Hepatitis C virus and renal transplantation.
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Disease Progression↗
Biomedical subjects
N Shah
Publications and source records attributed to N Shah.
Liver transplantation: who and when?
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Humans↗
Interaction of chloramphenicol and the calcineurin inhibitors in renal transplant recipients.
Several case reports have described a pharmacokinetic interaction between chloramphenicol and the calcineurin inhibitors (CNIs). Based on these reports, we set out to characterize the effects of chloramphenicol on cyclosporine and tacrolimus trough concentrations in renal transplant recipients. We retrospectively evaluated daily trough CNI concentrations and compared them with baseline CNI concentrations prior to chloramphenicol. Six adult renal or pancreas/kidney transplant recipients received 11 courses of chloramphenicol. Of these, three received cyclosporine (6 episodes) and three received tacrolimus (5 episodes). The mean dose and duration of chloramphenicol was not significantly different between groups. Chloramphenicol coadministration increased mean cyclosporine troughs maximally by 41.3% on day 4, though overall differences were not significant using analysis of variance (anova). Tacrolimus trough levels increased to 99% above baseline on day 2, 151% on day 3, 161% on day 4, 191% on day 5, and to 207% on day 6 and reached statistical significance by anova (P = 0.001). These results confirm case reports and suggest that careful trough monitoring should be implemented if chloramphenicol is to be used with the CNIs.
Adult↗
Case 4. Chronic urticaria due to strongyloidiasis.
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Chronic Disease↗
Spectroscopy enhances the information content of optical mammography.
Near-infrared (NIR) diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on quantitative measurements of functional contrast between healthy and diseased tissue. In this study we measured the spectral dependence of tissue absorption (mu(a)) and reduced scattering (mu'(s)) in the breasts of 30 healthy women and one woman with a fibroadenoma using a seven-wavelength frequency-domain photon migration probe. Subjects included pre- and postmenopausal women between the ages of 18 and 64. Multi-spectral measurements were used along with a four-component fit to determine the concentrations of de-oxy and oxy-hemoglobin, water and lipids in breast. The scattering spectral shape was also quantified. Our measurements demonstrate that the measured concentrations of NIR analytes correlate well with known breast physiology. Although the tissue scattering at a single wavelength was found to have little value as a functional parameter, the dependence of the scattering on wavelength provided key insights into breast composition and physiology. Lipids and scattering spectra in the breast were found to increase and decrease, respectively, with increasing body mass index. Simple calculations are also provided to demonstrate potential penalties from ignoring the contributions of water and lipids in breast measurements. Finally, water is shown to be a possible indicator for detecting a fibroadenoma, whereas the hemoglobin saturation was found to be a poor indicator. Multi-spectral measurements, compared to measurements restricted to one or two wavelengths, provide additional information that may be useful in managing breast disease.
Breast↗
Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided prostate biopsy: a double-blind randomized controlled study.
PURPOSE: We performed a randomized, placebo controlled double-blind trial to evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom), that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: Patients referred for transrectal ultrasound guided prostate biopsy for the first time as an outpatient procedure were recruited subject to exclusion criteria and randomized to breathe Entonox or air via similar breath activated devices. At the end of the procedure patients completed a visual pain analog scale. Patients who refused study participation also completed the visual analog pain scale to assess the placebo effect of receiving gas through a mask. RESULTS: A total of 110 patients were studied. Statistical analysis using 1-way analysis of variance showed a highly significant difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001). This significant decrease in pain was noted in the Entonox versus air and Entonox versus placebo groups. There was no significant difference in the air and placebo groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy during the procedure, which resolved at completion of the procedure. In this group 49 patients would undergo this procedure again if needed. In 2 of the 45 patients in the group receiving air the procedure was abandoned due to pain, while another 19 would prefer more analgesia and 2 would prefer general anesthesia if the procedure was to be repeated. CONCLUSIONS: Our study shows that Entonox is a safe, rapidly acting and effective form of analgesia for the pain of prostate biopsy. We believe that it should be the analgesia of choice for this procedure.
Aged↗
Irreducible dorsal radiocarpal fracture dislocation with dissociation of the distal radioulnar joint: a case report.
We report a case of dorsal radiocarpal fracture dislocation with dissociation of the distal radioulnar joint. Closed reduction was unsuccessful due to interposition of the osteochondral fragments and open reduction and fixation was carried out with a satisfactory end result. The advantages of volar approach and use of external fixator in the management of this injury are discussed.
Adult↗
Therapeutic potential of yoga practices in modifying cardiovascular risk profile in middle aged men and women.
AIMS OF STUDY: To study effect of yoga on the physiological, psychological well being, psychomotor parameter and modifying cardiovascular risk factors in mild to moderate hypertensive patients. METHODS: Twenty patients (16 males, 4 females) in the age group of 35 to 55 years with mild to moderate essential hypertension underwent yogic practices daily for one hour for three months. Biochemical, physiological and psychological parameters were studied prior and following period of three months of yoga practices, biochemical parameters included, blood glucose, lipid profile, catecholmines, MDA, Vit. C cholinesterase and urinary VMA. Psychological evaluation was done by using personal orientation inventory and subjective well being. RESULTS: Results showed decrease in blood pressure and drug score modifying risk factors, i.e. blood glucose, cholesterol and triglycerides decreased overall improvement in subjective well being and quality of life. There was decrease in VMA catecholamine, and decrease MDA level suggestive decrease sympathetic activity and oxidant stress. CONCLUSION: Yoga can play an important role in risk modification for cardiovascular diseases in mild to moderate hypertension.
Adaptation, Physiological↗
Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein.
The most common chromosomal abnormality of infant acute lymphoblastic leukemia (ALL) is the t(4;11)(q21;q23) that gives rise to the MLL/AF4 fusion gene. Leukemic blasts expressing MLL/AF4 are arrested at an early progenitor stage with lymphoid or monocytoid characteristics. A novel B-lineage ALL cell line termed B-lineage-3 (BLIN-3) requiring human bone marrow (BM) stromal cell contact and interleukin-7 (IL-7) for optimal proliferation has been established. BLIN-3 cells have a CD19(+)/CD10(-) phenotype typical of infant ALL, and they harbor the t(4;11)(q21;q23) chromosomal translocation. Reverse transcription-polymerase chain reaction and Western blot analysis confirmed the presence of the MLL/AF4 fusion mRNA and protein in BLIN-3. Initial BLIN-3 cultures had a pro-B cell phenotype and did not express cytoplasmic or surface mu heavy chain. After approximately 5 months in culture on BM stromal cells plus IL-7, BLIN-3 sublines emerged expressing mu heavy chain and VpreB on the cell surfaces (ie, pre-B-cell receptor [BCR](+)). BLIN-3 cells expressing pre-BCR had the t(4;11)(q21;q23) translocation and expressed the MLL/AF4 fusion protein. Cross-linking the BLIN-3 pre-BCR led to enhanced cell proliferation, demonstrating that BLIN-3 expressed a functional pre-BCR. Increased acquisition of surface pre-BCR in BLIN-3 sublines was associated with loss of DJ rearrangements and the appearance of VDJ rearrangements. These results indicate that expression of the MLL/AF4 fusion protein is compatible with BM stromal cell and cytokine dependency, functional immunoglobulin gene segment rearrangement, and subsequent expression of a potentially diverse antigen receptor repertoire. Thus, the expression of MLL/AF4 is compatible with the normal developmental program of human B-lineage cells.
Antibodies, Monoclonal↗
Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis.
INTRODUCTION: Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? METHODS: Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. RESULTS: Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. CONCLUSIONS: Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.
Adult↗
Evaluation of use of a single intravaginal swab to detect multiple sexually transmitted infections in active-duty military women.
The accuracy and suitability of use of a single intravaginal swab (SIS) for polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and human papillomavirus infection was assessed in a cross-sectional study of 841 active-duty military women. The SIS, compared with standard diagnostic tests, allowed detection of more gonorrhea, more chlamydial infection, and more trichomoniasis. Sensitivity and specificity of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and 97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and 92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to those with cervical swabs tested for human papillomavirus. Assay of clinician-collected and self-collected SISs yielded prevalences similar to those of standard diagnostic tests for all sexually transmitted infections. Therefore, the use of SISs is acceptable for the simultaneous diagnosis of multiple sexually transmitted infections and has potential for use as a self-administered diagnostic tool with widespread applicability among women.
Administration, Intravaginal↗
Influence of injection drug use behavior on reported antiretroviral therapy use among women in the HIV Epidemiology Research study: on-site versus referral care.
BACKGROUND: HIV-infected injection drug users consistently report poor antiretroviral therapy use and little contact with health care providers. It has been suggested that the clinical setting where patients are seen affects the use of highly active antiretroviral therapy. OBJECTIVES: The purpose of this study was to determine whether ease of access to medical care affects self-report of taking antiretroviral therapy, particularly among female injection drug users. DESIGN: The study is a cross-sectional analysis from a prospective cohort study of HIV-infected women. SETTING: Women were enrolled at four sites in the United States: Detroit, Michigan, and Providence, Rhode Island, where on-site HIV care and treatment were offered, and Baltimore, Maryland, and the Bronx, New York, where all participants were referred elsewhere for HIV care and treatment. PATIENTS: Patients were HIV-infected women with no AIDS diagnosis or women who were at risk for HIV infection either through self-reported injection drug use since 1985 or through sexual contact. MEASUREMENTS: The study measured self-reported use of antiretroviral therapy (ART) alone or combined with Pneumocystis carinii (PCP) prophylaxis in the previous 6 months. RESULTS: In multivariate analysis including type of study site (on-site compared with referral care) and injection drug use, any self-reported ART use associated with low CD4 cell count category, older age, and race. However, at on-site care centers, women were equally likely to report ART use regardless of current, former, or no injection drug use, whereas at referral sites only women identified as sexual contacts were more likely to report any ART use, independent of all other variables. CONCLUSIONS: Easy access to medical care has an important impact on HIV-infected women receiving ART, particularly those who are active injection drug users.
Adolescent↗
Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation.
BACKGROUND: The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively. METHODS AND RESULTS: One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by >/=15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2+/-8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by >/=15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9+/-8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential). CONCLUSIONS: Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.
Adolescent↗
Dimer decimation and intricately nested localized-ballistic phases of a kicked Harper model.
A new decimation scheme is introduced to study localization transitions in tight binding models with long range interaction. Within this scheme, the lattice models are mapped to a vectorized dimer where an asymptotic dissociation of the dimer is shown to correspond to the vanishing of the transmission coefficient through the system. When applied to the kicked Harper model, the method unveils an intricately nested extended and localized phases in two-dimensional parameter space. In addition to computing transport characteristics with extremely high precision, the renormalization tools also provide a new method to compute quasienergy spectrum.
Journal Article↗
Clonal variation in the B-lineage acute lymphoblastic leukemia response to multiple cytokines and bone marrow stromal cells.
The acquisition of genetic abnormalities in human B-lineage acute lymphoblastic leukemia (ALL) culminates in the clonal expansion of bone marrow (BM)-derived leukemic blasts. However, the response of leukemic cells to signals transduced by the BM microenvironment is not completely understood. The present study describes a new human B-lineage ALL cell line designated BLIN-4 (B LINeage-4). BLIN-4 cells respond to multiple cytokines/human BM stromal cell-derived molecules. One subline (BLIN-4E) undergoes cell death in the absence of BM stromal cells or cytokines and slowly proliferates on human BM stromal cells supplemented with interleukin (IL)-7 + FLT3-ligand. Another subline (BLIN-4L) slowly proliferates in the absence of cytokines and BM stromal cells and shows robust proliferation on BM stromal cells supplemented with IL-7 + FLT3-ligand. Although human BM stromal cells are comparable with IL-7 + FLT3-ligand in supporting proliferation of BLIN-4L cells, neutralizing antibody experiments demonstrate that BLIN-4L expansion on BM stromal cells is IL-7/FLT3-ligand independent. BLIN-4L could also respond to human thymic stromal lymphopoietin. BLIN-4E and BLIN-4L have the identical immunoglobulin heavy chain rearrangement and a CD10(+)/CD19(+)/CD20(-)/CD22(+)/CD40(+)/mu heavy chain(-) phenotype. The original BM leukemic blasts harbored a ring chromosome 4 with a low percentage of cells also having either trisomy 8 or trisomy 18. The BLIN-4 sublines maintained the ring chromosome 4, but the trisomy 8 and trisomy 18 segregated into BLIN-4E and BLIN-4L, respectively. Thus, the BLIN-4 sublines exhibit biological characteristics consistent with a potential evolution in B-lineage ALL involving subclones with decreasing requirements on the BM microenvironment.
Adolescent↗
Noninvasive functional optical spectroscopy of human breast tissue.
Near infrared diffuse optical spectroscopy and diffuse optical imaging are promising methods that eventually may enhance or replace existing technologies for breast cancer screening and diagnosis. These techniques are based on highly sensitive, quantitative measurements of optical and functional contrast between healthy and diseased tissue. In this study, we examine whether changes in breast physiology caused by exogenous hormones, aging, and fluctuations during the menstrual cycle result in significant alterations in breast tissue optical contrast. A noninvasive quantitative diffuse optical spectroscopy technique, frequency-domain photon migration, was used. Measurements were performed on 14 volunteer subjects by using a hand-held probe. Intrinsic tissue absorption and reduced scattering parameters were calculated from frequency-domain photon migration data. Wavelength-dependent absorption (at 674, 803, 849, and 956 nm) was used to determine tissue concentration of oxyhemoglobin, deoxyhemoglobin, total hemoglobin, tissue hemoglobin oxygen saturation, and bulk water content. Results show significant and dramatic differences in optical properties between menopausal states. Average premenopausal intrinsic tissue absorption and reduced scattering values at each wavelength are 2.5- to 3-fold higher and 16-28 % greater, respectively, than absorption and scattering for postmenopausal subjects. Absorption and scattering properties for women using hormone replacement therapy are intermediate between premenopausal and postmenopausal populations. Physiological properties show differences in mean total hemoglobin (7.0 microM, 11.8 microM, and 19.2 microM) and water concentration relative to pure water (10.9 %, 15.3 %, and 27.3 %) for postmenopausal, hormone replacement therapy, and premenopausal subjects, respectively. Because of their unique, quantitative information content, diffuse optical methods may play an important role in breast diagnostics and improving our understanding of breast disease.
Breast Neoplasms↗
Improvement of anemia among HIV-infected injection drug users receiving highly active antiretroviral therapy.
Although anemia is common during HIV infection, it is unclear whether potent antiretroviral therapy would improve or worsen anemia. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a cohort of HIV-positive injection drug users (IDUs) in Baltimore, Maryland. At baseline, the overall prevalence of anemia was 40%. During mean follow-up of one year, among 102 subjects who received HAART, there was a mean increase in hemoglobin of 3.6 +/- 1.7 g/L (p =.0003) [corrected] and a mean decrease in log(10) plasma HIV load of 0.25 +/- 0.06 copies/ml (p <.0002) [corrected]. Among 103 control subjects who were not receiving antiretroviral medications, there was a mean decrease in hemoglobin of 4.2 +/- 1.1 g/L (p <.04) [corrected] and mean increase in log(10) plasma HIV load of 0.78 +/- 0.17 copies/ml (p <.0001) [corrected]. Multivariate analysis using mixed linear models showed that HAART was associated with an increase of hemoglobin of 0.223 g/L per month (p <.0001) after adjusting for body mass index, opportunistic infections, and gender. HAART was associated with an improvement in anemia, and potential mechanisms that may be involved include a reduction in opportunistic infections and the anemia of chronic disease and an improvement in nutritional status.
AIDS-Related Opportunistic Infections↗
Regulation of estrogenic and nuclear factor kappa B functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells.
The natural polyamines -putrescine, spermidine, and spermine- are essential for cell growth and differentiation. Polyamines are involved in several gene regulatory functions, although their mechanism(s) of action has not been elucidated. We investigated the role of polyamines in the function of NF-kappa B and estrogen receptor-alpha (ER alpha), two transcription factors implicated in breast cancer cell proliferation and cell survival, using MCF-7 breast cancer cells. We found that spermine facilitated the binding of ER alpha and NF-kappa B to estrogen response element (ERE)- and NF-kappa B response element (NRE), respectively, and enhanced ER alpha-mediated transcriptional activation in transient transfection experiments. We also found that the association of the co-regulatory protein CBP/p300 with ER alpha and NF-kappa B was increased by spermine treatment of MCF-7 cells. Spermine also increased the nuclear translocation of NF-kappa B compared to the control. In contrast, treatment of MCF-7 cells with polyamine analogs, BE-3-4-3 and BE-3-3-3, resulted in transcriptional inhibition of both ERE- and NRE-driven reporter plasmids. In addition, polyamine analogs inhibited the association of ER alpha and NF-kappa B with CBP/p300 and were unable to facilitate nuclear translocation of NF-kappa B. APO-BRDU assay demonstrated that polyamine analogs induced apoptosis, with a loss of the anti-apoptotic protein Bcl-2. These data show a gene regulatory function of polyamines involving transcriptional activation of ER alpha and NF-kappa B, potentially leading to the up-regulation of genes involved in breast cancer cell proliferation. Our results with BE-3-4-3 and BE-3-3-3 suggest that down-regulation of ER alpha- and NF-kappa B-regulated genes is a possible mechanism for the action of polyamine analogs in inducing apoptosis of breast cancer cells.
Apoptosis↗