Anti-Erwinia asparaginase antibodies during treatment of childhood acute lymphoblastic leukemia and their relationship to outcome: a case-control study

PURPOSE: A case-control study was performed to determine whether patients who had been treated with Erwinia asparaginase as part of their treatment for childhood acute lymphoblastic leukemia (ALL) and who showed relapsed of their disease more often developed anti-asparaginase antibodies than patients who remained in remission. METHODS: A group of 13 patients who showed relapsed of their disease (median follow-up 35 months) were randomly matched with control patients of the same risk group (two control patients to each case), who had received therapy of the same intensity during the same period (median follow-up 70 months). Anti- Erwinia asparaginase antibodies were measured (ELISA method) during maintenance therapy after asparaginase treatment (30,000 IU/m(2) daily for 10 days in all patients plus twice weekly for 2 weeks in intermediate-risk and high-risk ALL patients). RESULTS: The overall incidence of anti- Erwinia asparaginase antibodies was 8% (3 of 39 patients). There was no statistically significant difference in the incidence of antibody formation between patients who had suffered relapse (1 of 13) and those who had not (2 of 26). In two of the three patients who developed antibodies, the antibodies disappeared after some time, whereas one patient had measurable antibody levels for more than a year after asparaginase therapy. CONCLUSIONS: In this study, the development of anti-Erwinia asparaginase antibodies was rare and was unrelated to the risk of relapse.     

Partial loss of dopaminergic neurons in the substantia nigra,ventrotegmental area and the retrorubral area -- model of the early beginning of Parkinson's symptomatology?

Summary. To test substances which might have protective effects on the dopaminergic system it is necessary to use models with a pathological symptomatology of the early beginning, i.e. models in which the chance exists to arrest the otherwise progressive pathological processes (see Heim et al., 2001). 6-hydroxydopamine (6-OHDA) injected unilaterally into the ventrolateral striatum of rats (6 μg dissolved in 2 μl 0.2% ascorbic acid) leads to specific stereotyped movements after subcutaneous injection of apomor-phine both 3 and 13 weeks after surgery. Ten weeks after surgery decreased spontaneous motor activity could be observed. Twelve weeks after 6-hydroxydopamine injection, the animals had difficulties in performing a spatial navigation task when the submerged escape platform was moved to another position. The switching of motor programs was less pronounced. The application of tyrosine-hydroxylase-staining showed a loss of ipsilateral neurones of the substantia nigra compacta as well as of dendrites in the pars reticulata, neurones in the ventral tegmental area and in the retrorubral area ipsilaterally as well as a loss of dopaminergic fibres both ipsilaterally and contralaterally in the striatum which should belong to the contralateral acting substantia nigra afferents. The loss of the neurones and the afferents was induced by the retrograde denervation following the 6-OHDA injection within the ventrolateral striatum. The question arises whether the model used here with the partially loss of dopaminergic neurons and fibres reflects some of pathological symptoms of Parkinson's disease in the early states. Received December 21, 2001; accepted February 25, 2002     

Direct deconvolution algorithms based on Laplace transforms in nuclear medicine applications

A set of algorithms is presented for direct deconvolution of the residue signal of an organ with the input signal to the organ. The deconvolution process yields the residual impulse response from which the distribution of transit times and the important mean transit time can be readily determined. The deconvolution method is based on the Laplace transform and it requires that the input signal can be fitted with an expression consisting of one, two or three exponentials with or without a bolus term at zero time or a constant term. These types of exponential expressions for the input signal cover a wide range of the input signals encountered in nuclear medicine applications. Simulation studies of the residue signal by convolution of various input signals with a number of residual impulse response models yielded an excellent accuracy of the deconvoluted residual impulse response for a suitably small sampling time. The simulations provide an opportunity to understand further the shapes of the residue curves depending on the shape of the input signal and the distribution of transit times. Simulations with Gaussian-distributed noise and noise spikes superimposed on the residue signal were also made to investigate the robustness of the direct deconvolution algorithm using apparently real-life data.     

Mouse-isolated plexus differentiates neural crest precursors into enteric neuroblasts.

Aim of this study was to investigate, for the first time, whether isolated newborn mouse enteric plexus could induce in vitro differentiation of the vagal neural crest-derived cells into enteric neuroblasts. Fragments of the myenteric plexus were isolated from the small intestine of 6-day-old Swiss mice and were collected and stored in DMEM-F12 medium, then cultured on polymerized human fibronectin layer. The vagal portion of the neural tube, isolated from a 9.5-day-old Swiss mouse embryo, was put in the same chamber slides where the isolated myenteric plexus had been cultured for 3 days. The vagal neural crest-derived cells migrated onto the polymerized human fibronectin layer and formed a crown of cells around the neural tube. After 6 days, the cultures were stopped and studied immunohistochemically for anti-NF160 KD, anti-TH, and RetR5 antibodies to analyse the differentiation stage of the cultured cells. Analysis of results included the comparison of two culture groups: Group 1, used as control, in which vagal neural crest-derived cells were put in DMEM-F12, supplemented only with 10 % of FCS; Group 2, in which vagal neural crest-derived cells were put in the same medium as Group 1, with the addition of myenteric plexus fragments isolated from newborn mice to form the co-culture. The following results were obtained: in Group 1 the neural tubes originated a cell population strongly positive for anti-NF160 and anti-TH Ab, but negative for RetR5 Ab. This positivity was found both in the cells adjacent to the neural tube and in those migrating from it distally. The Group 2 originated cells, which after migration were positive for anti-NF160 and for anti-TH antibodies. In addition, in this culture group, the cells which migrated from the neural tube were positive for anti-RetR5 antibody. The co-culture used in this study induces the differentiation of vagal stem cells into enteric neuroblasts, cells TH+ and RetR5+. These cells, after reaching the embryonic intestine, migrate to colonize the hindgut and form the ENS. Therefore this biotechnology seems a good method to obtain in vitro enteric precursors of ENS.     

Age‐related decrease in energy expenditure at rest parallels reductions in mass of internal organs

This study explores to what extent the mass of internal organs may impact the age‐related decrease in energy expenditure at rest (EErest). The relationship between direct measurements of EErest in elderly women and predicted EErest based on equations deriving from the metabolic activity in tissue from younger women were also elucidated. Body composition of elderly women was measured by an impedance method. EErest was measured by the Douglas bag method after an overnight fast. These data were compared with predicted values of EErest based on equations derived from studies in younger women. The mass of internal organs was obtained from autopsy material. Young women (mean age 31.7 years, range 14–60, n = 104) and elderly women of 65 years (n = 22), 75 years (n = 26), and 85 years (n = 31) participated in this study. Autopsy data were obtained from women (n = 238) from the same birth cohorts as the elderly women who died at ages 42–87 years. EErest showed a progressive age‐related decline, which appeared to parallel a similar reduction in the mass of internal organs derived from autopsy material of women who died at the same ages. In contrast, FFM was identical in the group of 65 and 75‐year‐old women, but was lower in the 85‐year‐old women. Predicted and measured EErest revealed a strong correlation in elderly women. Modest reductions in the mass of internal organs with a high metabolic rate appear to contribute markedly to the decline in EErest observed in aging. Further, it is also possible to predict EErest from the body composition of elderly women using equations developed from younger women. Am. J. Hum. Biol. 14: 486–493, 2002. © 2002 Wiley‐Liss, Inc.     

Osteoblastic tartrate-resistant acid phosphatase: its potential role in the molecular mechanism of osteogenic action of fluoride.

Although type 5 TRACP is recognized as a histochemical and biochemical marker of osteoclasts, there is evidence that bone forming cells, osteoblasts, and osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP has been purified from human osteoblasts and from bovine cortical bone matrices. Comparison of biochemical properties of osteoblastic type 5 TRACP with those of osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5 TRACP may be relevant to its physiological functions: (1) it acts as a protein-tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically relevant conditions, and (2) it is sensitive to inhibition by clinically relevant concentrations of fluoride. Because fluoride is a stimulator of osteoblastic proliferation and differentiation and a potent osteogenic agent and because protein tyrosine phosphorylation plays an important regulatory role in cell proliferation and differentiation, these unique properties and other evidence summarized in this review led to the proposal that the osteogenic action of fluoride is mediated, at least in part, by the fluoride-mediated inhibition of osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a stimulation of osteoblast proliferation and differentiation, and subsequently, an increase in bone formation.     

Nerve biopsy and conduction studies in diabetic neuropathy.

Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres, segmental demyelination was found in only a few fibres. Axonal degeneration and Schwann cell damage seem to proceed independently of each other. The relation between recorded conduction velocity and that expected from the diameter of the largest fibres indicated that slowing of 20 to 30% was due to causes other than fibre loss; a grossly diminished conduction velocity was caused mainly by fibre loss. Electrophysiological findings in the sural nerve were largely representative of findings in other nerves, though abnormalities were less marked in the median nerve. In half the endoneurial vessels from diabetic neuropathy the perivascular space was thickened or contained more layers of basal laminae than normal. The same abnormalities were found in one-quarter of the endoneurial vessels from other acquired neuropathies.     

Bilirubin appears to be the only independent variable affecting mortality on liver transplant waiting list if waiting time exceeds 1 year

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been shown to be the best predictor of short-term mortality on the liver transplant waiting list in the United States but waiting time often exceeds 1 year in many countries. We wanted to identify the factors affecting mortality on the liver transplant waiting list in Singapore where waiting time for liver transplant exceeds 1 year. PATIENTS AND METHODS: All patients who were listed on the liver transplant waiting list in Singapore from January 1997 to December 2003 excluding those who were transplanted were analyzed. MELD was calculated according to the United Network for Organ Sharing formula. Univariate analysis was performed to identify factors affecting mortality on the waiting list and multivariate analysis by logistic regression. Categorical and continuous variables were compared with the chi-square and Mann-Whitney U tests. RESULTS: There were 48 patients in the study. We found that on univariate analysis, bilirubin, INR, MELD score, and Child's score significantly influenced mortality on the waiting list but on multivariate analysis, bilirubin was the only independent prognostic indicator of mortality on the waiting list (LR = 1.97; 95% confidence interval = 1.08 to 3.61). INR was found to be significantly correlated to bilirubin with Pearson correlation (R = 0.63, P < .001). CONCLUSION: Bilirubin is the only independent factor affecting mortality on the liver transplant waiting list where waiting time exceeds 1 year.     

An unusual case of Dantrolene sodium-induced urinary retention in post-traumatic minimally responsive state

Introduction: An unusual case of urinary retention is reported occurring during the inpatient rehabilitation of minimally responsive state (MRS) following severe traumatic brain injury (TBI). Clinical picture: Urodynamic evaluation showed detrusor acontractility and subsequent management involved intermittent bladder catheterization and treatment of a single urinary tract infection. Treatment: Factors contributing to her bladder paralysis included severe immobility, tetraplegia and treatment of diffuse spasticity with oral Dantrolene sodium 250 mg per day. Constipation, diabetes and spinal cord injury were absent. In addition, she received unilateral partial sciatic neurolysis with 50% alcohol for severe knee flexor spasticity and intra-muscular Botulinum toxin A to both spastic upper limbs. Outcome: Bladder acontractility resolved completely when Dantrolene was reduced with subsequent achievement of a catheter-free status and small post-void residual volumes. Repeat urodynamics showed spontaneous detrusor contractions. Conclusion: A discussion of possible aetiologic factors for detrusor acontracility following TBI is presented including a brief review of the literature.     

Health promotion aspects in reorganization of a centralized operating department

In many health care institutions (eg, hospitals), employees' health and satisfaction are not the main concern. However, if health and productivity are affected by high sickness rates and low motivation, health and satisfaction of the employees become important. This applies especially to hospitals engaged in acute patient care. We showed that a complete reorganisation of the central O. R. resulted in employees' working satisfaction, low illness rates (- 70 %) and increased motivation. In addition, the new structure increased the efficacy (> 500 operations more per year), improved the economy (savings of 500,000 annually) and increased patient satisfaction as expected and desired.