Rhabdomyolysis in 119 students after repetitive exercise.

Exercise induced rhabdomyolysis is well known, but has rarely been reported in high school students. This is the report of 119 cases in high school students who exercised vigorously (120 push ups in five minutes) in cold weather. Most of them developed muscle pain and dark urine within two to four days of the exercise.

Low molecular weight heparin in hemodialysis patients with a bleeding tendency.

Efficacy and safety of a low-molecular-weight heparin (LMWH) were studied in 33 stable maintenance hemodialysis patients who had a bleeding tendency on unfractionated heparin. The optimal dose of LMWH for each patient was titrated before the study; the mean total LMWH dosage was 1,152 +/- 574 IU. No major bleeding or clot formation was noted in a total of 2,470 hemodialysis sessions during 6 months of LMWH administration. The mean value of plasma anti-factor Xa (anti-Xa) activity increased from 0.05 +/- 0.03 IU/ml before dialysis to 0.34 +/- 0.28 IU/ml after 2 h of dialysis and returned to 0.15 +/- 0.09 IU/ml after 4 h of dialysis; the mean activated partial thromboplastin time was 26.1 +/- 4.4 s before dialysis, 30.7 +/- 9.5 s (an 18% increase) after 2 h of dialysis, and 26.2 +/- 4.4 s after 4 h of dialysis. No significant change in serum antithrombin levels was noted throughout the whole study period. We conclude that a low dosage of LMWH is safe and effective in hemodialysis patients who have a risk of bleeding with unfractionated heparin. Serum anti-Xa activity is better than activated partial thromboplastin time and antithrombin in assessing the optimal dose of LMWH. A plasma anti-Xa activity of 0.37 IU/ml after 2 h of hemodialysis may represent an optimal dosage of LMWH for most patients.

Low molecular weight heparin in diabetic and nondiabetic hypercholesterolemic patients receiving long-term hemodialysis.

Dyslipidemia is a major factor associated with cardiovascular disease, which is the leading cause of death in hemodialysis patients. Low molecular weight heparin (LMWH) is superior to conventional unfractionated heparin in treating hyperlipidemia in nondiabetic long-term hemodialysis patients and has fewer side-effects. Only a few reports have addressed the influence of LMWH on serum lipids in diabetic patients, although dyslipidemia is common among this population. We investigated the effect of LMWH on serum lipids in 12 nondiabetic and eight diabetic hypercholesterolemic patients receiving long-term hemodialysis. Patients had been receiving hemodialysis with unfractionated heparin for a minimum of 6 months before beginning the study. Continuous LMWH infusion during hemodialysis was administered to all patients for 2 months, followed by unfractionated heparin administration for 2 months. During LMWH treatment, plasma anti-factor Xa activity increased from 0.06 +/- 0.04 IU/mL before dialysis to 0.49 +/- 0.25 IU/mL after 3 hours. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (Apo B) in both nondiabetic and diabetic patient groups and lipoprotein (a) (Lp(a)) in patients with higher initial values (> or = 15 mg/mL) decreased significantly after LMWH treatment (TC from 6.38 +/- 1.14 to 5.07 +/- 1.09 mmol/L, LDL-C from 3.08 +/- 0.93 to 2.15 +/- 0.88 mmol/L, Apo B from 100 +/- 18 to 78 +/- 18 mg/dL, all p < 0.01; Lp(a) from 41.8 +/- 34.5 to 28.5 +/- 22.8, p < 0.05). They rebounded to pre-LMWH levels after the 2 months on unfractionated heparin (TC 5.72 +/- 1.11 mmol/L, LDL-C 2.97 +/- 1.01 mmol/L, Apo B 98 +/- 20 mg/dL, Lp(a) 38.1 +/- 29.0 mg/dL). We conclude that continuous infusion of LMWH during dialysis reduces serum total cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B concentrations in both diabetic and nondiabetic hypercholesterolemic hemodialysis patients, and does not increase the risk of bleeding compared with unfractionated heparin.

Idiotypic mimicry and the assembly of a supramolecular structure: an anti-idiotypic antibody that mimics taxol in its tubulin-microtubule interactions.

Taxol, originally extracted from the bark of the western yew, Taxus brevifolia, is reportedly the first of a new class of anti-cancer agents. It acts by promoting and irreversibly stabilizing microtubule assembly, thus interfering with the dynamic processes required for cell viability and multiplication. With the aim of using immunological techniques to study the mechanism of action of taxol, a monoclonal anti-idiotypic antibody that mimics taxol was prepared, using an auto-anti-idiotypic strategy. It and its Fab fragment inhibited the binding of [3H]taxol to microtubules. Moreover, like taxol, both promoted the assembly of tubulin into microtubules. These findings provide an example of an anti-idiotypic antibody capable of assembling an organized supramolecular structure from soluble cellular components. In addition, it further establishes the ability of anti-idiotypic antibodies to be functional mimics of ligand molecules bearing no structural similarity to immunoglobulins. The variable regions of the antibody have been sequenced. With the exception of the complementarity-determining region 3, the sequence of the heavy chain variable region is strikingly similar to that of an anti-idiotypic antibody raised to anti-insulin. The finding that a polypeptide can mimic taxol raises the possibility that taxol acts as a peptidomimetic compound that interferes with the function of an endogenous polypeptide.

Characterization of polyclonal and monoclonal anti-taxol antibodies and measurement of taxol in serum.

Anti-taxol antibodies were generated in the rabbit using a taxol-bovine serum albumin conjugate prepared from 2'-succinyltaxol using a mixed anhydride procedure. Immunization with 2'-succinyltaxol-bovine serum albumin gave rise to polyclonal anti-taxol antibodies. By a radioimmunoassay using [3H]taxol, a standard curve gave a 50% inhibitory concentration of 1.0 nM. Taxol levels in human serum could be measured, with the lower limit of detection and measurement being 0.1 nM or 0.085 ng/ml. Two mouse monoclonal anti-taxol antibodies were isolated by immunizing BALB/c mice with the same antigen. One was an immunoglobulin G1 (69E4A8E) and the other was immunoglobulin M (29B7B3C). The specificity of these antibodies was determined by a competitive enzyme-linked immunosorbent assay with taxol and 10 different related derivatives and analogues. 29B7B3C had higher binding affinities for biologically active derivatives and markedly lower affinities for inactive derivatives; i.e., the specificity was consistent with the results of tubulin disassembly and cytotoxicity studies using the same taxol derivatives, making it suitable for screening for taxol or taxol-like compounds in extracts of natural products. 69E4A8E recognized the benzamidocarbamyl group at the C-3' position of taxol and had a lower affinity for other active compounds with different substitutions. Taxol levels in human serum could be detected and measured by 69E4A8E using a competitive enzyme-linked immunosorbent assay. The lower limit of measurement was about 50 nM or approximately 42 ng/ml. Similar measurements could be made by radioimmunoassay.

Immunoassay of taxol and taxol-like compounds in plant extracts.

A mouse monoclonal anti-taxol antibody (69E4A8E) and a rabbit polyclonal anti-taxol antiserum were used to measure taxol levels in plant extracts in a double-blind experiment in conjunction with assays by HPLC. 69E4A8E was previously shown by ELISA to be specific for taxol with only a slight cross reaction with another bioactive compound, cephalomannine; the antiserum, on the other hand, was, by radioimmunoassay (RIA), essentially equally reactive with taxol and cephalomannine. Immunoassays of the plant extracts gave results in agreement with that found by HPLC, suggesting that the antibodies can be used in simple routine procedures for the quantification of taxol or taxol-like compounds in extracts of plants or other potential natural sources.