TLS-CHOP and the role of RNA-binding proteins in oncogenic transformation.
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Adipose Tissue↗
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Results for “TLS”
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Portable modular transducer system for the measurement of stabilizing forces in TLS-HKA orthoses.
We describe an instrumentation package built for the measurement of stabilizing forces in thoraco-lumbar-sacral-hip-knee-ankle orthoses. The system uses inexpensive and robust transducers mounted on the orthoses. Instrumentation is contained in a back-pack; the associated software package may be used for a wide variety of transducer applications.
Adolescent↗
Macromolecular TLS refinement in REFMAC at moderate resolutions.
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Chemistry Techniques, Analytical↗
Relationship of BAL and lung tissue CD4+ and CD8+ T lymphocytes, and their ratio in idiopathic pulmonary fibrosis.
BACKGROUND: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. STUDY OBJECTIVE: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. PATIENTS AND METHODS: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens of 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. RESULTS: In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAL fluid (r = 0.846 and p = 0.001 vs r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). CONCLUSION: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.
Bronchoalveolar Lavage Fluid↗
Equal distribution of competitive long-term repopulating stem cells in the CD34+ and CD34- fractions of Thy-1lowLin-/lowSca-1+ bone marrow cells.
CD34 antigen is present on most, if not all, human hematopoietic stem cells (HSCs). Consistent with this pattern of expression, we recently reported that primitive murine HSCs defined as competitive long-term repopulating units (CRUs) are highly enriched among CD34+ bone marrow (BM) cells (one CRU/2500 cells). However, in agreement with one recent report that some murine HSCs do not express CD34 (Science 273:242), we observed that 15% of phenotypically defined Thy-1lowLin-/lowSca-1+ (TLS) stem cells were CD34- by fluorescence-activated cell sorting. To examine further the nature of CD34 expression on murine hematopoietic cells, we separated TLS cells into CD34+ (0.022% of BM cells) and CD34- (0.005% of BM cells) fractions, confirmed their phenotype by reverse transcriptase-polymerase chain reaction analysis of CD34 transcripts, and evaluated them in a variety of in vitro and in vivo assays. The CD34+ TLS population contained most (93-95%) of the day 12 spleen colony-forming units (CFU-S) and in vitro colony-forming cells (CFCs). Cobblestone area-forming cells (CAFCs) able to proliferate on a murine bone marrow stromal cell line (SyS-1) represented one of every 5 CD34+ TLS and one of every 31 CD34 TLS cells. When lethally irradiated mice were injected with 100 CD34+ TLS cells, all animals survived and began to recover circulating leukocytes, platelets, and erythrocytes by 15 days. In contrast, only 40% of mice injected with 100 CD34- TLS cells were radioprotected, and hematopoietic reconstitution in surviving mice was not apparent until 21 days. The frequency of CRUs in CD34+ and CD34 TLS cells was determined by injecting limiting numbers of cells into lethally irradiated Ly-5 congenic hosts together with 10(5) "compromised" BM cells to provide radioprotection. CRUs able to regenerate and maintain lymphoid and myeloid cells for at least 6 months in primary and 5 months in secondary hosts represented one of every 156 CD34+ TLS and one of every 35 CD34- TLS cells. However, when normalized for the proportion of TLS cells that were CD34+ or CD34-, it was determined that the recovery of CRU among CD34+ and CD34- TLS cells was equivalent (46% and 54%, respectively). These data are consistent with the previous description of repopulating HSCs among CD34-c-kit+Sca-1+Lin- cells (Science 273:242, 1996) and provide additional evidence that TLS cells are functionally heterogeneous and can be further fractionated on the basis of CD34 expression. Overall, approximately 95% of CFCs, CFU-S, and CAFCs in the TLS population were found to be CD34+, whereas more primitive CRU were distributed equally among CD34+ and CD34 TLS cells. These results should enable better characterization of the most primitive stem cells in murine BM.
Animals↗
Incidence, medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin's lymphoma in four European countries.
Hyperuricemia (HU) and tumour lysis syndrome (TLS) are complications of acute leukaemia and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective of this study was to define incidence and calculate health care cost associated with HU and TLS. 788 acute leukaemia and NHL patients from Belgium, The Netherlands, Spain and UK were screened retrospectively for HU and TLS. Resource use related to HU and TLS was recorded and costs were calculated applying local unit costs. Results showed that HU occurred in 18.9% of patients, and 27.8% of them fulfilled TLS criteria. The cost of HU without TLS was 672 euros (SE 181), the cost of TLS 7,342 euros (SE 1,412). TLS requiring dialysis incurred an average cost of 17,706 euros. In conclusion, it is noted that the observed incidence rates were lower than earlier reports. In addition, some risk factors for HU and TLS (e.g. paediatric patients versus adults) were not associated with increased rates of HU or TLS as a consequence of higher rates of prevention. TLS cases incurred 11 times higher costs than HU cases in which TLS was absent. The main cost drivers in TLS are interventions requiring intensive care.
Acute Disease↗
In vivo packaging of brome mosaic virus RNA3, but not RNAs 1 and 2, is dependent on a cis-acting 3' tRNA-like structure.
The four encapsidated RNAs of brome mosaic virus (BMV; B1, B2, B3, and B4) contain a highly conserved 3' 200-nucleotide (nt) region encompassing the tRNA-like structure (TLS) which is required for packaging in vitro (Y. G. Choi, T. W. Dreher, and A. L. N. Rao, Proc. Natl. Acad. Sci. USA 99:655-660, 2002). To validate these observations in vivo, we performed packaging assays using Agrobacterium-mediated transient expression of RNAs and coat protein (CP) (P. Annamalai and A. L. N. Rao, Virology 338:96-111, 2005). Coexpression of TLS-less constructs of B1 or B2 or B3 and CP mRNAs in Nicotiana benthamiana leaves resulted in packaging of TLS-less B1 and B2 but not B3, suggesting that packaging of B3 requires the TLS in cis. This conjecture was confirmed by the efficient packaging of a B3 chimera in which the viral TLS was replaced with a cellular tRNA(Tyr). When N. benthamiana leaves were infiltrated with a mixture of transformants containing wild-type B1 (wtB1) plus wtB2 plus a TLS-less B3 (wtB1+wtB2+TLS-lessB3), the 3' end of progeny B3 was restored by heterologous recombination with that of either B1 or B2. This intrinsic cis-requirement of TLS in promoting B3 packaging was further confirmed when a mixture containing agrotransformants of TLS-less B1+B2+B3 was supplemented with either wtB4 or a 3' 200-nt or 3' 336-nt untranslated region (UTR) of B3. Northern blot analysis followed by sequencing of B3 progeny revealed that replication of TLS-less B3, but not TLS-less B1 or B2, was fully restored due to recombination with TLS from transiently expressed wtB4 or the B3 3' UTR. Collectively, these observations suggested that the requirement of a cis-acting TLS is distinct for B3 compared with B1 or B2.
3' Untranslated Regions↗
Tear lipocalins: potential lipid scavengers for the corneal surface.
PURPOSE: To investigate the dynamic effect of tear lipocalins (TLs), the major lipid-binding protein in tears, at aqueous-cornea and lipid-aqueous interfaces, and their potential contribution to surface tension in the tear film. METHODS: Human apo- and holo-TLs were applied to the aqueous subphase in a Langmuir trough, and changes in surface pressure were measured. Changes in the contact angle of tear components were observed on Teflon and ferric-stearate-treated surfaces. A nitroxide-labeled derivative of lauric acid and a fluorescence-labeled derivative of palmitic acid were used to monitor the dynamic interaction of lipid removed from a hydrophobic surface by the major tear components in solution. RESULTS: TLs increase the surface pressure at the aqueous-air interface by penetrating, spreading, and rearranging on the surface. Apo-TLs show a longer diffusion-dependent induction time than holo-TLs due to more extensive oligomerization of the apoprotein. Kinetic analysis of relaxation time suggests that apo-TLs have more rapid surface penetration and rearrangement than holo-TLs, indicative of a more flexible structure in apo-TLs. TLs reduce the contact angle of solutions on lipid films, a property that is greater with TLs than other tear proteins. TLs, unlike lysozyme and lactoferrin, remove labeled lipids from hydrophobic surfaces and deliver them into solution. CONCLUSIONS: TLs are potent lipid-binding proteins that increase the surface pressure of aqueous solutions while scavenging lipids from hydrophobic surfaces and delivering them to the aqueous phase of tears. These data suggest important functional roles for TLs in maintaining the integrity of the tear film.
Carrier Proteins↗
Temporary DPOAE level shifts, ABR threshold shifts and histopathological damage following below-critical-level noise exposures.
DPOAE temporary level shift (TLS) at 2f(1)-f(2) and f(2)-f(1), ABR temporary threshold shift (TTS), and detailed histopathological findings were compared in three groups of chinchillas that were exposed for 24 h to an octave band of noise (OBN) centered at 4 kHz with a sound pressure level (SPL) of 80, 86 or 92 dB (n=3,4,6). DPOAE levels at 39 frequencies from f(1)=0.3 to 16 kHz (f(2)/f(1)=1.23; L(2) and L(1)=55, 65 and 75 dB, equal and differing by 10 dB) and ABR thresholds at 13 frequencies from 0.5 to 20 kHz were collected pre- and immediately post-exposure. The functional data were converted to pre- minus post-exposure shift and overlaid upon the cytocochleogram of cochlear damage using the frequency-place map for the chinchilla. The magnitude and frequency place of components in the 2f(1)-f(2) TLS patterns were determined and group averages for each OBN SPL and L(1), L(2) combination were calculated. The f(2)-f(1) TLS was also examined in ears with focal lesions equal to or greater than 0.4 mm. The 2f(1)-f(2) TLS (plotted at f(1)) and TTS aligned with the extent and location of damaged supporting cells. The TLS patterns over frequency had two features which were unexpected: (1) a peak at about a half octave above the center of the OBN with a valley just above and below it and (2) a peak (often showing enhancement) at the apical boundary of the supporting-cell damage. The magnitudes of the TLS and TTS generally increased with increasing SPL of the exposure. The peaks of the TLS and TTS, as well as the peaks and valleys of the TLS pattern moved apically as the SPL of the OBN was increased. However, there was little consistency in the pattern relations with differing L(1), L(2) combinations. In addition, neither the 2f(1)-f(2) nor f(2)-f(1) TLS for any L(1), L(2) combination reliably detected focal lesions (100% OHC loss) from 0.4 to 1.2 mm in size. Often, the TLS went in the opposite direction from what would be expected at focal lesions. Recovery from TLS and TTS was also examined in seven animals. Both TLS and TTS recovered partially or completely, the magnitude depending upon exposure SPL.
Animals↗
CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis.
BACKGROUND: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. METHODS: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. RESULTS: Elastase positive cells accounted for the 7.04% +/- 1.1 of total cells, CD68+ cells for the 16.6% +/- 2, CD3+ TLs for the 28.8% +/- 7, CD4+ TLs for the 14.5 +/- 4 and CD8+ TLs for the 13.8 +/- 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01). CONCLUSION: In UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.
CD8-Positive T-Lymphocytes↗
[Possible synergic action of some drug combinations against Mycoplasma gallisepticum].
Yamamoto and Adler's method (1956), making use of the modified medium of Edward, was employed to determine the minimal concentrations of gentamicin (GMC), erytrhomycin (ERM), oleandomycin (OMC) spectinomycin (SPM), tetracycline (TC), tylosin (TLS), and chloramphenicol (CA), all of them showing bactericidal effects on Mycoplasma gallisepticum-S6, applied alone or in combination. In vitro studies showed that relatively most effective were TLS, GMC, and SPM, when used alone. Combining the antibiotics by two in the most cases led to a pronounced synergic effect. Comparatively most effective were the combinations of TLS+ERM; TLS+TC; CA+TC; CA+OMC; TLS+CA; TLS+OMC; SPM+TC; and SPM+CA. Lowest absolute concentrations of the individual components showed the combinations of TLS+GMC; TLS+TC; TLS+ERM; TLS+CA; TLS+SPM; TLS+OMC; SPM+TC; and SPM+CA.
Anti-Bacterial Agents↗
Acute tumor lysis syndrome in solid tumors--a case report and review of the literature.
PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.
Adult↗
Allele-specific suppression of a defective trans-Golgi network (TGN) localization signal in Kex2p identifies three genes involved in localization of TGN transmembrane proteins.
Kex2 protease (Kex2p) and Ste13 dipeptidyl aminopeptidase (Ste13p) are required in Saccharomyces cerevisiae for maturation of the alpha-mating factor in a late Golgi compartment, most likely the yeast trans-Golgi network (TGN). Previous studies identified a TGN localization signal (TLS) in the C-terminal cytosolic tail of Kex2p consisting of Tyr-713 and contextual sequences. Further analysis of the Kex2p TLS revealed similarity to the Ste13p TLS. Mutation of the Kex2p TLS results in transport of Kex2p to the vacuole by default. When expression of a GAL1 promoter-driven KEX2 gene is shut off in MAT(alpha) cells, the TGN becomes depleted of Kex2p, resulting in a gradual decline in mating competence which is greatly accelerated by TLS mutations. To identify the genes involved in localization of Kex2p, we isolated second-site suppressors of the rapid loss of mating competence observed upon shutting off expression of a TLS mutant form of Kex2p (Y713A). Seven of 58 suppressors were allele specific, suppressing point mutations at Tyr-713 but not deletions of the TLS or entire C-terminal cytosolic tail. By linkage analysis, the allele-specific suppressors defined three genetic loci, SOI1, S0I2, and S0I3. Pulse-chase analysis demonstrated that these suppressors increased net TGN retention of both Y713A Kex2p and a Ste13p-Pho8p fusion protein containing a point mutation in the Ste13p TLS. SOI1 suppressor alleles reduced the efficiency of localization of wild-type Kex2p to the TGN, implying an impaired ability to discriminate between the normal TLS and a mutant TLS. soi1 mutants also exhibited a recessive defect in vacuolar protein sorting. Suppressor alleles of S0I2 were dominant. These results suggest that the SOI1 and S0I2 genes encode regulators or components of the TLS recognition machinery.
Alleles↗
Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia.
PURPOSE: To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. RESULTS: Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. CONCLUSION: TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality.
Adult↗
Triple lipid screening test: a homogeneous sequential assay for HDL-cholesterol, total cholesterol, and triglycerides.
BACKGROUND: The analysis of lipids in serum lipoprotein fractions is useful in assessing the risk for coronary artery disease, but it typically involves performing multiple tests. An automated single-tube assay, referred to as the triple lipid screening (TLS) test, can be used for measuring HDL-cholesterol (HDL-C), total cholesterol, and triglycerides (TGs) with no specimen pretreatment. METHODS: The first part of the assay is based on a homogeneous assay for HDL-C that uses either an anti-apolipoprotein B antibody (TLS-A test) or a polyanion (TLS-B test) that blocks the enzymatic measurement of cholesterol on the non-HDL fraction. After the addition of deoxycholate, which solubilizes the unreacted cholesterol from the non-HDL fraction, the remaining cholesterol in the sample is subsequently measured enzymatically. Using the same enzyme detection system as the cholesterol assay, TGs are measured in the last step, after the addition of the enzymes for the TG assay. RESULTS: The TLS assay (y) had acceptable analytic performance and compared favorably with standard tests (x) for each analyte: for HDL-C, TLS-A = 0.99x + 0.19 (R = 0.980); TLS-B = 1.00x - 0.15 (R = 0.974); for total cholesterol, TLS-A = 1.03x + 0.12 (R = 0.997); TLS-B = 1.07x - 0.30 (R = 0.965); and for TGs, TLS-A = 1.02x + 0.02 (R = 0.988); TLS-B = 1.04x - 0.28 (R = 0.980). CONCLUSIONS: The TLS test is a single-tube homogeneous assay for the analysis of all of the major serum lipoprotein fractions and can be used as a simple screening test for the detection of hyperlipidemia.
Autoanalysis↗
Tumor lysis syndrome in children with non-Hodgkin lymphoma.
This study was designed to evaluate the incidence of tumor lysis syndrome (TLS) among children with non-Hodgkin lymphoma and to define whether renal involvement can be associated with higher incidence of TLS after chemotherapy. Medical charts of 59 patients were reviewed. TLS was diagnosed using laboratory and clinical criteria. Renal involvement was diagnosed based on ultrasound and CT scan findings. Laboratory TLS occurred in 7 patients (11.85%) and clinical TLS was observed in 7 patients (11.85%) as well. In 5 out of 14 TLS patients, hemodialysis was required to correct electrolyte abnormalities and TLS related death was reported overall in 3 patients. Sex, age, pretreatment LDH, and initial WBC count were not associated with higher incidence of TLS after chemotherapy, but a significant correlation was found between pretreatment renal involvement at imaging studies and development of TLS after chemotherapy (p = .027). The results indicate that despite all preventive measures, tumor lysis syndrome still occurs in children with non-Hodgkin lymphoma following chemotherapy. Patients who have evidence of renal involvement at imaging studies are more likely to develop TLS after chemotherapy.
Child↗
New data on the short-term effects of tone exposure.
Three experiments studied the short-term effects of moderate- and high-level tone exposures on threshold and loudness. Experiment 1 measured temporary threshold and loudness shifts (TTS and TLS) due to a 1000-Hz exposure at a moderate level (65 dB SPL) as a function of exposure duration. Whereas there was no significant TTS, TLS was as high as 11 dB and recovered rapidly. TLS was significantly larger for the highest test levels. TTS and TLS were practically independent of exposure duration. Experiment 2 measured TTS and TLS as a function of test frequency following exposures to 500-, 1000-, or 3000-Hz tones at 65 dB SPL. The frequency patterns of TLS were established at test levels of 20-60 phons. TLS and TTS had similar frequency patterns with a maximum at the exposure frequency, but TLS patterns were higher and more extended than those of TTS. In experiment 3, subjects were exposed to a 1000-Hz tone at a high level (90 dB SPL). Frequency patterns for TTS or TLS at a 60-dB test level were measured repeatedly during 5 1/2 min after the end of exposure. Two short-term effects were observed immediately after the exposure: (1) a slight TTS (4.5 dB) at the exposure frequency which disappeared 2 to 3 min later; and (2) a large TLS (9 dB) which extended over the whole range of test frequencies, recovered rapidly, and had disappeared by 330 s after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustic Stimulation↗
Rasburicase for the management of tumor lysis syndrome in neonates.
OBJECTIVE: To describe the management of tumor lysis syndrome (TLS) with rasburicase in 2 patients who presented with cancer within the first month of life and compare and contrast both cases with respect to their underlying renal physiology, management, and eventual outcome. CASE SUMMARY: TLS developed in 2 neonates born at 38 weeks' gestational age; both were managed in part with rasburicase. One patient was a 21-day-old infant who received 2 days of induction chemotherapy for the treatment of congenital Stage IV-S neuroblastoma. With a single 0.2 mg/kg dose of rasburicase, the serum urate level normalized and the infant completed therapy without incident. The second patient was a 4-day-old neonate with congenital precursor-B cell acute lymphoblastic leukemia who presented with spontaneous TLS complicated by renal dysfunction. Despite several doses of intravenous rasburicase (2 doses of 0.1 mg/kg and 4 doses of 0.2 mg/kg), as well as aggressive supportive therapy, the infant died of complications arising from uncontrolled TLS. DISCUSSION: Neonates may be at particular risk for TLS given their immature renal function and its predisposition toward metabolic derangements. While rasburicase has the potential to provide a rapid reversal of TLS in this patient population, when TLS is complicated by pre-existing acute renal failure, additional interventions and alternative anti-tumor strategies may be necessary for a successful outcome. When managing TLS in infancy, clinicians must consider the relative degree of renal immaturity and its predisposition toward metabolic derangements. CONCLUSIONS: Rasburicase appears to be well tolerated and effective in lowering serum urate concentrations in the treatment of therapy-related TLS in neonates. However, in instances of spontaneous TLS complicated by the normally low glomerular filtration rate in the newborn infant, the use of rasburicase and other supportive care measures may still be inadequate, warranting further study.
Adrenal Gland Neoplasms↗