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Biomedical subjects

K Parker

Publications and source records attributed to K Parker.

At least 19 recordsLinked to original sources

Deaths caused by bedrails.

OBJECTIVES: To determine how bedrails cause death in order to suggest clinical and ergonomic changes to prevent such deaths and to promote research to improve the use and design of bed systems. DESIGN: A review of reports of adult deaths and injuries from bedrails contained in the United States Consumer Product Safety Commission Death Certificate File and its Reported Incidents File and its National Injury Information Clearinghouse Accident Investigations from 1993 to 1996. Deaths involving the use of vest restraints were excluded. We reconstructed, reenacted, and have graphically depicted major patterns of deaths. A review of the literature to 1966 was also done. RESULTS: The 74 deaths described are categorized into three types: (1) 70% were entrapments between the mattress and a rail so that the face was pressed against the mattress, (2) 18% were entrapment and compression of the neck within the rails, and (3) 12% were deaths caused by being trapped by the rails after sliding partially off the bed and having the neck flexed or the chest compressed. CONCLUSIONS: Deaths from bedrails are underrecognized and preventable clinical events that can occur in any medical setting. Preventing these events will require a unified redesign of the relationships between rails, mattresses, and beds, which are now often assembled and used as separate products. Clinicians can prevent many of these deaths by using bedrails much more judiciously, confirming the proper relationships between beds, rails and mattresses, and using alarms.

Aged

Child psychiatric consultation service to community agencies: a collaborative approach involving three community agencies.

OBJECTIVE: To report the early experience of a multiagency child psychiatric consultation service. METHOD: The program is described, and the demographic characteristics of clients referred to the consultation program over the first 25 months of operation are presented. Referrals were examined for demographics and the questions consultees wanted to have answered. RESULTS: In 59 of 100 consultations, physical and/or sexual abuse was proved or highly suspected. In 82 of the 100 cases, consultees had questions pertaining to management issues. Questions related to diagnostic issues numbered 62, and there were 45 questions about safety issues. CONCLUSION: Effective psychiatric consultations services to rural areas can be established. Once established, the questions of consultees can provide an effective training ground for future community-oriented child psychiatrists.

Adolescent

Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells.

Proteinase 3 is present in high concentration in the primary granules of acute and chronic myeloid leukemia blasts, and may represent a potential T-cell target antigen. We screened proteinase 3 against the binding motif of HLA-A2.1. Based on its high predicted binding, a 9-mer peptide, "PR-1," was synthesized and tested for binding to HLA-A2.1 using the T2 cell line. PR-1 at 100 micrograms/mL significantly increased expression of HLA-A2.1, with median channel of fluorescence increasing from 22 to 294. Binding half-life was determined to be 1,460 minutes by I125-labeled beta 2-microglobulin incorporation. HLA-A2.1+ peripheral blood mononuclear cells from a normal donor were used to generate a T-cell line specific for PR-1. The line demonstrated 85% PR-1-specific lysis at an E:T ratio of 50:1, compared with 20% lysis without PR-1, using T2 cells as targets. It also showed 79% specific lysis to fresh chronic myelogenous leukemia blasts, 54% to fresh acute myelogenous leukemia blasts, and only background lysis (< 20%) to HLA-A2.1+ normal allogeneic marrow cells. The amount of lysis of HLA-A2.1+ myeloid cells was proportional to cytoplasmic proteinase 3 expression. Thus, HLA-A2.1-restricted cytotoxic T cells, raised against a peptide contained in proteinase 3, preferentially lysed fresh human leukemic cells.

Amino Acid Sequence

Strengthening patient education for ORT services in the Central African Republic.

This paper describes the design and implementation of a health worker training program in diarrhea case management and its effect on patient education in health facilities in the Central African Republic (C.A.R.). In 1989, a facility-based assessment of health worker practices in managing diarrheal disease in children under 5 years of age documented serious deficiencies in patient education as performed by health workers. Based on these results, the Ministry of Health (MOH) designed an inservice training program that promoted education as an integral component of curative care. The training program was implemented in all five health regions of the country. An evaluation of the training's impact on the delivery of patient education indicated dramatic increases in the number of messages health workers communicated to mothers. This experience demonstrated that the patient education practices of health workers can be improved through inservice training that integrates the teaching of clinical and communication skills. Additional study in C.A.R. is needed to (1) further improve the quality of patient education for diarrhea and other childhood communicable diseases, (2) determine the impact of patient education on the care provided by mothers in the home following a clinic visit, and (3) assess how operational research can be conducted within the limitations of inservice training programs and routine clinical operations.

Central African Republic

Cumulative trauma disorders among apparel manufacturing employees in the southeastern United States.

Factors associated with cumulative trauma disorders (CTDs) of the upper extremities were studied retrospectively, using data from three apparel manufacturing plants in the southeastern United States. Reported CTDs among the employees at risk during fiscal years 1991 and 1992 were analyzed focusing on individual and plant variables. Results showed that CTD rates increased from 1991 to 1992 and fluctuated in a cyclical pattern each year, peaking during January, March, and August. Employee age and duration of employment were associated with CTD rates. Employees aged 45 to 49 had higher CTD rates than those in any other age groups. Employees with 1 to 3 years' experience had higher CTD rates than employees with more years of service.

Adolescent

MR features of an intracerebellar chloroma.

Granulocytic sarcoma (chloroma) is a rare tumor almost always associated with leukemia. Intraaxial brain lesions are rare, and can mimic infection or primary neoplasm. This intracerebellar chloroma arose after autologous bone marrow transplantation in a 29-year-old woman with leukemia. On T1-weighted MR images, the lesion was isointense with gray matter, and enhanced homogeneously. On T2-weighted and proton density-weighted MR sequences, the center was isointense with gray matter and the periphery was isointense with white matter. The lesion's tendency to remain isointense on sequences with long repetition times is presumably attributable to the presence of myeloperoxidase.

Adult

Phase I trial of an interleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies: complete response in a patient with Hodgkin's disease refractory to chemotherapy.

BACKGROUND: DAB486IL-2 is a recombinant fusion toxin in which the native diphtheria toxin-receptor binding-domain has been replaced with human interleukin-2 (IL-2). This molecule is specifically cytotoxic in vitro within 30 minutes for cells that express the high-affinity IL-2 receptor (IL-2R). METHODS: This was a Phase I/II study of DAB486IL-2 as a brief infusion in 15 patients with refractory lymphoid malignancies. Five patients per cohort received DAB486IL-2 as a 30-60 minute intravenous infusion at dose levels of 0.075, 0.115, and 0.2 mg/kg daily for 5 days. RESULTS: The maximal tolerated dose (MTD) of DAB486IL-2 was determined to be 0.2 mg/kg daily on the basis of hypersensitivity-like symptoms and reversible hepatic transaminase elevations. Other adverse effects included mild creatinine elevations, proteinuria, and hypoalbuminemia. The presence of antibodies to diphtheria toxin or DAB486IL-2 was correlated with hypersensitivity-like effects but did not prevent an antitumor effect. One complete response was observed in a patient with Hodgkin's disease in relapse with bilateral pulmonary nodules after autologous bone marrow transplantation. He remains free of disease more than 2 years after completion of therapy. CONCLUSIONS: The dramatic antitumor response seen in one patient and the relative tolerability of DAB486IL-2 indicates the potential utility of this targeted agent in IL-2-expressing hematologic malignancies.

Adult

Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants.

The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.

Adolescent

DNA structure, hydration and dynamics.

Although the double helical model of DNA structure is now 40 years old, there is still considerable effort being made to elucidate the range of conformations that can be adopted by this flexible molecule. We review the current state of our knowledge of DNA structure which is available from both experimental and computational approaches.

DNA

Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies.

DAB486IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB486IL-2, administered as a 6 hour continuous intravenous infusion on days 1, 2, 8, 9, 15, and 16 of each 28 day cycle. Cohorts of 3 to 6 patients were treated with escalating doses. The starting dose was 0.1 mg/kg/day with increments of 0.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, anemia, thrombocytopenia, fever, and creatinine elevation. A partial response of approximately nine months duration was observed in a patient with small cell lymphocytic non-Hodgkin's lymphoma, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB486IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.

Adult

Phase I trial of a 90-minute infusion of the fusion toxin DAB486IL-2 in hematological cancers.

DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we conducted a single arm, dose escalation study of a 90-min infusion of DAB486IL-2 daily for 5 days. Patients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentially more effective therapy were eligible for enrollment. Fifteen men and 8 women with a median age of 49 years were given a total of 51 courses of DAB486IL-2. The maximum tolerated dose was 0.3 mg/kg/day defined by renal insufficiency associated with hemolysis and thrombocytopenia. The clearance of DAB486IL-2 from serum fit a one-compartment model with a half-life of 11.5 +/- 4.3 (SD) min at the 0.2-mg/kg dose. Two patients sustained a partial response and 4 patients had tumor reduction not qualifying for an objective response. No tumors that were negative for expression of the p55 subunit of the receptor responded to DAB486IL-2 treatment. Reduction in size occurred in 2 tumors in which p55 expression was unknown and 4 patients with tumors that were known to be p55 positive. Dosing determined by specific activity rather than mass also appeared to be an important determinant of response. This study suggests that the presence of p55 expression on tumor cells is necessary, but alone may not be sufficient to achieve a tumor response. The correlation of additional variables such as specific activity of DAB486IL-2 and tumor expression of the p75 subunit of the IL-2 receptor and receptor function will also require further study.

Adult

Exclusion of linkage of genetic focal sharp waves to the HLA region on chromosome 6p in families with benign partial epilepsy with centrotemporal sharp waves.

Benign partial epilepsy with centrotemporal sharp waves (benign rolandic epilepsy, BRE) is a common form of idiopathic, localisation-related epilepsy of childhood. The characteristic age-dependent focal sharp wave (fsw) found on the EEG in this disorder segregates as an autosomal dominant trait in families with probands with BRE and acts as a neurobiological marker for the increased risk of developing BRE, other benign partial epilepsies of childhood, and other developmental disorders in these families. One of the genes for idiopathic generalised epilepsy (IGE), designated EJM1, has been mapped in families with probands with juvenile myoclonic epilepsy, by linkage to the HLA region on chromosome 6. As BRE and IGE are benign, idiopathic, age-dependent epilepsies, EJM1 is a candidate locus for the fsw underlying BRE and related disorders. Genetic linkage analysis was undertaken in 11 families with probands with BRE and one or more first degree relatives with fsw, with or without BRE, using a polymorphic DNA marker within the HLA region. Apparently unaffected individuals were classed as affection status unknown. Assuming autosomal dominant inheritance with a penetrance of 0.9 gave a lod score of -2.3 at zero recombination, excluding the candidate gene region around HLA. These observations exclude an important candidate gene for this common disorder, and suggest a fundamental molecular and genetic distinction between the benign partial epilepsies of childhood and the idiopathic generalised epilepsies.

Adolescent

Benign childhood epilepsy with centrotemporal spikes and the focal sharp wave trait is not linked to the fragile X region.

Benign childhood epilepsy with centrotemporal spikes (BCECS, benign rolandic epilepsy) is a common form of genetically determined localisation-related epilepsy of childhood. The characteristic age-dependent focal sharp wave (fsw) found on the EEG in this disorder segregates as a dominant trait in families with probands with BCECS. Seizures occur in a significant proportion of individuals with the fragile X syndrome in association with EEG abnormalities comparable to those found in BCECS. The possibility of a common genetic basis for these disorders was investigated by linkage analysis. Six pedigrees with probands with BCECS were analysed using a marker locus DXS548, close to the fragile X site, fra (X). Obligate recombinants between DXS548 and the fsw trait were observed in all six families. Assuming X-linked dominant inheritance and penetrance values of 0.4 (male) and 0.1 (female) a negative lod score of -6.823 was obtained at zero recombination and lod scores of -2.0 at 10cM either side of the fra (X) locus. These results exclude an important candidate gene for this common childhood disorder.

Adolescent

The evaluation and treatment of sleep disturbances in young children.

This study examines the accuracy of parents' reports about their children's sleep behavior and their response to a behavioral treatment. Twenty-eight sleep-disordered and thirty control children aged 12-36 months were filmed during three nights using an infrared camera and their sleep behavior compared with parental reports. There were significant differences among the groups with parents of good sleepers being less accurate in reporting on their children's sleep behavior. Poor sleepers also had more behavior problems, a more difficult temperament and more adverse early medical histories. The good sleepers woke up as frequently as the poor sleepers. However, they managed to soothe themselves back to sleep without disturbing anyone. Virtually all poor sleepers showed significant improvement following treatment.

Adult