Magainin-mediated disruption of stratum corneum lipid vesicles.
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Animals↗
Biomedical subjects
A Krishnan
Publications and source records attributed to A Krishnan.
Colorectal cancer among users of aspirin and non-steroidal antiinflammatory drugs.
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Adult↗
Craniofacial surgery in Oman: a preliminary study of 10 cases.
Craniofacial surgery requires a highly specialized surgical team, appropriate precision delicate instruments, dedicated anesthetist, and upgraded intensive care unit facilities. This type of surgery is undertaken in a large number of congenital problems such as encephalocele, craniosynostosis, hypertelorism, tumors of the craniofacial region, and for craniofacial injuries. We present our experience with craniofacial surgery in 10 patients during a 15-month period at Khoula Hospital, Muscat, Sultanate of Oman. These operations were the first of this kind to be done in this part of the world. This article highlights the need for developing craniofacial units in the Gulf region.
Adolescent↗
Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease.
We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn's disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8alpha(+)TCRalphabeta(+) T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8alpha(+)TCRgammadelta(+)/CD8alpha(+)TCRalphabeta(+) ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-gamma and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn's disease.
Adoptive Transfer↗
Hematologic Aspects of HIV/AIDS.
This review addresses various aspects of HIV infection pertinent to hematology, including the consequences of HIV infection on specific aspects of hematopoiesis and an update on the current biologic, epidemiologic and therapeutic aspects of AIDS-related lymphoma and Hodgkin's disease. The results of the expanding use of progenitor cell transplantation in HIV infected patients are also reviewed. In Section I, Dr. Scadden reviews the basis for HIV dysregulation of blood cell production, focusing on the role of the stem cell in HIV disease. T cell production and thymic function are discussed, with emphasis placed upon the mechanisms of immune restoration in HIV infected individuals. Results of clinical and correlative laboratory studies are presented. In Section II, Dr. Levine reviews the recent epidemiologic trends in the incidence of lymphoma, since the widespread availability of highly active anti-retroviral therapy (HAART). The biologic aspects of AIDS-lymphoma and Hodgkin's disease are discussed in terms of pathogenesis of disease. Various treatment options for these disorders and the role of concomitant anti-retroviral and chemotherapeutic intervention are addressed. Drs. Zaia and Krishnan will review the area of stem cell transplantation in patients with AIDS related lymphoma, presenting updated information on clinical results of this procedure. Additionally, they report on the use of gene therapy, with peripheral blood CD34+ cells genetically modified using a murine retrovirus, as a means to treat underlying HIV infection. Results of gene transfer experiments and subsequent gene marking in HIV infected patients are reviewed.
Acquired Immunodeficiency Syndrome↗
Gunshot wounds to the ureter: a 40-year experience at Grady Memorial Hospital.
PURPOSE: Because of the morbidity associated with missed ureteral injuries, a high index of suspicion must be present to diagnose this type of injury. We reviewed our 40 years of trauma experience at Grady Memorial Hospital. MATERIALS AND METHODS: We retrospectively reviewed the records of 118 patients with ureteral injuries secondary to a gunshot wound to the ureter from 1960 to 1999. All cases were reviewed for the mechanism of injury, location, initial urinalysis, imaging modalities, associated injuries, operative procedures and complications. RESULTS: Our population consisted of patients 14 to 71 years old, of whom 66 had right ureteral, 51 had left ureteral and 1 had bilateral injury. Urinalysis revealed no evidence of blood in the urine in 15% of the patients in whom the test was performed. Excretory urography had a false-negative rate of 33%. The injury was located at the proximal, mid and distal ureter in 43, 38 and 37 cases, respectively. Multiple surgical approaches were used depending on the location and severity of the defect. Only 1 patient had an isolated ureteral injury, while the remainder had associated injuries. Complications were present in 24 cases. CONCLUSIONS: To our knowledge this series of ureteral injuries is the largest reported to date. Because preoperative urinalysis and imaging studies are unreliable for ruling out injury, a high index of suspicion must be present. Furthermore, a predefined trauma protocol, as defined in our algorithm, decreases the number of missed ureteral injuries that may potentially complicate the outcome of an already critical case.
Adolescent↗
Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.
We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)
Adolescent↗
Optimization of inclusion body solubilization and renaturation of recombinant human growth hormone from Escherichia coli.
Recombinant human growth hormone (r-hGH) was expressed in Escherichia coli as inclusion bodies. In 10 h of fed-batch fermentation, 1.6 g/L of r-hGH was produced at a cell concentration of 25 g dry cell weight/L. Inclusion bodies from the cells were isolated and purified to homogeneity. Various buffers with and without reducing agents were used to solubilize r-hGH from the inclusion bodies and the extent of solubility was compared with that of 8 M urea as well as 6 M Gdn-HCl. Hydrophobic interactions as well as ionic interactions were found to be the dominant forces responsible for the formation of r-hGH inclusion bodies during its high-level expression in E. coli. Complete solubilization of r-hGH inclusion bodies was observed in 100 mM Tris buffer at pH 12.5 containing 2 M urea. Solubilization of r-hGH inclusion bodies in the presence of low concentrations of urea helped in retaining the existing native-like secondary structures of r-hGH, thus improving the yield of bioactive protein during refolding. Solubilized r-hGH in Tris buffer containing 2 M urea was found to be less susceptible to aggregation during buffer exchange and thus was refolded by simple dilution. The r-hGH was purified by use of DEAE-Sepharose ion-exchange chromatography and the pure monomeric r-hGH was finally obtained by using size-exclusion chromatography. The overall yield of the purified monomeric r-hGH was approximately 50% of the initial inclusion body proteins and was found to be biologically active in promoting growth of rat Nb2 lymphoma cell lines.
Animals↗
Radiographic findings in tuberculosis of the calvarium.
We reviewed the pattern of involvement of the calvarium by tuberculosis (TB) in five patients and the role of imaging in its management. Four patients presented with localised scalp swelling and one with generalized seizures. Radiographs revealed lucent lesions with minimal surrounding sclerosis in the frontal (2), parietal (2) and occipital (1) bones. CT showed lesions involving the entire thickness of the calvarium and accompanying contrast-enhancing soft tissue. The patient presenting with seizures had a ring-enhancing lesion in the parietal lobe in addition to the extra-axial lesions. Although radiographs in all cases demonstrated calvarial TB, CT showed the extent of the defect, involvement of adjacent soft tissues, and in one case an intra-axial lesion. Radiographs suffice for follow-up of these patients.
Adolescent↗
Imaging in isolated sacral tuberculosis: a review of 15 cases.
OBJECTIVE: To review imaging studies of isolated involvement of the sacrum due to tuberculosis and determine the role of imaging in the diagnosis and management of these patients. DESIGN AND PATIENTS: A retrospective analysis of 15 cases of isolated sacral tuberculosis imaged with MR imaging was performed. The CT images were also reviewed where available, and the various lesion characteristics were identified. We also reviewed the medical records in an attempt to determine the impact of the imaging studies on the management of these patients. RESULTS: Fifteen patients (5 male, 10 female) presented with symptoms of 3-15 months' duration. Chronic localized backache with muscle spasm was the commonest presenting symptom; discharging sinuses with abscess formation was found in six patients, five of whom were children. MR imaging of the sacrum revealed a hypointense marrow signal on T1-weighted images and hyperintense signal on T2-weighted images in 14 of 15 patients, the S2 vertebra being always involved. CT revealed osteolytic changes in the sacrum in all the five patients in whom CT was performed. All patients showed marked clinical improvement within 1 year of anti-tuberculous chemotherapy. CONCLUSION: Isolated tuberculosis of the sacrum is uncommon but should be suspected in patients presenting with chronic low backache or children with discharging sinuses/abscesses and showing sacral destruction on CT or MR imaging. MR imaging can identify cases and enables early institution of antituberculous chemotherapy.
Adolescent↗
Inferring Physical Parameters from Images of Vibrating Carbon Nanotubes.
We describe a hidden parameter inferencing algorithm for deducing the length, width, and vibration profile from images of thermally excited single-wall carbon nanotubes. With accurate estimates of these parameters, the Young's modulus can be deduced. The algorithm is sensitive to shot noise in the image, primarily because of the low nanotube image contrast. Noise causes the nanotube length and width to be overestimated, and the vibration amplitude to be underestimated. After correcting for shot noise, we infer an average value of the Young's modulus of = 1.20 +/- 0.20 TPa, which is larger than the currently accepted value for graphite.
Journal Article↗
Characteristics of patients presenting with central retinal artery occlusion with and without giant cell arteritis.
BACKGROUND: In patients with concurrent central retinal artery occlusion (CRAO) and giant cell arteritis (GCA), prompt recognition and early treatment are crucial to prevent further visual loss in the contralateral eye. The objective of this study was to describe a series of patients with CRAO resulting from GCA and to compare them with patients with isolated CRAO. METHODS: The patient database for a retina service in Philadelphia was searched to identify patients admitted between 1983 and 1993 with a diagnosis of biopsyproven GCA and CRAO. For every patient with CRAO caused by GCA, the next patient admitted for management of acute isolated CRAO was identified; these latter patients constituted the control group. The visual acuity and baseline characteristics of the two groups were compared. RESULTS: Eleven patients with acute CRAO and GCA were admitted during the study period. In both the case and control groups seven patients (64%) were women and nine patients (82%) were white. Six subjects (54%) in the case group and seven (64%) in the control group had a history of hypertension; the values for diabetes mellitus were two (18%) and zero respectively. Four patients (36%) with CRAO and GCA were cigarette smokers, compared with eight patients (73%) with CRAO alone. None of these differences were statistically significant. Patients with CRAO related to GCA were more likely than those with isolated CRAO to have counting fingers or better vision at presentation (odds ratio 2.22 [95% confidence interval 0.37 to 13.2]), but this trend was not statistically significant. INTERPRETATION: Patients who presented with CRAO related to GCA were more than twice as likely as those with CRAO alone to have counting fingers or better visual acuity at the time of presentation. However, owing to the small sample, the power of this study to detect a true difference between the two groups was limited.
Adult↗
Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.
We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.
Acute Disease↗
Effects of allogeneic bone marrow transplantation on recipient bone mineral density: A prospective study.
Allogeneic bone marrow transplant (BMT) recipients have many known risk factors for developing decreased bone mineral density (BMD) after transplantation. We performed a prospective sequential evaluation of BMD in the lumbar spine and nondominant hip using dual-energy x-ray absorptiometry (DEXA) in a cohort of 47 adult patients (median age, 43 years) who were undergoing radiation-based BMT for hematologic malignancies. Baseline DEXA studies were performed before BMT and repeated at 3 to 4 months, 6 to 8 months, and 12 to 14 months after BMT. The majority of patients (60%) had been minimally treated with combination cytotoxic chemotherapy, having received no more than 1 treatment regimen before BMT. Graft-versus-host disease prophylaxis consisted of cyclosporine in combination with either methotrexate or prednisone, or both. Mean lumbar spine and hip BMD were normal before BMT (spine: 1.01 g/cm2, z score = 96%; hip: 0.86 g/cm2, z score = 100%) and gradually decreased (spine: 0.98 g/cm2, z score = 94%; hip: 0.76 g/cm2, z score = 91%) at 12 to 14 months. These declines were statistically significant (P < .006 and < .002 for lumbar spine; P < .001 and < .001 for hip). In addition, the sharpest decline occurred during the first 6 months after BMT and was more marked in the hip than the lumbar spine. These data suggest that BMT adversely affects BMD in this patient population.
Absorptiometry, Photon↗
Isolated optic nerve pseudotumour.
Isolated optic nerve involvement by the idiopathic inflammatory process is a rare finding and very few reports are available. Here a case of an isolated optic nerve inflammatory pseudotumour presenting with gradually progressive unilateral loss of vision is described. It showed dramatic response to a trial of steroids and its differential diagnoses are discussed.
Adult↗
Upregulation of endothelin B receptors in kidneys of DOCA-salt hypertensive rats.
Experiments were designed to elucidate the role of endothelin B receptors (ET(B)) on arterial pressure and renal function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy and were treated with either DOCA and salt (0.9% NaCl to drink) or placebo. DOCA-salt rats given the ET(B)-selective antagonist, A-192621, for 1 wk (10 mg. kg(-1). day(-1) in the food) had significantly greater systolic arterial pressure compared with untreated DOCA-salt rats (208 +/- 7 vs. 182 +/- 4 mmHg) whereas pressure in placebo rats was unchanged. In DOCA-salt, but not placebo rats, A-192621 significantly decreased sodium and water excretion along with parallel decreases in food and water intake. To determine whether the response in DOCA-salt rats was due to increased expression of ET(B) receptors, endothelin receptor binding was performed by using membranes from renal medulla. Maximum binding (B(max)) of [(125)I]ET-1, [(125)I]ET-3, and [(125)I]IRL-1620 increased from 227 +/- 42, 146 +/- 28, and 21 +/- 1 fmol/mg protein, respectively, in placebo rats to 335 +/- 27, 300 +/- 38, and 61 +/- 6 fmol/mg protein, respectively, in DOCA-salt hypertensive rats. The fraction of receptors that are the ET(B) subtype was significantly increased in DOCA-salt (0.88 +/- 0.07) compared with placebo (0.64 +/- 0.01). The difference between [(125)I]ET-3 and [(125)I]IRL-1620 binding is consistent with possible ET(B) receptor subtypes in the kidney. These results indicate that ET(B) receptors in the renal medulla are up-regulated in the DOCA-salt hypertensive rat and may serve to maintain a lower arterial pressure by promoting salt and water excretion.
Animals↗
Diastematomyelia and epidermoid cyst in the hemicord.
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Child, Preschool↗
Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma.
The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5-69 years). The median number of prior chemotherapy regimens was 2 (range, 1-4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3-158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1-12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%-61%), 47% (95% CI: 40%-53%), and 47% (95% CI: 40%-54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%-81%) as compared to 30% (95% CI: 16%-45%) for induction failure and 34% (95% CI: 26%-42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.
Adolescent↗