Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT).

1. Growing knowledge of the pathogenesis of human immunodeficiency virus (HIV)-1 infection has led to the identification of potential virus sanctuary sites within the central nervous system and gut-associated lymphoid tissue. 2. Maraviroc is a novel CCR5 antagonist for the treatment of HIV-1 infection. Disposition studies have been performed within the preclinical testing of maraviroc to determine its distribution to these anatomical sites. 3. Maraviroc, which is a substrate of the efflux transporter P-glycoprotein, shows limited distribution to the central nervous system as evidenced by cerebrospinal fluid concentrations that were 10% of the free plasma concentration following intravenous infusion to rats. Tissue distribution studies also indicated limited distribution of radioactivity into brain tissue of rats. 4. Radioactivity in gut-associated lymphoid tissue lymph nodes exceeded the concentrations in blood and concentrations in the contents of thoracic ducts of the lymphatic system were similar to blood levels following intravenous administration to rats.

Enhancing adherence following abnormal Pap smears among low-income minority women: a preventive telephone counseling strategy.

BACKGROUND: Although the incidence of precancerous conditions of the cervix has recently been increasing, prompt initial and long-term follow-up care can effectively reduce unnecessary morbidity and mortality. For example, the 4-year survival rates among those individuals at greatest risk for cervical cancer (i.e., minority women of low socioeconomic status) approach 95% with early detection. Women who present with advanced disease have a much poorer outlook (0%-39% survival). Yet, high-risk individuals are least likely to adhere to recommended diagnostic regimens. PURPOSE: We tested the effectiveness of a brief telephone counseling intervention directed to low-income, inner-city women after they had received an abnormal Pap smear result. The women were counseled on the importance of having an initial and 6-month repeat follow-up diagnostic procedure (i.e., colposcopic examination of the cervix). METHODS: A randomized trial design was used to compare the effects on these women of telephone counseling with (n = 192) or without (n = 203) a booster counseling telephone call prior to the appointment for a repeat colposcopy 6 months later, with a telephone appointment confirmation/reminder call (n = 216) and with standard care (i.e., no telephone contact) (n = 217). The telephone counseling protocol probed for and addressed three psychologic barriers to adherence (i.e., attendance at appointment for colposcopy examination): 1) encoding/expectancy (e.g., did the patient understand her risk of developing cervical cancer?); 2) affective/emotional (e.g., was the woman worried about the condition and its consequences?); and 3) self-regulatory/practical (e.g., was the woman likely to forget medical appointments?). Logistic regression was used to analyze the effects of the intervention group and the type of psychologic barriers elicited on colposcopy adherence. RESULTS: The results of logistic regression analysis (using those who received an appointment confirmation/reminder telephone call as the comparison group) revealed that telephone counseling produced significantly higher adherence rates to the initial colposcopy visit compared with telephone confirmation (300 [76%] of 395 women versus 147 [68%] of 216; odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.04-2.17). Additionally, standard care resulted in significantly lower adherence rates than did telephone confirmation (109 [50%] of 217 women versus 147 [68%] of 216; OR = 0.47; 95% CI = 0.32-0.73). Regarding attendance at the 6-month repeat colposcopy appointments, the 80 patients who had received telephone counseling prior to the initial visit (and were recommended for follow-up colposcopy) were significantly more likely to adhere than were the 47 patients who had received telephone confirmation (49 [61%] of 80 women versus 17 [36.2%] of 47; OR = 2.70; 95% CI = 1.15-6.51). The 6-month adherence rates for patients in the telephone confirmation group and the standard care group (n = 30) were low and did not differ significantly (17 [36.2%] of 47 women versus nine [30.0%] of 30; OR = 1.08; 95% CI = 0.40-2.89). Forgetting medical appointments (OR = 0.31; 95% CI = 0.19-0.51) and having scheduling conflicts (OR = 0.45; 95% CI = 0.28-0.72) were also associated with lower rates of adherence. CONCLUSION: The use of telephone counseling appears to be an effective strategy for enhancing initial and long-term adherence to a follow-up cervical diagnostic procedure in a traditionally underserved population. Patients who respond to a positive Pap test result with a particular profile of psychologic barriers may require more intensive and targeted counseling interventions.

Plasma leptin influences gestational weight gain and postpartum weight retention.

BACKGROUND: Leptin, a product of the obese (ob) gene, is released from adipocytes. At the same body mass index, women have higher concentrations than men. Thus, during pregnancy, leptin may influence gestational weight gain and retention of a portion of that gain postpartum. OBJECTIVE: We examined the relation between plasma leptin at entry to prenatal care and subsequent changes in weight from entry to prenatal care (at 17 wk gestation, baseline) until 6 mo postpartum. DESIGN: This was an observational study of leptin, gestational weight gain, and postpartum weight retention (at 6 wk and 6 mo postpartum) in 103 low-income pregnant women from Camden, NJ, with a pregravid body mass index (in kg/m2) in the normal range (19.8-26). RESULTS: After potential confounding variables were controlled for, leptin at entry significantly (P < 0.05) predicted weight gain in pregnancy, including measured rate of weight gain (x +/- SEE: 0.25 +/- 0.13 kg x unit log leptin(-1) x wk(-1)), measured rate of third-trimester weight gain (0.37 +/- 0.15 kg x unit log leptin(-1) x wk(-1)), rate of weight gain from recalled pregravid weight (0.23 +/- 0.09 kg x unit log leptin(-1) x wk(-1)), and net rate of gestational weight gain (0.22 +/- 0.09 kg x unit log leptin(-1) x wk(-1)). The leptin concentration at entry also significantly predicted retained weight in the postpartum period (at 6 mo: 7.29 +/- 3.33 kg/unit log leptin at entry) and marginally predicted changes in the sum of skinfold thicknesses (at 6 mo: 14.7 +/- 7.5 mm/unit log leptin at entry). CONCLUSION: These results suggest that a high leptin concentration at entry to prenatal care may predict an increased risk of overweight and obesity in vulnerable women.

Organization of face representation in the cingulate cortex of the rhesus monkey.

Neuroanatomical and electrophysiological methods were used to investigate the organization of face representation in the cingulate gyrus of four rhesus monkeys. Injections of fluorescent tracers placed into electrophysiologically defined sectors of the primary (M1) and supplementary (M2) motor cortices demonstrated that the rostral part of area 24c and the rostral part of area 23c send projections to the face representations of M1 and M2. Injections of biotinylated dextran amine involving the rostral part of area 24c and rostral part of area 23c demonstrated a direct projection from both areas to the facial nucleus of the pons. Our data suggest that areas 24c (M3) and 23c (M4) each contain a face representation which directly affects cortical as well as subcortical neural centers controlling facial activity.

Segregated parallel inputs to the brachial spinal cord from the cingulate motor cortex in the monkey.

The corticospinal projection from the cingulate motor cortex to the lower cervical enlargement (C5-T1) was investigated in four rhesus monkeys. Each received an injection of biotinylated dextran amine involving the arm representation of M3 (area 24c) or M4 (area 23c). In M3 cases, contralateral terminal label occurred in the lateral part of laminae V and VI of the intermediate zone including the reticulated marginal border. Lighter labeling was found in laminae IV, VII and the dorsolateral part of the anterior horn (lamina IX). In marked contrast, M4 cases demonstrated contralateral terminal labeling in the medial part of the dorsal and intermediate zones (laminae III, IV, V and VI). Lighter labeling involved the medial part of laminae VII, X and the dorsolateral anterior horn (lamina IX). Our experiments demonstrate that the corticospinal projection from the arm representations of M3 and M4 innervate distinct and separate parts of the spinal gray. Along with the noted differences in the cortical inputs to M3 and M4, these data suggest that the two cingulospinal systems may mediate independent and specialized forms of information effecting upper limb movement.

Applications of the monitoring process model to coping with severe long-term medical threats.

Guided by the monitoring process model (MPM), the authors explored the illness responses of 2 samples: high monitors (who are cognitively vigilant to and amplify threat-related cues) and low monitors (who avoid them and blunt their impact). Both samples-101 women with human papillomavirus-related precancerous cervical dysplasia and 75 HIV-infected gay men-were undergoing long-term medical follow-up and management. Structural equation analysis showed an adequate fit of the MPM to the data within each sample, supporting the model's heuristic value: High monitors experienced greater disease-related intrusive ideation, which triggered greater avoidant ideation to forestall panic, particularly in the more threatened HIV-positive sample. However, efforts to avoid disturbing intrusive thoughts were ineffective, requiring increasingly extreme defensive strategies (i.e., denial and mental and behavioral disengagement).

[Contact allergens in the standard patch test series from 1980-2004 at the University Clinic Aachen]. / Kontaktallergene der Standardreihe von 1980-2004 an der Universitätshautklinik Aachen.

Allergic contact dermatitis is a common disease whose specific therapy is avoidance of allergens. It is critical to identify frequency of occurrence of allergic reactions to initiate preventive measures (e.g. elimination of substances with an especially high allergic potential). This study analyzes results of patch testing performed between 1980 and 1993 at the University Clinic of the RWTH Aachen. Additionally, age and sex-related distribution was evaluated. The data is compared to published patch test results covering the years 1995-2001 and patch test results from 2004 in the University Clinic Aachen.

Communicating with hard-to-reach patients.

The blocks to communication that hinder work with certain patients with organically based illnesses can be overcome with imagination and forethought. This article has identified some techniques found useful in working with such patients, but, in the end, it is critical that workers do not let their frustration with communicating alienate them from their patients. Feelings of inadequacy cannot be allowed to separate workers from their patients. Devising techniques to enhance communication with the hard-to-reach patient is an area of social work practice greatly in need of exploration.

Calculation of photopolymerization energy required for optical fiber coating.

The UV flux density required for photopolymerization is calculated, primarily based on an estimation of the overall system efficiency and the activation energy of the photoinitiator added to the prepolymer solution. We found that there is a linear relationship between the flux density and coating speed. The experimental results support the relation. Furthermore, it is noted that full curing has been achieved at speeds >5 m/sec with the 10-kW output power. The 10-kW system delivers 1.5 kW of UV power in the 300-400-nm spectral range.

High speed coating of optical fibers with UV curable materials at a rate of greater than 5 m/sec.

A newly designed 7.3-m high tower is reported that is equipped with a 10-kW curing system capable of coating a fiber with 50-microm thickness of UV curable resin at a speed in excess of 5 m/sec. Performance of fibers coated at two different speeds (V(f) = 1.5 and 5 m/sec) were evaluated. It was found that there were no noticeable differences in the measured values of mechanical and optical properties such as strength, coating thickness, transmission loss, bandwidth.

Prospecting for customers in the small employer market: the experience of Arizona Health Care Group.

The findings of this study provide an interesting profile of the small employer "prospects" for prepaid health plans, where a prospect is defined as an employer that responds to a mass mailing effort with a request for information and further contact. About 60% of these prospects already have insurance, with 40% having group insurance. Therefore, a substantial portion of prospects are seeking to replace their existing health benefit package with a different one. Of those who do not offer existing insurance, the most common reason is that it is "too expensive" or the employer is "not profitable." A very small proportion do not offer insurance because they do not qualify for it due to medical underwriting considerations. Prospects tend to be larger than non-prospects in terms of sales, but employ lower wage employees, on average. About half of prospects are in service industries, a proportion typical of small employers in general. Somewhat surprisingly, most prospects have been in operation for over five years. They are not new firms attempting to establish their benefit packages. This is consistent with the findings on gross sales, suggesting that some maturity is necessary before an employer considers offering group health insurance as a benefit. The prepaid plans in this study also appeared to target established employers for their marketing efforts. In responding to questions about their attitudes towards health insurance, over one-quarter of prospects indicated that they would be unwilling to offer insurance at rates so low that they would not normally apply to the coverages offered by prepaid plans. Thus, although they were "prospects" by the study's definition, they were unlikely to eventually contract with prepaid plans. Those prospects that had offered insurance previously, but had discontinued it, tended to cite premium increases as the reason. This suggests that prospects among small employers are likely to be very price sensitive, and that further prescreening of prospects by phone, during which premium levels are discussed, might be cost-effective in following up leads from mass mailings. The study data also suggest the importance of quick follow-up for mass mailing leads, as the drop-off in recall and interest appears to be substantial. About half of the prospects interviewed stated that they were unaware of AHCG, although they or someone in their business had returned a mailer requesting more information. In addition to their implications for marketing to small employers, the results of the study appear to have broader policy implications as well.(ABSTRACT TRUNCATED AT 400 WORDS)

Rapid sample preparation method for PCR-based detection of Escherichia coli O157:H7 in ground beef.

AIM: To develop an improved, rapid and sensitive sample preparation method for PCR-based detection of Escherichia coli O157:H7 in ground beef. METHODS AND RESULTS: Fresh ground beef samples were experimentally inoculated with varying concentrations of E. coli O157:H7. PCR inhibitors were removed and bacterial cells were concentrated by filtration and centrifugation, and lysed using enzymatic digestion and successive freeze/thaw cycles. DNA was purified and concentrated via phenol/chloroform extraction and the Shiga toxin 1 gene (stx1) was amplified using PCR to evaluate the sample preparation method. Without prior enrichment of cells in broth media, the detection limit was 103 CFU g-1 beef. When a 6 h enrichment step was incorporated, the detection limit was 1 CFU g-1 beef. The total time required from beginning to end of the procedure was 12 h. CONCLUSIONS: The sample preparation method developed here enabled substantially improved sensitivity in the PCR-based detection of E. coli O157:H7 in ground beef, as compared to previous reports. SIGNIFICANCE AND IMPACT OF THE STUDY: Superb sensitivity, coupled with quick turn-around time, relative ease of use and cost-effectiveness, makes this a useful method for detecting E. coli O157:H7 in ground beef.

Prechirper to relax the timing restrictions for soliton-dragging logic gates.

The timing restrictions for soliton-dragging logic gates can be relaxed by asymmetrizing the interaction between the orthogonally polarized control and signal pulses. In particular, by prechirping the signal pulse in a normal group-velocity dispersion fiber, we find experimentally that the timing restriction can be loosened from less than 2 pulse widths to over 3.3 pulse widths. For this passive prechirper arrangement the timing restrictions are loosened at the expense of increased minimum switching energy. Soliton-dragging logic gates with a signal prechirper can provide timing restoration as well as logic-level restoration, so that two inverter gates can be cascaded to implement an ultrafast, all-optical pulse regenerator.