol involving palpation, ultrasonography, and bilateral mammography of the breast and axilla. Subsequently the preoperative findings were correlated to the postoperative histopathological reports. Cancer-specific criteria evaluated were tumor size, location, histologic type, histoarchitecture, and calcification, as well as status of regional nodes. Patient-specific criteria included age, size, and density of the breast and presence of associated benign breast disease. Percentage sensitivity, specificity, and positive and negative predictive values were determined for MG, US, and P as well as MG + P and US + P. RESULTS: In assessment of the primary tumor, P, MG, and US showed an overall sensitivity of 88%, 92%, and 90%, respectively; MG + P and US + P had a sensitivity of 99% each. In nodal assessment, P, MG, and US showed an overall sensitivity of 88%, 69%, and 77%, respectively; MG + P and US + P had a sensitivity of 90% and 94%, respectively. Mammography understaged the tumor, whereas US and P overstaged tumors as well as nodes. US was particularly better than MG in younger women, smaller breast size, denser breast consistency, with or without associated benign breast disease, and cystic or necrotic tumors with invasive ductal histology. In addition, US was comparable to MG in most of the other criteria as well. Disadvantages of US over MG were its complete inability to detect microcalcification and certain intraductal cancers. CONCLUSION: We conclude that: (1) the combination of US and P provides equivalent preoperative efficacy as MG, (2) the combination is more cost-effective preoperative assessment for subsequent selection of therapeutic modality, and (3) in certain well-defined circumstances discussed by us, mammography is most useful and should be considered as the imaging modality of choice.

Premature separation of centromere and aneuploidy: an indicator of high risk in unaffected individuals from familial breast cancer families?

It is estimated that one in every four women with a first-degree relative affected by breast cancer will develop the disease. Recent evidence suggests that susceptibility to breast cancer can be inherited. We have carried out cytogenetic analysis on PHA-stimulated lymphocyte cultures of breast cancer patients (familial and sporadic), patients with benign breast lesions, unaffected individuals from families with a history of breast cancer and healthy controls. A high incidence of premature separation of centromere (PSC) and aneuploidy was observed in a significant proportion of familial breast cancer patients and patients with fibrocystic disease as well as in some unaffected individuals from breast cancer families. These observations are also supported by cytogenetic analysis of EBV-transformed lymphoblastoid cell lines established from some of these individuals. No such aberrations were detected in the controls. Further, most of the affected and unaffected individuals with these two anomalies also exhibited structural chromosomal aberrations of 1q, 6q, 7q, 16q, 18q, or Xq. Based on these observations, we propose that the presence of both PSC and aneuploidy in lymphocyte cultures of unaffected individuals from breast cancer families can be used as an important predictive parameter to determine the risk of developing cancer.

Interpectoral nodes in carcinoma of the breast: requiem or resurrection.

Fifty-eight consecutive patients undergoing a modified radical mastectomy were subjected to complete dissection and pathological assessment of the interpectoral fascia and the group of lymph nodes it contains. The dissection was carried out in all patients, irrespective of whether they were palpable or not. Interpectoral nodes (IPNs) were anatomically present in 28 patients (48%) and were completely absent in 30 patients (52%). Ten patients were Stage I, 18 were Stage II, and 30 were Stage III. Of the 25% (15/58) of patients with microscopic metastasis, only 12/15 had palpable nodes; 66% (10/15) of patients had axillary and apical nodes positive. Significantly, two patients with negative nodes in the axillary and apical group had metastatic Rotter's nodes. Of the 15 patients with positive IPNs, nine had primary tumors located within the upper quadrants of the breast, whereas only five had tumors in lower quadrants and one had a centrally located tumor. The neurovascular bundle to the pectoralis major could be safely preserved in 93% (54/58) of patients. The incidence of impalpable nodes with microscopic metastasis and the evidence of exclusively metastatic interpectoral nodes with uninvolved axillary and apical nodes prompt the following conclusions: (1) interpectoral fascia and nodes should be mandatorily dissected in all patients irrespective of the nodes being palpable or not; (2) the dissection is anatomic and is associated with almost no additional morbidity; (3) the group of patients with IPNs positive and the axillary group negative, would benefit maximally from the IPN dissection. Similarly, this dissection in all other groups of patients would enable a more accurate staging and selection of therapeutic strategies.

Cost effective treatment of osteogenic sarcoma of the extremities.

In an ongoing trial at our institute 10 patients of high grade osteogenic sarcoma of the extremities have been treated with preoperative chemotherapy including ifosfamide 2 mg/M2/day i.v. for 5 days, doxorubicin 20 mg/M2/day i.v. for 3 days and cisplatinum 120 mg/M2 i.v. on day 1 at 3-4 weeks interval for 2 courses followed by surgery. One patient refused surgery and further treatment. Pathological study of the 9 surgical specimens showed grade IV necrosis in 5, grade III necrosis in 2 and grade I & II necrosis in 2. Overall response rate (Grade III & IV) was 87.5%. The patients showing Grade III/IV response received a further 3 cycles of the same chemotherapy postoperatively. The patient who refused surgery is still alive at 30 months. Our followup ranges from 4-34 months. All patients developed myelosuppression and one patient died after 4th course of chemotherapy due to septicemia. We expect grade IV response to preoperative chemotherapy will be translated into longer disease free survival. Protocols followed in western countries are not practicable in Asian countries. Hence this new combination has been developed without compromising response rate.

Tuberculosis of the breast masquerading as carcinoma: a study of 100 patients.

One hundred patients with tuberculous mastitis were referred to the Tata Memorial Hospital, a cancer center, with a clinical diagnosis of malignancy. This study identifies the possible causes of misdiagnosis and reviews the management of these patients. A lump in the breast with or without ulceration was the commonest presentation, the others being diffuse nodularity and multiple sinuses. Concomitant axillary lymph nodes were found in one-third of the patients. Tuberculosis lesions such as nodular mastitis, disseminated mastitis, and sclerosing lesions clinically mimicked a fibroadenoma, carcinoma, and fibrocystic mastitis depending on the mode of presentation. A young, multiparous, lactating woman with a lesion should arouse the suspicion of tuberculous mastitis, although pretherapeutic pathologic confirmation of a benign disease is mandatory. Mammography, fine-needle aspiration cytology, and excision biopsy for this purpose are successful in 14%, 12%, and 60% of cases, respectively. Acid-fast bacilli were identified in 12% patients. All patients received antituberculous chemotherapy, and 14% patients required simple mastectomy, due to either lack of response to chemotherapy (10%) or large painful, ulcerative lesions involving the entire breast (4%). Axillary dissection was performed in only 8% patients with large ulcerated axillary nodes. All patients, followed for a minimum of 2 years, were free of disease after therapy.

Lymphocyte proliferation, IFN-gamma production and limiting dilution analysis of T-cell responses to ICRC and Mycobacterium leprae antigens in leprosy patients.

Lymphocyte proliferative responses and interferon-gamma (IFN-gamma) production after stimulation with antigens of ICRC, Mycobacterium leprae, and purified protein derivative (PPD) were assessed in leprosy patients and healthy donors. The patients studied were newly diagnosed as having lepromatous leprosy (LL), multidrug therapy (MDT) responders (MDT-R LL), MDT nonresponders (MDT-NR LL), borderline lepromatous (BL), and borderline tuberculoid/tuberculoid (BT/TT) leprosy. The tuberculoid leprosy patients showed increased lymphocyte proliferation and IFN-gamma production in response to stimulation with ICRC, M. leprae, and PPD antigens compared to other groups of LL patients and healthy donors. Although lymphocytes from LL patients showed low responses to ICRC and M. leprae antigens, their responses to PPD were not grossly affected. MDT-R LL patients showed higher lymphocyte proliferative responses and IFN-gamma production after stimulation with ICRC and PPD but not with M. leprae antigens. Tuberculoid leprosy patients showed higher T-cell frequencies to ICRC and M. leprae antigens compared to MDT-R LL and MDT-NR LL patients. The increased lymphocyte proliferative responses to ICRC observed in the MDT-R LL patients was reflected in the increased T-cell frequency to ICRC compared to M. leprae.