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1.
Nature ; 618(7966): 708-711, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37277615

ABSTRACT

Dust grains absorb half of the radiation emitted by stars throughout the history of the universe, re-emitting this energy at infrared wavelengths1-3. Polycyclic aromatic hydrocarbons (PAHs) are large organic molecules that trace millimetre-size dust grains and regulate the cooling of interstellar gas within galaxies4,5. Observations of PAH features in very distant galaxies have been difficult owing to the limited sensitivity and wavelength coverage of previous infrared telescopes6,7. Here we present James Webb Space Telescope observations that detect the 3.3 µm PAH feature in a galaxy observed less than 1.5 billion years after the Big Bang. The high equivalent width of the PAH feature indicates that star formation, rather than black hole accretion, dominates infrared emission throughout the galaxy. The light from PAH molecules, hot dust and large dust grains and stars are spatially distinct from one another, leading to order-of-magnitude variations in PAH equivalent width and ratio of PAH to total infrared luminosity across the galaxy. The spatial variations we observe suggest either a physical offset between PAHs and large dust grains or wide variations in the local ultraviolet radiation field. Our observations demonstrate that differences in emission from PAH molecules and large dust grains are a complex result of localized processes within early galaxies.

2.
Front Immunol ; 15: 1383644, 2024.
Article in English | MEDLINE | ID: mdl-38915397

ABSTRACT

Background: Existing criteria for predicting patient survival from immunotherapy are primarily centered on the PD-L1 status of patients. We tested the hypothesis that noninvasively captured baseline whole-lung radiomics features from CT images, baseline clinical parameters, combined with advanced machine learning approaches, can help to build models of patient survival that compare favorably with PD-L1 status for predicting 'less-than-median-survival risk' in the metastatic NSCLC setting for patients on durvalumab. With a total of 1062 patients, inclusive of model training and validation, this is the largest such study yet. Methods: To ensure a sufficient sample size, we combined data from treatment arms of three metastatic NSCLC studies. About 80% of this data was used for model training, and the remainder was held-out for validation. We first trained two independent models; Model-C trained to predict survival using clinical data; and Model-R trained to predict survival using whole-lung radiomics features. Finally, we created Model-C+R which leveraged both clinical and radiomics features. Results: The classification accuracy (for median survival) of Model-C, Model-R, and Model-C+R was 63%, 55%, and 68% respectively. Sensitivity analysis of survival prediction across different training and validation cohorts showed concordance indices ([95 percentile]) of 0.64 ([0.63, 0.65]), 0.60 ([0.59, 0.60]), and 0.66 ([0.65,0.67]), respectively. We additionally evaluated generalization of these models on a comparable cohort of 144 patients from an independent study, demonstrating classification accuracies of 65%, 62%, and 72% respectively. Conclusion: Machine Learning models combining baseline whole-lung CT radiomic and clinical features may be a useful tool for patient selection in immunotherapy. Further validation through prospective studies is needed.


Subject(s)
Antibodies, Monoclonal , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Tomography, X-Ray Computed , Humans , Lung Neoplasms/mortality , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Male , Female , Tomography, X-Ray Computed/methods , Antibodies, Monoclonal/therapeutic use , Middle Aged , Aged , Machine Learning , Risk Assessment , Antineoplastic Agents, Immunological/therapeutic use , Prognosis , B7-H1 Antigen , Radiomics
3.
Horm Metab Res ; 45(1): 47-53, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22956309

ABSTRACT

Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and may delay emptying. The aim of this work was to identify relationships between serum nutrition markers including 25-OH vitamin D and gastric motility measures in Gp patients. We enrolled 59 consecutive gastric motility clinic patients (48 females, 11 males; mean age 44 years; 42 idiopathic; 17 diabetes mellitus) with Gp symptoms. The 25-OH vitamin D levels, for most patients slightly above the lower limit of normal (96.98 nmol/l ± 60.99), were lowest in diabetic range (DM) (75.68 nmol/l ± 34.22) vs. idiopathic (ID) (105.03 nmol/l ± 67.08) gastroparesis patients. First hour GET: one unit increase in 25-OH vitamin D level was associated 0.11% improvement (95% CI -0.22, 0.01 p=0.056) in gastric motility in all patients; this association, although marked in ID Gp patients, (-0.13, CI -0.25, -0.01 p=0.034), was not seen in DM Gp, (0.2, CI -0.45, 0.87, p=0.525). Fourth hour GET: Every unit increase of 25-OH vitamin D was associated with significant improvement in all patients, ( 0.11% CI -0.23, 0.01, p=0.053), and some weak improvement in ID group, (0.11% -0.24, 0.01, p=0.076) and absent in patients with DM (0.03, CI -0.66, 0.72, p=0.932). It is concluded that 25-OH vitamin D levels may influence gastric emptying. Underlying mechanisms for this observation might include the impact of 25-OH vitamin D on the health of the enteric nervous system. 25-OH vitamin D contributions to enteric nerve functions should be explored, particularly where autonomic nervous system comorbidities exist.


Subject(s)
Gastrointestinal Motility/physiology , Gastroparesis/blood , Gastroparesis/physiopathology , Vitamin D/blood , Adult , Blood Proteins/metabolism , Female , Gastric Emptying , Humans , Male , Micronutrients/blood
5.
Trauma Case Rep ; 33: 100479, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34027002

ABSTRACT

Hypercoagulability after trauma is a known entity. Following significant trauma, most guidelines advise anticoagulation treatment for venous thromboembolism (VTE) prophylaxis. VTE following minor trauma convoyed with arterial or systemic embolization dictate the need to search for uncommon source of thromboembolic complications. This is a report of an unusual case of pulmonary and systemic emboli complicated by splenic abscess following minor trauma in a patient with Diabetes Mellitus as the first presentation of patent foramen ovale (PFO).

6.
IEEE Trans Pattern Anal Mach Intell ; 30(4): 746-51, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18276979

ABSTRACT

A framework for robust foreground detection that works under difficult conditions such as dynamic background and moderately moving camera is presented in this paper. The proposed method includes two main components: coarse scene representation as the union of pixel layers, and foreground detection in video by propagating these layers using a maximum-likelihood assignment. We first cluster into "layers" those pixels that share similar statistics. The entire scene is then modeled as the union of such non-parametric layer-models. An in-coming pixel is detected as foreground if it does not adhere to these adaptive models of the background. A principled way of computing thresholds is used to achieve robust detection performance with a pre-specified number of false alarms. Correlation between pixels in the spatial vicinity is exploited to deal with camera motion without precise registration or optical flow. The proposed technique adapts to changes in the scene, and allows to automatically convert persistent foreground objects to background and re-convert them to foreground when they become interesting. This simple framework addresses the important problem of robust foreground and unusual region detection, at about 10 frames per second on a standard laptop computer. The presentation of the proposed approach is complemented by results on challenging real data and comparisons with other standard techniques.


Subject(s)
Algorithms , Artificial Intelligence , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Pattern Recognition, Automated/methods , Signal Processing, Computer-Assisted , Video Recording/methods , Reproducibility of Results , Sensitivity and Specificity
7.
Otolaryngol Head Neck Surg ; 138(2): 209-16, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18241718

ABSTRACT

OBJECTIVE: Randomized, double-blinded, placebo-controlled, clinical trial to determine the effectiveness of palatal implants for treatment of mild/moderate obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN AND SETTING: Sixty-two non-obese adults with history of snoring, daytime sleepiness, and mild/moderate OSAHS, were randomized to receive palatal implants (n = 31) or placebo procedure (n = 31). Complete follow-up including quality of life (QOL, SF-36), snoring visual analog scale (VAS), and Epworth Sleepiness Scale (ESS) data were obtained in 62 patients. Seven patients refused follow-up polysomnography for a total of 55 patients (29 implant and 26 placebo). RESULTS: The treatment group (change in score of -7.9 +/- 7.7) was significantly improved compared with the placebo group (change in score of 0.9 +/- 4.3) for apnea/hypopnea index (AHI) (P < 0.0001), QOL, SF-36 (P < 0.0001), snoring VAS (P < 0.0001), and ESS (P = 0.0002). CONCLUSIONS: Palatal implants improve AHI, QOL, snoring intensity, and daytime sleepiness for selected patients with mild/moderate OSAHS.


Subject(s)
Palate, Soft/surgery , Prostheses and Implants , Prosthesis Implantation/methods , Sleep Apnea, Obstructive/surgery , Snoring/surgery , Adult , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Polysomnography , Prospective Studies , Prosthesis Design , Quality of Life , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/physiopathology , Snoring/diagnosis , Snoring/physiopathology , Surveys and Questionnaires , Syndrome , Treatment Outcome
8.
Article in English | MEDLINE | ID: mdl-29205691

ABSTRACT

BACKGROUND: Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility. METHODS: Fourteen patients with symptoms of gastroparesis (Gp) who were refractory to drug/device were selected from 443 Gp patients from 2013 to 2015 who were treated at the University of Louisville motility center. All patients underwent a structural and psychiatric evaluation along with detailed psychological and behavioral examination to rule out eating disorders. We performed detailed neuromuscular evaluation and all 14 patients received at least 12 weeks of intravenous immunoglobulin (400 mg/kg infusion weekly). Response was defined subjectively (symptomatic improvement) using standardized IDIOM score system. KEY RESULTS: All 14 patients had serological evidence and/or tissue evidence of immunological abnormality. Post-IVIG therapy, there was a significant improvement in symptoms scores for nausea, vomiting, early satiety, and abdominal pain. CONCLUSIONS AND INFERENCES: Although limited by the absence of placebo group, the data illustrate the role of autoimmunity and neuromuscular evaluation in patients with gastroparesis and support the utility of a diagnostic trial of immunotherapy in an effort to improve therapeutic outcomes for such patients.


Subject(s)
Gastroparesis/therapy , Immunoglobulins, Intravenous/therapeutic use , Immunotherapy/methods , Adolescent , Adult , Female , Gastroparesis/immunology , Humans , Male , Middle Aged , Symptom Assessment , Treatment Outcome , Young Adult
9.
IEEE Trans Image Process ; 16(2): 545-53, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17269646

ABSTRACT

A framework for inpainting missing parts of a video sequence recorded with a moving or stationary camera is presented in this work. The region to be inpainted is general: it may be still or moving, in the background or in the foreground, it may occlude one object and be occluded by some other object. The algorithm consists of a simple preprocessing stage and two steps of video inpainting. In the preprocessing stage, we roughly segment each frame into foreground and background. We use this segmentation to build three image mosaics that help to produce time consistent results and also improve the performance of the algorithm by reducing the search space. In the first video inpainting step, we reconstruct moving objects in the foreground that are "occluded" by the region to be inpainted. To this end, we fill the gap as much as possible by copying information from the moving foreground in other frames, using a priority-based scheme. In the second step, we inpaint the remaining hole with the background. To accomplish this, we first align the frames and directly copy when possible. The remaining pixels are filled in by extending spatial texture synthesis techniques to the spatiotemporal domain. The proposed framework has several advantages over state-of-the-art algorithms that deal with similar types of data and constraints. It permits some camera motion, is simple to implement, fast, does not require statistical models of background nor foreground, works well in the presence of rich and cluttered backgrounds, and the results show that there is no visible blurring or motion artifacts. A number of real examples taken with a consumer hand-held camera are shown supporting these findings.


Subject(s)
Algorithms , Artifacts , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Information Storage and Retrieval/methods , Video Recording/methods , Motion , Numerical Analysis, Computer-Assisted , Signal Processing, Computer-Assisted
10.
Otolaryngol Head Neck Surg ; 137(3): 471-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17765778

ABSTRACT

OBJECTIVES: To confirm feasibility of transnasal placement of a wireless pH-monitoring capsule in the upper esophagus, and to determine the positive predictive value of LPR and GERD signs and symptoms for diagnosis of LPR in patients with OSAHS. STUDY DESIGN: Prospective, nonrandomized, IRB-approved study of 89 OSAHS patients with and without symptoms and signs of LPR. METHODS: After complete history including QOL survey and fiberoptic laryngoscopy, patients underwent transnasal placement of the pH-monitoring capsule and wireless data collection for 24 hours. RESULTS: 77 of 89 consecutive patients underwent successful placement of wireless pH-monitoring capsule (86.5% success rate) and completed the study. 55 (71.4%) OSAHS patients had positive pH studies. 10.4% of these patients reported no symptoms or signs of LPR, indicating occult disease. CONCLUSION: Success rates of placement, tolerability, morbidity, and complications are excellent. Wireless upper esophageal pH monitoring is safe and effective for diagnosing LPR in patients with OSAHS.


Subject(s)
Esophageal pH Monitoring/instrumentation , Esophagoscopy/methods , Gastroesophageal Reflux/diagnosis , Hypopharynx , Nasal Cavity , Adult , Feasibility Studies , Female , Gastroesophageal Reflux/complications , Humans , Male , Middle Aged , Predictive Value of Tests , Sleep Apnea, Obstructive/complications
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 1087-1090, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28268514

ABSTRACT

The Mitral Valve is a structure on the left side of the human heart that regulates the flow of oxygenated blood into the Left Ventricle and also helps maintain the pressure within the Left Ventricle when the blood gets pumped to the rest of the body from the Left Ventricle. Pathology of the Mitral Valve often manifests through structural changes in the anatomy. Assessment of Mitral Valve pathology as well as determination of specific interventions require quantification of various structures of the Mitral Valve and one of these structures of interest is the Mitral Valve annulus. Three dimensional echocardiography is a popular imaging technique that clinicians use for volumetric quantification of cardiac structures - but manual quantification is cumbersome and subjective. In this paper we describe a semi-automated approach for maximum-a-posteriori estimation of the Mitral Valve annulus from three-dimensional echocardiography images using a simple analytic shape model coupled with a Näive Bayes classifier. We validate our approach against manual annotations on over 15 real patient cases with an average localization error ≤ 2.59 mm.


Subject(s)
Echocardiography, Three-Dimensional , Mitral Valve/diagnostic imaging , Bayes Theorem , Humans
12.
IEEE Trans Biomed Eng ; 63(2): 449-58, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26258932

ABSTRACT

GOAL: Rheumatoid arthritis (RA) is characterized by inflammation within the joint space as well as erosion or destruction of the bone surface. We believe that volumetric (3-D) ultrasound imaging of the joints in conjunction with automated image-analysis tools for segmenting and quantifying the regions of interest can lead to improved RA assessment. METHODS: In this paper, we describe our proposed algorithms for segmenting 1) the 3 -D bone surface and 2) the 3-D joint capsule region. We improve and extend previous 2-D bone extraction methods to 3-D and make our algorithm more robust to the intensity loss due to surface normals facing away from incident acoustic beams. The extracted bone surfaces coupled with a joint-specific anatomical model are used to initialize a coarse localization of the joint capsule region. The joint capsule segmentation is refined iteratively utilizing a probabilistic speckle model. RESULTS: We apply our methods on 51 volumes from 8 subjects, and validate segmentation results with expert annotations. We also provide the quantitative comparison of our bone detection with magnetic resonance imaging. These automated methods have achieved average sensitivity/precision rates of 94%/93% for bone surface detection, and 87%/83% for joint capsule segmentation. Segmentations of normal and inflamed joints are compared to demonstrate the potential of using proposed tools to assess RA pathology at the joint level. CONCLUSION: The proposed image-analysis methods showed encouraging results as compared to expert annotations. SIGNIFICANCE: These computer-assisted tools can be used to help visualize 3-D anatomy in joints and help develop quantitative measurements toward RA assessment.


Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Algorithms , Finger Joint/diagnostic imaging , Foot Joints/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Ultrasonography
13.
Int J Radiat Oncol Biol Phys ; 40(4): 845-50, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9531369

ABSTRACT

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.


Subject(s)
Ependymoma/radiotherapy , Infratentorial Neoplasms/radiotherapy , Spinal Cord Neoplasms/radiotherapy , Supratentorial Neoplasms/radiotherapy , Adolescent , Adult , Analysis of Variance , Child , Ependymoma/mortality , Female , Humans , Infratentorial Neoplasms/mortality , Male , Neoplasm Recurrence, Local , Prognosis , Radiotherapy/adverse effects , Spinal Cord Neoplasms/mortality , Supratentorial Neoplasms/mortality , Survival Rate
14.
Int J Radiat Oncol Biol Phys ; 42(1): 147-54, 1998 Aug 01.
Article in English | MEDLINE | ID: mdl-9747832

ABSTRACT

PURPOSE: Time-dose relationships have proven important in many cancer sites. This study evaluates the time factors involved in the successful postoperative radiotherapy of medulloblastoma, based on a 30-year experience in a single institution. METHODS AND MATERIALS: Fifty-three patients with medulloblastoma received postoperative craniospinal radiotherapy with curative intent between 1963 and 1993. Seven patients (13%) underwent biopsy alone, 28 patients (53%) had subtotal excision, and 18 patients (34%) had gross total excision. Eleven patients received adjuvant chemotherapy. The mean posterior fossa dose was 53.1 Gy; most patients received 54.0 Gy (range, 34.3 to 69.6 Gy). For 41 patients receiving once-a-day therapy, the mean dose was 50.6 Gy (range, 34.3 to 56.0 Gy). For 12 patients receiving twice-a-day therapy, the mean dose was 61.8 Gy (range, 52.6 to 69.6 Gy). Minimum follow-up was 2 years, and median follow-up was 10.7 years. Survival, freedom from relapse, and disease control in the posterior fossa were calculated using the Kaplan-Meier method, and multivariate analysis was performed for prognostic factors. Variables related to radiotherapy were examined, including dose to the craniospinal axis, dose to the posterior fossa, fractionation (once-a-day vs. twice-a-day), use of adjuvant chemotherapy, risk group [high (> or =T3b or > or =M1) or low (< or =T3a and M0-MX)], interval between surgery and radiotherapy (excluding patients receiving chemotherapy before radiotherapy), and duration of radiotherapy. RESULTS: At 5 and 10 years, overall survival rates were 68 and 64%, respectively, and freedom-from-relapse rates were 61 and 52%, respectively. Rates of disease control in the posterior fossa at 5 and 10 years were 79 and 68%, respectively. At 5 years, absolute survival rates after biopsy alone, subtotal excision, and gross total excision were 43, 67, and 78%, respectively (p=0.04), and posterior fossa control rates were 27, 89, and 83%, respectively (p=0.004). Duration of the treatment course was the only radiotherapy-related variable with a significant impact on freedom from relapse and posterior fossa control. For patients whose radiation treatment duration was < or =45 days, posterior fossa control was 89% at 5 years, compared with 68% for those treated for >45 days (p=0.01). Duration of treatment also affected freedom from relapse at 5 years: < or =45 days (76%) compared with >45 days (43%), p=0.004. CONCLUSION: Our study demonstrates that if adequate doses are used, then radiotherapy treatment duration will significantly affect the outcome in terms of control of disease in the posterior fossa and freedom from relapse. Fractions of at least 1.75 Gy given once a day, or a twice-a-day regimen should yield optimal local control results.


Subject(s)
Cerebellar Neoplasms/radiotherapy , Cranial Irradiation , Medulloblastoma/radiotherapy , Adolescent , Adult , Aged , Analysis of Variance , Cerebellar Neoplasms/surgery , Child , Child, Preschool , Combined Modality Therapy , Cranial Fossa, Posterior , Disease-Free Survival , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Male , Medulloblastoma/surgery , Middle Aged , Time Factors
15.
Pediatrics ; 83(6): 986-92, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2657628

ABSTRACT

Behcet disease is rare in children. There are only two reports of Behcet disease in childhood, describing seven patients. Three pediatric patients are described, in whom the age of onset ranged from 6 to 11 years. Aphthous stomatitis and arthritis were present in all of the patients; genital ulcers, iridocylitis, erythema nodosum, and CNS involvement were present in two patients. Other manifestations included Stevens-Johnson-like eruption, fever of unknown origin, and testicular involvement. All of the patients responded to glucocorticoids; two were also treated with colchicine and one was treated with chlorambucil. In two patients, follow-up of more than 10 years was done, with complete cure in one patient and benign course of illness in the other. Because of the rarity of the disease in childhood and the difficulty in making the diagnosis, there is not enough awareness by pediatricians concerning this disease.


Subject(s)
Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Behcet Syndrome/etiology , Behcet Syndrome/pathology , Child , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Recurrence
16.
Bone Marrow Transplant ; 24(12): 1323-7, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10627642

ABSTRACT

The pharmacokinetics of tacrolimus have been studied in healthy volunteers and in adults undergoing bone marrow transplantation. However, there is little information on the pharmacokinetics of tacrolimus in children undergoing BMT. We studied pharmacokinetics of tacrolimus in seven patients (age 8-17 years) undergoing allogeneic stem cell transplantation. Four patients received matched unrelated donor (MUD) transplants, two underwent HLA-matched related donor transplants, and one underwent an umbilical cord blood donor transplant. All patients received tacrolimus by continuous infusion at 0.03-0.04 mg/kg/day beginning on the day prior to transplant. Tacrolimus whole blood concentrations were monitored by microparticle enzyme immunoassay. Our goal was to maintain a blood tacrolimus level of 10-20 microg/ml. Once patients were tolerating oral medications, tacrolimus infusion was converted to oral dosing using a 4:1 conversion. Dose of tacrolimus and resulting tacrolimus concentrations were recorded and the total body clearance of tacrolimus was calculated retrospectively. The mean clearance, based on first steady-state tacrolimus concentrations necessary for achieving a therapeutic level (10-20 microg/ml), was 108.1 ml/h/kg (range 79.7-142.0 ml/h/kg), greater than that reported in adult BMT patients (71 +/- 34 ml/h/kg). The average dose required to achieve that therapeutic range was 0.0354 mg/kg/day as an intravenous continuous infusion. Over the entire course of intravenous tacrolimus, mean clearance was 97.0 ml/h/kg (range 33.4-153.3 ml/h/kg). In six of the seven patients, clearance values dropped after 2-4 weeks of therapy by an average of 32.5 ml/h/kg. In two patients, sharp drops in clearance were temporally related to changes in liver function tests. Three of the seven patients died of severe acute GVHD; all these had undergone matched unrelated donor transplantation, and two of these three had initial clearance levels over 120 ml/h/kg. Thus, children appear to have more rapid tacrolimus clearance than adults and may need to begin therapy earlier in order to obtain stable and optimal levels. More studies are needed to confirm these preliminary results.


Subject(s)
Tacrolimus/pharmacokinetics , Adolescent , Bone Marrow Transplantation/methods , Child , Dose-Response Relationship, Drug , Female , Graft vs Host Disease/drug therapy , Humans , Liver Function Tests , Male , Retrospective Studies , Tacrolimus/administration & dosage , Tacrolimus/blood , Time Factors
17.
Bone Marrow Transplant ; 34(5): 405-11, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15247929

ABSTRACT

The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.


Subject(s)
Anemia, Sickle Cell/therapy , Cord Blood Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Anemia, Sickle Cell/epidemiology , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/immunology , Graft vs Host Disease/immunology , HLA-A Antigens/immunology , HLA-B Antigens/immunology , HLA-DR Antigens/immunology , HLA-DRB1 Chains , Humans , Male , Risk Factors , Tissue Donors , Transplantation Chimera , Transplantation, Homologous
18.
Radiat Res ; 94(3): 508-12, 1983 Jun.
Article in English | MEDLINE | ID: mdl-6856787

ABSTRACT

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100-1500 rad: Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0-300 rad, followed by a decline between 300-750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad.


Subject(s)
Growth Hormone/metabolism , Pituitary Gland, Anterior/radiation effects , Animals , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Male , Pituitary Gland, Anterior/cytology , Pituitary Gland, Anterior/metabolism , Rats , Rats, Inbred Strains
19.
J Clin Pharmacol ; 33(9): 811-5, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8227477

ABSTRACT

The pharmacokinetics of codeine were determined after oral administration of codeine sulfate (60 mg) with sickle cell patients (SCPs) and healthy controls (HCs). Plasma concentrations of codeine were measured by reversed-phase high-pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated using both compartmental and noncompartmental analysis. No significant differences were observed in time to reach maximum peak plasma concentration (tmax) (1.0 +/- 0.4 versus 1.4 +/- 1.0 hours), maximum peak plasma concentration (Cmax) (172 +/- 25 versus 225 +/- 97 ng/mL), area under the curve (AUC infinity) (590 +/- 96 versus 779 +/- 234 ng*h/mL), and Cl/F (104 +/- 17 versus 89 +/- 27 L/h) between SCPs and HCs. Conversely, significant differences were observed in mean residence time (MRT) (3.7 +/- 0.3 versus 4.7 +/- 0.3 hours) and half-life (t1/2) (1.7 +/- 0.2 versus 2.8 +/- 0.3 hours). In a separate study, significant differences were observed in the in vitro plasma protein binding of codeine in SCPs (66.0 +/- 8.6%) and HCs (30.5 +/- 2.7%) as well as in vivo binding (68.4 +/- 11.1% for SCPs versus 29.2 +/- 3.4% for HCs). Codeine is a relatively high-extraction drug that is primarily eliminated by metabolism in the liver. Generally, the clearance of such drugs is approximately equal to hepatic blood flow and is not affected by changes in protein binding. Therefore, the change in t1/2 observed in SCPs can be attributed to changes in volume of distribution rather than clearance.


Subject(s)
Anemia, Sickle Cell/metabolism , Codeine/pharmacokinetics , Adult , Anemia, Sickle Cell/blood , Codeine/blood , Dose-Response Relationship, Drug , Half-Life , Humans
20.
Urology ; 14(3): 256-9, 1979 Sep.
Article in English | MEDLINE | ID: mdl-483500

ABSTRACT

To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.


Subject(s)
Hypertension/physiopathology , Indomethacin/pharmacology , Kidney/blood supply , Animals , Blood Pressure/drug effects , Dogs , Erythropoietin/biosynthesis , Female , Hypertension/drug therapy , Indomethacin/therapeutic use , Ischemia/physiopathology , Kidney/metabolism , Male , Nephrectomy , Prostaglandins E/biosynthesis , Prostaglandins F/biosynthesis , Regional Blood Flow , Renal Artery Obstruction/physiopathology , Renin/biosynthesis
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