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C Watts

Publications and source records attributed to C Watts.

243 records · Page 14Linked to original sources

Towards a protocol for the preparation and delivery of striatal tissue for clinical trials of transplantation in Huntington's disease.

There is a growing body of scientific evidence contributing to the development of clinical transplantation programs in patients with Huntington's disease. Phase I clinical trials have already commenced in France and North America and are starting in the near future in Sweden and the UK. Protocols for patient selection, surgical implantation, and pre- and postoperative follow-up are well defined. However, considerable variability exists with respect to the harvesting, preparation, and timing of implantation of the donor material. In this article we review the scientific evidence on which a rational protocol for donor tissue preparation and delivery may be based. Strategies aimed at minimizing the variability of tissue preparation should reduce the variability of functional outcome of striatal transplantation observed in animal models of Huntington's disease.

Animals↗

The morphology, integration, and functional efficacy of striatal grafts differ between cell suspensions and tissue pieces.

In order to develop a surgical protocol for use in clinical trials of striatal transplantation in Huntington's disease (HD), the issues involved in the preparation and implantation of the embryonic striatal tissue must be addressed. Rodent models of HD offer the best experimental paradigm with which to study various aspects of striatal transplantation. In this article we present the results of an investigation of the role of trypsin and the process of trituration in the preparation of cell suspensions compared to the use of solid pieces of tissue. The embryonic material was derived from the lateral ganglionic eminence (LGE) and implanted into the excitotoxically lesioned striatum of the host rats. Twelve weeks following implantation, retrograde tracing of projections from the graft to the globus pallidus was performed. Grafts derived from cell suspensions triturated in the presence of trypsin contained larger quantities of striatal tissue within the graft and more DARPP-32-positive medium spiny neurons than grafts implanted as fragments of tissue. Afferent and efferent connectivity was also better in the trypsinized suspension graft group. Modest recovery in paw reaching was observed contralateral to the grafted side in animals implanted with solid fragments of embryonic striatal tissue. No relationship was observed between functional effect and the graft anatomy. These results suggest that local graft host interaction may also be involved in graft-mediated functional recovery.

Acetylcholinesterase↗

The development of intracerebral cell-suspension implants is influenced by the grafting medium.

The effect of preparing and grafting embryonic striatal and nigral tissue in four different media was evaluated in vitro and in vivo. The proportion of TH-positive and DARPP-32-positive neurons was determined after 2 days in vitro in standard culture medium following preparation in the different media. The effects were more marked for striatal neurons where DARPP-32 expression in tissue prepared in HBSS was poor compared to other media. TH expression was unaffected by the preparation medium. Striatal grafts derived from tissue prepared and grafted in HBSS were smaller, with fewer DARPP-32 cells, compared to other media. Survival of grafts in combined HBSS and DMEM was very poor. Graft volume and TH cell content was enhanced in tissue prepared in DMEM. These results suggest that preparation protocols optimized for one type of embryonic neuronal population do not necessarily transfer to other neuronal populations.

Animals↗

Complications of chemonucleolysis for lumbar disc disease.

In 13,700 patients who received one or more lumbar disc injections of chymopapain, 401 complications, adverse reactions, and delayed untoward events were recorded, including eight deaths. The deaths were secondary to anaphylaxis, pulmonary embolism, discitis with subacute bacterial endocarditis, ruptured abdominal aortic aneurysms (two patients), encephalitis (of unknown etiology), and myocardial infarction. Of these, the deaths secondary to anaphylaxis and discitis with subacute bacterial endocarditis can be attributed directly to the procedure of chemonucleolysis.

Anaphylaxis↗

Testing of cerebrospinal fluid shunt systems under dynamic flow conditions.

There exists considerable disagreement regarding the experimental methods that are used to evaluate cerebrospinal fluid (CSF) shunts. Nearly everyone who has studied CSF shunts has attempted to define shunt characteristics by either steady pressure or steady flow-rate tests of only the valve component of the shunt. However, a valved shunt assembly must actually function in a very dynamic environment. A series of bench tests have been designed to determine the dynamic characteristics of complete shunt systems. Thirty CSF shunt assemblies, consisting of six assemblies from five different manufacturers, have been tested. The tests show that the response times for CSF shunts vary from 0.17 min to 0.46 min, and that the mean pressure maintained in a dynamic flow environment may be very different from the pressure maintained under steady flow conditions.

Cerebrospinal Fluid Shunts↗

Loss adjusters.

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Aftercare↗