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Biomedical subjects

S Bhatia

Publications and source records attributed to S Bhatia.

At least 73 records · Page 4Linked to original sources
PubMed1996

Breast cancer and other second neoplasms after childhood Hodgkin's disease.

BACKGROUND: Patients who survive Hodgkin's disease are at increased risk for second neoplasms. As survival times increase, solid tumors are emerging as a serious long-term complication. METHODS: The Late Effects Study Group followed a cohort of 1380 children with Hodgkin's disease to determine the incidence of second neoplasms and the risk factors associated with them. RESULTS: In this cohort, there were 88 second neoplasms as compared with 4.4 expected in the general population (standardized incidence ratio, 18.1; 95 percent confidence interval, 14.3 to 22.3). The estimated actuarial incidence of any second neoplasm 15 years after the diagnosis of Hodgkin's disease was 7.0 percent (95 percent confidence interval, 5.2 to 8.8 percent); the incidence of solid tumors was 3.9 percent (95 percent confidence interval, 2.3 to 5.5 percent). Breast cancer was the most common solid tumor (standardized incidence ratio 75.3; 95 percent confidence interval, 44.9 to 118.4), with an estimated actuarial incidence in women that approached 35 percent (95 percent confidence interval, 17.4 to 52.6 percent) by 40 years of age. Older age (10 to 16 vs. <10 years) at the time of radiation treatment (relative risk, 1.9) and a higher dose (2000 to 4000 vs. <2000 cGy) of radiation (relative risk, 5.9) were associated with significantly increased risk of breast cancer. The estimated actuarial incidence of leukemia reached a plateau of 2.8 percent (95 percent confidence interval, 0.8 to 4.8 percent) 14 years after diagnosis. Treatment with alkylating agents, older age at the diagnosis of Hodgkin's disease, recurrence of Hodgkin's disease, and a late stage of disease at diagnosis were risk factors for leukemia. CONCLUSIONS: The risk of solid tumors, especially breast cancer, is high among women who were treated with radiation for childhood Hodgkin's disease. Systematic screening for breast cancer could be important in the health care of such women.

Actuarial Analysis↗
PubMed1996

Structural analysis of the rDNA intergenic spacer of Brassica nigra: evolutionary divergence of the spacers of the three diploid Brassica species.

EcoRI restriction of the B. nigra rDNA recombinants, isolated from a lambda genomic library, showed that the 3.9-kb fragment corresponded to the Intergenic Spacer (IGS), which was sequenced and found to be 3,928 bp in size. Sequence and dot-matrix analyses showed that the organization of the B. nigra rDNA IGS was typical of most rDNA spacers, consisting of a central repetitive region and flanking unique sequences on either side. The repetitive region was composed of two repeat families-RF 'A' and RF 'B.' The B. nigra RF 'A' consisted of a tandem array of three full-length copies of a 106-bp sequence element. RF 'B' was composed of 66 tandemly repeated elements. Each 'B' element was only 21-bp in size and this is the smallest repeat unit identified in plant rDNA to date. The putative transcription initiation site (TIS) was identified as nucleotide position 3,110. Based on the sequence analysis it was suggested that the present organization of the repeat families was generated by successive cycles of deletions and amplifications and was being maintained by homogenization processes such as gene conversion and crossing-over.A detailed comparison of the rDNA IGS sequences of the three diploid Brassica species-namely, B. nigra, B. campestris, and B. oleracea-was carried out. First, comparisons revealed that B. campestris and B. oleracea were close to each other as the repeat families in both showed high sequence homology between each other. Second, the repeat elements in both the species were organized in an interspersed manner. Third, a 52-bp sequence, present just downstream of the repeats in B. campestris, was found to be identical to the B. oleracea repeats, thereby suggesting a common progenitor. On the other hand, in B. nigra no interspersion pattern of organization of repeats was observed. Further, the B. nigra RF 'A' was identified as distinct from the repeat families of B. campestris and B. oleracea. Based on this analysis, it was suggested that during speciation B. campestris and B. oleracea evolved in one lineage whereas B. nigra diverged into a separate lineage. The comparative analysis of the IGS helped in identifying not only conserved ancestral sequence motifs of possible functional significance such as promoters and enhancers, but also sequences which showed variation between the three diploid species and were therefore identified as species-specific sequences.

Base Sequence↗
PubMed1996

Design of peptides: synthesis, crystal structure and molecular conformation of N-Boc-L-Val-delta Phe-L-Val-OC H3.

The dehydropeptide Boc-L-Val-delta Phe-L-Val-OC H3 was synthesized by azlactone method in solution phase. The peptide crystallized from its solution in a methanol/water mixture (70:30) in space group P2(1)2(1)2(1) with a = 13.638(1)A, b = 22.864(3)A, c = 27.600(2)A, V = 8606(1)A3. The structure was determined by direct methods and refined to an R value of 0.089 for 3326 observed [1 > or = 2 sigma(I)] reflections. The structure contains three crystallographically independent molecules. Two molecules (A and B) adopt identical conformations with phi 1(A) = -130(1), phi 1(B) = -139(1), psi 1(A) = 153(1), psi 1(B) = 145(1), phi 2(A) = 62(1), phi 2(B) = 56(1), psi 2(A) = 33(1), psi 2(B) = 33(1), phi 3(A) = -75(1), phi 3(B) = -77(1) psi 3T(A) = 152(1) and psi 3T(B) = 163(1) degrees. The conformation of the third molecule (C) is different as in that torsion angle psi 1 is rotated by 180 degrees. The backbone torsion angles are phi 1 = -128(2), psi 1 = -37(2), phi 2 = 65(1), psi 2 = 35(1), phi 3 = -84(1) and psi 3T = 169(1). It is significant that a characteristic beta-turn II conformation as observed in peptides with a delta Phe residue at (i+2) position has not been observed in this case. Thus the present structure demonstrates that an (i+2) substituted delta Phe with branched beta-carbon residue Val on both sides of it in a three peptide unit sequence does not adopt a folded conformation. The three independent molecules in the asymmetric unit form three hydrogen bonds between each pair of molecules and generates a tightly interacting unit of three molecules. These units pack into the crystalline state with hydrogen bonds involving N1, N2 and N3 of molecule C and O1' and O2' of symmetry related molecule A. The structure confirms that a peptide containing a delta Phe residue at (i+2) position with branched beta-carbon residues as its immediate neighbours on both sides does not adopt a folded conformation. This structure further demonstrates that the unfolded structures without any intramolecular hydrogen bond can be influenced by intermolecular forces, thus causing conformational variations in saturated residues. It is noteworthy that the conformation of the delta Phe residue remains unchanged in all the three molecules.

Crystallography, X-Ray↗
PubMed1996

Radiocephalometric evaluation of a family with mandibulofacial dysostosis.

Persons from four generations of a family with mandibulofacial dysostosis (MFD), known as Treacher Collins (TC) Syndrome, were examined for the presence of clinical signs traditionally associated with this syndrome. In this family, 14 adults, who had been judged trait bearers by an earlier family study were included in this study. Maxillary and mandibular study models were taken of affected and unaffected family members. Panoramic cephalograms and lateral radiographs were taken. The lateral cephalograms were traced and digitized on a computer system and compared. The 117 cephalometric values of the trait bearers were compared with known standard values and nontrait bearing family members. In the trait bearing group, 81 of the 117 values and, in the nontrait bearing group, 72 of the 117 values were significantly different (p < 0.05) when comparing mean values to the accepted normal range. The interfamily comparison between trait-bearing and nontrait members revealed nine values to be significantly different. This indicates that cephalometric analysis of these patients, some of whom have minimal clinical expression of the gene, may have potential value for screening and further characterization of this condition. The results also suggest that intrafamily comparisons may be of greater value for diagnostic confirmation of TC than comparison with literature norms.

Adult↗
PubMed1996

Vestibular schwannoma and the only hearing ear.

With the recent advances in the management of vestibular schwannomas, it is possible not only to save the facial nerve function but also preserve hearing in a small percentage of cases. Difficulties arise while managing patients with vestibular schwannoma in their only hearing ear. In this article we summarize our experience in managing seven of these patients. We recommended a watch and wait policy with a regular follow-up with audiometric testing and gadolinium-enhanced magnetic resonance imaging (MRI). Gamma knife radiosurgery is advised in cases with deterioration of hearing or increase in tumour size. Surgery is usually avoided unless there are brainstem compression symptoms.

Adult↗
PubMed1996

Thyroid Abnormalities after Therapy for Hodgkin's Disease in Childhood.

BACKGROUND: Involvement of the thyroid gland is an important morbidity of therapy for Hodgkin's disease, which should be well recognized by caretakers of these patients. However, the roles of age at the time of therapy for Hodgkin's disease, chemotherapy, treatment with reduced dose of radiation and lymphangiography in causing thyroid abnormalities have not been defined. MATERIALS AND METHODS: Eighty-nine pediatric and young adult patients (less than 21 years old at diagnosis) with Hodgkin's disease who were treated with either radiation alone (57 patients), radiation and chemotherapy (20 patients), or chemotherapy alone (12 patients) at the University of Minnesota between 1971 and 1986 were periodically evaluated. RESULTS: The median age at diagnosis was 14 years, and the median duration of follow up was 11 years. Of 89 patients evaluable for thyroid abnormalities, 51 patients developed biochemical hypothyroidism. The median time to development of hypothyroidism was six years. The estimated actuarial risk of developing hypothyroidism was 60% at 11 years. Radiation to the thyroid region was associated with an elevated risk of development of hypothyroidism (relative risk = 9.9), with patients receiving mantle irradiation alone developing hypothyroidism earlier (median time 2.5 years) than patients receiving combined modality treatment (median time 6 years; p = 0.001). Dose of radiation was the chief correlate for the development of hypothyroidism (relative risk increasing by 1.02/Gy; p < 0.001). Age, gender, chemotherapy and prior lymphangiography were not shown to be significant risk factors for the development of hypothyroidism. Four patients were diagnosed with thyroid nodules, (diagnosed 7.6 to 14.3 years after treatment of Hodgkin's disease), with histology showing multinodular goiter (2), single colloid nodule (1) and papillary carcinoma (1). Transient hyperthyroidism developed in two patients 8 and 13 months after treatment for Hodgkin's disease. CONCLUSIONS: There is a high risk for development of thyroid disease after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation of such patients.

Journal Article↗
PubMed1996

Congenital cholesteatomas of the middle ear: a different experience.

A retrospective analysis is presented of 44 cases of congenital cholesteatoma of the middle ear. Twenty-one patients had cholesteatoma localized to the posterosuperior mesotympanum in complete contrast to the commonly reported anterosuperior location seen in only two cases. The remaining 21 patients had cholesteatoma involving either the entire mesotympanum or epitympanum or both. The posteriorly located congenital cholesteatomas might represent a completely different entity and originate from the trapped epithelial cell rests in the posterior mesotympanum during the development of temporal bone. All but one patient were treated by using a closed tympanoplasty. Eight patients underwent a single-stage surgery. A preplanned second-stage procedure was performed in 33 patients, and three are awaiting their second stage. Residual disease was seen in 19 (57%) patients undergoing second-stage surgery. No patient has had recurrent disease so far. Thirty-eight (85%) patients had a preoperative air-bone gap of > or = 30 dB. Of the 33 patients considered for hearing results, 16 (48%) had a postoperative gap within 10 db.

Adolescent↗
PubMed1996

Melioidosis: a rare but not forgotten cause of fever of unknown origin.

Melioidosis is widely prevalent in Southeast Asia and northern Australia. Although it is believed to pose no current threat to the populations of developed countries, the increased mobility of people around the world and of Southeast Asian refugees to Western countries may change this. Its long incubation period may put a relatively large number of currently asymptomatic people at risk. It should be considered in the differential diagnosis of any febrile illness in a person who has visited an endemic area, especially if the presenting features are those of fulminant respiratory failure, if multiple pustular or necrotic skin or subcutaneous lesions develop, or if there is a radiologic pattern of tuberculosis from which tubercle bacilli cannot be demonstrated.

Adult↗
PubMed1995

DNA fingerprinting of Brassica juncea cultivars using microsatellite probes.

The genetic variability in the Brassica juncea cultivars was detected by employing in-gel hybridization of restricted DNA to simple repetitive sequences such as (GATA)4, (GACA)4 and (CAC)5. The most informative probe/enzyme combination was (GATA)4/EcoRI, yielding highly polymorphic fingerprint patterns for the B. juncea cultivars. This technique was found to be dependable for establishing the variety specific patterns for most of the cultivars studied, a prerequisite for germplasm preservation. The results of the present study were compared with those reported in our earlier study in which random amplification of polymorphic DNA (RAPD) was used for assessing the genetic variability in the B. juncea cultivars.

Base Sequence↗
PubMed1995

Thyrotropin receptor T cell epitopes in autoimmune thyroid disease.

The human TSH receptor represents the primary target of thyroid-stimulating immunoglobulins responsible for the hyperthyroidism of Graves' disease. In the present series of investigations, the distribution of T cell epitopes has been mapped using synthetic peptides spanning the entire extracellular region of the human TSH receptor. In vitro proliferative responses of the mononuclear cells were measured using flow cytometric analysis of bromodeoxyuridine incorporation into nuclei. In 8 of 11 samples from patients with Graves' disease, at least one (and up to 9) regions of the human TSH receptor induced proliferation, with the mean stimulation index being 39.8 +/- 47.3. No single universal stimulatory peptide was identified. In contrast, stimulation was not observed in three control subjects, while one control subject showed minimal stimulation (index of 5.7) to peptides encompassing a limited area (amino acids 31-65). The immunodominant epitope of patients with recent-onset Graves' disease was localized between amino acids 271 and 365, whereas the immunodominant epitope of patients with disease duration greater than 1 year localized between amino acids 91 and 215. We conclude that the bromodeoxyuridine incorporation method is a useful and important tool for detecting antigen-induced lymphocyte proliferation. The TSH receptor-specific T cells from different Graves' disease patients recognize variable distinct sites within the extracellular region of the TSH receptor, and the immunodominant epitope apparently shifts toward the N-terminus of the receptor protein during the course of treated Graves' disease.

Bromodeoxyuridine↗
PubMed1995

Surgical treatment of cholesteatoma in children.

Treating cholesteatoma in children is still controversial. This article reviews 93 cases of pediatric cholesteatoma operated on from 1983 to 1991 in the Gruppo Otologico, Placenza, Italy, and details the results in 83 children who underwent the intact canal wall technique. During second-stage surgery, residual cholesteatoma was detected in 38% of patients. Recurrent cholesteatoma was detected in 10% of patients treated with the intact canal wall technique. Residual cholesteatoma was seen in the middle ear cleft in 63%, in the epitympanum in 26%, and in the mastoid in 11% of cases. Social hearing level (< 25 dB) was achieved in 85% of cases with suprastructure, whereas only 53% of patients without suprastructure had these levels. In the treatment of cholesteatoma in children by use of the intact canal wall technique, a preplanned second-look operation is mandatory to eradicate the disease.

Adolescent↗
PubMed1995

Canal wall down mastoidectomy: causes of failure, pitfalls and their management.

Managing patients with failed canal wall down mastoidectomy, requires a meticulous approach to control the disease and restore hearing. The present article reviews the causes of failure of the primary procedure and pitfalls encountered in 105 patients referred to our centre for revision canal wall down mastoidectomy. At post-revision surgery there were no cases with residual or recurrent cholesteatoma. The failures in our revision procedure were due to tympanic membrane perforation which occurred in five per cent (n = 4) and intermittent otorrhoea in two per cent (n = 2). A dry cavity with adequate middle ear space allowed for optimum audiological function even in revision canal wall down procedures.

Adolescent↗
PubMed1995

Intratemporal hemangiomas involving the facial nerve: diagnosis and management.

Intratemporal vascular tumors involving the facial nerve are rare benign lesions. Because of their variable clinical features, they are often misdiagnosed preoperatively. This study presents a series of 21 patients with such lesions managed from 1977 to 1994. Facial nerve dysfunction was the most common complaint, present in 60% of the cases, followed by hearing loss, present in 40% of cases. High-resolution computed tomography, magnetic resonance imaging with gadolinium, and a high index of clinical suspicion is required for preoperative diagnosis of these lesions. Early surgical resection of these tumors permits acceptable return of facial nerve function in many patients.

Journal Article↗
PubMed1995

An easy, cost-effective and time-conserving method of studying the vascular anatomy of the base of the skull.

In this work we present a simple, rapid, cost-effective and time-conserving method of studying the vascular anatomy of the base of the skull. This method is based on the injection of the arteries and veins with an appropriate coloring solution that possesses the property of rapid solidification. This technique of preparation of the coloring solution and the method of injection is described in detail. The advantages and disadvantages of this technique are also discussed.

Journal Article↗
PubMed1995

Epidemiology of childhood acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is the second most common leukemia in children, with approximately 400 new cases occurring annually in the United States. Worldwide, the highest rates of childhood AML occur in Asia and the lowest rates are reported from India and South America. Numerous genetic risk factors for childhood AML have been defined, including Down syndrome, neurofibromatosis, and Fanconi anemia. Research into environmental risk factors has been limited by the rarity of this disease; however, studies of AML in adults have implicated ionizing radiation, solvents, and petroleum products as potential etiologic agents. The largest analytic study of childhood AML found that occupational exposures of either parent to pesticides, paternal exposure to petroleum products, and postnatal exposures to pesticides are increased in children with AML. In addition, maternal use of marijuana during pregnancy was associated with an increased risk of AML, especially the monocytic subtypes. Further study of childhood AML, including occurrence of the disease as a second malignancy, is needed in order to confirm these findings and to increase our understanding of this leukemia.

Adolescent↗