Human granulocyte-macrophage colony-stimulating factor (hGM-CSF): identification of a binding site for a neutralizing antibody.

One approach to the localization of functionally active regions of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is to map the epitopes recognized by neutralizing anti-hGM-CSF monoclonal antibodies. We have defined the epitope recognized by one neutralizing antibody (LMM102) using proteolytic fragments obtained by enzymic digestion of bacterially synthesized hGM-CSF. RP-HPLC fractionation of a tryptic digest resulted in the identification of an immunoreactive "tryptic core" peptide containing 66 amino acids (52% of the protein). Further digestion of this "tryptic core" with S. aureus V8 protease produced a unique immunoreactive hGM-CSF product comprising two peptides, residues 86-93 and 112-127, linked by a disulfide bond between residues 88 and 121. The individual peptides, generated by reduction with dithiothreitol, were not recognized by the antibody. An analog of this peptide has been synthesized chemically and shown to have similar immunoreactivity to the epitope obtained by enzymic digestion. A series of modified peptides has also been synthesized to identify further the region required for antibody recognition.     

Self-selection in responding to a health risk appraisal: are we preaching to the choir?

Abstract The objectives of the present study were a) to examine behavioral and sociodemographic factors associated with voluntary response to a health risk appraisal (HRA), and b) to assess the effect of HRA feedback on subsequent preventive health behaviors and risk-taking behaviors. After collection of health behavior data from a larger sample participating in a Navy-wide health promotion evaluation, an HRA was mailed to a random subsample of 625 individuals. A total of 270 (43 %) people responded to the HRA and received printed feedback. Follow-up health behavior data were collected one year later from 93 of the 270 HRA respondents. These 93 individuals were then matched with a control group who did not receive an HRA but had provided health behavior data both times. Analyses revealed that HRA respondents were older, better educated, had higher health status, smoked less, consumed less alcohol, and used seat belts more often than nonrespondents. Separate analyses of HRA respondents and matched controls indicated that HRA participation had no significant effect on subsequent preventive health behaviors or risk-taking behaviors. Results suggest limitations of the HRA as an effective due to behavior change.     

Human Antibody Fragments Specific for the Epidermal Growth Factor Receptor Selected from Large Non-immunised Phage Display Libraries

Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2 nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (k_a and k_d). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.     

A systematic review and meta-analysis of the role of radiology in the diagnosis of occult inguinal hernia

Background

Inguinal hernias are a common cause of groin pain. Most hernias are detectable by clinical examination and many patients proceed to hernia repair on the basis of history and examination findings alone. However, a significant proportion of patients with symptoms suggestive of groin hernia are found to have a normal clinical examination. Several radiological techniques have been developed to solve the dilemma posed by occult inguinal hernias. No systematic review or meta-analysis has addressed this common clinical problem.

Methods

A systematic review and meta-analysis were undertaken of relevant articles in Medline, Embase, and the Cochrane database. Studies were assessed using the QUADAS tool. Statistical analysis was undertaken.

Results

We have shown in this meta-analysis that ultrasound has a sensitivity of 86 % and a specificity of 77 % in occult inguinal hernias. Computed tomography has a sensitivity of 80 % and a specificity of 65 %. Herniography has a sensitivity of 91 % and a specificity of 83 %.

Conclusions

Based on this systematic review, herniography should be considered as the initial investigation for occult inguinal hernia where available. In centers where this is not available, ultrasound of the groin should be used with good clinical judgment. When there is still diagnostic uncertainty, further investigation with magnetic resonance imaging should be considered to exclude alternative pathology.     

A novel tissue culture model for evaluating the effect of aging on stem cell fate in adult microvascular networks

GeroScience - In vitro models of angiogenesis are valuable tools for understanding the underlying mechanisms of pathological conditions and for the preclinical evaluation of therapies. Our...     

Toxidrome recognition to improve efficiency of emergency urine drug screens

We correlated clinical symptom complexes of drugs (toxidromes) to results of 204 consecutive toxicological screens ordered in our emergency department. The toxidromes were divided into eight categories: sedative hypnotic, narcotic, stimulant, coma-apnea-seizure, hallucinogenic, anticholinergic, unknown, and "no drugs." Emergency medicine nurses, clinical pharmacists, and medical residents were asked to choose one or more of the above toxidromes independently when ordering the toxicology screen. The nurses achieved the highest symptom complex recognition of the drug (55 of 61, 88%) followed by medical residents (76 of 90, 84%) and clinical pharmacists (27 of 34, 79.4%), but the differences were not statistically significant. We conclude that the major determinant in selecting correct toxidromes is clinical experience of the practitioners. Given the percentages of toxidrome recognition, it should be possible to increase efficiency of laboratory use by ordering tests only for the drugs clinically suspected in a particular toxic patient.     

Physical therapists' perceptions of family involvement in the rehabilitation process

The purpose of this qualitative study was to describe how physical therapists working in rehabilitation settings involved families in the patient's rehabilitation program and what factors facilitated or impeded this involvement. Forty physical therapists practicing in the eastern United States were individually interviewed on their involvement of families in a patient's rehabilitation. The interview data were transcribed, coded, and analyzed for main themes. Family involvement was found to be a significant aspect of a patient's rehabilitation. Factors pertaining to the family, the patient, the healthcare organization and the physical therapist were identified. Factors, such as the family's knowledge, attitudes and skills of the family, their relationship with the patient prior to the injury or disability, the availability and opportunity of family members to be involved, and their physical capabilities, all influenced the degree to which the family participated. Therapists also perceived the cognitive status of the patient as a factor which dictated the proper amount of family participation. The health-care organization was an important factor which needed to encourage and support the family participation. With decreased lengths of stay there is less time for families to be independent in caring for their loved one. The organization of the department could be instrumental in this by providing multiple formal and informal avenues for family training, such as support groups, home visits, ‘open door’ policy visiting hours, and scheduling changes. Finally, the physical therapists might have been the single most significant factor in facilitating family involvement. It was important for them to establish open and honest communication and be pro-activists for their patients and their families. The findings were consistent with the existing literature base in relation to the patient and family. Additional findings present physical therapists and healthcare organizations with suggestions for improving family education. Copyright © 1996 Whurr Publishers Ltd.