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Biomedical subjects

A Wichman

Publications and source records attributed to A Wichman.

At least 19 recordsLinked to original sources

The impact of disease severity on the informed consent process in clinical research.

PURPOSE: To assess the efficacy of informed consent in subjects differing in disease severity, ranging from those with immediately life-threatening disease to healthy volunteers. SUBJECTS AND METHODS: A total of 127 subjects, enrolled in four types of clinical research protocols, were tested. Subjects completed questionnaires before entry into the protocol, within 24 hours of signing the primary protocol's consent document, and 4 to 6 weeks after entry. RESULTS: Healthy volunteers retained the most information about risks and side effects, and severely ill Phase I subjects retained the least (P <0.0001). Phase I and II subjects had the best long-term retention of information about procedures, whereas Phase III subjects and healthy volunteers retained the least (P <0.001). Information about the scientific purpose and confidentiality of data were retained best by symptom-free, Phase III subjects (P <0.05). Phase I subjects entered the study primarily for treatment purposes, and the consent document was rated less useful by subjects with more advanced disease (P <0.05). CONCLUSIONS: Subjects with differing disease processes and illness severities focused on and retained different aspects of experimental protocols for dissimilar reasons. During the informed consent process, research staff should inquire of potential subjects' personal goals for participating in experimental protocols and develop means for ensuring subjects' understanding of the inherent risks and alternative interventions available.

Adult↗

Bioethics at the National Institutes of Health.

The National Institutes of Health is the largest biomedical research institution in the world. It has become one of the world's most highly respected research centers in part because of its efforts over the years to provide the research community with leadership in both the ethical and scientific parameters of research involving humans. As its 113th birthday approaches at the turn of the century, its great legacy is providing an environment to stimulate and nourish the diversity and creativity of ideas, and thereby enable science to progress. This research must continue to be guided and tempered by consistent and critical federally-supported ethical analyses.

Advisory Committees↗

Long-term administration of 3'-azido-2',3'-dideoxythymidine to patients with AIDS-related neurological disease.

3'-Azido-2',3'-dideoxythymidine (AZT) has been administered to 7 patients with human immunodeficiency virus-associated neurological disease: 3 with dementia, 2 with peripheral neuropathy, 1 with dementia and peripheral neuropathy, and 1 with T-10 paraplegia. Six of the patients showed improvement in their neurological dysfunction on being administered AZT, as assessed by clinical evaluation, neuropsychological testing, nerve conduction studies, and/or positron emission tomographic scans. Three of these 6 patients showed sustained improvement 5 to 18 months after the initiation of AZT therapy. These results suggest that certain human immunodeficiency virus-associated neurological abnormalities are at least partially reversible following the administration of antiretroviral therapy and provide a rationale for further studies using antiretroviral chemotherapy.

Acquired Immunodeficiency Syndrome↗

Response of human-immunodeficiency-virus-associated neurological disease to 3'-azido-3'-deoxythymidine.

Four patients with human-immuno-deficiency-virus-associated neurological disease were treated with 3'-azido-3'-deoxythymidine (AZT). Three (two with chronic dementia, and one with chronic dementia and peripheral neuropathy) improved as assessed by clinical examination, psychometric tests, nerve conduction studies, and/or positron emission tomography; there was no improvement in the fourth patient who presented with paraplegia. These results support the hypothesis that certain AIDS-virus-associated neurological abnormalities are reversible by antiretroviral chemotherapy.

Acquired Immunodeficiency Syndrome↗

Rapid purification of monoclonal antibodies by high-performance liquid chromatography.

Three different high-performance liquid chromatographic (HPLC) techniques, i.e., ion-exchange, hydrophobic interaction and hydroxyapatite chromatography, have been used to purify monoclonal antibodies from ascites fluid. The monoclonal antibodies were raised against coagulation factor VIII. Precipitation of the antibodies by ammonium sulphate prior to HPLC made it possible to purify the antibody in one chromatographic step. In sodium dodecyl sulphate-polyacrylamide gel electrophoresis this highly pure preparation revealed only one extra polypeptide besides the light- and heavy-chain immunoglobulin polypeptides. Attempts were also made to purify the antibody without prior ammonium sulphate precipitation. A combination of ion-exchange and hydrophobic interaction chromatography resulted in an antibody preparation comparable in purity to the one obtained from ammonium sulphate-precipitated immunoglobulin. The rapid HPLC techniques were found to be very useful for purification of monoclonal antibodies on a preparative scale, where sample loadings of up to 25 mg of ascites protein were fully resolved in satisfactory yields.

Ammonium Sulfate↗

Autosomal recessive congenital cerebellar hypoplasia.

We report three sibling pairs with congenital cerebellar hypoplasia. All six children presented in the first years of life with delays in motor and language development. All patients showed cerebellar and/or vermal dysfunction and, on formal psychometric testing, cognitive abilities ranged from normal to moderately retarded. Abnormalities on CT scan ranged from prominent valleculla to an enlarged cisterna magna with hypoplasia of the cerebellar hemispheres and vermis. The pedigrees are consistent with autosomal recessive inheritance.

Adolescent↗

Peripheral neuropathy in hypereosinophilic syndrome.

We evaluated seven patients with the hypereosinophilic syndrome (HES) to define the clinicopathologic spectrum of the peripheral neuropathy. Clinically, three had evident polyneuropathy; the others were asymptomatic, although they had electrophysiologic evidence of neuropathy. Nerve conduction studies and EMG were compatible with axonal neuropathy. Morphometry of sural nerves from four patients ranged from normal to marked axonal loss, more prominent in large myelinated fibers. Demyelination was rare, and there was no evidence of vasculitis. Neuropathy may be produced by an eosinophil-derived neurotoxin.

Adult↗

Peripheral neuropathy in abetalipoproteinemia.

We studied the peripheral neuropathy of three sisters with abetalipoproteinemia. Clinically, a sensory neuropathy progressively increased in severity. There was a diminution in the amplitude of sensory action potentials and a slight-to-moderate slowing in maximum sensory conduction velocity, initially most marked in distal portions of the nerves. Motor conduction was normal, although EMG indicated subclinical signs of partial chronic denervation. The sural nerves showed a decreased number of large fibers (greater than 7 micron); in the patient with the neuropathy of shortest duration, small fibers and clusters of regenerating fibers indicated regeneration. In the two patients with advanced neuropathy, one-half the segments of teased fibers showed paranodal demyelination. Also, unmyelinated fibers showed evidence of regeneration.

Abetalipoproteinemia↗

Sarcoma arising from a gliosarcoma.

An 18-year-old woman with headaches and visual abnormalities was found upon biopsy to have an occipital gliosarcoma, which was treated with irradiation and chemotherapy for a year. Cells in the gliosarcoma tissue were positive for GFAP. At necropsy, only the sarcoma was evident at the site of original surgical removal. The sarcoma had spread widely along meningeal routes, causing the patient's death. The biologic behavior and histologic features of the sarcoma were clearly malignant. Cells cultured from the biopsy specimen maintained features in common with sarcoma.

Adolescent↗