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Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 [mu]g/mL (baseline, n = 28), 5.59 ± 2.24 [mu]g/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 [mu]g/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 [mu]g/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 [mu]g/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned. [ABSTRACT FROM AUTHOR]

The article discusses the research program which assembled a database of autopsy report on intrauterine fetal death and stillbirth with the aim of providing a record for assessment and diagnosis. It states that lifestyle choices play an important role in reproductive outcomes. Topics discussed include the analysis on body and organ weight measurement, the histological examination of the autopsies and the importance of placenta in investigating the fetal deaths.

Focuses on the prevalence of defects in disposable anesthetic equipment. Design and construction of anesthetic equipment; Recommendation on testing and examination of the equipment prior to use; Methods in the examination of the equipment.

Background and Aims Methods Results Discussion The Charcot–Marie–Tooth Disease Health Index (CMT‐HI) is a disease‐specific, patient‐reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18–75 years) underwent clinical outcome assessments (COAs), including the CMT‐HI, to capture their longitudinal perspective on the disease burden.Two hundred and fifteen participants underwent serial COAs including the CMT‐HI, CMT Functional Outcome Measure (CMT‐FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES‐R). Correlations between the total and subscale scores for the CMT‐HI and other COAs were determined. Changes in the CMT‐HI scores over 12 months were assessed using paired t‐tests. The minimum clinically important difference (MCID) for the CMT‐HI and its subscales were calculated by anchoring to a participant global impression of change scale.At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18–75) and 58% were women. The mean CMT‐HI was 25.7 ± 18.8 (range: 0–91.9; 100 reflecting maximal disease burden). The CMT‐HI correlated with the CMT‐FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES‐R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT‐HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT‐HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT‐HI total score was 3.8 points (95% CI: 1.7–5.9).Patient‐reported disease burden in CMT1A as measured by the CMT‐HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A. [ABSTRACT FROM AUTHOR]

Mesenteric lymphoblasts have a predilection to localize selectively in the murine small intestine within 24 hr after adoptive transfer. In this report, we quantify the localization and intraintestinal distribution of radiolabelled mesenteric lymph node (MLN) T and B blasts in relation to the in situ distribution of intestinal T and B cells which were detected immunohistochemically. Our results show that, within 24 hr after transfer, MLN T blasts localized predominantly in the intestinal epithelium and villus lamina propria, whereas B blasts were found mostly in the basal lamina propria of the gut. In the epithelium and villus lamina propria, 100% and 68%, respectively, of labelled were of thymic origin; this cell type comprised 54% of labelled cells in the basal lamina propria. This pattern of localization was the reverse of the distribution of T lymphocytes and B-cell derived plasmacytes residing in the intestinal wall. These results suggest that MLN T lymphocytes may be a component of common mucosal immunological system and may be integrated with peripheral immunity according to the immunological needs of the host. [ABSTRACT FROM AUTHOR]

We examined whether protein-calorie (PC) and vitamin A (VA) deficiencies altered the intestinal localization of mesenteric lymph node (MLN) lymphoblasts using an adoptive lymphocyte transfer method. MLN cells from donor rats were labelled in vitro with [125I]-deoxyuridine and injected i.v. into various recipients. Twenty-two to twenty-four hours after transfer of labelled cells prepared from PC-deficient donors, the percentage of radioactivity in the small intestine of normal recipients was two-thirds of that detected after transfer of cells obtained from normal donors. When donor cells were obtained from rats suffering both PC and VA malnourishment, this decrease was even greater, being only one-third of the normal donor cell control. Other experiments indicated that the defect in localization behaviour was associated with the donor blasts and not the recipient intestine. These findings suggest that defective localization in mucosal lymphoblasts may be a factor contributing to morbidity in malnourished populations. [ABSTRACT FROM AUTHOR]

We have studied the effect of altering the numbers of lymphoblasts from the mesenteric lymph node (MLN) transferred into syngeneic female CBA/J mice on their distribution and abundance 24 hr later. The frequency of (³H]-thymidine-labelled donor MLN cells in the recipient small intestine and lungs was directly related to the numbers transferred. Of the donor MLN lymphoblasts in the small intestine, 62.5% ± 0.9% were seen in the basal lamina propria, 32.5%± 0.9% in the villus lamina propria and 5%±0.6% in the epithelium. Of the MLN lymphoblasts localizing in the lungs, 90% ± 2.3% were in the parenchyma while 6.7%±1.8% and 3.3%±1.0% appeared in the bronchus-associated lymphoid tissue (BALT) and the bronchial epithelium, respectively. Although few peripheral lymph node (PLN)-derived lymphoblasts localized in the small intestine, the numbers of PLN lymphoblasts in the lungs were similar to those observed after transfer of comparable doses of MLN lymphoblasts. However, PLN lymphoblasts were found only in the pulmonary parenchyma and did not appear in either BALT or bronchial epithelium. These data suggest that the number of MLN, but likely not PLN, lymphoblasts in the circulation, directly influences the numbers of lymphoblasts which localize in intestinal mucosa, BALT and bronchial epithelium. Even at the highest doses of MLN lymphoblasts transferred we could not saturate the capacity of these tissues to accommodate MLN lymphoblasts nor was their intra-intestinal distribution altered. [ABSTRACT FROM AUTHOR]

Covalent conjugates of hen egg lysozyme (HEL) and anti-major histocompatibility complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice intranasally. Three weeks after intranasal (IN) priming, mice responded rapidly to IN challenge with a mixture of HEL and cholera toxin (CT), by producing large titres of anti-HEL IgA and IgGl antibody in serum, and IgA antibody in nasal secretions. No secondary response to HEL plus CT occurred in mice that received no priming or mice primed with HEL alone. The secondary serum IgG antibody response was dominated by the IgGl subclass. HEL combined with CT adjuvant worked much better than HEL alone in producing the secondary response. Control conjugates, containing an IgG isotype-matched mAb without specificity for mouse tissues, provided poor priming. Mice expressing MHC class II molecules, to which the anti-MHC II mAb could not bind, produced a weak antibody response compared with those that expressed the appropriate MHC class II molecule. Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that systemic and mucosal administration of soluble antigens in biodegradable microparticles can potentiate antigen-specific humoral and cellular immune responses. However, current microparticle formulations are not adequate for all vaccine antigens, necessitating the further development of microparticle carrier systems. In this study, we developed a novel microparticle fabrication technique in which human serum albumin (HSA) was entrapped in starch microparticles grafted with 3-(triethoxysilyl)-propyl-terminated polydimethyisiloxane (TS-PDMS), a biocompatible silicone polymer. The immunogenicity of HSA was preserved during the microparticle fabrication process. Following intraperitoneal immunization of mice, TSPDMS-grafted microparticles (MP) dramatically enhanced serum IgG responses compared with ungrafted MP and soluble HSA alone (P < 0.001). When delivered orally, both TS-PDMS-grafted and ungrafted microparticles elicited HSA-specific IgA responses in gut secretions, in contrast to orally administered soluble antigen. Indeed, TS-PDMS-grafted microparticles stimulated significantly stronger serum IgC; (P < 0.005) and IgA (P < 0.001) responses compared with those elicited by ungrafted microparticles. These findings indicate that TS-PDMS-grafted starch microparticles have potential as systemic and mucosal vaccine delivery vehicles. [ABSTRACT FROM AUTHOR]

This research focuses on a relatively unexplored phenomenon-black female juvenile offenders. Both theoretical and research work are weak or nonexistent regarding these offenders. This paper seeks to fill some of these gaps. In addition, this research effort draws on a source of data that has infrequently been adapted to study offenders, National Crime Survey (NCS) victimization data. Utilizing NCS data from 1973 through 1981, a comparative analysis of NCS rates of juvenile offenses by black females, black males, white females, and white males is presented and discussed. A number of propositions which are found in the literature regarding black female offenders are examined. Trends in offending by black females compared with trends for other age-race-sex subgroups are also presented and analyzed. Finally, some implications for future theoretical and research efforts are presented. [ABSTRACT FROM AUTHOR]

A newborn baby boy was referred to the Paediatric Dermatology Unit with a solitary asymptomatic nodule overlying his right nasolabial fold. Complete physical examination, full blood count, serum chemistry, liver function tests and baseline imaging were unremarkable. Histopathological examination showed an atypical dermal infiltrate of mononuclear cells that stained positive with CD1a and S100. A diagnosis of congenital solitary Langerhans cell histiocytoma was made. The lesion completely resolved by 4 months of age. The baby is now 15 months old and repeat systemic evaluation has remained normal., (© 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.)

Objectives/hypothesis: To evaluate our initial experience with a novel technique, endoscopic anterior maxillotomy (EAM), for improved access to the anterior-lateral skull base. Clinical and radioanatomic data are presented to describe and define this novel technique., Study Design: Case series., Methods: Surgical patients with lesions of the pterygopalatine fossa, infratemporal fossa, and anterior-lateral maxilla treated from 2006 to 2008 are reviewed. Demographic data and surgical technique are presented. A radioanatomic analysis pre- and post-EAM is performed to describe increased access. Matched-paired analysis was performed for statistical evaluation., Results: Thirty-two patients had surgical treatment of anterior-lateral skull base lesions. EAM was utilized in 16 cases. Fifty-six percent extended lateral to V2 and 56% extended posterior to the maxillary sinus. Complete resection was achieved in 11 patients. There was one unplanned subtotal resection. Radioanatomic measurements demonstrated an increase in the radius of surgical access to the ipsilateral skull base using the EAM when compared with both standard transnasal techniques (33.1° vs. 14.8°; P < .0001) and extended approaches removing the nasolacrimal duct (33.1° vs. 23.5°; P < .001). Similar findings were noted for lateral access to the contralateral skull base., Conclusions: Endoscopic anterior maxillotomy is a novel technical addition to the skull base surgeon's armamentarium. Radioanatomic analysis demonstrates a significant improvement in access to the anterolateral skull base., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain., Methods: Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI)., Results: High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks., Conclusions: Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.

Objectives: In most reports, the prevalence of PD in mainland China is lower than in western populations. To estimate PD prevalence in China, we performed a cross-sectional study in a rural population in Linxian County, China., Primary Outcomes: Clinical diagnosis of PD., Results: Among the 16,488 participants examined, the overall age- and gender-adjusted prevalence rate of PD was 522/100,000 (95% CI: 477-567) assuming no cases of PD would be found among those younger than 50 years of age. The gender-adjusted prevalence rates were 103 (95% CI: 83-123), 621 (95% CI: 572-670), 902 (95% CI: 843-961), and 1744 (95% CI: 1662-1826) per 100,000 in age groups 50-59, 60-69, 70-79, and 80 and above, respectively., Conclusions: The estimated prevalence of PD in Linxian, China is higher than most of those reported from other areas in China, and similar to those reported from non-Asian populations., (Copyright Blackwell Munksgaard 2005.)

Objective: To investigate genetic susceptibility in the first Indian family identified as having an autosomal dominantly inherited periodic fever syndrome. The inflammatory disease was characterized chiefly by arthralgia, skin rashes, and AA amyloidosis., Methods: Markers from known periodic fever susceptibility loci were investigated in 7 affected and 11 healthy members of a north Indian family. These included the TNFRSF1A locus (formerly known as TNFRI), which is involved in autosomal dominant tumor necrosis factor receptor-associated periodic syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold urticaria (MWS/FCU) locus on distal chromosome 1q44., Results: Linkage to both TNFRSF1A and MEFV was definitively excluded, and DNA sequencing of these genes revealed no mutations. Furthermore, there was no evidence of linkage to the HIDS locus. In contrast, significant logarithm of odds scores for 5 markers from the MWS/FCU region were obtained in this family, and the disease segregated with the same haplotype in all affected members., Conclusion: We have identified an inherited inflammatory disease in a north Indian family with clinical features overlapping some of those of MWS and FCU. The susceptibility gene maps to distal chromosome 1q44, a region already implicated in both MWS and FCU. Different mutations in the same (or a closely related) gene may be responsible for an inflammatory disease with a broad phenotype among diverse ethnic populations.

Objectives: This paper describes implementation of the learner-centred learning goal within the primary care clerkship at a Midwestern, United States medical school., Design: The learner-centred learning goal exercise was developed to tailor students' educational activities to their personal level of development and to enhance their commitment to life-long learning in medicine. In the learner-centred learning goal exercise, each student records three specific learning goals early in the primary care clerkship. Students record the methods by which they will pursue and document achievement of each goal. Attainment of the learner-centred learning goal is evaluated based on an oral presentation at the end of the clerkship. We compiled presented learning goals along with the corresponding grade. Students' ratings of the learner-centred learning goal exercise were also compiled. Evaluations and ratings were made on a 1-5 Likert scale, where 1 is the best rating and 5 is worst., Setting: Department of Medicine, Northwestern University Medical School, Chicago, USA., Subjects: One hundred and seventy-seven third- and fourth-year medical students who presented learner-centred learning goals between 1 July 1995 and 30 June 1996., Results: Students rated pursuing their individual learning goals more worthwhile than most clerkship lectures but less worthwhile than the office experience. Several learning goals were chosen by a disproportionate number of students, potentially indicative of some perceived deficiencies elsewhere in the curriculum. Third-year students ranked the learner-centred learning goal exercise more favourably than fourth-year students (2.14 vs. 2. 51, P = 0.03)., Conclusions: The learner-centred learning goal exercise is a feasible and well-received method within our primary care clerkship. Further study is required to determine whether the exercise promotes independent learning after formal medical school education is completed.

The authors present a model for incorporating multifamily therapy in the treatment of chemical dependency and investigate the association of family participation in multifamily therapy group with treatment retention in a sample of 164 alcohol- and/or cocaine-dependent outpatients. Results indicate that level of family attendance at a multifamily group strongly predicted completion of short-term and long-term out-patient treatment. Effects were greater for cocaine-dependent than for alcohol-dependent subjects in analyses of short-term treatment retention. Multifamily therapy may be a powerful method to engage patients families in treatment and promote treatment retention, especially in the early, intensive phases of treatment for cocaine dependency.

Objective: We have recently shown that administration of long-term, low-dose methotrexate (MTX) causes severe osteopenia in female rats. This osteopenia is characterized both by decreased osteoblast function without a decrease in osteoblast numbers, and by increased bone resorption that is believed to represent a physiologic remodeling response by osteoclasts. The present study investigates the effects of varying doses of MTX on mouse bone cells in culture., Methods: Cells were obtained by sequential digestion of neonatal mouse calvariae, and cultured with fetal calf serum (10% for osteoblast-like cells and 2% for osteoclast-like cells). After 1 week, MTX was added to each culture in concentrations of 0.6 microM, 0.4 microM, 0.2 microM, 0.1 microM, 1 nM, and 0.5 nM. All experiments were done on 24 wells for each MTX concentration and for the controls. The effect on osteoblastic cells was assessed, at 7 days, by cell counts and by measurement of lysate alkaline phosphatase and supernatant osteocalcin levels, and, at 21 days, by analysis of the calcified matrix production, which was cultured with ascorbic acid and beta-glycerophosphate. For osteoclastic cells, cell count and lysate acid phosphatase levels were determined., Results: Levels of osteoblastic cells and lysate alkaline phosphatase were not changed by any of the concentrations of MTX. Matrix calcification and supernatant osteocalcin levels were diminished by MTX in a dose-responsive manner. Osteoclast-like cell numbers and acid phosphatase levels were not significantly affected by MTX., Conclusion: These results suggest that diminished mouse osteoblastic cell function occurs with very low mean concentrations of MTX, in a dose-responsive manner. The mechanism seems to be inability of the cell to synthesize and calcify matrix, possibly through defective osteocalcin production. Thus, low-dose MTX may have an important impact on bone density by slowing osteoblastic matrix production.

Objective: To evaluate the role of the T cell receptor beta chain locus (TCRB) in genetic susceptibility to rheumatoid arthritis (RA)., Methods: Twenty-eight multiplex RA families were recruited from 3 rheumatology outpatient departments. All members were genotyped for a highly informative microsatellite (V beta 6.7), a V beta 12.2 SSCP marker, and a biallelic C beta restriction fragment length polymorphism. Data were analyzed by the SIBPAL program to assess identity-by-descent in affected sib-pairs., Results: Using the V beta 12.2 marker, there was suggestive evidence of increased sib-pair sharing (P = 0.005) in affected offspring (a P value of 0.001 is generally taken to establish linkage). Data for V beta 6.7 and C beta yielded significance levels of 0.06 and 0.19, respectively., Conclusion: These data suggest that a gene in or linked to the TCRB complex may confer genetic susceptibility to RA in these families. Confirmation in a larger panel of families is required.

Objective: To ascertain the effects of low-dose methotrexate (MTX) on bone metabolism and histomorphometry in rats., Methods: Female Sprague-Dawley rats (6 months old, n = 42) were divided into the following 4 groups: intraperitoneal (IP) injections of MTX, with and without ovariectomy, and IP saline (controls), with and without ovariectomy. Injections were given for 16 weeks. The MTX dose was equivalent to a standard dose for rheumatoid arthritis in humans that would yield similar serum MTX levels (0.6 +/- 0.1 mumoles)., Results: Bone formation (assessed by serum alkaline phosphatase and osteocalcin levels and histomorphometry) was significantly lower in the MTX groups, and bone resorption (assessed by urinary hydroxyproline levels and histomorphometry) was increased in the MTX groups. Bone mass was significantly diminished in the MTX groups., Conclusion: Prolonged administration of low-dose MTX in rats causes significant osteopenia via suppression of osteoblast activity and stimulation of osteoclast recruitment, which results in increased bone resorption.