Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma.

BACKGROUND: Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium. OBJECTIVE: To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline. METHODS: We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls. RESULTS: In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients. CONCLUSIONS: Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.     

A locus for Bowen-Conradi syndrome maps to chromosome region 12p13.3

Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder with an estimated incidence of 1 in 355 live births in the Hutterite population. A few cases have been reported in other populations. Here, we report the results of a genome-wide scan and fine mapping of the BCS locus in Hutterite families. By linkage and haplotype analysis the BCS locus was mapped to a 3.5 cM segment (1.9 Mbp) in chromosome region 12p13.3 bounded by F8VWF and D12S397. When genealogical relationships among the families were taken into account in the linkage analysis, the evidence for linkage was stronger and the number of potentially linked regions was reduced to one. Under the assumption that all the Hutterite patients were identical by descent for a disease-causing mutation, haplotype analysis was used to infer likely historical recombinants and thereby narrow the candidate region to a chromosomal segment shared in common by all the affected children. This study also demonstrates that BCS and cerebro-oculo-facial-skeletal syndrome (COFS) are genetically distinct.     

Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Nucleotide sequence of the coat protein gene of a necrotic strain of potato virus Y from New Zealand

Summary The sequence of the 3-terminal 1,134 nucleotides of the genome of a New Zealand isolate of a necrotic strain of potato virus Y (PVY^N) has been determined. This sequence contains one large open reading frame of 796 nucleotides, the start of which was not identified, which is capable of encoding a protein of 264 amino acid residues with a molecular weight of 29,631. Comparison of the amino acid sequence with a published coat protein sequence of another strain, PVY-D, and with the amino acid sequence deduced from PeMV cDNA sequence data, confirms that the 3 cistron encodes the viral coat protein in PVY^N. Adjacent to the 3 end of the coding region there is an untranslatable sequence of 326 nucleotides terminating in a polyadenylate tract. An alignment of the PVY^N amino acid sequence with the coat protein sequences of six other potyviruses revealed significant sequence similarities in the internal and carboxy terminal regions. Much amino acid sequence similarity was found between PVY^N, PVY-D, and PeMV (91–93%), suggesting that PeMV should be regarded as a PVY strain. An analysis of the 3-untranslated region of the six potyviruses revealed PVY^N and PeMV as the only viruses displaying sequence similarity in this region. The 3-untranslated sequences of PVY^N and PeMV were further examined for secondary structure.     

Rhabdoid tumor of the kidney with primitive neuroectodermal tumor of the central nervous system: Associated tumors with different histologic,cytogenetic, and molecular findings

Rhabdoid tumor of the kidney (RTK) is associated with tumors of the central nevous system (CNS) in approximately 15% of cases. We describe the clinical features, histologic and cytogenetic findings, and molecular analysis of renal and CNS tumors from the same patient. The histology of the renal tumor was consistent with rhabdoid tumor. The CNS tumor was a primitive neuroectodermal tumor (PNET). The karyotype of the RTK was normal male. The PNET of the brain demonstrated monosomy 22 as the only cytogenetic abnormality, similar to reported cases of malignant rhabdoid tumor of the brain, but dissimilar to nonrandom cytogenetic findings in other CNS PNETs. Molecular cytogenetic and DNA marker studies confirmed loss of chromosome 22 in this patient's brain tumor. DNA allelotyping showed retention of both parental chromosome 22 alleles in the RTK and loss of the maternal allele in the PNET. Evaluation of additional RTKs and brain tumors occurring in the same patient may provide insight into the origins and relationships of these enigmatic tumors.     

Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy

Sympathetic vasoconstriction is normally attenuated in exercising muscles of young men and women. Recent evidence indicates that such modulation, termed functional sympatholysis, may be impaired in older men. Whether a similar impairment occurs in older women, and what role oestrogen deficiency might play in this impairment, are not known. Based on the strong positive correlation between circulating oestrogen levels and functional sympatholysis previously reported in female rats, we hypothesized that sympatholysis would be impaired in oestrogen-deficient postmenopausal women, and that this impairment would be reversed by oestrogen replacement. To test these hypotheses, we measured vasoconstrictor responses in the forearms of pre- and postmenopausal women using near infrared spectroscopy to detect decreases in muscle oxygenation in response to reflex activation of sympathetic nerves evoked by lower body negative pressure (LBNP). In eight premenopausal women, LBNP decreased muscle oxygenation by 20 ± 1% in resting forearm, but only by 3 ± 2% in exercising forearm  ( P < 0.05)  . In contrast, in eight postmenopausal women, LBNP decreased muscle oxygenation by 15 ± 3% in resting forearm, and by 12 ± 4% in exercising forearm  ( P > 0.05)  . After 1 month of transdermal oestradiol replacement in these women, the normal effect of exercise to blunt sympathetic vasoconstriction was restored (rest, −19 ± 3%; exercise, −2 ± 3%;   P < 0.05  ). These data indicate that functional sympatholysis is impaired in oestrogen-deficient postmenopausal women. The effect of short-term unopposed oestrogen replacement to correct this impairment implicates a role for oestrogen in the sympathetic neural control of muscle haemodynamics during exercise.     

COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia

The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making.     

Psychosocial factors related to long-term survival with HIV/AIDS

Only a few studies of long-term survivors of AIDS (those who survive more than twice the median expected time) have been done but these reveal a constellation of psychological characteristics including, but not limited to, those with active coping, social support, life involvement, ability to communicate, and active collaboration with one's doctor. Another related literature consists of longitudinal studies following people infected with the HIV virus to determine whether psychological characteristics are related to disease progression. These studies have focused on coping, depression, negative expectancies and social support as predictors. This article reviews and integrates the two bodies of literature combining the variables identified into four psychosocial strategies related to longer survival with HIV/AIDS: following healthy self care; maintaining connectedness; having a sense of meaning or purpose in life; and maintaining perspective. Affect, beliefs, and behaviour are all seen as important. Biological variables, SES and psychological resources that the person brings to the situation and external stresses are seen as important variables to consider in prediction studies. The pathways through which these four strategies may operate (both psychological and biological) to impact on health are discussed. Psychological pathways include distress and behavioural disengagement, while biological pathways involve the sympathetic nervous system, neuroendocrine and immune mediation. Finally suggestions for future research are given.     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Total Hip Arthroplasty in Patients With Osteoarthritis Associated With Legg-Calve-Perthes Disease: Perioperative Complications and Patient-Reported Outcomes

BackgroundComplications and patient-reported outcomes (PROs) of total hip arthroplasty (THA) in patients with Legg-Calve-Perthes disease (LCPD) have demonstrated variable results. The purpose of this study was to use a validated grading scheme to analyze complications associated with THA in patients with residual LCPD deformities. Second, we report PROs and intermediate-term survivorship in this patient population.MethodsA retrospective, single-center review was performed on 61 hips in 61 patients who underwent THA for residual Perthes disease. Average patient age was 42 years and 26% of hips had previous surgery. Complications were determined and categorized using a validated grading scheme that included five grades based on the treatment required to manage the complication and on persistent disability. PROs were compared from preoperative to most recent follow-up time points.ResultsMajor complications (grade III) occurred in three patients (5%) which each required a second surgical intervention. The most common minor grade I or II complications (11.5%) were asymptomatic heterotopic ossification (3.3%). Patients were lengthened on the surgical side an average of 1.4 cm with no nerve palsies. All patient PROs improved from preoperative to postoperative time points with the modified Harris Hip Score improving from 46.9 preoperatively to 85.4 postoperatively (P < .01). Patients free from revision for any reason at final follow-up (5.6 years; range 2-13 years) was 98.4% with one patient needing a revision of their femoral component.ConclusionsTHA for the sequelae of the LCPD has an acceptable complication rate and provides excellent patient reported outcomes at mid-term follow-up.