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Biomedical subjects

M Gold

Publications and source records attributed to M Gold.

At least 37 records · Page 2Linked to original sources
PubMed2001

HMO provider networks in Medicare+Choice: comparing Medicare and commercial lines of business.

The Medicare+Choice (M+C) program was intended to expand choice of managed care plans for Medicare beneficiaries. In the past few years, the opposite has occurred as many participating HMOs reduced Medicare service areas or withdrew from the program. This paper presents findings from a study of the provider networks of 85 HMOs that were participating in M+C in 1999. The study shows that provider networks serving Medicare enrollees are usually similar to those developed for HMOs' commercial line of business, but when they are different, Medicare provider networks are smaller. Most HMOs also had at least some problems maintaining their Medicare provider networks. These findings have implications for the future of the Medicare+Choice program and Medicare enrollees' access to health care.

Aged↗
PubMed2000

A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease.

OBJECTIVE: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. DESIGN: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. RESULTS: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. CONCLUSION: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.

Aged↗
PubMed2000

Thermodynamic and functional characterization of protein W from bacteriophage lambda. The three C-terminal residues are critical for activity.

Gene product W (gpW), the head-tail joining protein from bacteriophage lambda, provides a fascinating model for studying protein interactions. Composed of only 68 residues, it must interact with at least two other proteins in the phage, and probably with DNA. To study the structural and functional properties of gpW, plasmids were constructed expressing gpW with hexahistidine tag sequences at either the N or C terminus. The purified wild type fusion proteins were found to be stably folded and biologically active. The protein is monomeric as judged by equilibrium ultracentrifugation, and appears to unfold by a cooperative two-state mechanism. Circular dichroism studies indicate that the protein is 47% helical, with a T(m) of 71.3 degrees C, and a DeltaG(u) of 3.01 kcal/mol at 25 degrees C. Mutagenesis of the three hydrophobic C-terminal residues of gpW showed that they are critical for activity, even though they do not contribute to the thermodynamic stability of the protein. Using secondary structure prediction as a guide, we also designed destabilized gpW mutants. The hydrophobic nature of the gpW C terminus caused these mutants to be degraded by the ClpP-containing proteases in Escherichia coli.

Amino Acid Sequence↗
PubMed2000

Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,).

Transition state analogue boronic acid inhibitors mimicking the structures and interactions of good penicillin substrates for the TEM-1 beta-lactamase of Escherchia coli were designed using graphic analyses based on the enzyme's 1.7 A crystallographic structure. The synthesis of two of these transition state analogues, (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1) and (1R)-1-acetamido-2-(3-carboxy-2-hydroxyphenyl)ethylboronic acid (2), is reported. Kinetic measurements show that, as designed, compounds 1 and 2 are highly effective deacylation transition state analogue inhibitors of TEM-1 beta-lactamase, with inhibition constants of 5.9 and 13 nM, respectively. These values identify them as among the most potent competitive inhibitors yet reported for a beta-lactamase. The best inhibitor of the current series was (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1, K(I) = 5.9 nM), which resembles most closely the best known substrate of TEM-1, benzylpenicillin (penicillin G). The high-resolution crystallographic structures of these two inhibitors covalently bound to TEM-1 are also described. In addition to verifying the design features, these two structures show interesting and unanticipated changes in the active site area, including strong hydrogen bond formation, water displacement, and rearrangement of side chains. The structures provide new insights into the further design of this potent class of beta-lactamase inhibitors.

Acylation↗
PubMed2000

Gender-specific association of the angiotensin converting enzyme gene with Alzheimer's disease.

Epidemiological studies have demonstrated that risk factors for vascular disease are also risk factors for Alzheimer's disease (AD). The gene for the angiotensin converting enzyme (ACE) has recently been reported to be associated with risk for AD. We have investigated the possibility of such an association in 98 clinic-based and 73 community-based AD cases versus 175 community-based controls and find a gender-specific association of ACE genotype with AD in the female clinic population. These data suggest that gender may interact with genetic factors to influence risk for AD. Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension. However, the results may also be a consequence of the known anomalies that arise in genetic association studies as a consequence of sample selection.

Alzheimer Disease↗
PubMed2000

Adverse events following immunisation associated with the 1998 Australian Measles Control Campaign.

The Measles Control Campaign (MCC) conducted in Australia from August to November 1998 resulted in a total of 1.7 million school children being vaccinated. This article reports on the Adverse Events Following Immunisation (AEFI) associated with measles-mumps-rubella vaccine (MMR) administered as part of the MCC. Reports of adverse events that occurred within 30 days of administration of the MMR vaccine were assessed by an expert panel that assigned a causality rating to each AEFI. Reports with missing onset dates or uncertain causality were excluded. Eighty-nine AEFI were classified as associated with MMR vaccine and the overall rate of adverse events was 5.24 per 100,000 doses of vaccine administered. Of these 46 were thought to be certainly caused by MMR vaccine, 23 were probably and 20 were possibly associated with the vaccine. Although 46 reactions were categorised to be certainly caused by the MMR vaccine, the majority of these were syncopal fits, syncope, local reactions, and allergic reactions that were short-lived, and all of these children recovered. The most commonly occurring adverse reaction was syncopal fit with a rate of 1.24 per 100,000. There was only one anaphylactic reaction, giving a rate of 0.06 per 100,000. The combined rate for anaphylaxis, anaphylactoid and allergic reactions was 1.06 per 100,000 administered doses. The rate of seizures (febrile and afebrile) was 0.30 and encephalopathy was 0.06 per 100,000 doses administered. Of the 89 children who had an AEFI, 43 did not require hospitalisation or medical attention while 13 were seen in an emergency room, 14 were hospitalised and 19 were seen by a doctor. There were no deaths reported resulting from the administration of the MMR vaccine during the period of the campaign. All children who had an AEFI have recovered although 9 children could not be followed up for reasons of confidentiality. The overall rate of adverse events was lower than that observed in the 1994 measles campaign conducted in the United Kingdom. On comparing the risks and benefits of MMR vaccine, the benefits of this MCC far outweigh the incidence of serious adverse events associated with immunisation.

Adolescent↗
PubMed2000

An open-label trial of bromocriptine in nonfluent aphasia: a qualitative analysis of word storage and retrieval.

Anomia is a commonly found in aphasia and has been attributed to a loss of representations (storage deficit) or to a loss of access to these representations (retrieval deficit). Bromocriptine, a dopamine agonist, was tested on four patients, two men and two women, with nonfluent aphasia. The patients were tested in an open-label ABBA design using a stochastic model that measured the degree of storage and retrieval deficits. All patients showed significant improvements in word retrieval. Bromocriptine may be a useful adjunct in the treatment of selected patients with a nonfluent aphasia in which retrieval deficits play a major role.

Aged↗
PubMed2000

Oil and water? Lessons from Maryland's effort to protect safety net providers in moving to Medicaid managed care.

Studies have highlighted the tensions that can arise between Medicaid managed care organizations and safety net providers. This article seeks to identify what other states can learn from Maryland's effort to include protections for safety net providers in its Medicaid managed care program--HealthChoice. Under HealthChoice, traditional provider systems can sponsor managed care organizations, historical providers are assured of having a role, patients can self-refer and have open access to certain public health providers, and capitation rates are risk adjusted through the use of adjusted clinical groups and claims data. The article is based on a week-long site visit to Maryland in fall 1998 that was one part of a seven-state study. Maryland's experience suggests that states have much to gain in the way of "good" public policy by considering the impact of their Medicaid managed care programs on the safety net, but states should not underestimate the challenges involved in balancing the need to protect the safety net with the need to contain costs and minimize the administrative burden on providers. No amount of protection can compensate for a poorly designed or implemented program. As the health care environment continues to change, so may the need for and the types of protections change. It also may be most difficult to guarantee adequate protections to those who need it most--among relatively financially insecure providers that have a limited management infrastructure and that depend heavily on Medicaid and the state for funds to care for the uninsured.

Community Participation↗
PubMed2000

Improving value measurement in cost-effectiveness analysis.

OBJECTIVE: Before cost-effectiveness analysis (CEA) can fulfill its promise as a tool to guide health care allocation decisions, the method of incorporating societal values into CEA may need to be improved. DESIGN: The study design was a declarative exposition of potential fallacies in the theoretical underpinnings of CEA. Two values held by many people-preferences for giving priority to severely ill patients and preferences to avoid discrimination against people who have limited treatment potential because of disability or chronic illness-that are not currently incorporated into CEA are discussed. CONCLUSIONS: Traditional CEA, through the measurement of quality-adjusted life years (QALYs), is constrained because of a "QALY trap." If, for example, saving the life of a person with paraplegia is equally valuable as saving the life of a person without paraplegia, then current QALY methods force us to conclude that curing paraplegia brings no benefit. Basing cost-effectiveness measurement on societal values rather than QALYs may allow us to better capture public rationing preferences, thereby escaping the QALY trap. CEA can accommodate a wider range of such societal values about fairness in its measurements by amending its methodology.

Attitude to Health↗
PubMed2000

Performance of a new steroid-eluting coronary sinus lead designed for left ventricular pacing.

The Ventak CHF/CONTAK CD Biventricular Pacing Study is a prospective randomized trial to examine the safety and efficacy of biventricular (BV) pacing in patients with standard indications for an ICD, symptomatic heart failure, a LVEF < or = 0.35, and a QRS > or = 120 ms. Patients underwent implantation of a BV pacing and sensing system with backup defibrillation capability, which includes a steroid-eluting coronary venous lead that is advanced into the coronary venous vasculature by over-the-wire techniques. LV pacing threshold, BV impedance, and BV R wave amplitude were measured in 58 consecutive patients. Using a percutaneous over-the-wire insertion technique, steroid-eluting coronary venous leads were associated with satisfactory mean LV pacing threshold, BV impedance, and BV R wave amplitude acutely up to 4 months after implantation. Pacing threshold stabilized 2 weeks after lead implantation and sensing threshold remained stable from the time of implant.

Cardiac Surgical Procedures↗
PubMed2000

Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service.

BACKGROUND: In Australia an adverse event following immunisation (AEFI), with the exception of anaphylaxis and encephalopathy, is no longer considered an absolute contraindication to continuing vaccination with the suspect vaccine. Despite these recommendations there is a paucity of information on the re-vaccination of such children. AIMS: To describe the re-vaccination of a large number of children with a past history of an AEFI. METHODS: A review of children attending special immunisation services in three Australian tertiary care paediatric centres. RESULTS: During the review 970 children attended of whom 469 had experienced a past AEFI. Of these, 293 had experienced minor while 176 children had experienced significant neurological or allergic reactions. The majority (421/469) were re-vaccinated, with only one child having a significant neurological event; this was transient and resolved spontaneously. CONCLUSIONS: Re-vaccination of children who have a past history of an AEFI appears safe. A special immunisation service should be part of a comprehensive immunisation programme.

Adolescent↗
PubMed2000

Visual search in complex displays: factors affecting conflict detection by air traffic controllers.

Recent free flight proposals to relax airspace constraints and give greater autonomy to aircraft have raised concerns about their impact on controller performance. Relaxing route and altitude restrictions would reduce the regularity of traffic through individual sectors, possibly impairing controller situation awareness. We examined the impact of this reduced regularity in four visual search experiments that tested controllers' detection of traffic conflicts in the four conditions created by factorial manipulation of fixed routes (present vs. absent) and altitude restrictions (present vs. absent). These four conditions were tested under varying levels of traffic load and conflict geometry (conflict time and conflict angle). Traffic load and conflict geometry showed strong and consistent effects in all experiments. Color coding altitude also substantially improved detection times. In contrast, removing altitude restrictions had only a small negative impact, and removing route restrictions had virtually no negative impact. In some cases conflict detection was actually better without fixed routes. The implications and limitations of these results for the feasibility of free flight are discussed. Actual or potential applications include providing guidance in the selection of free flight operational concepts.

Aircraft↗
PubMed2000

"Second-generation" Medicaid managed care: can it deliver?

This article offers insight into what we term "second-generation" Medicaid managed care. In case studies of seven States, we examined three critical questions: (1) Does managed care experience facilitate program operations? (2) Can Medicaid managed care deliver on important goals? and (3) Can States extend the program beyond low-income families and children to others? The answers are encouraging but also suggest caution. Medicaid managed care is not a solution to fundamental problems facing the Medicaid program. It may be a tool to encourage better delivery of care. This requires a long-term commitment and adequate financing to develop stable partnerships with all stakeholders.

Aged↗