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PubMed2006

Bortezomib-induced tumor lysis syndrome in multiple myeloma.

Tumor lysis syndrome (TLS) is exceedingly rare in multiple myeloma because of the relatively slow proliferation and response of the malignant cells. Bortezomib is a novel agent that inhibits proteasome and has shown activity against multiple myeloma. We report 8 episodes of TLS seen in 7 patients with bortezomib therapy, with or without dexamethasone, among 496 patients treated on 3 phase II multicenter studies. Biochemical abnormalities resolved with supportive therapy in 6 patients (including hemodialysis in 2) but proved fatal in 1. Clinicians should be alert for TLS in patients with myeloma with significant disease burden treated with bortezomib because of the potential for rapid onset of cell lysis with this agent.

Antineoplastic Agents↗

PubMed2006

Spontaneous tumor lysis syndrome in acute myeloid leukemia: two cases and a review of the literature.

Spontaneous tumor lysis syndrome (TLS) is a constellation of electrolyte abnormalities and acute renal failure, which occurs in the setting of rapid cell turnover prior to the administration of cytotoxic chemotherapy. While spontaneous TLS is well described in patients with Burkitt's lymphoma, it is thought to occur less commonly in other hematologic malignancies. We present two cases of spontaneous TLS in patients with newly diagnosed acute myeloid leukemia (AML) followed by a review of the literature in this field.

Aged↗

PubMed2000

Correlation between bone mineral density and sexual hormones in healthy Chinese women.

Osteoporosis is a common disease in women, but not in men. It is usually induced by the deficiency of estrogen after menopause. The lumbar spine is most often affected. We examined 74 healthy Chinese women in whom we measured serum estradiol (E2), estriol (E3), and total testosterone (TTT) by radioimmunoassay (RIA). The bone mineral density (BMD) of the total lumbar spine in the anterior (TLS-A) and lateral (TLS-L) position, the region of interest (ROI) of lateral spine (M-IALS), the forearm, and the total hip (TH) were scanned by a dual-energy X-ray absorptiometer. We found that (1) E2 and all BMD determinations declined significantly after menopause (p < 0.05 for all), except the BMD of TH; (2) the BMD of TLS-L, TH, and forearm correlated significantly with E2 (r = 0.2986, p < 0.05), E3 (r = 0.3380, p < 0.05), and TTT (r = 0.2867, p < 0.05), respectively, by partial correlation analysis. In conclusion, BMD at different sites of the skeleton correlated with the level of different sex hormones. It seems that BMD at different sites of the body is controlled by different sex hormones. Whether this phenomenon should be considered in the choice of hormone replacement therapy, or in improving the BMD diagnostic standard, needs further study.

Adult↗

PubMed2001

The total laboratory solution: a new laboratory E-business model based on a vertical laboratory meta-network.

Major forces are now reshaping all businesses on a global basis, including the healthcare and clinical laboratory industries. One of the major forces at work is information technology (IT), which now provides the opportunity to create a new economic and business model for the clinical laboratory industry based on the creation of an integrated vertical meta-network, referred to here as the "total laboratory solution" (TLS). Participants at the most basic level of such a network would include a hospital-based laboratory, a reference laboratory, a laboratory information system/application service provider/laboratory portal vendor, an in vitro diagnostic manufacturer, and a pharmaceutical/biotechnology manufacturer. It is suggested that each of these participants would add value to the network primarily in its area of core competency. Subvariants of such a network have evolved over recent years, but a TLS comprising all or most of these participants does not exist at this time. Although the TLS, enabled by IT and closely akin to the various e-businesses that are now taking shape, offers many advantages from a theoretical perspective over the current laboratory business model, its success will depend largely on (a) market forces, (b) how the collaborative networks are organized and managed, and (c) whether the network can offer healthcare organizations higher quality testing services at lower cost. If the concept is successful, new demands will be placed on hospital-based laboratory professionals to shift the range of professional services that they offer toward clinical consulting, integration of laboratory information from multiple sources, and laboratory information management. These information management and integration tasks can only increase in complexity in the future as new genomic and proteomics testing modalities are developed and come on-line in clinical laboratories.

Chemistry, Clinical↗

PubMed2003

[Acute myelogenous leukemia complicated with severe tumor lysis syndrome after a single day of idarubicin/cytarabine chemotherapy].

We describe a patient with acute myelogenous leukemia (AML) who was complicated with severe tumor lysis syndrome (TLS) after a single day of chemotherapy; a previously unreported occurrence. A 48-year-old man was admitted because of fever and bleeding tendency, and was diagnosed as having AML: M1. His white blood cell count (WBC) was 66, 300/microliter with 96% myeloblasts. Chemotherapy with idarubicin and cytarabine was started. On the second day of the therapy, he developed acute renal failure (ARF) and deterioration of disseminated intravascular coagulation (DIC) with a marked reduction in his WBC (8500/microliter). Immediately after a diagnosis of tumor lysis syndrome (TLS), the following chemotherapy was discontinued. Hemodiafiltration and hemofiltration were initiated to treat the ARF, concomitant with anticoagulant and antifibrinolysis therapy for the DIC. Chemotherapy with daunorubicin and cytarabine was resumed on the 12th day, recognizing a regrowth of leukemic cells. Thereafter a complete remission was achieved without recurrence of the TLS.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Emergency care: the tumor lysis syndrome.

The Tumor Lysis Syndrome (TLS) is a constellation of metabolic disturbances due to the rapid tumoral cell destruction, either spontaneous or induced by cytoreduction therapy, which manifests as an acute, subacute or chronic renal insufficiency. Hyperuricemia is the hallmark of the TLS. The therapy consists in management of hydro-electrolytic and metabolic disturbances, treatment of hyperuricemia (Allopurinol and a new therapeutical agent, Uricase), hemodialysis. If promptly supported during the TLS, a number of these patients have an excellent probability of long-term remission.

Adult↗

PubMedDate not supplied

Acute tumor lysis syndrome caused by palliative radiotherapy in patients with diffuse large B-cell lymphoma.

Acute tumor lysis syndrome (TLS) is a condition that results from the rapid destruction of tumor cells accompanied with a massive release of cellular breakdown products. Acute renal failure resulting from TLS has been reported in cases of hematologic malignancies, spontaneous or treatment induced, the latter especially by chemotherapy. We present the case of a patient with diffuse large B-cell lymphoma who developed radiotherapy-induced TLS and subsequently acute renal failure. He presented with a large mediastinal tumor compressing the airway, thus causing dyspnea. After 6 Gy/3 fractions/3 days of palliative radiotherapy for the tumor, a decrease in urine volume was noted as well as rapid tumor shrinking. Because this patient died despite previous prophylaxic anti-uric acid treatment and hemodialysis, his case illustrates the need to anticipate the development of acute renal failure, even though there may be no remarkable serum uric acid elevation after the initiation of radiotherapy.

Acute Disease↗

PubMed2005

[VEGF-induced tubulogenesis of endothelial cells from human brain malignant glioma in the three dimentional model].

OBJECTIVE: To compare the tubulogenesis capability of malignant glioma-derived microvessel endothelial cells (GDMEC) from human brain with that of ECV304 cells in a three dimentional model and to explore the significance of GDMEC in the study on angiogenesis. METHODS: The GDMEC were isolated from malignant gliomas of human brain and purified by selective binding to the monoclonal antibody against CD105 bound to the magnetic MACS MicroBeads. GDMEC and endothelial-like cell line ECV304 were compared with their capabilities of formatting tubule-like structure (TLS) in the three dimentional collagen matrix, with or without inducement by various concentration of vascular endothelial growth factor (VEGF). RESULTS: The obtained GDMEC had a high purification (98%) and could be successfully cultured in vitro. GDMECs formed more TLS than ECV304 cells of the same number and at the same time points. VEGF could induce rapid formation of TLS in a dose-dependent manner, however, ECV304 cells were less response to VEGF stimulation. CONCLUSIONS: GDMEC could maintain their endothelial characteristics and potential capability of angiogenesis. They were more response to VEGF than ECV304, therefore, more suitable for in vitro studies on tumor angiogenesis.

Brain Neoplasms↗

PubMed1996

[Hyperuricemia in hematological disorders].

Hyperuricemia is a common manifestation in various hematological disorders such as hemolytic anemias, megaloblastic anemia malignant lymphomas and leukemias. Tumor lysis syndrome (TLS) is a serious complication consists of hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia due to massive cell lysis, which occurs shortly after the onset of chemotherapy or radiotherapy for acute leukemias and malignant lymphomas. Acute renal failure may develop due to uric acid nephropathy. The risk factors of TLS are heavy tumor cell burden, rapid cell turn over rate and renal involvement of neoplastic cells. To prevent and control TLS, adequate intravenous hydration to keep patient's urine volume, alkalization of urine by sodium bicarbonate and inhibition of uric acid production by high dose allopurinol is recommended.

Bone Marrow↗

PubMed1999

Severe tumor lysis syndrome following splenic irradiation.

A 72-year-old man suffering from non-Hodgkin's lymphoma is described. After failing to respond to chlorambucil-prednisone regimen for three months, he was treated by splenic irradiation (total dose 500 cGY) in 10 consecutive daily doses. Two days after the last irradiation, the patient developed acute tumor lysis syndrome (TLS) with extreme blood levels of uric acid (33.7 mg/dl), phosphorus (13.7 mg/dl), potassium (6.08 mEq/l), and calcium (6.8 mg/dl). It should be remembered that the acute TLS, which usually occurs following chemotherapy, can also be radiation-induced.

Aged↗

PubMed1984

Cell surface phenotypes and expression of viral antigens of various human cell lines carrying human T-cell leukemia virus.

Human T-cell leukemia/lymphoma virus (HTLV)-carrying cells from various origins were characterized by cell surface markers and expression of HTLV antigens. Eight cell lines named TCL were obtained by transformation of peripheral blood leukocytes (PBL) of healthy donors or HTLV carriers in cocultures with HTLV-producer MT-2 cells. Nine cell lines named ILT were interleukin 2 (IL2)-dependent cell lines cloned from PBL of ATL patients and healthy HTLV-carriers. Tc-Kan9 cell line was also an IL2-dependent cell line clonally established from PBL culture stimulated with autologous TCL cells. Five cell lines named TL were established in vitro directly from PBL of an adult T-cell leukemia (ATL) patient and from ILT cells of an ATL patient and three HTLV-carriers, respectively, to grow autonomously without IL2. All the TCLs, ILTs, TLs and Tc-Kan9 possessed Leu-I antigen, a pan-T-cell marker. Leu3a antigen, a helper/inducer T-cell marker, was expressed on five of eight TCLs and all of the ILTs and TLs. Leu-2a, a cytotoxic/suppressor T-cell marker, was detected only on Tc-Kan9 but not others. Fresh ATL leukemic cells of patients had a helper/inducer T-cell marker. Ia, OKT9 and Tac antigens, markers for activated and differentiated T cells, were strongly expressed on all of the cell lines tested and fresh ATL leukemic cells were weakly positive for these antigens. Expression of HTLV antigens detected by mouse monoclonal antibodies and an ATL-patient serum varied among these cell lines. One TL, two ILTs and most of the fresh ATL leukemic cells did not express HTLV antigens on the cell surface. The other cell lines were all positive for the surface viral antigens. However, molecular species of antigens defined by radioimmunoprecipitation with an ATL-patient serum were not always identical among the cell lines. Molecular weights of polypeptides detectable in most of the cell lines were 62K, 46K, 40K, 24K, 21K and 19K which could never be detected in several control T-cell lines. 68K and 28K polypeptides were frequently detected in MT-2 and TGLs. GIN14, a mouse monoclonal antibody against HTLV core protein (p19) detected not only p19 in various cell lines but also p28, p29, p31 or p40 in certain cell lines tested. B-cell lines named LCL were established and cloned from PBL of two HTLV-carriers by EB-virus-induced transformation and they also expressed HTLV antigens, Ia, OKT9 and Tac antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2006

Acute renal failure in African children with Burkitt's lymphoma: a comparison of two treatment regimens.

BACKGROUND: The outcome for patients presenting with acute renal failure and Burkitt lymphoma (BLARF) without dialysis is poor. This was a retrospective non-randomized comparative study designed to determine the outcome of two different treatment protocols. METHODS: One group of patients (TPA) received oral allopurinol, intravenous (IV) cyclophosphamide, vincristine, methotrexate, furosemide, 8.4% sodium bicarbonate, and intrathecal (IT) methotrexate; the other (TPB) alternate day IV infusion of low dose cyclosphosphamide (125 mg/m(2) x 4 doses), IT methotrexate (Days 1 and 5) and aggressive pre-emptive anti-tumor lysis syndrome therapy including oral allopurinol and calcium lactate, IV calcium gluconate, salbutamol, insulin and infusions of furosemide, sodium bicarbonate and glucose. RESULTS: Nine of 16 received TPA, 7 received TPB. Post chemotherapy anemia was more severe with TPA (P < 0.05). TPB patients received significantly more chemotherapy than those in TPA (P = 0.04). All 16 had tumor lysis syndrome (TLS). Six of nine patients with TPA died from this (three from other causes), two deaths in TPB were due to causes other than tumor lysis. Other evaluated outcome indices were similar in both groups. CONCLUSION: Slow IV infusion of low dose cyclophosphamide given on alternate days in addition to pre-emptive anti-TLS measures (TPB) were associated with better outcome in BLARF patients compared to a high dose multiple chemotherapy regimen (TPA).

Acute Kidney Injury↗

PubMed2003

Atomic resolution structure of prokaryotic phospholipase A2: analysis of internal motion and implication for a catalytic mechanism.

We have found a secreted phospholipase A(2) (PLA(2), EC 3.1.1.4) from Streptomyces violaceoruber A-2688, which is the first PLA(2) identified in prokaryote, and determined its tertiary structure by NMR and X-ray analyses. In this study, we collected the X-ray diffraction data of the bacterial PLA(2) at room temperature (297 K) using conventional MoK(alpha) radiation and refined the structure at a 1.05 A resolution. The atomic resolution analysis led us to introduce disordered conformations and hydrogen atoms into a full anisotropic model. The molecular motion, which is expressed as the sum of rigid-body motion and internal motion of protein, is roughly estimated as the thermal motion when the X-ray diffraction data are collected at room temperature. In this study, we applied a TLS (rigid-body motion in terms of translation, libration, and screw motions) model to analyze the rigid-body motion of the bacterial PLA(2) and calculated the internal motion by subtracting the estimate of the rigid-body motion from the observed anisotropic temperature factor. We also subjected the TLS model to estimate the internal motion of the bovine pancreatic PLA(2) using the anisotropic temperature factor deposited in the Protein Data Bank. Both results indicate that the localization of regions exhibiting larger internal motion in the bacterial PLA(2) is almost the same as that in the bovine pancreatic PLA(2), suggesting that although the tertiary structure of the bacterial PLA(2) is strikingly different from that of the bovine pancreatic PLA(2), the internal motion, which is associated with the calcium(II) ion-binding, phospholipid-binding, and allosteric interfacial activation, is commonly observed in both PLA(2)s.

Anisotropy↗

PubMed1998

Spectral parameter estimation by an iterative quadratic maximum likelihood method.

An iterative quadratic maximum likelihood (IQML) method is applied to spectral parameter estimation of 1D NMR data. A careful comparison of the linear prediction (LP) method based on the singular value decomposition, the total least squares (TLS) method, and IQML has clearly demonstrated that IQML is superior to both the LP and TLS methods in terms of the accuracy and bias of the estimation. The superiority of the IQML method lies in the fact that constraints on the NMR signal can easily be incorporated into the iterative process. The iterative quadratic maximum likelihood method can be used to analyze NMR data directly or to provide a starting point for further data refinement.

Algorithms↗

PubMed1998

Transfer RNA mimicry in a new group of positive-strand RNA plant viruses, the furoviruses: differential aminoacylation between the RNA components of one genome.

Recent sequencing of the genomes of several furoviruses--fungus-transmitted rod-shaped positive-strand plant viruses--has suggested the presence of tRNA-like structures (TLSs) at the 3' ends of the genomic RNAs. We show here that the genomic RNAs of soil-borne wheat mosaic virus (SBWMV), beet soil-borne virus (BSBV), potato mop-top virus (PMTV), peanut clump virus (PCV), and Indian peanut clump virus (IPCV) all possess functional TLSs that are capable of high-efficiency valylation. While the SBWMV, BSBV, and PMTV TLSs are similar to those found in tymoviruses, the PCV and IPCV TLSs harbor an insertion of about 40 nucleotides between the two halves of the TLS. The valylated SBWMV and BSBV RNAs formed tight complexes with wheat germ EF-1 alpha.GTP (Kd = 2 to 11 nM), whereas valylated PMTV, PCV, and IPCV RNAs bound EF-1 alpha.GTP weakly (Kd > or = 50 nM). The TLS of PCV RNA2 differs from PCV RNA1 in lacking the major valine identity nucleotide in the anticodon and consequently is capable of only very inefficient valylation. This is the first case of differential aminoacylation between the RNA components of one genome.

Acylation↗

PubMed2002

Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

Adult↗

PubMed2005

From networks to populations: the development and application of respondent-driven sampling among IDUs and Latino gay men.

One of the challenges in studying HIV-risk behaviors among gay men is gathering information from a non-biased sample, as traditional probability sampling methods cannot be applied in gay populations. Respondent-Driven Sampling (RDS) has been proposed as a reliable and bias-free method to recruit "hidden" populations, such as gay men. The aim of this study is to assess the feasibility and effectiveness of RDS to sample Latino gay men and transgender persons. This was carried out when we used RDS to recruit participants into a study that investigated community involvement on HIV/AIDS sexual risk behaviors among Latino gay and bisexual men, and transgender (male-to-female) persons in Chicago and San Francisco. The population coverage of RDS was then compared to simulated time-location sampling (TLS). Recruitment differences were observed across cities, but the samples were comparable. RDS showed broader population coverage than TLS, especially among individuals at high risk for HIV.

Adult↗

PubMed1993

Electrocorticography in patients with medically intractable temporal lobe seizures. I. Quantification of epileptiform discharges prior to resective surgery.

We studied retrospectively the intraoperative preresection electrocorticograms (ECoGs) of 72 patients undergoing surgery for medically intractable, mostly complex partial, temporal lobe seizures (TLS). Quantification of interictal epileptiform discharges (EDs) detected visually at each electrode location in 2 min recording epochs included computations of ED rates (EDs/min) and cumulative voltages (CuVs) (microV/min). Of 6388 EDs, 81% involved the infratemporal surface, 18% the lateral temporal surface and 1% the orbital frontal area. Forty-eight patients (67%) demonstrated multiple (up to 5 or more), temporally independent foci. Dominant foci in medial and lateral infratemporal locations were about equally common and were significantly more frequent than in lateral temporal locations. Rankings of ED CuVs and rates at individual cortical locations defined 4 areas of "relative interictal cortical epileptogenicity." These were arranged in an orderly pattern with the anterior parahippocampal gyrus and the inferomedial surface of the temporal tip displaying the highest and the lateral temporal and posterior infratemporal cortices showing the lowest propensity to the interictal epileptiform discharge. Individual areas were not characterized by distinct clinical seizure manifestations. Preresection ECoGs provide information on the epileptogenic dysfunction that involves most of the temporal lobe of patients with medically intractable TLS.

Adolescent↗