Biomedical subjects
Publications and source records attributed to R Gruber.
A follow-up study was done on 92 newborn and infants with subdural and intraventricular haemorrhage. External drainage is discussed as the primary therapy of choice. Its efficiency especially in chronic subdural haematoma is exemplified. Advantages and disadvantages of this therapy compared against intermittent puncturing, craniotomy and shunt therapy are discussed.
Flow rate studies on various membrane and slit valve shunt combinations in the upright (hanging) position were carried out to compare their function with and without an Anti-Siphon-Device (ASD) in relationship to various proximal pressures and various distal catheter lengths. Advantages and disadvantages of the numerous valve types and shunt combinations and the optimal position of the ASD are established. The necessity of an ASD in every shunt is experimentally verified and theoretically discussed.
A check-up of 124 children with medium to severest contusio cerebri showed a posttraumatic late epilepsy rate of 8% at an average control period of 12 years. A third of all children received a long-term anticonvulsive prophylaxis of approximately 4 years, under which 13% showed a manifest late epilepsy, while the rate of the non-protected group was 6% (each 5 patients). Even with a full anticonvulsion therapy it was not possible to avoid further convulsion in any of the children. By these results and new publications, a posttraumatic anticonvulsive prophylaxis is questioned and it is recommended to start an anticonvulsion therapy only if late epilepsy has become definitely manifest.
A follow-up study was performed on 41 hydrocephalic children with primary (10 patients) or secondary (31 patients) placement of an anti-siphon device (ASD) connected to their shunt. The clinical course before and after ASD implantation was compared in these two groups, including studies of the head circumference, the radiological ventricular size, cerebrospinal fluid pressure studies on the supine and upright patient, and the history of shunt-induced complaints and complications leading to hospitalization. The authors discuss the pathophysiological concept of the "chronic overdrainage " or slit-ventricle syndrome based on ventricular collapse due to chronic suction-induced overdrainage by the vertical shunt system in the upright patient. The use of an ASD in connection with the regular shunt system of children with hydrocephalus is proposed. This ASD-shunt combination successfully reduced the number of complaints and shunt dysfunctions over a period of more than 6 years.
A comparative clinical and radiological follow-up study was conducted on 109 hydrocephalic children to study the criteria of shunt dependency. 50 children had a normal functioning shunt, 34 children had an ASD-shunt combination, 14 children had a non-functioning shunt without pressure symptoms and 11 children had the shunt previously removed. None of the cases showed pressure symptoms during examination. The following conclusions could be drawn: 1. The smaller the ventricular system, the higher the complication rate. 2. The standard of well-being did not correspond with the amount of the redevelopment of the compressed brain tissue. 3. A "well-drained" ventricular system was not necessarily a sign of an adequate hydrocephalic therapy, but rather a sign of a pathologic overdrainage. 4. The broader ventricular aspects of the suction-protected ASD shunt resembled the findings of the "arrested hydrocephalus" and seemed to be closer to the goal of hydrocephalus therapy, namely, shunt independency.
One hundred and nine shunt-treated hydrocephalic children were reviewed. The size of the ventricular system was related to the psychomotor development, recurrent symptomatology and the frequency of shunt complications. Three groups were identified: children with normal functioning shunts, children with a shunt-ASD combination and children whose shunt ceased functioning or had been removed for ten years or more. It is concluded that retarded psychomotor development, recurrent symptoms and ventricular catheter obstructions are more frequent in patients with small ventricles compared to those with residually enlarged ventricles. A "normalised" ventricular system is more likely to be associated with shunt dependency and may, in fact, hinder the ultimate goal of shunt-independence.
A follow-up study of 64 hydrocephalic children with a ventriculo-atrial or ventriculoperitoneal shunt is presented to correlate clinical manifestations of chronic ventricular overdrainage with the aetiology of ventricular shunt complications. A clinical, radiographic and CT scan examination combined with the results of the continuously monitored proximal shunt pressure in the mobilised patient was performed to reveal the incidence and the pathophysiological mechanism of the slit ventricle syndrome. The clinical and therapeutical consequences are discussed.
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The subject dealt with is the prognosis of residual axis deviations following finger fractures in the growing phase. By means of individual examples it is shown that the axis deviation in the frontal plane does not undergo any correction during further growth, whereas the axis deviation in the movement plane - the sagittal plane - can still be completely corrected even in cases of premature joins. Thus the limits of conservative treatment are shown: fractures with axis derivation in the sagittal pland can in most instances be treated conservatively. Fractures with axis deviation in the frontal plane, on the other hand, are better treated operatively, if up to consolidation there is no certainty of stabilizing the correction of this fault by the conservative method.
The etiology of the refracture after forearm fractures in childhood has been studied in a follow-up examination of 199 patients with dislocated forearm fractures. The incidence of the refracture was 13%. In all cases the primary fracture was a greenstick fracture of at least one of the two forearm bones. The incompletely broken through greenstick fracture was found to be significantly responsible for the refracture. Duration of immobilisation or residual axis deviation at consolidation showed no relationship. The pathophysiology is briefly discussed. In every greenstick-fracture of the forearm the necessity of completing the fracture by total reposition is emphasized to prevent a refracture.
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Unlike monoclonal antibodies, clinical application of bispecific antibodies has so far lagged behind because of difficult, low-yield production techniques as well as considerable toxicity attributed to bispecific antibody preparations containing immunoglobulin-Fc parts and anti-CD3 homodimers. These difficulties were overcome by recombinant generation of a bispecific single-chain antibody (bscAb) joining two single-chain Fv fragments via a five-amino-acid glycine-serine linker. The anti-CD3 specificity directed against human T cells was combined with another specificity against the epithelial 17-1A antigen. The following domain arrangement was critical in this individual case to obtain a fully functional bscAb: VL17-1A-VH17-1A-VHCD3-VLCD3. The bscAb was expressed in chinese hamster ovary cells with a yield of 15 mg/l culture supernatant whereas numerous attempts to obtain a functional protein expression in Escherichia coli failed. The low-molecular-mass bispecific construct (60 kDa) could easily be purified by its C-terminal histidine tail. The antigen-binding properties are indistinguishable from those of the corresponding univalent single-chain Fv fragments as shown by enzyme immunoassay and flow cytometry. We could show that the bscAb, which lacks Fc parts and anti-CD3 homodimers is highly cytotoxic for 17-1A positive tumor cells in nanomolar concentrations and in the presence of human T cells. Most remarkable, it does not stimulate T lymphocyte proliferation in the absence of tumor cells and, moreover, does not induce CD25 up-regulation and the secretion of potentially toxic lymphokines such as tumor necrosis factor alpha, interleukin-6 and interferon gamma. Maximal cytotoxicity (51Cr release) was achieved without notable costimulation and was not further enhanced by adding costimulatory signals such as those delivered by anti-CD28 antibodies. CD8+ as well as CD4+ T cell subpopulations were recruited to exert cytotoxicity against tumor cells with different kinetics. CD8+ cells induced high 51Cr release within 4 h while CD4+ cells required a 20-h incubation. The systemic application of the 17-1A/CD3-bscAb could be a major improvement in therapy against disseminated micrometastatic tumor cells. A prospective, randomized clinical trial showing that an anti-17-1A monoclonal antibody could prolong survival of colorectal cancer patients after 5 and 7 years, warrants an assessment of the clinical efficacy of this bscAb exhibiting a 1000-fold higher specific cytotoxicity against tumor cells in vitro.