Primary Care Physicians’ Attitudes Regarding Race-Based Therapies

Background  

There is little to no information on whether race should be considered in the exam room by those who care for and treat patients. How primary care physicians understand the relationship between genes, race and drugs has the potential to influence both individual care and racial and ethnic health disparities.     

Retrospective population-based assessment of medically attended injection site reactions,seizures, allergic responses and febrile episodes after acellular pertussis vaccine combined with diphtheria and tetanus toxoids

BACKGROUND: Since 1997 diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccines have been recommended for the five dose pertussis vaccination series. To assess rates of medically attended injection site reactions (ISRs), seizures, allergic responses and febrile episodes after Tripedia DTaP vaccine administered in the context of routine care, we conducted a retrospective assessment among the population of Group Health Cooperative from 1997 through 2000. METHODS: Administrative databases were used to identify medical visits linked with diagnostic codes potentially indicative of ISRs, seizures, allergic responses and febrile episodes after DTaP vaccine. Outcomes were confirmed by medical record review. RESULTS: During the study period 76 133 doses of DTaP were administered. Of the 26 ISRs identified, 6 followed DTaP given as the fourth dose and 18 followed DTaP given as the fifth dose, for rates of 1 per 2779 and 1 per 900 vaccinations, respectively. During the study period nearly all children receiving DTaP as the fifth dose had received whole cell pertussis vaccine for their primary series, and all of the fifth dose ISRs were among that group. Four of those reactions involved the entire upper arm. The rate of febrile seizures within 2 days of DTaP among children <2 years of age was 1 per 19 496 vaccinations. CONCLUSIONS: The low rate of febrile seizures and other serious events confirms the safety of DTaP vaccine. The risk of medically attended ISRs was highest with DTaP given as the fifth dose, and whole arm reactions were reported, but medically attended ISRs were relatively uncommon and were self-limited.     

Parental anxiety associated with referral of a child to a pediatric cardiologist for evaluation of a Still's murmur

OBJECTIVE: We assessed factors contributing to parental anxiety when children are referred to a cardiology clinic for evaluation of a Still's murmur. METHODS: Parents of 95 children completed questionnaires designed to assess family and patient characteristics, parents' ratings of their anxiety and the reassurance they received from their pediatrician, and current (state) and general anxiety levels. RESULTS: Parents reported anxiety about multiple issues including the need for medication (49%), sports restrictions (41%), cardiac surgery (29%), cardiac risk for siblings (20%), and premature death (13%). Of reporting mothers, 19% felt the murmur resulted from something they did wrong during pregnancy. Although 54% of parents were extremely reassured by their pediatrician, only 17% had no anxiety associated with the specialty visit. After reassurance from the cardiologist, 7% of parents had persistent anxiety. In multivariable analysis, 2 features, both related to the referring pediatrician, were significantly related to parental anxiety level. High parental anxiety was associated with lower pediatrician reassurance ratings and greater pediatrician practice years. CONCLUSIONS: Parental anxiety is common among parents of children referred for specialty evaluation. Educational strategies to improve pediatrician communication skills with parents may improve quality of care.     

Effectiveness of Respondent-Driven Sampling to Recruit High Risk Heterosexual Men Who Have Multiple Female Sexual Partners: Differences in HIV Prevalence and Sexual Risk Behaviours Measured at Two Time Points

Regular HIV bio-behavioural surveillance surveys (BBSS) among high risk heterosexual (HRH) men who have multiple female sexual partners is needed to monitor HIV prevalence and risk behaviour trends, and to improve the provision and assessment of HIV prevention strategies for this population. In 2006 and 2008 we used respondent-driven sampling to recruit HRH men and examine differences in HIV prevalence and risk behaviours between the two time points. In both surveys, the target population had little difficulty in recruiting others from their social networks that were able to sustain the chain-referral process. Key variables reached equilibrium within one to six recruitment waves and homophily indices showed neither tendencies to in-group nor out-group preferences. Between 2006 and 2008 there were significant differences in condom use with main sexual partners; numbers of sexual partners; and alcohol consumption. Further BBSS among this population are needed before more reliable trends can be inferred.     

Balance rehabilitation and dual-task ability in older adults

Background/PurposeRecent evidence suggests that an impaired ability to allocate attention to balance during dual-task situations is a powerful predictor of falls. Increased difficulty under dual-task conditions may result from cognitive or motor impairments or both. The extent to which interventions should be directed at cognitive or motor impairments is unclear. The goal of this study was to examine the extent to which standard balance rehabilitation improves dual-task ability.MethodsA retrospective chart review of patients without vestibular or neurological disorders who were referred to physical therapy for disequilibrium was performed. Patients were assessed initially and at discharge for balance-related confidence, gait speed, fall risk, sensory integration, and dual-task ability. Balance rehabilitation involved weekly sessions plus home training for strengthening, endurance, center of gravity control training, multisensory training and postural strategy training. Specific dual-task training was not included.ResultsAverage age was 75.8 ± 7.5 years, with 49% of participants being female. Participants improved significantly in all outcome measures, including measures of dual-task ability (p < 0.05). Percent improvement from initial to discharge assessment was significantly greater for balance confidence, fall risk and sensory integration than dual-task ability.ConclusionStandard balance rehabilitation significantly improved all measures of gait and balance, including dual-task measures; however, measures of dual-task ability did not improve to the same extent. Improvements of underlying motor impairments may not adequately address impaired dual-task ability.     

In vivo observation of intracellular oximetry in perfluorocarbon‐labeled glioma cells and chemotherapeutic response in the CNS using fluorine‐19 MRI

Preclinical development of therapeutic agents against cancer could greatly benefit from noninvasive markers of tumor killing. Potentially, the intracellular partial pressure of oxygen (pO₂) can be used as an early marker of antitumor efficacy. Here, the feasibility of measuring intracellular pO₂ of central nervous system glioma cells in vivo using ¹⁹F magnetic resonance techniques is examined. Rat 9L glioma cells were labeled with perfluoro‐15‐crown‐5‐ether ex vivo and then implanted into the rat striatum. ¹⁹F MRI was used to visualize tumor location in vivo. The mean ¹⁹F T₁ of the implanted cells was measured using localized, single‐voxel spectroscopy. The intracellular pO₂ in tumor cells was determined from an in vitro calibration curve. The basal pO₂ of 9L cells (day 3) was determined to be 45.3 ± 5 mmHg (n = 6). Rats were then treated with a 1× LD10 dose of bischloroethylnitrosourea intravenously and changes in intracellular pO₂ were monitored. The pO₂ increased significantly (P = 0.042, paired T‐test) to 141.8 ± 3 mmHg within 18 h after bischloroethylnitrosourea treatment (day 4) and remained elevated (165 ± 24 mmHg) for at least 72 h (day 6). Intracellular localization of the perfluoro‐15‐crown‐5‐ether emulsion in 9L cells before and after bischloroethylnitrosourea treatment was confirmed by histological examination and fluorescence microscopy. Overall, noninvasive ¹⁹F magnetic resonance techniques may provide a valuable preclinical tool for monitoring therapeutic response against central nervous system or other deep‐seated tumors. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Mycobacterium tuberculosis Cpn60.2 and DnaK Are Located on the Bacterial Surface,Where Cpn60.2 Facilitates Efficient Bacterial Association with Macrophages

Mycobacterium tuberculosis, the causative agent of tuberculosis, initially contacts host cells with elements of its outer cell wall, or capsule. We have shown that capsular material from the surface of M. tuberculosis competitively inhibits the nonopsonic binding of whole M. tuberculosis bacilli to macrophages in a dose-dependent manner that is not acting through a global inhibition of macrophage binding. We have further demonstrated that isolated M. tuberculosis capsular proteins mediate a major part of this inhibition. Two-dimensional polyacrylamide gel electrophoresis analysis of the capsular proteins showed the presence of a wide variety of protein species, including proportionately high levels of the Cpn60.2 (Hsp65, GroEL2) and DnaK (Hsp70) molecular chaperones. Both of these proteins were subsequently detected on the bacterial surface. To determine whether these molecular chaperones play a role in bacterial binding, recombinant Cpn60.2 and DnaK were tested for their ability to inhibit the association of M. tuberculosis bacilli with macrophages. We found that recombinant Cpn60.2 can inhibit ∼57% of bacterial association with macrophages, while DnaK was not inhibitory at comparable concentrations. Additionally, when polyclonal F(ab′)₂ fragments of anti-Cpn60.2 and anti-DnaK were used to mask the surface presentation of these molecular chaperones, a binding reduction of ∼34% was seen for anti-Cpn60.2 F(ab′)₂, while anti-DnaK F(ab′)₂ did not significantly reduce bacterial association with macrophages. Thus, our findings suggest that while M. tuberculosis displays both surface-associated Cpn60.2 and DnaK, only Cpn60.2 demonstrates adhesin functionality with regard to macrophage interaction.The initiation of a tuberculous infection involves the adherence and phagocytosis of Mycobacterium tuberculosis bacilli by host cells. It is generally thought that the primary host niche of M. tuberculosis is the alveolar macrophage (Mφ). To access this cell, ligands on the outer surface of the M. tuberculosis bacillus must come in contact with surface receptors of the Mφ. Although a significant amount of information concerning the Mφ receptors involved in this interaction is available (15, 71), the identities of the mycobacterial cell surface components that mediate this binding are less well understood. However, evidence for the involvement of mycobacterial lipoarabinomannans (57), capsular polysaccharides (8), glycopeptidolipids (72), 19-kDa antigen (9), mycotin (21), and Apa glycoprotein (47) has been reported previously.For any of the aforementioned moieties to be involved in the binding of mycobacteria to host cells, they would have to be located on the surface of the bacterium. Early reports suggested that the outer surface of mycobacteria was composed of mycosides (10, 11). Later studies indicated the presence of an outer polysaccharide-rich layer (45, 50), which could explain the presence of the so-called electron-transparent zone often seen in electron micrographs of mycobacteria inside Mφ (13, 18) and more recently in axenically grown bacteria (17, 42, 43, 51). Support for this contention has come from studies describing the presence of an outer surface capsule on M. tuberculosis (12). Carbohydrates make up 85% of the capsule, and the predominant sugar is glucan (approximately 70% of all sugars present). Arabinomannan and mannan are also present in significant quantities, as are a number of proteins, some of which are glycosylated. While about 10% of the capsule is composed of proteins, there is very little lipid present (31, 37). No evidence for the presence of lipoarabinomannan in the capsule was found, though phosphatidylinositol mannoside (PIM) was identified (38). The presence of a glycan-rich capsule surrounding intracellular mycobacteria has been confirmed using specific monoclonal antibodies (MAbs) against arabinomannan and glucan (58, 59).We have shown previously that mechanical removal of capsular material from M. tuberculosis results in a 10-fold increase in bacterial binding to Mφ, suggesting that the capsule can act as an antiphagocytic barrier that limits the interaction of M. tuberculosis with Mφ (65). However, even though the capsule reduces binding of M. tuberculosis to Mφ, it does not eliminate it, and it is clear that at least some bacteria maintain the capacity to bind to Mφ. These observations, along with our earlier studies showing that only certain populations of Mφ efficiently bind M. tuberculosis (64, 67), suggest that the M. tuberculosis capsule modulates the interaction of bacteria with host cells, preventing uptake by some populations of Mφ and directing the bacteria to specific Mφ types or particular receptor-ligand interactions. In this study, we have evaluated the diversity of proteins present in the M. tuberculosis capsule and assessed the role of two bacterial molecular chaperones, Cpn60.2 and DnaK, in host cell binding. Using both competitive-inhibition and epitope-masking strategies, we have shown that while both Cpn60.2 and DnaK are present on the bacterial surface, only Cpn60.2 appears to be necessary to facilitate efficient bacterial association with Mφ.