Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.

Community Networks↗

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Glycoantigen expression is regulated both temporally and spatially during development in the cellular slime molds Dictyostelium discoideum and D. mucoroides.

Six monoclonal antibodies were isolated which react with common antigens shared by multiple glycoconjugate species in the cellular slime mold Dictyostelium discoideum. Based on competition of antibody binding by glycopeptides and simple sugars, and inhibition of antibody binding by antigen pretreatment with Na periodate, it is argued that at least five of the six antibodies recognize epitopes which contain carbohydrate. These epitopes are consequently referred to as glycoantigens (GAs). Three of the GAs are expressed during growth and throughout the developmental cycle, but are eventually enriched in prestalk and stalk cells. The remaining three are expressed only during and/or after aggregation and are exclusively expressed or highly enriched in prespore cells and spores. These conclusions are derived from Western blot immunoanalysis of purified cell types, immunofluorescence, and EM immunocytochemistry. The two GAs found only in prespore cells appear to be exclusively enclosed within prespore vesicles. The third GA of this type, which is only enriched in prespore cells compared to prestalk cells, is also found in other vesicle types as well as on the cell surface. Two of the GAs enriched in prestalk cells are initially found in all cells of the slug. They are undetectable in spores and prominent in stalk cells. The third GA, though found in the interiors of both prestalk and prespore cells, is enriched on the cell surface of prestalk cells. The chief characteristics of expression of four of these GAs are conserved in the related species D. mucoroides. This species is characterized by continuous transdifferentiation of prespore cells into prestalk cells. This shows that the prespore cells maintain specific mechanisms for turning over their cell type specific GAs and that prestalk cells express a specific mechanism for inducing at least one of their cell-type specific GAs. These observations identify specific carbohydrate structures (as GAs) whose synthesis, subsequent localization and turnover are developmentally regulated. The exclusive association of two GAs with prespore vesicles identifies these GAs as markers for this organelle and raises questions regarding the functional significance of this association. The restricted cell surface localization of the other four GAs, together with data from cell adhesion studies, suggest the possibility of a potential role for these GAs in intercellular recognition leading to cell sorting.

Antibodies, Monoclonal↗

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Efficacy and tolerability of subcutaneous sumatriptan administered using the IMITREX STATdose System.

The efficacy and tolerability of subcutaneous (SC) sumatriptan administered with the IMITREX (sumatriptan succinate) STATdose System, which circumvents the need for patients or health care professionals to handle a syringe, were evaluated in two randomized, double-masked, parallel-group, placebo-controlled, multicenter studies. In the clinic, 158 adults with migraine diagnosed according to International Headache Society criteria received SC sumatriptan (6 mg) or placebo delivered with the IMITREX STATdose System for treatment of a migraine attack. By 120 minutes after SC dosing, 73% and 79% of sumatriptan-treated patients, compared with 28% and 37% of placebo-treated patients in studies 1 and 2, respectively, experienced headache relief (a statistically significant difference). Clinical disability scores 120 minutes after dosing showed that 75% and 85% of sumatriptan-treated patients, compared with 30% and 42% of placebo-treated patients, were normal or only mildly impaired (a statistically significant difference). Similar efficacy rates were observed for nausea, phonophobia, and photophobia. No serious or unusual adverse events occurred, and no clinically relevant abnormalities in laboratory test values were reported. Based on these results, we concluded that SC sumatriptan (6 mg) administered using the IMITREX STATdose System is effective for the treatment of migraine. The efficacy and tolerability profiles of SC sumatriptan administered with this device are similar to those reported for SC sumatriptan administered with a conventional syringe.

Adult↗

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Cerebellar stimulation for cerebral palsy spasticity, function, and seizures.

Chronic cerebellar stimulation (CCS) applied to the superio-medial cortex reduces generalized cerebral spasticity, athetoid movements, and seizures. Eighteen clinics have reported on 600 cerebral palsy (CP) patients who comprise 90% of those treated with CCS. CP patients have varying degrees of limited abilities interfered with by spasticity (primitive reflexes, increased muscle tone, co-contractions, and spasms) and by athetoid movements in two-thirds of the patients. With CCS, spasticity reduction occurred in 85% (marked 25%, moderate 34%, mild 27%) and resulted in improvements in patient drooling, speech, respiration, posture, motor performance, gait, joint range of motion, and mood states. Radiofrequency (RF)-linked stimulators were used initially with serious equipment and calibration problems; 68% of 422 patients improved. When totally implantable controlled-currrent stimulators were used, 86% of 178 patients improved. Our double-blind study of 20 CP patients using this implantable stimulator showed 12 (60%) improved in motor performance, joint range of motion, and profile of mood states when the stimulator was ON. When abilities are graded (1: poor to 9: best), the seven patients with the higher functioning grades (5-8) all improved (99% confidence level). Intractable seizures occurred in 27 (8%) of our CP patients. At a 17-year follow-up, 19 patients contacted were using or had used CCS with 10 (53%) seizure-free and 6 (32%) with reduced seizures. CCS should be given by a totally implanted controlled-current stimulator (1-4 microCoulombs/sq. cm. /phase, 150-200 Hz) applied intermittently to the superio-medial cerebellar cortex for safe, effective, and continuous results.

Athetosis↗

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Health screening in Hawaii.

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Aged↗

PubMedDate not supplied

You can go home again.

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Aged↗

PubMedDate not supplied

Effect of PDI overexpression on recombinant protein secretion in CHO cells.

In eukaryotic cells, protein disulfide isomerase (PDI) found in the endoplasmic reticulum (ER) catalyzes disulfide bond exchange and assists in protein folding of newly synthesized proteins. PDI also functions as a molecular chaperone and has been found associated with proteins in the ER. In addition, PDI functions as a subunit of two more complex enzyme systems: the prolyl-4-hydroxylase and the triacylglycerol transfer proteins. Increasing PDI activity in bacterial, yeast, and insect cell expression systems can lead to increased secretion of heterologous proteins containing disulfide bridges. Since Chinese hamster ovary (CHO) cells are widely used for the expression of recombinant proteins, we expressed recombinant human PDI (rhu PDI) in CHO cells to increase cellular PDI levels and examined its effect on the secretion of two different recombinant proteins: interleukin 15 (IL-15) and a tumor necrosis factor receptor:Fc fusion protein (TNFR:Fc). Secretion of TNFR:Fc (a disulfide-rich protein) is decreased in cells overexpressing PDI; the TNFR:Fc protein is retained inside these cells and colocalizes with the overexpressed rhu PDI protein in the endoplasmic reticulum. PDI overexpression did not result in intracellular retention of IL15. The nature of the interaction between PDI and TNFR:Fc was further investigated by expressing a disulfide isomerase mutant PDI in CHO cells to determine if the functional activity of PDI is involved in the cellular retention of TNFR:Fc protein.

Animals↗

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Holographic community: reconceptualizing the meaning of community in an era of health care reform.

Despite the call for community consciousness and humanistic values in today's health care reform environment, a clarified meaning of community to help guide redesign efforts is lacking. The Holographic Community is offered as a perspective to understand the meaning of community in new ways.

Community Participation↗

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Alexithymia and the interpretation of hostile-provoking situations.

BACKGROUND: To examine the relationship between alexithymia and the interpretation of hostility-provoking situations. METHODS: Sixty-two college students completed the TAS-20 and the Test for the Interpretation of Provoking Situations (TIPS). The TIPS measures how accurately participants can select the most likely explanation for the occurrence of a hypothetical, potentially provoking situation; it also measures how accurately participants judge whether explanations for events are innocent or noninnocent. RESULTS: Higher levels of alexithymia were associated with greater degrees of accuracy in interpreting the innocence of interpersonal information. The facets of alexithymia that were most strongly associated with interpretation accuracy varied by gender. CONCLUSIONS: Alexithymia is not associated with a general affect recognition deficit. The results are consistent with social factors playing a central role in alexithymia.

Adolescent↗

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Control of spasticity and involuntary movements--cerebellar stimulation.

By stimulating the medial aspect of the superior surface of the cerebellum with relatively short, low current stimulating pulses, spasticity and some involuntary movements have been reduced. Voluntary movements, as a result, are able to come through better; however, if the child has little voluntary ability, he is at least more relaxed, thus allowing the parents to care for him more easily. The children and adults with cerebral palsy have not been transformed from their previous status, although CCS has allowed them to become more independent, more ambulatory, and more communicative.

Cerebellum↗

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AutoCyte Interactive Screening System. Experience at a university hospital cytology laboratory.

OBJECTIVE: To evaluate the AutoCyte Interactive Screening System (AutoCyte-Screen) as a prescreener for the cytologic detection of cervicovaginal abnormalities. STUDY DESIGN: Eight hundred fifty-six AutoCyte Preparation System from cervicovaginal samples were evaluated by AutoCyte-Screen. AutoCyte-Screen displayed 120 cell images and 6 low-power images for review by the cytotechnologist. The cytotechnologist classified the case as WNL, abnormal or unsatisfactory. AutoCyte-Screen then revealed its classification as either unsatisfactory, WNL, abnormal or undecided. These classifications were combined to form an interactive result that was compared to the diagnosis from previous manual review. RESULTS: Interactive results were as follows: 251 (29.3%) abnormal, 581 (67.9%) WNL and 24 (2.8%) unsatisfactory. The abnormal interactive result contained 15 ASCUS/AGUS and 25 SILs; the WNL interactive result contained 5 ASCUS/AGUS and 2 SILs. No ASCUS/AGUS or SILs were in the unsatisfactory interactive category. The false negative proportion was 10.5% for the interactive diagnostic method vs. 15.7% for manual review for LSIL. CONCLUSION: The interactive use of AutoCyte-Screen can effectively select those cases which are most likely to contain an epithelial abnormality and could therefore be used as a triage system to select cases for manual review. A case with an interactive result of unsatisfactory and abnormal should receive full manual review, while those classified as WNL may require a less extensive review for quality assurance purposes. This resultant decrease in the manual screening load could increase laboratory efficiency.

False Negative Reactions↗