Enzyme therapy for Pompe disease: from science to industrial enterprise

Pompe disease or glycogen storage disease type II (OMIM 232300) is a metabolic myopathy with a broad clinical spectrum. Generalised muscle weakness combined with cardiomegaly presents within the first 3 months after birth, if the lysosomal α-glucosidase (AGLU) deficiency is complete. Residual enzyme activity prevents cardiac involvement and delays onset of muscle weakness. Enzyme therapy, by intravenous administration of acid AGLU, aims to supplement the missing enzyme activity. At the SHS symposium on Glycogen Storage Diseases Type I and II, in Fulda, two interim accounts were given of studies on the efficacy of enzyme therapy for Pompe disease; one with recombinant human acid AGLU produced in Chinese hamster ovary cells and the other with the same enzyme produced in the milk of transgenic rabbits.Conclusion: this review focuses on the latter study, discusses the scientific, technological and commercial aspects of the enterprise, and addresses the prospects and challenges of enzyme therapy for Pompe disease. Published online: 13 August 2002     

Children and young adults in a prolonged unconscious state due to severe brain injury: outcome after an early intensive neurorehabilitation programme

Primary objective. The Rehabilitation Centre Leijpark in the Netherlands provides an Early Intensive Neurorehabilitation Programme (EINP) to children and young adults in a prolonged unconscious state after severe brain injury. In an extensive research project the effects of EINP were studied. This part of the project focused on the outcome in terms of level of consciousness (LOC) in relation to the specific characteristics of a retrospectively studied cohort. Research design. This study was executed according to a one-group archived pre-test-post-test design. Subjects. Subjects were all consecutively admitted patients (n = 145, 72% male) between December 1987-January 2001. Inclusion criteria were: age 0-25 years, within 6 months after injury, LOC at admission vegetative state (VS) or minimally conscious state (MCS). One hundred and four patients (72%) suffered a traumatic injury and 41 patients (28%) a non-traumatic injury. Methods and procedures. All patients had received EINP until they reached consciousness or until it was concluded that no progress was achieved during 3 months after the start of EINP. Medical files were investigated to collect the patients' characteristics and injury data, to determine the LOC at admission and at discharge and to determine the discharge destination. Results. Almost two-thirds of the patients reached full consciousness. LOC at admission, aetiology and interval since injury were found to be significant prognostic factors. Traumatic patients had a much better outcome than non-traumatic patients. A comparison with earlier outcome studies showed a more favourable outcome than expected. It is argued that a multi-centre study is needed to confirm possible effects of EINP.     

Comparison of changes in physical self-concept, global self-esteem, depression and anxiety following two different psychomotor therapy programs in nonpsychotic psychiatric inpatients

BACKGROUND: The first objective of this study was to compare the changes in physical self-concept, global self-esteem, depression and anxiety after participation in one of two 16-week psychomotor therapy programs for nonpsychotic psychiatric inpatients. The second objective was to study the relationship between changes in these variables. METHODS: One hundred and ninety-nine inpatients were randomly assigned to either a personalized psychomotor fitness program, consisting of aerobic exercise and weight training, or a general program of psychomotor therapy, consisting of different forms of physical exercises and relaxation training. Physical self-concept was evaluated using the Dutch version of the Physical Self-Perception Profile at baseline, after 8 weeks, and after completion of the 16-week interventions. At the same time points, additional variables of global self-esteem, depression and anxiety were assessed by means of the Rosenberg Self-Esteem Inventory, the Beck Depression Inventory and the Trait Anxiety Inventory, respectively. RESULTS: After 16 weeks, both groups showed significant improvements in all outcome measures (p values ranged from 0.01 to < 0.0001), with no between-group differences. In both groups, the improvement in physical self-concept was correlated with increased global self-esteem and decreased depression and anxiety levels (p < 0.01). CONCLUSIONS: The results suggest that both psychomotor therapy programs are equally effective in enhancing physical self-concept. The relationship between improvements in physical self-concept and enhancements in global self-esteem, depression and anxiety supports the potential role of the physical self-concept in the recovery process of depressed and anxious psychiatric inpatients.     

Current therapeutic strategies in Hodgkin lymphoma

Zum Thema In den letzten Jahren haben sich die Behandlungsstrategien der Hodgkin-Lymphome gewandelt. Für die frühen und mittleren Stadien der Hodgkin-Lymphome hat sich der risikoadaptierte kombinierte Einsatz von Chemotherapie und Strahlentherapie durchsetzen k?nnen.In frühen und intermedi?ren Stadien liegt das Gesamtüberleben nach 5 Jahren bei über 90%.Mit Einsatz neuer Chemotherapieprotokolle in den fortgeschrittenen Stadien überleben langfristig etwa 80% aller Patienten nach intensiver Chemotherapie mit additiver Strahlentherapie auf Resttumoren und Bulk.Nachfolgend werden die gegenw?rtigen Studienkonzepte der Deutschen Hodgkin-Lymphom-Studiengruppe (DHSG) detailliert dargestellt. Prof.Dr.V. Diehl Klinik I für Innere Medizin, Universit?t zu K?ln, 50924 K?ln, E-Mail: V.Diehl@uni-koeln.de     

Diagnosis of vegetative state as a basis for medical treatment on the borderline between life and death

The term 'vegetative state' is most appropriate for the state which develops when patients open their eyes after a comatose phase, without regaining consciousness. The definition and the diagnostic criteria from the Multi Society Task Force on Persistent Vegetative State are usable for the clinical practice in the Netherlands. The vegetative state must be differentiated from coma, locked-in syndrome and minimally conscious state. A systematic, multidisciplinary approach under the direction of a physician is key to diagnosing vegetative state. To this end, a clinical assessment is recommended with reassessment and verification of the diagnosis at appropriate moments. Careful observation remains the fundamental to the diagnosis.     

Do repeated runs of a cell saver device increase the pro-inflammatory properties of washed blood?

OBJECTIVE: Intra-operative cell salvage is increasingly used, especially in longer cases with continuing blood loss. However it is unknown if the quality of processed blood is affected when larger quantities of blood are processed. We hypothesized that the quality of the washed blood decreases after multiple runs. METHODS: Intra-operative cell salvage was performed in 42 consecutive patients undergoing cardiac surgery. When 1250 ml of blood was collected in the blood collection reservoir, this was processed and returned to the patient. In 21 patients more than 2500 ml of blood was collected during the whole procedure, thus allowing at least two subsequent runs with the auto-transfusion device. Blood samples were drawn from the blood collection reservoir of the cell saver device before, and from the processed blood after each run. RESULTS: After the first run interleukin-6 concentrations were reduced with 85% (from 21+/-35 microg/l to 3.1+/-4.4 microg/l), whereas after the second run 72% was removed (63+/-69 microg/l to 17.6+/-25.3 microg/l). Leukocyte counts almost doubled after both processing runs (from 2.6+/-1.5 x 10(9)/l to 5+/-3.6 x 10(9)/l) and from 3.9+/-2.2 x 10(9)/l to 7.7+/-5.9 x 10(9)/l), hemoglobin concentration (14.8+/-1.6 mmol/l vs 15.0+/-1.1 mmol/l), free hemoglobin (2.3+/-1.6g/l vs 2.1+/-1.4 g/l) and platelet counts (18+/-9 x 10(9)/l vs 28+/-23 x 10(9)/l) were not different between the two runs. CONCLUSIONS: Our results suggest, based on interleukin-6 and free hemoglobin washout that the quality of the processed blood remains constant with multiple runs of the cell saver device.